TW200906801A

TW200906801A - Isoquinolinone derivatives as NK3 antagonists

Info

Publication number: TW200906801A
Application number: TW097114780A
Authority: TW
Inventors: Klaus Baek Simonsen; Jan Kehler; Karsten Juhl; Nikolay Khanzhin; Soren Moller Nielsen
Original assignee: Lundbeck & Co As H
Priority date: 2007-04-26
Filing date: 2008-04-23
Publication date: 2009-02-16
Also published as: KR20100015933A; AR066260A1; CL2008001227A1; CO6251250A2; IL201721A0

Abstract

Isoquinolone derivatives of the general formula are provided. The compounds are NK3 antagonists and useful for the treatment of e. g. psychosis and schizophrenia.

Description

200906801 九、發明說明：【發明所屬之技術領域】本發明係關於適用於治療，允並、A 士欣尤其治療精神病 (psychosis)之化合物，包含該等化合物之組合物，及包含投予該等化合物之治療疾病的方法。【先前技術】目前核可之抗精神病藥具有降低大腦中之多巴胺 (dopamine)信號轉導的共同特徵。此係藉由多巴胺ο] 受體拮抗作用或部分促效作用實現。第一代抗精神病藥（亦稱為「典型」）通常與錐體外副作用有關，因此此等藥劑之用途被削弱。第二代或「非典型」抗精神病藥除對D2 受體親和力外，對血清素（ser〇t〇nin )受體( 5-Ητ ) 亦具有親和力。一些非典型抗精神病藥另外對5 hT2c、A5_ ΗΤδ或5-HT7受體具有親和力。非典型抗精神病藥引起較少錐體外副作用，但仍因體重增加及QTc作用而受阻。非典型藥物之實例為氯氮平（cl〇zapine )、奥氮平（olanzapine ) 及利培_ (risperidone)。最近，已建議神經激肽（neur〇kinin )受體作為中樞神、.、工糸、，先（CNS )疾病之標乾[Albert, 14，1421_1433，2〇〇4]。神經激肽（或速激肽 (tachykinin))為神經肽家族，其包括p物質（sp)、神經激肽A ( NKA )及神經激肽b ( NKB )。此等物質之生物作用主要藉由與NK1、NK2及NK3三種神經激肽受 200906801 體結合且使其活化而實現。儘管可能存在一些交叉反應性，但SP對NK1具有最高親和力，且咸信其為NK1之内源性配位體，且NKA與NK2，及NKB與NK3之間同樣如此。 NK3主要集中表現於以下區域：包括皮質區，諸如額葉皮質、頂葉皮質及扣帶皮質；杏仁核，諸如基底核、中央核及外側核；海馬體；及中腦結構，諸如腹側被蓋區、黑質緻密部及中縫背核[Spooren專尺，Nature Reviews, A, 967-97 5, 2005]。NK3受體表現於多巴胺神經元，且Spooren 等人已提出NK3拮抗劑之抗精神病作用係藉由抑制多巴胺性狀（dopamine tone)(尤其在D2受體處）結合降低血清素性狀（serotonergic tone)(尤其5-HT2a受體處）而介導。已臨床上測試他奈坦（talnetant ) 及奥沙奈坦 (osanetant )兩個結構上不同之NK3抬抗劑之抗精神病作用，及尤其抗精神***作用。200906801 IX. INSTRUCTIONS OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to a compound suitable for use in the treatment, augmentation, A, and especially for the treatment of psychosis, a composition comprising the same, and the inclusion of such a compound A method of treating a disease with a compound. [Prior Art] Currently approved antipsychotic drugs have a common feature of reducing dopamine signaling in the brain. This is achieved by dopamine ο] receptor antagonism or partial agonism. The first generation of antipsychotics (also known as "typical") is often associated with extrapyramidal side effects, and the use of such agents is therefore impaired. Second-generation or "atypical" antipsychotic drugs have affinity for the serotonin (ser〇t〇nin) receptor (5-Ητ) in addition to the D2 receptor affinity. Some atypical antipsychotics have additional affinity for the 5 h T2c, A5_ΗΤδ or 5-HT7 receptors. Atypical antipsychotic drugs cause fewer extrapyramidal side effects, but are still blocked by weight gain and QTc effects. Examples of atypical drugs are clonazepine, olanzapine, and risperidone. Recently, neurokinin (neur〇kinin) receptors have been suggested as the backbone of central nervous system, ., work, and (CNS) diseases [Albert, 14, 1421_1433, 2〇〇4]. Neurokinin (or tachykinin) is a family of neuropeptides including substance p (sp), neurokinin A (NKA), and neurokinin b (NKB). The biological effects of these substances are mainly achieved by binding and activation of the three neurokinins of NK1, NK2 and NK3 by 200906801. Although there may be some cross-reactivity, SP has the highest affinity for NK1 and is believed to be an endogenous ligand for NK1, as well as between NKA and NK2, and between NKB and NK3. NK3 is mainly concentrated in the following areas: including cortical areas such as frontal cortex, parietal cortex and cingulate cortex; amygdala, such as basal nucleus, central nucleus and lateral nucleus; hippocampus; and midbrain structures, such as ventral ventral Cover area, substantia nigra pars compacta and nucleus dorsal nucleus [Spooren, Nature Reviews, A, 967-97 5, 2005]. The NK3 receptor is expressed in dopamine neurons, and Spooren et al. have suggested that the antipsychotic effect of NK3 antagonists reduces serotonergic tone by inhibiting dopamine tone (especially at the D2 receptor). Especially mediated by the 5-HT2a receptor). The antipsychotic effects of two structurally distinct NK3 antagonists, talnetant and osanetant, have been clinically tested, and in particular, anti-schizophrenia.

奥沙奈坦他奈坦在臨床試驗中證實奥沙奈坦優於安慰劑，尤其對精神 6 200906801 病之正性症狀（positive symptoms )，亦即妄想（delusi〇ns )、幻覺（hallucinations)及偏執（paranoia) μ心， 161，2004, 975-984]。類似地，已在臨床試驗中證明他奈坦改善精神***症患者之認知行為[Cwrr. g， 717-721，2005]。然而，兩種化合物皆因不良藥物代謝動力學及藥效學特性而受阻，包括不良溶解性、不良生物可用性、相對較高之清除率及不良血腦障壁穿透性 revkw，4, 967-975, 2〇05]。此等結果支持NK3受體為（例如）精神病治療的有前景標靶之觀點，然而強調需要鑑別具有適當藥物代謝動力學及藥效學特性之化合物。 W095/32948揭示一系列喹啉衍生物，包括作為NK3 拮抗劑之他奈坦。最近’ W0 2006/130080揭示具有如下核心組織之化合物，Oxalatin tantanide demonstrated in clinical trials that oxatanide is superior to placebo, especially for the positive symptoms of mental 6 200906801, namely delusi〇ns, hallucinations and paranoia ( Paranoia) μ heart, 161, 2004, 975-984]. Similarly, it has been demonstrated in clinical trials that statin improves cognitive behavior in patients with schizophrenia [Cwrr. g, 717-721, 2005]. However, both compounds are hampered by poor pharmacokinetics and pharmacodynamic properties, including poor solubility, poor bioavailability, relatively high clearance, and poor blood-brain barrier revkw, 4, 967-975 , 2〇05]. These results support the notion that NK3 receptors are promising targets for (for example) psychiatric treatment, but emphasize the need to identify compounds with appropriate pharmacokinetic and pharmacodynamic properties. W095/32948 discloses a series of quinoline derivatives, including talnetan as an NK3 antagonist. Recently, 'W0 2006/130080 discloses a compound with the following core organization,

該等化合物據稱為NK3拮抗劑；且WO 2006/050991 及WO 2006/05 0992揭示另外的喹琳羧醯胺衍生物，該等衍生物據稱為NK3拮抗劑。 WO 2005/014575揭示下式之化合物： 200906801Such compounds are said to be NK3 antagonists; and WO 2006/050991 and WO 2006/05 0992 disclose additional quinoline carboxamide derivatives which are said to be NK3 antagonists. WO 2005/014575 discloses compounds of the formula: 200906801

其中R表示含N雜環，亦即吡唑基、***基及四唑基。最後，iwU.C/zew· Seci/ow 5, 18B, 304-306，1979 揭示對具有以下核心組織之化合物的合成法之研究Wherein R represents an N-containing heterocyclic ring, that is, pyrazolyl, triazolyl and tetrazolyl. Finally, iwU.C/zew·Seci/ow 5, 18B, 304-306, 1979 reveals the synthesis of compounds with the following core structures

【發明内容】發明概要本發明者已意外地發現某些異喹啉酮衍生物為有效 NK3拮抗劑，其可原樣用於治療（例如）精神病。因此，本發明之一具體實例係關於式I化合物 200906801 R14 人/R13 Γ丨丄SUMMARY OF THE INVENTION The present inventors have unexpectedly discovered that certain isoquinolinone derivatives are potent NK3 antagonists which are useful as such for the treatment of, for example, psychosis. Thus, one specific embodiment of the invention relates to a compound of formula I 200906801 R14 human/R13 Γ丨丄

R16^>^A-R1 R17 IR16^>^A-R1 R17 I

其中A表示N、CH或CR1 ; 其中各R1獨立地表示氫、Cw烷基、C2-6烯基、C2.6 炔基、·<：(0)-(ν6 烷基、-c(0)-c2_6 烯基、-c(o)-c2-6 炔基、 -0(0)-0-(^-6 烧基、-C(0)-0-C2.6 烯基、-C(0)-0_C2.6 炔基或笨基’其中該苯基、C16烷基、C2 6烯基或c2 6炔基視情況經一或多個選自以下基團之取代基取代：齒素、羥基、鹵基CV6烷基、硝基、CV6烷氧基及NR2R3 ; \. 其中X表示氫、（^_6烷基、c2_6烯基 -OR2、·〇-(：(ο)Κ2、_0c(0)nr2r3、_c(〇) nr2r3、_n(r2) c=)R3、-N(r2)_c(0)nr2r3 或 Nr2r3，或 x 表示具有 416 個環原子之單環、雙環或三環部分，環原子中之一者為氮，且其中1個、2個或3個額外環原子可為選自N、〇及s =原子，且其中該單環、雙環或三環部分可視情況經一 :夕個取代基W取代，其中w係選自氫、經基、齒素、 =、（，'_〇·(叫,〇·’其中或 3(螺）、（cH2)d，，、中d為5或6(螺)、C“燒基〜浠基、快 200906801 炫* 氧基、-C ( Ο ) - C 1 _ 6 烧基、-C ( Ο ) - C 2 _ 6 稀基、-c ( Ο ) - C 2 · 6 快基、-CHOhO-Cu 烷基、-c(o)-〇-c2.6 烯基、-c(o)-〇-c2-6 炔基、-O-CCCO-Cu 烷基、-0-C(0)-C2.6 烯基、-o-c(o)-c2· 6 炔基、-C(0)H、COOH;或其中 W 表示式-(CH2)a-Y_(CH2)b-Z 部分；其中a及b獨立地表示選自0、1、2及3之整數；其中 Y 表示一鍵、C(O)、〇、s、-O-C(o)、-C(0)-0-、 -NR2-、-NR2-C(0)·、-C(0)-NH-或 S(0)2 ; 其中z表示氫'C!·6烷基、nr2r3、氰基或包含4至12 個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、〇及s之雜原子，且其中該單環或稍合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：_素、氰基、Ci·6烷基、羥基及Cl—烷氧基、。比啡基、苯基、吡啶基及經鹵素取代之苯基； ^其中r4-R8、r9-r12及R13-R”中之每一者獨立地表示氫、c】_6烷基、c2 6烯基、炔基、鹵素、nr2r3、羥基氰基、硝基、（:w烷氧基、鹵基Ci_6烷基或羥基ci6烷基. 其中R2及R3獨立地表示氫、（：w烷基、c2_6烯基、c 块基、經基C!-6烷基、鹵基Cl.6烷基或苯基；及其醫藥學上可接受之鹽。Wherein A represents N, CH or CR1; wherein each R1 independently represents hydrogen, Cw alkyl, C2-6 alkenyl, C2.6 alkynyl, ·<:(0)-(ν6 alkyl, -c(0 )-c2_6 alkenyl, -c(o)-c2-6 alkynyl, -0(0)-0-(^-6 alkyl, -C(0)-0-C2.6 alkenyl, -C( 0)-0_C2.6 alkynyl or stylyl' wherein the phenyl, C16 alkyl, C2 6 alkenyl or c2 6 alkynyl group is optionally substituted with one or more substituents selected from the group consisting of dentate, Hydroxy, halo CV6 alkyl, nitro, CV6 alkoxy and NR2R3; wherein X represents hydrogen, (^_6 alkyl, c2_6 alkenyl-OR2, 〇-(:(ο)Κ2,_0c(0 Nr2r3, _c(〇) nr2r3, _n(r2) c=)R3, -N(r2)_c(0)nr2r3 or Nr2r3, or x represents a monocyclic, bicyclic or tricyclic moiety having 416 ring atoms, ring One of the atoms is nitrogen, and one, two or three additional ring atoms may be selected from N, 〇 and s = atoms, and wherein the monocyclic, bicyclic or tricyclic moiety may be as follows: a substituent W substituted, wherein w is selected from the group consisting of hydrogen, thiol, dentate, =, (, '_〇·(called, 〇·' or 3 (spiral), (cH2)d, , , where d is 5 or 6 (spiral), C "burning base ~ thiol, fast 2 00906801 炫 * oxy, -C ( Ο ) - C 1 _ 6 alkyl, -C ( Ο ) - C 2 _ 6 dilute, -c ( Ο ) - C 2 · 6 fast radical, -CHOhO-Cu alkane Base, -c(o)-〇-c2.6 alkenyl, -c(o)-〇-c2-6 alkynyl, -O-CCCO-Cu alkyl,-0-C(0)-C2.6 Alkenyl, -oc(o)-c2·6 alkynyl, -C(0)H, COOH; or wherein W represents a moiety of the formula -(CH2)a-Y_(CH2)bZ; wherein a and b independently represent An integer from 0, 1, 2, and 3; where Y represents a bond, C(O), 〇, s, -OC(o), -C(0)-0-, -NR2-, -NR2-C ( 0)·, -C(0)-NH- or S(0)2; wherein z represents hydrogen 'C!·6 alkyl, nr2r3, cyano or a monocyclic or fused bicyclic ring containing 4 to 12 ring atoms In part, one, two or three of the ring atoms are heteroatoms selected from N, oxime and s, and wherein the monocyclic or slightly bicyclic moiety is optionally selected from the group consisting of one or more selected from the group consisting of Substituent substituents of the group: _, cyano, Ci. 6 alkyl, hydroxy and Cl-alkoxy, morphinyl, phenyl, pyridyl and halogen substituted phenyl; ^ where r4-R8, Each of r9-r12 and R13-R" independently represents hydrogen, c]-6 alkyl, c2 6 alkenyl, alkynyl, Halogen, nr2r3, hydroxycyano, nitro, (:w alkoxy, halo-Ci-6 alkyl or hydroxy ci6 alkyl. wherein R2 and R3 independently represent hydrogen, (:w alkyl, c2_6 alkenyl, c-block) a base, a trans-based C!-6 alkyl group, a halogenated Cl.6 alkyl group or a phenyl group; and a pharmaceutically acceptable salt thereof.

在一具體實例中，本發明係關於用於治療之式J化人物及其醫藥學上可接受之鹽。 Q 在一具體實例中’本發明係關於包含式I化入毅鏟興μ 7r ϋ 口物及其商樂予上可接焚之鹽的醫藥組合物。 200906801 在-具體實例中，本發明係關於治療方法，該等方法包含向有需要之患者投予治療有效量之式I化合物及其醫藥學上可接受之鹽。，在一具體實例中，本發明係關於式I化合物及其醫藥學上可接受之鹽之用途，其係用於製造醫藥品。在具體實例中，本發明係關於用於治療疾病之式^ 化合物及其醫藥學上可接受之鹽。定義 f 、，在本文中，「烷基」意指直鏈、支鏈及/或環狀飽和烴。詳5之，「Cy烷基」意指具有！個、2個、3個、4個、 5個或6個碳原子之該烴。Cy烷基之實例包括曱基、乙基丙基丁基、戊基、己基、環丙基、環丁基、環戊基、壤己基、2-甲基-丙基、第三丁基及環丙基甲基。在本文中，「烯基」意指包含至少一個碳_碳雙鍵之直鏈、支鏈及/或環烴。詳言之，「CM烯基」意指具有2個、 3個、/個、5㈣6個碳原子之該烴。c2 6烯基之實例包枯乙烯基、K丙烯基、2-丙烯基、1-丁烯基、2_丁烯基、3_ 丁烯基及環已烯基。在本文中，「炔基」意指包含至少一個碳-碳參鍵且情況亦包含—或多個碳-碳雙鍵的直鏈、支鏈及/或環烴详吕之’ 「C：2_6炔基」意指具有2個、3個、4個、5個 6個碳原子之該烴。CM炔基之實例包括乙炔基、κ丙炔基 2_丙炔基、炔基、2_丁炔基、3_丁炔基及丁-1_烯_ 炔基。 11 200906801 例如：本ί中，「*素」意指元素週期表第7族之成員，例如鼠、氯、溴及碘。 _在本文中，「烷氧基」意指式-OR，之部分，其中R，表 ΠίΓ斤定義之烷基。詳言之，「C“6烷氧基」意指烷土。刀/、有1個、2個、3個、4個、5個或6個碳原子之該部分。在本文中，鹵基烷基意指經一或多個_素取代之如上斤疋義之燒基。洋言之，鹵基燒基意指烧基部分具有1個、2個、3個、4個、5個或6個碳原子之部分。函基烧基之一實例為三氟曱基。在本文中，醫藥學上可接受之鹽包括醫藥學上可接受之酸加成鹽、醫藥學上可接受之金屬鹽、銨鹽及烷基化銨鹽。酸加成鹽包括無機酸以及有機酸之鹽。合適無機酸之實例包括鹽酸、氫溴酸、氫碘酸、璘酸、硫酸、胺磺酸、硝酸及其類似酸。In one embodiment, the invention relates to a human of the formula and a pharmaceutically acceptable salt thereof for use in therapy. Q In a specific example, the present invention relates to a pharmaceutical composition comprising the formula I into the Yishouxing μ 7r mouthwash and its cola. In the specific example, the invention relates to a method of treatment comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I, and a pharmaceutically acceptable salt thereof. In one embodiment, the invention relates to the use of a compound of formula I, and a pharmaceutically acceptable salt thereof, for the manufacture of a medicament. In a specific example, the invention relates to a compound of the formula and a pharmaceutically acceptable salt thereof for use in the treatment of a disease. Definitions f, and herein, "alkyl" means a straight-chain, branched-chain, and/or cyclic saturated hydrocarbon. In detail, "Cy alkyl" means having! The hydrocarbon of 2, 3, 4, 5 or 6 carbon atoms. Examples of the Cyalkyl group include a mercapto group, an ethylpropylbutyl group, a pentyl group, a hexyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a hexyl group, a 2-methyl-propyl group, a tert-butyl group, and a ring. Propylmethyl. As used herein, "alkenyl" means a straight, branched and/or cyclic hydrocarbon comprising at least one carbon-carbon double bond. In detail, "CM alkenyl" means the hydrocarbon having 2, 3, /, 5 (four) 6 carbon atoms. Examples of c2 6 alkenyl groups include cumyl, K propylene, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl and cyclohexenyl. As used herein, "alkynyl" means a straight-chain, branched-chain, and/or cyclic hydrocarbon containing at least one carbon-carbon bond and, in some cases, a plurality of carbon-carbon double bonds. "C:2_6 "Alkynyl" means a hydrocarbon having 2, 3, 4, 5 6 carbon atoms. Examples of CM alkynyl groups include ethynyl, κpropynyl-2-propynyl, alkynyl, 2-butynyl, 3-butynyl and but-1-enyl-alkynyl. 11 200906801 For example: in this ί, “*素” means a member of Group 7 of the Periodic Table of the Elements, such as rat, chlorine, bromine and iodine. As used herein, "alkoxy" means a moiety of the formula -OR, wherein R is an alkyl group as defined by the formula. In detail, "C"6 alkoxy" means an alkane. The knife has one, two, three, four, five or six carbon atoms. As used herein, haloalkyl means the above-mentioned alkyl group substituted by one or more _ s. In other words, a haloalkyl group means a moiety having 1, 2, 3, 4, 5 or 6 carbon atoms in the alkyl group. An example of a functional group is a trifluoromethyl group. As used herein, pharmaceutically acceptable salts include pharmaceutically acceptable acid addition salts, pharmaceutically acceptable metal salts, ammonium salts, and alkylated ammonium salts. Acid addition salts include inorganic acids as well as salts of organic acids. Examples of suitable inorganic acids include hydrochloric acid, hydrobromic acid, hydroiodic acid, citric acid, sulfuric acid, amine sulfonic acid, nitric acid and the like.

V 合適有機酸之實例包括甲酸、乙酸、三氯乙酸、三氟乙酸、丙酸、苯曱酸、肉桂酸、檸檬酸、反丁烯二酸、乙醇酸、衣康酸、乳酸、曱烷磺酸、順丁烯二酸、蘋果酸、丙二酸、扁桃酸、草酸、苦味酸、丙酮酸、水揚酸、號拍酸、曱烷磺酸、乙烷磺酸、酒石酸、抗壞血酸、雙羥萘酸、雙亞甲基水揚酸、乙烷二磺酸、葡萄糖酸、檸康酸、天冬胺酸、硬脂酸、棕櫊酸、EDTA、乙醇酸、對胺基苯甲酸、麩胺酸、笨磺酸、對甲笨磺酸、茶鹼乙酸以及8-鹵基茶鹼，例如8-溴茶鹼及其類似酸。醫藥學上可接受之無機酸加成 12 200906801 鹽或有機酸加成睡之执i之其他實例包括J_ Pharm. Sci. 1977,66,2 中所列的醫藥學上可接受文中。金屬鹽之實例包括鋰鹽、鈉鹽、鉀鹽、鎂鹽及其類之鹽，其係以引用的方式併入本鹽似 f —錄鹽及烷基化銨鹽之實例包括銨鹽、甲基_、二甲基_、 :甲基二乙基…羥基乙基-、二乙基-、正丁基-、第二丁第一丁基-、四甲基銨鹽及其類似鹽。俜選^文中’「環原子」意指構成環之原子’且環原子诉避自C、N、Π菸c 你3 作為舉例而言，苯及甲苯皆具有6個碳子，而吼°定具有5個碳及i個氮作為環原子。在本文中，「置：&rr \ 構。類似地，「雔=分」意指僅包含一個環之成環結兩個環可在各環：衣°刀」意指包含兩個接合環之結構。雙環部I:兩=環原子處接合，在該狀況下該個環在單個環祠合雙環部分之實例。或者，兩螺…氧雜接合，在該狀… 實例。或者，兩個環可在：[4.5]癸烷為螺形式之雙環部分之在,&、、兄in磁在各％之兩個非相鄰環原子處接合，隹4狀況下該雙環部分处按口蘢雙環部分之實例。「_ ’、" H雙環[3·2.2]壬炫為結構。如上文針對.^環部分」意指包含三個接合環之螺或蘢，或實際上為其組合。』為稠合、在本文中，術語化合物之「治療有效予該化合物之治療」意明包含投 ' 中足以治癒、減輕或部分抑制指定 13 200906801 疾病及其併發症之臨床表現之量。足以實現此目的之量定 ::广療有效里」。達成各目的之有效量將視個體之疾病或知傷嚴重程度以及體重及—般狀況而^。應瞭解，可使二常規實驗’藉由建造多值矩陣且測試矩陣中之不同點獲得適當劑量，此均在受訓醫師一般技能内。在本文中，術語「治療」意謂管理及照料患者以達抗击兄（諸如疾病或病症）之目的。該術語意欲包括患者 1〜之扣疋病況的全範圍治療，諸如投予活性化合物以減 p症狀或併發症、延遲疾病、病症或病況之進展、減輕或；狀及併發症及/或治癒或消除疾病、病症或病況以及預防病況，波由h & ，、干預防應理解為管理及照料患者以達抗擊疾 :兄或病症之目的，且包括投予活性化合物以預防症太5 、症之發作。然而，預防性（防止性）及治療性（治癒性）治療為太旅么月之兩個獨立態樣。待治療之患者較佳為哺乳動物，尤其為人類。Examples of V suitable organic acids include formic acid, acetic acid, trichloroacetic acid, trifluoroacetic acid, propionic acid, benzoic acid, cinnamic acid, citric acid, fumaric acid, glycolic acid, itaconic acid, lactic acid, decane sulfonate. Acid, maleic acid, malic acid, malonic acid, mandelic acid, oxalic acid, picric acid, pyruvic acid, salicylic acid, acesulfonic acid, decanesulfonic acid, ethanesulfonic acid, tartaric acid, ascorbic acid, bishydroxy Naphthoic acid, bismethylene salicylic acid, ethane disulfonic acid, gluconic acid, citraconic acid, aspartic acid, stearic acid, palmitic acid, EDTA, glycolic acid, p-aminobenzoic acid, glutamine Acid, stupid sulfonic acid, p-butanesulfonic acid, theophylline acetic acid, and 8-halotheophylline, such as 8-bromophylline and the like. Pharmaceutically acceptable mineral acid additions 12 200906801 Salt or organic acid additions to sleep Other examples include the pharmaceutically acceptable texts listed in J. Pharm. Sci. 1977, 66, 2. Examples of the metal salt include a lithium salt, a sodium salt, a potassium salt, a magnesium salt, and the like, which are incorporated herein by reference. Examples of the salt and the alkylated ammonium salt include ammonium salts, Base, dimethyl-, :methyldiethyl-hydroxyethyl-, diethyl-, n-butyl-, second butyl first butyl-, tetramethylammonium salt and the like. In the selection of the text, '"ring atom" means the atom constituting the ring' and the ring atom evades from C, N, Π 烟 c. 3 As an example, both benzene and toluene have 6 carbons, and It has 5 carbons and 1 nitrogen as a ring atom. In this context, "set: & rr \ structure. Similarly, "雔 = min" means that only one ring is formed into a loop. Two loops are available in each ring: a knife is meant to include two joint rings. The structure. Bicyclic moiety I: Two = ring atomic junctions, in which case the ring is exemplified by a double ring moiety in a single ring. Or, two snails...oxo-bonded, in this shape... Example. Alternatively, the two rings may be in the [4.5] decane as a snail form of the bicyclic moiety, &, brother in magnetic at each of the two non-adjacent ring atoms, in the case of 双4, the bicyclic portion An example of a double-loop portion of a mouthpiece. "_", " H double loop [3·2.2] is a structure. As described above, the "ring portion" means a screw or a snail containing three joint rings, or a combination thereof. "Fused, herein, the term "therapeutic effective treatment of the compound" is intended to encompass an amount sufficient to cure, alleviate or partially inhibit the clinical manifestations of the disease and its complications. A quantity that is sufficient for this purpose. The effective amount for each purpose will depend on the individual's disease or the severity of the injury and the weight and general condition. It will be appreciated that the second routine experiment can be performed by constructing a multi-valued matrix and different points in the test matrix to obtain appropriate doses, all within the general skill of the trained physician. As used herein, the term "treatment" means the management and care of a patient for the purpose of combating a brother, such as a disease or condition. The term is intended to include a full range of treatments for the patient's condition, such as administration of the active compound to reduce the symptoms or complications of the p, delaying the progression of the disease, condition or condition, alleviation or complication and/or healing or Eliminating diseases, illnesses or conditions and preventing conditions, wave by h &, dry prevention should be understood as managing and caring for patients to fight the disease: the purpose of the brother or illness, and including the administration of active compounds to prevent the disease too 5, The attack. However, prophylactic (preventive) and therapeutic (healing) treatments are two separate aspects of the month. The patient to be treated is preferably a mammal, especially a human.

【實施方式】發明詳述本發明之化合物係由下式ι所定 14 200906801 R14[Embodiment] DETAILED DESCRIPTION OF THE INVENTION The compound of the present invention is determined by the following formula: 14 200906801 R14

其中A表示N、CH或CR1 ; 其中各R1獨立地表示氫、Ci 6烷基、C2_6烯基、c 炔基、-qco-Cw烷基、-c(0)_c2_6烯基、-c(0)-c2_6 炔基、 -CCCO-O-Cu 烷基、-c(o)-o-c2.6 烯基、-c(o)-o-c2.6 块基或苯基，其中該苯基、Cw烷基、（：2_6烯基或C2·6炔基視情況經一或多個選自以下基團之取代基取代：_素、經基、 A基Cw烷基、硝基、Cl6烷氧基及nr2r3 ; 其中X表示氫'Cw烷基、Cw烯基、c：2·6炔基、氰基、 -OR2、-0_C(0)R2、_〇c(〇)nr2r3、_c(〇)_nr2r3、_ N(R2)c(o)R3、_n(r2)_c(0)nr2r3 或 N 2 欢入衣不具有 4-16個環原子之單環、雙環或三環部分，環原子中之— 為氮，且其中1個、2個或3個額外環原子可為選自者及S之雜原子，且其中該單環、雙環或三環、N、〇經一或多個取代基w取代，其中w 77 °視情況去β 1 / 選自虱、羥基、鹵素、亂基、（=〇)、-0_(CH2)c_0-，其中 C 為 2 或 3 其中d為5或6(螺）、C,.6烷基、C2_6烯基、Γ 2d 2-6块基、C卜6 15 200906801 烷氧基、-CCCO-Cw 烷基、_c(0)-C2.6 烯基、_c(0)-C2_6 炔基、-C(0)-0-Ch6 烷基、_c(0)-0-C2.6 烯基、_c(0)-0-C2_6 炔基、-O-CCCO-Cu 烷基、_0_c(0)_c2 6 烯基、_〇_c(〇)_c2 6 炔基、-C(0)H、COOH;或其中 W 表示式 _(CH2)a_Y_(CH2)b_z 之部分；其中a及b獨立地表示選自〇、丨、2及3之整數；其中 Y 表示一鍵、c(0)、0、S、-o-c(o)、(：(0)-〇-、 -NR2·、-NR2-C(0)-、-C(〇)-NH-或 S(0)2 ; 其中z表示氫、Ci_6烷基、NR2R3、氰基或包含個環原子之單環或稠合雙環部分，環原子中視情況丨個、 2個或3個為選自N、〇及s之雜原？，且其十該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：虐素、氰基、Ci 0烷基、羥基及k烷氧基比啡基、本基、0比0定基及經鹵素取代之苯基； "其中R丨3_R"中之每一者獨立地表示氫、C丨·6烷基、C2 6烯基、C2·6炔基、鹵素、NR2R3、羥美不氰基、硝基、c〗.6烷氧基、鹵基Ci-6烷基或 2 、中R及R3獨立地表示氫、Ci·6烷基、Cw烯炔基、羥基Cl.6烷基、齒基q_6烷基或苯基；土、 2·6 及其醫藥學上可接受之鹽。在一具體實例中，R、R*表示氫。在一具體實例中，R9_Rl2表示氫。在一具體實例中，Rl3_Rn表示氫。在一具體實例中，本發明化合物係由式h所定義： 16 200906801Wherein A represents N, CH or CR1; wherein each R1 independently represents hydrogen, Ci6 alkyl, C2_6 alkenyl, c alkynyl, -qco-Cw alkyl, -c(0)_c2_6 alkenyl, -c(0 )-c2_6 alkynyl, -CCCO-O-Cu alkyl, -c(o)-o-c2.6 alkenyl, -c(o)-o-c2.6 or phenyl, wherein the phenyl , Cw alkyl, (: 2_6 alkenyl or C2 · 6 alkynyl optionally substituted by one or more substituents selected from the group consisting of: _, trans, A, C, alkyl, nitro, Cl6 Oxyl and nr2r3; wherein X represents hydrogen 'Cw alkyl, Cw alkenyl, c: 2·6 alkynyl, cyano, -OR2, -0_C(0)R2, _〇c(〇)nr2r3, _c(〇 )_nr2r3, _ N(R2)c(o)R3, _n(r2)_c(0)nr2r3 or N 2 is a monocyclic, bicyclic or tricyclic moiety having 4-16 ring atoms, in a ring atom - is nitrogen, and wherein one, two or three additional ring atoms may be a hetero atom selected from the group consisting of S, and wherein the monocyclic, bicyclic or tricyclic, N, fluorene has one or more substituents w substitution, where w 77 ° optionally depends on β 1 / selected from hydrazine, hydroxy, halogen, chaotic, (=〇), -0_(CH2)c_0-, where C is 2 or 3 wherein d is 5 or 6 ( Spiro), C, .6 alkyl, C2_6 alkenyl Γ 2d 2-6 block base, CBu 6 15 200906801 alkoxy group, -CCCO-Cw alkyl group, _c(0)-C2.6 alkenyl group, _c(0)-C2_6 alkynyl group, -C(0)- 0-Ch6 alkyl, _c(0)-0-C2.6 alkenyl, _c(0)-0-C2_6 alkynyl, -O-CCCO-Cu alkyl, _0_c(0)_c2 6 alkenyl, _〇 _c(〇)_c2 6 alkynyl, -C(0)H, COOH; or wherein W represents a moiety of the formula _(CH2)a_Y_(CH2)b_z; wherein a and b are independently selected from 〇, 丨, 2 And an integer of 3; where Y represents a bond, c(0), 0, S, -oc(o), (:(0)-〇-, -NR2·, -NR2-C(0)-, -C (〇)-NH- or S(0)2; wherein z represents hydrogen, Ci_6 alkyl, NR2R3, cyano or a monocyclic or fused bicyclic moiety containing a ring atom, as the case may be, 2 or 3 are heterogenes selected from N, oxime and s, and 10 of the monocyclic or fused bicyclic moieties are optionally substituted by one or more substituents selected from the group consisting of: narcisin, cyanide a base, a Ci 0 alkyl group, a hydroxyl group and a k alkoxy group, a benzyl group, a 0-0 base group, and a halogen-substituted phenyl group; " wherein each of R丨3_R" independently represents hydrogen, C丨·6 alkyl, C 2 6 alkenyl, C 2 ·6 alkynyl, , NR2R3, hydroxymethicone, nitro, c. 6. alkoxy, haloCi-6 alkyl or 2, R and R3 independently represent hydrogen, Ci.6 alkyl, Cw alkynyl , hydroxyCl.6 alkyl, dentyl q_6 alkyl or phenyl; earth, 2.6 and pharmaceutically acceptable salts thereof. In a specific example, R, R* represent hydrogen. In a specific example, R9_Rl2 represents hydrogen. In a specific example, Rl3_Rn represents hydrogen. In a specific example, the compound of the invention is defined by the formula h: 16 200906801

[la][la]

其中A表示N、CH或CR1 ; 其中各R1獨立地表示氫、（V6烷基、-(^(CO-Cw烷基、 _(：(〇)-〇-^·6烷基或苯基，其中該苯基或Cl —烷基視情況經一或多個選自以下基團之取代基取代：_素、羥基、函基Cw烷基、硝基、Cl_6烷氧基及NR2R3 ; 其中X表示氫、c!.6烷基、氰基 -u-U(〇)R2 、 •〇C(0)NR2R3 , -C(0)-NR2R3 ^ -N(R2)C(0)R3 > -N(R2).C(〇)Wherein A represents N, CH or CR1; wherein each R1 independently represents hydrogen, (V6 alkyl, -(^(CO-Cw alkyl, _(:(〇)-〇-^.6 alkyl or phenyl, Wherein the phenyl or Cl-alkyl group is optionally substituted with one or more substituents selected from the group consisting of: -, hydroxy, Cf alkyl, nitro, Cl-6 alkoxy and NR2R3; wherein X represents Hydrogen, c..6 alkyl, cyano-uU(〇)R2, •〇C(0)NR2R3, -C(0)-NR2R3^-N(R2)C(0)R3 > -N(R2 ).C(〇)

Nr2r3或NR2R3，或X表示具有4-16個環原子之單環、雙 %或三環部分，環原子中之一者為氮，且其中1個、2個或3個額外環原子可為選自N、0及S之雜原子，且其中 „亥單環、雙環或二環部分可視情況經一或多個取代基W取代其中W係選自氫、羥基、鹵素、氰基、… (CHU，其中4 2或3(螺）、（cH2)d,其中d為5或6(螺）、烷基、Cw 烷氧基、烷基、基、-〇-c(o)_Cl 6 烷基、_c(〇)H、c〇〇H ;或 1 ’元式-(CH2)a-Y_(CH2)b_z 之部分；、"表示 17 200906801 其中a及b獨立地表示選自0、1、2及3之整數；其中 Y 表示一鍵、C(O)、◦、S、-〇-C(0)… -NR2- ' -NR2-C(0)-、-C(0)-NH-或 S(〇)2 ; 其中Z表示氫、C!-6烷基、NR2R3、氰基或包含4至12 個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、0及S之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：鹵素、氰基、Ci.6烷基、羥基及Ci 6 .家l 基、°比啡基、苯基、吼咬基及經鹵素取代之苯基；其中R4-R8、R9-Ri2及R13-Ri7中之每一者獨立地表示虱、C〗-6烧基、C2_6烯基、C2_6炔基、鹵素、]SiR2R3、經基、氰基、硝基、C!—6烷氧基、鹵基C!_6烷基或羥基Ci-6烷基；其中R2及R3獨立地表示氫、Cw烷基、C2-6烯基、c 炔基、羥基C!_6烷基、函基Cm烷基或苯基；及其醫藥學上可接受之鹽。詳言之，A表示CH且R1表示c!.6烷基，諸如乙基或環丙基。在本發明化合物係由式Ia所定義之一具體實例中，χ 表示氫、CV6 烷基、氰基、-0r2、_〇_c(0)R2、-0C(0)NR2R3、 -C(〇)-NR2R3-、-N(R2)C(〇)r3、-N(R2)-C(0)NR2R3 或 NR2R3，其中R2及R3獨立地表示氫、CV6烷基、羥基Cw烷基、鹵基（^-6烷基或苯基。詳言之，χ表示氫、甲基或nr2R3，其中R2及R3獨立地表示氫、Cl 6烷基或羥基Cl.6烷基，且尤其提及R2及R3獨立地表示氫、環丙基甲基、曱基、乙基或環丙基。 18 200906801 在本發明化合物係由4 Ia所定義之_具體實例中，x 表示具有4_16個環原子之單環、雙環或三環部分，環原子 y之-者為氮’且其中i個、2個或3個額外環原子可為 h自Ν Ο及s之雜原子，且其中該單環、雙環或三環部分可視情況經一或多個取代基w取代，其中w係選自氫、羥基、㈣、氰基十〇)、_〇_(CH2)c-〇·，其中。為2或3⑻、 (CH2)d，其中以5或6(螺）、Ci6烧基、氧基、_c叫c 烷基、-c⑼-〇_u基、_〇_c(〇) Ci 6 烧基、_〇啊二 C(0)H、COOH ;或其中 w 表示式 _(CH2)a Y (cHA_z 部分；其中a及b獨立地表示選自^卜之^之整數；其中 Y表示-鍵、C(0)、0、s、_〇_c(〇)、_c(〇)_〇·、 -NR -、-NR2-C(〇)-、_C(〇)_NH 或 s(〇h ; 其中Z表示氫、C16烧基、NR2R3、氰基或包含4至U 個環原子之單環或稠合雙環部分，環原子中視情況i個、 2個或3個為選自]^、〇及8夕皰庙工 ^ 次^之雜原子，且其中該單環或稠合雙核部分視情況經一或多也|、登ή山月几4次夕個選自由以下基團組成之群的取代基取代：_素、氰基、〜土 1!·6烷基、羥基及Ci.6烷氧基、吡啡基、苯基、吡啶基及經齒素取代之苯基；其中R2及R3獨立地表示氫、風Cl-6烷基、羥基（：丨-6烷基、鹵基Cw烷基或苯基。在本發明化合物係由式I — 主_ a > 田八、所疋義之一具體實例中，x 表不具有5個環原子之單援邱日甘Α 卞之皁W分’環原子中之-者為氮，且八中1個、2個或3個額外ρ ^ ,Nr2r3 or NR2R3, or X represents a monocyclic, double or tricyclic moiety having 4 to 16 ring atoms, one of the ring atoms is nitrogen, and one, two or three additional ring atoms may be selected From the heteroatoms of N, 0 and S, and wherein the monocyclic, bicyclic or bicyclic moiety is optionally substituted with one or more substituents W wherein the W is selected from the group consisting of hydrogen, hydroxy, halogen, cyano, ... (CHU Wherein 4 2 or 3 (spiro), (cH2)d, wherein d is 5 or 6 (spiro), alkyl, Cw alkoxy, alkyl, yl, -〇-c(o)-Cl 6 alkyl, _c(〇)H, c〇〇H; or a part of 1 'element-(CH2)a-Y_(CH2)b_z; , " indicates 17 200906801 where a and b independently represent 0, 1, 2 And an integer of 3; wherein Y represents a bond, C(O), ◦, S, -〇-C(0)... -NR2- '-NR2-C(0)-, -C(0)-NH- or S(〇)2; wherein Z represents hydrogen, C!-6 alkyl, NR2R3, cyano or a monocyclic or fused bicyclic moiety containing from 4 to 12 ring atoms, as the case may be 1, 2 or 3 a hetero atom selected from N, 0 and S, and wherein the monocyclic or fused bicyclic moiety is optionally one or more selected from the group consisting of the following groups Substituent substitution: halogen, cyano, Ci.6 alkyl, hydroxy and Ci 6 . yl, phenyl, phenyl, thiol and halogen substituted phenyl; wherein R4-R8, R9- Each of Ri2 and R13-Ri7 independently represents 虱, C -6 alkyl, C 2_6 alkenyl, C 2_6 alkynyl, halogen, ]SiR 2 R 3 , thiol, cyano, nitro, C -6 alkoxy a halogen group, a C?-6 alkyl group or a hydroxy Ci-6 alkyl group; wherein R2 and R3 independently represent hydrogen, Cw alkyl, C2-6 alkenyl, c alkynyl, hydroxy C!-6 alkyl, and Cm An alkyl or phenyl group; and a pharmaceutically acceptable salt thereof. In particular, A represents CH and R1 represents c..6 alkyl, such as ethyl or cyclopropyl. The compounds of the invention are those of formula Ia. In one specific example, χ represents hydrogen, CV6 alkyl, cyano, -0r2, _〇_c(0)R2, -0C(0)NR2R3, -C(〇)-NR2R3-, -N(R2 C(〇)r3, -N(R2)-C(0)NR2R3 or NR2R3, wherein R2 and R3 independently represent hydrogen, C6 alkyl, hydroxy Cw alkyl, halo (^-6 alkyl or phenyl) In particular, χ represents hydrogen, methyl or nr2R3, wherein R2 and R3 independently represent hydrogen, Cl 6 alkyl or hydroxy C.6 alkyl, and in particular R2 R3 independently represents hydrogen, cyclopropylmethyl, decyl, ethyl or cyclopropyl. 18 200906801 In the case where the compound of the invention is defined by 4 Ia, in the specific example, x represents a single ring having 4 to 16 ring atoms. a bicyclic or tricyclic moiety, wherein the ring atom y is nitrogen' and wherein i, 2 or 3 additional ring atoms may be heteroatoms of h from Ν and s, and wherein the monocyclic, bicyclic or tertiary The ring moiety may optionally be substituted with one or more substituents w, wherein w is selected from the group consisting of hydrogen, hydroxy, (iv), cyanodecene, _〇_(CH2)c-〇. Is 2 or 3 (8), (CH2)d, wherein 5 or 6 (spiro), Ci6 alkyl, oxy, _c is c alkyl, -c(9)-〇_u, _〇_c(〇) Ci 6 is burned Base, _〇二 two C(0)H, COOH; or where w represents the formula _(CH2)a Y (cHA_z portion; where a and b independently represent an integer selected from ^^^; where Y represents a - bond , C(0), 0, s, _〇_c(〇), _c(〇)_〇·, -NR-, -NR2-C(〇)-, _C(〇)_NH or s(〇h; Wherein Z represents hydrogen, C16 alkyl, NR2R3, cyano or a monocyclic or fused bicyclic moiety containing 4 to U ring atoms, and wherein i, 2 or 3 of the ring atoms are selected from the group consisting of 8 疱庙庙 ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ Substituents: _, cyano, 1,4- 1 1-6 alkyl, hydroxy and Ci. 6 alkoxy, pyranyl, phenyl, pyridyl and phenyl substituted by dentate; wherein R 2 and R 3 are independent Hydrogen, wind Cl-6 alkyl, hydroxy (: 丨-6 alkyl, halo Cw alkyl or phenyl. The compound of the invention is of formula I - main _ a > 8. In one specific example of the derogatory case, the x table does not have 5 ring atoms of the single aid Qiu Ri Gan Α 卞卞 W W W ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' Extra ρ ^ ,

〇個頸外％原子可為選自Ν、Ο及S 之雜原子，且其中該單環部分干衣司刀可視情況經一或多個取代基 19 200906801 W取代，其中W係選自氫、羥基、鹵素、氰基、（=0)、_ 0-(CH2)c-0-，其中c為2或3(螺）、（CH2)d，其中d為5或 6(螺）、cK6 烷基、Ci 6 烷氧基、_c(0)_Ci 6 烷基、_c(〇)_〇_ Cl-6 烷基、-O-QCO-Cu 烷基、-O-C(O)-、-C(0)H、COOH ; 或其中W表示式_(CH2)a_Y_(CH2)b_z部分；干a及b獨立地表示選自〇、I 其中 Y 表示一鍵、C(0)、〇、s、_〇_c(〇)、_c(〇)_〇_ -NR2_、_NR2-C(0)-、-C(0)-NH-或 s(0)2 ; 成其中2表示氫、〇：16烷基、从[12尺3、氰基或包含4至12 個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或”固為選自m 3之雜原子，且其中該單環或 =:::部分視情況經一或多個選自由以下基團組成之群 A 土取代·齒素、氰基、Ci-6院基、經基及Cl 6燒氧土、㈣基、苯基"比°定基及經i素取代之苯基； J二* 立地表示氫、CM烧基、經基基、由基k烷基或苯基。該具有邱之實例包括。比略m対、里=子之早&部分咯啉、四唑、咪唑，、坐、吡咯啶、吡咪啉、吡唑啶及吡唑啉。在本明化合物係由式rThe one-corner % atom may be a hetero atom selected from the group consisting of ruthenium, osmium, and S, and wherein the single-ring portion of the dry-knife knife may be optionally substituted with one or more substituents 19 200906801 W, wherein the W system is selected from the group consisting of hydrogen, Hydroxyl, halogen, cyano, (=0), _ 0-(CH2)c-0-, wherein c is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), cK6 alkane , Ci 6 alkoxy, _c(0)_Ci 6 alkyl, _c(〇)_〇_Cl-6 alkyl, -O-QCO-Cu alkyl, -OC(O)-, -C(0 H, COOH; or where W represents the formula _(CH2)a_Y_(CH2)b_z; stems a and b independently represent 〇, I where Y represents a bond, C(0), 〇, s, _〇 _c(〇), _c(〇)_〇_-NR2_, _NR2-C(0)-, -C(0)-NH- or s(0)2; wherein 2 represents hydrogen, 〇:16 alkyl From [12 ft 3, cyano or a monocyclic or fused bicyclic moiety containing 4 to 12 ring atoms, as the case may be 1, 2 or "solid" a hetero atom selected from m 3 , and wherein The monocyclic or =::: moiety is optionally substituted by one or more groups A selected from the group consisting of: dentate, cyano, Ci-6, thiol, and pyridene, (4) , phenyl " ratio ° base and by i Substituted phenyl; J bis* stands for hydrogen, CM alkyl, via, benzyl or phenyl. Examples of the qi include: slightly earlier than m対, 里 = early & a porphyrin, a tetrazole, an imidazole, a sityr, a pyrrolidine, a pyridinium, a pyrazolidine, and a pyrazoline.

表示具有6個環原； -體實例中，X 且其中！個、2個^〜刀’環原子中之-者為氮， 2個或3個額外環原Indicates that there are 6 ring primitives; - in the body instance, X and where! One, two ^~ knives, among the ring atoms, are nitrogen, two or three additional ring

之雜原子’且其中該單環^ 了為選自N、0及S W取代，其中w 刀一 f月况經—或多個取代基 0-(CH2)c-〇_，ι 中11、經基、鹵素、氰基、（=0)、_ 或3(螺）卞灿，其中或 20 200906801 6(螺）、CV6 烷基 ' Cl.6 烷氧基、-c(0)_ci-6 烷基、-C(0)-〇-ci-6 烧基、-0-C(0)-C卜6 炫基、-〇_C(〇)-、-C(0)H、COOH ; 或其中W表示式_(cH2)a_Y_(CH2)b-Z部分；其中a及b獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、C(O)、◦、S、-O-C(O)、-C(0)-〇-、 -NR2-、-NR2-C(〇)-、-C(0)-NH-或 S(0)2 ; 其中Z表示氫、c!·6烷基、NR2R3、氰基或包含4至12 個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、〇及s之雜原子，且其中該單環或稠合雙％部分視情況經一或多個選自由以下基團組成之群的取代基取代：i素、氰基、Ci 6烷基、羥基及Cw烷氧基、吡啡基、苯基、吡啶基及經鹵素取代之苯基；其中R及R獨立地表示氫、C16院基、經基C】_6烧基、齒基烧基或苯基。該具有6個環原子之單環部分之實例包括吡啶、吡畊、嘧 ^ 嚯疋合啡、哌啶、哌啡 '二氫吼啶、四氫吼啶及嗎福林。在本發明化合物传± a τ &a hetero atom 'and wherein the monocyclic ring is selected from the group consisting of N, 0 and SW substitutions, wherein the w-knife is a month-- or a plurality of substituents 0-(CH2)c-〇_, i. Base, halogen, cyano, (=0), _ or 3 (spiro), wherein or 20 200906801 6 (spiro), CV6 alkyl 'Cl. 6 alkoxy, -c(0)_ci-6 alkane Base, -C(0)-〇-ci-6 alkyl group, -0-C(0)-Cb6 炫, -〇_C(〇)-, -C(0)H, COOH; or W represents a formula _(cH2)a_Y_(CH2)bZ moiety; wherein a and b independently represent an integer selected from 〇, 1, 2, and 3; wherein Y represents a bond, C(O), ◦, S, -OC (O), -C(0)-〇-, -NR2-, -NR2-C(〇)-, -C(0)-NH- or S(0)2; wherein Z represents hydrogen, c!·6 An alkyl group, NR2R3, cyano group or a monocyclic or fused bicyclic moiety containing 4 to 12 ring atoms, wherein one, two or three of the ring atoms are heteroatoms selected from N, fluorene and s, and wherein The monocyclic or fused double % moiety is optionally substituted with one or more substituents selected from the group consisting of i, cyano, Ci 6 alkyl, hydroxy and C alkoxy, pyrenyl a phenyl group, a pyridyl group and a halogen-substituted phenyl group; wherein R And R independently represents hydrogen, a C16 building group, a trans group C)-6 alkyl group, a dentate group or a phenyl group. Examples of the monocyclic moiety having 6 ring atoms include pyridine, pyridin, pyrimidine, piperidine, piperidine 'dihydroacridine, tetrahydroacridine and ifolin. In the compounds of the invention, ± a τ &

’、式a所定義之一具體實例中，X 表示具有7個環原子 ,,, 之早糸部分，環原子中之一者為氮，且其中1個、2個或3個雜& _ Ε 個額外％原子可為選自Ν、〇In a specific example defined by the formula a, X represents 7 ring atoms, ,, the early 糸 moiety, one of the ring atoms is nitrogen, and one, two or three of them are _ Ε Extra % of atoms can be selected from Ν, 〇

之雜原子’且其中該單俨加ν 、 ujn。及S w取代，中W γ衣°P y刀可視情況經一或多個取代基 W取代其中w係選自氫、經 o-(ch2)c-o-，其中 c 為）+ 图京氣基、（-0)、- 6⑻、C 或3(螺）、（<：灿，其中d為5或 6(螺）Cl J基、匕6缔基烧基、-C(0)-C,6 土、_〇-c(〇)_Ci 6 烷基、_c(〇)H、 21 200906801 COOH ;或其中W表示式—(cH2)a_Y_(CH2VZ部分；其中a及1?獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、c(0)、0、S、-o-c(o)、、 -NR2-、-NR2-C(0)-、-C(0)-NH_ 或 S(0)2 ; 其中Z表示氫、Ci·6烷基、NR2R3'氰基或包含4至12 個環原子之單環或稠合雙環部分，環原子中視情況丨個、 2個或3個為選自N、〇及s之雜原+，且其中該翠環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：齒素、氣基、Ci6烧基、經基及k燒氧基、吡畊基、苯基、吡啶基及經卣素取代之苯基；其中V及V獨立地表示氫、k烧基、;基CM烧基:鹵基Cl_6 &基或苯基。該具有7個環原子之單環部分之貝例包括氮雑環庚烷（azepa ) 〇 , , , ^ ； U，4]—氮雑環庚烷及 2,3,4,5-四虱-1H-[1，4]二氮雑環庚烷。在本發明化合物係由式j所定The hetero atom 'and the 俨, ν, ujn. And S w substitution, wherein the W γ γ°P y knife can be replaced by one or more substituents W, wherein w is selected from hydrogen, via o-(ch2)co-, wherein c is)+ (-0), - 6 (8), C or 3 (spiro), (<: can, where d is 5 or 6 (spiro) Cl J group, 匕6 aryl group, -C(0)-C, 6 Soil, _〇-c(〇)_Ci 6 alkyl, _c(〇)H, 21 200906801 COOH; or wherein W is a formula - (cH2)a_Y_ (CH2VZ moiety; wherein a and 1? independently represent an oxime, An integer of 1, 2, and 3; wherein Y represents a bond, c(0), 0, S, -oc(o), -NR2-, -NR2-C(0)-, -C(0)-NH_ Or S(0)2; wherein Z represents hydrogen, Ci.6 alkyl, NR2R3'cyano or a monocyclic or fused bicyclic moiety containing 4 to 12 ring atoms, as the case may be, 2 or 3 And the fused ring moiety is optionally substituted with one or more substituents selected from the group consisting of dentate, gas, a phenyl group substituted with a hexyl group, a benzyl group, a phenyl group, a pyridyl group, a phenyl group, a pyridyl group and a halogen; wherein V and V independently represent hydrogen, a k-alkyl group; a group of Cl_6 & phenyl or phenyl. The shell of the monocyclic moiety having 7 ring atoms includes azepa 庚, , , ^; U, 4]-azacycloheptane and 2, 3,4,5-tetraindole-1H-[1,4]diazepine cycloheptane. The compounds of the invention are determined by formula j

s 疋義之一具體實例中，X 表不，、有8個％原子之單環或雙 ό ^ 叉衣#分，核原子中之一者為11，且其中1個、2個或3個額外環及S之雜疮工 ^ 衣原子可為選自N、〇及S之雜原子，且其中該單環或雙環部分可In one specific example of s 疋 ,, X is not, there are 8% atomic single ring or double ό ^ forks # points, one of the nuclear atoms is 11, and one, two or three additional The ring of the ring and the S soothing agent can be a hetero atom selected from N, 〇 and S, and wherein the single ring or double ring part can be

多個取代基w取代，其中W係選自月/ A S 基、（=〇)、-〇-(CH2)c-0_，其中。為2風、f基、齒素、氰其中d為5或6(螺）、Cl.6貌基、烷基、_C(0)-〇_c 浐 A、丨-6 烷虱基、-C(〇)_Cl_6 coom, (〇)·υ基、-c⑼η、或Mw表部分；兵中a及b獨立地表示選自〇' 、2及3之整數； 22 200906801 ，、中 Y 表示一鍵、C(0)、ο、s、-O-C(O)、-c(o)-〇-、 -NR -、.NR2-C(0)-、-C(0)-NH-或 S(0)2 ; 其中Z表示氫、Ci 6烷基、NR2R3、氰基或包含4至個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、〇 & s之雜原子，且其中該單環或稠〇雙％部分視情況經—或多個選自由以下基團組成之群的取代基取代：鹵素、氰基、C】_6炫基、經基及Ci 6燒氧基比啡基、笨基、。比°定基及經鹵素取代之苯基；其中R2及R3獨立地表示氫、Ci 6烷基、羥基Cw烷基、鹵基烷基或苯基。該具有8個環原子之單環或雙裒口P刀之只例包括；!昆咬（quinnucHdine )、8·氮雜-雙環[3 2 1] 辛烧及2-氮雜-雙環[2·2.辛烷。在本發明化合物係由< Ia所定義之一具體實例中，χ 表示具有9個環原子之單環或雙環部分，環原子中之一者為氮且其中1個、2個或3個額外環原子可為選自N、〇及S之雜原子，且其中該單環或雙環部分可視情況經一或多個取代基W取代，其巾胃係選自氫、經基、齒素、氰其中d為5或6(螺）、Cy烷基、Ci6烷氧基、_c(〇)_Ci 6 烧基、-C(〇)-〇_Cl.6 烧基、_〇_c(〇)_Ci6 烧基、_c(〇)h、 COOH ;或其中W表示式_(CH2)a_Y_(CH丄·z部分；其中a及b獨立地表示選自〇、丨、2及3之整數；其中 Y 表示一鍵、C(〇) ' 〇、s、(⑺、_c(⑺_&、 -NR2-、-NR2-C(0)-、-C(0)-NH·或 S⑼2 ; 23 200906801 其中Z表示氮、ρ ^ ^ iSt ^ _ K6烷基、NR R3 '氰基或包含4至12 單環或稠合雙環部分，環原子中視情況1個、二=選自Ν、…之雜原子，且其中該單環或 δ又％〇[5分視情況經一的取代基取代4♦、氰個選自由以Τ基團組成之群基1啡基、，基1::二L广、經基及烧氣定基及經_素取代之苯基；块基及R獨立地表示氫、Ci-6烧基、C2.6稀基、c2_6 環：子t烷基、齒基Cl·6烷基或苯基。該具有9個 ::二Γ哀或雙環部分之實例包括吲哚畊、異吲哚、3乐 '卞口弓口木、1H_〇弓卜坐、臂呤、十朵琳及異十朵琳。在本發明化合物係初係由式1a所定義之一具體實例中，Χ :有1(MSI %原子之單環或雙環部分，環原子中之〜氮且其中1個' 2個或3個額外環原子可為選自N、 ^之雜原子，且其中該單環或雙環部分可視情況經〜個取代基W取代，其巾1係選自氫、經基、㈣、 1 t (、〇) 〇 (CH2)c-〇_ ’ 其中 C 為 2 或 3(螺）、（CH2)d， ^ d為5或6(螺）、Ci 6貌基、c“6燒氧基、兀土、-C(0)-0-Cl.6 烧基、基、_c(〇)H、 C00H ;或其中W表示式-(CH2)a-Y_(CH2 VZ部分；其中a及b獨立地表示選自〇、卜2及3之整數；其中 Y 表示一鍵、C(0)、〇、s、_〇 c(〇)、_c(〇) 〇、 -NR2-、_nr2_c(〇)…_c(〇) Nh 或 s(〇)^ 其中Z表示氫、Ci·6烷基、NR2R3、氰基或包含斗至個環原子之單環或稠合雙環部分，㈣子中視情況1個、 24 200906801 2個或3個為選自N' 〇及s之雜原子’且其中該單環或稠合雙環部分視情況經—或多個選自由以下基團組成之群的取代基取代：_素、氰基、Ci6院基、經基及U氧基、吡啡基、笨基、吡啶基及經齒素取代之苯基；Substituted by a plurality of substituents w, wherein W is selected from the group consisting of month/A S group, (=〇), -〇-(CH2)c-0_, wherein. Is 2 wind, f base, dentate, cyanogen, where d is 5 or 6 (spiro), Cl.6 base, alkyl, _C(0)-〇_c 浐A, 丨-6 alkyl fluorenyl, -C (〇)_Cl_6 coom, (〇)·υ base, -c(9)η, or Mw table part; in soldiers, a and b independently represent integers selected from 〇', 2, and 3; 22 200906801, where Y represents a bond, C(0), ο, s, -OC(O), -c(o)-〇-, -NR -, .NR2-C(0)-, -C(0)-NH- or S(0) Wherein Z represents hydrogen, Ci 6 alkyl, NR 2 R 3 , cyano or a monocyclic or fused bicyclic moiety containing 4 to ring atoms, and optionally 1, 2 or 3 of the ring atoms are selected from N, 〇 & s heteroatoms, and wherein the monocyclic or fused bis- moieties are optionally substituted with - or a plurality of substituents selected from the group consisting of halogen, cyano, C -6 cyclyl, The base and the Ci 6 alkoxy group are more than a phenyl group. A phenyl group substituted with a halogen group and a halogen group; wherein R2 and R3 independently represent hydrogen, Ci 6 alkyl group, hydroxy Cw alkyl group, haloalkyl group or phenyl group. Examples of the single-ring or double-mouth P-knife with 8 ring atoms include: quinnucHdine, 8 aza-bicyclo[3 2 1] octyl and 2-aza-bicyclo[2· 2. Octane. In a specific example in which the compound of the present invention is defined by <Ia, χ represents a monocyclic or bicyclic moiety having 9 ring atoms, one of the ring atoms is nitrogen and one, two or three additional The ring atom may be a hetero atom selected from the group consisting of N, hydrazine and S, and wherein the monocyclic or bicyclic moiety may be optionally substituted with one or more substituents W, the stomach of which is selected from the group consisting of hydrogen, thiol, dentate and cyanide. Wherein d is 5 or 6 (spiro), Cy alkyl, Ci6 alkoxy, _c(〇)_Ci 6 alkyl, -C(〇)-〇_Cl.6 alkyl, _〇_c(〇)_Ci6 Burning group, _c(〇)h, COOH; or wherein W represents the formula _(CH2)a_Y_(CH丄·z part; wherein a and b independently represent an integer selected from 〇, 丨, 2, and 3; wherein Y represents One bond, C(〇) ' 〇, s, ((7), _c((7)_&, -NR2-, -NR2-C(0)-, -C(0)-NH· or S(9)2; 23 200906801 where Z represents nitrogen , ρ ^ ^ iSt ^ _ K6 alkyl, NR R3 'cyano or contains 4 to 12 monocyclic or fused bicyclic moieties, as in the case of a ring atom, one or two = heteroatoms selected from fluorene, ... Monocyclic or δ and % 〇 [5, depending on the case, the substituent is substituted by 4, and the cyanide is selected from the group consisting of fluorenyl a group consisting of a group of 1 phenyl group, group 1:: two L, a base and a gas-burning base and a phenyl substituted by phenyl; the block and R independently represent hydrogen, Ci-6 alkyl, C2. 6 dilute base, c2_6 ring: sub-t-alkyl, dentate Cl. 6-alkyl or phenyl. Examples of having 9:: dioxins or bicyclic moieties include sorghum, isoindole, 3 Le'卞Mouth bowwood, 1H_〇 bow sitting, arm scorpion, ten lin and ten different lin. In the specific example of the compound of the present invention defined by the formula 1a, Χ: there is 1 (MSI % atom a monocyclic or bicyclic moiety, a nitrogen atom in the ring atom and wherein one '2 or 3 additional ring atoms may be a hetero atom selected from N, ^, and wherein the monocyclic or bicyclic moiety may optionally be ~ Substituted with a substituent W, the towel 1 is selected from the group consisting of hydrogen, thiol, (iv), 1 t (, 〇) 〇(CH2)c-〇_ ' where C is 2 or 3 (spiro), (CH2)d, ^ d Is 5 or 6 (spiro), Ci 6 appearance group, c "6 alkoxy group, alumina, -C(0)-0-Cl.6 alkyl group, group, _c(〇)H, C00H; or The formula -(CH2)a-Y_(CH2 VZ moiety; wherein a and b independently represent an integer selected from the group consisting of 〇, 卜2 and 3; wherein Y represents a , C(0), 〇, s, _〇c(〇), _c(〇) 〇, -NR2-, _nr2_c(〇)..._c(〇) Nh or s(〇)^ where Z represents hydrogen, Ci· 6 alkyl, NR2R3, cyano or a monocyclic or fused bicyclic moiety containing a ring to a ring atom, (iv) as the case, 24 200906801 2 or 3 are heteroatoms selected from N' 〇 and s' And wherein the monocyclic or fused bicyclic moiety is optionally substituted with - or a plurality of substituents selected from the group consisting of: cyano, cyano, Ci6, thiol and oxy, pyridyl a stylyl group, a pyridyl group, and a phenyl substituted by dentate;

其中R2及R3獨立地表示氫、Ci—ό烷基、羥基Ci 6烷基、鹵基C!·6烷基或苯基。該具有1〇個環原子之單環戈雙環部分之實例包括4H-喹畊、異喹啉、喹啉、酞畊、嶠啶、喹聘啉、d辛啉、喋啶、四氫-異喹啉酮、m 三乳雜-螺[4_5]癸烧及1，2,3,4-四氫-喧琳。在一具體貫例中，本發明化合物係由式“所定義， / I η κιWherein R2 and R3 independently represent hydrogen, Ci-decyl, hydroxy Ci6 alkyl, halo C!.6 alkyl or phenyl. Examples of the monocyclic gebicyclic moiety having 1 ring of ring atoms include 4H-quinoline, isoquinoline, quinoline, sorghum, acridine, quinolin, d octyl, acridine, tetrahydro-isoquine Linoleone, m tri-milk-spiro[4_5] anthraquinone and 1,2,3,4-tetrahydro-indole. In a specific example, the compounds of the invention are defined by the formula " / I η κι

1或2 (W)1 or 2 (W)

其中Α表示Ν、CH或CR1 ; 其中各R1獨立地表示氫、CN6烷基、-CCCO-Cu烷基、 -(:(0)-0-(:^烷基或苯基，其中該苯基或Cl_6烷基視情況經一或多個選自以下基團之取代基取代：鹵素、羥基、鹵 25 200906801 基c1-6烷基、硝基、Cl_6烷氧基及nr2r3 ; 其中W係選自氫、羥基、鹵素、氰基、（=〇)、-〇-(CH2)c-〇_，其中c為2或3(螺）、（CH2)d，其中d為5或6(螺）、 1.6 烷基、Cl 6 烷氧基、_C(〇)-Cl.6 烷基、_c(〇)_〇_Ci 6 烷基、-〇-C(〇)_Cl-6 烷基、-C(0)H、COOH ;或其中 w 表示一 (CH2)a-Y_(CH2)b_z 部分；其中a及b獨立地表示選自0、1、2及3之整數；其中 Y 表示一鍵、C(O)、Ο、S、-O-C(O)、_c(〇)-0-、 -NR2-、-NR2-C(0)_、-C(0)-NH-或 S(0)2 ; 其中z表示氫、CV6烷基、NR2R3、氰基或包含4至12 個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、0及S之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：_素、氰基、Cl6烷基、羥基及Cl_6烷氧基、D比啡基、苯基、吼唆基及經鹵素取代之苯基； , 其中R2及R3獨立地表示氫、Cw烷基、羥基Cl.6烷 :K . 基、幽基c〗_6烷基或苯基；及其醫藥學上可接受之鹽。詳言之，A表示CH，且R1表示Cw烷基，諸如乙基或環丙基。在本發明化合物係由式Ib所定義之一具體實例中，w 表示式-(CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、c(o)、〇、S、-o-c(o)、-c(o)-〇_、 -NR2-、-NR2-C(0)-、-C(〇)-NH-或 S(0)2 ; 26 200906801 其中z表示氫、c〗.6烷基、NR2R3、氰基或包含4至12 個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、〇及S之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：函素、氰基、Ci·6烷基、羥基及Ci6烷氧基、吼畊基、苯基、吡啶基及經齒素取代之苯基；其中R2及R3獨立地表示氫、Cu烷基、羥基（^_6烷基、_基Cw烧基或苯基。在另一具體實例中，γ表示— 鍵、C(O)或s(0)2 ;其中a+b為〇、1、2、3或4;且其中 Z表示包含5至12個碳環原子及視情況丨個、2個或3個選自N、〇及s之雜原子之單環或稠合雙環部分，且其中該單環或雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：画素、氰基、Cy烷基、羥基及Ci6 烷氧基、苯基、吡啡基、吡啶基及經鹵素取代之笨基。尤其提及以下具體實例，其中γ表示一鍵或c(〇)，且為〇、1、2或3。詳言之，z包含5_9個環原子，諸如5個、 6個或9個環原子。具有5個環原子之z之實例包括ργΓΓ〇π& 及環戊基；具有6個環原子之2之實例包括苯基、嘧啶基、嗎福林基及吼絲；具有9個環原子之z之實例包括咬喃并[3.2-Cp比啶基。z之特定實例為嗎福林基，其（例如）經氮與W部分之剩餘部分連接，且視情況經一或多個選自由以下基團組成之群的取代基取代：自素、氰基、烧基&基及C"烧氧基、苯基"比啡基、〇比咬基及經齒素絰取代之本基。Z之另一特定實例為哌啶基，#(例 27 200906801 經氮與w部分之剩餘部分連接，且視情況經一或多個選自由以下基團組成之群的取代基取代：豳素、氰基、Cm烷基、羥基及Cl·6烷氧基、苯基、吡阱基、吡啶基及經二: 經取代之笨基。Z之另一特定實例為吡啶基，其（例如）經氮與w部分之剩餘部分連接。z之另一特定實例為吡啶基，其（例如）在2、3或4位置與W部分之剩餘部分連接，且視情況經一或多個選自由以下基團組成之群的取代基取代：1S素、氰基、Cy烷基、羥基及Ci 6烷氧基、吡啡基、苯基、η比咬基及經鹵素取代之苯基。z之另一特定實例為苯基，其視情況經一或多個選自由以下基團組成之群的取代基取代：鹵素、氰基、CW烷基、羥基及CW烷氧基、苯基、吡啡基、吡啶基及經齒素經取代之苯基。Z 之另特疋實例為°比σ各D定基，其視情況經一或多個選自由以下基團組成之群的取代基取代：_素、氰基、C16烷基、經基及C】_6烷氧基、吡哄基、苯基、吡啶基及經_素經取代之苯基。z之另一特定實例為吲哚基，其（例如）在4、 5、6或7位置與W部分之剩餘部分連接，且視情況經一或多個選自由以下基團組成之群的取代基取代：鹵素、氰基、ci·6院基、羥基及Cu烧氧基、苯基、响啡基、吡啶基及經#素取代之苯基。Z之其他特定實例包括環戊基、呋喃并。比啶基、四氫呋喃基、苯并[14]_啡基、苯并以4] 二聘啡基、苯并[I·2·5]噻二唑及喹唑啉基。在本發明化合物係由式Ib所定義之一具體實例中，γ 表示一鍵、C(o)、-C(0)-0-、C(0)-NH-、-〇-或 S(〇)2 ; a+b 28 200906801 C 1 ·6烧基’諸如甲為0、1、2、3或4;且其中2表示氫、基、異丙基、異丁基或第三丁基、取久或氮基。在本發明化合物係由式1所定義之—具體實例中A 表不CH; R〗表示Ci6烷棊’諸如乙基或環丙基，w 自氫、羥基、齒素、氰基、（=0) ' _〇·( 烷氧基、烷基、_c(〇)_〇_c …㈤、卿)d，…為…(螺上^絲中二為 6 烧基、-C(0)H、C00H。在一具體實例中，本發明化合物係由式定Wherein Α represents Ν, CH or CR1; wherein each R1 independently represents hydrogen, CN6 alkyl, -CCCO-Cualkyl, -(:(0)-0-(:^alkyl or phenyl, wherein the phenyl Or a Cl 6 alkyl group is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, halo 25 200906801 base c 1-6 alkyl, nitro, Cl 6 alkoxy and nr 2 r 3 ; wherein W is selected from Hydrogen, hydroxy, halogen, cyano, (=〇), -〇-(CH2)c-〇_, where c is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), 1.6 alkyl, Cl 6 alkoxy, _C(〇)-Cl.6 alkyl, _c(〇)_〇_Ci 6 alkyl, -〇-C(〇)_Cl-6 alkyl, -C(0 H, COOH; or wherein w represents a (CH2)a-Y_(CH2)b_z moiety; wherein a and b independently represent an integer selected from 0, 1, 2, and 3; wherein Y represents a bond, C(O) ), Ο, S, -OC(O), _c(〇)-0-, -NR2-, -NR2-C(0)_, -C(0)-NH- or S(0)2; where z Represents hydrogen, CV6 alkyl, NR2R3, cyano or a monocyclic or fused bicyclic moiety containing from 4 to 12 ring atoms. One, two or three of the ring atoms are optionally selected from N, 0 and S. Atom, and wherein the monocyclic or fused bicyclic moiety Substituted by one or more substituents selected from the group consisting of: γ, cyano, Cl 6 alkyl, hydroxy and Cl 6 alkoxy, D morphinyl, phenyl, fluorenyl and substituted by halogen And phenyl; A, A represents CH, and R1 represents Cw alkyl, such as ethyl or cyclopropyl. In a specific example in which the compound of the invention is defined by formula Ib, w represents the formula -(CH2)aY-(CH2) a bZ moiety; wherein a and b independently represent an integer selected from the group consisting of 〇, 1, 2, and 3; wherein Y represents a bond, c(o), 〇, S, -oc(o), -c(o)-〇 _, -NR2-, -NR2-C(0)-, -C(〇)-NH- or S(0)2; 26 200906801 where z represents hydrogen, c..6 alkyl, NR2R3, cyano or contains a monocyclic or fused bicyclic moiety of 4 to 12 ring atoms, wherein 1, 2 or 3 of the ring atoms are heteroatoms selected from N, fluorene and S, and wherein the monocyclic or fused bicyclic moiety The situation is substituted by one or more substituents selected from the group consisting of: a element, a phenyl group, a Ci. 6 alkyl group, a hydroxyl group, and a Ci6 alkoxy group, a hydrazine group, a phenyl group, a pyridyl group, and a dentate substituted phenyl group; wherein R 2 and R 3 independently represent hydrogen, a Cu alkyl group, a hydroxyl group (^ _6 alkyl, _ group Cw alkyl or phenyl. In another embodiment, γ represents — bond, C(O) or s(0)2; wherein a+b is 〇, 1, 2, 3 or 4; and wherein Z represents 5 to 12 carbon ring atoms And optionally, 2 or 3 monocyclic or fused bicyclic moieties selected from the heteroatoms of N, hydrazine and s, and wherein the monocyclic or bicyclic moiety is optionally selected from the group consisting of one or more The substituents of the constituent group are substituted: a pixel, a cyano group, a Cy alkyl group, a hydroxyl group, and a Ci6 alkoxy group, a phenyl group, a pyridyl group, a pyridyl group, and a halogen-substituted stupid group. In particular, the following specific examples are mentioned, wherein γ represents a bond or c (〇) and is 〇, 1, 2 or 3. In particular, z contains 5-9 ring atoms, such as 5, 6 or 9 ring atoms. Examples of z having 5 ring atoms include ργΓΓ〇π& and cyclopentyl; examples of 2 having 6 ring atoms include phenyl, pyrimidinyl, fluolinin and fluorene; z having 9 ring atoms Examples include chitosan and [3.2-Cp than pyridine. A specific example of z is holphalin, which is, for example, attached to the remainder of the W moiety via nitrogen, and optionally substituted with one or more substituents selected from the group consisting of: arginyl, cyano , burnt base & base and C " alkoxy, phenyl " phenanthrenyl, oxime base and dentate 绖 substituted base. Another specific example of Z is piperidinyl, #(Example 27 200906801 is attached to the remainder of the w moiety via nitrogen, and optionally substituted with one or more substituents selected from the group consisting of: halogen, a cyano group, a Cm alkyl group, a hydroxyl group and a Cl. 6 alkoxy group, a phenyl group, a pyridyl group, a pyridyl group, and a second: substituted group. Another specific example of Z is a pyridyl group, which is, for example, Nitrogen is attached to the remainder of the w moiety. Another specific example of z is pyridinyl, which is attached, for example, at the 2, 3 or 4 position to the remainder of the W moiety, and optionally one or more selected from the group consisting of Substituents of the group consisting of 1S, cyano, Cy alkyl, hydroxy and Ci 6 alkoxy, pyranyl, phenyl, η than dimethyl and phenyl substituted by halogen. A specific example is phenyl, which is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, CW alkyl, hydroxy and CW alkoxy, phenyl, pyrenyl, Pyridyl and phenyl substituted by dentate. Another special example of Z is the ratio of σ to σ, which may be selected by one or more Substituted by a group of substituents: _, cyano, C16 alkyl, thiol and C -6 alkoxy, pyridinyl, phenyl, pyridyl and phenyl substituted by phenyl Another specific example of z is a fluorenyl group which is attached, for example, at the 4, 5, 6 or 7 position to the remainder of the W moiety, and optionally, via one or more groups selected from the group consisting of: Substituent substitution: halogen, cyano, ci.6, hydroxy and Cu alkoxy, phenyl, morphine, pyridyl and phenyl substituted by #. Other specific examples of Z include cyclopentyl, Furan. Bipyridyl, tetrahydrofuranyl, benzo[14]-morphinyl, benzo with 4]diphenyl, benzo[I.2·5]thiadiazole and quinazolinyl. In the present invention In a specific example in which the compound is defined by the formula Ib, γ represents a bond, C(o), -C(0)-0-, C(0)-NH-, -〇- or S(〇)2; a+b 28 200906801 C 1 ·6 alkyl group such as A is 0, 1, 2, 3 or 4; and wherein 2 represents hydrogen, benzyl, isopropyl, isobutyl or tert-butyl, long-lasting or nitrogen The compound of the present invention is defined by Formula 1 - in the specific example, A represents C H; R represents a Ci6 alkane 诸如 'such as ethyl or cyclopropyl, w from hydrogen, hydroxy, dentate, cyano, (=0) ' _ 〇 (alkoxy, alkyl, _c (〇) _ 〇 _c ... (5), qing) d, ... is ... (Spiral on the wire II is 6 burning base, -C (0) H, C00H. In a specific example, the compound of the invention is determined by the formula

2 或 [lc] 其中A表示N、CH或CR1 ; 其中各R1獨立地表示氫、Cu烷基、烷基、 -ccco-o-c!-6烷基或苯基，其中該苯基或c16烷基視情況經一或多個選自以下基團之取代基取代：函素、羥基、鹵基cv6烧基、確基、Ci.6院氧基及nr2r3 ; 29 200906801 其中w係選自氫、羥基、鹵素、氰基、（=〇 ' vJ ·· (CH2)c-0_’其中c為2或3(螺）、（CH2)d，其中d為5或6(螺）、 Cu 烷基、Cl 6 烷氧基、_c(〇)_Ci 6 烷基、_c( 〇_c 基、-0-C(〇)_Ci 6 烷基、_c(〇)H、c〇〇H ;或其中 w 表示式-(CH2)a-Y_(CH2)b_z 部分；其中a及b獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、C(O)、Ο、S、-O-C(O)、_c(0)-〇_、 •NR2_、_NR2-C(〇)-、-C(0)-NH-或 S(0)2 ; 其中Z表示氫、Ci·6烷基、NR2R3、氰基或包含4至Q 個％原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、〇及s之雜原子，且其中該單環或稠s雙環部分視情況經一或多個選自由以下基團組成之^ 的取代基取代：_素、氣基、Ci 6烷基、羥基及Ci ^烷氧基、°比啡基、笨基、β比π定基及經鹵素取代之苯基；其中R2及R3獨立地表示氫、Cl·6烷基、羥基Ci 6烷基鹵基烧基或苯基；及其醫藥學上可接受之鹽。詳言之，A表示表示Ci_6烷基，諸如乙基或環丙在本發明化合物係由式Ic所定義之一具體實例中，w 獨立地表示氫、羥基、苯基、經Ci 6 哌啶基、吡啶基、-〇_(CH2)c_〇_ ,其中烷氧基取代之苯基、其中c為2或3(螺）、 N(CH3)2、CN6 烷基、—(CH2)a_c(〇)_〇_(CH2)b_H，其中 a+b 為1、2或3，或2 or [lc] wherein A represents N, CH or CR1; wherein each R1 independently represents hydrogen, Cu alkyl, alkyl, -ccco-oc!-6 alkyl or phenyl, wherein the phenyl or c16 alkyl Optionally substituted with one or more substituents selected from the group consisting of: a hydroxyl group, a hydroxyl group, a halogen group cv6 alkyl group, an exact group, a Ci.6 alkoxy group, and an nr2r3; 29 200906801 wherein w is selected from the group consisting of hydrogen and hydroxyl groups. , halogen, cyano, (=〇' vJ ··(CH2)c-0_' where c is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), Cu alkyl, Cl 6 alkoxy, _c(〇)_Ci 6 alkyl, _c(〇_c,-0-C(〇)_Ci 6 alkyl, _c(〇)H, c〇〇H; or wherein w is a formula - (CH2)a-Y_(CH2)b_z moiety; wherein a and b independently represent an integer selected from 〇, 1, 2, and 3; wherein Y represents a bond, C(O), Ο, S, -OC(O ), _c(0)-〇_, •NR2_, _NR2-C(〇)-, -C(0)-NH- or S(0)2; wherein Z represents hydrogen, Ci.6 alkyl, NR2R3, cyanide a monocyclic or fused bicyclic moiety containing 4 to Q % of atoms, wherein 1, 2 or 3 of the ring atoms are heteroatoms selected from N, fluorene and s, and wherein the monocyclic or fused s Double ring part as the case One or more substituents selected from the group consisting of: _, gas, Ci 6 alkyl, hydroxy, and Ci^ alkoxy, phageyl, stupid, β, π, and a halogen-substituted phenyl group; wherein R 2 and R 3 independently represent hydrogen, a Cl 6 alkyl group, a hydroxy Ci 6 alkyl haloalkyl group or a phenyl group; and a pharmaceutically acceptable salt thereof. In detail, A represents Representing a Ci_6 alkyl group, such as ethyl or cyclopropane, in a particular embodiment wherein the compound of the invention is defined by formula Ic, w independently represents hydrogen, hydroxy, phenyl, Ci6 piperidinyl, pyridyl, -indole _(CH2)c_〇_ , wherein alkoxy substituted phenyl, wherein c is 2 or 3 (spiro), N(CH3)2, CN6 alkyl, —(CH2)a_c(〇)_〇_( CH2)b_H, where a+b is 1, 2 or 3, or

其中a表示1、2或3。 30 200906801 在一具體實例中，本發明化合物係由式id所定義Where a represents 1, 2 or 3. 30 200906801 In a specific example, the compound of the invention is defined by the formula id

1或2 [Id] 其中A表示N、CH或CR1 ; 其中各R1獨立地表示氫、Cl-0烷基、烷基、 -qoto-c^·6烷基或苯基，其中該苯基或Ci6烷基視情況經-或多個選自以下基團之取代基取代：自素、羥基、_ 基Cl-6烧基、硝基、Cl_6烷氧基及NR2R3 ; 其中w係選自氫、羥基、鹵素、氰基、（=〇)、七_ (CH2)c-〇_，其中 c4 2 或 3(螺）、（CH2)d，其中 d為 5 或 6(螺）、 Cu 烷基、cN6 烷氧基、_c(0)_Ci 6 烷基、_c(〇)_〇_Cu 烷基、_0_C(0)-ci-6 烷基、-C(0)H、COOH ; 其中R2及R3獨立地表示氫、Cu烷基、羥基Ci 6烷基、鹵基Cw烷基或苯基；其中R9_Rl2獨立地表示氫或鹵素；及其醫藥學上可接受之鹽。詳言之，八為（：11;汉1表不Gw烷基，諸如乙基或環丙基；且^、尺丨2中之每一者獨 31 200906801 立地表示氫或鹵素。在一具體實例中，本發明化合物係由式Ie所定義，1 or 2 [Id] wherein A represents N, CH or CR1; wherein each R1 independently represents hydrogen, Cl-0 alkyl, alkyl, -qoto-c^.6 alkyl or phenyl, wherein the phenyl or The Ci6 alkyl group is optionally substituted with or a plurality of substituents selected from the group consisting of: a self group, a hydroxyl group, a yl group C-6 alkyl group, a nitro group, a Cl_6 alkoxy group, and NR2R3; wherein w is selected from the group consisting of hydrogen, a hydroxyl group, a halogen, a cyano group, (=〇), a hepta-(CH2)c-〇_, wherein c4 2 or 3 (spiro), (CH 2 )d, wherein d is 5 or 6 (spiro), Cu alkyl, cN6 alkoxy, _c(0)_Ci 6 alkyl, _c(〇)_〇_Cu alkyl, _0_C(0)-ci-6 alkyl, -C(0)H, COOH; wherein R2 and R3 are independent The ground represents hydrogen, Cu alkyl, hydroxy Ci 6 alkyl, halo Cw alkyl or phenyl; wherein R9_Rl2 independently represents hydrogen or halogen; and pharmaceutically acceptable salts thereof. In detail, eight are (:11; Han 1 is not Gw alkyl, such as ethyl or cyclopropyl; and ^, each of the two are independent 31 200906801 standing on behalf of hydrogen or halogen. In a specific example Wherein the compound of the invention is as defined by formula Ie,

( [le] 其中A表示n、CH或CR1 ; 其中各R1獨立地表示氫、C16烷基、-(^(CO-Cu烷基、 -C(0)-0_Ci-6烷基或苯基，其中該苯基或（^.6烷基視情況經一或多個選自以下基團之取代基取代：_素、羥基、鹵基C"烧基、硝基、cN6烷氧基及NR2R3 ; 其中W係選自氫、羥基、鹵素、氰基、（=〇)、-◦_ (CH2)c-0-’其中C為2或3(螺）、（CH2)d，其中d為5或6(螺）、 C,_6 烷基、CV6 烷氧基、-qCO-Cw 烷基、6 烷基、-O-CCCO-Cu 烷基、-C(0)H、COOH ;或其中 W 表示式—(CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、C(O)、Ο、S、-O-C(O)、_c(0)-0-、 NR2、-NR2-C(0)-、-C(0)-NH-或 S(0)2 ; 其中Z表示氫、C!·6烷基、NR2R3、氰基或包含4至12 32 200906801 個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、〇a s之雜原子，且其令該單環或 _ °雙核部分視情況經—或多個選自由以下基團組成之 :取，基取代：齒素、氰基、C16烷基、羥基I k烷氧哄基、本基、吼唆基及經鹵素取代之苯基；義其中R2及R3獨立地表示氫、c,·6烷基、羥基Ci —烷 2鹵基Cw烷基或苯基；及其醫藥學上可接受之鹽。詳二之，A為CH，且Ri表示^丨6烷基，諸如乙基或環丙子之Z包含5-9個環原子，諸如5個、6個或9個環原具”有5個環原子之Z之實例包括pyrr〇iide及環戊基； ^有6個ί衣原子之z之實例包括苯基、嘧啶基、嗎福林基定基，具有9個環原子之z之實例包括呋喃并[3 2_ %啶基. 在一具體實例中，本發明化合物係由式卜所定義，([le] wherein A represents n, CH or CR1; wherein each R1 independently represents hydrogen, C16 alkyl, -(^(CO-Cualkyl, -C(0)-0-Ci-6 alkyl or phenyl, Wherein the phenyl or (^.6 alkyl group is optionally substituted with one or more substituents selected from the group consisting of: _, hydroxy, halo C" alkyl, nitro, cN6 alkoxy and NR2R3; Wherein W is selected from the group consisting of hydrogen, hydroxy, halogen, cyano, (=〇), -◦_(CH2)c-0-' wherein C is 2 or 3 (spiro), (CH2)d, where d is 5 or 6(spiro), C, _6 alkyl, CV6 alkoxy, -qCO-Cw alkyl, 6 alkyl, -O-CCCO-Cu alkyl, -C(0)H, COOH; or wherein W is —(CH2)aY-(CH2)bZ moiety; wherein a and b independently represent an integer selected from the group consisting of 〇, 1, 2, and 3; wherein Y represents a bond, C(O), Ο, S, -OC(O ), _c(0)-0-, NR2, -NR2-C(0)-, -C(0)-NH- or S(0)2; wherein Z represents hydrogen, C!·6 alkyl, NR2R3, a cyano group or a monocyclic or fused bicyclic moiety containing 4 to 12 32 200906801 ring atoms, wherein one, two or three of the ring atoms are heteroatoms selected from N, 〇as, and the ring is selected Or _ ° dual core part as the case - or more Free radical consisting of: base substitution: dentate, cyano, C16 alkyl, hydroxyl alkoxyalkyl, benzyl, fluorenyl and halogen substituted phenyl; wherein R2 and R3 are independent Ground represents hydrogen, c, .6 alkyl, hydroxy Ci-alkanohalo Cw alkyl or phenyl; and pharmaceutically acceptable salts thereof. In detail, A is CH and Ri represents ^6 6 alkane a group, such as ethyl or cyclopropene, Z contains 5-9 ring atoms, such as 5, 6 or 9 ring originals. Examples of Z having 5 ring atoms include pyrr〇iide and cyclopentyl; Examples of z having six yoke atoms include a phenyl group, a pyrimidinyl group, a morpholinyl group, and examples of z having 9 ring atoms include furan [3 2_ % pyridine group. In a specific example, The inventive compound is defined by the formula,

[ΙΠ 其中A表示n、CH或CR1 ; 其中各R1獨立地表示氫、Ci 6烷基、_c(0)_Ci 6烷基、 33 200906801 -ccco-o-c^.6烷基或苯基，其中該苯基或c1-6烷基視情況經一或多個選自以下基團之取代基取代：_素、羥基、鹵基c,_6烷基、硝基、Cu烷氧基及NR2R3 ; 其中W係選自氳、經基、鹵素、氰基、（=〇)、_〇_ (CH2)£-〇-，其中c為2或3(螺）、（CH2)d，其中d為5或6(螺）、 Ci-6 烧基、Ci.6 烧氧基、-C(0)-C丨·6 烧基、_c(〇)-〇-C丨-6 炫基、-O-CXOhCu烧基、-C(0)H、COOH ;或其中w表示式-(CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、C(O)、Ο、S、-O-C(o)、_C(0)-0-、 NR2、-NR2-C(0)-、-C(0)-NH-或 S(0)2 ; 其中Z表示氫、Cw烷基、NR2R3、氰基或包含4至12 個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、〇及S之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：鹵素、氰基、Cw烷基、羥基及Cl6烷氧基、°比畊基、苯基、吡啶基及經鹵素取代之苯基；其中R2及R3獨立地表示氫' C1-6烷基、羥基Ci.6烷基、鹵基<^·6烷基或苯基；及其醫藥學上可接受之鹽。詳言之’ A為CH，且R1表示C!·6烷基，諸如乙基或環丙基。 s羊言之’ Z包含5-9個環原子，諸如5個、6個或9個環原子。具有5個環原子之z之實例包括pyrrolide及環戊基；具有6個環原子之Z之實例包括苯基、嘧啶基、嗎福林基及。比π定基；具有9個環原孑之Z之實例包括呋喃并[3.2-c] 34 200906801 。比。定基。在一具體實例中，本發明化合物係由式％所定義，[wherein A represents n, CH or CR1; wherein each R1 independently represents hydrogen, Ci 6 alkyl, _c(0)-Ci 6 alkyl, 33 200906801 -ccco-oc^.6 alkyl or phenyl, wherein The phenyl or c1-6 alkyl group is optionally substituted with one or more substituents selected from the group consisting of: _, hydroxy, halo c, -6 alkyl, nitro, Cu alkoxy and NR 2 R 3 ; Is selected from the group consisting of ruthenium, ruthenium, halogen, cyano, (=〇), _〇_(CH2)£-〇-, where c is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), Ci-6 alkyl, Ci.6 alkoxy, -C(0)-C丨·6 alkyl, _c(〇)-〇-C丨-6 炫, -O-CXOhCu alkyl And -C(0)H, COOH; or wherein w represents a formula -(CH2)aY-(CH2)bZ moiety; wherein a and b independently represent an integer selected from 〇, 1, 2 and 3; wherein Y represents a Key, C(O), Ο, S, -OC(o), _C(0)-0-, NR2, -NR2-C(0)-, -C(0)-NH- or S(0)2 Wherein Z represents hydrogen, Cw alkyl, NR2R3, cyano or a monocyclic or fused bicyclic moiety containing from 4 to 12 ring atoms, and one, two or three of the ring atoms are selected from N, oxime and a hetero atom of S, and wherein the monocyclic or fused bicyclic moiety is optionally Substituted by one or more substituents selected from the group consisting of halogen, cyano, Cw alkyl, hydroxy and Cl6 alkoxy, phage, phenyl, pyridyl and halogen substituted benzene Wherein R 2 and R 3 independently represent hydrogen ' C 1-6 alkyl, hydroxy Ci. 6 alkyl, halo < 6 alkyl or phenyl; and pharmaceutically acceptable salts thereof. In detail, 'A is CH, and R1 represents C!·6 alkyl, such as ethyl or cyclopropyl. The s sheep's 'Z contains 5-9 ring atoms, such as 5, 6 or 9 ring atoms. Examples of z having 5 ring atoms include pyrrolide and cyclopentyl; examples of Z having 6 ring atoms include phenyl, pyrimidinyl, orolinin and . An example of Z having 9 ring precursors includes furan [3.2-c] 34 200906801. ratio. Set the foundation. In a specific example, the compound of the invention is defined by the formula %,

其中A表示N、CH或CR1 ; 其中各R1獨立地表示氫、Cl 6烷基、-C(〇)_Ci 6烷基、烷基或苯基，其中該苯基或Cl.6烷基視情況經一或多個選自以下基團之取代基取代：鹵素、羥基、鹵基cv6烷基、硝基、cv6烷氧基及nr2r3 ; 其中W係選自氫、羥基、鹵素、氰基、（=〇)、-0-(CH2)c-0-，其中C為2或3(螺）、（CH2)d，其中d為5或6(螺）、 cv6 烷基、Cw 烷氧基、-ccco-Cu 烷基、-ccohO-Cu 烷基、-O-CCCO-Cw 烷基、-N(R2)-C(0)-R3、-C(0)H、COOH ; 或其中W表示式-(CH2)a-Y-(CH2)b-Z部分；其中a及b獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、c(o)、〇、S、-o-c(o)、-c(o)_o-、 NR2、-NR2-C(0)-、-C(0)-NH-或 S(0)2 ; 其中z表示氫、Cw烷基、NR2R3、氰基或包含4至12 35 200906801 個環原子之單環或稠合雙環部分，環原子中視情況丨個 2個或3個為選自N、〇及S之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：鹵素、氰基、C!.6烷基、羥基及ci6院氧基、°比啡基、苯基、D比β定基及經函素取代之苯基；其中R2及R3獨立地表示氫、Cu烷基、羥基Cl 6烷基、鹵基Ci_6烧基或苯基’及其醫藥學上可接受之鹽。詳言之，A為CH，且R1表示Cu烷基，諸如乙基或環丙基。詳§之’ Z包含5-9個環原子’諸如5個、6個或9個環原子。具有5個環原子之Z之實例包括pyrr〇lide及環戊基；具有6個環原子之z之實例包括苯基、嘧啶基、嗎福林基及吼咬基；具有9個環原子之Z之實例包括呋喃并[3.2-c] 。比0定基。在一具體實例中’本發明化合物係由式Ih所定義，Wherein A represents N, CH or CR1; wherein each R1 independently represents hydrogen, Cl 6 alkyl, -C(〇)_Ci 6 alkyl, alkyl or phenyl, wherein the phenyl or Cl.6 alkyl group is optionally the case Substituted by one or more substituents selected from the group consisting of halogen, hydroxy, halo cv6 alkyl, nitro, cv6 alkoxy and nr2r3; wherein W is selected from the group consisting of hydrogen, hydroxy, halogen, cyano, =〇), -0-(CH2)c-0-, wherein C is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), cv6 alkyl, Cw alkoxy, - ccco-Cu alkyl, -ccohO-Cu alkyl, -O-CCCO-Cw alkyl, -N(R2)-C(0)-R3, -C(0)H, COOH; or wherein W is a formula - (CH2) aY-(CH2)bZ moiety; wherein a and b independently represent an integer selected from 〇, 1, 2, and 3; wherein Y represents a bond, c(o), 〇, S, -oc(o) , -c(o)_o-, NR2, -NR2-C(0)-, -C(0)-NH- or S(0)2; wherein z represents hydrogen, Cw alkyl, NR2R3, cyano or contains 4 to 12 35 200906801 A monocyclic or fused bicyclic moiety of a ring atom, wherein 2 or 3 of the ring atoms are heteroatoms selected from N, fluorene and S, and wherein the monocyclic or fused bicyclic moiety One or more choices as appropriate Substituted by a substituent consisting of a halogen group, a cyano group, a C..6 alkyl group, a hydroxyl group, and a ci6-oxyl group, a phenanthyl group, a phenyl group, a D-β group, and a benzene substituted by a conjugated group. And R 2 and R 3 independently represent hydrogen, Cu alkyl, hydroxy C 6 alkyl, halo Ci-6 alkyl or phenyl ' and pharmaceutically acceptable salts thereof. In detail, A is CH, and R1 represents a Cu alkyl group such as an ethyl group or a cyclopropyl group. The detail 'Z contains 5-9 ring atoms' such as 5, 6 or 9 ring atoms. Examples of Z having 5 ring atoms include pyrr〇lide and cyclopentyl; examples of z having 6 ring atoms include a phenyl group, a pyrimidinyl group, a morpholinyl group, and a tick base; Z having 9 ring atoms Examples include furo[3.2-c]. More than 0. In a specific example, the compound of the invention is defined by the formula Ih,

其中A表示N、CH或CR1 ; 其中各R1獨立地表示氫、〇γ6烷基、烷基、 36 200906801 (yoc!—6院基或笨基，其中該苯基或I —烷基視情況經一或多個選自以下基團之取代基取代：_素、羥基、鹵基Cl·6燒基、硝基、c,.6烷氧基及NR2R3 ; 其中W係選自氫、羥基、鹵素、氰基、（=〇)、·〇_ (CH2)c-〇_’其中c為2或3(螺）、（CH2)d，其中d為5或6(螺）、烷基、cy6 烷氧基、_c(0)_Ci 6 烷基、_c(〇)_〇_Ci 6 烷Wherein A represents N, CH or CR1; wherein each R1 independently represents hydrogen, 〇γ6 alkyl, alkyl, 36 200906801 (yoc!-6) or stupid, wherein the phenyl or I-alkyl is optionally Substituted by one or more substituents selected from the group consisting of: -, hydroxy, halo, hexyl, nitro, c, .6 alkoxy and NR2R3; wherein W is selected from the group consisting of hydrogen, hydroxy, halogen , cyano, (=〇), ·〇_(CH2)c-〇_' where c is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), alkyl, cy6 alkane Oxy, _c(0)_Ci 6 alkyl, _c(〇)_〇_Ci 6 alkane

基、-〇-c(〇)_Ci 6 烷基、_c(〇)H、c〇〇H ;或其中 w 表示式 _(CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自〇、ι、2及3之整數；其中 Y 表示一鍵、C(0)、〇、s、_〇_c(〇)、_c(〇)_〇、 NR2、-NR2'C(〇)-、-C(0)-NH-或 S(0)2 ; π其中Z表示氫、Gy烷基、NR2r3、氰基或包含斗至a 個％原子之單環或稠合雙環部分，環原子巾視情況1個、 2個或=個為選自N、〇及s之雜原子，且其中該單環或稠口又％邛分視情況經一或多個選自由以下基團組成之群的取代基取代：鹵素、氰基、烷基、羥基a (V6烷氧基、°比啡基、笨基、。比α定基及經函素取代之苯基；其中R2及R3獨立地表示氫、C16烷基、羥基c w烷基、鹵基q.6烷基或苯基；及其醫藥學上可接受之鹽。詳為CH且R1表示烧基，諸如乙基或環丙基。詳言之’ Z包含5-9個環原子，諸如”固、6個或9個環原子-有5個王衣原子之z之實例包括^及環戍基；具有6個環原子之之之實例包括苯基、嘧啶基、嗎福林基及吡α疋基’具有9個環原子之Z之實例包括呋喃并[3.2-c] 37 200906801 。比α定基。在一具體實例中，本發明化合物係由式L所定義，a group, -〇-c(〇)_Ci 6 alkyl, _c(〇)H, c〇〇H; or wherein w represents a moiety of the formula _(CH2)aY-(CH2)bZ; wherein a and b independently represent An integer from 〇, ι, 2, and 3; where Y is a key, C(0), 〇, s, _〇_c(〇), _c(〇)_〇, NR2, -NR2'C(〇) -, -C(0)-NH- or S(0)2; π wherein Z represents hydrogen, Gy alkyl, NR2r3, cyano or a monocyclic or fused bicyclic moiety containing a to a % atom, ring atom The towel, as the case may be, one, two or one is a hetero atom selected from N, oxime and s, and wherein the single ring or the fused ring is further divided into one or more groups selected from the group consisting of the following groups. Substituted substituents: halogen, cyano, alkyl, hydroxy a (V6 alkoxy, phageyl, stylyl, phenyl substituted by α- and phenyl); wherein R2 and R3 independently represent hydrogen , C16 alkyl, hydroxy cw alkyl, haloq. 6 alkyl or phenyl; and pharmaceutically acceptable salts thereof, in detail CH and R1 represents an alkyl group such as ethyl or cyclopropyl. 'Z contains 5-9 ring atoms, such as "solid, 6 or 9 ring atoms - there are 5 examples of the king's atom z including ^ Examples of a ring having one of 6 ring atoms, including a phenyl group, a pyrimidinyl group, a mufflein group, and a pyridinyl group, and having 9 ring atoms, Z, include furan [3.2-c] 37 200906801. a specific base, in a specific example, the compound of the invention is defined by formula L,

[H] 其中A表示N、CH或CR1 ; 其中各R1獨立地表示氫、C〗.6烷基、-CCCO-Cu烷基、 -ccco-o-c^·6烷基或苯基，其中該苯基或Cl_6烷基視情況經一或多個選自以下基團之取代基取代：_素、羥基、_ 基Cw烷基、硝基、Ci_6烷氧基及NR2R3 ; 其中W係選自氫、經基、鹵素、氰基、（=〇)、_〇_ (CH2)c-0-，其中C為2或3(螺）、（CH2)d，其中d為5或6(螺）、 CV6 烧基、Cu 烧氧基、-0(0)-(^.6 烧基、燒基、-O-qCO-Cu烷基、-C(0)H、COOH ;或其中X表示式-(CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、c(o)、〇、S、-o-c(o)、-c(o)-o-、 NR2、-NR2-C(0)-、-C(0)-NH-或 S(0)2 ; 其中Z表示氫、c!_6院基、NR2R3、氰基或包含4至12 38 200906801 個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、〇及s之雜原子，且其中該單稠合雙環部分視情況經—或多個選自由以下基團組成= 的取代基取代：函素、氰基、u基m Cl_6燒氣基比啡基、本基、°比°定基及經鹵素取代之苯基；[H] wherein A represents N, CH or CR1; wherein each R1 independently represents hydrogen, C..6 alkyl, -CCCO-Cualkyl, -ccco-oc^.6 alkyl or phenyl, wherein the benzene The base or Cl-6 alkyl group is optionally substituted with one or more substituents selected from the group consisting of: -, hydroxy, keyl Cw alkyl, nitro, Ci-6 alkoxy, and NR2R3; wherein W is selected from hydrogen, Merid, halogen, cyano, (=〇), _〇_(CH2)c-0-, where C is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), CV6 Alkyl group, Cu alkoxy group, -0(0)-(^.6 alkyl group, alkyl group, -O-qCO-Cu alkyl group, -C(0)H, COOH; or wherein X represents a formula - (CH2 aY-(CH2)bZ moiety; wherein a and b independently represent an integer selected from 〇, 1, 2, and 3; wherein Y represents a bond, c(o), 〇, S, -oc(o), - c(o)-o-, NR2, -NR2-C(0)-, -C(0)-NH- or S(0)2; wherein Z represents hydrogen, c!_6, NR2R3, cyano or a monocyclic or fused bicyclic moiety comprising from 4 to 12 38 200906801 ring atoms, wherein one, two or three of the ring atoms are heteroatoms selected from N, hydrazine and s, and wherein the single fused bicyclic moiety Depending on the situation - or multiple selected from the following = Composition substituents: letter, cyano, u m Cl_6 burning gas yl group than coffee group, this group, compared ° ° given group, and the halogen-substituted phenyl group;

V 其中R2及R3獨立地表示氫、Ci·6烷基、羥基Ci 6烷基、鹵基C!·6烷基或苯基；及其醫藥學上可接受之鹽。詳 &之A為CH，且R1表示Cu烷基，諸如乙基或環丙基。詳言之，Z包含5-9個環原子，諸如5個、6個或9個環原子。具有5個環原子之z之實例包括pyrr〇Hde及環戊基；具有6個環原子之Z之實例包括苯基、嘧啶基、嗎福林基及吡啶基；具有9個環原子之Z之實例包括呋喃并[3.2_c] 0比。定基。在一具體實例中，本發明化合物係由式丨』所定義 R14 R15\J-v/R13 r16r^^And wherein R2 and R3 independently represent hydrogen, Ci.6 alkyl, hydroxyCi6 alkyl, halo C!.6 alkyl or phenyl; and pharmaceutically acceptable salts thereof. A & A is CH, and R1 represents a Cu alkyl group such as an ethyl group or a cyclopropyl group. In particular, Z contains 5-9 ring atoms, such as 5, 6 or 9 ring atoms. Examples of z having 5 ring atoms include pyrr〇Hde and cyclopentyl; examples of Z having 6 ring atoms include phenyl, pyrimidinyl, fluolinin, and pyridyl; Z having 9 ring atoms Examples include furo[3.2_c] 0 ratios. Set the foundation. In one embodiment, the compound of the invention is defined by the formula R14 R15\J-v/R13 r16r^^

R5 R6 其中A表示N、CH或CR1 ; 39 200906801 其中各R1獨立地表示氫、Ci 6烷基、_c(0)_Ci-6烷基、 _C(〇)_〇-Cl-6烧基或苯基，其中該苯基或<^·6烷基視情況經一或多個選自以下基團之取代基取代：函素、羥基、鹵基CV6烧基、硝基、ci 6烷氧基及NR2R3 ; 其中X表示氫、Cw烷基、氰基、_〇R2、_〇_C(〇)r2、 -0C(0)NR2R3 λ -C(0)-NR2R3 ^ -N(R2)C(0)R3 ^ -N(R2)- ^◦州^或Nr2r3,或χ表示具有4-16個環原子之單環、雙裱或二環部分，環原子中之一者為氮，且其中1個、2 個或3個額外環原子可為選自N、〇及s之雜原子，且其中5亥單％、雙環或三環部分可視情況經一或多個取代基W 取代，其中W係選自氫、羥基、函素、氰基、（=〇)、 (CH2)c-0-’其中〇為2或3(螺）、（CH2)d,其中d為5或6(螺）、 cv6 烷基、cy6 烷氧基、_c(0)_Ci 6 烷基、_c(〇)_〇_Ci_6 烷基、-〇_C(0)_Ci-6 烷基、-C(0)H、COOH ;或其中 W 表示式-(CH2)a-Y_(CH2)b_z 部分；其中a及b獨立地表示選自〇、ι、2及3之整數；其中 Y 表示一鍵、c(o)、〇、S、-O-C(O)、-C(〇)_0… -NR2-、-NR2-C(0)-、-C(0)-NH·或 S(0)2 ; 其中Z表示氫、Ci 6烷基、NR2R3、氰基或包含4至u 個壞原子之單環或稠合雙環部分，環原子中視情況丨個、 2個或3個為選自>^、〇及8之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：_素、氰基、Ci_6烷基、羥基及Cm烷氧基、本基、°比°定基及經ιέ素取代之苯基； 200906801 其中r4-r8中之一者表示鹵素且其餘表示氫；其中 r13-r17中之一者表示鹵素且其餘表示氫；其中R2及R3獨立地表示氫、Cl.6烷基、羥基Cu烷基、鹵基C!.6烷基或苯基；及其醫藥學上可接受之鹽。詳言之，A表示CHMR1表示C,-6烷基，諸如乙基或環丙基； Rl4表示鹵素；且R5或R8表示鹵素。尤其提及以下具體實例’其中X表示經一或兩個取代基W取代之旅啡基或1 _ 哌啶基，其中該W為式—(CH2)a_Y_(CH2)b_z部分，其中a 及b獨立地表示〇、l、2或3;Y表示一鍵'〇、_nr2_c(〇)-; 且其中Z表示氫、C!·6烧基、派D定基、嗎福林基、吼啶基、本基、經C !·6炫乳基取代之苯基或〇比洛咬基。在一具體實例中，本發明化合物係由式、所定義， R15N^xv/R13R5 R6 wherein A represents N, CH or CR1; 39 200906801 wherein each R1 independently represents hydrogen, Ci 6 alkyl, _c(0)-Ci-6 alkyl, _C(〇)_〇-Cl-6 alkyl or benzene a group wherein the phenyl or <6. 6 alkyl group is optionally substituted with one or more substituents selected from the group consisting of: a hydroxyl group, a hydroxyl group, a halogen CV6 alkyl group, a nitro group, a ci 6 alkoxy group And NR2R3; wherein X represents hydrogen, Cw alkyl, cyano, _〇R2, _〇_C(〇)r2, -0C(0)NR2R3 λ -C(0)-NR2R3 ^ -N(R2)C( 0) R3 ^ -N(R2)- ^◦州^ or Nr2r3, or χ represents a monocyclic, bicyclic or bicyclic moiety having 4-16 ring atoms, one of the ring atoms being nitrogen, and wherein 1 , 2 or 3 additional ring atoms may be heteroatoms selected from the group consisting of N, hydrazine and s, and wherein 5 %, bicyclic or tricyclic moieties may optionally be substituted by one or more substituents W, wherein W Selected from hydrogen, hydroxyl, hydroxyl, cyano, (=〇), (CH2)c-0-' wherein 〇 is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), Cv6 alkyl, cy6 alkoxy, _c(0)_Ci 6 alkyl, _c(〇)_〇_Ci_6 alkyl, -〇_C(0)_Ci-6 alkyl, -C(0)H, COOH Or where W is the expression -(CH2)a-Y_ (CH2)b_z portion; wherein a and b independently represent an integer selected from the group consisting of 〇, ι, 2, and 3; wherein Y represents a bond, c(o), 〇, S, -OC(O), -C(〇 )_0... -NR2-, -NR2-C(0)-, -C(0)-NH. or S(0)2; wherein Z represents hydrogen, Ci 6 alkyl, NR2R3, cyano or contains 4 to u a monocyclic or fused bicyclic moiety of a bad atom, as the case may be, 2 or 3 of the ring atoms are heteroatoms selected from the group consisting of >^, 〇 and 8, and wherein the monocyclic or fused bicyclic moiety is optionally Substituted by one or more substituents selected from the group consisting of: _, cyano, Ci-6 alkyl, hydroxy and Cm alkoxy, benzyl, decyl and phenyl substituted 200906801 wherein one of r4-r8 represents halogen and the remainder represents hydrogen; wherein one of r13-r17 represents halogen and the remainder represents hydrogen; wherein R2 and R3 independently represent hydrogen, Cl.6 alkyl, hydroxycapane a halogen group, a C..6 alkyl group or a phenyl group; and a pharmaceutically acceptable salt thereof. In detail, A represents that CHMR1 represents C, -6 alkyl, such as ethyl or cyclopropyl; R14 represents halogen; and R5 or R8 represents halogen. In particular, reference is made to the following specific examples 'wherein X represents a benzyl group or a 1-piperidinyl group substituted by one or two substituents W, wherein the W is a moiety of the formula -(CH2)a_Y_(CH2)b_z, wherein a and b Independently represents 〇, l, 2 or 3; Y represents a bond '〇, _nr2_c(〇)-; and wherein Z represents hydrogen, C!·6 alkyl, D group, morpholin, acridinyl, The base is substituted with a C?6 emulsified base or a phenyl or carbene base. In one embodiment, the compound of the invention is defined by the formula, R15N^xv/R13

其中R1表示氫、Cw烷基、c 其中X表示氫、CV6烷基、c j 6歸基或C2_6炔基；風1丨_6机|、匕2_6烯基、 5-9個環原子之單環或4 或X表示具有5-9個環原子之 C2-6 快基或 NR2R3，或雙環部分，環原子中 41 200906801 之一者為氮’且其中1個、2個或3 自Ν' 〇及S之雜原子，且其尹該環原子可為選況經一或多個取代基w取代，其_ w或雙環部分可視情羥基、烷基、c2-6烯基 1選自氫、齒素、或其中W表示式偶)a-Y-(CH2V2=基、W，其中…獨立地表示選“、及3之整數；其中Y表示一鍵，且盆φ 7本_ 之單環部分，環原子中視情況i個二二個環原子二™，且其一分==選以下基__之群的取代基取代羥基及cN6烷氧基； Ύ 1-6烷基、其中R4-R8中之每一者獨立地表示氫或齒素；其中中之每—者獨立地表示氣戍齒辛條件為中之至少一者表示^素；乳W其限制其中R13-R”中立卞<母—者獨立地表示氣或鹵素；其中R 2及R 3在甚a t L 士块基；及其醫藥風上：表示氫、Cl·6燒基、C2-趣、C“ 可接受之鹽。詳言之，由式“定義之化合物可進-步由式V定義義之 42 200906801 R1Wherein R1 represents hydrogen, Cw alkyl, c wherein X represents hydrogen, C.sub.6 alkyl, cj6-group or C2_6 alkynyl; wind 1丨_6 machine|, 匕2_6 alkenyl, 5-9 ring atomic single ring Or 4 or X represents a C2-6 fast radical or NR2R3 having 5-9 ring atoms, or a bicyclic moiety, in the ring atom 41 200906801 one of which is nitrogen 'and one, two or three of which are Ν' a hetero atom of S, and the ring atom of the ring may be optionally substituted with one or more substituents w, the _ w or bicyclic moiety may be hydroxy, alkyl, c 2-6 alkenyl 1 is selected from hydrogen, dentate , or where W represents an even) aY-(CH2V2=base, W, where... independently represents an integer of 3, and 3; wherein Y represents a bond, and the ring φ 7 is a single ring moiety, ring atomic In the case of two or two ring atoms, two TM, and one of them == a substituent of the group of the following group __ is substituted for the hydroxy group and the cN6 alkoxy group; Ύ 1-6 alkyl group, wherein each of R4 to R8 Respectively represent hydrogen or dentate; each of them independently represents at least one of the gas gingival conditions, and the milk is limited to the R13-R" neutral 卞 < mother - independent Gas or halogen Wherein R 2 and R 3 are in the at at L L Block basis; and in the pharmaceutical genre: hydrogen, Cl·6 alkyl, C2- interesting, C “acceptable salt. In detail, defined by the formula The compound can be further defined by the formula V. 42 200906801 R1

其tR1係選自k烧基；其'中X係撰白Θ ry k自虱、Cw烷基或NR2R3，或X表示 5-9個環原子 ^衣不具^ 之早環或雙環部分，環原子中之一者且其中1個額夕卜户店^ 、飞卜衣原子可為選自N之雜原子，且其中該環或雙環部分可葙蜱π , /、甲肩，視睛况經—或多個取代基W取代，其中\ 係選自氫、經美、（一土（一〇)、C1-6烷基，或其中W表示式 (CH2)a-Y-(CH2)b_z 部分； /、中a及b獨立地表示選自〇、1、2及3之整數；、表示鍵’且其中Z表示包含5至6個環原— 之單衣。P刀，墩原子中視情況！個為選自N、〇及S之聋原子且其中該單環部分視情況經一或多個選自由以下』團、·且成之群的取代基取代：齒素、Gw烧基、經基及c! 烷氧基；其中R12表示鹵素； R13-R15各自獨立地表示氫或鹵素；及其醫藥學上可接受之鹽。詳言之，R1表示曱基、 43 200906801 基、環丙基、環丁基、環戊基或環己基，且X表示 N*The tR1 is selected from the group consisting of k-alkyl; the 'X-form is Θ ry k 虱 k 虱 C, Cw alkyl or NR 2 R 3 , or X represents 5-9 ring atoms ^ clothing does not have an early or bicyclic moiety, ring atom One of them and one of them is a hetero atom selected from N, and wherein the ring or bicyclic portion can be 葙蜱π, /, a shoulder, depending on the condition - Or a plurality of substituents W, wherein the \ is selected from the group consisting of hydrogen, sulphate, (a terpenes), a C1-6 alkyl group, or wherein W represents a moiety of the formula (CH2) aY-(CH2)b_z; Wherein a and b independently represent an integer selected from the group consisting of 〇, 1, 2, and 3; a single coat representing a bond 'and wherein Z is a ring containing 5 to 6 ring atoms. P knives, as in the case of a pier atom; a ruthenium atom of N, 〇 and S and wherein the monocyclic moiety is optionally substituted with one or more substituents selected from the group consisting of dentate, Gw alkyl, thiol and c! Alkyl; wherein R12 represents halogen; R13-R15 each independently represent hydrogen or halogen; and pharmaceutically acceptable salts thereof. In particular, R1 represents fluorenyl, 43200906801, cyclopropyl, cyclobutyl, Cyclopentyl Cyclohexyl group, and X represents N *

1或21 or 2

(W) 1或2 C* \ -NR2R3，或氫。 *表示連接點(W) 1 or 2 C* \ -NR2R3, or hydrogen. * indicates the connection point

NN

1或2 (W) 在本發明化合物传士 _ 糸由式Ik，所定義之一具體實例中，R1 表示曱基、乙基、環兩甘1 or 2 (W) In the specific example of the compound of the present invention, _ 糸 is defined by the formula Ik, R1 represents a thiol group, an ethyl group, a ring ganyl group

(W) ^ 内基、環丁基、環戊基或環己基，X f 1或2(W) ^ internal group, cyclobutyl, cyclopentyl or cyclohexyl, X f 1 or 2

N N*N N*

表示 ’且：a： rK (CH2)a-Y-(CH2)b-Z。詳 W 表不風、(-〇)、Cl·6 烷基或-基、異丙基'異丁基i w表示氫、甲基、環丙基甲Represents 'and: a: rK (CH2)a-Y-(CH2)b-Z. Detailed Table W is not wind, (-〇), Cl·6 alkyl or —yl, isopropyl 'isobutyl i w represents hydrogen, methyl, cyclopropyl

其中㈣為2且Z係^丁基、（ = θ)或_(CH(CH2)a-Z，。比洛咬基。、4_嗎福林基、#基、1-派咬或L 在本發明化合物係表示甲基、乙基、環^ k’所定義之—具體實例中，R1Wherein (4) is 2 and Z is a butyl group, (= θ) or _(CH(CH2)aZ, piroxime, 4 _folinin, #基, 1-bite or L in the present invention The compound is represented by methyl, ethyl, and ring ^k' - in a specific example, R1

基、環丁基、環戊基或環己基，X N* 表示或Base, cyclobutyl, cyclopentyl or cyclohexyl, X N* represents or

N 烷基或-(CH2)a-Y-(Cl_j2：) _z 丁基，或a+b為〇，其中w表示氫、羥基、c 詳言之’ W表示氫、經基、 -6' 或2且Z表示4·嗎福林基、第視情況經 44 200906801 C〗_6娱*氧基取代之苯基或4 -旅唆基。 (W)N alkyl or -(CH2)aY-(Cl_j2:) _z butyl, or a+b is 〇, where w represents hydrogen, hydroxy, c, in detail 'W denotes hydrogen, thiol, -6' or 2 and Z represents 4·Folinin, the first case is 44 200906801 C〗 _6 entertainment * oxy substituted phenyl or 4 - british base. (W)

在本發明化合物係由式ik，所定義之一具體實例中，Rl 表示曱基、土基、環丙基、環丁基、環戊基或環己基，X 1或2 表示 ’且W表示（=〇)，且詳言之，χ表示在本發明化合物係由式Ik，所定義之一具體實例中，Rl 表示曱基、乙基、環丙基、環丁基、環戊基或環己基，χ 表示—NR2R3。詳言之，R2及R3獨立地表示氫或Cl_6烷基，且尤其提及以下化合物，其中R2表示氫，且R3表示環丙基、異丁基或第三丁基。 -在本發明化合物係由式Ik，所定義之一具體實例中，R1In a specific example in which the compound of the present invention is defined by the formula ik, R1 represents a fluorenyl group, a soil group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, and X 1 or 2 represents 'and W represents ( = 〇), and in particular, χ indicates that in the specific example of the compound of the present invention defined by the formula Ik, R1 represents a decyl group, an ethyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group. , χ means -NR2R3. In particular, R2 and R3 independently represent hydrogen or Cl-6 alkyl, and in particular, the following compounds are mentioned, wherein R2 represents hydrogen and R3 represents cyclopropyl, isobutyl or tert-butyl. - in the specific example in which the compound of the invention is defined by the formula Ik, R1

表:甲基'乙基、環丙基、環丁基、環戊基或環己基，X 為氫。在具體實例中，本發明化合物係由式Ik，，所定義，Table: methyl 'ethyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, X is hydrogen. In a specific example, the compound of the invention is as defined by formula Ik,

45 200906801 其中R1表示乙基、環丙基或環丁基；其中R12表示氟或氯；且 R13、R14及R15各自獨立地表示氫、氟或氯，其中R13、 R14及R15中之兩者表示氫；及其醫藥學上可接受之鹽。詳言之，該化合物基本上為式Ik’ ’’中所示之S對映異構體45 200906801 wherein R 1 represents ethyl, cyclopropyl or cyclobutyl; wherein R 12 represents fluorine or chlorine; and R 13 , R 14 and R 15 each independently represent hydrogen, fluorine or chlorine, wherein two of R 13 , R 14 and R 15 represent Hydrogen; and pharmaceutically acceptable salts thereof. In particular, the compound is essentially the S enantiomer shown in Formula Ik''

RR

R12 Ο [Ik，.，] 其中R1表示乙基或環丙基； ν 其中R12表示氟或氯；且 R13、R14及R15各自獨立地表示氳、氟或氯，其中R13 R14及R15中之兩者表示氫。在一具體實例中，本發明化合物係由式Id’所定義， 46 200906801 R14R12 Ο [Ik,.,] wherein R1 represents ethyl or cyclopropyl; ν wherein R12 represents fluorine or chlorine; and R13, R14 and R15 each independently represent hydrazine, fluorine or chlorine, wherein two of R13 R14 and R15 Represents hydrogen. In one embodiment, the compound of the invention is defined by the formula Id', 46 200906801 R14

[Id·] ( 其中R1表示乙基或環丙基； R12表示鹵素； R13、R14及R15各自獨立地表示氫或鹵素；及其醫藥學上可接受之鹽。在一具體實例中，本發明化合物係由式Id’ ’所定義，[Id.] (wherein R1 represents an ethyl group or a cyclopropyl group; R12 represents a halogen; and R13, R14 and R15 each independently represent hydrogen or a halogen; and a pharmaceutically acceptable salt thereof. In a specific example, the present invention The compound is defined by the formula Id''

RR

d 基丙環或基·，乙II 示或表氯 R1示中2表其R1 47 200906801 R12、R14及R15各自獨立地表示氫、氯或氟，其中RU、 R14及R15中之兩者表示氫；及其醫藥學上可接受之鹽。詳言之，該化合物基本上為式Id’’’中所示之S對映異構體 R1d propyl ring or yl group, ethyl II or chlorophene R1 is shown in Table 2, R1 47 200906801 R12, R14 and R15 each independently represent hydrogen, chlorine or fluorine, wherein two of RU, R14 and R15 represent hydrogen And its pharmaceutically acceptable salts. In particular, the compound is substantially the S enantiomer R1 shown in the formula Id''

ld, 其中R表示乙基或環丙基； R12表示氯或氟； R 、R及R15各自獨立地表示氫、氯或氟，其中Rl2、 R14及R15中之兩者表示氫；及其醫藥學上可接受之鹽。在一具體實例中’本發明化合物係選自以下列表。為方便起見，化合物名稱之前以黑體表示之編號係指相應實例編號。 la 3-曱基-1-側氧基-2-苯基q，〗-二氫·異喹啉-4-羧酸 ((S)-l-苯基-丙基）-醯胺 lb 3,6-二曱基-1-侧氧基-2-笨基-i 2_二氫-異喹啉_4_羧 48 200906801 酸（（s)-i_苯基-丙基）_酿胺 1C 7-氣-3-甲基-1-側氧基_2_苯基-1，2-二氫-異喹啉-4-羧酸（（s)-i_苯基-丙基）-酿胺Ld, wherein R represents ethyl or cyclopropyl; R12 represents chlorine or fluorine; R, R and R15 each independently represent hydrogen, chlorine or fluorine, wherein two of Rl2, R14 and R15 represent hydrogen; Acceptable salt. In a specific example, the compounds of the invention are selected from the list below. For convenience, the compound name in bold before it refers to the corresponding instance number. La 3-mercapto-1-yloxy-2-phenyl q,-dihydroisoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine lb 3, 6-Dimercapto-1-yloxy-2-phenyl-i 2_dihydro-isoquinoline_4_carboxy 48 200906801 Acid ((s)-i-phenyl-propyl)-bristamine 1C 7-Ga-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-i-phenyl-propyl)- amine

Id 7-溴-3 -甲基-1-側氧基_2_苯基-1，2-二氫-異喹啉羧酸（（S)-l-苯基-丙基）-醯胺 le 6-氟-3-甲基-1-側氧基_2·苯基-i，2-二氫-異喹啉·4-鲮酸（（s)-i -苯基-丙基）-醯胺Id 7-bromo-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinolinecarboxylic acid ((S)-l-phenyl-propyl)-decylamine 6-fluoro-3-methyl-1-oxo-2·phenyl-i,2-dihydro-isoquinoline·4-decanoic acid ((s)-i-phenyl-propyl)-醯amine

If 3,5-二甲基-1-側氧基_2_苯基_ι，2_二氫-異喹啉_4_鲮酸苯基-丙基）-醯胺 lg 7-氟-3-甲基-1-側氧基-2-苯基_1，2-二氫-異喹琳_4· 缓酸（（S)-l -苯基-丙基）-醯胺 lh 3,7-二曱基-1-側氧基_2_苯基_152_二氫_異喹啉-鲮酸（（S)-l-苯基-丙基）-醯胺 li 8-氯-3-甲基_1_側氧基_2_苯基“，厂二氫_異喹啉_4-羧酸（（s)-i_苯基-丙基）-酿胺 lr 3甲基-1-側氧基_2_本基·ι，2_二氫-異啥琳_4_缓酸 ((S)-環丙基-苯基-甲基）-醯胺If 3,5-dimethyl-1-oxooxy-2_phenyl_ι,2_dihydro-isoquinoline_4_decanoic acid phenyl-propyl)-guanamine lg 7-fluoro-3 -Methyl-1-oxooxy-2-phenyl-1,2-dihydro-isoquinoline_4·saudic acid ((S)-l-phenyl-propyl)-decylamine lh 3,7 -didecyl-1-indolyl_2_phenyl_152_dihydro-isoquinoline-decanoic acid ((S)-l-phenyl-propyl)-decylamine li 8-chloro-3- Methyl-1_sideoxy-2_phenyl", plant dihydro-isoquinoline-4-carboxylic acid ((s)-i-phenyl-propyl)-bristamine lr 3 methyl-1- Sideoxy_2_benyl·ι,2_dihydro-isoindole_4_slow acid ((S)-cyclopropyl-phenyl-methyl)-guanamine

Is 3 -甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉_4•羧酸 [(S)-環丙基-(3-氟-苯基）-甲基]-醯胺 lj 3,8-二甲基-1_側氧基苯基二氫-異喹啉_4羧酸（（S)-l -苯基-丙基）-酿胺 lk 2-(2-氟·苯基）_3_甲基-1-側氧基二氫_異喹琳_4_ 叛酸（（S)-l -苯基-丙基）-醯胺， Π 3-曱基-1-側氧基_2_鄰甲苯*4,2_二氫-異喹啉_4_羧 49 200906801 酸（（S)-l -苯基·丙基）-酿胺 lm 2-(2-氯-苯基）-3-曱基-1_側氧基_1，2_二氫-異喹啉_4_ 缓酸（（S)-l -苯基-丙基）-酿胺Is 3 -Methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline _4•carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)- Methyl]-nonylamine lj 3,8-dimethyl-1_yloxyphenyldihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-bristamine lk 2 -(2-Fluorophenyl)_3_methyl-1-oxooxydihydro-isoquinoline_4_ Resin ((S)-l-phenyl-propyl)-decylamine, Π 3-曱Base-1-sideoxy-2_o-toluene*4,2-dihydro-isoquinoline_4_carboxy 49 200906801 Acid ((S)-l-phenyl-propyl)-bristamine lm 2-( 2-Chloro-phenyl)-3-indolyl-1_sideoxy-1,2-dihydro-isoquinoline_4_ sialic acid ((S)-l-phenyl-propyl)-nitramine

In 2-(2,6-二氟-苯基）_3_曱基-1-侧氧基_i,2-二氫-異喹琳-4-叛酸（（S)-l -笨基-丙基）_酿胺 lo 2-(3-氟-苯基）-3-甲基-1-側氧基-i，2_二氫·異喹啉·4-缓酸（（S)-l-苯基-丙基）-醢胺 lp 3 -曱基-1-側氧基_2-間曱苯基-i，2-二氫-異喹啉_4_羧 ('酸苯基-丙基）-酿胺 lq 2-(3-氯-苯基）_3_甲基-i_側氧基-L2·二氳-異喹啉_4_ 叛酸（（S)-l -苯基-丙基）-酿胺In 2-(2,6-Difluoro-phenyl)_3_indolyl-1-yloxy_i,2-dihydro-isoquinoline-4-indolic acid ((S)-l-stupyl- Propyl)-bristamine lo 2-(3-fluoro-phenyl)-3-methyl-1-oxo-i,2-dihydro-isoquinoline·4-acid ((S)-l -Phenyl-propyl)-guanamine lp 3 -mercapto-1-oxo-2,m-p-phenylene-i,2-dihydro-isoquinoline_4_carboxyl ('acid phenyl-propane Base)-bristamine lq 2-(3-chloro-phenyl)_3_methyl-i_sideoxy-L2·diindole-isoquinoline_4_ retinoic acid ((S)-l-phenyl-propenyl Base

It 8_氯_3-曱基-1-側氧基_2_苯基_丨，2_二氫-異喹啉_4_羧酸[(S)-環丙基-(3-氟-苯基）_曱基]_醯胺 2a 3-二甲基胺基曱基-丨_側氧基_2_笨基_丨，2_二氫-異喹。林-4-缓酸（（S)-l-苯基-丙基）_醯胺 2b 3-曱基胺基曱基_丨_側氧基_2_苯基.it二氫·異喹啉· 、 4-羧酸（（S)-1-苯基-丙基）-醯胺 2c 3-乙基胺基甲基小侧氧基-2_苯基二氫_異喹啉_ 4-羧酸（（S)-1-苯基-丙基）-醯胺 2d 3-環丙基胺基曱基-卜側氧基_2_苯基-i，2_二氫-異喹啉-4_羧酸（（S)-l-苯基-丙基）_醯胺 2e 3-[(環丙基甲基-胺基）_甲基]_卜側氧基_2_苯基-U2_ 二氫-異喹琳-4-羧酸（（S)-l-苯基-丙基醯胺 2f 3-(3,6-二氫-2H-吡啶-1-基甲基）-1-側氧基-2-苯基- 50 200906801 I，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2g 3-[4-(2-曱氧基-苯基）-哌畊-1-基曱基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2h 3-[4-(4-氟-苯基）-哌啡-1·基甲基]-1-側氧基_2_苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2i 3-(4-曱醯基-哌畊-1-基甲基）-l-側氧基_2_苯基d，2_ 二氫-異喹啉-4-羧酸(（S)-l-苯基-丙基）-醯胺 2j 4-[1-側氧基-2-苯基-4-(1-苯基-丙基胺甲醯基）-l，2-一氣-異喧嚇·-3-基曱基]-派啡-1 -叛酸乙醋 2k 3-(4_甲基-哌畊_1_基曱基）_1_側氧基_2_苯基-12-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 21 1-側氧基-2-苯基-3-(1，3,4,9-四氫-β-咔琳-2-基甲基）-I，2-二氫-異喹啉羧酸苯基-丙基）_醯胺 2m 1-側氧基·2_苯基_3_η底啡-ΐ_基甲基- j，2_二氫-異啥啉-4-羧酸（（S)-l-苯基-丙基）·醯胺 2n 3_(3_甲基-旅啡_ι_基甲基）]_侧氧基_2_苯基·^2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2〇 3-(3,5-二甲基-哌啡-^基甲基）!_側氧基_2_苯基_ 1，2-二氫-異喹啉_4_羧酸（（s)]•笨基-丙基）·醯胺 2p 3-(4-苯甲基-哌畊·！_基甲基）“_側氧基_2_苯基_丨，2_ 二氫-異喹啉_4·羧酸（（S)-l-苯基-丙基）_醯胺 2q 1-側氧基·3-[4-(2-側氧基-2-吡咯啶-1-基-乙基）_哌啡-1-基曱基]苯基_1，2_二氫-異喹啉羧酸（(8)_卜苯基- 丙基）-醯胺 51 200906801 2r 3-嗎福林-4-基曱基-1-側氧基_2-苯基-1,2-二氫-異喹琳-4-幾酸苯基-丙基）-醯胺 283-(2,6-二甲基_嗎福林_4-基甲基）_1_侧氧基_2_苯基_ 1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2t 1-側氧基-2-苯基-3-硫代嗎福林_4_基曱基_ι，2_二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基醯胺 2u 3-(1,4-二氧雜-8-氮雜-螺[4.5]癸·8-基甲基）_卜侧氧基-2-苯基-1,2-二氫-異喹啉_4_羧酸（〇·〗_苯基-丙基醯胺 2ν 1-側氧基-2-苯基-3-哌啶-1-基甲基— it二氫-異喹啉 -4-羧酸（（S)-l-苯基-丙基）-醢胺 2w 3-(2-曱基-哌啶_1_基曱基）」_侧氧基_2_苯基_1>2_二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基醯胺 2*3-(2,6-二甲基-哌啶_1_基甲基）_1_側氧基_2_苯基_ 1，2-二氫-異喹啉-4-羧酸（（S)-l-笨基-丙基）_醯胺 2y 3-(2-羥基甲基-哌啶_丨_基甲基）“_側氧基_2_苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2z 1-[1-侧氧基_2_苯基-4-(1-苯基-丙基胺曱醯基二氫-異喹琳-3-基甲基]-哌啶_3_羧酸乙酯 2aa 3-(3-曱基-哌啶基甲基分卜側氧基_2苯基-I。-二氫-異喹啉_4_羧酸（（S)-l-苯基-丙基）-醯胺 2ab 3-(4-羥基-哌啶_丨_基甲基）_丨_側氧基_2_苯基_丨，2_二氫-異喹啉-4-羧酸（（s)-〗 —苯基_丙基）_醯胺 2ac 1-側氧基_2_苯基_3-(4-苯基-哌啶_丨_基甲基）4,2-二氫-異喹啉-4-羧酸（（s)」—苯基_丙基）_醯胺 52 200906801 2ad 1-[1-側氧基-2-苯基-4-(1-苯基-丙基胺甲醯基）4,2 二氫-異喧淋-3-基曱基]-η底咬-4-竣酸乙酯 2ae 3-(4-曱基-哌啶-1-基甲基）_丨_側氧基_2_苯基-丨，^二氫-異嗜琳-4-缓酸（（S)-l-苯基-丙基）_酿胺 2af 1-側氧基_2·苯基_3_(4_吡啶_2_基_哌啡-卜基甲基）_ 1,2-一氫-異喹琳-4-竣酸（（S)-l -笨基-丙基）_醯胺 2ag 3-(八氫-喹啉-1-基曱基側氧基_2_苯基_152_二虱-異噎琳-4-緩酸（（S)-l -苯基-丙基）_醯胺 f 、 2ah 3 -氮雑環庚烧-1-基甲基-1-側氧基-2-苯基_ι，2-二氫 -異啥1#-4 -叛酸（（S)-l -苯基-丙基）-醯胺 2ai 3-(3-羥基-哌啶-1-基甲基側氧基_2_苯基_12_二氫-異噇：嚇>-4-缓酸（（S)-l-苯基-丙基）-醯胺 2aj 3·[4·(2,4-二甲基-苯基）-β底啡_ι_基甲基]小侧氧基_ 2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基分醯胺 2ak 3-[4-(3,4-二甲基-苯基）-哌畊-1-基曱基]側氡基_ 2 -本基-1,2 - 一乳-異喧淋-4-叛酸（（S)-l -苯基-丙基）_酿胺、 2al 3_(4_二甲基胺基-哌啶-1-基曱基）-1-側氧基-2-苯基 -1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基·丙基）_醯胺 2am 3-[4-(2,5-二甲基-苯基）-哌啡-1-基曱基]-1-側氧基 -2 -苯基-1,2-二氫-異喧琳-4-羧酸（（S)-l-苯基-丙基）_酿胺 2an 3-[4-(2-氟-苯基）-哌畊-1-基甲基]-1-侧氧基-2-苯基 -1，2-二氫-異噎琳-4-缓酸（（S)-l-苯基-丙基）-醢胺 2ao 3-[4-(3·甲氧基-苯基）-哌畊-1-基甲基]-i_側氧基·2-苯基-1,2-二氫-異喧琳-4-缓酸（（S)-l -苯基-丙基）_酿胺 53 200906801 2ap卜側氧基-2-苯基-3-(4-間曱苯基-哌啡小基甲基）_ 1，2-二氫-異喹啉-4-羧酸（（S)-l·苯基-丙基）_醯胺 2aq 3-[4-(4-甲氧基-苯基）-哌啡基甲基；側氧基_2_ 苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l_苯基-丙基）_醯胺 2ar 1-側氧基-3-(4-苯乙基-哌啡·丨_基甲基）_2·苯基_ι，2_ 二氫-異喹啉-4-羧酸（（S)-l-笨基-丙基；)·醯胺 2as 1-侧氧基-2-苯基-3-(4-嘧啶_2_基-哌啡-1-基曱基）· 1，2-二氫-異啥淋-4-叛酸（（S)-l-苯基-丙基）_酿胺 2at 3-[4-(2_氰基-苯基）-哌啡-1-基曱基]-卜側氧基_2_苯基_1，2_二氫-異啥琳-4-缓酸（（S)-l -苯基-丙基）_醯胺 2au 3-[4-(4-氯-苯基）-哌畊-1-基曱基]-1-側氧基_2·苯基 _1，2-二氫-異喧琳-4-叛酸（（S)-l-苯基-丙基）_酿胺 2av 3-((lS，3R，5R)-3-羥基-8-氮雜-雙環[3.2.1]辛-8-基甲基）-1 -側氧基-2-苯基-1,2-二氫-異啥琳-4-缓酸（（S)-l -苯基 -丙基）-醯胺 2aw 3-(4-乙醢基-哌啡-1-基曱基）-1-側氧基_2_苯基-1，2 - —氮_異哇琳-4 -叛酸（（S)-l-本基-丙基）-酿胺 2ax 3·(4-甲基-[1,4]二氮雑環庚烷-1-基曱基）_丨·側氧基本基-1,2-·—鼠-異嗤淋-4-叛酸（（S)-l-苯基-丙基）_酿胺 2ay 3-(4-乙基-哌畊-1-基曱基）-1-侧氧基_2_苯基-u2_二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2az 3-((2S，6R)-2,6-二曱基-嗎福林-4-基甲基）_ι_侧氧基 -2-苯基-1，2-二氫-異啥琳-4-缓酸（（S)-l-苯基-丙基）_醯胺 2ba 3-[4-(2,4-二氟-苯基）-哌啡-1-基曱基]_M則氧基_2_ 54 200906801 苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2bb 3-[4-(3-二甲基胺基-丙基）-哌畊-1-基甲基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）·醯胺 2bc 3-(4-異丙基底明基甲基）_1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S )-1-苯基-丙基）-醯胺 2bd 3-(3-氮雜-雙環[3.2.2]壬-3-基甲基）-1-侧氧基_2·苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2be 3-(4-環戊基-哌啩-1-基甲基）-1-側氧基-2-苯基-1,2-( ' 二氫-異喹啉-4-羧酸（（S)-l-苯基·丙基）-醯胺 2bf 3-[1，4·]聯哌啶-1·-基甲基-1-侧氧基-2-苯基-1,2-二氫-異啥淋-‘叛酸（（s)-l-苯基-丙基）-醯胺 2bg 3-(3,4-二氫-1H-異喹啉-2-基甲基）-1_側氧基-2_苯基-1,2-二氫-異0^琳-4-叛酸（（S)-l -苯基-丙基）_醯胺 21>113-[4-(2-二甲基胺基-乙基）-哌啡-1_基甲基]_1_側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基醯胺 2bi 3-(4-羥基甲基-哌啶-1-基曱基）_1_側氧基_2•苯基_ I 1,2-二氫-異喹琳-4-羧酸（（s)-i-苯基-丙基）-醯胺 2bj 1-側氧基_2·苯基·3·[4·(四氫-呋喃_2_羰基）―派啡-卜基甲基]-1,2-二氫-異喹啉-4-羧酸（（s)-l-苯基-丙基）_醯胺 2bk 3-(4_異丁基-哌啡-1-基甲基）_ι_侧氧基_2_苯基-丨，2_ 二氫-異喧琳_4_叛酸（（S)-l -苯基·丙基）_酿胺 2bl 3-[4-(2-甲氧基-乙基）-哌啡_ι_基甲基側氧基_2_ 苯基-I，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2bm 3-[4-(2_嗎福林基-乙基）_哌啡]基甲基]j側 55 200906801 氧基-2-苯基-1,2-二氫-異嗜嚇·_4-叛酸（（S)-l -苯基-丙基）-酿胺 2bn 3-(1,3-二氫-異0引0朵-2-基甲基）-1-側氧基-2 -苯基-1,2-二氫-異喧琳-4-缓酸-苯基-丙基）-酿胺 2bo 3-[4-(1-甲基-哌啶-4-基）-哌畊-1-基甲基]-1-側氧基 -2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2bp 1-側氧基-2-苯基-3-[4-(2-哌啶-1-基-乙基）-哌畊·1_ 基甲基]-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）·醯胺 2bq 1-側氧基-2-苯基-3-[4-(2-吡咯啶-1-基-乙基）-哌畊_ 1-基曱基]-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）·醯胺 2br 3-(4-二甲基胺曱醯基甲基-哌畊-1_基曱基）_1-侧氧基-2-本基-1，2-二氫-異啥琳-4-缓酸（（S)-l -苯基-丙基）-酿胺 2bs 3-(八氫-吡啶并[i，2_a]吡啡_2_基甲基）_丨_側氧基_2_ 苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l·苯基·丙基）_醯胺 2bt 3-(4-甲醯基-[1，4]二氮雑環庚烷_1_基甲基）_1_側氧基-2-苯基-1，2-二氫-異喹啉_4_羧酸（（s)-l-苯基·丙基）_醯胺 2bu 3-[4-(4-氰基-苯基）_哌畊_1_基甲基；|_1_侧氧基_2_苯基-1，2-二氫-異喹啉_4_羧酸（（s)·!·苯基-丙基）_醯胺 2bv 1-侧氧基_2_苯基-3-(4-吡啶-4-基甲基·哌畊-i_基甲基）-1，2-二氫-異喹啉_4_羧酸苯基_丙基）_醢胺 2bw Μ則氧基-2_苯基_3·[4·(3_吡咯啶_丨_基_丙基）_哌畊小基甲基]-1，2-二氫-異喹琳_續酸（⑻]•苯基-丙基）·醯胺 2bx 1-側氧基_2·笨基·3_(4_〇比啶_2_基甲基_旅啡小基甲基）-1，2-二氫-異喹琳_4_幾酸（(8)小苯基_丙基）_酿胺 56 200906801 2by 3-(4-乙確醯基底啡-1-基甲基）-1 -側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-笨基-丙基）-醯胺 2bz 3-(4-第二丁基-哌明基甲基）-1-侧氧基-2-苯基- 1.2- 二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2ca 3-[4-(1-乙基-丙基）·哌啡-1-基甲基]-卜側氧基-2-笨基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基醯胺 2cb 3-[4-(2-氰基-乙基）-哌畊-1-基甲基]-1-侧氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基醯胺 2cc 3-(4-甲續酿基底明"-1-基甲基）-1-側氧基-2-苯基-1，2-·—風-異嘻淋-4-竣酸（（S)-l -本基-丙基）_酿胺 2cd {1-[1-側氧基-2-苯基-4-(1-苯基-丙基胺甲醯基）_ 1，2-二氫-異喧琳-3-基甲基]-°底°定-4-基}-乙酸乙酯 2ce 3-[4-(3-氟-苯基）-哌啡-1-基甲基]-1-側氧基_2-苯基 -1，2-二氫-異喹琳-4-羧酸（（8)-1-苯基-丙基）_醯胺 2cf 1-侧氧基-2 -苯基-3-((S)-3_苯基·略咬·;^基甲基）_ 1.2- 二氫-異喧淋-4-缓酸（（S)-l-苯基-丙基）_醯胺 2cg 1-側氧基-2-苯基-3-[4-(吡咯啶_1_羰基）-哌啡」·基甲基]-1，2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）_醯胺 2ch 3-[4-(嗎福林-4-羰基）-哌啡-1-基甲基]側氧基_2_ 本基-1,2-二氫-異啥琳-4-叛酸（（S)-l·苯基-丙基）_醯胺 2ci 3-(4-曱氧基-略咬-1-基曱基）-1_側氧基_2_苯基-1，2_ 一氫_異喹淋-4-缓酸（（S)-l-苯基-丙基）-酿胺 2cj 3-(4’ -經基-3’，4’，5’，6'-四氫-2Ή-[3,4']聯 η比。定 _1'_基曱基）-1-側氧基-2-苯基-1,2-二氫-異喧琳_4-缓酸（(s)_i_苯基 57 200906801 -丙基）-醯胺 2ck 3-(4-羥基-3,4,5,6-四氫-2H-[4,4’]聯吡啶-1-基甲基）-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（3)-1-苯基_ 丙基醯胺 2cl 3-(3H-螺[異苯并呋喃_1，4，-哌啶]-1’_基甲基）-1-側氧基-2-苯基-1,2-二氫-異嗜淋-4-叛酸（（S)-l-苯基-丙基）-醯胺 2cm 3-(4-羥基-4-甲基-哌啶-1-基曱基）-1-側氧基-2-苯基-1，2-二氫-異噎琳-4-緩酸（（s)-l -苯基-丙基）-S篮胺 1 2cn 3-(六氳-螺[苯并[1，3]二腭唑_2,4，-哌啶]-1，-基甲基）-1·側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2co 1-側氧基-2-苯基-3-(3,4,5,6-四氫-2H-[4,4，]聯吡啶- 1- 基甲基）-1,2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）-醯胺 2cp 3-[4-(2-二甲基胺基-乙基）-哌啶-1-基甲基]_ι_側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2cq 3-(4-二甲基胺磺醯基-哌明：_1_基曱基側氧基_2_ 本基-1，2-一氣-異啥嚇·_4-叛酸（（S)-l -苯基-丙基）-酿胺 2cr 3-(l，l-二側氧基-硫代嗎福林·4-基曱基）_1_側氧基- 2- 苯基-l，2-二氫-異喹琳-4-羧酸（（S)-l-苯基-丙基）·醯胺 2cs 1-侧氧基-2-苯基-3-(2-°比咬-2-基甲基-u底咬_ι_基曱基）-1,2 - 一風-異啥淋-4 -缓酸（（S)-l -笨基-丙基）_酿胺 2ct 3-(2-嗎福林-4-基甲基-哌啶-1-基甲基）_!_側氧基_2· 苯基-1,2-二氫-異啥淋-4-叛酸（(S)-l-苯基-丙基）_醯胺 2cu 3-(4_呋喃并[3,2-C]吡啶_4·基-哌畊-卜基甲基）_丨_侧 58 200906801 氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（(s)-i-苯基-丙基）_醯胺 2(^3-(4-環丙基甲基-哌啡_1_基曱基）_1_側氧基_2_苯基 -1，2-二氫-異喹>#-4-羧酸（（8)-1-苯基-丙基）_醯胺 2cw 3-[4-(2_嗎福林_4_基-乙基）-哌啶小基甲基]_丨·側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l_苯基-丙基醯胺 2cx 1-側氧基-2-苯基-3-(4-嘧啶-2-基-[ι，4]二氮雑環庚烷-1-基甲基）-1,2-二氫-異喹啉-4-羧酸（(s)_i_苯基-丙基）_醯 / ，胺 2cy 3-(4-甲基- 6,7-二氫-4H-隹吩并[3,2-C]n比唆-5-基甲基）-1-側氧基-2 -苯基-1,2 -二氫-異啥琳_4_叛酸（（s)_i_苯基_ 丙基）-醯胺 2cz 3-[1，4]二氮雜環庚烧-1-基甲基-丨_側氧基_2_苯基_ 1，2_二氫-異唾淋-4-缓酸（（S)-l-苯基-丙基）_酿胺 2da 3-((2S，5R)-2,5-二甲基-哌啡-i_基甲基）」_側氧基_ 2-苯基-1,2-二氫-異喧琳-4-缓酸（（S)-l-苯基_丙基）_醯胺 U 2db 3-((S)-3-曱基-旅畊-1-基曱基）小側氧基_2_苯基_ 1，2-二氫-異喧琳-4-緩酸（（S)-l·苯基-丙基）_酿胺 2dc 3-((R)-3 -曱基-0底啡-1-基甲基侧氧基_2_苯基-1，2-二氯-異啥淋-4-叛酸（（S)-l -苯基·丙基）_酿胺 2dd 3-[3-(3-氯-苯基）-旅畊-1-基甲基側氧基_2_苯基 -1，2·二鼠-異喧琳-4-缓酸（（S)-l -苯基-丙基）_酿胺 2de 3-[4-(1Η-吲哚_4_基）-哌啡-1-基曱基]小側氧基_2_ 苯基-1,2-二氫-異啥琳-4-幾酸（（S)-l -苯基-丙基）_醯胺 59 200906801 2df 1-侧氧基-3-(3-侧氧基-哌畊」—基甲基）_2_苯基二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2dg 3-[4-(1Η-吲哚基）_哌阱_卜基甲基]側氧基_2_ 苯基-1，2-二氫-異喹啉-4-羧酸（〇_!_苯基-丙基）_醯胺 2dh 3-(6,9-一氮雜-螺[4.5]癸_9_基甲基）-1-側氧基_2-笨基-1，2-二氫-異喹啉-4-羧酸（（s)-i-苯基-丙基醯胺 2di 3-(M-二氮雜·螺[5.5]十一 _4_基甲基}1_側氧基_2_ 苯基-1，2-二氫-異喹啉-4-羧酸（（s)-l-苯基-丙基）_醯胺 2dj 3-(3-異丙基-哌畊_1_基甲基）_丨_侧氧基_2_苯基-n 二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2dk 3-(3,3-二甲基-哌啡_1_基甲基）_卜側氧基_2_苯基_ 1.2- 二氫-異喹琳-4-缓酸（（S)-l-苯基-丙基）_醯胺 2dl 3-[3_(4 -氟-本基）-ί底啡基甲基]_!•側氧基_2_苯基 -1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2dm 1-側氧基-2-本基- 3- (3 -對甲苯基_〇底啡_ι_基甲基）_ 1.2- 二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2dn 4-[1 -側氧基-2-笨基-4-(1 -苯基_丙基胺曱酿基）_丨，2_ 二氫-異淋-3-基甲基]-π底啡_ι_叛酸第三丁醋 2do 3-(4-曱基胺曱醯基甲基-哌畊基甲基_側氧基 -2-苯基-1,2-二氫-異啥琳-4-羧酸（（s)-i-苯基-丙基）_醯胺 2dp 8-氯-3-二甲基胺基甲基_ι·側氧基_2_笨基-^2-二氫-異d奎琳-4-叛酸（（S)-l-苯基-丙基）·酿胺 2dr 3-環戊基胺基甲基-1-側氧基_2_苯基·ι，2-二氫·異唾琳-4-缓酸（（S)-l -苯基-丙基）-醮胺 200906801 2ds 3-環己基胺基甲基·N側氧基_2_苯基_丨，2_二氫-異啥琳-4-叛酸（（S)-1-苯基-丙基）_醯胺 2dt 3-{[(2-羥基-乙基）_甲基_胺基]•曱基}-1_侧氧基_2_ 苯基-I，2-二氫-異喹啉-4-羧酸（ο】_苯基-丙基）_醯胺 2du 3-咪唑_1-基甲基_ι_側氧基_2_苯基_丨,2_二氫-異喹琳-4-羧酸（（S)-l -笨基-丙基）_醯胺 2dv 3-(2-甲基·咪唑-l_基甲基）_〗_側氧基·2_苯基“，^二氫-異喹啉_4_羧酸苯基·丙基）_醯胺 2dw 3-(4-甲基-咪唑-1-基甲基）“_侧氧基_2_苯基n 一氫-異喹琳-4-羧酸（（S)-l-苯基-丙基）_醯胺 2dx 3-(2,5-二氫比咯_1_基甲基）_卜側氧基_2_苯基]，2_ 二氫-異喹琳-4-羧酸（（S)-l-苯基-丙基）_醯胺 2dy 3-(2,5-二甲基-2,5-二氫-吡咯_；[_基甲基側氧基_ 2-苯基_1，2-二氫-異喹啉_4_羧酸苯基-丙基）_醯胺 2dz 1-側氧基-2-苯基-3-d比洛咬小基甲基_丨，2_二氫_異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 V 2ea 1_側氧基-2-苯基-3-(噻唑-2-基胺基甲基）_ι，2-二氫- 異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2eb 1-側氧基-2-苯基-3-(嘧啶-4-基胺基甲基）_ι，2-二氫 -異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2ec 3-(第三丁基胺基-甲基）_丨_側氧基_2_苯基-丨，2_二氫 •異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2ed 3-[(2-羥基-1,1-二甲基-乙基胺基）_甲基]•卜側氧基_ 2-苯基-1，2-二氫-異喹啉·4-羧酸（（s)-l-苯基-丙基）_醯胺 61 200906801 2ee 3-(異丙基胺基-甲基）_卜側氧基_2_苯基_丨，2_二氯_ 異喹啉-4-羧酸（（s)-^·苯基-丙基）_醯胺 2ef 3-[(2,基-1-曱基-乙基胺基）_曱基]+側氧基_2苯基-1,2-二氫-異喹琳_4_羧酸（（s)-i_苯基-丙基）·醯胺 2eg 3-[(1-羥基曱基-丙基胺基曱基]_丨_側氧基_2_苯基 -1,2-二氫-異喹啉_4-羧酸（（S)-l-苯基-丙基醯胺 2eh 3-[(2,2-二甲基-丙基胺基;)·甲基]侧氧基·2_苯基· 1.2- 二氫-異喹啉_4_羧酸（（s)-l_苯基-丙基醯胺 2ei 1-側氧基-2-苯基-3-丙-2-炔基胺基甲基-1,2-二氫_ 異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2ej 3-烯丙基胺基曱基-；!_側氧基_2_苯基-丨,2_二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2ek 3-[(甲基-丙_2_块基-胺基）-甲基]_ι_側氧基_2_苯基- 1.2- 二氫-異喹啉-4-羧酸（（s)-l·苯基-丙基）_醯胺 3- 一烯丙基胺基甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基·丙基）-醯胺 ' 2em 3_二乙基胺基甲基-卜側氧基-2-笨基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2eii 3-[(異丙基-甲基-胺基）-甲基侧氧基_2_苯基_ 1，2 - 一氫-異啥琳-4 -缓酸（（S)-l -苯基-丙基）-醯胺 2eo 3-[((S)-2-羥基-1-甲基-乙基胺基）_甲基卜^側氧基-2-苯基-1，2-二氫-異喹啉_4_羧酸（（S )-1-苯基-丙基）_醯胺 2ep 3-[((R)-2-羥基-1-甲基-乙基胺基）_甲基]+侧氧基_ 2 -本基-1,2 - 一風-異喹琳-4-竣酸（（S)-l·苯基-丙基）_酿胺 62 200906801 2eq 3-{[(2-曱氧基-乙基）-曱基-胺基]-曱基}_1_側氧基_ 2-苯基-l，2-二氫-異喧琳-4-叛酸（（S)-l-苯基-丙基）_醯胺 2er 3-((R)-3-羥基-吡咯啶-1-基甲基）-1-側氧基-2-苯基- 1.2- 二氫-異哇琳-4-羧酸（（S)-l-苯基-丙基）-醯胺 2es 3-((S)-3_羥基比咯啶-1-基甲基）-1-侧氧基-2-苯基- 1.2- 二氫-異喧琳_4-缓酸（（S)-l-苯基-丙基）-醢胺 3-[(環戊基-曱基-胺基）-甲基]-i_侧氧基_2_苯基_ 1，2-·—鼠-異哇嚇·_4 -緩酸（（S)-l -苯基-丙基）-酿胺 2eu 3-{[(2-羥基-1-甲基-乙基）-甲基-胺基]-甲基}_丨側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）_醯胺 2ev 3-{[乙基-(2-羥基-乙基）-胺基]-甲基卜丨·側氧基_2_ 苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基醯胺 2ew 3-[(乙基-甲基-胺基）-甲基侧氧基_2_苯基·12_ 一虱-異喧嚇>-4 -叛酸（（S)-l -苯基-丙基）-醯胺 2ex 3-環丁基胺基甲基-1-側氧基_2_笨基_丨，2_二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ey 3-四氫吖唉-1-基曱基-i_側氧基·2_苯基_丨，2_二氫_ 異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ez 3-(4-第三丁基-哌啡_1_基曱基）]•側氧基_2_苯基_ 1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2fa 3-[4-(2_羥基-乙基）_哌畊小基甲基]小側氧基·2_苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2fb 3-{4-[2-(2-羥基-乙氧基）_乙基]_哌啡基甲基 63 200906801 側氧基-2-本基- i，2_二氫-異喧琳_4_缓酸（(S)-l-苯基-丙基）_ 醯胺 2fc 3-[4-(3-氯-5·三氟甲基-吡啶-2-基）-哌啡-1-基曱基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基_ 丙基）-醯胺 2fd 3 [4-(3,5-,一氯定-4-基）-口底啡-1-基甲基]·1_側氧基-2_苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2fe 4-[1-側氧基_2_苯基苯基_丙基胺甲醯基）_ I，2-二氫-異喹啉_3_基甲基]_哌畊小緩酸苯甲酯 2ff 3-[4-(3-嗎福林-4-基-丙基）-〇底啡-i_基甲基]_ι_侧氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（s)-l-苯基-丙基）_醯胺 2fg 1-側氧基_2_苯基_3_[4_(3_娘咬-^基―丙基）_π底啡-卜基甲基]-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2fh 3-[4-(4,6-一曱氧基-。密咬-2-基甲基）_π底啡_ι_基甲基]-1-侧氧基-2-苯基-1,2-二氫-異喹琳_4-敌酸（(s)_卜苯基_ 丙基）-醯胺 2fi 3-[4-(3-羥基-丙基）-哌畊-1-基甲基•側氧基_2_苯基-1,2-二氫-異喹琳-4-羧酸（(S)-l-苯基-丙基）_醯胺 2fj 3-[4-(2,3-二羥基-丙基）_哌畊·基甲基側氧基_ 2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-1-苯基-丙基）_醯胺 2fk (2-側氧基-2-{4-[1·侧氧基苯基_4·(1_苯基-丙基胺甲醯基）-1，2-二氫-異喹啉-3·基甲基]-哌啡_丨_基卜乙基）_ 胺基甲酸第三丁酯 2fl 3-[4-(lH-吲唑-5-基）_哌啡基甲基]_卜侧氧基·2_ 64 200906801 苯基-1，2-二氫-異啥琳_4_叛酸（（s)-i·笨基-丙基）-醯胺 2fm 1-側氧基-2-苯基-3-(4-喹啉-6-基-哌明基甲基）_ 1,2-二氫-異喹啉-4_羧酸（（8)-1-苯基-丙基）-醯胺 2fn 3-[4-(6,7-二甲氧基-嗜u坐琳_4_基）-旅明^1-基曱基]_ 1 -側氧基-2-苯基-1，2·二氫-異喹琳_4_叛酸（(S)-l -苯基-丙基）-醯胺 2f〇 4-{4-[1-側氧基_2_苯基_4_(1_苯基-丙基胺曱醯基）- 1，2_二氫-異喹啉-3-基曱基]-哌畊基卜哌啶-1·羧酸第三丁 V 酯 2fp 3-{4-[2-(4-氯-苯氧基）_乙基]_哌畊_1_基甲基}小側氧基-2-苯基_1，2-二氫-異喹啉_4_羧酸（（S)-l-苯基-丙基）_醯胺 2fq {4-[1-側氧基_2_苯基_4-(1-苯基-丙基胺甲醯基）-1，2-二氫-異喹啉-3-基曱基]-哌明：_ι_基卜乙酸第三丁酯 2fr 1-側氧基_2_苯基_3-[4-(3,3,3-三氟-2-經基-丙基）-0底畊-1-基甲基]-1,2-二氫-異喹啉_4_羧酸（巧）。·苯基-丙基醯 (，胺 2fs 3_[4_(2-羥基-丙基）-哌啡-1-基曱基]-1-側氧基-2-苯基-I，2-二氫-異喹啉_4-羧酸（（S)-l-苯基-丙基）-醯胺 2fu 3-[4_(4-胺基_6,7-二曱氧基-喹唑啉-2-基）-哌畊-1-基曱基]-1_侧氧基-2-苯基_ι,2-二氫-異喹啉_4-羧酸（（S)-l-苯基-丙基）-醯胺 2fv (2-{4-[1-側氧基_2_苯基_4_(1_苯基-丙基胺甲醯基）_ 1,2-一氳-異喧啉_3-基甲基]-哌啡-丨_基}_乙基）_胺基甲酸第 65 200906801 三丁酯 2fw I-側氧基-3-{4_[2-(2-側氧基-咪唑啶-1-基）-乙基]_ 哌畊-1-基甲基}_2_苯基-I，2-二氫-異喹啉_4_羧酸（（S)-l-苯基-丙基）-酿胺 2fx 3-{4-[(4,6-二曱氧基-嘧啶-2-基）-苯基-曱基]-哌明τ-ΐ-基曱基 }-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（s)-l-苯基-丙基）-醯胺 2fy 3-(4-苯并[1,2,5]噻二唑_4-基-哌畊-1-基甲基）-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2fz 3-[4-(2,3-二氫-苯并[1,4]二腭畊-5-基）-哌啡-l_基甲基]-1_側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基：)-醯胺 2ga 3-[4-(4-甲基-喧郝-2-基）-<»底啡-1-基甲基]-i_側氧基 -2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-笨基-丙基）-醯胺 2gb 1-侧氧基-2 -苯基-3-[4-(n比咬-2-基胺甲醯基甲基）_ 0底啡-1-基甲基]-1,2-二氫-異喧淋-4-叛酸（(S)-l -苯基·丙基）_ 醯胺 2gc 3-[4-(6-氯-3-側氧基-3,4-二氫-2H-苯并[1，4]聘啡. 8-基）-旅明=-1-基甲基]-1-側氧基-2-苯基-1,2-二氫-異喧琳_4_ 羧酸（（S)-l-苯基-丙基）-醯胺 2gd 3-(4-胺曱醯基甲基-旅畊_ι·基甲基）_丨_側氧基_2_苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l·苯基·丙基）_醯胺 2ge 3-(4-經基-4-苯基-旅。定小基曱基）小側氧基_2_苯 66 200906801 基-1，2-二氮-異啥琳-4-竣酸（（S)-l -苯基-丙基）-酿胺 2gf 3-[4-(4-氯-苯基）-4-羥基-哌啶-1-基甲基]-1-侧氧基 -2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l·苯基-丙基）-醯胺 2gg 1-[1-側氧基-2-苯基-4-(1-苯基-丙基胺曱醯基）-1,2-二鼠-異嗜琳-3-基甲基]-d底。定-4-缓酸 2gh 3-(4-氰基-4-苯基-哌啶-1-基曱基）_ΐ-側氧基_2_苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2gi 3-(4-苯甲基-4-羥基-哌啶-1-基甲基）_ι_側氧基·2_苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2gj 1_[1_側氧基-2-本基- 4- (1-苯基-丙基胺甲酿基）_ι,2_ 二氫-異啥琳-3-基曱基]-4-苯基-η底咬-4-叛酸乙醋 2gk 1-側氧基-2-苯基-3-[4-(苯基-丙醯基_胺基）_哌啶_卜基甲基]-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2g丨甲基侧氧基-2·苯基-4-(1-苯基-丙基胺甲醯基）-1，2 - 一虱-異啥嚇·-3-基甲基]底〇定_4_基}·胺基曱酸第三丁酯 2gm 1-側氧基-2-苯基-3-[4·(2-吡咯啶_1_基-乙基）_哌啶 -1-基甲基]-1，2-二氫-異喹啉-4-羧酸苯基_丙基）_醯胺 2gn 3-{4-[5-(4-氟-苯基Hu〆]聘二唑_2_基]_哌啶小基曱基}-1-側氧基-2-苯基-l，2-二氫-異喹啉·4_羧酸苯基-丙基）-酿胺 2go 1-側氧基_2_本基。·[心^“比咬·4·基-[I，2,4]聘二唾 5-基）-α底11疋-1-基甲基]-1，2-二氫-異啥琳·4·緩酸苯基· 丙基）-醯胺 67 200906801 2gp 1-側氧基·2-苯基 _3_[4_(3_^bD^_2-基-[1，2,4]聘二唑-5-基）-哌啶-1-基甲基μ〗，〉二氫-異喹啉_4_羧酸苯基_ 丙基）-醯胺 2gq 1-側氧基-2-苯基_3-[4-(3-吡啶-4-基-[1，2,4]腭二唑- 5-基）-哌啶-1-基甲基]_丨，2_二氫_異喹啉_4_羧酸（（8)_丨_苯基_ 丙基）-醢胺 2gr 3-(4’-羥基 _3'，4'，5，，6’-四氫-2Ή-[2,4，]聯吡啶-1'·基甲基）-1-側氧基-2-苯基-ΐ，2-二氫-異喹啉_4-羧酸（(S)-l-苯基 -丙基）-醯胺 2gs 3-(螺[異二氫苯并旅喃旅咬]基甲基）卜側氧基-2-苯基_l，2-二氫_異喹啉_4_羧酸苯基-丙基醯胺 3-[4-羥基-4-(3-甲氧基-苯基）胃哌啶_卜基甲基]_卜侧氧基-2-苯基_l，2-二氳·異喹啉_4_羧酸苯基-丙基醯胺 2gu 3-[4-(3-氯-苯基）_‘羥基_哌啶_丨_基甲基]_卜侧氧基 _2-苯基-1，2-二氳-異喹啉_4_羧酸（(y—b苯基-丙基醯胺 3-(6-氯-3H-螺[異苯并呋喃q 基）-醯胺哌啶小基甲基)小側氧基·2_苯基十2_二氫-異喹啉_4_羧酸 ((S)-l -苯基-丙基）_醢胺 2gx 3-(1-乙醯基·螺[哨D朵琳·，-基甲基）_卜側 68 200906801 氧基-2-苯基-i，2_二氳-異喹啉-4-羧酸（(S)-l_苯基-丙基）_醯胺 2gy 3-(1-乙醯基-5 -氟-螺[0弓丨嗓琳-3,4’-〇底。定]_ι，_基甲基）-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（s)·；^苯基_ 丙基）-醯胺 2gz 1-側氧基-3-(4-侧氧基-1-苯基-1,3,8-三氮雜-螺[4.5] 癸-8-基曱基）_2_苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基_ 丙基）-酿胺 2ha 3-(4-乙醯基胺基底。定-1-基甲基）_卜側氧基_2_苯基 -1，2-二氫-異喧琳_4_黢酸（（S )-1-苯基-丙基）_醯胺 2hb 1-侧氧基_3-(1-側氧基-2,8-二氮雜-螺[4.5]癸-8-基甲基）-2-苯基-i，2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基醯胺 2hc 3-[4-羥基-4-(3-三氟甲基-苯基）_哌啶-丨_基甲基μι_ 側氧基-2-苯基-l，2-二氫-異喹啉-4-羧酸（（s)-l-苯基-丙基;)_ 醯胺 2hd 1-侧氧基-2-苯基- 3-(4-三氟甲基_〇底。定-1-基甲基）_ 1，2-二氫-異喹啉_4_羧酸苯基-丙基）_醯胺 2he 3-[4-(4_甲基-〇底啡-1-獄基）_0底。定-卜基甲基]_ι_側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）-醯胺 2hf 3-(5-異丙基-3H-螺[異苯并吱喃_ι，4:娘咬]-1’-基甲基）-1-側氧基-2-苯基-1，2-二氫-異喹啉_4_羧酸（（S)-l-苯基_ 丙基）-醯胺 2hg 3-[4-(乙醯基-曱基-胺基）_4_笨基-哌啶-1-基曱基]_ 69 200906801 卜侧氧基-2-苯基-1，2-二氫-異啥琳-4 -緩酸（（S)-l ·苯基-丙基）-醯胺 2hh 4-{1-[1-側氧基-2-苯基- 4- (1-苯基-丙基胺甲酿基）_ 1，2-二氫-異噎琳-3-基甲基]-π底咬_4-基}-派啡_ι_叛酸第三丁酯 2hi (2-{1-[1-側氧基-2-苯基- 4- (1-苯基-丙基胺甲酿基）_ 1,2-二氫-異喧琳-3-基曱基]-n辰η定-4-基}-乙基）-胺基甲酸第三丁酯 2hj 3-(4 -甲基胺基-4-苯基- η底I»定-1-基甲基）-1-側氧基_2_ 苯基-1，2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）-醯胺 2hk 3-(4-乙醯基胺基_4_苯基-哌啶-1-基曱基）_丨_側氧基 -2-苯基-1，2-二氫-異喹琳_4_叛酸（（S)-l-苯基-丙基）-醯胺 2h丨3-[4-乙醯基胺基_4-(3-氟-苯基）-哌啶-1-基甲基]-1-側氧基-2-苯基-1,2-二氫-異喹啉_4_羧酸（(S)-l-苯基-丙基）-醯胺 2hm 1-側氧基-3·[4_(4_侧氧基-哌啶-丨·羰基）_哌啶-卜基甲基]-2-苯基-1，2-二氫-異喹啉_4-羧酸（（S)-l-苯基-丙基）-醯胺 2hn 3_[4,4’]聯哌啶-1-基甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-鲮酸（（yd•苯基·丙基醯胺 2ho {1-[1-侧氧基_2苯基_4 (1_苯基-丙基胺甲醢基）_ 1，2-二氫-異喧啉_3_基甲基]-哌啶_4_基胺基甲酸第三丁酯 2hp 3-[1，4']聯哌啶-1·-基甲基-1-側氧基-2-苯基-1,2-二氯-異啥琳-4-幾酸[環丙基_(3_氟_苯基）_甲基]_醯胺 200906801 2hq 1-側氧基-3-(4-苯乙基-哌畊-1-基甲基）-2-苯基_ 1,2-二氫-異喹啉-4-羧酸[環丙基_(3_氟-苯基）-甲基]_醯胺 2hr 3-(4-異丙基-哌啡-丨_基甲基）·卜側氧基-2_苯基_丨，2_ 二氫-異喹啉-4-羧酸[環丙基_(3_氟_苯基;)_甲基醯胺 2hs 3-[4-(2·嗎福林_4_基·乙基）_〇辰啡-1_基甲基]_ι_側氧基-2-苯基_1，2_二氫-異喹啉羧酸[環丙基_(3_氟_苯基）_曱基]-醯胺 2ht 3-[4_(1-甲基-哌啶-4-基）-哌畊-1-基甲基]―卜側氧基 -2-苯基-1，2-二氫-異喹啉_4_羧酸[環丙基_(3_氟_苯基）_曱基]-醯胺 2»iu 1-側氧基_2_苯基_3吖4_(2_哌啶_丨_基乙基）_哌畊-卜基甲基]-1，2-二氫-異喹啉_4_羧酸[環丙基_(3_氟-苯基分甲基]-醯胺 2hv 1-側氧基-2-苯基_3_[4_(2“比咯咬」基-乙基卜底啡_ 基甲基]-1,2-二氫-異啥嘛{叛酸[環丙基_(3_敗-苯基）·甲基]-醯胺心卜側氧基·2_苯基吼咬-4-基甲基-旅啡小基甲基^^二氯-異㈣-^酸味丙基分氟-苯奸甲奸醯胺四二氫-異喹啉-4-羧酸[環丙基-(3-氟 2hx 3-(4-羥基-3,4,5,6. 基）-1-側氧基-2-苯基-l，2--苯基）-甲基]-醯胺氫-2H-[4,4’]聯吼啶-1-基甲 2:y 3-[4_(2_嗎福林-A乙基)_哌啶小基甲基w-側氧基-2-本基-1，2-一 SL-異啥琳_4，酸[環丙基_(3_氟苯基）_曱 71 200906801 基]-醯胺 2hz 3-[4-羥基-4-(3-曱氧基-苯基）-哌啶-1-基甲基]-1-側氧基-2-苯基-1，2-二氮-異喧嚇^-4-魏酸[環丙基- (3 -氣·苯基）_ 曱基]-醯胺 2ia 3-[4-(乙醯基-甲基-胺基）-4-苯基-哌啶-1·基曱基]-1-側氧基-2-苯基-1，2-二氮-異喧琳-4-缓酸[環丙基- (3 -氣-苯基）-曱基]-醯胺 2ib 2-(2 -鼠-苯基）-1-側氧基- 3- (4-苯乙基-娘明1 -1 -基曱基）-1，2-二鼠-異喧淋·4-繞酸（（S)-l-苯基-丙基）-S蓝胺 2ic 2-(2_氟-苯基）·3-(4·異丙基·娘啡-1-基甲基）-1-側氧基-1，2 -二氮-異啥琳-4-竣酸（（S)-l -苯基-丙基）-酿胺 2id 3-[1，4’]聯哌啶-l’_基甲基-2-(2-氟-苯基）-1_側氧基-1，2 -二氮-異嗜琳-4-繞酸（（S)-l-苯基-丙基）-酿胺 2ie 2·(2 -氣-苯基）-3-[4-(2-嗎福林-4·基-乙基）-派明1 - 1 _ 基甲基]-1-側氧基-1，2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）-驢胺 2if 2-(2 -氣-苯基）-3-[4-(1-曱基-派°定-4-基）派明1 -1 基曱基]-1-側氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）- 酿胺 2ig 2-(2-氣-苯基）-1-側氧基_3_[4-(2 -派σ定-1-基-乙基）_ 哌畊-1-基曱基]-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）- 醯胺 2ih 2-(2 -氣-苯基）-1 -側乳基-3-[4-(2 - °比洛。定-1 -基-乙基）-哌畊-1-基甲基]-1，2-二氫-異喹啉-4-羧酸（（S)-l·苯基-丙 72 200906801 基）-醯胺 2ii 2-(2 -亂-苯基）-1-側乳基- 3- (4 -0比〇定-4-基曱基-〇辰明1 -1-基甲基）-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ij 2-(2-氟-苯基）-3-(4-羥基-3,4,5,6-四氫-2H-[4,4’]聯吡啶-卜基甲基）-1-側氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ik 2-(2 -乳-笨基）-3-[4-(2-嗎福林-4-基-乙基）-旅0定-1 _ 基曱基]-1-側氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙 ί 基）-醯胺 2il 2-(2-氟-苯基）-3-[4-羥基_4-(3-甲氧基-苯基）-哌啶-1-基曱基]-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2im 3-[4-(2-嗎福林-4 -基-乙基）-旅明^ -1 -基曱基]-1 -側氧基-2-鄰甲苯基-1，2-二氳-異喹啉-4-羧酸（（S)-l-苯基-丙基）- 醯胺 2iπ 1 -側乳基-3 - [4-(2 -旅。定-1 -基-乙基）-派明1 -1 -基甲、基]-2-鄰曱苯基-1,2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）- 醯胺 2 i ο 1 -側氧基-3 - ( 4 - °比0定-4 -基甲基-旅明1 -1 -基曱基）-2 -鄰甲苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ip 2-(3_亂-苯基）-1-側氧基-3_(4_苯乙基-旅明：-1 -基曱基）-1，2 -二氮-異哇嚇 - 4-叛酸（（S)-l-苯基-丙基）-酿胺 2iq 2-(3_氣-苯基）-3-(4·異丙基-派啡-1-基甲基）-1-側氧基-1，2 -二鼠-異喧琳-4-竣酸（（S)-l -苯基-丙基）-酿胺 73 200906801 2ir 3-[1，4·]聯哌啶-1’-基甲基-2-(3-氟-苯基）-1-側氧基-1，2-二氮-異p奢嚇· - 4-竣酸（（S)-l-苯基-丙基）-酿胺 2is 2-(3 -氣-苯基）-3-[4-(2-嗎福林-4-基-乙基）-旅明1 -1 基曱基]-1-側氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2it 2-(3 -氣-苯基）-3-[4-(1-曱基-痕咬-4-基）-B底啡-1 -基甲基]-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）- 醯胺 2iu 2-(3-氟-苯基）-1-侧氧基-3-[4-(2-哌啶-1-基-乙基）-哌畊-1-基甲基]-1,2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）- 醯胺 2iv 2-(3-氣-苯基）-1 -側氧基- 3- [4-(2 -β比洛0定-1 -基-乙基）-哌畊_1_基甲基]_1，2_二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2iw 2-(3-氟-苯基）-1-側氧基-3-(4-吡啶-4-基曱基-哌畊-1-基甲基）-1，2-二氳-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 21\2-(3-氣-苯基）-3-[4-(2-嗎福林-4-基-乙基）-旅。定-1_ 基甲基]-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2iy 2-(3 -氣-苯基）-3-[4 -輕基-4-(3 -甲氧基-苯基）-π底°定_ 1- 基甲基]-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2iz 3-[4-(乙醯基-甲基-胺基）-4-苯基-哌啶-1-基甲基]- 2- (3-氟-苯基）-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯 74 200906801 基-丙基醯胺 2ja 2-(3-氯-本基）-1-側氧基- 3- (4-苯乙基-旅啡_ι_基甲基）-1,2-二氫-異啥琳-4-缓酸（（S)-l-苯基-丙基）_醯胺 2jb 2-(3_氣-苯基）-3_(4_異丙基-哌啡-1-基曱基）_l側氧基_1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2jC 3-[1，4']聯哌啶-l，_基甲基_2-(3_氣_苯基）_丨_側氧基_ 1，2-二氫·異喹啉_4_羧酸（（S)-l-苯基-丙基）_醯胺 2-(3_氣-苯基）_3_[4_(2_嗎福林_4_基-乙基）_哌啡土甲基]-1-側氧基_1，2-二氫-異喹啉_4-羧酸苯基·丙基）-醯胺 2je 2-(3-氯-苯基）_3-[4-(1-甲基-派。定_4·基）_旅啡_卜基曱基]-1-側氧基_丨，2_二氫_異喹啉_4_羧酸（〇〗_苯基-丙基）_ 醯胺 2 (3-氯_苯基）_丨_側氧基_3_[4_(2_派。定_卜基-乙基）_ 哌畊小基甲基]_1，2·二氫-異喹啉_4·羧酸（（S)-l-苯基-丙基）· 醯胺 (3 -氯-苯基）-側氧基_3-[4-(2- η比略咬_ 1 _基_乙土）尤啡基曱基卜以-工氫-異喹啉-4_緩酸（（s)-l-苯基-丙基）-酿胺 2 1 h 2 (3氣-笨基）_ι·側氧基_3_(4-<7比〇定_4_基曱基_0底啡 1-基甲基）-19 ..，-一虱-異喹啉-4-羧酸（（S)-l-苯基-丙基）·醯胺 75 1 (3氣-苯基）-3-[4_(2·嗎福林_4·基-乙基）_D底啶基曱基]-1 -伽备„；氧基_1，2-二氫-異喹啉-4-羧酸（(S)-l_苯基_丙 200906801 2jj 2_(3_氯-本基）-3-[4-經基-4-(3-甲氧基-苯基）-α底。定- 1- 基甲基]-1_侧氧基-1，2-二氫-異喹啉_4_羧酸（(S)_i_苯基-丙基）-醯胺 2jk 3-[4-(乙醢基-甲基_胺基）_4_苯基_哌啶基甲基]_ 2- (3-氯-苯基）-1-側氧基-12.二氫_異喹啉_4_羧酸（^-^苯基-丙基）-酿胺 2jl 1-侧氧基-3-(4-苯乙基-哌畊_丨_基甲基）_2_間甲苯基_ 1，2-二氫-異喹啉-4-羧酸（（s)-l-苯基-丙基）_醯胺 2jm 3-[1，4’]聯哌啶·ι，·基曱基側氧基_2_間甲苯基_ 1，2_二氫-異喹啉-4-羧酸（（s)-l-苯基-丙基）_醯胺 2jn 3-[4-(2_嗎福林_心基-乙基）_哌啡小基曱基]小側氧基-2-間曱苯基_ι，2-二氫-異喹啉_4_羧酸（（幻—卜苯基-丙基）_ 醯胺 2jo 3-[4-(1-甲基-哌啶_4_基）_哌畊_丨_基甲基]_丨_側氧基 -2-間甲苯基·ι，2-二氫-異喹啉_4_羧酸苯基_丙基醯胺 2jp 1-侧氧基-3-[4-(2-哌啶-1-基-乙基）-哌啡_丨_基甲基]·2-間甲笨基_i，2-二氫-異喹啉_4_羧酸（(s)-i-苯基_丙基）_ 酸胺 2jq 1-側氧基-3-[4-(2-吡咯啶-1-基-乙基）_哌哄小基甲基]-2-間甲苯基-i，2-二氫-異喹啉_4_羧酸（(s)_i_苯基_丙基）_ 酿胺 2jr 1-側氧基-3-(4-吡啶-4·基甲基-哌畊_丨·基曱基）_2_間甲苯基-1，2-二氳·異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 76 200906801 2js 3 [4-(2-嗎福林_4_基-乙基）-d底u定_ι_基甲基]_ι_側氧基-2-間曱苯基―；!，、二氫_異喹啉_4_羧酸（（”_〗_苯基-丙基醯胺 2jt 3-[4-羥基_4_(3_甲氧基_苯基）_哌啶基曱基μι•側氧基-2-間曱苯基—丨,二氫_異喹啉_4_羧酸（^^丨-笨基-丙基）-醯胺 2ju 3-[4-(乙醯基_甲基_胺基）_4_苯基_哌啶_丨_基甲基]_ 1-側氧基-2-間甲苯基-丨，；^二氫_異喹啉_4_羧酸苯基_ 丙基）-酿胺 3a 1_側氧基_3_(2-側氧基比咯啶-1-基曱基）_2_苯基_ 1,2_二氫異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 3b 8-氯-1-側氧基_3_(2_側氧基_吡咯啶_丨_基甲基）_2_苯基-1,2-二氫-異喹啉_4_羧酸（（”_〗_苯基-丙基）_醯胺 4a 3-氰基曱基側氧基_2_苯基_1>2_二氫_異喹啉_4-羧酸（（S)-l -苯基-丙基）_醯胺 5a 3甲基-1_側氧基_2_苯基_ι，2_二氫-異哇琳_4_緩酸 N，N-二苯基肼 5b N’-(3-甲基-1·侧氧基_2_苯基二氫_異喹啉_心幾基）-N-苯基-肼羧酸甲酯 laa 2-(3 -甲氧基-本基）-3 -甲基-1-側氧基_ι，2-二氫_異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 lab 2-(4 -曱乳基-本基）-3 -甲基-1-側氧基-1,2-二氫_異喹啉-4-羧酸（（S)-l·苯基-丙基）-醯胺 lac 2-(4-氟-苯基）-3-曱基_ι·側氧基二氫_異啥琳_ 77 200906801 4-羧酸（（S)-l-苯基-丙基）-醯胺 lad 2-(4-氣-苯基）-3-甲基-1-側氧基-i，2-二氫·異喹啉_ 4 -叛酸（（S)-l -苯基-丙基）-δδ胺 lae 3-甲基-1-侧氧基-2-對甲苯基-l，2-二氫-異喹啉-4-緩酸（（S)-l -苯基-丙基）-醯胺 laf 2-(3-甲氧基-苯基）-3-甲基-1-側氧基_1，2_二氫-異喹 #-4-缓酸[(S)-環丙基- (3 -氟-苯基）-甲基]-醯胺 lag 2-(4-甲氧基-苯基）-3 -甲基-1-側氧基-1,2-二氫-異喹琳-4-緩酸[(S)-環丙基-(3 -氟-苯基）-甲基]-醯胺 lah 2-(4-氟-苯基）·3-甲基-1-側氧基-1,2-二氳-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺 lai 2-(4-氣-苯基）-3-曱基-1-側氧基-l，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）·甲基]-醯胺 laj 3-甲基-1-側氧基-2-對甲苯基-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺 lak 2-(2-甲氧基-苯基）-3 -甲基-1-侧氧基- l，2-二氫-異喹啉_4_羧酸（（S)-l-苯基-丙基）-醯胺 lal 2-(2-甲氧基-苯基）-3-曱基-1-側氧基-l，2-二氫-異喹琳-4-叛酸[(S)-環丙基- (3 -氟-苯基）-甲基]-醯胺 lam 3-甲基-8-硝基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4 -諼酸（（S)-l -苯基-丙基）-醯胺 lan 3 -甲基-8-石肖基-1-側氧基-2-苯基-1，2-二氫-異喧琳_ 4-缓酸[(S)-環丙基- (3 -氟-苯基）-甲基]-醯胺 lao 8-甲氧基-3-甲基-1-側氧基_2_苯基-1,2-二氫-異喧 78 200906801 啉-4-羧酸苯基-丙基）_醯胺 lap 8 -甲氧基-3 -甲基-1-側氧基苯基- L2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）_甲基]_醯胺 laq 8-胺基-3-甲基-1-側氧基_2_苯基-1,2-二氫-異喧琳-4_羧酸（（S)-l-苯基-丙基）-醯胺 lar 8-氰基-3-甲基-1-側氧基-2-苯基_ι,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 las 8 -氯-3-曱基-1-側氧基-2-苯基- i，2-二氫異1Ί:琳-4-缓酸[(S)-1-(4-氯-苯基）-丙基]-酿胺 lat 8-氯-3-甲基-1-侧氧基-2-苯基-1,2-二氫-異喹啉-4-叛酸[(S)-l-(4 -氟-苯基）-丙基]-醯胺 lau 8-氯-3-曱基-1-側氧基-2-苯基_1，2_二氫-異喹啉-4-羧酸[(S)-l-(2-氟-苯基）-丙基]-醯胺 lav 8-氯-3-甲基-1-侧氧基-2-苯基_ι，2-二氫-異喹啉-4-幾酸[(S)-l-(3-氯-苯基）-丙基]-酿胺 law 8-氣-3-曱基-1-側氧基.2-苯基_1，2_二氫-異喹啉-4-叛酸[(S)-(3-氯-苯基）_環丙基-曱基]_酿胺 lax 8·氯-3-甲基-1-侧氧基-2-苯基-1,2-二氫-異喹啉-4-竣酸[(S)-(4-氯-苯基）_環丙基-曱基]_酿胺 lay 8-氯-3-甲基-1-侧氧基-2-苯基-12·二氫-異喹啉-4-羧酸[(S)-1-(3-氟-苯基）_丙基]-醯胺 laz 8-氯-3 -甲基-1-側氧基_2_苯基-12-二氫-異喹啉-4-羧酸（（S)-2-甲基·ι_苯基-丙基醯胺 lba 8-氯-3-甲基·1_側氧基_2_苯基_ΐ，2-二氫-異喹啉-4- 79 200906801 羧酸[(S)-環丙基-(4-氟-苯基）-甲基]-醯胺 lbb 8 -乳-3-曱基-1-側氧基-2-苯基-1,2-二氫-異喧琳- 4-羧酸[(S)-1-(2-氯-苯基）-丙基]-醯胺 lbc 8 -氯-3-甲基-1-側氧基-2-苯基-1,2-二氫-異喧琳-4-羧酸（（S)-環戊基-苯基-甲基）·醯胺 lbd 8-氯-3-甲基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸[(S)-(2-氯-苯基）-環丙基-甲基]-醯胺 lbe 8-氯-3-甲基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸[(S)-環丙基-(2-氟-苯基）-甲基]-醯胺 lbf 8-氯-3-甲基-1·側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-環己基-苯基-甲基）_醯胺It 8_Chloro-3-3-indolyl-1-sideoxy_2_phenyl-indole, 2-dihydro-isoquinoline_4_carboxylic acid [(S)-cyclopropyl-(3-fluoro- Phenyl)-indenyl]-nonylamine 2a 3-dimethylaminoindenyl-indole_sideoxy-2_stupyl-indole, 2-dihydro-isoquine. Lin-4-supplemented acid ((S)-l-phenyl-propyl)-decylamine 2b 3-decylamino fluorenyl 丨侧侧侧 _2 _2 _2 _2 侧侧侧侧侧侧侧二二· 4-carboxylic acid ((S)-1-phenyl-propyl)-nonylamine 2c 3-ethylaminomethyl small side oxy-2_phenyldihydro-isoquinoline _ 4-carboxylate Acid ((S)-1-phenyl-propyl)-nonylamine 2d 3-cyclopropylaminoindolyl-b-oxy-2-phenyl-i,2-dihydro-isoquinoline-4 _carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2e 3-[(cyclopropylmethyl-amino)-methyl]-b-oxy 2_phenyl-U2_ Hydrogen-isoquinolin-4-carboxylic acid ((S)-l-phenyl-propyl decylamine 2f 3-(3,6-dihydro-2H-pyridin-1-ylmethyl)-1-side oxygen Benzyl-2-phenyl- 50 200906801 I,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2g 3-[4-(2-曱Oxy-phenyl)-pipedino-1-ylindenyl]-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l- Phenyl-propyl)-guanamine 2h 3-[4-(4-fluoro-phenyl)-piperidin-1ylmethyl]-1-yloxy-2-phenyl-1,2-di Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2i 3-(4-mercapto-piperidin-1-ylmethyl)-l-side oxygen Base_2_phenyl d,2_dihydro-isoquinoline 4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2j 4-[1-o-oxy-2-phenyl-4-(1-phenyl-propylaminecarbamyl) )-l,2-one-gas-isoindole-3-ylindenyl]-parphine-1-rebel acid vinegar 2k 3-(4-methyl-piperidin-1_ylindenyl)_1_ side Oxy-2_phenyl-12-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 21 1-sided oxy-2-phenyl-3 -(1,3,4,9-tetrahydro-β-indol-2-ylmethyl)-I,2-dihydro-isoquinolinecarboxylic acid phenyl-propyl)-decylamine 2m 1-side Oxy.2_Phenyl_3_η-Des-Phenyl-indoleyl-J,2-dihydro-isoindoline-4-carboxylic acid ((S)-l-phenyl-propyl)·decylamine 2n 3_(3_Methyl-Benary _ι_ylmethyl)]_Sideoxy_2_phenyl·^2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl -propyl)-nonylamine 2〇3-(3,5-dimethyl-piperidin-ylmethyl)!_Sideoxy_2_phenyl_ 1,2-dihydro-isoquinoline _ 4_carboxylic acid ((s)]·stupyl-propyl)·guanamine 2p 3-(4-benzyl-piperidin·!-ylmethyl) "_sideoxy_2_phenyl_丨, 2_ Dihydro-isoquinoline _4·carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2q 1-sided oxy- 3-[4-(2- oxo-2- Pyrrolidin-1-yl-ethyl)-piperidin-1-ylindenyl]benzene Base_1,2_dihydro-isoquinolinecarboxylic acid ((8)-phenylphenyl-propyl)-decylamine 51 200906801 2r 3-forfolin-4-ylmercapto-1-oneoxy_ 2-phenyl-1,2-dihydro-isoquinolin-4-carboxylic acid phenyl-propyl)-decylamine 283-(2,6-dimethyl-norfosin-4-ylmethyl) _1_Sideoxy_2_phenyl_ 1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2t 1-sideoxy-2 -phenyl-3-thiofenofin_4_ylmercapto_ι,2_dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl decylamine 2u 3- (1,4-Dioxa-8-aza-spiro[4.5]癸8-ylmethyl)_b-oxy-2-phenyl-1,2-dihydro-isoquinoline_4_ Carboxylic acid (〇·〗_Phenyl-propyl decylamine 2ν 1-sided oxy-2-phenyl-3-piperidin-1-ylmethyl- it dihydro-isoquinoline-4-carboxylic acid ( (S)-l-phenyl-propyl)-guanamine 2w 3-(2-mercapto-piperidinyl-1-ylindenyl)"-sideoxy-2_phenyl_1>2_dihydrogen -isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl decylamine 2*3-(2,6-dimethyl-piperidinyl-1-ylmethyl)_1_sideoxy _2_Phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-styl-propyl)-decylamine 2y 3-(2-hydroxymethyl-piperidine _丨_ylmethyl) "_sideoxy_2_phenyl -1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2z 1-[1-o-oxy-2-phenyl-4-( Ethyl 1-phenyl-propylaminodecyldihydro-isoquinolin-3-ylmethyl]-piperidine-3-carboxylate 2aa 3-(3-indolyl-piperidinylmethylindole Sideoxy-2phenyl-I. -Dihydro-isoquinoline_4_carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ab 3-(4-hydroxy-piperidinylhydrazinylmethyl)_丨_ side oxygen Base 2_phenyl-indole, 2_dihydro-isoquinoline-4-carboxylic acid ((s)-〗-phenyl-propyl)-decylamine 2ac 1-sideoxy_2_phenyl_ 3-(4-Phenyl-piperidine-indenylmethyl) 4,2-dihydro-isoquinoline-4-carboxylic acid ((s)"-phenyl-propyl)-decylamine 52 200906801 2ad 1-[1-Alkyloxy-2-phenyl-4-(1-phenyl-propylaminemethanyl) 4,2 dihydro-isoindolin-3-ylindenyl]-η bottom bite- 4-ethyl decanoate 2ae 3-(4-mercapto-piperidin-1-ylmethyl) 丨侧侧 _2 _2 _2 _2 _2 _2 ^ ^ ^ ^ ^ ^ ^ ^ ^ ((S)-l-phenyl-propyl)_nitral amine 2af 1-sideoxy-2·phenyl_3_(4_pyridine_2_yl-piperidin-buylmethyl)_ 1,2 -monohydro-isoquinoline-4-decanoic acid ((S)-l-styl-propyl)-decylamine 2ag 3-(octahydro-quinolin-1-ylindenyloxy-2_benzene _152_二虱-isoindolin-4-o-acid ((S)-l-phenyl-propyl)-decylamine f, 2ah 3 -azaindole-heptan-1-ylmethyl-1- Oxyloxy-2-phenyl_ι,2-dihydro-isoindole 1#-4 - tacrotic acid ((S)-l-phenyl-propyl)-nonylamine 2ai 3-(3-hydroxy-piperidin Pyridin-1-yl Base side oxy-2_phenyl_12_dihydro-isoindole: scare >-4-sodium acid ((S)-l-phenyl-propyl)-decylamine 2aj 3·[4·(2 ,4-dimethyl-phenyl)-β-formyl-yl-methyl-small-oxyl-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S) -l-phenyl-propyl isonidine 2ak 3-[4-(3,4-dimethyl-phenyl)-piped-1-ylindenyl] side fluorenyl _ 2 -benyl-1, 2 - a milk-isoindole-4-deoxy acid ((S)-l-phenyl-propyl)-bristamine, 2al 3_(4-dimethylamino-piperidin-1-ylindenyl) -1-Sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2am 3-[4-( 2,5-Dimethyl-phenyl)-piperidin-1-ylindenyl]-1-yloxy-2-phenyl-1,2-dihydro-isoindolin-4-carboxylic acid (( S)-l-phenyl-propyl)-bristamine 2an 3-[4-(2-fluoro-phenyl)-pipedino-1-ylmethyl]-1-oxo-2-phenyl- 1,2-dihydro-isoindolin-4-o-acid ((S)-l-phenyl-propyl)-decylamine 2ao 3-[4-(3.methoxy-phenyl)-piped -1-ylmethyl]-i_sideoxy·2-phenyl-1,2-dihydro-isoindolin-4-o-acid ((S)-l-phenyl-propyl)-nitramine 53 200906801 2ap oxime oxy-2-phenyl-3-(4-m- fluorenyl-piperidinyl Base)_ 1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l·phenyl-propyl)-decylamine 2aq 3-[4-(4-methoxy-phenyl) -piperidinylmethyl; sideoxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2ar 1-side Oxy-3-(4-phenethyl-piperidin-yl-methyl)_2-phenyl-ι,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-styl- Propyl;)·guanamine 2as 1-sided oxy-2-phenyl-3-(4-pyrimidin-2-yl-piperidin-1-ylindenyl)· 1,2-dihydro-isoindole -4-Resin ((S)-l-phenyl-propyl)-bristamine 2at 3-[4-(2-cyano-phenyl)-piperidin-1-ylindenyl]-b. Base 2_phenyl_1,2_dihydro-isoindolin-4-o-acid ((S)-l-phenyl-propyl)-decylamine 2au 3-[4-(4-chloro-benzene Base)-piperidin-1-ylindenyl]-1-sideoxy-2·phenyl_1,2-dihydro-isoindole-4-deoxalate ((S)-l-phenyl-propionate Base) _ 2 amine 3-a ((lS,3R,5R)-3-hydroxy-8-aza-bicyclo[3.2.1] oct-8-ylmethyl)-1 - oxo-2-benzene 1,2-dihydro-isoindolin-4-o-acid ((S)-l-phenyl-propyl)-nonylamine 2aw 3-(4-ethylindenyl-piperidin-1-ylindole Base)-1-sideoxy-2_phenyl-1,2 -nitrogen_isowa -4 - tacrotic acid ((S)-l-benyl-propyl)-bristamine 2ax 3·(4-methyl-[1,4]diazepinecycloheptan-1-ylindenyl)_丨·Side-oxygen-based-1,2-·-murine-isoindole-4-deoxy acid ((S)-l-phenyl-propyl)_bristamine 2ay 3-(4-ethyl-piped- 1-ylmercapto)-1-indolyl-2-phenyl-u2_dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2az 3- ((2S,6R)-2,6-dimercapto-wfolin-4-ylmethyl)_ι_lateral oxy-2-phenyl-1,2-dihydro-isoindol-4- Acid ((S)-l-phenyl-propyl)-decylamine 2ba 3-[4-(2,4-difluoro-phenyl)-piperidin-1-ylindenyl]_M-oxy-2_1 54 200906801 Phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2bb 3-[4-(3-dimethylamino) -propyl)-piperidin-1-ylmethyl]-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl -propyl)·guanamine 2bc 3-(4-isopropyl-based Benylmethyl)-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S) -1-phenyl-propyl)-nonylamine 2bd 3-(3-Aza-bicyclo[3.2.2]indol-3-ylmethyl)-1-yloxy_2·phenyl-1,2 -Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propane - indoleamine 2be 3-(4-cyclopentyl-piperazin-1-ylmethyl)-1-oxo-2-phenyl-1,2-( 'dihydro-isoquinoline-4- Carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2bf 3-[1,4·]bipiperidin-1·-ylmethyl-1-oxo-2-phenyl-1 ,2-dihydro-isoindole-'Resin ((s)-l-phenyl-propyl)-guanamine 2bg 3-(3,4-dihydro-1H-isoquinolin-2-yl Base)-1_Sideoxy-2_phenyl-1,2-dihydro-iso-O-line-4-deoxalate ((S)-l-phenyl-propyl)-decylamine 21>113- [4-(2-Dimethylamino-ethyl)-piperidin-1-ylmethyl]_1_sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylate Acid ((S)-l-phenyl-propyl decylamine 2bi 3-(4-hydroxymethyl-piperidin-1-ylindenyl)_1_sideoxy-2•phenyl_I 1,2- Dihydro-isoquinolin-4-carboxylic acid ((s)-i-phenyl-propyl)-guanamine 2bj 1-sideoxy-2·phenyl·3·[4·(tetrahydro-furan_ 2_carbonyl)-parpheny-bromomethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-l-phenyl-propyl)-decylamine 2bk 3-(4 _Isobutyl-piperidin-1-ylmethyl)_ι_sideoxy_2_phenyl-indole, 2_dihydro-isoindole_4_ tacrotic acid ((S)-l-phenyl·propyl Base)_bristamine 2bl 3-[4-(2-methoxy-ethyl)-piperidin _ι_ylmethyl sideoxy_2_phenyl-I,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2bm 3-[4- (2_?Folinin-ethyl)_piperidinyl]methyl]j side 55 200906801 Oxy-2-phenyl-1,2-dihydro-isostimulated·_4-rebel ((S) -l-phenyl-propyl)-bristamine 2bn 3-(1,3-dihydro-iso- 0-oxo-2-ylmethyl)-1-yloxy-2-phenyl-1,2 -dihydro-isoindolin-4-o-acid-phenyl-propyl)-bristamine 2bo 3-[4-(1-methyl-piperidin-4-yl)-piped-1-ylmethyl ]-1-Sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2 bp 1-sideoxy -2-phenyl-3-[4-(2-piperidin-1-yl-ethyl)-piperidine·1_ylmethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ( (S)-l-phenyl-propyl)·guanamine 2bq 1-sided oxy-2-phenyl-3-[4-(2-pyrrolidin-1-yl-ethyl)-piped _ 1 -ylindolyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)·decylamine 2br 3-(4-dimethylaminoguanidino Methyl-piperidin-1_ylmercapto)_1-p-oxy-2-benyl-1,2-dihydro-isoindolyl-4-acid ((S)-l-phenyl-propyl )-Taolin 2bs 3-(octahydro-pyrido[i,2_a]pyridin_2_ Methyl)_丨_sideoxy_2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l·phenyl·propyl)-decylamine 2bt 3-(4 -Mercapto-[1,4]diazepine cycloheptan-1-ylmethyl)_1_sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ( (s)-l-phenyl·propyl)-decylamine 2bu 3-[4-(4-cyano-phenyl)-piperidin-1_ylmethyl;|_1_sideoxy_2_benzene Base-1,2-dihydro-isoquinoline_4_carboxylic acid ((s)·!·phenyl-propyl)-decylamine 2bv 1-sideoxy-2_phenyl-3-(4- Pyridin-4-ylmethyl·piperidin-i-ylmethyl)-1,2-dihydro-isoquinoline_4_carboxylic acid phenyl-propyl)-decylamine 2bw oxime oxy-2_ Phenyl_3·[4·(3_pyrrolidinyl-indole-yl-propyl)_pipedipylmethyl]-1,2-dihydro-isoquinoline-continued acid ((8)]•phenyl- Propyl)·guanamine 2bx 1-sideoxy-2·stupyl·3_(4_〇啶 _2 _ _ _ _ _ _ 旅旅 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 _4_acid ((8) small phenyl-propyl) _ olamine 56 200906801 2by 3-(4- acetyl phenyl phenyl-1-ylmethyl)-1 - oxo-2-phenyl -1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-styl-propyl)-nonylamine 2bz 3-(4-t-butyl-perphenidylmethyl)-1 - Oxy-2-phenyl-1.2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ca 3-[4-(1-ethyl-propyl (S)-Phenyl-1-ylmethyl]-b-oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl Indole 2cb 3-[4-(2-cyano-ethyl)-pipedino-1-ylmethyl]-1-oxo-2-phenyl-1,2-dihydro-isoquinoline- 4-carboxylic acid ((S)-l-phenyl-propyl decylamine 2cc 3-(4-methyl ketone base "-1-ylmethyl)-1-yloxy-2-phenyl- 1,2-·-Wind-isoindole-4-decanoic acid ((S)-l-benyl-propyl)_Arylamine 2cd {1-[1-Sideoxy-2-phenyl-4- (1-phenyl-propylaminemethanyl)_ 1,2-dihydro-isoindolin-3-ylmethyl]-° bottom -4-yl}-ethyl acetate 2ce 3-[4 -(3-fluoro-phenyl)-piperidin-1-ylmethyl]-1-oxooxy-2-phenyl-1,2-dihydro-isoquinolin-4-carboxylic acid ((8) -1-phenyl-propyl)-guanamine 2cf 1-sided oxy-2 -phenyl-3-((S)-3_phenyl·slightly bite; ^ylmethyl)_1.2-dihydrogen -isoindole-4-o-acid ((S)-l-phenyl-propyl)-decylamine 2cg 1-sided oxy-2-phenyl-3-[4-(pyrrolidine_1-carbonyl) -piperidyl-ylmethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l -Phenyl-propyl)-nonylamine 2ch 3-[4-(Nalfolin-4-carbonyl)-piperidin-1-ylmethyl] sideoxy-2_benyl-1,2-dihydro- Isoindolin-4-deoxy acid ((S)-l·phenyl-propyl)-decylamine 2ci 3-(4-decyloxy-slightly -1-ylindenyl)-1_sideoxy_ 2_Phenyl-1,2_-hydro-isoquinoline-4-acid ((S)-l-phenyl-propyl)-bristamine 2cj 3-(4'-radio-3',4' , 5',6'-tetrahydro-2Ή-[3,4'] η ratio.定_1'_基基基)-1-Sideoxy-2-phenyl-1,2-dihydro-isoindole_4-sodium acid ((s)_i_phenyl 57 200906801 -propyl) -guanamine 2ck 3-(4-hydroxy-3,4,5,6-tetrahydro-2H-[4,4']bipyridin-1-ylmethyl)-1-oxo-2-phenyl -1,2-dihydro-isoquinoline-4-carboxylic acid ((3)-1-phenyl-propyl decylamine 2cl 3-(3H-spiro[isobenzofuran-1,4,-piperidine ]-1'-ylmethyl)-1-oxo-2-phenyl-1,2-dihydro-isoxan-4-derivative ((S)-l-phenyl-propyl)- Indoleamine 2cm 3-(4-hydroxy-4-methyl-piperidin-1-ylindenyl)-1-oxo-2-phenyl-1,2-dihydro-isoindol-4- Acid ((s)-l-phenyl-propyl)-S basket amine 1 2cn 3-(hexamethylene-spiro[benzo[1,3]dioxazole-2,4,-piperidine]-1, -ylmethyl)-1. oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2co 1 -Sideoxy-2-phenyl-3-(3,4,5,6-tetrahydro-2H-[4,4,]bipyridyl-1-ylmethyl)-1,2-dihydro-iso Quinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2cp 3-[4-(2-dimethylamino-ethyl)-piperidin-1-ylmethyl ]_ι_Sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl - indoleamine 2cq 3-(4-dimethylaminesulfonyl-pemamine: _1_ylindenyloxy 2_benyl-1,2-one gas-isoindole _4-rebel acid ((S )-l-phenyl-propyl)-bristamine 2cr 3-(l,l-di- oxy-thio-allinone 4-ylindenyl)_1_sideoxy- 2-phenyl-l ,2-dihydro-isoquinolin-4-carboxylic acid ((S)-l-phenyl-propyl)·guanamine 2cs 1-sided oxy-2-phenyl-3-(2-° ratio bite -2-ylmethyl-u bottom bite_ι_ylmercapto)-1,2 - one wind-isoindole-4 - slow acid ((S)-l-stupyl-propyl)_bristamine 2ct 3-(2-Folinin-4-ylmethyl-piperidin-1-ylmethyl)_!_Sideoxy_2·Phenyl-1,2-dihydro-isoindole-4 Acid ((S)-l-phenyl-propyl)-decylamine 2cu 3-(4_furo[3,2-C]pyridine_4·yl-piperidin-buylmethyl)_丨_ side 58 200906801 Oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-i-phenyl-propyl)-decylamine 2 (^3-(4-ring) Propylmethyl-piperidin-1_ylmercapto)_1_sideoxy_2_phenyl-1,2-dihydro-isoquine>#-4-carboxylic acid ((8)-1-benzene Base-propyl)-nonylamine 2cw 3-[4-(2_ofofolin-4-yl-ethyl)-piperidinemethyl]]-quinone-oxy-2-phenyl-1, 2-dihydro-isoquinoline-4-carboxylic acid ( S)-l-phenyl-propyl decylamine 2cx 1-p-oxy-2-phenyl-3-(4-pyrimidin-2-yl-[ι,4]diazepine cycloheptan-1-yl Methyl)-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)_i_phenyl-propyl)_醯/ , amine 2cy 3-(4-methyl- 6,7-di Hydrogen-4H-carbo[3,2-c]n is more than 唆-5-ylmethyl)-1-yloxy-2-phenyl-1,2-dihydro-isoindole_4_ Acid ((s)_i_phenyl-propyl)-guanamine 2cz 3-[1,4]diazepan-1-ylmethyl-oxime_sideoxy_2_phenyl_1 2_Dihydro-iso-salt-4-butyric acid ((S)-l-phenyl-propyl)-bristamine 2da 3-((2S,5R)-2,5-dimethyl-piperidin- I_ylmethyl)"_sideoxy_2-phenyl-1,2-dihydro-isoindolyl-4-hypoacid ((S)-l-phenyl-propyl)-nonylamine U 2db 3-((S)-3-indolyl-Brigade-1-ylindenyl)-small-oxyl_2_phenyl_ 1,2-dihydro-isoindolin-4-acid ((S) -l·phenyl-propyl)_bristamine 2dc 3-((R)-3-indolyl-0-endo-1-ylmethyl-oxyl_2-phenyl-1,2-dichloro- Isoindole-4-deoxy acid ((S)-l-phenyl-propyl)-bristamine 2dd 3-[3-(3-chloro-phenyl)-bred-1-ylmethyl-oxyl _2_Phenyl-1,2·two-iso-isoline-4-acid ((S)-l-phenyl-propyl)_ Amine 2de 3-[4-(1Η-吲哚_4_yl)-piperidin-1-ylindenyl]-small-oxy-2_phenyl-1,2-dihydro-isoindole-4- Acid ((S)-l-phenyl-propyl)-decylamine 59 200906801 2df 1-sided oxy-3-(3-sideoxy-piperidinyl)-ylmethyl)_2_phenyldihydro- Isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2dg 3-[4-(1Η-indenyl)-piperidin-buylmethyl] sideoxy_ 2_Phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid (〇_!_phenyl-propyl)_decylamine 2dh 3-(6,9-aza-spiro[4.5]癸_9_ylmethyl)-1-oxooxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-i-phenyl-propyl decylamine 2di 3 -(M-diazaspiro[5.5]undec-4-ylmethyl}1_sideoxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s) -l-phenyl-propyl)-decylamine 2dj 3-(3-isopropyl-piperidin-1_ylmethyl)_丨_sideoxy_2_phenyl-n dihydro-isoquinoline 4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2dk 3-(3,3-dimethyl-piperidinyl-1-ylmethyl)_b-oxy-2_1 Phenyl _ 1.2-dihydro-isoquinolin-4-o-acid ((S)-l-phenyl-propyl)-decylamine 2dl 3-[3_(4-fluoro-yl)- lysyl Methyl]_!•sideoxy_2_ Base-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2dm 1-sideoxy-2-benyl- 3- (3 - p-Tolyl-indole- _ι_ylmethyl)_1.2-Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2dn 4-[1 - Sideoxy-2-phenyl-4-(1-phenyl-propylamine oxime)_丨,2_dihydro-isolin-3-ylmethyl]-π-endo- _ι_ Tributyl vinegar 2do 3-(4-decylamine decylmethyl-piperidinylmethyl-p-oxy-2-phenyl-1,2-dihydro-isoindolin-4-carboxylic acid (( s)-i-phenyl-propyl)-decylamine 2dp 8-chloro-3-dimethylaminomethyl-methane-side oxy-2_stupyl-^2-dihydro-iso-d-quine -4-Resin ((S)-l-phenyl-propyl)-bristamine 2dr 3-cyclopentylaminomethyl-1-yloxy_2_phenyl·ι,2-dihydro· Isosulfan-4-acid ((S)-l-phenyl-propyl)-decylamine 200906801 2ds 3-cyclohexylaminomethyl·N-side oxy-2_phenyl_丨, 2_2 Hydrogen-isoindolin-4-deoxy acid ((S)-1-phenyl-propyl)-decylamine 2dt 3-{[(2-hydroxy-ethyl)-methyl-amino]-indenyl} -1_Sideoxy_2_Phenyl-I,2-dihydro-isoquinoline-4-carboxylic acid (ο)-phenyl-propyl)-decylamine 2du 3-imidazole_1 -ylmethyl_ι_sideoxy_2_phenyl-indole, 2_dihydro-isoquinolin-4-carboxylic acid ((S)-l-stupyl-propyl)_nonylamine 2dv 3- (2-Methyl-imidazole-l-ylmethyl)_〗_Sideoxy·2_Phenyl", ^Dihydro-isoquinoline_4_carboxylic acid phenyl propyl) decylamine 2dw 3 -(4-methyl-imidazol-1-ylmethyl) "_sideoxy-2_phenyl n-hydro-isoquinolin-4-carboxylic acid ((S)-l-phenyl-propyl) _ decylamine 2dx 3-(2,5-dihydropyrrolidine-1-ylmethyl)-p-oxy-2-phenyl], 2-dihydro-isoquinolin-4-carboxylic acid ((S) -l-phenyl-propyl)-decylamine 2dy 3-(2,5-dimethyl-2,5-dihydro-pyrrole_;[_ylmethyl-oxyl-2-phenyl-1, 2-Dihydro-isoquinoline_4_carboxylic acid phenyl-propyl)-decylamine 2dz 1-sided oxy-2-phenyl-3-d piroxime small group methyl 丨, 2 _ Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine V 2ea 1_sideoxy-2-phenyl-3-(thiazol-2-ylaminomethyl) Base, 2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2eb 1-sided oxy-2-phenyl-3-(pyrimidine- 4-ylaminomethyl)_ι,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ec 3-(t-butylamino group- methyl _丨_Sideoxy_2_Phenyl-indole, 2_Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ed 3-[(2- Hydroxy-1,1-dimethyl-ethylamino)methyl]-dioxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)- L-phenyl-propyl)-decylamine 61 200906801 2ee 3-(Isopropylamino-methyl)-b-oxy-2_phenyl-indole, 2-dichloro-isoquinoline-4- Carboxylic acid ((s)-^·phenyl-propyl)-decylamine 2ef 3-[(2,yl-1-indolyl-ethylamino)-indenyl]+oxy 2phenyl- 1,2-dihydro-isoquinoline_4_carboxylic acid ((s)-i-phenyl-propyl)·guanamine 2eg 3-[(1-hydroxyindolyl-propylaminoindenyl)_丨_Sideoxy_2_phenyl-1,2-dihydro-isoquinoline_4-carboxylic acid ((S)-l-phenyl-propyl decylamine 2eh 3-[(2,2-di) Methyl-propylamino; (methyl) pendant oxy 2-phenyl] 1.2-dihydro-isoquinoline _4-carboxylic acid ((s)-l-phenyl-propyl decylamine 2ei 1-Phenoxy-2-phenyl-3-prop-2-ynylaminomethyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propane Base) 醯醯 2ej 3-allylamino fluorenyl-;!_sideoxy 2_phenyl-indole, 2_dihydro-isoquinoline-4-carboxylic acid ((S)-l- Phenyl-propyl)_醯2ek 3-[(Methyl-propionyl-2-yl)-amino]-methyl]_ι_yloxy-2-phenyl-1.2-dihydro-isoquinoline-4-carboxylic acid ((s) -l·phenyl-propyl)-nonylamine 3-monoallylaminomethyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ( (S)-l-phenyl-propyl)-nonylamine '2em 3_diethylaminomethyl-b-oxy-2-phenyl-1,2-dihydro-isoquinoline-4- Carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2eii 3-[(isopropyl-methyl-amino)-methyl-oxo-oxy-2_phenyl_ 1,2- - Hydrogen-isoindolin-4 - tempering acid ((S)-l-phenyl-propyl)-nonylamine 2eo 3-[((S)-2-hydroxy-1-methyl-ethylamino)_ Methyl bromoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-nonylamine 2ep 3-[(( R)-2-hydroxy-1-methyl-ethylamino)methyl]+ oxo _ 2 -benyl-1,2 - Iso-isoquine-4-indole ((S) -l·Phenyl-propyl)_Taolin 62 200906801 2eq 3-{[(2-Methoxy-ethyl)-indolyl-amino]-indenyl}_1_sideoxy_ 2-phenyl -l,2-dihydro-isoindolin-4-deoxalate ((S)-l-phenyl-propyl)-decylamine 2er 3-((R)-3-hydroxy-pyrrolidin-1-yl Methyl)-1-side oxygen -2-phenyl-1.2-dihydro-isowolin-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2es 3-((S)-3-hydroxypyrrolidine- 1-ylmethyl)-1-oxo-2-phenyl-1.2-dihydro-isoindolyl_4-sodium acid ((S)-l-phenyl-propyl)-decylamine 3-[ (cyclopentyl-fluorenyl-amino)-methyl]-i_sideoxy-2_phenyl_ 1,2-·-rat-isowa scary_4-slow acid ((S)-l - Phenyl-propyl)-bristamine 2eu 3-{[(2-hydroxy-1-methyl-ethyl)-methyl-amino]-methyl}_丨-oxy-2-phenyl-1 ,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ev 3-{[ethyl-(2-hydroxy-ethyl)-amino] -Methyldiazine·Sideoxy_2_Phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl decylamine 2ew 3-[(ethyl -Methyl-Amino)-Methyl-Alkyloxy_2_Phenyl·12_Isole-isoindole>-4 - Resin ((S)-l-phenyl-propyl)-nonylamine 2ex 3-cyclobutylaminomethyl-1-yloxy-2_styl-indole, 2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)- Indole 2ey 3-tetrahydroindol-1-ylindenyl-i_sideoxy·2_phenyl-indole, 2_dihydro-isoquinoline-4-carboxylic acid ((S)-l-benzene Base-propyl)-guanamine 2ez 3- (4-tert-butyl-piperidin-1-ylindenyl)]•Sideoxy_2_phenyl_ 1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l- Phenyl-propyl)-nonylamine 2fa 3-[4-(2-hydroxy-ethyl)-piperidinylmethyl]small oxime-2-phenyl-1,2-dihydro-isoquine Porphyrin-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2fb 3-{4-[2-(2-hydroxy-ethoxy)-ethyl]-piperidinylmethyl 63 200906801 Sideoxy-2-benyl-i,2_dihydro-isoindole_4_slow acid ((S)-l-phenyl-propyl)_ decyl 2fc 3-[4-(3 -chloro-5·trifluoromethyl-pyridin-2-yl)-piperidin-1-ylindenyl]-1-oxooxy-2-phenyl-1,2-dihydro-isoquinoline-4 -carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2fd 3 [4-(3,5-,-chloro-di-4-yl)----------- 1_Sideoxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2fe 4-[1- side oxygen Base 2_phenylphenyl-propylaminemethanyl)_ I,2-dihydro-isoquinoline_3_ylmethyl]_piperidine small acid benzyl ester 2ff 3-[4-( 3-fosolin-4-yl-propyl)-depressin-i-ylmethyl]_ι_ oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-l-phenyl-propyl)-decylamine 2fg 1-side Oxy-2_phenyl_3_[4_(3_Nylonbityl-yl-propyl)_π-desothyl-bromomethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid (( S)-l-Phenyl-propyl)-decylamine 2fh 3-[4-(4,6-monodecyloxy-. Bite-2-ylmethyl)_π-endophthyl-ι-ylmethyl]-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline_4-dihydroacid ((s) _Phenyl-propyl)-guanamine 2fi 3-[4-(3-hydroxy-propyl)-piped-1-ylmethyl•sideoxy-2_phenyl-1,2-dihydro -isoquinolin-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2fj 3-[4-(2,3-dihydroxy-propyl)-piperidinyl-methyl side Oxy- 2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 2fk (2-o-oxy-2-{ 4-[1·Phenoxyphenyl_4·(1-phenyl-propylaminemethanyl)-1,2-dihydro-isoquinolin-3-ylmethyl]-piperidin_丨_ Benzate ethyl)-tert-butyl carbamic acid 2fl 3-[4-(lH-indazol-5-yl)-piperidinylmethyl]-b-oxyl-2_ 64 200906801 Phenyl-1,2- Dihydro-isoindole _4_ tacrotic acid ((s)-i·stupyl-propyl)-guanamine 2fm 1-sided oxy-2-phenyl-3-(4-quinolin-6-yl -pepirinylmethyl)_ 1,2-dihydro-isoquinoline-4-carboxylic acid ((8)-1-phenyl-propyl)-nonylamine 2fn 3-[4-(6,7-di Methoxy-isophilic _4_yl)-Luming^1-ylindenyl]_ 1 -sideoxy-2-phenyl-1,2.dihydro-isoquinoline_4_oleic acid ((S)-l-phenyl-propyl)-醯2f〇4-{4-[1-Sideoxy_2_phenyl_4_(1-phenyl-propylaminoindenyl)-1,2-dihydro-isoquinolin-3-ylindenyl ]-Peptinopipipridin-1·carboxylic acid tert-butyl V ester 2fp 3-{4-[2-(4-chloro-phenoxy)-ethyl]-piperidin-1_ylmethyl} Small pendant oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2fq {4-[1-side oxygen Base 2_phenyl_4-(1-phenyl-propylaminemethanyl)-1,2-dihydro-isoquinolin-3-ylindenyl]-piperidine: _ι_ kibacetic acid Tributyl ester 2fr 1-sided oxy-2_phenyl_3-[4-(3,3,3-trifluoro-2-yl-propyl)-0-propan-1-ylmethyl]- 1,2-Dihydro-isoquinoline-4-carboxylic acid (clear). Phenyl-propyl hydrazine (, amine 2fs 3_[4_(2-hydroxy-propyl)-piperidin-1-ylindenyl]-1-yloxy-2-phenyl-I,2-dihydro -isoquinoline_4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2fu 3-[4-(4-amino-6,7-dimethoxy-quinazoline-2 -yl)-piperidin-1-ylindenyl]-1_sideoxy-2-phenyl_ι,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl- Propyl)-nonylamine 2fv (2-{4-[1-Sideoxy_2_phenyl_4_(1-phenyl-propylaminemethyl)- 1,2-indenyl-isoporphyrin _3-ylmethyl]-piperidin-indole_yl}-ethyl)-aminocarboxylic acid 65th 200906801 Tributyl ester 2fw I-sideoxy-3-{4_[2-(2-sideoxy- Imidazolidin-1-yl)-ethyl]_pipedino-1-ylmethyl}_2_phenyl-I,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl -propyl)-bristamine 2fx 3-{4-[(4,6-dioxalyl-pyrimidin-2-yl)-phenyl-indenyl]-perpenyl tau-indenyl}}-1 -Phenoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-l-phenyl-propyl)-nonylamine 2fy 3-(4-benzo[ 1,2,5]thiadiazole_4-yl-pipedino-1-ylmethyl)-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2fz 3-[4-(2,3-dihydro-benzene [1,4] Diterpenic-5-yl)-piperidin-l-ylmethyl]-1_ oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl:)-guanamine 2ga 3-[4-(4-methyl-喧hao-2-yl)- <»Desphedo-1-ylmethyl]-i_sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-stupyl-prop ))-nonylamine 2gb 1-tertiaryoxy-2-phenyl-3-[4-(n-But-2-ylaminocarbamimidylmethyl)- 0- phenyl-l-ylmethyl]-1 ,2-dihydro-isoindole-4-deoxy acid ((S)-l-phenyl-propyl)_ decylamine 2gc 3-[4-(6-chloro-3- oxo-3,4 -Dihydro-2H-benzo[1,4] agonistic. 8-yl)-tumidine =-1-ylmethyl]-1-yloxy-2-phenyl-1,2-dihydro-喧喧琳_4_ Carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2gd 3-(4-Aminomethylmethyl-bred tillage_ι·ylmethyl)_丨_side oxygen Base 2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l·phenyl·propyl)-decylamine 2ge 3-(4-pyridyl-4-benzene基-旅. 定小基曱基)小侧氧_2_苯66 200906801 基-1,2-Diazin-isoindolin-4-decanoic acid ((S)-l-phenyl-propyl) -Branched amine 2gf 3-[4-(4-chloro-phenyl)-4-hydroxy-piperidin-1-ylmethyl]-1-yloxy-2-phenyl-1,2-dihydro- Isoquinoline-4-carboxylic acid ((S)-l·phenyl-propyl)-guanamine 2gg 1-[1-o-oxy-2-phenyl-4-(1-phenyl-propylamine Mercapto)-1,2-di-mouse-iso-terin-3-ylmethyl]-d. -4-butylic acid 2gh 3-(4-cyano-4-phenyl-piperidin-1-ylindenyl)-indole-sideoxy-2_phenyl-1,2-dihydro-isoquinoline 4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2gi 3-(4-benzyl-4-hydroxy-piperidin-1-ylmethyl)_ι_ sideoxy 2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2gj 1_[1_sideoxy-2-benyl- 4-(1-Phenyl-propylamine methyl)_ι,2_dihydro-isoindolin-3-ylindenyl]-4-phenyl-η bottom bite-4-resinic acid vinegar 2gk 1- Oxyloxy-2-phenyl-3-[4-(phenyl-propionyl-amino)-piperidinyl-p-methyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2g 丨methyl-l-oxy-2·phenyl-4-(1-phenyl-propylaminecarbamyl)-1,2 -虱-isoindole-3-ylmethyl] 〇〇 4 4 4 _ _ _ 胺胺胺胺胺胺胺胺胺胺胺胺胺胺胺胺胺 2 2 2 2 2 2 2 2 Pyrrolidine_1-yl-ethyl)-piperidin-1-ylmethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid phenyl-propyl)-nonylamine 2gn 3-{4 -[5-(4-Fluoro-phenyl-Hu〆)-assised diazol-2-yl]-piperidinyl fluorenyl}-1-yloxy-2-phenyl-l,2-dihydro-iso Quinoline·4_carboxylic acid phenyl-propyl)-bristamine 2go 1-sided oxy-2_local. ·[Heart ^" than bite · 4 · base - [I, 2, 4] hired two saliva 5-base) - α bottom 11疋-1-ylmethyl]-1,2-dihydro-isophthalene 4·slow-acid phenyl·propyl)-decylamine 67 200906801 2gp 1-sideoxy·2-phenyl_3_[4_(3_^bD^_2-yl-[1,2,4]-diazole- 5-yl)-piperidin-1-ylmethyl μ, >dihydro-isoquinoline-4-carboxylic acid phenyl-propyl)-guanamine 2gq 1-sideoxy-2-phenyl_3 -[4-(3-Pyridin-4-yl-[1,2,4]oxadiazole-5-yl)-piperidin-1-ylmethyl]-indole, 2-dihydro-isoquinoline 4-carboxylic acid ((8)_丨_phenyl-propyl)-guanamine 2gr 3-(4'-hydroxy_3',4',5,6'-tetrahydro-2Ή-[2,4 ,]bipyridyl-1'-ylmethyl)-1-oxo-2-phenyl-indole, 2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propane ))-guanamine 2gs 3-(spiro[iso-dihydrobenzo-branthine) methyl group) oxime-2-phenyl-l,2-dihydro-isoquinoline_4_carboxylic acid Phenyl-propyl decylamine 3-[4-hydroxy-4-(3-methoxy-phenyl)-piperidinyl-b-ylmethyl]-p-oxy-2-phenyl-l,2- Diterpene·isoquinoline_4_carboxylic acid phenyl-propyl decylamine 2gu 3-[4-(3-chloro-phenyl)_'hydroxy-piperidine-indenylmethyl]-di-oxyl _2-phenyl-1,2-diindole- Isoquinoline_4_carboxylic acid ((y-bphenyl-propyl decylamine 3-(6-chloro-3H-spiro[isobenzofuran]yl)-guanidine piperidinylmethyl) small side Oxy.2-Phenyl-deca-2-dihydro-isoquinoline_4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2gx 3-(1-ethylindenyl-spiral [whistle D-Dallin,-ylmethyl)_b side 68 200906801 Oxy-2-phenyl-i,2_diindole-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl )_醯amine 2gy 3-(1-ethylindolyl-5-fluoro-spiro[0丨嗓丨嗓琳-3,4'-〇底.定]_ι,_ylmethyl)-1-sideoxy- 2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)·;^phenyl-propyl)-guanamine 2gz 1-sideoxy-3-(4-side oxygen 1-phenyl-1,3,8-triaza-spiro[4.5]dec-8-ylindenyl)_2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ( (S)-l-phenyl-propyl)-bristamine 2ha 3-(4-ethylhydrazinyl substrate. -1-ylmethyl)-dioxy 2_phenyl-1,2- Dihydro-isoindole _4_decanoic acid ((S)-1-phenyl-propyl)-decylamine 2hb 1-sideoxy_3-(1-sideoxy-2,8-diaza - Spiro[4.5]dec-8-ylmethyl)-2-phenyl-i,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl decylamine 2hc 3 -[4-hydroxy-4-(3-trifluoromethyl- Phenyl)-piperidine-hydrazinyl-methylimum-oxo-2-phenyl-l,2-dihydro-isoquinoline-4-carboxylic acid ((s)-l-phenyl-propyl; ) 醯 guanamine 2hd 1-tertiaryoxy-2-phenyl-3-(4-trifluoromethyl). Ding-1-ylmethyl)- 1,2-dihydro-isoquinoline-4-carboxylic acid phenyl-propyl)-decylamine 2he 3-[4-(4-methyl-decorphin-1 - Prison base) _0 bottom. D-bulkylmethyl]_ι_ oxooxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2hf 3-(5-isopropyl-3H-spiro[isobenzopyrano_ι,4: Ninjabita]-1'-ylmethyl)-1-oxo-2-phenyl-1,2- Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2hg 3-[4-(ethinyl-indenyl-amino)_4_styl-piperidin Acridine-1-ylindenyl]_ 69 200906801 oxime oxy-2-phenyl-1,2-dihydro-isoindolene-4 -hyal acid ((S)-l.phenyl-propyl)- Indole 2hh 4-{1-[1-Sideoxy-2-phenyl-4-(1-phenyl-propylamine)- 1,2-dihydro-isoindolin-3-yl Methyl]-π bottom bite_4-yl}-peptide_ι_remediate t-butyl ester 2hi (2-{1-[1-sideoxy-2-phenyl-4-(1-phenyl) -propylaminomethyl)- 1,2-dihydro-isoindol-3-ylindenyl]-n-n-n--4-yl}-ethyl)-aminocarboxylic acid tert-butyl ester 2hj 3 -(4-Methylamino-4-phenyl-[eta]I»dine-1-ylmethyl)-1-oxooxy-2_phenyl-1,2-dihydro-isoquinoline-4- Carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2hk 3-(4-ethylhydrazinoamino-4-phenyl-piperidin-1-ylindenyl)-hydrazine -2-phenyl-1,2-dihydro-isoquine _4_ rebellion ((S)-l-phenyl-propyl)-guanamine 2h丨3-[4-ethylhydrazino group 4-(3-fluoro-phenyl)-piperidin-1-ylmethyl]- 1-Phenoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2hm 1-sidedoxy-3 [4_(4_Phenoxy-piperidine-hydrazinylcarbonyl)-piperidinyl-p-methyl]-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S )-l-phenyl-propyl)-guanamine 2hn 3_[4,4']bipiperidin-1-ylmethyl-1-l-oxy-2-phenyl-1,2-dihydro-iso Quinoline-4-decanoic acid ((yd•phenyl·propyl decylamine 2ho {1-[1- sideoxy_2phenyl_4 (1_phenyl-propylaminemethanyl)) 1, 2-Dihydro-isoindoline_3_ylmethyl]-piperidine-4-ylcarbamic acid tert-butyl ester 2hp 3-[1,4']bipiperidin-1·-ylmethyl-1 -Sideoxy-2-phenyl-1,2-dichloro-isoindolyl-4-acid [cyclopropyl-(3-fluoro-phenyl)-methyl]-decylamine 200906801 2hq 1-side Oxy-3-(4-phenethyl-piperidin-1-ylmethyl)-2-phenyl_ 1,2-dihydro-isoquinoline-4-carboxylic acid [cyclopropyl_(3_ Fluoro-phenyl)-methyl]-nonylamine 2hr 3-(4-isopropyl-piperidin-indole-ylmethyl)·pi-oxy-2_phenyl-indole, 2_dihydro-isoquine Porphyrin-4-carboxylic acid [cyclopropyl-(3_fluoro-phenyl;) _Methylguanamine 2hs 3-[4-(2·Nofofolin_4_yl·ethyl)_〇辰啡-1_ylmethyl]_ι_lateral oxy-2-phenyl_1,2 _Dihydro-isoquinolinecarboxylic acid [cyclopropyl-(3-fluoro-phenyl)-indolyl]-nonylamine 2ht 3-[4_(1-methyl-piperidin-4-yl)-piped -1-ylmethyl]-b-oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [cyclopropyl-(3_fluoro-phenyl)-indenyl] - indoleamine 2»iu 1-sideoxy-2_phenyl_3吖4_(2_piperidine-indolylethyl)_pipedyl-bromomethyl]-1,2-dihydro-iso Quinoline_4_carboxylic acid [cyclopropyl-(3-fluoro-phenylmethyl)-decylamine 2hv 1-sideoxy-2-phenyl_3_[4_(2" than bite" base - Ethylphenidin _ ylmethyl]-1,2-dihydro-isoindole {Resin [cyclopropyl-(3_ s-phenyl)-methyl]-nonylamine 2_Phenyl acetophenone-4-ylmethyl-Bergyl small group methyl^^Dichloro-iso(tetra)-(acidic propyl fluoride)-benzoic acid amphetamine tetrahydrogen-isoquinoline-4- Carboxylic acid [cyclopropyl-(3-fluoro 2hx 3-(4-hydroxy-3,4,5,6yl)-1-yloxy-2-phenyl-l,2-phenyl)- Methyl]-decylamine hydrogen-2H-[4,4']-bidecidin-1-ylmethyl 2:y 3-[4_(2_ofofolin-Aethyl)-piperidineylmethyl -Sideoxy-2-bens-1,2-a SL-isoindole_4, acid [cyclopropyl_(3_fluorophenyl)_曱71 200906801 base]-nonylamine 2hz 3-[4-hydroxy-4-(3-decyloxy-phenyl) -piperidin-1-ylmethyl]-1-yloxy-2-phenyl-1,2-diaza-isoindole^-4-weilic acid [cyclopropyl-(3- gas·phenyl) ) 曱 ] ]]-nonylamine 2ia 3-[4-(ethylidene-methyl-amino)-4-phenyl-piperidine-1·ylindenyl]-1-oxo-2-benzene Base-1,2-diaza-isoindolin-4-o-acid [cyclopropyl-(3- gas-phenyl)-indolyl]-decylamine 2ib 2-(2-rat-phenyl)-1 -Sideoxy- 3-(4-phenethyl-Nymidine 1 -1 -ylindenyl)-1,2-dimur-isoindole- 4-acid ((S)-l-phenyl- Propyl)-S leucine 2ic 2-(2-fluoro-phenyl)·3-(4.isopropyl-indenyl-1-ylmethyl)-1-oxo-1,2-diazo -isoindolin-4-decanoic acid ((S)-l-phenyl-propyl)-nitramine 2id 3-[1,4']bipiperidin-l'-ylmethyl-2-(2- Fluoro-phenyl)-1_sideoxy-1,2-diaza-iso-lin-4-cyclo-acid ((S)-l-phenyl-propyl)-bristamine 2ie 2·(2 - gas -phenyl)-3-[4-(2-norfosin-4-yl-ethyl)-phenyl-1 - 1 ylmethyl]-1-yloxy-1,2-dihydro-iso Quinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2if 2 -(2- gas-phenyl)-3-[4-(1-indolyl-pyridin-4-yl)-derivative 1-1 fluorenyl]-1-yloxy-1,2-di Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-bristamine 2ig 2-(2- gas-phenyl)-1-yloxy_3_[4-(2 - sigma-1 -yl-ethyl)_piped-1-ylindenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl ) - Indole 2ih 2-(2- gas-phenyl)-1 - flavonyl-3-[4-(2 - ° pir. Ding-1 -yl-ethyl)-pipedino-1-ylmethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l·phenyl-propane 72 200906801) - indoleamine 2ii 2-(2-disorgano-phenyl)-1-flankyl- 3- (4-0-pyridin-4-ylindolyl-indenein-1-ylmethyl)-1 ,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ij 2-(2-fluoro-phenyl)-3-(4-hydroxy-3 , 4,5,6-tetrahydro-2H-[4,4']bipyridyl-buylmethyl)-1-yloxy-1,2-dihydro-isoquinoline-4-carboxylic acid (( S)-l-phenyl-propyl)-decylamine 2ik 2-(2-milo-styl)-3-[4-(2-norfosin-4-yl-ethyl)-Brigade 0- 1 _ mercapto]-1-oxooxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl-yl)-nonylamine 2il 2-(2 -fluoro-phenyl)-3-[4-hydroxy-4-(3-methoxy-phenyl)-piperidin-1-ylindenyl]-1-yloxy-1,2-dihydro- Isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2im 3-[4-(2-isofolin-4-yl-ethyl)-Lvming ^ -1 -ylindenyl]-1 -p-oxy-2-o-tolyl-1,2-diindole-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2iπ 1 - flank-3 - [4-(2 - bridging. -1 -yl-ethyl)-pyrene 1 -1 -yl ,-2-ylindole phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2 i ο 1 -oxyl -3 - (4 - ° ratio 0 -4 -ylmethyl-Budamine 1-1 - fluorenyl)-2 -o-tolyl-1,2-dihydro-isoquinoline-4-carboxylic acid ( (S)-l-phenyl-propyl)-nonylamine 2ip 2-(3_disorder-phenyl)-1-oxooxy-3_(4-phenylethyl-tvamide:-1 -ylindenyl )-1,2-dinitro-isowa scary 4- 4-acid ((S)-l-phenyl-propyl)-bristamine 2iq 2-(3_qi-phenyl)-3-(4· Isopropyl-peptidyl-1-ylmethyl)-1-oxoyl-1,2-di-isoindolin-4-indole ((S)-l-phenyl-propyl)- Amine 73 200906801 2ir 3-[1,4·]bipiperidin-1'-ylmethyl-2-(3-fluoro-phenyl)-1-yloxy-1,2-diaza-iso-p luxury吓 · - 4-decanoic acid ((S)-l-phenyl-propyl)-bristamine 2is 2-(3- gas-phenyl)-3-[4-(2-norfolin-4-yl) -ethyl)-Luming 1-1 mercapto]-1-oxooxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)- Indole 2it 2-(3- gas-phenyl)-3-[4-(1-indolyl-tide-4-yl)-B-phenyl-l-ylmethyl]-1-yloxy- 1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)- Indole 2iu 2-(3-fluoro-phenyl)-1-oxo-3-[4-(2-piperidin-1-yl-ethyl)-piped-1-ylmethyl]-1 ,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2iv 2-(3- gas-phenyl)-1 -oxyl-3 [4-(2 -βBiluol0-1,4-ethyl-ethyl)-pipedyl-1-ylmethyl]_1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l -phenyl-propyl)-guanamine 2iw 2-(3-fluoro-phenyl)-1-oxo-3-(4-pyridin-4-ylindenyl-piped-1-ylmethyl) -1,2-di-p-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 21\2-(3- gas-phenyl)-3-[4- (2-Folinin-4-yl-ethyl)-Brigade. -1 -ylmethyl]-1-oxooxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2iy 2-(3 - gas-phenyl)-3-[4-methoxy--4-(3-methoxy-phenyl)-π-decyl-1-1-ylmethyl]-1-yloxy-1,2- Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2iz 3-[4-(ethinyl-methyl-amino)-4-phenyl- Piperidin-1-ylmethyl]-2-(3-fluoro-phenyl)-1-yloxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-benzene 74 200906801 propyl-propyl decylamine 2ja 2-(3-chloro-benzyl)-1-yloxy- 3-(4-phenylethyl-branolyl-ι-ylmethyl)-1,2-di Hydrogen-isoindolin-4-o-acid ((S)-l-phenyl-propyl)-decylamine 2jb 2-(3_-phenyl-phenyl)-3_(4-isopropyl-piperidin-1 -ylindolyl)-l-oxyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2jC 3-[1,4'] Bipiperidine-l, _ylmethyl_2-(3_gas_phenyl)_丨_sideoxy_ 1,2-dihydro-isoquinoline_4_carboxylic acid ((S)-l- Phenyl-propyl)-nonylamine 2-(3-va-phenyl)_3_[4_(2_ofofolin-4-yl-ethyl)-piperidinylmethyl]-1-sideoxy 1,2-dihydro-isoquinoline-4-carboxylate phenyl)propylamine 2je 2-(3 -Chloro-phenyl)_3-[4-(1-methyl-pyrene. _4·yl)-Norphine-Bulkyl]-1-indolyl-丨,2_dihydro-isoquine啉___carboxylic acid (〇 _ phenyl-propyl) _ decyl 2 (3-chloro-phenyl) 丨丨 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ )_ Piperidinylmethyl]_1,2·dihydro-isoquinoline_4·carboxylic acid ((S)-l-phenyl-propyl)·decylamine (3-chloro-phenyl)-side Oxygen _3-[4-(2- η ratio slightly biting _ 1 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Base-propyl)-bristamine 2 1 h 2 (3 gas-stupyl)_ι·sideoxy_3_(4- <7 ratio _4_ mercapto-[endoryl 1-ylmethyl)-19 ..,-mono-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propane ) 醯 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 75 1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl-200906801 2jj 2_(3-chloro-benyl)-3-[4-pyridyl-4-(3) -methoxy-phenyl)-α- bottom. 1-methyl-1-yloxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)_i_phenyl -propyl)-guanamine 2jk 3-[4-(ethinyl-methyl-amino)_4_phenyl-piperidinylmethyl]_ 2-(3-chloro-phenyl)-1- side Oxy-12-dihydro-isoquinoline_4_carboxylic acid (^-^phenyl-propyl)-bristamine 2jl 1-sideoxy-3-(4-phenethyl-pipeline_丨_ Methyl)_2-m-tolyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-l-phenyl-propyl)-decylamine 2jm 3-[1,4'] Bipiperidine·ι,·yl fluorenyl sideoxy_2_m-tolyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-l-phenyl-propyl)_醯Amine 2jn 3-[4-(2_ofofolin_heart-ethyl)-piperidinyl fluorenyl] small side oxy-2-indolyl phenyl-ι,2-dihydro-isoquinoline _4_carboxylic acid ((magic Phenyl-propyl)_ decylamine 2jo 3-[4-(1-methyl-piperidinyl-4-yl)-piperidin-丨-ylmethyl]_丨_sideoxy-2-m-toluene Base·ι,2-dihydro-isoquinoline_4_carboxylic acid phenyl-propyl decylamine 2jp 1-tertiaryoxy-3-[4-(2-piperidin-1-yl-ethyl)- Piperyl 丨基基甲基 ] _ _ _ _ _ i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i -Phenoxy 3-[4-(2-pyrrolidin-1-yl-ethyl)-piperidinylmethyl]-2-m-tolyl-i,2-dihydro-isoquinoline_4 _carboxylic acid ((s)_i_phenyl-propyl)_bristamine 2jr 1-sided oxy-3-(4-pyridin-4-ylmethyl-piperidin-丨曱曱 ))_2_ Tolyl-1,2-dioxa-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 76 200906801 2js 3 [4-(2-?福林_4_ --ethyl)-d bottom _ι_ylmethyl]_ι_sideoxy-2-m-phenylene-;!,, dihydro-isoquinoline _4_carboxylic acid (("_〗 _Phenyl-propyl decylamine 2jt 3-[4-hydroxy_4_(3-methoxy-phenyl)-piperidinyl fluorenyl μι • side oxy-2-indolyl phenyl-hydrazine, dihydrogen _isoquinoline_4_carboxylic acid (^^丨-stupyl-propyl)-guanamine 2ju 3-[4-(ethenyl-methyl-amino)_4_phenyl_piper Acridine-丨-ylmethyl]_ 1-o-oxy-2-m-tolyl-indole, ;dihydro-isoquinoline_4-carboxylic acid phenyl-propyl)-bristamine 3a 1_side oxygen _3_(2-Sideoxypyrrolidin-1-ylindenyl)_2_phenyl_ 1,2-dihydroisoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl - indoleamine 3b 8-chloro-1-yloxy_3_(2_sideoxy-pyrrolidinyl-indoleyl)_2_phenyl-1,2-dihydro-isoquinoline_4_ Carboxylic acid (("___phenyl-propyl)-decylamine 4a 3-cyanoguanidino sideoxy_2_phenyl_1>2_dihydro-isoquinoline_4-carboxylic acid (( S)-l-phenyl-propyl)-guanamine 5a 3 methyl-1_sideoxy_2_phenyl_ι,2_dihydro-isowaline_4_slow acid N,N-di Phenylhydrazine 5b N'-(3-methyl-1. sideoxy-2_phenyldihydro-isoquinoline-cardiyl)-N-phenyl-indolecarboxylic acid methyl ester laa 2-(3 -Methoxy-benzyl)-3-methyl-1-oxooxyl,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-oxime Amine lab 2-(4-mercapto-yl)-3-methyl-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l·phenyl -propyl)-guanamine lac 2-(4-fluoro-phenyl)-3-indenyl_ι·sideoxydihydro-isoindole_ 77 200906801 4-carboxylic acid ((S)-l-benzene base- -) guanamine lad 2-(4- gas-phenyl)-3-methyl-1-oxo-i,2-dihydro-isoquinoline _ 4 - oxo acid ((S)-l - Phenyl-propyl)-δδ amine lae 3-methyl-1-oxo-2-p-tolyl-l,2-dihydro-isoquinoline-4-hypoacid ((S)-l-benzene -propyl)-decylamine laf 2-(3-methoxy-phenyl)-3-methyl-1-oxooxyl-1,2-dihydro-isoquino #-4-hypoacid [ S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-guanamine lag 2-(4-methoxy-phenyl)-3-methyl-1-oxo-1,2 -dihydro-isoquinolin-4-acid acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-guanamine lah 2-(4-fluoro-phenyl)·3- Methyl-1-oxo-1,2-dioxa-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-nonylamine lai 2 -(4-Gas-phenyl)-3-indolyl-1-yloxy-l,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro- Phenyl)·methyl]-nonylamine laj 3-methyl-1-oxo-2-p-tolyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropane -(3-Fluoro-phenyl)-methyl]-nonylamine lak 2-(2-methoxy-phenyl)-3-methyl-1-oxo-l,2-dihydro-iso Quinoline _4_carboxylic acid ((S)-l-phenyl-propyl)-nonylamine lal 2-(2-methoxy-benzene曱-3-mercapto-1-yloxy-1,2-dihydro-isoquinolin-4-retensive acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]- Indole lam 3-methyl-8-nitro-1-oxo-2-phenyl-1,2-dihydro-isoquinolin-4-indoleic acid ((S)-l-phenyl-propane -) decylamine lan 3 -methyl-8-succinyl-1-yloxy-2-phenyl-1,2-dihydro-isoindole _ 4-acidic acid [(S)-cyclopropyl- (3-fluoro-phenyl)-methyl]-nonylamine lao 8-methoxy-3-methyl-1-oxooxy-2_phenyl-1,2-dihydro-isoindole 78 200906801 porphyrin 4-carboxylic acid phenyl-propyl)-decylamine lap 8 -methoxy-3-methyl-1-oxophenylphenyl-L2-dihydro-isoquinoline-4-carboxylic acid [(S )-cyclopropyl-(3-fluoro-phenyl)-methyl]-decylamine laq 8-amino-3-methyl-1-yloxy-2-phenyl-1,2-dihydro- Isoindolin-4_carboxylic acid ((S)-l-phenyl-propyl)-guanamine lar 8-cyano-3-methyl-1-oxo-2-phenyl_ι,2- Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine las 8 -chloro-3-indolyl-1-yloxy-2-phenyl-i, 2-Dihydroisoindole: Lin-4-acid acid [(S)-1-(4-chloro-phenyl)-propyl]-bristamine lat 8-chloro-3-methyl-1-yloxy -2-phenyl-1,2-dihydro-isoquinoline-4-resorbed acid [(S)-l-(4-fluoro-phenyl)- Propyl]-decylamine lau 8-chloro-3-indolyl-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-l-( 2-fluoro-phenyl)-propyl]-nonylamine lav 8-chloro-3-methyl-1-oxo-2-phenyl-ι,2-dihydro-isoquinoline-4-acid [(S)-l-(3-Chloro-phenyl)-propyl]-bristaminelaw 8-ox-3-fluorenyl-1-yloxy.2-phenyl-1,2-dihydro- Isoquinoline-4-tagamic acid [(S)-(3-chloro-phenyl)-cyclopropyl-indenyl]-bristamine lax 8·chloro-3-methyl-1-oxo-2- Phenyl-1,2-dihydro-isoquinoline-4-decanoic acid [(S)-(4-chloro-phenyl)-cyclopropyl-indenyl]-bristamine lay 8-chloro-3-methyl -1-la-oxy-2-phenyl-12-dihydro-isoquinoline-4-carboxylic acid [(S)-1-(3-fluoro-phenyl)-propyl]-nonylamine laz 8 -Chloro-3-methyl-1-oxooxy-2_phenyl-12-dihydro-isoquinoline-4-carboxylic acid ((S)-2-methyl·ι_phenyl-propyl hydrazine Amine lba 8-chloro-3-methyl·1_sideoxy-2_phenyl-indole, 2-dihydro-isoquinoline-4- 79 200906801 Carboxylic acid [(S)-cyclopropyl-(4 -fluoro-phenyl)-methyl]-nonylamine lbb 8 - lact-3-yl-1-yloxy-2-phenyl-1,2-dihydro-isoindole- 4-carboxylic acid [ (S)-1-(2-chloro-phenyl)-propyl]-nonylamine lbc 8 -chloro-3-methyl-1-oxo-2-phenyl-1,2-dihydro-iso喧琳-4- Acid ((S)-cyclopentyl-phenyl-methyl)-guanamine lbd 8-chloro-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline 4-carboxylic acid [(S)-(2-chloro-phenyl)-cyclopropyl-methyl]-nonylamine lbe 8-chloro-3-methyl-1-oxo-2-phenyl- 1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(2-fluoro-phenyl)-methyl]-nonylamine lbf 8-chloro-3-methyl-1 ·Sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-cyclohexyl-phenyl-methyl)-decylamine

Ibg 8-氣-3-曱基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-環丙基-苯基-甲基）_醯胺 lbh 8-氣-3-曱基-1-侧氧基-2-苯基-1,2-二氫-異喹啉-4-叛酸[(S)-% 丁基苯基）-曱基]-酿胺Ibg 8-ox-3-mercapto-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-cyclopropyl-phenyl-methyl ) 醯醯 amine lbh 8-gas-3-mercapto-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-deoxalate [(S)-% butylphenyl )-曱基]-bristamine

Ibi 8-氣-3-甲基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-缓酸[(S)-環丁基- (4 -氟-苯基）-甲基]-醢胺Ibi 8-gas-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-hypoacid [(S)-cyclobutyl-(4-fluoro- Phenyl)-methyl]-guanamine

Ibl 8-氯-3 -曱基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸[(R)-環丙基- (3 -氟-苯基）-甲基]-酿胺Ibl 8-chloro-3-mercapto-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(R)-cyclopropyl-(3-fluoro- Phenyl)-methyl]-bristamine

Ibn 8-氯-3-甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)環丁基-苯基-曱基）_醯胺Ibn 8-chloro-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)cyclobutyl-phenyl-fluorenyl) _ guanamine

Ibo 8-氣-3-甲基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸[環丁基-(2-氟-苯基）-曱基]-醯胺 2ka 3-(4-第三丁基-哌畊-1-基曱基氯-1-側氧基-2_ 200906801 苯基-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟·苯基）-甲基]-醯胺 2kb 8-氯-3-(4-異丙基-哌啡-1-基甲基）-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2kc 8-氯-3-(4-異丁基-哌畊-1-基甲基）-1-側氧基-2-苯基-1，2-二氫-異喧琳-4-竣酸（（S)-l-苯基-丙基）-5篮胺 2kd 8 -氣- 3- (八風-〇比0定并[l，2-a]0比明1 -2-基甲基）-1 -側氧基-2 -苯基-1,2-二氫-異啥淋-4 -叛酸（（S)-l-苯基-丙基）_醯胺 2ke 8 -乱-3-(4 -經基- 3,4,5,6 -四風- 基曱基）-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基 -丙基）-酿胺 2kf 8-氯-3-(4-環丙基曱基-哌啡-1-基曱基）_；[_側氧基_2_ 苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2kg 8 -氯- 3-[4-(2 -嗎福林-4-基-乙基）-η底β定_ι_基甲基]_ 1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（(S)-l -笨基-丙基）-醯胺 2kh 8-氯-3-[1，4]二氮雑環庚烷-i_基曱基-卜側氧基_2_ 苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2ki 8_氯-3_((S)-3·甲基_〇辰啡_ι_基曱基）」_侧氧基_2_苯基_1，2_二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基醯胺 2kj 8-氣-3H1-基甲基小側氧基_2_笨基_ls2_二氮_ 異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2kk 8-氯-3-(4·甲基-咪唑_丨_基甲基）_卜側氧基_2_苯基_ 1，2-二氫-異喹啉-4-羧酸（（s)-l_苯基-丙基）_醯胺 81 200906801 2kl 3-(第三丁基胺基-甲基）-8-氯-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2km 8-氯-3-(異丙基胺基-甲基）·ι_側氧基_2_苯基-丨，2_ 二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2kn 8-氣-3-[4-羥基-4-(3-曱氧基-苯基）_哌啶-}•基曱基]-1-侧氧基-2-苯基- l，2-二氫-異喹啉_4·羧酸（（s)-l-苯基_ 丙基）-醯胺 2ko 3-(4-第三丁基-哌明：-丨_基曱基）_8•氣·側氧基_2_ 苯基-1，2-二氫·異喹啉-4·羧酸（（S)-l-苯基-丙基）_醯胺 2kp 3-苯并咪唑-1_基甲基_丨_侧氧基_2_苯基」，2二氫_ 異啥琳-4-羧酸（（S)-l -苯基-丙基）_酿胺 2kq卜側氧基-2-苯基-3-n比唑-1-基甲基_1，2_二氫-異啥琳-4-羧酸（（S)-l -苯基-丙基）-醯胺 2kr 3-(4-甲基-吡唑_1_基甲基）_卜側氧基_2_苯基·丨，2-二氫-異喹啉-4-羧酸（（S)-l-苯基·丙基醯胺 2ks 1-側氧基-2-苯基-3-[1,2,3]***-1-基甲基_ι，2_二氫 -異唾琳-4-叛酸（（S)-l-苯基-丙基）_酿胺 2kt 2-(3-甲氧基-苯基）_ι_側氧基_3_(4_0比0定_4_基甲基_ 哌畊-1-基甲基）-1，2-二氫·異喹啉_4_羧酸苯基_丙基）_ 醯胺 2ku 2-(4 -甲氧基-苯基）_3_[4_(2_嗎福林·4·基·乙基）_0底畊-1-基甲基]-1-側氧基-1,2-二氫-異喹啉_4_羧酸（(”“_苯基 -丙基）-酿胺 2kv 2-(4_氟-苯基）-ΐ-側氧基-3 — (4_苯乙基·哌啡·〗·基甲 82 200906801 基）-1，2-二氫-異喹啉羧酸（（y—i苯基_丙基）_醯胺 2kw 2-(4_氟.求基）_3_(4_異丙基_〇底啡4•基甲基）-卜側氧基-1，2-二氫-異喹啉_4_羧酸（0)4 —笨基-丙基）_醯胺 2kx 3-[1，4’]聯哌啶_r_基曱基_2_(4_氟_苯基）_i_側氧基_ 1,2_二氫異喹啉_4-羧酸（（S)-l-苯基-丙基）_醯胺 2ky 2-(4-氟.苯基）·3_[4_(2_嗎福林_4_基_乙基哌畊-卜基甲基]-1-側氧基-1,2-二氫·異喹啉·4_羧酸（(”-卜苯基-丙基）-醯胺 2kz 2-(4_氟-苯基）_3_[4_(卜甲基底咬基）_〇底啡-卜基甲基]-1-側氧基-1，2-二氫·異喹啉_4_羧酸苯基-丙基）_ 醯胺 21a 2-(4-氟-苯基）_卜側氧基_3_[4_(2_〇比咯啶_丨_基-乙基）-哌啡-1-基曱基]-12-二氫-異喹啉_4_羧酸（(y s苯基-丙基）-醯胺 21b 2-(4-氟-苯基）-3-[4-羥基-4-(3-甲氧基-苯基）-哌啶_ 1-基曱基]-1-侧氧基_1，2_二氫-異喹琳·4·緩酸（（s)_i_苯基-丙基）-醯胺 21c 2-(4 -氣-苯基）-1-側氧基_3-(4 -苯乙基-派明：_卜基甲基）-1，2-二氫-異喹啉_4_羧酸（（s)·]^苯基_丙基醯胺 21d 2-(4-氣-苯基）-3-(4-異丙基-n底啡_ι_基甲基）_ι_側氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 21e 3-[1，4']聯哌啶-1'-基甲基-2-(4-氯-苯基）-1-側氧基-1，2-二氫·異喹啉羧酸（（S)·〗-苯基-丙基）_醯胺 21f 2-(4-氯-苯基）-3-[4-(2 -嗎福林_4-基-乙基）-派啡-1- 83 200906801 基甲基]-1-側氧基-以二氫·異喹啉_4_羧酸（⑻小苯基-丙基）-醯胺 21g 2-(4-氯-苯基）_3_[4_(卜甲基_哌啶_4_基）-哌啡―卜基曱基]-1-側氧基-1，2-二氫-異喹啉_4_羧酸（^-丨-苯基-丙基醯胺 21h 2-(4-氣-苯基）侧氧基_3_[4_(2_哌啶-丨―基-乙基）_ 哌阱-1-基甲基]-1，2-二氫-異喹啉_4_羧酸•苯基·丙基醯胺 21i 2-(4 -氣-苯基）_1_側氧基_3-[4-(2-n比α各唆_1-基_乙基）-哌畊-1-基甲基]_1，2-二氫-異喹啉-4-羧酸（(8)_丨_苯基-丙基）-醯胺 21]3-(4-第三丁基-哌畊_1_基曱基）_8_氟-1_側氧基_2_笨基-1，2-二氫-異喹啉_4_羧酸（（S)-l-苯基-丙基）_醯胺 21k 8-氣-3-環丙基胺基甲基-1-側氧基_2-苯基-1,2-二氫 -異喹啉-4-羧酸（(S)-l-苯基-丙基）-醯胺 211 3-(4•第三丁基-哌畊-1-基曱基）-8-氟-1-侧氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]_ 醯胺 21m 8-氟-1-側氧基-2-苯基·3-哌畊-1-基甲基_1，2_二氫_ 異喹啉-4-羧酸[(S)-環丙基-(3-氟-笨基）-曱基]-醯胺 21η 8-氟-1-側氧基-3-(3-侧氧基-11比唑啶-1-基曱基）-2-笨基-1,2-二氫-異喹啉-4-羧酸[(S)_環丙基-(3_氟-苯基）_甲基]- 醯胺 21〇 8-氟-1-側氧基-3-(3-側氧基-哌啡-1-基甲基）-2-笨基 84 200906801 -1,2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-曱基]-醯胺 3c 1-側氧基-2-苯基-3-(1Η-[1，2,4]***-3-基硫烷基甲基）-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 3d 8-氣-1-側氧基-3-(2-側氧基-吡咯啶-1-基甲基）·2-苯基-1，2-二氫-異喹啉-4-羧酸[(S)·環丙基-(3-氟-苯基）-甲基]· 醯胺 3e 8-氟-1-侧氧基-3-(2-側氧基-吡咯啶-1-基甲基）_2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 3f 8-氟-1·侧氧基-3-(2-側氧基-吡咯啶-1-基甲基）-2-苯基-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]_ 醯胺 3g 8-氟-1-側氧基-3-(5-侧氧基-吡唑啶-1-基甲基）_2_苯基-1,2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）_甲基;]_ 醯胺 3h 8-氟-1-側氧基-3-(2-側氧基-哌啡-1-基甲基）·2-苯基 -1,2-二氫-異啥琳-4-羧酸[(S)-環丙基_(3_氟-苯基）-甲基]-醯胺 8-氟-1-側氧基-3-(2-側氧基-哌啶-1-基曱基）-2-苯基_ 1,2-二氫-異琳-4-缓酸[(S)-環丙基- (3-IL-苯基）-曱基]-酿胺 4b 8-氣-3-氰基甲基-卜側氧基-2-苯基-1，2-二氫-異喹啉 -4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺 6a 2-(3,4-二氯-苯基）-3•曱基側氧基-1，2-二氫-異啥 85 200906801 琳-4-竣酸（（S)-l-苯基-丙基）·醯胺 6b 8-氟-1-側氧基-3-(2-側氧基-吡咯啶-i_基甲基）-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)_環丙基-苯基-甲基）_醯胺 6c 8-氟-3-甲基-1-側氧基_2_苯基十之·二氫-異喧啉_4_缓酸（（S)-環丙基-苯基-甲基）_醯胺 7a 3-乙基-1-側氧基-2-苯基_1,2_二氫-異喹啉-4-羧酸 ((S)-l -苯基-丙基）-酿胺 7b 8-氟-3 -甲基-1-側氧基_2_苯基-1,2-二氫-異喹啉-4-C 1 缓酸（（s)-i -苯基-丙基）-酿胺 7c 8-氟-2-(3-氟-苯基）-3-曱基-1-侧氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 7d 8-氟-2-(4-氟-苯基）_3_甲基側氧基心，〗-二氫_異喹琳-4-羧酸（（S)-l-苯基-丙基）_醯胺 8 -氣-3-曱基-1-側氧基_2_苯基-1，2-二氫-異啥琳-4-叛酸[(S)-環丙基-(3-氟-苯基）_曱基]-酿胺 7f 8-氟-2-(3-氟-苯基）·！_側氧基·3·(2-側氧基比咯啶-ί/ 卜基曱基）-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-酿胺 7g 8-氟-2-(4-氟-苯基）-1-側氧基-3-(2-側氧基-β比洛咬-1-基甲基）-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3 -氟-苯基）_曱基]-酿胺 7h 8-氟-3-曱基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸[(S)-環丁基-(3-氟-苯基）-甲基]-醯胺 7i 8-氟-2-(2-氟-苯基）-3-甲基-1-側氧基-1,2-二氫-異喹 86 200906801 啉-4-羧酸[(S)-環丙基-(3-氟-苯基）_曱基卜醯胺 8-氟-2-(3-氟-笨基）_3-甲基-1-側氧基-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）_曱基]_醯胺 7k 8-氟-2-(4-氟-苯基；)_3_甲基側氧基_12_二氫_異喹啉_4-羧酸[(S)-環丙基-(3_氟_苯基）_曱基]_醯胺 71 6,8_二氟_3_曱基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸[(S)-環丙基_(3_氟_笨基）_甲基]_醯胺 f 7m 5,8-二氟-3-甲基側氧基_2_苯基4,2—二氫-異喹啉 -4-羧酸[(S)_環丙基_(3_氟_苯基）_甲基]_醯胺 7n 3-甲基側氧基·2_苯基_8_三氟甲基二氫-里喹啉-4-羧酸（（S)-! —苯基-丙基）_醯胺 8a 基-1，2-醯胺， 3-(1-第三丁基-娘咬·4_基甲基）_8_氣小側氧基_2-苯二氫-異㈣-4-竣酸[⑻·環丙基_(3氣_苯基）_甲基卜 π丹嚣樂学此外’本發明化合物可接受之溶劑（諸如水、乙醇=悉劑合物以及與醫藥學上合物形式存在。-般而言，對=^似物）所形成之溶劑合物形式與非溶劑合物形式等效。發明之目的’認為溶劑本發明化合物可能具有—或何光學異構體（亦即對映對稱中，。且預期任分離、純或部分純化之光學異構體，2=構體）’如經括外消旋混合物，亦即立體異 ”任料合物（包發明範圍内。詳t之冬、此合物）均包括於本 ……示CH或CR1時，A可能為 87 200906801 光于中“，產生R形式及s形式兩種光學異構體。在—具月立κ例中，本發明化合物具有s形式。Ibo 8-gas-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [cyclobutyl-(2-fluoro-phenyl)-曱基]-nonylamine 2ka 3-(4-t-butyl-piperidin-1-ylmercaptochloro-1-oxo-2) 200906801 Phenyl-1,2-dihydro-isoquinoline-4 -carboxylic acid [(S)-cyclopropyl-(3-fluorophenyl)-methyl]-nonylamine 2 kb 8-chloro-3-(4-isopropyl-piperidin-1-ylmethyl) -1-Sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2kc 8-chloro-3- (4-isobutyl-piperidin-1-ylmethyl)-1-oxo-2-phenyl-1,2-dihydro-isoindolin-4-indole ((S)-l- Phenyl-propyl)-5 basket amine 2kd 8 - gas - 3- (eight wind-helium ratio 0 and [l,2-a]0 to clear 1 -2-ylmethyl)-1 -oxyl -2 -Phenyl-1,2-dihydro-isoindole-4 - Tresic acid ((S)-l-phenyl-propyl)-decylamine 2ke 8 - chaotic-3-(4 - mercapto- 3,4,5,6-tetracycline-yl fluorenyl-1-ylidene-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-benzene -propyl)-bristamine 2kf 8-chloro-3-(4-cyclopropylindolyl-piperidin-1-ylindenyl)_;[_sideoxy_2_phenyl-1,2-di Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2kg 8 -chloro- 3-[4 -(2-fluorolin-4-yl-ethyl)-η bottom β定_ι_ylmethyl]_ 1-oxo-2-phenyl-1,2-dihydro-isoquinoline- 4-carboxylic acid ((S)-l-styl-propyl)-guanamine 2kh 8-chloro-3-[1,4]diazepinee-heptane-i-ylindenyl-b-oxyl_ 2_Phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ki 8_chloro-3_((S)-3·methyl _〇辰啡_ι_基曱基)"_Sideoxy_2_phenyl_1,2_dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl hydrazine Amine 2kj 8-gas-3H1-ylmethyl small sideoxy-2_stupyl_ls2_diaza_isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2kk 8-chloro-3-(4.methyl-imidazolium-hydrazinylmethyl)-p-oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s )-l_phenyl-propyl)-decylamine 81 200906801 2kl 3-(Tertiarybutylamino-methyl)-8-chloro-1-oxo-2-phenyl-1,2-di Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2km 8-chloro-3-(isopropylamino-methyl)·ι_sideoxy_ 2_Phenyl-indole, 2_dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2kn 8- gas-3-[4-hydroxy-4-( 3-decyloxy-phenyl)-piperidine-}• group -1-yloxy-2-phenyl-l,2-dihydro-isoquinoline _4·carboxylic acid ((s)-l-phenyl-propyl)-decylamine 2ko 3-(4 -T-butyl-peipamine: -丨_ylindenyl)_8•gas·sideoxy_2_phenyl-1,2-dihydroisoquinoline-4·carboxylic acid ((S)-l- Phenyl-propyl)-nonylamine 2kp 3-benzimidazole-1_ylmethyl-丨_sideoxy_2_phenyl", 2 dihydro-isophthalocyanine-4-carboxylic acid ((S) -l-phenyl-propyl)_bristamine 2kq oxime oxy-2-phenyl-3-n-pyrazol-1-ylmethyl-1,2-dihydro-isoindol-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2kr 3-(4-methyl-pyrazole-1-ylmethyl)-di-oxy 2_2-phenyl-indole 2-2- Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl decylamine 2ks 1-sided oxy-2-phenyl-3-[1,2,3]triazole-1- Methyl-M, i-dihydro-iso-Salvin-4-Resin ((S)-l-phenyl-propyl)-bristamine 2kt 2-(3-methoxy-phenyl)_ι_ Side oxy_3_(4_0 ratio 0 _4_ ylmethyl _ piperidin-1-ylmethyl)-1,2-dihydro-isoquinoline _4_carboxylic acid phenyl propyl) 醯Amine 2ku 2-(4-methoxy-phenyl)_3_[4_(2_morphine·4·yl·ethyl)_0 bottomed-1-ylmethyl]-1-yloxy-1, 2-dihydro-isoquinoline_4 _carboxylic acid ((""-phenyl-propyl)-bristamine 2kv 2-(4-fluoro-phenyl)-fluorene-tertiaryoxy-3 - (4-phenylethyl·piperidinyl)甲82 200906801 基)-1,2-Dihydro-isoquinolinecarboxylic acid ((y-iphenyl-propyl)-decylamine 2kw 2-(4-fluoro.inquiry)_3_(4_isopropyl _ 〇啡 4 4 基 ) 4 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 2 2 2 2 2 2 2 2 2 2 2 2 2 , 4']bipiperidin_r_ylindenyl_2_(4-fluoro-phenyl)_i_sideoxy-1,2-dihydroisoquinoline-4-carboxylic acid ((S)-l- Phenyl-propyl)-nonylamine 2ky 2-(4-fluoro.phenyl)·3_[4_(2_ofofolin_4_yl_ethylpiped-bromomethyl]-1-side oxygen 1,2-dihydro-isoquinoline·4-carboxylic acid (("-phenyl-propyl)-decylamine 2kz 2-(4-fluoro-phenyl)_3_[4_( ) 〇啡 - - 卜 - 甲基 - - - - - -1 -1 -1 -1 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 21 Phenyl)-p-oxy3_[4_(2_〇b-pyridyl-hydrazinyl-ethyl)-piperidin-1-ylindenyl]-12-dihydro-isoquinoline_4_carboxylate Acid ((ysphenyl-propyl)-decylamine 21b 2-(4-fluoro-phenyl)-3-[4-hydroxy-4-(3-methoxy-phenyl)-piperidine _ 1-ylindenyl]-1-yloxy-1,2-dihydro-isoquinoline·4·slow acid ((s)_i_phenyl-propyl)-decylamine 21c 2-(4- Gas-phenyl)-1-oxooxy-3-(4-phenylethyl-p-phenethyl:-diylmethyl)-1,2-dihydro-isoquinoline-4-carboxylic acid ((s) ·]Phenyl-propyl decylamine 21d 2-(4-Gas-phenyl)-3-(4-isopropyl-n-endophthyl)-yloxy-1,2 -Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 21e 3-[1,4']bipiperidin-1'-ylmethyl-2- (4-Chloro-phenyl)-1-oxooxy-1,2-dihydro-isoquinolinecarboxylic acid ((S)·〗-phenyl-propyl)-decylamine 21f 2-(4-chloro -phenyl)-3-[4-(2-norfosin-4-yl-ethyl)-parphin-1-83 200906801 methyl-l-l-oxyl-dihydro-isoquinoline _4_carboxylic acid ((8) small phenyl-propyl)-nonylamine 21g 2-(4-chloro-phenyl)_3_[4_(p-methyl-piperidin-4-yl)-piperidin-bupropenyl] -1-Sideoxy-1,2-dihydro-isoquinoline-4-carboxylic acid (^-丨-phenyl-propyl decylamine 21h 2-(4-gas-phenyl) pendant oxy group_3_ [4_(2_piperidin-oxime-yl-ethyl)_piperid-1-ylmethyl]-1,2-dihydro-isoquinoline_4_carboxylic acid phenyl propyl decylamine 21i 2-(4- gas-phenyl _1_Sideoxy_3-[4-(2-n ratio α 唆_1-yl-ethyl)-piped-1-ylmethyl]_1,2-dihydro-isoquinoline-4- Carboxylic acid ((8)_丨_phenyl-propyl)-nonylamine 21]3-(4-tert-butyl-piperidin-1_ylindenyl)_8_fluoro-1_sideoxy-2 _stupyl-1,2-dihydro-isoquinoline_4_carboxylic acid ((S)-l-phenyl-propyl)-decylamine 21k 8-a-3-cyclopropylaminomethyl- 1-Phenoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 211 3-(4•third Butyl-piperidin-1-ylindenyl)-8-fluoro-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropane --(3-fluoro-phenyl)-methyl]-decylamine 21m 8-fluoro-1-oxo-2-phenyl·3-pipedino-1-ylmethyl-1,2-dihydrogen _ Isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-indolyl]-nonylamine 21η 8-fluoro-1-indolyl-3-(3-side Oxy-11-pyrazin-1-ylindenyl)-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-benzene ))-Methyl]-decylamine 21〇8-fluoro-1-oxo-3-(3-o-oxy-piperidin-1-ylmethyl)-2-indolyl 84 200906801 -1,2 -Dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-indolyl]-decylamine 3c 1-side Oxy-2-phenyl-3-(1Η-[1,2,4]triazol-3-ylsulfanylmethyl)-1,2-dihydro-isoquinoline-4-carboxylic acid (( S)-l-phenyl-propyl)-nonylamine 3d 8-gas-1-oxooxy-3-(2-o-oxy-pyrrolidin-1-ylmethyl)·2-phenyl-1 ,2-dihydro-isoquinoline-4-carboxylic acid [(S)·cyclopropyl-(3-fluoro-phenyl)-methyl]·decylamine 3e 8-fluoro-1-yloxy-3 -(2-Sideoxy-pyrrolidin-1-ylmethyl)_2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl) - indoleamine 3f 8-fluoro-1. pendant oxy-3-(2-o-oxy-pyrrolidin-1-ylmethyl)-2-phenyl-1,2-dihydro-isoquinoline-4 -carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-decylamine 3g 8-fluoro-1-oxooxy-3-(5-o-oxy-pyrazolidine -1-ylmethyl)_2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl;]_ Indoleamine 3h 8-fluoro-1-oxooxy-3-(2-o-oxy-piperidin-1-ylmethyl)·2-phenyl-1,2-dihydro-isoindole-4- Carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-nonylamine 8-fluoro-1-oxo-3- (2-o-oxy-piperidin-1-曱 ))-2-phenyl _ 1,2-dihydro-isoline-4-hypoacid [(S)-cyclopropyl-(3-IL-phenyl)-fluorenyl]- 4b 8-Galy-3-cyanomethyl-b-oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro -phenyl)-methyl]-nonylamine 6a 2-(3,4-dichloro-phenyl)-3•indolyloxy-1,2-dihydro-isoindole 85 200906801 琳-4-竣Acid ((S)-l-phenyl-propyl)·decylamine 6b 8-fluoro-1-oxo-3-(2-o-oxy-pyrrolidinium-i-ylmethyl)-2-benzene -1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-cyclopropyl-phenyl-methyl)-decylamine 6c 8-fluoro-3-methyl-1-yloxy _2_Phenyl-decahydro-isoporphyrin_4_jujubilic acid ((S)-cyclopropyl-phenyl-methyl)-decylamine 7a 3-ethyl-1-yloxy-2 -phenyl_1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-bristamine 7b 8-fluoro-3-methyl-1-oxooxy _2_Phenyl-1,2-dihydro-isoquinoline-4-C 1 acid ((s)-i-phenyl-propyl)-bristamine 7c 8-fluoro-2-(3-fluoro -phenyl)-3-indolyl-1-yloxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 7d 8- Fluorin-2-(4-fluoro-phenyl)_3_methyl oxirane, s-dihydro-isoquinolin-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 8-air-3-mercapto-1-oneoxy-2_phenyl-1,2-di - Lin Han -4- iso betray acid [(S) - cyclopropyl - (3-fluoro-phenyl) - _ Yue-yl] - amine stuffed 7f 8- fluoro-2- (3-fluoro-phenyl) - *! _Sideoxy·3·(2-Sideoxypyrrolidine-ί/ benzylidene)-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-( 3-fluoro-phenyl)-methyl]-bristamine 7g 8-fluoro-2-(4-fluoro-phenyl)-1-oxo-3- (2-o-oxy-β-Bile bite- 1-ylmethyl)-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-indenyl]-nitramine 7h 8-fluorine -3-fluorenyl-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenyl)- Methyl]-nonylamine 7i 8-fluoro-2-(2-fluoro-phenyl)-3-methyl-1-oxooxy-1,2-dihydro-isoquino 86 200906801 porphyrin-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-hydrazinylamine 8-fluoro-2-(3-fluoro-phenyl)-3-methyl-1-oxo-1 2-Dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-indolyl]-decylamine 7k 8-fluoro-2-(4-fluoro-benzene Base;)_3_methyl-oxyl_12_dihydro-isoquinoline_4-carboxylic acid [(S)-cyclopropyl-(3_fluoro-phenyl)-fluorenyl]-decylamine 71 6 ,8_Difluoro_3_mercapto-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3_fluoro _笨基)_Methyl]_decylamine f 7m 5,8-difluoro-3-methyl-oxyl-2-phenyl 4,2-dihydro-isoquinoline-4-carboxylic acid [(S )_ Cyclopropyl-(3-fluoro-phenyl)-methyl]-decylamine 7n 3-methyl-oxo-oxy-2-phenyl-8-trifluoromethyldihydro-riquinolin-4-carboxylic acid ((S)-!-Phenyl-propyl)-decylamine 8a-based-1,2-decylamine, 3-(1-tert-butyl-Nymphoteric 4-ylmethyl)_8_ gas small side Oxy-2-benzenedihydro-iso(tetra)-4-nonanoic acid [(8)·cyclopropyl_(3 gas_phenyl)_methyl b π 嚣嚣此外此外此外 ' ' ' ' Water, ethanol = the composition of the composition and the form of the pharmaceutical composition. In general, the solvate form formed by the analogy is equivalent to the unsolvated form. OBJECTS OF THE INVENTION 'Thinking Solvents The compounds of the present invention may have - or any optical isomers (i.e., in the enantiosymmetric, and are expected to be isolated, pure or partially purified optical isomers, 2 = constructs)' Including a racemic mixture, that is, a stereoisomer, which is included in the scope of the invention. In the case of CH or CR1, A may be 87 200906801 "There are two optical isomers of the R form and the s form. In the case of 月月 , the compound of the present invention has the s form.

在特疋具體實例中，本發明化合物在a周圍具有以下絕對構型，A為CHIn a specific embodiment, the compound of the invention has the following absolute configuration around a, A is CH

^在本文中應理解，當指明對映異構形式時，則化合物係對映異構過量’例如基本上為純形式。因此，本發明之具體貫例係關於具有至少6〇%、至少7〇%、至少、至少85。/。、至少90%、至少96%，較佳至少㈣對映異構過量之本發明化合物。 #外消旋形式可藉由已知方法拆分為光學對映體，例如 / V. 藉由以光學活性酸使其非對映異構鹽分離，且藉由以鹼處理釋放光學活性胺化合物。將外消旋體拆分為光學對映體之另-方法係基於光學活性基質的層析。亦可藉由形成非對映異構衍生物來拆分本發明化合物。可使用熟習此項技術者已知的拆分光學異構體之其他方法。該等方法包括彼等由 J· J，eS，A. C〇llet 及 S_ Wilen 在「e職如聽S， Racemates，and Res〇luti〇ns」，J〇hn _ s應， Y-k (蘭)中所揭示者。亦可由光學活性起始物質製備光學活性化合物。此外，當分子中存在雙鍵或完全或部分飽和環系統時， 88 200906801 :形成幾何異構體。預期任何幾何異構圍内。同樣，== 物均包括於本發明範構體預轉之鍵的分子可能形成幾何異構體。預期此等異構體亦包括於本發明範圍内。订異此外’本發明之某些化合物可以不同互變異構形式存 ’且預期本發明化合物所能形成之任何互變異構形式均包括於本發明範圍内。 f 除上文所述之精神病及精神***症之外，nk3受體拮抗劑已牵連於多種疾病中。Langh)is等人在 n’299, 712-717, 2001中推斷NK3拮抗劑一般可應用於CNS疾病中，且尤其可應用於焦慮及抑鬱症。等人在 122, 715巧22, 1997 中進一步將 ΝΚ3 拮抗劑牽連於不同大腦功能，諸如皮質處理、學習及記憶、神經内为/必及行為調卽。其他研究已展示ΝΚΒ及ΝΚ3受體與疼痛有關’且ΝΚ3拮抗劑具有抗傷害感受及鎮痛作用 [Fioramonti, Neurogastroenterol.Motil.,\5, 363-369, 2003] ° Mazelin 等人在 h/e 5W·，63, 293-304，1998 中展示 NK3 拮抗劑對腸炎有作用且推斷該等拮抗劑可用於治療大腸急躁症（IBS )。此外，在活體内模型中已證明NK3拮抗劑適用於治療氣道相關疾病，諸如哮喘、氣道過度反應、咳嗷及支氣管收縮（bronchorestriction)。[Daoui, Care 158，42-48，1998]。Maubach 等人在/VeMroic/·，83, 1047-1062，1998 中展示 NKB 及 NK3 促效劑 senktide 增加癲癇樣放電之頻率及持續時間’且因此推斷NK3拮抗劑具 89 200906801 有抗驚厥潛力。最終，Kernel等人在《/.iVewroscz·.，22 1929 1936, 2002中提議使用NK3拮抗劑治療帕金森氏症 (Parkinson’s Disease)。因此，臨床、臨床前、活體内及活體外研究均支持NK3 受體拮抗劑適用於治療或預防多種病症，包括精神病、精神***症、抑鬱症、焦慮、認知障礙、肥胖症、阿茲海默氏症（Alzheimer’s disease)、帕金森氏症、疼痛、驚厥、咳嗽、哮喘、氣道過度反應、微血管過敏、支氣管收縮、腸炎及發炎性腸病。將精神***症分為幾個亞類。偏執型（paran〇id type )，特徵為妄想及幻覺，且不存在思維障礙（th〇ught di_dM )，錯亂行為（disorganized behavior)及情感平淡（affecHve flattening)。錯亂型（disorganized type)，在國際疾病分類（ICD)中亦稱之為「青春型精神***症（“心口匕印卜 schizophrenia)」，其中思維障礙及情感平淡共同存在。緊張型（catatonic type)，其中明顯以精神運動障礙為主 (prominent psychomotor disturbances)，且症狀可包括緊張性木僵（catatonic stupor )及蠟樣屈曲（waxy flexibility )。未分化型（undifferentiated type )，其中存在精神病症狀，但尚未滿足偏執型、錯亂型或緊張型之標準。精神***症之症狀自身通常表現為三大類’亦、即正性、負性及認知症狀。正性症狀為彼等表現「過度」正常經驗者，諸如幻覺及妄想。貞性症狀為彼等患者遭受缺乏正f經驗者，諸如快感缺乏Unhedonia )及缺少社會互動（iack 〇f s〇ciai 90 200906801 interaction)。認知症狀係關於精神***症中之認知障礙，諸如缺少持續注意力及決策缺陷。當前的抗精神病藥在治療正性症狀中相當成功，但對於負性及認知症狀而言進展不佳。與此相反，已在臨床上證實NK3拮抗劑改良精神分裂症中之正性與負性症狀161， 204]，且根據上述論述，亦預期其亦對認知症狀發揮作用。認知障礙包括認知功能或認知域受損，例如工作記憶、注意力及警覺力、語文學習及記憶、視覺學習及記憶、推 f '理及問題解決（例如執行功能）、處理速度及/或社會認知。詳言之，認知障礙可能表明注意力缺陷、思維混亂、思維緩慢、理解困難、注意力不集中、問題解決能力減弱^記憶力變差、難以表現想法及/或難以整合想法，感覺及行為，或難以消除不相關想法。在一具體實例中’本發明係關於適用於治療之本發明化合物。在一具體實例中’本發明係關於治療選自以下疾病之 t 疾病的方法：精神病；精神***症；類精神***症 (schizophrenoform disorder );***情感性障礙（schiz〇affective disorder);妄想症（delusional disorder);暫時性精神病 (brief psychotic disorder);共享型精神病（shared psych〇tic disorder);歸因於一般醫學狀況之精神病；物質或藥物引發之精神病（古柯鹼、酒精、***等）：類精神*** 人格異常（schizoid personality disorder);精神***型人格異常（schizoptypal personality disorder);與重度憂營 91 200906801 症有關之精神病或精神***症；雙極性情感疾患、阿茲海默氏症或帕金森氏症；重度憂鬱症，·一般性焦慮症；雙極性情感疾患（維持治療、復發預防及穩定化）；躁狂（mania); 輕症躁狂（hyP〇mania );認知障礙；注意力缺乏過動症 (ADHD )，肥胖症；食慾降低；阿茲海默氏症；帕金森氏症；疼痛；驚厥；咳嗷；哮喘；氣道過度反應；微血管過敏；支氣管收縮；慢性阻塞性肺病；尿失禁；腸炎；及發炎性腸病，該方法包含向有需要之患者投予治療有效量之本發明化合物。在一具體實例中，本發明係關於治療精神***症之方法，該方法包含向有需要之患者投予治療有效量之本發明化口物。詳5之，該治療包括治療精神***症之正性、負性及/或認知症狀。在一具體實例中，本發明係關於治療認知障礙之方法， "玄方法包合向有需要之患者投予治療有效量之本發明化合物。詳言之，該認知障礙表現為工作記憶、注意力及警覺力浯文學習及記憶、視覺學習及記憶、推理及問題解決 (例如執行功能）、處理速度及/或社會認知衰退。、典型及非典型抗精神病藥，詳言之D2拮抗劑之抗精神病作用’係經由抑制突觸後D2受體而實現。然而，突觸别D2自冑受體亦受此等化合物之投予所影冑，引起多 =胺神經元衝動頻率（fiHng崎）增加，此實際上抵消抗知神病作用。增加之衝動頻率一直持續至突觸前自身受體乍用被阻斷（去極化阻斷）為止，通常在以典型或非典 92 200906801 型抗精神病攀县、A & t /、長4 >D療約3週後。此模型解釋當起始d2 才。抗d〜療時，通常可見臨床效果高達3週之延遲。NR〗秸抗劑看似抑制由D2拮抗劑引起之突觸前D2自身受體所 "^之夕巴胺神、經元衝動的增加，因此預期NK3拮抗劑及 D2拮抗劑之組合投予使臨床效果更快顯現。此外，已知D2 乜抗刈乓加促礼素（pr〇lactin )含量，此可能導致嚴重副作用諸如月質疏鬆症。眾所周知NK3促效劑使促乳素增加’由此可推斷NK3拮抗劑將降低增高之促乳素含量（亦即’使其正常化）°因此，組合使用NK3拮抗劑及D2拮抗J叮解決些與D2拮抗劑投予有關之安全問題。類似地，NK3拮抗劑可與以下標靶中之一或多者的拮抗劑/反向促效劑/負性調節劑/部分促效劑一起投予：多巴胺受體、多巴胺D3受體、多巴胺！)4受體、磷酸二酯酶pDE丨〇、血清素5-HT1A受體、血清素5-Ht2a受體、血清素5_Ht6 受體、腎上腺素α2受體、***鹼丨型受體、組織胺h3受體、環加氧酶、鈉通道或甘胺酸轉運蛋白GiyTl ;或與以下標革巴中之一或多者的促效劑/正性調節劑/部分促效劑一起投予：血清素5-HT2C受體、KCNQ通道、NMDA受體、 AMPA受體、煙鹼α_7受體、蕈毒鹼Ml受體、葦毒鹼M4 受體、代謝性麩胺酸受體mGluR2、代謝性麩胺酸受體 mGluR5、多巴胺D1受體或多巴胺D5受體。本發明化合物與其他抗精神病化合物（諸如D2拮抗劑' D2部分促效劑、PDE10拮抗劑、5七丁2八拮抗劑、5-HT6 拮抗劑或KCNQ4拮抗劑）之該組合投予可相繼或相伴進 93 200906801 行。D2 #抗劑或部分促效劑之實例包括氟哌啶醇 (hal〇perid〇1 )、氯丙啡（chI〇rpr〇mazine )、舒必利 (sulpirid)、利培酮、齊拉西酮（ziprasid〇n)、奥氮平、喹硫平（quetiapin)及氯氮平。在-具體實例中，本發明化合物係以每日每公斤體重約0.001 mg至每公斤體重約1〇〇 mg之量投予。詳古之，每曰劑量可在每曰每公斤體重〇.〇1邮至每公斤體重。約5〇 mg範圍内。確切劑量將取決於投予頻率及模式、待治療個體之J·生別年齡、體重及一般狀況、待治療病況之種類及嚴重程度、待治療之任何併發症、所要治療效果及彼等熟習此項技術者已知的其他因素。典型成人口服劑量將在每天M000 物，諸如每天UOma圍内。 ^ 在具體實例中，本發明係關於本發明化合物在製造用於/口療選自以下疾病之疾病的醫藥品中之用途：精神病，精神7刀裂症；類精神***症；***情感性障礙；妄想症暫時[生精神病共享型精神病；歸因於一般醫學狀況之精神病’物質或藥物引發之精神病（古柯驗、酒精、安 p等）’類精神分^人格異常；精神***型人格異常；重度憂臀症有關之精神病或精神***症；雙極性情感疾患、阿茲海默氏症或帕金森氏症；重度憂鬱症；一般性焦 .雙極H If感疾患（維持治療、復發預防及穩定化）、幸症％狂’認知障礙；ADHD ;肥胖症；食慾降低 °海’犬氏症’帕金森氏症；疼痛；驚厥；咳漱；哮喘 94 200906801 軋迢過度反應；微血管過敏；支氣管收縮；慢性阻塞性肺病；尿失禁；腸炎；及發炎性腸病。在一具體實例中，本發明係關於本發明化合物在製造用於治療精神***症之醫藥品中的用途。詳言之，該治療包括治療精神***症之正性、負性及/或認知症狀。在一具體實例中，本發明係關於本發明化合物在製造用於治療認知障礙之醫藥品中的用途。詳言之，該認知障礙表現為工作記憶、注意力及警覺力、語文學習及記憶、視覺學習及記憶、推理及問題解決（例如執行功能）、處理速度及/或社會認知衰退。在—具體實例中，本發明係關於用於治療選自以下疾病之疾病的本發明化合物：精神病；精神***症；類精神 ***症；***情感性障礙；妄想症；暫時性精神病；共享里精神病；歸因於一般醫學狀況之精神病；物質或藥物引發之精神病（古柯鹼、酒精、***等）：類精神*** 人格異常；精神***型人格異常；與重度憂鬱症有關之精神病或精神***症；雙極性情感疾患、阿茲海默氏症或帕金秫氏症；重度憂鬱症；一般性焦慮症；雙極性情感疾患 (維持治療、復發預防及穩定化）；躁狂；輕症躁狂；認知障礙；ADHD ;肥胖症；食慾降低；阿茲海默氏症；帕金森氏症；疼痛；驚厥；咳嗷；哮喘；氣道過度反應；微血管過敏；支氣管收縮；慢性阻塞性肺病；尿失禁；腸炎；及發炎性腸病。在—具體實例中’本發明係關於用於治療精神***症 95 200906801 之本發明化合物。詳言之，該治療包括治療精神***症之正性、負性及/或認知症狀。在一具體實例中，本發明係關於用於治療認知障礙之本發明化合物。詳言之，該認知障礙表現為工作記憶、注意力及警覺力、語文學習及記憶、視覺學習及記憶'推理及問題解決（例如執行功能）、處理速度及/或社會認知衰退〇 f 本發明化合物可作為純化合物單獨投予或與醫藥學上可接又之載劑或賦形劑一起以單劑或多劑投予。可根據彼等諸如 Remington : The Science and Practice 〇fpharmacy，第 M 版，Gennaro 編，Mack PubHshing c〇，以“⑽，pA，Η% 中所揭不之習知技術，以醫藥學上可接受之載劑或稀釋劑、及任何其他已知佐劑及賦形劑調配本發明之醫藥組合物。醫藥組合物可經特定調配以藉由任何合適途徑投予，諸如經口、經直腸、經鼻、經肺、局部（包括經頰及舌下）、經皮、腦池内、腹膜内、經***及非經腸（包括皮下、肌肉内、鞘内、靜脈内及皮内）途徑，較佳為經口途徑。應瞭解’較佳途徑將取決於待治療之個體的一般狀況及年齡’待治療病況之種類及所選擇之活性成份。用於經口投予之醫藥組合物包括固體劑型，諸如膠囊、錠劑、糖衣藥丸、丸劑、***劑、散劑及顆粒劑。若適當，則其可經製備具有包衣。用於經口投予之液體劑型包括溶液、乳液、懸浮液、 96 200906801 糖漿及酏劑。用於非經腸投予之醫藥組合物包括無菌水性及非水性可注射溶液、分散液、懸浮液或乳液以及待在使用前在無菌可注射溶液或分散液中復水之無菌散劑。其他合適投予形式包括栓劑、噴霧、軟膏、乳膏、凝膠、吸入劑、皮膚貼片、植入物等。便利地’本發明化合物係以含有約〇.丨至5〇〇 mg之量的該等化合物，諸如10mg、5〇mg、1〇〇mg、15〇mg、2⑽ mg或250 mg本發明化合物之單位劑型投予。對於諸如靜脈内、鞘内、肌肉内及類似投予之非經腸途徑而言，典型劑量約為經口投予所採用之劑量約一半。對於非經腸投予而言，可採用本發明化合物在無菌水各液、丙二醇水溶液、維生素E水溶液或芝麻油或花生油中之/奋液。右必要，則該等水溶液應合適地經緩衝且液體稀釋劑首純得以足夠生理食鹽水或葡萄糖等渗。水溶液尤其適於靜脈内、❿肉内、皮下及腹膜内投予。所採用之無菌水性介質均易於藉由彼等熟習此項技術者已知之標準技術獲得。 …合適醫藥載劑包括惰性固體稀釋劑或填充劑、無菌水办液及各種有機溶劑。固體載劑之實例為乳糖、白土（⑽以 aIba)、藉、糖、環糊精、滑石、明膠、瓊脂、果膠、阿拉伯膠、硬脂酸鎂、硬脂酸及纖維素之低碳烧基醚。液體載 =之實例為糖漿、花生油、撖欖油、磷脂、脂肪酸、脂肪胺1氧化乙烯及水。藉由使本發明化合物與醫藥學上 97 200906801 可接受之載劑組合所形成投予途徑之多種劑型容易地物隨後以適於所揭示如工口技予之本發明調配物可呈離散單位形式（諸 ==㈣其各自含有預定量之活性成 ^ ==劑。此外，經™物可為散劑或顆粒射 ::::::一液购、或…或… 以散劑或^ Γ載^用於經口投予，則製劑可為鍵劑，例如 ***劑:式2式置於硬明膠膠囊中，或其可呈糖鍵或約…固體載劑之量可變’但-般將為約25叫至若使用液體裁劑囊或無菌可注射液體液）形式。則製劑可呈糖漿、乳液、軟明膠膠諸如水性或非水性液體懸浮液或溶 ρ由使活性成份與―般佐劑及/或稀釋㈣合，將：：物在習知製鍵機中愿縮而製備錠劑。佐劑或稀釋劑之只列包含.玉米澱粉、馬鈴薯澱粉、滑石、硬脂酸鎂、 :月膠、乳糖、膠及其類似物。可使用一般用於諸如著：其與令:二等：的之任何其他佐劑或添加劑，限制條件為體實例中，本發明係關於包含本發明化合物以及弟:抗精神病藥劑之醫藥組合物。在—具體實例中，該第一抗精神病藥劑係選自以下標靶之拮抗劑/反向促效劑/ 負性調節劑/部分促效劑：多巴胺D2受體、多巴胺卯受 98 200906801 體夕巴胺D4受體、磷酸二酯酶PDE1〇、血清素5_HTia 又體、血清素5_HT2a受體、血清素5-HT6受體、腎上腺素 α2文體、***鹼1型受體、組織胺H3受體、環加氧酶、鈉通運或甘胺酸轉運蛋白GlyT1 ;或以下標靶之促效劑/正陡σ周節劑/部分促效劑：血清素5-HT2c受體、KCNQ通道、 NMDA文體、AMPA受體、煙鹼α_7受體、蕈毒鹼mi受體蕈毋鹼M4受體、代謝性麩胺酸受體m(}luR2、代謝性麵胺酸受體mGluR5、多巴胺D1受體或多巴胺D5受體。在一具體實例中，該第二抗精神病藥劑係選自典型抗精神病藥、非典型抗精神病藥、D2拮抗劑、部分D2促效劑、 PDE10拮抗劑、5_Ht2a拮抗劑、5_ht6拮抗劑及KCNQ4拮抗劑’尤其為非典型抗精神病藥、D2拮抗劑、部分促效劑。該等抗精神病藥之特定實例包括氟哌啶醇、氯丙啡、舒必利、利培鲖、齊拉西酮、奥氮平、喹硫平及氣氮平。在一具體實例中，本發明係關於一種醫藥套組，其包含一包含本發明化合物之容器及一包含抗精神病藥之獨立容器。該抗精神病藥係選自典型抗精神病藥、非典型抗精神病藥、D2拮抗劑、部分D2促效劑、PDE10拮抗劑、5-HTm拮抗劑、5-HT6拮抗劑及KCNQ4拮抗劑，尤其為非典型抗精神病藥、D2拮抗劑、部分D2促效劑。該等抗精神病藥之特定實例包括氟旅咬醇、氯丙明：、舒必利、利培鲷、齊拉西酮、奥氮平、喹硫平及氯氮平。本文中引用之所有參考文獻，包括公開案、專利申請案及專利均以引入的方式全部併入，且其併入之程度如各 99 200906801 參考文獻以引入的方式個別本文t般““併入且全部闡明於出之二二許之最大程度），而不管本文別處作、疋文獻的任何單獨提供之併入。除非本文另外說明或上下文明明之上下「― 射盾，否則描述本發為」及及類似指示物應解釋為涵皿·早數及複數兩者。舉例而短扭「姑人，陈非另外說明，否則 ϋ勿」應理解為提及本發明之各種「化合物」或特定描述之態樣。除非另外說明，否則太令姐M i . 古則本文k供之所有確切值代表相應 u值（例如，關於特定因子或量測提供之所有例示性確切值亦可認為提供相應近似量測值，若適當，則藉由修飾）。」除非另外3兒明或上下文明顯矛盾，否則關於要素使用諸如「包含」、「具有」、「包括」或「含有」之術語的本發明任何態樣於本文的描述意欲為由、基本上由彼特定要素、、且成或貝貝上包含彼特定要素之本發明類似態樣提供支持、（例如’除非另外說明或上下文明顯矛盾，否則本文、，為匕g特疋要素之組合物應理解為亦描述由彼要素組成之組合物）。合成途徑本發明之通式I化合物（其中R1_R17、Α及X係如上文所定義）可藉由以下反應流程及實施例所述之方法製備。在所述方法中可能使用自身為熟習此項技術之化學家已知或對一般热習此項技術者顯而易見的變體或修正。此 100 200906801 外，熟習此項技術者根據以下反應流程及實施例將顯而易見製備本發明化合物之其他方法。在通式I-XX之中間化合物中，、A及X係如式 1所定義。對於可作為兩種或兩種以上互變異構體之混合物或平衡形式存在之化合物而言，流程中僅說明一種互變異構體’但其可能並非最穩定之互變異構體。對於可作為對映異構體、立體異構體或幾何異構體形式存在之化合物而、 S ’指明其幾何構型；否則，該結構表示立體異構體之混合物。該等化合物包括（但不限於）通式IV及VII化合物之1，3-酮酯或烯胺’其可以酮或烯醇形式之間的平衡存在，且後者亦可以熟習此項技術之化學家熟知的Z及E異構體形式存在。該等化合物亦包括通式I之本發明化合物，其可類似於亦為熟習此項技術者熟知的鄰，鄰雙取代聯芳基化合物中之滯轉異構現象’由於繞碳-碳單鍵之限制性旋轉而作為滯轉異構體之混合物形式存在。It is to be understood herein that when an enantiomeric form is indicated, the compound is in an enantiomeric excess', e.g., substantially pure form. Thus, a specific embodiment of the invention is directed to having at least 6%, at least 7%, at least, at least 85. /. At least 90%, at least 96%, preferably at least (four) enantiomeric excess of the compound of the invention. The racemic form can be resolved into the optical antipodes by known methods, for example /V. by separating the diastereomeric salts with an optically active acid, and releasing the optically active amine compound by treatment with a base. . The other method of splitting the racemate into optical enantiomers is based on optically active matrix chromatography. The compounds of the invention may also be resolved by the formation of diastereomeric derivatives. Other methods of splitting optical isomers known to those skilled in the art can be used. These methods include those by JJ, eS, A. C〇llet and S_Wilen in "e job such as listening to S, Racemates, and Res〇luti〇ns", J〇hn _ s should, Yk (lan) Revealed in the middle. Optically active compounds can also be prepared from optically active starting materials. Furthermore, when a double bond or a fully or partially saturated ring system is present in the molecule, 88 200906801: geometric isomers are formed. Any geometric isomerism is expected. Likewise, molecules whose == are included in the bond pre-rotated by the inventive body may form geometric isomers. It is contemplated that such isomers are also included within the scope of the invention. Further, it is intended that certain compounds of the invention may exist in different tautomeric forms and that any tautomeric forms which the compounds of the invention can be formed are intended to be included within the scope of the invention. f In addition to the psychosis and schizophrenia described above, nk3 receptor antagonists have been implicated in a variety of diseases. Langh)is et al. in n'299, 712-717, 2001 concluded that NK3 antagonists are generally applicable to CNS diseases and are particularly useful for anxiety and depression. Etc. 12, 715, 22, 1997 further implicated ΝΚ3 antagonists in different brain functions, such as cortical treatment, learning and memory, and neurological/required behavioral disorders. Other studies have shown that ΝΚΒ3 and ΝΚ3 receptors are associated with pain' and ΝΚ3 antagonists have antinociceptive and analgesic effects [Fioramonti, Neurogastroenterol. Motil., \5, 363-369, 2003] ° Mazelin et al. at h/e 5W ·, 63, 293-304, 1998 shows that NK3 antagonists have an effect on enteritis and it is concluded that these antagonists can be used to treat colorectal dysfunction (IBS). In addition, NK3 antagonists have been shown to be useful in the treatment of airway related diseases such as asthma, airway hyperresponsiveness, cough and bronchorestriction in in vivo models. [Daoui, Care 158, 42-48, 1998]. Maubach et al., /VeMroic/, 83, 1047-1062, 1998, show that NKB and the NK3 agonist senktide increase the frequency and duration of epileptiform discharges' and therefore conclude that NK3 antagonists have an anticonvulsant potential. Finally, Kernel et al., in "/.iVewroscz., 22 1929 1936, 2002, proposed the use of NK3 antagonists to treat Parkinson's Disease. Therefore, clinical, preclinical, in vivo and in vitro studies support NK3 receptor antagonists for the treatment or prevention of a variety of conditions, including psychosis, schizophrenia, depression, anxiety, cognitive impairment, obesity, Alzheimer's Alzheimer's disease, Parkinson's disease, pain, convulsions, cough, asthma, airway hyperreactivity, microvascular allergy, bronchoconstriction, enteritis, and inflammatory bowel disease. Divide schizophrenia into several subcategories. Paran〇id type, characterized by delusions and hallucinations, and without thinking disorder (th〇ught di_dM), disorganized behavior and affecHve flattening. Disorganized type, also known as "young-type schizophrenia" in the International Classification of Diseases (ICD), in which mental retardation and emotional dullness coexist. Catatonic types, which are predominantly psychomotor disturbances, and symptoms may include catatonic stupor and waxy flexibility. An undifferentiated type in which psychotic symptoms exist, but the criteria for paranoid, disordered, or tense are not met. Symptoms of schizophrenia usually manifest themselves in three major categories, namely, positive, negative, and cognitive symptoms. Positive symptoms are those who show "excessive" normal experience, such as hallucinations and delusions. Spastic symptoms are those in which patients suffer from a lack of positive experience, such as a lack of Unhedonia, and lack of social interaction (iack 〇f s〇ciai 90 200906801 interaction). Cognitive symptoms are related to cognitive impairment in schizophrenia, such as lack of sustained attention and decision deficits. Current antipsychotics have been quite successful in treating positive symptoms, but have not progressed well for negative and cognitive symptoms. In contrast, NK3 antagonists have been clinically proven to improve positive and negative symptoms in schizophrenia 161, 204], and it is also expected to play a role in cognitive symptoms based on the above discussion. Cognitive impairment includes impaired cognitive or cognitive domains, such as working memory, attention and alertness, language learning and memory, visual learning and memory, push and problem solving (eg executive function), processing speed and/or society Cognition. In detail, cognitive impairment may indicate attention deficit, confusion, slow thinking, difficulty understanding, lack of concentration, weak problem-solving skills, poor memory, difficulty in expressing ideas, and/or difficulty in integrating ideas, feelings, and behaviors, or It is difficult to eliminate irrelevant ideas. In one embodiment, the invention relates to compounds of the invention that are suitable for use in therapy. In one embodiment, the invention relates to a method of treating a disease selected from the group consisting of: psychosis; schizophrenia; schizophrenoform disorder; schiz〇affective disorder; paranoia ( Delusional disorder; shared psychotic disorder; shared psych〇tic disorder; psychosis attributed to general medical conditions; psychosis caused by substance or drug (***e, alcohol, amphetamine, etc.): Schizoid personality disorder; schizoptypal personality disorder; psychosis or schizophrenia associated with severe stagnation 91 200906801; bipolar affective disorder, Alzheimer's disease or pa Jinsen's disease; severe depression, general anxiety disorder; bipolar emotional disorder (maintenance treatment, recurrence prevention and stabilization); mania; hypopyrosis (hyp〇mania); cognitive impairment; attention Lack of hyperactivity disorder (ADHD), obesity; decreased appetite; Alzheimer's disease; Parkinson's disease Symptoms; pain; convulsions; cough; asthma; airway hyperreactivity; microvascular hypersensitivity; bronchoconstriction; chronic obstructive pulmonary disease; urinary incontinence; enteritis; and inflammatory bowel disease, the method comprising administering a therapeutically effective amount to a patient in need thereof A compound of the invention. In one embodiment, the invention is directed to a method of treating schizophrenia comprising administering to a patient in need thereof a therapeutically effective amount of a mouthbo of the invention. In detail, the treatment includes the treatment of positive, negative and/or cognitive symptoms of schizophrenia. In one embodiment, the invention is directed to a method of treating a cognitive disorder, "the method of inclusion is to administer a therapeutically effective amount of a compound of the invention to a patient in need thereof. In particular, the cognitive impairments are characterized by working memory, attention and alertness, learning and memory, visual learning and memory, reasoning and problem solving (eg, executive function), processing speed, and/or social cognitive decline. Typical and atypical antipsychotics, in detail the antipsychotic effect of D2 antagonists, are achieved by inhibition of postsynaptic D2 receptors. However, the D2 autoreceptor receptor is also affected by the administration of these compounds, causing an increase in the frequency of the multi-amine neuron impulse (fiHng), which actually counteracts the anti-know effect. The increased impulse frequency continues until the presynaptic autoreceptor is blocked (depolarization block), usually in the typical or SARS 92 200906801 antipsychotic climbing county, A & t /, long 4 &gt ;D treatment is about 3 weeks later. This model explains when starting d2. When anti-d treatment, it is usually seen that the clinical effect is up to 3 weeks. NR〗 Straw antibiotics appear to inhibit the increase in the presynaptic D2 autoreceptor caused by D2 antagonists, and the combination of NK3 antagonists and D2 antagonists is expected. Make clinical effects appear faster. In addition, D2 is known to be resistant to pr〇lactin, which may result in serious side effects such as urethr. It is well known that NK3 agonists increase prolactin', thus it can be inferred that NK3 antagonists will reduce the increased prolactin content (ie, 'normalize it). Therefore, the combination of NK3 antagonist and D2 antagonist J Safety issues related to D2 antagonist administration. Similarly, an NK3 antagonist can be administered with an antagonist/reverse agonist/negative modulator/part agonist of one or more of the following targets: dopamine receptor, dopamine D3 receptor, dopamine ! 4 receptor, phosphodiesterase pDE丨〇, serotonin 5-HT1A receptor, serotonin 5-Ht2a receptor, serotonin 5_Ht6 receptor, adrenergic α2 receptor, cannabinoid receptor, histamine H3 receptor, cyclooxygenase, sodium channel or glycine transporter GiyTl; or with one or more of the following agonists/positive regulators/partial agonists: serum 5-HT2C receptor, KCNQ channel, NMDA receptor, AMPA receptor, nicotine α_7 receptor, muscarinic M1 receptor, muscarinic M4 receptor, metabolic glutamate receptor mGluR2, metabolic bran Amino acid receptor mGluR5, dopamine D1 receptor or dopamine D5 receptor. The combination of a compound of the invention and other antipsychotic compounds, such as a D2 antagonist 'D2 partial agonist, PDE10 antagonist, 5 hepta-8 antagonist, 5-HT6 antagonist or KCNQ4 antagonist, may be administered sequentially or Accompanied by 93 200906801 line. Examples of D2 #antibiotics or partial agonists include haloperidol (hal〇perid〇1), chloropropanophene (chI〇rpr〇mazine), sulpirid, risperidone, ziprasidone (ziprasid) 〇n), olanzapine, quetiapin and clozapine. In a specific embodiment, the compound of the present invention is administered in an amount of from about 0.001 mg per kilogram of body weight per day to about 1 mg per kilogram of body weight. In detail, each dose can be delivered to each kilogram of body weight per kilogram of body weight per kilogram. Approximately 5 〇 mg range. The exact dose will depend on the frequency and mode of administration, the age of the individual to be treated, the age and weight of the individual, the type and severity of the condition to be treated, any complications to be treated, the desired therapeutic effect and their familiarity. Other factors known to the skilled person. A typical adult oral dose will be in M000 per day, such as daily UOma. ^ In a specific example, the invention relates to the use of a compound of the invention in the manufacture of a medicament for/oral treatment of a disease selected from the group consisting of psychosis, mental 7-split; schizophrenia; schizoaffective disorder Paranoia temporary [psychiatric shared psychosis; psychosis attributed to general medical conditions] substance or drug-induced psychosis (coca test, alcohol, p, etc.) class mentality ^ personality abnormalities; schizophrenic personality abnormalities Severe sorrow and schizophrenia; bipolar affective disorder, Alzheimer's disease or Parkinson's disease; severe depression; general focus. Bipolar H If sensation (maintenance treatment, recurrence prevention) And stabilization), fortunateness, madness, 'cognitive disorder; ADHD; obesity; loss of appetite; sea' canine's disease, Parkinson's disease; pain; convulsions; cough; asthma 94 200906801 over-reaction; Bronchial contraction; chronic obstructive pulmonary disease; urinary incontinence; enteritis; and inflammatory bowel disease. In one embodiment, the invention relates to the use of a compound of the invention in the manufacture of a medicament for the treatment of schizophrenia. In particular, the treatment includes the treatment of positive, negative and/or cognitive symptoms of schizophrenia. In one embodiment, the invention relates to the use of a compound of the invention in the manufacture of a medicament for the treatment of a cognitive disorder. In particular, the cognitive impairment manifests as working memory, attention and alertness, language learning and memory, visual learning and memory, reasoning and problem solving (eg, executive function), processing speed, and/or social cognitive decline. In a specific embodiment, the invention relates to a compound of the invention for use in the treatment of a disease selected from the group consisting of: psychosis; schizophrenia; schizophrenia; schizoaffective disorder; paranoia; temporary psychosis; Psychosis attributed to general medical conditions; psychosis caused by substance or drug (***e, alcohol, amphetamine, etc.): schizophrenic personality abnormalities; schizophrenic personality abnormalities; psychosis or schizophrenia associated with severe depression Bipolar affective disorder, Alzheimer's disease or Parkin's disease; severe depression; general anxiety disorder; bipolar affective disorder (maintenance treatment, recurrence prevention and stabilization); mania; mild mania Cognitive impairment; ADHD; obesity; loss of appetite; Alzheimer's disease; Parkinson's disease; pain; convulsions; cough; asthma; airway hyperreactivity; microvascular allergy; bronchoconstriction; chronic obstructive pulmonary disease; Enteritis; and inflammatory bowel disease. In a specific example, the invention relates to a compound of the invention for use in the treatment of schizophrenia 95 200906801. In particular, the treatment includes the treatment of positive, negative and/or cognitive symptoms of schizophrenia. In one embodiment, the invention relates to compounds of the invention for use in the treatment of cognitive disorders. In particular, the cognitive impairment manifests as working memory, attention and alertness, language learning and memory, visual learning and memory 'inference and problem solving (eg, executive function), processing speed, and/or social cognitive decline. The compound can be administered as a neat compound alone or in combination with a pharmaceutically acceptable carrier or excipient in a single or multiple doses. According to their patents such as Remington: The Science and Practice 〇fpharmacy, Mth Edition, Gennaro, Mack PubHshing c〇, with the techniques known in (10), pA, Η%, pharmaceutically acceptable The pharmaceutical composition of the present invention is formulated with a carrier or diluent, and any other known adjuvants and excipients. The pharmaceutical composition may be formulated to be administered by any suitable route, such as orally, rectally, nasally, Transpulmonary, topical (including buccal and sublingual), transdermal, intracisternal, intraperitoneal, transvaginal and parenteral (including subcutaneous, intramuscular, intrathecal, intravenous and intradermal) routes, preferably Oral route. It should be understood that 'the preferred route will depend on the general condition and age of the individual to be treated' and the type of condition to be treated and the active ingredient selected. Pharmaceutical compositions for oral administration include solid dosage forms such as capsules. , lozenges, dragees, pills, buccal preparations, powders and granules, if appropriate, may be prepared with a coating. Liquid dosage forms for oral administration include solutions, emulsions, suspensions, 96 20 0906801 Syrups and elixirs. Pharmaceutical compositions for parenteral administration include sterile aqueous and nonaqueous injectable solutions, dispersions, suspensions or emulsions, and reconstituted in sterile injectable solutions or dispersions before use. Sterile powders. Other suitable forms of administration include suppositories, sprays, ointments, creams, gels, inhalants, dermal patches, implants, etc. Conveniently the compounds of the invention contain about 〇.丨 to 5〇. Such compounds in an amount of 〇mg, such as 10 mg, 5 mg, 1 mg, 15 mg, 2 (10) mg or 250 mg, are administered in unit dosage form for the compounds of the invention. For example, intravenous, intrathecal, intramuscular, and For a parenterally-administered parenteral route, the typical dose is about half of that used for oral administration. For parenteral administration, the compounds of the invention may be employed in sterile aqueous solutions, aqueous propylene glycol solutions, vitamins. E solution in aqueous solution or sesame oil or peanut oil. If necessary, the aqueous solution should be properly buffered and the liquid diluent first is sufficiently isotonic enough to be physiological saline or glucose. Intrapulmonary, intramuscular, subcutaneous and intraperitoneal administration. The sterile aqueous medium employed is readily obtainable by standard techniques known to those skilled in the art. Suitable pharmaceutical carriers include inert solid diluents or fillers. , sterile water solution and various organic solvents. Examples of solid carrier are lactose, white clay ((10) with aIba), borrow, sugar, cyclodextrin, talc, gelatin, agar, pectin, acacia, magnesium stearate, Stearic acid and low-carbon alkyl ether of cellulose. Examples of liquid loading are syrup, peanut oil, eucalyptus oil, phospholipid, fatty acid, fatty amine 1 ethylene oxide and water. By making the compound of the present invention and medicinal 97 200906801 Acceptable Carrier Combinations A variety of dosage forms for forming a route of administration are readily available. The formulations of the invention, which are suitable for use in the disclosed embodiments, can be in discrete units (the ==(d) each containing a predetermined amount of activity Into ^ = = agent. In addition, the TM substance may be a powder or a granule:::::: one liquid, or ... or ... by a powder or a sputum for oral administration, the preparation may be a key agent, such as a buccal agent The formula 2 is placed in a hard gelatin capsule, or it may be in the form of a sugar bond or a solid carrier, but will generally be about 25 calls to a liquid capsule or a sterile injectable liquid. form. The preparation may be in the form of a syrup, an emulsion, a soft gelatin glue such as an aqueous or non-aqueous liquid suspension or a solution of the active ingredient and the "adjuvant adjuvant" and/or dilution (4). The tablet is prepared in a reduced manner. The list of adjuvants or diluents comprises corn starch, potato starch, talc, magnesium stearate, moon glue, lactose, gums and the like. Any other adjuvant or additive which is generally used for, for example, the following: and the like, the present invention relates to a pharmaceutical composition comprising the compound of the present invention and an antipsychotic agent. In a specific embodiment, the first antipsychotic agent is selected from the group consisting of antagonists/reverse agonists/negative regulators/partial agonists: dopamine D2 receptor, dopamine quinone 98 98068068 Pamine D4 receptor, phosphodiesterase PDE1〇, serotonin 5_HTia, serotonin 5_HT2a receptor, serotonin 5-HT6 receptor, adrenergic α2 stroma, cannabinoid type 1 receptor, histamine H3 receptor , cyclooxygenase, sodium transport or glycine transporter GlyT1; or the following target agonist / positive steep sigma / partial agonist: serotonin 5-HT2c receptor, KCNQ channel, NMDA style , AMPA receptor, nicotine α_7 receptor, muscarinic mi receptor muscarinic M4 receptor, metabolic glutamate receptor m (}luR2, metabolic facial acid receptor mGluR5, dopamine D1 receptor or Dopamine D5 receptor. In a specific example, the second antipsychotic agent is selected from the group consisting of a typical antipsychotic, an atypical antipsychotic, a D2 antagonist, a partial D2 agonist, a PDE10 antagonist, a 5_Ht2a antagonist, 5_ht6 Antagonists and KCNQ4 antagonists are especially atypical antipsychotics, D2 antagonists, and partial promotion Specific examples of such antipsychotics include haloperidol, chloropropanol, sulpiride, risperidone, ziprasidone, olanzapine, quetiapine, and nitrozapine. In a specific example, The present invention relates to a medical kit comprising a container comprising a compound of the invention and a separate container comprising an antipsychotic. The antipsychotic is selected from the group consisting of a typical antipsychotic, an atypical antipsychotic, a D2 antagonist, Part of the D2 agonist, PDE10 antagonist, 5-HTm antagonist, 5-HT6 antagonist and KCNQ4 antagonist, especially atypical antipsychotics, D2 antagonists, partial D2 agonists. Specific examples include fluoride brittle alcohol, chlorpromide, sulpiride, risperidone, ziprasidone, olanzapine, quetiapine, and clozapine. All references cited herein, including publications, patent applications The patents and patents are hereby incorporated by reference in their entirety in their entirety, in the extent of the extent of the in the Regardless of this Elsewhere for any individual piece goods provided documents are incorporated. Unless otherwise stated or clearly stated above in the context of "----------------------------------------------------------------------------------------------------------------------- For example, a short twist "guest, Chen Fei, otherwise, otherwise" should be understood as referring to various "compounds" or specific descriptions of the present invention. Unless otherwise stated, all of the exact values provided by the syllabus represent the corresponding u values (for example, all exemplary exact values provided for a particular factor or measurement may also be considered to provide corresponding approximations, If appropriate, by modification). The use of any aspect of the invention in terms of elements such as "including," "having," "including," or "including" is intended to be The invention provides support for a particular aspect of the invention, or a similar aspect of the invention containing a particular element on the babe (eg, 'unless otherwise stated or the context clearly contradicts, otherwise, the composition of the element is understood To also describe a composition consisting of the elements. Synthetic route The compounds of the formula I according to the invention (wherein R1_R17, hydrazine and X are as defined above) can be prepared by the following reaction schemes and the methods described in the examples. It is possible in the method to use variants or modifications that are known to the chemist who are familiar with the art or that are apparent to those skilled in the art. Other methods of preparing the compounds of the present invention will be apparent to those skilled in the art from the following reaction schemes and examples. In the intermediate compound of the formula I-XX, A and X are as defined in formula 1. For compounds which may exist as a mixture or a balanced form of two or more tautomers, only one tautomer is described in the scheme but may not be the most stable tautomer. For compounds which may exist as enantiomers, stereoisomers or geometric isomers, S' indicates its geometry; otherwise, this structure represents a mixture of stereoisomers. Such compounds include, but are not limited to, 1,3-ketoesters of the compounds of Formula IV and VII or enamines which may exist in a balance between ketone or enol forms, and the latter may also be chemists skilled in the art. Well-known Z and E isomer forms exist. The compounds also include the compounds of the invention of formula I which may be similar to the rheological isomerism in ortho-disubstituted aryl compounds which are well known to those skilled in the art' due to the carbon-carbon single bond The restriction rotation is present as a mixture of the isomers.

I " 通式111、VI及XI之起始物質係自概述於表2中之商業來源購得或其可藉由文獻中所述之標準方法或其修正容易地製備。使通式II之2-溴苯甲酸與通式III之酮基-酯在強驗（諸如氫化鈉）及銅或諸如溴化銅（I)之銅鹽存在下在合適溶~ (諸如1，4-二聘烷、乙腈或過量之上述酮基-酯）中在合適溫度下（諸如回流或在70°C下）偶合，形成通式iv化人物。該芳基化反應一般以銅催化之厄爾曼型偶合反鹿 101 200906801 (Ullmann-type coupling reaction)熟知（評論：s.V. Ley, A.W. Thomas Angew. Chem. Int. Ed. 2003, 42, 5400 ) 〇同樣，在此特定狀況下，當偶合反應涉及使諸如通式IV化合物之亞曱基化合物在銅或銅鹽存在下活化時，則該反應稱為亨特利反應（Hurtley reaction X W.R.H. Hurtley 乂 c/jew.I " The starting materials of Formulas 111, VI and XI are commercially available from commercial sources as summarized in Table 2 or can be readily prepared by standard methods described in the literature or modifications thereof. The 2-bromobenzoic acid of the general formula II and the keto-ester of the formula III are suitably dissolved in the presence of a strong test (such as sodium hydride) and copper or a copper salt such as copper (I) bromide (such as 1, 4-dioxane, acetonitrile or an excess of the above keto-esters are coupled at a suitable temperature (such as reflux or at 70 ° C) to form a character of the formula iv. The arylation reaction is generally well known as copper catalyzed Ullmann-type coupling reaction (Comment: sV Ley, AW Thomas Angew. Chem. Int. Ed. 2003, 42, 5400) 〇 Similarly, in this particular case, when the coupling reaction involves the activation of a sulfhydryl compound such as a compound of formula IV in the presence of a copper or copper salt, the reaction is referred to as the Hunter's reaction (Hurtley reaction X WRH Hurtley 乂c). /jew.

Soc. 1929, 1870 )。 f 接著使所獲得之通式IV化合物與通式VI之苯胺使用或不使用適當溶劑在加熱條件下反應，經由中間形成通式 VII之稀胺（其通常不自反應混合物分離）而形成通式viii 之異喹啉酮。或者，通式VII之烯胺可在適當脫水劑（諸如，四乙氧基矽烷）存在下在加熱條件下或在環境溫度不在催化量之酸（諸如，乙酸）存在下自通式VI之苯胺獲得。接著，可在如上文所述之加熱條件下或在環境溫度下在適當偶合劑（諸如EDC/HOBT)存在下進行形成通式νιπ 之異喹啉酮的環化反應。此外，可自起始通式質子化烯胺在涉及7(TC下進行之亨特利反應的經改質一鍋式程序中（形成通式ΥΠ化合物且隨後在較高溫度下進行環化）直接獲得通式VIII之異喹啉酮。自酮基酯Ιπ及苯胺VI在上文針對製備通式VII之烯胺所述的條件下容易= 獲得通式V之稀胺。通式vm化合物在熟習此項技術之化學家熟知㈣水解條件下容易地水解為通式IX之酸。最終，隨Soc. 1929, 1870). f. The resulting compound of the formula IV is then reacted with an aniline of the formula VI with or without the use of a suitable solvent under heating to form a formula by intermediate formation of a dilute amine of the formula VII which is generally not isolated from the reaction mixture. Isoquinolinone of viii. Alternatively, the enamine of formula VII can be derived from the aniline of formula VI in the presence of a suitable dehydrating agent such as tetraethoxynonane under heating or at ambient temperature in the absence of a catalytic amount of an acid such as acetic acid. obtain. Next, the cyclization reaction to form the isoquinolinone of the formula νιπ can be carried out under heating conditions as described above or at ambient temperature in the presence of a suitable coupling agent such as EDC/HOBT. In addition, the protonated enamine can be used in a modified one-pot procedure involving a Hunter's reaction at 7 (the formation of a general oxime compound and subsequent cyclization at higher temperatures). The isoquinolinone of the formula VIII is obtained directly. From the ketoesters Ιπ and aniline VI, it is easy to obtain the dilute amine of the formula V under the conditions described above for the preparation of the enamine of the formula VII. The chemist familiar with the art is well known (4) easily hydrolyzed to the acid of the formula IX under hydrolysis conditions.

C)或通4 XI之肼（A = N)的偶合形成本發明之通式I 102 200906801 化合物。該等偶合反應一般係經由以適當偶合劑或活化叫 (諸如（但不限於）亞硫醯氯）使酸活化，形成相應酿氯而進行。通式I之肼（其中= H)可藉由與適當醯基化試劑或烷基化試劑（諸如（但不限於）醯氯、胺曱酿氯、氯甲酸酯或烷基_化物）進行醯基化、烷基化或芳美化反應而轉化為同一通式之雙取代之肼（其中Rl不為氫）。 f 叫存=二：物（其中X為氫）可藉由在諸如壤之漠化月子在下的區域選擇性溴化反應轉化為通式χιι化合物。 =發==通式XW'各種親核試劑取：，形瞭解，=合物。彼等熟習此項技術者將容易地 1 妷及硫親核試劑（諸如（但不限於）胺方無胺、醯胺、雜瑗、轳β , 卩Γ於）胺、換所需之中性戈去暂匕物或硫醇）以該等轉若必要化陰離子：式購得或容易地獲得。、了在取代基R-R及X；虛# m 項技術者已知的標準有機合成方法進行進：一般熟習此換。仃進—步衍生化或轉 103 200906801Coupling of C) or by 肼 (A = N) forms a compound of the formula I 102 200906801 of the invention. Such coupling reactions are generally carried out by activating the acid with a suitable coupling agent or activation such as, but not limited to, sulfinium chloride to form the corresponding brewed chlorine. The oxime of formula I (wherein = H) can be carried out by reacting with an appropriate guanylating agent or alkylating agent such as, but not limited to, ruthenium chloride, amine ruthenium chloride, chloroformate or alkylate. The thiolation, alkylation or aromatization reaction is converted to a disubstituted oxime of the same formula (wherein R1 is not hydrogen). f is stored as = two: the substance (where X is hydrogen) can be converted to a compound of the formula χιι by a regioselective bromination reaction under the desertification phase such as soil. = hair = = formula XW 'various nucleophiles take:, shape understanding, = compound. Those skilled in the art will readily be able to sulphur and nucleophilic reagents (such as, but not limited to, amine-free amines, guanamines, hydrazines, 轳β, oxime) amines, to change the required neutrality. Go to the temporary sputum or thiol) to obtain the anion: if necessary, the formula is purchased or easily obtained. In the case of the substituents R-R and X; the standard organic synthesis method known to the technical experts of the virtual #m is carried out: it is generally familiar with this change.仃进-step derivatization or transfer 103 200906801

R17 NH, 流程2R17 NH, Process 2

104 200906801 流程3.升酞酸酐之合成 R9104 200906801 Scheme 3. Synthesis of sulphuric anhydride R9

AcCI/甲笨AcCI/A stupid

R12R12

R9 C02H R10R9 C02H R10

Ov^ 62% H2S04 160°C R11' T 'C〇2H R12Ov^ 62% H2S04 160°C R11' T 'C〇2H R12

流程4 R10 R11Process 4 R10 R11

XXVil XXVI R8^ ^R6 R7 或者，可如流程4中所示自通式XVIII之經取代之升酞酸軒（homophthalic anhydride )開始製備通式I化合物。 105 200906801 高鄰苯二甲酸酐為市售產品人J如/鼠3所不分別自通式 ΧΠΙ及XVI1之相應鄰氟苯甲腈«氟苯甲酸㈣其在驗（諸如碳酸鉀或碳酸绝）存在下在加熱條件下在適當溶劑（諸如二甲亞硪）中經歷與氰基乙酸乙冑训的芳族親核取代反應。偶合產物在㈣（諸如硫酸或鹽酸）存在下在水t在加熱條件下水解，形成通式⑽之二酸。最終’二酸在脫水劑（諸如（但不限於）乙酿氯）存在下不使用溶劑或在適當溶劑（諸如甲苯）中在加熱條件下（諸XXVil XXVI R8^^R6 R7 Alternatively, a compound of formula I can be prepared starting from a homophthalic anhydride of formula XVIII as shown in Scheme 4. 105 200906801 High phthalic anhydride is a commercially available product of human J, such as / mouse 3, which is not separately from the formula ΧΠΙ and XVI1 corresponding o-fluorobenzonitrile «Fluorobenzoic acid (IV) It is tested (such as potassium carbonate or carbonic acid) An aromatic nucleophilic substitution reaction with ethyl cyanoacetate is carried out in the presence of a suitable solvent such as dimethyl hydrazine under heating. The coupling product is hydrolyzed under heating in water (t) such as sulfuric acid or hydrochloric acid to form the diacid of the formula (10). The final 'diacid is used in the presence of a dehydrating agent such as, but not limited to, B-brewed chlorine, or in a suitable solvent such as toluene under heating conditions (

如回流）轉化為通式XVIII之高鄰苯二f酸酐。通式XVIII之高鄰苯二甲酸針可在室溫下或在加熱條件下在適當溶劑（諸如乙腈）中區域選擇性轉化為通式XIX 之酸-醯胺。接著其分別以通式xx及XXI之適當酸酐或醯氯在不存在或存在鹼（諸如三乙胺及DMAP )之狀況下在適當浴劑（一般為乙腈）中在室溫下或在溫和加熱條件（τ < +100 C )下處理。此轉換首先提供通式χχπ之中間物烯嗣•縮胺’其進一步經歷醯化反應，形成通式χχιπ化合物。在較高溫度（諸如+15(rc )下進一步加熱引起重排，形成通式XIV之醯胺。通式XXIII及XXIV化合物皆可在環境溫度下以水性甲醇或水性四氫呋喃作為溶劑中之適當驗 (諸如氫氧化鈉）容易地水解。所獲得之通式XXV之酮基-酸或通式ΧΧΙΠ之烯酮-縮胺藉由與通式VI之苯胺在上文針對與通式IV之酮基-酸縮合所述相同的條件下縮合而轉化為通式I之本發明最終化合物。Conversion, such as refluxing, to the high phthalic anhydride of formula XVIII. The high phthalate needle of formula XVIII can be regioselectively converted to the acid-guanamine of formula XIX at room temperature or under heating conditions in a suitable solvent such as acetonitrile. Subsequent heating of the appropriate anhydrides or hydrazine chlorides of the formula xx and XXI, respectively, in the absence or presence of a base such as triethylamine and DMAP in a suitable bath (typically acetonitrile) at room temperature or in mild warming Condition (τ < +100 C ). This conversion first provides an intermediate olefin hydrazine of the formula χχ π which further undergoes a oximation reaction to form a compound of the formula χχιπ. Further heating at a higher temperature (such as +15 (rc) causes rearrangement to form a guanamine of formula XIV. Compounds of formula XXIII and XXIV can be suitably tested in aqueous methanol or aqueous tetrahydrofuran at ambient temperature. Easily hydrolyzed (such as sodium hydroxide). The obtained keto-acid of the formula XXV or the ketene-amine of the formula 藉 is directed to the ketone group of the formula IV by the aniline of the formula VI - The condensation of the acid under the same conditions to convert to the final compound of the invention of formula I.

或者，通式XIX之酸-醯胺可藉由與適當通式XXVII 106 200906801 之亞胺氯（其可自相應通式XXVI之醯胺容易地獲得，而通式XXVI之醯胺可藉由通式VI之笨胺分別與通式XX及 XXI之相應羧酸或其酸酐或醯氯之間熟知的偶合反應容易地製備）縮合直接轉化為本發明通式I化合物。實施例分析型LC-MS ’方法A (除非另外說明，否則用於多數情形）：在Sciex API 150EX分析型LC/MS系統上獲得數據，該系統裝備有Applied Biosystems API150EX單個四 f 極質譜儀及大氣壓光電離（APPI )離子源、shimadzu LClOADvp LC 泵（3X) 、Shimadzu SPD - M20A 光電二極體陣列偵測器、SEDERE Sedex 85 -低溫蒸發光散射偵測器 (ELSD) 、Shimadzu CBM-20A系統控制器、由分析軟體控制的Gilson 215自動取樣器及Gilson 864脫氣裝置。管柱：30 X 4.6 mm Waters Symmetry C18 管柱，粒徑 3.5 μηι ; 注射體積：15 pL ;管柱溫度：60°C ;溶劑系統：A =水/ 三氟乙酸（100:0.05 )及B =水/乙腈/三氟乙酸 v ( 5:95:0.035 ):方法：2_4 分鐘 10% B 至 100% B 接著 0.4 分鐘10% B之線性梯度溶離，流動速率為3.3 mL/min。滯留時間（tR)基於254 nm下UV-迹線（UV-trace)以分鐘表示。分析型LC-MS，方法B :在Sciex API3 00分析型LC/MS 系統上獲得數據，該系統裝備有具有大氣壓光電離（Αρρι) 離子源之Applied Biosystems API300三重四極質譜儀、Alternatively, the acid-guanamine of the formula XIX can be readily obtained by reacting an imine chloride of the formula XXVII 106 200906801 (which can be readily obtained from the guanamine of the corresponding formula XXVI, while the guanamine of the formula XXVI can be passed through The condensate of formula VI is readily prepared by a well-known coupling reaction with the corresponding carboxylic acid of formula XX and XXI or its anhydride or hydrazine chloride. The condensation is directly converted to the compound of formula I of the present invention. EXAMPLES Analytical LC-MS 'Method A (usually used in most cases unless otherwise stated): Data was obtained on a Sciex API 150EX analytical LC/MS system equipped with an Applied Biosystems API 150EX single quad-f-pole mass spectrometer and Atmospheric pressure photoionization (APPI) ion source, shimadzu LClOADvp LC pump (3X), Shimadzu SPD - M20A photodiode array detector, SEDERE Sedex 85 - low temperature evaporative light scattering detector (ELSD), Shimadzu CBM-20A system Controller, Gilson 215 autosampler controlled by analysis software and Gilson 864 degasser. Column: 30 X 4.6 mm Waters Symmetry C18 column, particle size 3.5 μηι; injection volume: 15 pL; column temperature: 60 ° C; solvent system: A = water / trifluoroacetic acid (100:0.05) and B = Water/acetonitrile/trifluoroacetic acid v (5:95:0.035): Method: 2_4 minutes 10% B to 100% B followed by a linear gradient of 10% B over 0.4 minutes with a flow rate of 3.3 mL/min. The residence time (tR) is expressed in minutes based on UV-trace at 254 nm. Analytical LC-MS, Method B: Data obtained on a Sciex API3 00 analytical LC/MS system equipped with an Applied Biosystems API 300 triple quadrupole mass spectrometer with an atmospheric pressure photoionization (Αρρι) ion source,

Shimadzu LClOADvp LC 泵（3X) 、Shimadzu SPD-M20A 107 200906801 光電二極體陣列偵測器、Polymer Labs PL-ELS 2 100-低溫蒸發光散射偵測器（ELSD) 、Shimadzu SCL10A VP系統控制器、由分析軟體控制的Gilson 215自動取樣器及Gilson 864 脫氣裝置。管柱：Syrnrnetry C183.5 μιη，4.6x30 mm 30 x 4.6 mm ;注射體積：5叫；管柱溫度：6(TC ;溶劑系統： A =水/三氟乙酸（1〇〇:〇〇5 )及b =水/乙腈/三氟乙酸 (5:95:0.035 );方法：ι·45 分鐘 1〇% B 至 100% B 接著 0.55 分鐘1 0% B之線性梯度溶離，且流動速率為5.5 mL/min : 時間，min. %B 0.00 10.0 1.45 100.0 1.55 10.0 2.0 10.0 滯留時間（tR )係基於254 nm下UV-迹線以分鐘表示。製備型LC-MS純化係在同一 Sciex API 150EX系統上進行，其裝備有 Gilson 333 及 334 泵、Shimadzu LClOADvp 泵、Gilson UV/VIS 155 UV 偵測器、Gilson 233XL 自動取樣器、Gilson FC204餾份收集器、Gilson 506C系統介面、 Gilson 864 脫氣裝置、DIY 分流器（約 1:1〇〇〇 )及 LC Packings Accurate 分流器（140 ml/min 下 1:1〇·〇〇〇) 。MS 及餾份收集器係由Masschrom軟體（Macintosh PC )控制，LC系統係由Unipoint軟體控制。對於小規模（<20 mg )純化而言，使用 Symmetry C18 5 μπι，10 X 50 mm 管柱，0-300 pL 注 108 200906801 射體積，5.7 ml/min流動速率及8 min持續時間，於4 ml 小航中收集餾份。梯度：時間，min. %B 0.00 10.0-50.0 (可視樣本變化） 7.00 100.0 7.10 10.0-50.0 8.00 10.0-50.0 屯NMR譜係在 Bruker Avance DRX-500 儀 T=303.3 K下於500.13 MHz記錄。可變溫度lH NMR譜係在Bruker Avance DPX-250儀器上於250 MHz記錄。除非另外說明，否則將氘化二甲亞砜（DMSO-d6，99.8%D)用作溶劑。將四甲基矽烧用作内部參照標準。化學位移值係以相對於四甲基矽烷之ppm值表示。以下縮寫或其組合係用於NMR #號多樣性：s=單蜂·，d=二重峰；t=三重峰，q= 四重峰，qui =五重峰，卜七重峰，dd=雙二重峰，ddd=雙重雙二重峰，dt=雙重三重峰，dq=雙重四重峰，u=三重三重峰’ m =多重峰且br=寬峰或寬單峰。使用購自 Personal Chemistry 之 Emrys Synthesizer 或 Emrys Optimizer EXP 或購自 MUest〇ne 之 MUest〇neShimadzu LClOADvp LC pump (3X), Shimadzu SPD-M20A 107 200906801 Photodiode array detector, Polymer Labs PL-ELS 2 100-low temperature evaporative light scattering detector (ELSD), Shimadzu SCL10A VP system controller, by Analyze the software-controlled Gilson 215 autosampler and the Gilson 864 degasser. Column: Syrnrnetry C183.5 μιη, 4.6x30 mm 30 x 4.6 mm; injection volume: 5; column temperature: 6 (TC; solvent system: A = water/trifluoroacetic acid (1〇〇: 〇〇5) And b = water / acetonitrile / trifluoroacetic acid (5:95:0.035); method: ι · 45 minutes 1 〇 % B to 100% B followed by 0.55 minutes 1 0% B linear gradient dissolution, and flow rate of 5.5 mL /min : time, min. %B 0.00 10.0 1.45 100.0 1.55 10.0 2.0 10.0 The residence time (tR) is expressed in minutes based on the UV-trace at 254 nm. The preparative LC-MS purification is performed on the same Sciex API 150EX system. It is equipped with Gilson 333 and 334 pumps, Shimadzu LClOADvp pump, Gilson UV/VIS 155 UV detector, Gilson 233XL autosampler, Gilson FC204 fraction collector, Gilson 506C system interface, Gilson 864 degasser, DIY split (about 1:1 〇〇〇) and LC Packings Accurate splitter (1:1 〇·〇〇〇 at 140 ml/min). MS and fraction collector are controlled by Masschrom software (Macintosh PC), LC system Controlled by Unipoint software. For small scale (<20 mg) purification, use Symmetr y C18 5 μπι, 10 X 50 mm column, 0-300 pL Note 108 200906801 Shooting volume, 5.7 ml/min flow rate and 8 min duration, collect fractions in 4 ml voyage. Gradient: time, min. %B 0.00 10.0-50.0 (visible sample change) 7.00 100.0 7.10 10.0-50.0 8.00 10.0-50.0 The 屯 NMR spectrum was recorded at 500.13 MHz on a Bruker Avance DRX-500 instrument T=303.3 K. Variable temperature lH NMR spectrum at Bruker Avance The DPX-250 instrument was recorded at 250 MHz. Deuterated dimethyl sulfoxide (DMSO-d6, 99.8% D) was used as the solvent unless otherwise stated. Tetramethyl oxime was used as an internal reference standard. Chemical shift values It is expressed in ppm relative to tetramethylnonane. The following abbreviations or combinations thereof are used for NMR #number diversity: s = single bee, d = doublet; t = triplet, q = quartet, Qui = Wuzhongfeng, Buqifeng, dd=doublet, ddd=double doublet, dt=double triplet, dq=double quartet, u=triple triplet 'm=multiple peak and br = wide peak or wide single peak. Use Emrys Synthesizer or Emrys Optimizer EXP from Personal Chemistry or MUest〇ne from MUest〇ne

Microsynth儀器在密封處理小瓶（pr〇cess vial)或反應器中進行微波實驗。在密封處理小瓶之前，用氬氣沖洗。當反應物在微波儀器中加熱時，在隨後處理步驟之前冷卻至 25〇C。 109 200906801 中間物製備The Microsynth instrument performs microwave experiments in a sealed vial or reactor. Rinse with argon before sealing the vial. When the reactants were heated in a microwave instrument, they were cooled to 25 °C before the subsequent processing steps. 109 200906801 Intermediate preparation

2-(1-乙氧基羰基-2-側氧基-丙基）_苯甲酸。向2-溴笨甲酸（20.1 g，〇.1 mol)及乙醯乙酸乙酯（丨3.〇1 g’ 0.1 mol)於1,4-二聘烷（200 ml)中之經攪拌冷（冰/ 水浴）混合物中分小份添加氫化鈉（8 g，〇.2 mol，礦物油令6〇%分散液）。添加後，移除冷浴槽且將反應混合物在壤境溫度下攪拌10分鐘。逐份添加溴化銅（〗）（ 15·2 g，〇,1〇6 mol )且將所獲得之混合物在回流下加熱丨小時。使其冷部且在壤境溫度下攪拌隔夜。所獲得之綠色懸浮液以乙酸乙醋（200 ml)及冰（300 g)驟冷且以濃HC1 ( 50 ml)酸化。有機相以2 M HC1水溶液（2 X 1 〇〇 ml )及鹽水洗滌，乾無（NaJO4)且真空蒸發。剩餘礦物油藉由以庚烷（3 χ 1〇〇 ml )振盛後傾析且蒸發而移除。產生約2〇g淺黃色油狀物。粗產物未經進—步純化用於隨後步驟中。LC_MS(m/z)2〇5 ([M C02] ) ’ tR=〇 91。lH nMR(5〇〇 MHz，DMSO-d6):至少 3種互變異構體之混合物。以下化合物係自相應2-溴苯曱酸類似地製備，且除非另外說明，否則去、& 只J未經進一步純化及表徵用於隨後步驟中： 110 2009068012-(1-Ethoxycarbonyl-2-oxo-propyl)-benzoic acid. To 2-bromobenzoic acid (20.1 g, 〇.1 mol) and ethyl acetate (丨3.〇1 g' 0.1 mol) in 1,4-dioxane (200 ml) Sodium hydride (8 g, 〇.2 mol, mineral oil to 6 〇% dispersion) was added in small portions in an ice/water bath mixture. After the addition, the cold bath was removed and the reaction mixture was stirred at the soil temperature for 10 minutes. Copper bromide (>) (15. 2 g, hydrazine, 1 〇 6 mol) was added portionwise and the obtained mixture was heated under reflux for a few hours. Allow to cool and stir overnight at the soil temperature. The obtained green suspension was quenched with ethyl acetate (200 ml) and ice (300 g) and acidified with concentrated HC1 (50 ml). The organic phase was washed with aq. 2M EtOAc (2×1······· The remaining mineral oil was removed by shaking with heptane (3 χ 1 〇〇 ml), decanting and evaporating. Approximately 2 gram of light yellow oil was produced. The crude product was used in the subsequent step without further purification. LC_MS (m/z) 2 〇 5 ([M C02] ) ’ tR = 〇 91. lH nMR (5 〇〇 MHz, DMSO-d6): a mixture of at least 3 tautomers. The following compounds were prepared analogously from the corresponding 2-bromobenzoic acid, and unless otherwise stated, the &, only J was used in the subsequent step without further purification and characterization: 110 200906801

2-(1-乙氧基羰基-2-側氧基-丙基）-4-甲基-苯甲酸。 LC-MS (m/z) 247.2 ([MH-H20] + ) ; tR = 1.05。2-(1-Ethoxycarbonyl-2-oxo-propyl)-4-methyl-benzoic acid. LC-MS (m/z) 422. ([MH-H20]+);

2-(1-乙氧基獄基-2-側氧基-丙基）-4 -氟-苯甲酸。2-(1-Ethoxyl-phenyl-2-oxo-propyl)-4-fluoro-benzoic acid.

5-氯-2-(1-乙氧基羰基-2-側氧基-丙基）-苯甲酸。5-Chloro-2-(1-ethoxycarbonyl-2-oxo-propyl)-benzoic acid.

111 200906801 5-溴-2-(1-乙氧基羰基-2-側氧基-丙基）-苯甲酸。111 200906801 5-Bromo-2-(1-ethoxycarbonyl-2-oxo-propyl)-benzoic acid.

2-(1-乙氧基叛基-2-側氧基-丙基）-5 -甲基-苯甲酸。2-(1-Ethoxycarbo-2-p-oxy-propyl)-5-methyl-benzoic acid.

2-(1-乙氧基幾基-2-側氧基-丙基）-5 -氟-苯甲酸。2-(1-Ethoxymethyl-2-oxo-propyl)-5-fluoro-benzoic acid.

V 2-(1-乙氧基羰基-2-側氧基-丙基）-3-曱基-苯甲酸。 112 200906801V 2-(1-ethoxycarbonyl-2-oxo-propyl)-3-indolyl-benzoic acid. 112 200906801

2-氣-6-( 1 -乙氧基幾基-2-側氧基-丙基）_苯甲酸。2-Ga-6-(1-ethoxylated-2-yloxy-propyl)-benzoic acid.

I 〇Ν^〇I 〇Ν^〇

y co2hy co2h

Cl 2-氣-6-(1-曱氧基羰基-2-側氧基_丙基）_笨曱酸。向2-溴-6-氣笨甲酸（20 g，85 mmol )、乙酿乙酸甲醋（310 ml，過量）與漠化銅⑴（12 2 g，85 _〇〗）之經攪拌混合物中逐份添加氫化鈉（8 5 g，212mm〇1，油中6〇%) 1 且接著在70t：下加熱16小時。所得混合物以水（ 600 ml) 稀釋且以***（ 3 x 500 ml)萃取。水相w2MHC1酸化且以乙酸乙酯（2 X 800 ml)萃取。經合併有機溶液以鹽水 (100 ml)洗滌，乾燥（Na2S〇4 )且蒸發。所獲得之油狀物以乙酸乙酯（20 ml)與庚烷（2〇〇 ml)之熱混合物處理且傾析2次，真空乾燥產生8g黃褐色固體，產率34%。 NMR (500 MHz, DMSO-d6): 1·73 (s，3H)，3.6 (s, 3H), 7.24 (d， 1H)，7.44 (t，2H), 7_5 (d，1H), 12.85 (s，1H,烯醇形式之 OH), 13.4 (br, 1H, C02H)。 113 200906801Cl 2-Ga-6-(1-decyloxycarbonyl-2-oxo-propyl)-cracked acid. To a stirred mixture of 2-bromo-6-gasoic acid (20 g, 85 mmol), ethyl acetate (310 ml, excess) and desertified copper (1) (12 2 g, 85 〇) Sodium hydride (85 g, 212 mm 〇1, 6% in oil) 1 was added as a portion and then heated at 70 t: for 16 hours. The resulting mixture was diluted with water (600 ml) and extracted with diethyl ether (3 x 500 ml). The aqueous phase w2MHC1 was acidified and extracted with ethyl acetate (2 X 800 mL). The combined organic solution was washed with brine (100 ml), dried (Na.sub.2) and evaporated. The oil obtained was treated with a hot mixture of ethyl acetate (20 ml) and heptane (2 mL). NMR (500 MHz, DMSO-d6): 1·73 (s, 3H), 3.6 (s, 3H), 7.24 (d, 1H), 7.44 (t, 2H), 7_5 (d, 1H), 12.85 (s , 1H, OH in the enol form, 13.4 (br, 1H, C02H). 113 200906801

2-(1-甲氧基羰基_2_側氧基_丙基）_6_硝基-苯曱酸2-(1-methoxycarbonyl_2_sideoxy-propyl)_6-nitro-benzoic acid

2-甲氧基-6-(1-曱氧基羰基_2_側氧基_丙基）_苯甲酸。2-Methoxy-6-(1-decyloxycarbonyl-2-epoxy-propyl)-benzoic acid.

3-甲基-1-側氧基-2-苯基-1,2-二氫-異喹啉_4_羧酸乙酯。將2-(1-乙氧基羰基-2-側氧基-丙基）_苯甲酸（76 g，3〇 4 mmol)與苯胺（1〇 ml，1〇8 mm〇1)之混合物以氬氣沖洗，密封於埃姆里斯（Emrys )處理小瓶中且在1 5〇它下在微波知、射下加熱1 5分鐘。將揮發物真空移除且將所獲得之餘物在乙酸乙酯（1 〇〇 ml )與2M HC1 ( 1 〇〇 mi )之間八货 114 200906801 有機層以鹽水（2 χ 20 ml)洗滌’乾燥（Na2S〇4)且蒸發產生8·7 g褐色油狀物，使其固化。所獲得之粗產物根據lH NMR為約90%純度，且可未經進一步純化用於隨後步驟中。或者，將粗產物溶解於熱乙酸乙酯（2〇 ml)中，以庚烷（60 ml)沈澱，冷卻，過濾且以***洗滌產生4_2 g淺褐色結晶固體，產率 45%。LC-MS (m/z) 308.2 (MH+) ; tR = 1.43。ifi NMR (500 MHz, DMSO-d6): 1_34 (t, 3H), 1.97 (s， 3H)，4.41 (q，2H), 7.38 (d，2H)，7.51 (t，1H), 7.56 (t (重疊 m)，3H)，7.62 (d，1H)，7.8 (t，1H)，8.22 (d，1H)。以下化合物係自相應粗2-(1-乙氧基羰基-2-側氧基-丙基）-心甲基苯甲酸及相應苯胺類似地製備。3-Methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ethyl ester. a mixture of 2-(1-ethoxycarbonyl-2-oxo-propyl)-benzoic acid (76 g, 3 〇 4 mmol) and aniline (1 〇ml, 1 〇 8 mm 〇1) as argon The air was flushed, sealed in an Emrys-treated vial and heated under microwave irradiation for 15 minutes at 15 Torr. The volatiles were removed in vacuo and the residue obtained was taken between ethyl acetate (1 〇〇ml) and 2M HCl (1 〇〇mi) </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; Dry (Na2S 〇 4) and evaporate to give 8.7 g of a brown oil which solidified. The crude product obtained was about 90% pure according to lH NMR and was used in the next step without further purification. Alternatively, the crude product was dissolved in EtOAc EtOAc (EtOAc)EtOAc. LC-MS (m/z). Ifi NMR (500 MHz, DMSO-d6): 1_34 (t, 3H), 1.97 (s, 3H), 4.41 (q, 2H), 7.38 (d, 2H), 7.51 (t, 1H), 7.56 (t ( Overlap m), 3H), 7.62 (d, 1H), 7.8 (t, 1H), 8.22 (d, 1H). The following compounds were prepared analogously from the corresponding crude 2-(1-ethoxycarbonyl-2-oxo-propyl)-cardiomethylbenzoic acid and the corresponding phenylamine.

115 200906801115 200906801

6_氣-3-甲基-1-側氧基-2-苯基-1,2-二氳-異喹啉-4-羧酸乙酉旨。粗產物未經結晶用於隨後步驟中。LC-MS (m/z) 326.3 !·54° Ή NMR (500 MHz, DMSO-d6): 1.33 (t, 3H), 2·〇 (s, 3H), 4.41 (q, 2H), 7.28 (t, 1H), 7.39 (d, 2H), 7.42 (m, 1H), 7.51 (t，ih)，7.57 (t，2H)，8.29 (dd，1H)。6_Gas-3-methyl-1-oxo-2-phenyl-1,2-diindole-isoquinoline-4-carboxylic acid. The crude product was not crystallized for use in the subsequent step. LC-MS (m/z) 326.3.·54° NMR (500 MHz, DMSO-d6): 1.33 (t, 3H), 2·〇(s, 3H), 4.41 (q, 2H), 7.28 (t , 1H), 7.39 (d, 2H), 7.42 (m, 1H), 7.51 (t, ih), 7.57 (t, 2H), 8.29 (dd, 1H).

116 200906801116 200906801

7->臭-3 -甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸乙酉旨。粗產物未經結晶用於隨後步驟中。LC-MS (m/z) 386.1 (MH+，79Br) ; tR = 171。iH nmr (500 MHz, DMSO-d6): 1.33 (t, 3H), 1.98 (Sj 3H), 4.4 (q, 2H), 7.39 (d, 2H), 7.51 (t, 1H), 7.57 (t，2H)，7.62 ⑷ 1H), 7.96 (dd，1H)，8.29 (d, 1H)。7->Smell-3-methyl-1-oxooxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid. The crude product was not crystallized for use in the subsequent step. LC-MS (m/z) 386.1 (MH+, 79Br); iH nmr (500 MHz, DMSO-d6): 1.33 (t, 3H), 1.98 (Sj 3H), 4.4 (q, 2H), 7.39 (d, 2H), 7.51 (t, 1H), 7.57 (t, 2H) ), 7.62 (4) 1H), 7.96 (dd, 1H), 8.29 (d, 1H).

3,7-—甲基-1-側氧基-2-笨基_i,2_二氣-異4淋-4-叛酸乙酯呈褐色油狀物之粗產物未經純化用於隨後步驟中。 LC-MS (m/z) 322.2 (MH+) ; tR = 159。 117 200906801The crude product of 3,7--methyl-1-oxo-2-phenyl-i,2_di-iso-iso-p-ethyl ester was obtained as a brown oil. In the steps. LC-MS (m/z) 322.2 (MH+); 117 200906801

7-氟-3-甲基-1-側氧基-2-苯基_;ι，2_二氫_異喹啉_4_羧酸乙酯。呈褐色油狀物之粗產物未經純化用於隨後步驟中。 LC-MS (m/z) 326.1 (MH+) ; tR = 0.79 (方法 B)。7-Fluoro-3-methyl-1-oxo-2-phenyl-; i, 2-dihydro-isoquinoline-4-carboxylic acid ethyl ester. The crude product as a brown oil was used in the next step without purification. LC-MS (m/z) 326.1 (MH+);

3,5_二甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸乙酯。粗產物未經純化用於隨後步驟中。LC-MS (m/z) 322.1 (MH+) ; tR ” 63。 118 2009068013,5-Dimethyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ethyl ester. The crude product was used in the subsequent step without purification. LC-MS (m/z) 322.1 (MH+); tR ” 63. 118 200906801

8-氯-3 -甲基-1-側氧基-2-苯基-1,2-二氳-異喹啉-4-羧酸乙酉旨。粗產物未經純化用於隨後步驟中。LC-MS (m/z) 342.0 (MH+) ; tR = 1.55。8-Chloro-3-methyl-1-oxo-2-phenyl-1,2-diindole-isoquinoline-4-carboxylic acid. The crude product was used in the subsequent step without purification. LC-MS (m/z) 422 (MH+);

, 2-(2 -氟-苯基）-3 -甲基-1-側氧基-1，2 -二氳-異啥琳-4-叛 \ 酸乙酯。 LC-MS (m/z) 326.5 (MH+) ; tR = 1.46。, 2-(2-Fluoro-phenyl)-3-methyl-1-oxooxy-1,2-diindole-isoindole-4-reposted acid ethyl ester. LC-MS (m/z) 326.5 (MH+);

119 200906801 2-(2,6-二氟-苯基）-3-甲基-1-側氧基-1,2-二氳-異喹啉- 4-羧酸乙酯。粗產物未經純化及表徵用於隨後步驟中。119 200906801 2-(2,6-Difluoro-phenyl)-3-methyl-1-oxooxy-1,2-diindole-isoquinoline-4-carboxylic acid ethyl ester. The crude product was used in the subsequent step without purification and characterization.

f 2-(2 -氯-苯基）-3 -甲基-1-側氧基-1,2-二氫-異唾嚇>-4-叛酸乙酯。粗產物未經純化及表徵用於隨後步驟中。f 2-(2-Chloro-phenyl)-3-methyl-1-oxooxy-1,2-dihydro-iso-staining>-4-etreic acid ethyl ester. The crude product was used in the subsequent step without purification and characterization.

3-甲基-1-側氧基-2-鄰甲苯基-1,2-二氫-異喹啉-4-羧酸乙酯。粗產物未經純化及表徵用於隨後步驟中。 120 200906801Ethyl 3-methyl-1-oxo-2-o-tolyl-1,2-dihydro-isoquinoline-4-carboxylate. The crude product was used in the subsequent step without purification and characterization. 120 200906801

2-(3 -氣-苯基）-3 -曱基-1-側乳基-1，2-二鼠-異喧嚇·_4 -叛酸乙酯。 LC-MS (m/z) 326.3 (ΜΗ+) ; tR = 1.47。2-(3- gas-phenyl)-3-mercapto-1-lactyl-1,2-dimur-isoindole·_4-etreic acid ethyl ester. LC-MS (m/z) 326.3 (?+);

2-(3-氯-苯基）-3-甲基-1-側氧基-1,2-二氫-異喹啉-4-羧酸乙酯。Ethyl 2-(3-chloro-phenyl)-3-methyl-1-oxo-1,2-dihydro-isoquinoline-4-carboxylate.

LC-MS (m/z) 342.1 (MH+) ; tR = 1.61。LC-MS (m/z) 3421. (MH+);

3-甲基-1 -側氧基-2-間甲苯基-1,2-二星-異喧嚇 -4-竣酸 121 200906801 乙酉旨。 LC-MS (m/z) 322.1 (MH+) ; tR = 1.57。 n r\3-Methyl-1 -p-oxy-2-m-tolyl-1,2-dioxa-isoindole-4-indole 121 200906801 LC-MS (m/z) 3221. (MH+); n r\

8-氯-3-甲基-i_側氧基_2_苯基-丨，2_二氫-異喹啉_4_綾酸曱酯。將2-氯-6-(1_甲氧基羰基_2_侧氧基-丙基苯甲酸（4 g ’ 1 5 mmol )、苯胺（1.369 ml ’15 mmol )及四乙氧基石夕烷（6_65 ml ’ 30 mmol)於曱醇（20 ml)中之混合物密封且在微波照射下在+1 5〇°C下加熱20分鐘。所獲得之溶液以水（150 ml)稀釋且以乙酸乙酯（2 X 3〇〇 m)萃取。將經合併之有機溶液乾燥（MgS〇4 )且蒸發。將所獲得之粗烯胺（2-氯-6-(1-曱氧基羰基_2_苯基胺基-丙烯基苯甲酸）溶解於二甲基甲醯胺（80 ml)中隨後添加丨_乙基_3_(3_二曱基胺基丙基）碳化二亞胺鹽酸鹽（EDC，4.3 g，22.5 mmol ) 及 1-經基本并二唾（HOBT ’ 3.04 g，22·5 mmol)。將其攪拌16小時且在水（ 250 ml)、***（25〇 ml)及乙酸乙醋（150 ml)之間分溶。有機相以〇 5 μ NaOH( 2 X 1〇〇 ml)、鹽水（2 χ 200 ml )洗滌，乾燥（MgS〇4 )且蒸發產生4·25呂褐色油狀物，其未經進一步純化用於隨後步驟中。產率 87%〇 LC-MS (m/z) 328.0 (MH+)； tR = 1.36〇 NMR (500 MHz, 122 200906801 CDC13): 2.02 (s, 3H), 3.98 (s, 3H), 7.23 (d, 2H), 7.44-7.55 (m, 6H)。8-Chloro-3-methyl-i_sideoxy-2_phenyl-indole, 2-dihydro-isoquinoline_4_decanoic acid decyl ester. 2-Chloro-6-(1-methoxycarbonyl-2-epoxy-propylbenzoic acid (4 g '15 mmol), aniline (1.369 ml '15 mmol) and tetraethoxy oxalate ( 6_65 ml '30 mmol) was sealed with a mixture of decyl alcohol (20 ml) and heated under microwave irradiation at +1 5 ° C for 20 min. The obtained solution was diluted with water (150 ml) and ethyl acetate (2 X 3〇〇m) extraction. The combined organic solution was dried (MgS〇4) and evaporated. The obtained crude enamine (2-chloro-6-(1-decyloxycarbonyl-2-benzene) Aminoamino-propenylbenzoic acid) is dissolved in dimethylformamide (80 ml) followed by the addition of 丨_ethyl_3_(3-didecylaminopropyl)carbodiimide hydrochloride (EDC) , 4.3 g, 22.5 mmol) and 1-substantially di-salt (HOBT '3.04 g, 22.5 mmol). Stir for 16 hours in water (250 ml), ether (25 ml) and ethyl acetate (150 ml) was partitioned. The organic phase was washed with 〇5 μ NaOH ( 2 X 1 〇〇ml), brine (2 χ 200 ml), dried (MgS 〇 4 ) and evaporated to give 4·25 br. , which was used in the next step without further purification. Yield 87% 〇LC-MS (m/z) 328.0 (MH+); tR = 1.36 NMR (500 MHz, 122 200906801 CDC13): 2.02 (s, 3H), 3.98 (s, 3H), 7.23 (d, 2H), 7.44-7.55 (m , 6H).

2 (2_曱氧基-本基）_3_曱基_1_側氧基-1,2-二氮-異喧琳-4-羧酸乙酯。標題化合物未經純化用於隨後步驟中。LC-MS (m/z) 338.3 (MH+) ； tR = 1.38 〇2 (2_曱-oxy-bens)_3_mercapto-1_sideoxy-1,2-diaza-isoindolin-4-carboxylic acid ethyl ester. The title compound was used in the next step without purification. LC-MS (m/z) 338.3 (MH+); tR = 1.38 〇

2_(3_曱氧基-笨基）-3-甲基-1-側氧基-1，2-二氫-異喹啉- 4-幾酸乙g旨。標題化合物未經純化用於隨後步驟中。LC-MS (m/z) 338_5 (MH+) ; tR = “I。2-(3-Hydroxy-phenyl)-3-methyl-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid. The title compound was used in the next step without purification. LC-MS (m/z) 338_5 (MH+); tR = "I.

123 200906801 2-(4-甲氧基-苯基）·3_甲基侧氧基心，二氫-異喹啉-4-羧酸乙酯。標題化合物未經純化用於隨後步驟中。LC-MS (m/z) 338.5 (MH+) ; tR = 1 4。 η η123 200906801 2-(4-Methoxy-phenyl)-3-methylxyloxy, ethyl dihydro-isoquinoline-4-carboxylate. The title compound was used in the next step without purification. LC-MS (m/z) 338.5 (MH+); η η

2_(4_氟笨基）-3 -曱基-1-側氧基-1，2-二氫-異喹啉-4-羧酸乙酯。標題化合物未經純化用於隨後步驟中。LC-MS (m/z) 326.2 (MH+) ; tR = 141。2-(4-fluorophenyl)-3-mercapto-1-yloxy-1,2-dihydro-isoquinoline-4-carboxylic acid ethyl ester. The title compound was used in the next step without purification. LC-MS (m/z) 326.2 (MH+);

2_(4_氯-苯基）-3-甲基-i_侧氧基-1，2-二氫-異喹啉-4-羧酸乙酯。才示題化合物未經純化用於隨後步驟中。LC-MS (m/z) 342·2(ΜΗ+); tR== 3。 124 2009068012-(4-Chloro-phenyl)-3-methyl-i-tertiaryoxy-1,2-dihydro-isoquinoline-4-carboxylic acid ethyl ester. The compound was shown to be used in the subsequent step without purification. LC-MS (m/z) 342·2 (ΜΗ+); tR== 3. 124 200906801

3_曱基-1·側氧基-2-對曱苯基-1,2-二氫乙酯。標題化合物未經純化用於隨後步驟中 321.7 (MH+) ; tR= 1>51。3_Mercapto-1·p-oxy-2-p-phenylene-1,2-dihydroethyl ester. The title compound was used in the next step without purification for 321.7 (MH+); tR = 1 > 51.

2_(3_氰基-苯基）-3 -甲基-1-側氧基-1，2- 羧酸乙酯。標題化合物未經純化用於隨後步驟中 ί ' 333.0 (MH+) ; tR = I」。Ethyl 2-(3-cyano-phenyl)-3-methyl-1-oxo-1,2-carboxylate. The title compound was used in the next step without purification. ί ' 333.0 (MH+); tR = I.

I r\ Γ\I r\ Γ\

3_曱基硝基-1-側氧基-2-苯基-1，2-二酸甲酯。心題化合物未經純化用於隨後步驟中 -異喹琳-4-羧酸。LC-MS (m/z) 二氫-異喹啉Ιο LC-MS (m/z) 氫-異喹啉-4-羧。LC-MS (m/z) 125 200906801 339.3 (MH+) ； tR = 1>26 〇3_Mercaptonitro-1-oxo-2-phenyl-1,2-dicarboxylate. The core compound was used in the subsequent step without purification - isoquinoline-4-carboxylic acid. LC-MS (m/z) dihydro-isoquinoline Ι δ LC-MS (m/z). LC-MS (m/z) 125 200906801 339.3 (MH+) ; tR = 1>26 〇

8-甲氧基-3 -甲基-側氧基_2_苯基-L2 —二氫-異喹啉_4_ 羧酸甲酯。標題化合物未經純化用於隨後步驟中。LC_MS (m/z) 324.3 (MH+) ; tR = 1>12。Methyl 8-methoxy-3-methyl-oxo-2-phenyl-L2-dihydro-isoquinoline-4-carboxylate. The title compound was used in the next step without purification. LC_MS (m/z) 324.3 (MH+); tR = 1 >

8_氰基-3_甲基-側氧基_2_苯基_丨，2_二氫·異喹啉_4_羧酸曱酷。將3-甲基-8-硝基-1-側氧基-2-苯基-1，2_二氫-異喹啉-4-羧酸甲酯（320 mg，0.95 mmol)及 Zn( 898 mg，13.8 mmol) 於THF ( 4.5 ml )及2M HC1水溶液（4.5 ml )中之懸浮液攪拌10分鐘，過濾且在乙酸乙酯（3 χ 150 ml)與飽和 NaHC03水溶液（1 〇〇 mi )之間分溶。將經合併之有機溶液乾燥（MgSOJ且蒸發產生呈深色油狀物之8_胺基_3_甲基 -1-側氧基-2-苯基-1，2-二氫-異喹啉_4_羧酸甲酯（ 200 mg, 0.645 mmo卜 69%產率）。LC-MS (m/z) 309.4 (MH+) ; t = 126 200906801 1_2。將其溶解於濃HC1水溶液（〇 4 ml)及h2〇 ( 3 25 ml) 中。在〇 c下向所獲得之溶液中逐滴添加NaN〇2 ( 46 3 ，〇·645 mmo卜0·12 ml h2〇中）。15分鐘後’將其以飽和 NaHC〇3水溶液中和（PH = 6_7 )產生重氮鹽溶液。在❹它下向KCN ( 202 mg，3 mmol )於水（〇·4 ml )中之溶液中逐滴添加 CuS04 · 5H20( 197 mg，0.774 mmol)於水（〇.8 ml) 中之溶液。添加完成後，添加苯（2 ml)且將混合物溫至 + 60°C。向此混合物中經15分鐘逐滴添加重氮鹽溶液，接 ί 著保持於70 C下歷時85分鐘。使其冷卻至室溫，以乙酸乙酯（10 ml)稀釋且經矽藻土塞過濾。有機層以鹽水（1〇 ml)洗務，乾燥（MgS〇4)且蒸發產生97·9 mg標題化合物（48%產率）。LC-MS (m/z) 319.2 (MH+) ; tR = 1-15。8_Cyano-3_methyl-sideoxy-2_phenyl-indole, 2_dihydro-isoquinoline_4_carboxylate 曱cool. 3-methyl-8-nitro-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid methyl ester (320 mg, 0.95 mmol) and Zn (898) The suspension of THF (4.5 ml) and 2M aqueous HCl (4.5 ml) was stirred for 10 min, filtered and evaporated in ethyl acetate (3 χ 150 ml) and saturated aqueous NaHC03 (1 〇〇mi) Disintegration. The combined organic solution was dried (MgSO.sub.sub.sub.sub.sub.sub.sub.sub. _4_Methyl carboxylate (200 mg, 0.645 mmo, 69% yield). LC-MS (m/z) 309.4 (MH+); t = 126 200906801 1_2. Dissolve in concentrated aqueous HC1 solution (〇4 ml And h2〇 (3 25 ml). Add NaN〇2 (46 3 , 〇·645 mmo Bu 0·12 ml h2〇) to the obtained solution under 〇c. After 15 minutes, ' It was neutralized with a saturated aqueous solution of NaHC〇3 (pH = 6_7) to produce a diazonium salt solution. Under the solution, CuS04 was added dropwise to a solution of KCN (202 mg, 3 mmol) in water (〇·4 ml). A solution of 5H20 (197 mg, 0.774 mmol) in water ( EtOAc (EtOAc). The diazonium salt solution was kept at 70 C for 85 minutes, allowed to cool to room temperature, diluted with ethyl acetate (10 ml) and filtered over a pad of Celite. Wash, dry (MgS〇4) and evaporate to produce 97.9 mg heading Were combined (48% yield) .LC-MS (m / z) 319.2 (MH +); tR = 1-15.

3 -苯基胺基-丁-2-稀酸乙S盲。該化合物係根據所述程序製備（Q. Dai，W. Yang，及X. Zhang Org. Letters 2005, 5343 )。 *H NMR (500 MHz, DMSO-d6): 1.19 (t, 3H), 2.01 (s, 3H), 4.06 (q，2H)，4.7 (s, 1H)，7.17 (重疊 t, 1H)，7.18 (重疊 d，2H)， 7.36 (t，2H)，10.36 (s, 1H)。 127 2009068013-Phenylamino-but-2-acid S-B blind. This compound was prepared according to the procedure (Q. Dai, W. Yang, and X. Zhang Org. Letters 2005, 5343). *H NMR (500 MHz, DMSO-d6): 1.19 (t, 3H), 2.01 (s, 3H), 4.06 (q, 2H), 4.7 (s, 1H), 7.17 (overlap t, 1H), 7.18 ( Overlap d, 2H), 7.36 (t, 2H), 10.36 (s, 1H). 127 200906801

3,8-二甲基-1-侧氧基-2-苯基-1，2-二氫-異喹啉·4_羧酸乙酯。向 2-溴 _6·甲基-苯甲酸（650 mg，3.023 mmol )及 3-苯基胺基-丁-2-稀酸乙酯（ 750 mg，3_65 mmol )於乙腈（1〇 ml)中之冷（冰/水浴）溶液中逐份添加氫化鈉（267 mg， 6.67 mmol，礦物油中60%分散液）。移除冷浴槽且將混合物在環境溫度下超音波處理直至氣體析出停止（1〇分鐘）。添加 >臭化銅（I) ( 95 7 mg，6_67 mmol )且將所獲得之懸浮液以氬氣沖洗’密封且在微波照射下在+8〇。(3下加熱30分鐘。LC-MS指示完全轉化為2_(1_乙氧基羰基_2_苯基胺基_ 丙烯基）-6-曱基-苯曱酸（LC-MS (m/z) 340.4 (MH+) ; tR = 1.59。將所獲得之懸浮液在微波照射下在+16〇°c下加熱3〇分鐘。將其以乙酸乙酯（50 ml )稀釋且過濾。所獲得之有機溶液以 1M HC1( 3 X 50 ml )、水（2 X 10 ml )及飽和 NaHC03 水溶液（30 ml)洗滌’吸附於Si〇2 ( 3 g)上且經si〇2急驟層析（50 g，梯度庚烷-庚烷中3 〇%乙酸乙酯）產生2 1 7 mg 黃色油狀物。產率 22%。LC-MS (m/z) 322.2 (MH+) ; tR = 1·62。iH NMR (500 MHz，DMSO-d6): 1.32 (t，3H)，1.91 (s, 3H)，2.74 (s，3H)，4.39 (q，2H)，7.3 (d，1H)，7.36 (重疊 m, 128 200906801 3H)，7.49 (m，1H)，7.55 (t，2H)，7.61 (t，1H)。3,8-Dimethyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline·4-carboxylic acid ethyl ester. To 2-bromo-6-methyl-benzoic acid (650 mg, 3.023 mmol) and ethyl 3-phenylamino-but-2-acetate (750 mg, 3_65 mmol) in acetonitrile (1 mL) Sodium hydride (267 mg, 6.67 mmol, 60% dispersion in mineral oil) was added portionwise to a cold (ice/water bath) solution. The cold bath was removed and the mixture was sonicated at ambient temperature until gas evolution ceased (1 min). Add > copper (I) (95 7 mg, 6_67 mmol) and the resulting suspension was flushed with argon and sealed at +8 Torr under microwave irradiation. (3 times heating for 30 minutes. LC-MS indicates complete conversion to 2_(1_ethoxycarbonyl-2-phenylamino-propenyl)-6-mercapto-benzoic acid (LC-MS (m/z) 340.4 (MH+); tR = 1.59. The obtained suspension was heated under microwave irradiation at +16 ° C for 3 hrs, diluted with ethyl acetate (50 ml) and filtered. The solution was washed with 1 M HCl (3 X 50 ml), water (2×10 ml) and saturated aqueous NaHC03 (30 ml). </ br> adsorbed onto Si〇2 (3 g) and subjected to flash chromatography (50 g, The gradient of heptane-heptane (3% EtOAc) yielded EtOAc (yield: ield: 22%). (500 MHz, DMSO-d6): 1.32 (t, 3H), 1.91 (s, 3H), 2.74 (s, 3H), 4.39 (q, 2H), 7.3 (d, 1H), 7.36 (overlapping m, 128 200906801 3H), 7.49 (m, 1H), 7.55 (t, 2H), 7.61 (t, 1H).

3-甲基-1-側氧基-2-苯基二氫_異喹啉_4·羧酸。將3_甲基―卜側氧基_2_苯基]，2_二氫-異喹琳冰叛酸乙醋（4.2g，13.7mm〇l)溶解於100ml熱甲醇中且添加Ν&〇Η (6 g)於水（20 ml)中之溶液。將反應混合物在回流下加熱2小時，以水（ 200 ml)稀釋且在環境溫度下攪拌隔夜。減壓移除有機揮發物且所獲得之水溶液以乙酸乙酯（2 X 50 ml)萃取。將水溶液倒入冰/2M HC1 ( 150 ml)中。將所獲得之懸浮液超音波處理，且將產物藉由過濾分離，以水洗條且真空乾燥產生2.9 g無色固體，產率76%。[(：-MS (m/z) 280.2 (MH+) ； tR = 0.9 ° NMR (500 MHz, DMSO-d6): 2.01 (s, 3H), 7.36 (d, 2H), 7.50 (t, 1H), 7.56 (q (重疊 m)，3H), 7.72 (d, 1H), 7·81 (t, 1H), 8.22 (d，1H), 13.5 (br, 1H)。以下酸係自相應乙酯類似地製備：3-Methyl-1-oxo-2-phenyldihydro-isoquinoline-4-carboxylic acid. Dissolve 3_methyl-b-oxy 2_phenyl], 2-dihydro-isoquine glacial acid (4.2 g, 13.7 mm 〇l) in 100 ml of hot methanol and add Ν&〇 Η (6 g) in water (20 ml). The reaction mixture was heated at reflux for 2 h, diluted with water (200 ml) and stirred at ambient temperature overnight. The organic volatiles were removed under reduced pressure and the obtained aqueous mixture was extracted ethyl acetate (2 X 50 ml). The aqueous solution was poured into ice/2M HC1 (150 ml). The obtained suspension was ultrasonicated, and the product was separated by filtration, washed with water and dried in vacuo to yield 2.9 g of colorless solid. [(:-MS (m/z) 280.2 (MH+); tR = 0.9 ° NMR (500 MHz, DMSO-d6): 2.01 (s, 3H), 7.36 (d, 2H), 7.50 (t, 1H), 7.56 (q (overlapping m), 3H), 7.72 (d, 1H), 7·81 (t, 1H), 8.22 (d, 1H), 13.5 (br, 1H). The following acids are similar to the corresponding ethyl esters. preparation:

129 200906801 Λ 3，6-二曱基-1-側氧基-2-苯基-1，2-二氮-異喧琳-4-缓酸。 LC-MS (m/z) 293.9 (MH+)； tR = 0.99= ]H NMR (500 MHz, DMSO-d6): 2.0 (s, 3H), 2.47 (s, 3H), 7.34 (d, 2H), 7.38 (d, 1H), 7.47 (s, 1H), 7.50 (d, 1H), 7.56 (t, 2H), 8.11 (d, 1H), 13_4 (br，1H)。129 200906801 Λ 3,6-Dimercapto-1-yloxy-2-phenyl-1,2-diaza-isoindolin-4-o-acid. LC-MS (m/z): 495 (MH+): MH (+) 7.38 (d, 1H), 7.47 (s, 1H), 7.50 (d, 1H), 7.56 (t, 2H), 8.11 (d, 1H), 13_4 (br, 1H).

6-氟-3 -曱基_1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸。 LC-MS (m/z) 298.4 (MH+); tR = 0.99。W NMR (500 MHz， DMSO-d6)： 2.05 (s5 3H), 7.37 (d, 2H), 7.41 (dt, 1H), 7.48 (dd, 1H)，7.51 (t，1H)，7.57 (t，2H)，8.28 (dd，1H), 13.6 (b，1H)。6-Fluoro-3-indolyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid. LC-MS (m/z). W NMR (500 MHz, DMSO-d6): 2.05 (s5 3H), 7.37 (d, 2H), 7.41 (dt, 1H), 7.48 (dd, 1H), 7.51 (t, 1H), 7.57 (t, 2H) ), 8.28 (dd, 1H), 13.6 (b, 1H).

7-氣-3-曱基-1-侧氧基_2-苯基-1，2-二氫-異喹啉-4-羧酸。7-Ga-3-indol-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid.

粗產物未經結晶用於隨後步驟中。LC-MS (m/z) 314.2 (MH+) ; tR = i 13。iH NMR (500 MHz，DMSO-d6): 4 NMR 130 200906801 (500 MHz, DMSO-d6): 2.03 (s, 3H), 7.38 (d, 2H), 7.51 (t, 1H), 7.57 (t, 2H), 7.79 (d, 1H), 7.86 (dd, 1H), 8.15(d, 1H), 13.55 (b，1H)。The crude product was not crystallized for use in the subsequent step. LC-MS (m/z) 314.2 (MH+); iH NMR (500 MHz, DMSO-d6): 4 NMR 130 200906801 (500 MHz, DMSO-d6): 2.03 (s, 3H), 7.38 (d, 2H), 7.51 (t, 1H), 7.57 (t, 2H) ), 7.79 (d, 1H), 7.86 (dd, 1H), 8.15(d, 1H), 13.55 (b, 1H).

7 -》臭-3 -甲基-1-側氧基-2-苯基-1，2 -二氳^異啥琳-4 -叛酸。 LC-MS (m/z) 358.1 (MH+，79Br) ; tR = 1.2。4 NMR (500 MHz, DMSO-d6): 2.02 (s, 3H), 7.38 (d, 2H), 7.51 (t, 1H), 7.57 (t, 2H), 7.72 (d, 1H), 7.97 (dd, 1H), 8.29 (d, 1H), 13.55 (b, 1H)。7 - "Smell-3 -Methyl-1-oxo-2-phenyl-1,2-dioxime-isoindole-4 - oxo acid. LC-MS (m/z) 358.1 (MH+, 79Br); s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, , 7.57 (t, 2H), 7.72 (d, 1H), 7.97 (dd, 1H), 8.29 (d, 1H), 13.55 (b, 1H).

3,7-二曱基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸。 LC-MS (m/z) 293.9 (MH+); tR = 1_02。NMR (500 MHz， DMSO-d6): 2.0 (s, 3H)，2.45 (s，3H)，7·34 (d, 2H)，7·5 (t，1H)， 7.56 (t，2H)，7.63 (m，2H)，8_02 (s, 1H)，13.38 (br, 1H)。 131 2009068013,7-Dimercapto-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid. LC-MS (m/z) 299 (MH+); NMR (500 MHz, DMSO-d6): 2.0 (s, 3H), 2.45 (s, 3H), 7·34 (d, 2H), 7·5 (t, 1H), 7.56 (t, 2H), 7.63 (m, 2H), 8_02 (s, 1H), 13.38 (br, 1H). 131 200906801

7 -氟-3 -甲基-1-側氧基-2-苯基-1,2-二氯-異啥琳-4 -缓酸。 LC-MS (m/z) 298.2 (MH+); tR = 1.01。4 NMR (500 MHz， DMSO-d6): 2.02 (s, 3H), 7.37 (d, 2H), 7.51 (t, 1H), 7.57 (t, 2H), 7.71 (dt, 1H), 7.83 (dd, 1H), 7.88 (dd, 1H), 13.54 (br, 1H)。7-Fluoro-3-methyl-1-oxo-2-phenyl-1,2-dichloro-isoindolin-4 -o-acid. NMR (500 MHz, DMSO-d6): 2.02 (s, 3H), 7.37 (d, 2H), 7.51 (t, 1H), 7.57 (t, 2H), 7.71 (dt, 1H), 7.83 (dd, 1H), 7.88 (dd, 1H), 13.54 (br, 1H).

3,5-二甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸。 LC-MS (m/z) 294.1 (MH+); tR = 1.09。4 NMR (500 MHz， DMSO-d6): 1.95 (s, 3H), 2.74 (s, 3H), 7.27-7.64 (m, 8H), 13.35 (b, 1H)。3,5-Dimethyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid. LC-MS (m/z) 294.1 (MH+); t,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, , 13.35 (b, 1H).

132 200906801 2-(2-^-苯基）-3 -甲基-1-側氧基-1,2-二氮-異啥嚇·_4 -叛酸。 LC-MS (m/ζ) 298·4 (ΜΗ+) ; tR = 0.83。132 200906801 2-(2-^-Phenyl)-3-methyl-1-oxooxy-1,2-diaza-isoindole _4 - oxo acid. LC-MS (m/ζ) 298·4 (ΜΗ+); tR = 0.83.

CO.HCO.H

2-(2,6-二氟-苯基）-3-甲基-1-側氧基-1，2-二氳-異喹啉- 4-羧酸。 LC-MS (m/z) 316.2 (MH+) ; tR = 1.03。2-(2,6-Difluoro-phenyl)-3-methyl-1-oxo-1,2-diindole-isoquinoline-4-carboxylic acid. LC-MS (m/z) 316.2 (MH+);

； 2-(2 -氯-苯基）-3 -甲基-1-側氧基-1,2 -二氫-異喧琳-4-叛酸。 LC-MS (m/z) 314.2 (MH+) ; tR = 1·0。2-(2-Chloro-phenyl)-3-methyl-1-oxo-1,2-dihydro-isoindole-4-deoxy acid. LC-MS (m/z) 314.2 (MH+);

3-甲基-1-側氧基-2-鄰甲苯基-1,2-二氫-異喹啉-4-羧 133 200906801 酸。 LC-MS (m/z) 294.1 (MH+) ; tR = 0·99。3-Methyl-1-oxo-2-o-tolyl-1,2-dihydro-isoquinoline-4-carboxyl 133 200906801 Acid. LC-MS (m/z) 422 (MH+);

2-(3 -鼠-苯基）-3 -甲基-1-側氧基-1，2-二氮-異啥嚇·_4-叛酸。 LC-MS (m/z) 298.4 (MH+); tR = 0.96。4 NMR (250 MHz, DMSO-d6): 2.02 (s, 3H), 7.24 (d, 1H), 7.32-7.42 (m, 2H), 7.5-7.65 (m, 2H), 7.71 (d, 1H), 7.81 (m, 1H), 8.21 (d, 1H), 13.49 (br, 1H)。2-(3-N-phenyl-phenyl)-3-methyl-1-oxooxy-1,2-diaza-isoindole _4-reacid. LC-MS (m/z) 298.4 (MH+); t, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, , 7.5-7.65 (m, 2H), 7.71 (d, 1H), 7.81 (m, 1H), 8.21 (d, 1H), 13.49 (br, 1H).

2-(3 -氣-苯基）-3 -甲基-1-側氧基-1,2-二鼠-異哇淋-4-叛酸。 LC-MS (m/z) 314.2 (MH+); tR = 1.09。4 NMR (500 MHz, DMSO-d6): 2.04 (s, 3H), 7.39 (t, 1H), 7.56 (t, 1H), 7.58-7.62 (m, 3H), 7.72 (d, 1H), 7.81 (t, 1H), 8.21 (d, 1H), 13.5 (br, 1H)。 134 2009068012-(3-Gas-phenyl)-3-methyl-1-oxooxy-1,2-di-rhamn-iso-vv-4-deoxy acid. LC-MS (m/z) 314.2 (MH+); s.s.ssssssssssssssssssssssssssssssssssss -7.62 (m, 3H), 7.72 (d, 1H), 7.81 (t, 1H), 8.21 (d, 1H), 13.5 (br, 1H). 134 200906801

二氫-異喹啉-4-羧酸Ο LC-MS (m/z) 293.9 (MH+); tR = 1.03= NMR (25 0 MHz, DMSO-d6): 2.02 (s, 3H)，2.38 (s，3H), 7 14 (重疊 d，1H), 7 16Dihydro-isoquinoline-4-carboxylic acid hydrazine LC-MS (m/z) 293.9 (MH+); tR = 1.03 = NMR (25 0 MHz, DMSO-d6): 2.02 (s, 3H), 2.38 (s , 3H), 7 14 (overlapping d, 1H), 7 16

(重疊 s，1H)，7_31 (d，1H)，7.44 (t，1H), 7.54 (t，1H), 7·71 (d， 1H)，7.8 (t，1H)，8.21 (d，1H)，13.46 (br，m)。(overlap s, 1H), 7_31 (d, 1H), 7.44 (t, 1H), 7.54 (t, 1H), 7·71 (d, 1H), 7.8 (t, 1H), 8.21 (d, 1H) , 13.46 (br, m).

3,8-二曱基-1-側氧基_2-笨基_1，2_二氳_異喹啉_4_羧 (酸。3,8-Dimercapto-1-yloxy-2-peptidyl-1,2-diindole-isoquinoline_4_carboxylate (acid.

將3,8-二甲基-1_側氧基_2_苯基_U2_二氫_異喹啉_4_羧酸乙醋（ 200 mg，0_62mmol)於 DMS〇(3ml)及 1NNa〇H 水/合液（2 nd，2 mmol)中之溶液在微波照射下在+12〇〇c 下加熱20分鐘且以水（3〇叫稀釋。將未裝填之雜質以乙鍵（30 ml)萃取且將水溶液倒入具冑2mhci水溶液（ ml )之冰（50 g )中。ϋ玄&也 g T 將所獲得之沈澱物過濾，以水洗滌且真空乾综產生75 mg黃色固體。產率41%。lc_ms (m/z) 293.9 (MH+) ; tR = 1.09。iH NMR (5〇〇 mhz，DMSO-d6): 1.95 135 200906801 (s, 3H)，2.74 (s，3H)，7.3 (d，1H)，7.32 (d, 2H)，7.48 (兩個重疊 m，2H)，7.55 (t，2H)，7.62 (t, 1H)，13.42 (b，1H)。3,8-Dimethyl-1_sideoxy-2_phenyl_U2_dihydro-isoquinoline-4-carboxylic acid ethyl acetate (200 mg, 0-62 mmol) in DMS (3 ml) and 1NNa〇 The solution in H water/liquid (2 nd, 2 mmol) was heated under microwave irradiation at +12 °c for 20 minutes and diluted with water (3 〇。. Unfilled impurities with B bond (30 ml) The aqueous solution was extracted and poured into ice (50 g) with 胄2mhci aqueous solution (ml). The obtained precipitate was filtered, washed with water and dried in vacuo to yield 75 mg of yellow solid. The rate is 41%. lc_ms (m/z) 293.9 (MH+); tR = 1.09. iH NMR (5〇〇mhz, DMSO-d6): 1.95 135 200906801 (s, 3H), 2.74 (s, 3H), 7.3 ( d, 1H), 7.32 (d, 2H), 7.48 (two overlaps m, 2H), 7.55 (t, 2H), 7.62 (t, 1H), 13.42 (b, 1H).

8-氯-3_甲基-1-側氧基-2 -苯基-1,2_二氫-異啥琳_4_叛8-Chloro-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoindole_4_ rebellion

酸。藉由在10 0 °c下使相應甲醋或乙醋水解而類似地製備標題化合物。LC-MS (m/z) 314.1 (MH+) ; tR = 1.03。acid. The title compound was prepared analogously by hydrolysis of the corresponding methyl acetal or ethyl acetate at 10 °C. LC-MS (m/z) 314.1 (MH+);

2-(2-曱氧基-苯基）-3-曱基-1-側氧基-1，2-二氫-異喹啉- 4-羧酸。標題化合物未經純化用於隨後步驟中。LC-MS (m/z) 310.3 (MH+) ； tR = 0.87 °2-(2-decyloxy-phenyl)-3-indolyl-1-yloxy-1,2-dihydro-isoquinoline-4-carboxylic acid. The title compound was used in the next step without purification. LC-MS (m/z) 310.3 (MH+); tR = 0.87 °

2-(3-曱氧基-苯基）_3•甲基-i_側氧基-1,2-二氫-異喹啉_ 4-羧酸。 136 200906801 標題化合物未經純化用於隨後步驟中。LC-MS (m/z) 310.4 (MH+) ; tR = 〇·9 02-(3-decyloxy-phenyl)_3•methyl-i_sideoxy-1,2-dihydro-isoquinoline-4-carboxylic acid. 136 200906801 The title compound was used in the next step without purification. LC-MS (m/z) 310.4 (MH+); tR = 〇·9 0

2_(4_甲氧基-笨基）-3-甲基-1-側氧基-1，2-二氫-異喹啉-4-羧酸。才示題化合物未經純化用於隨後步驟中。LC-MS (m/z) 3 1 0.4 (MH+) ; tR = 〇 89。2-(4-Methoxy-styl)-3-methyl-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid. The compound was shown to be used in the subsequent step without purification. LC-MS (m/z) 3 1 0.4 (MH+);

^題化合物未經純化用於隨後步驟中。LC-MS (m/z) 298.2 (MH+) ; tR = 〇 9。酸。The title compound was used in the subsequent step without purification. LC-MS (m/z) 298.2 (MH+); acid.

Cl 2_(4-氯-苯基甲基-1-側氧基-1，2-二氫-異喹啉-4-羧酸。 137 3-甲基_8-硝基-1-側氧基-2-苯基-1,2-二氫酸。標題化合物未經純化用於隨後步驟中。 325.5 (MH+) ； tR = 0.94 〇 200906801 標題化合物未經純化用於隨後步驟中。 314.2 (MH+) ; tR = 1.53 〇 r.n μCl 2 —(4-chloro-phenylmethyl-1-oxooxy-1,2-dihydro-isoquinoline-4-carboxylic acid. 137 3-methyl-8-nitro-1-oxooxy -2-Phenyl-1,2-dihydro acid. The title compound was used in the next step without purification. </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; ; tR = 1.53 〇rn μ

3_甲基-1·側氧基-2-對曱苯基-1,2-二氫酸。標題化合物未經純化用於隨後步驟中。 293.9 (MH+) ; tR = 0.99。3-methyl-1·oxy-2-p-phenylene-1,2-dihydrogen. The title compound was used in the next step without purification. 293.9 (MH+) ; tR = 0.99.

8_甲氧基-3_甲基-1-側氧基-2-苯基_1，2-二羧酸。軚題化合物未經純化用於隨後步驟中。 LC-MS (m/z) -異喹啉-4-羧 LC-MS (m/z) -異喹琳-4-羧 LC-MS (m/z) 氫-異喹琳-4-LC-MS (m/z) 138 200906801 310.6 (MH+) ； tR = 0.73 °8-Methoxy-3-methyl-1-oxo-2-phenyl-1,2-dicarboxylic acid. The title compound was used in the subsequent step without purification. LC-MS (m/z)-isoquinoline-4-carboxyl LC-MS (m/z)-isoquinoline-4-carboxyl LC-MS (m/z) Hydrogen-isoquine-4-LC- MS (m/z) 138 200906801 310.6 (MH+) ; tR = 0.73 °

8 -氰基-3-曱基-1-側氧基-2_苯基-1，2-二氫-異啥琳-4_叛酸。 LC-MS (m/z) 305.0 (MH+) ; tR = 〇_82。通式XVIII之高鄰笨二甲酸酐之合成：8-Cyano-3-mercapto-1-yloxy-2_phenyl-1,2-dihydro-isoindole-4_colic acid. LC-MS (m/z) 305.0 (MH+); Synthesis of high o-dicarboxylic anhydride of formula XVIII:

氰基-(2-氰基-3-氟-笨基）-乙酸乙酯。將氰基乙酸乙醋（26.7 mL，25 1 mmol )、2,6-二氟苯甲腈（33.2 g，239 mmol)及碳酸 _( 82.5 g，597 mmol) 於二曱亞砜（120 mL )中之混合物在+551：下攪拌1 6小時且倒入冰-水混合物（約400 mL)中。將其以濃HC1水溶液小心地酸化（C02析出）且以乙酸乙酯（600 ml )萃取。有機相以鹽水（100 mL)洗滌且蒸發產生55·1 g淺黃色固體’其未經進一步純化用於隨後步驟中。WMR (500 MHz， CDC13): 1.35 (t, J=7.0 Hz, 3H), 4.34 (m, 2H), 5.13 (s, 1H), ? 33 (t, J = 8.4 Hz, 1H), 7.57 (d, J=7.9 Hz, 1H), 7.33 (dd, J：a7.9 Hz，J=13.9 Hz，1H)。 139 200906801 ?crCyano-(2-cyano-3-fluoro-phenyl)-ethyl acetate. Ethyl cyanoacetate (26.7 mL, 25 1 mmol), 2,6-difluorobenzonitrile (33.2 g, 239 mmol) and carbonic acid (82.5 g, 597 mmol) in disulfoxide (120 mL) The mixture was stirred at +551: for 16 hours and poured into an ice-water mixture (about 400 mL). It was carefully acidified (C02 precipitated) in a concentrated aqueous HCl solution and extracted with ethyl acetate (600 ml). The organic phase was washed with brine (100 mL) and evaporated to give &lt WMR (500 MHz, CDC13): 1.35 (t, J=7.0 Hz, 3H), 4.34 (m, 2H), 5.13 (s, 1H), ? 33 (t, J = 8.4 Hz, 1H), 7.57 (d , J = 7.9 Hz, 1H), 7.33 (dd, J: a7.9 Hz, J = 13.9 Hz, 1H). 139 200906801 ?cr

F 2-缓基甲基-6-氟-苯曱酸。將62%硫酸（2:1水中之濃h2s〇4，400 ml)與氰基-(2-氰基-3-氟-苯基）_乙酸乙酯（52.0 g，224 mmol)之混合物在+150°C下攪拌隔夜（16小時）。將反應混合物倒入冰（約 500 g)中且在冷卻下以1〇8NNaOH水溶液（ 500 mL)中 ' 和。混合物以乙酸乙酯（3 X 500mL )萃取且經合併之有機溶液以鹽水洗滌，經]^§8〇4乾燥且蒸發產生4〇 28 g粗產物，其未經進一步純化用於隨後步驟中。藉由自甲苯-乙酸乙酯再結晶製備分析樣本。iH NMR (500 MHz, DMSO-d6): 3.4 (br, C02H + H20), 3.77 (s, 2H), 7.17 (d, J=7.9 Hz, 1H), 7.2 (重疊 i (未解析（unres·) dd)，1H)，7.45 (dd, J=7.9 Hz, J=13.9 Hz, 1H)，12.95 (br, C02H)。F 2-sulfomethyl-6-fluoro-benzoic acid. A mixture of 62% sulfuric acid (2:400 ml of concentrated h2s in 2:1 water) and ethyl cyano-(2-cyano-3-fluoro-phenyl)-acetate (52.0 g, 224 mmol) Stir at 150 ° C overnight (16 hours). The reaction mixture was poured into ice (ca. 500 g) and cooled to 1 <RTI ID=0.0>> The mixture was extracted with EtOAc (3 X EtOAc)EtOAc. Analytical samples were prepared by recrystallization from toluene-acetate. iH NMR (500 MHz, DMSO-d6): 3.4 (br, C02H + H20), 3.77 (s, 2H), 7.17 (d, J = 7.9 Hz, 1H), 7.2 (overlapping i (unresolved) Dd), 1H), 7.45 (dd, J = 7.9 Hz, J = 13.9 Hz, 1H), 12.95 (br, C02H).

F O 8 -鼠-異—風苯弁旅。南-1，3_二嗣。將乙醯氯（2 ml)中之2-羧基甲基-6-氟-笨甲酸（13〇 mg，0.65 mmol)在微波照射下在150°C下加熱1〇分鐘，接著真空濃縮產生標題化合物（120 mg，產率ι〇〇〇/) 化合物為吸濕性且在濕溶劑中或在潮濕氣氛下緩p水解口起始二酸。1H NMR (500 MHz, DMSO-d6): 4.29 (s，2H) 7 27 140 200906801 (d, J=7.8 Hz, 1H), 7.34 (dd, J = 8.5 Hz, J=ll Hz, 1H), 7.76 (dt, J = 5.3 Hz, J = 8 Hz，1H)。藉由上述3-步驟程序自相應氟苯甲腈及氰基乙酸乙酯類似地獲得以下高鄰苯二甲酸酐：F O 8 - mouse-iso-style benzoquinone brigade. South-1,3_two. 2-Carboxymethyl-6-fluoro-abdominic acid (13 mg, 0.65 mmol) in acetonitrile (2 ml) was heated at 150 ° C for 1 min under microwave, then concentrated in vacuo to give the title compound (120 mg, yield ι〇〇〇/) The compound is hygroscopic and the di-hydrolysis port starts the diacid in a wet solvent or in a humid atmosphere. 1H NMR (500 MHz, DMSO-d6): 4.29 (s, 2H) 7 27 140 200906801 (d, J = 7.8 Hz, 1H), 7.34 (dd, J = 8.5 Hz, J=ll Hz, 1H), 7.76 (dt, J = 5.3 Hz, J = 8 Hz, 1H). The following high phthalic anhydride was obtained analogously from the corresponding fluorobenzonitrile and ethyl cyanoacetate by the 3-step procedure described above:

CI 0 8-氯-異二氳苯并哌喃-1，3-二酮CI 0 8-chloro-isoindenyl benzopyran-1,3-dione

CF, Ο 8 -三貌甲基-異二氫苯并旅σ南-1，3 -二晒CF, Ο 8 - Tri-morphic methyl-iso-dihydrobenzo-branched sigma-1,3 - two sun

6,8-二氟-異二氫苯并哌喃-1，3-二酮6,8-difluoro-isodihydrobenzopyran-1,3-dione

F 0 5,8-二氟-異二氫苯并哌喃-1，3-二酮。通式XI之手性及外消旋胺的合成：F 0 5,8-difluoro-isodihydrobenzopyran-1,3-dione. Synthesis of chiral and racemic amines of formula XI:

141 200906801 (S)-(-)-2 -甲基-2-丙烧亞續醮胺。根據 D.J. Weix 及 J.A. Ellman Organic Syntheses 2005, 82，157之針對（R)-(+)-對映異構體所述之程序製備標題手性助劑。141 200906801 (S)-(-)-2 -Methyl-2-propenyl phthalocyanine. The title chiral auxiliary was prepared according to the procedure described for D(R)-(+)-enantiomers by D.J. Weix and J.A. Ellman Organic Syntheses 2005, 82,157.

(S)-2-甲基-2-丙烷亞磺酸1-環丙基-次曱基醯胺。根據 G. Liu、D.A. Cogan、T_D. Owens、T.P. Tang 及 J.A. Ellman J. Org. Chem. 1999，64，1278 所述之一般程序製備標題化合物：將環丙烷曱醛（35.0 g，0.5 mol ) 、2- 甲基-2-丙烷亞磺酸1-環丙基-次甲基醯胺（30 g，0.25 mol) 及無水 CuS04 ( 120 g，0.75 mol)於 CH2C12 ( 1500 mL) 中之混合物在室溫下攪拌隔夜。將反應混合物過濾且蒸發產生標題化合物（39 g，產率95% )，其未經進一步純化用於隨後步驟中。(S) 2-Methyl-2-propanesulfinic acid 1-cyclopropyl-decylguanamine. The title compound was prepared according to the general procedure described by G. Liu, DA Cogan, T_D. Owens, TP Tang and JA Ellman J. Org. Chem. 1999, 64, 1278: cyclopropanefurfural (35.0 g, 0.5 mol), Mixture of 2-methyl-2-propanesulfinic acid 1-cyclopropyl-methine decylamine (30 g, 0.25 mol) and anhydrous CuS04 (120 g, 0.75 mol) in CH2C12 (1500 mL) Stir under temperature overnight. The reaction mixture was filtered and evaporated to give crystall

(S)-2 -曱基-2-丙烧亞績酸[(S)-環丙基-(3 -氟-苯基）-曱基]-酿胺及（S)-2-甲基-2 -丙嫁亞續酸[(R)-核丙基氣-苯基）-甲基]-酿胺。根據 D.A. Cogan，G. Liu，J.A· Ellman，Tetrahedron 1999, 142 200906801 55，8883針對有機金屬試劑與亞磺醯基亞胺的擇性加成所述之一般程序獲得標題化合物。程序A :在氮氣下向無水氯化鋰（丨7 g，4〇中添加THF (20ml)隨後緩慢添加“ΡγΜ§(：ι ，τΗρ 中之2 Μ)且將所獲得之混合物在室溫下授拌隔夜。在〇。〔下將所獲得之i-PrMgCl.LiCl溶液逐滴添加至^溴」·氟苯 (5.6 g’ 33 mm〇1)於THF(25 ml)中之經攪拌溶液= f 12-立體選持續攪拌2小時。在_48t下將所獲得之格林納試劑 (Grignard reagent)添加至（S)_2_甲基_2_丙烷亞磺酸^環丙基-次甲基酿胺（2.5 g，14 mm〇l)於Ch2C12 (6〇中之溶液中。將混合物在-48t下攪拌5小時且接著在室溫下攪拌隔夜。反應混合物藉由添加飽和NH4C1水溶液（mL ) 驟冷且以CH^l2 (3 X 100 mL)萃取。將經合併之有機溶液乾燥（NajO4)且蒸發產生粗混合物，藉由矽膠管柱層析法（EtOAc/石油醚=1/1〇)純化。所獲得之非對映異構體混合物藉由SFC拆分產生作為主產物之標題（s，s)_異構 \ 體（1_5 g，產率37.5%)及標題（S,R)·異構體（〇 16 g，產率 4.0%)。程序或者，在 50。〇下向 Mg(13.4 g，〇55 m〇i) 於50 mL無水THF中之懸浮液中逐滴添加^溴_3_氟苯（89 〇 g，〇·50 m〇l)溶液。將混合物在+5〇t：下攪拌2小時且接著在50-60t：下將其逐滴添加至（S)-2-甲基_2_丙烷亞磺酸卜環丙基-次曱基醯胺（78.0 g，0.46 mol)於1〇〇 thF中之溶液中且攪拌2小時。將其以飽和NH4C1水溶液（loo 143 200906801 ml)、水（300 mL )驟冷，過渡，且固體與濾液以熱乙酸乙酯（600 mL)萃取且真空蒸發。在_2〇°C下將殘餘物自乙酸乙S旨與石油喊（1 · 1，200 mL )之混*合物結晶’產生呈白色粉末狀之80 g標題（S，S)-異構體，產率66%，根據手性 HPLC de 100% 。4 NMR (CDC13, 400 MHz, TMS=0 ppm): 7.34-7.28 (m, 1H), 7.16-7.12 (m, 2H), 7.00-6.96 (m, 1H), 3.68 (dd, J = 8.8 Hz, 3.2 Hz, 1H), 3.52 (s, 1H), 1.42 (s, 9H), 1.15-1.08 (m, 1H), 0.84-0.75 (m, lH), 0.69-0.61 (m, 1H), 0.55-0.46 (m, 1H)，0.28-0.21 (m，1H) 0(S)-2 - Mercapto-2-propanol-based acid [(S)-cyclopropyl-(3-fluoro-phenyl)-indenyl]-bristamine and (S)-2-methyl- 2-A-acrylic acid [(R)-nuclear propyl-phenyl-phenyl)-methyl]-bristamine. The title compound is obtained according to the general procedure described for D.A. Cogan, G. Liu, J.A. Ellman, Tetrahedron 1999, 142 200906801 55,8883 for the selective addition of organometallic reagents to sulfinylimine. Procedure A: Add THF (20 ml) to anhydrous lithium chloride (丨7 g, 4 Torr under nitrogen) and then slowly add “ΡγΜ§(:ι, τΗρ 2 Μ) and the obtained mixture at room temperature Mix overnight. In 〇. [Add the obtained i-PrMgCl.LiCl solution dropwise to bromine fluorobenzene (5.6 g' 33 mm 〇 1) in THF (25 ml) with stirring solution = f 12-stereoselection was continuously stirred for 2 hours. The obtained Grignard reagent was added to (S) 2 -methyl 2 -propane sulfinic acid / cyclopropyl - methine at _48t The amine (2.5 g, 14 mm 〇l) was taken in a solution of CH2C12 (6 EtOAc). The mixture was stirred at -48 s for 5 s and then stirred at room temperature overnight. The reaction mixture was added with saturated aqueous NH4C1 (mL) The mixture was extracted with EtOAc (EtOAc/EtOAc/EtOAc) The obtained mixture of diastereomers was subjected to SFC resolution to give the title (s, s) _ isomers (1, 5 g, yield 37.5%) and the title (S, R) Structure (〇16 g, yield 4.0%). Procedure, or add bromine_3_fluoride dropwise to a suspension of Mg (13.4 g, 〇55 m〇i) in 50 mL of anhydrous THF at 50. a solution of benzene (89 〇g, 〇·50 m〇l). The mixture was stirred at +5 〇t: for 2 hours and then added dropwise to (S)-2-methyl at 50-60 t: 2_propane sulfinic acid sulfopropyl-decyl decylamine (78.0 g, 0.46 mol) in a solution of 1 〇〇thF and stirred for 2 hours. It was taken as a saturated aqueous solution of NH4C1 (loo 143 200906801 ml), The water (300 mL) was quenched, the mixture was taken, and the solid and filtrate were extracted with hot ethyl acetate (600 mL) and evaporated in vacuo. The residue was transferred from acetic acid to the oil at _2 ° C (1 · 1) , 200 mL) of the mixture crystals gave 80 g of the title (S,S)-isomer as a white powder, yield 66%, according to chiral HPLC de 100%. 4 NMR (CDC13, 400 MHz , TMS=0 ppm): 7.34-7.28 (m, 1H), 7.16-7.12 (m, 2H), 7.00-6.96 (m, 1H), 3.68 (dd, J = 8.8 Hz, 3.2 Hz, 1H), 3.52 (s, 1H), 1.42 (s, 9H), 1.15-1.08 (m, 1H), 0.84-0.75 (m, lH), 0.69-0.61 (m, 1H), 0.55-0.46 (m, 1H), 0.28 -0.21 (m,1H) 0

(S)-( + )-C-[C-環丙基-C-(3-氟-苯基）]-曱基胺鹽酸鹽。在〇°C下向HC1於無水二聘烷（4〇0 ml )中之飽和溶液中添加（S)-2-甲基-2-丙烷亞磺酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺（80 g，0.3 mol )。在室溫下攪拌1小時後，將反應混合物真空蒸發。殘餘物以無水***（2 χ丨〇〇 ml ) 洗務且真空乾燥產生56 g呈白色固體狀之標題化合物，產率 93°/。，根據手性 Hplc ee 100%。[a]2D° = + 52_69 (c = 10 mg/mL’CI^OHpWNMRCCDWDJOOMHz’TMS^O)·· 7.44-7.39 (m, ιΗ)} 7.25-7.19 (m, 2H), 7.12-7.07 (m, 1H), 3.56 (d, i〇〇 HZ) 1H^ 1.37-1.28 (m, 1H), 0.78-0.75 (m, iH)，0.61-0.55 (m，2H)，〇 39_〇 36 (m，1H)。 144 200906801(S)-( + )-C-[C-cyclopropyl-C-(3-fluoro-phenyl)]-nonylamine hydrochloride. Add (S)-2-methyl-2-propanesulfinic acid [(S)-cyclopropyl-(3) to a saturated solution of HCl in anhydrous dioxane (4 〇 0 ml) at 〇 °C -Fluoro-phenyl)-methyl]-nonylamine (80 g, 0.3 mol). After stirring at room temperature for 1 hour, the reaction mixture was evaporated in vacuo. The residue was washed with EtOAc (EtOAc m. According to chiral Hplc ee 100%. [a]2D° = + 52_69 (c = 10 mg/mL 'CI^OHpWNMRCCDWDJOOMHz'TMS^O)·· 7.44-7.39 (m, ιΗ)} 7.25-7.19 (m, 2H), 7.12-7.07 (m, 1H), 3.56 (d, i〇〇HZ) 1H^ 1.37-1.28 (m, 1H), 0.78-0.75 (m, iH), 0.61-0.55 (m, 2H), 〇39_〇36 (m, 1H) ). 144 200906801

(R)-(-)-C-[C-環丙基-C-(3-氟-苯基）]_甲基胺鹽酸鹽。根據上述相同程序自（S)-2-曱基-2-丙烷亞磺酸[(R)_環丙基-(3 -氟-苯基）_甲基]-醯胺（〇16g，〇·6 min〇i )製備標題化合物，產生〇.n6g呈白色固體狀之標題化合物。[α]2。。(R)-(-)-C-[C-Cyclopropyl-C-(3-fluoro-phenyl)]-methylamine hydrochloride. According to the same procedure as above, (S)-2-mercapto-2-propanesulfinic acid [(R)-cyclopropyl-(3-fluoro-phenyl)-methyl]-decylamine (〇16g, 〇· The title compound was prepared as a white solid. [α] 2. .

49.18 (c = 1〇 mg/mL，CH3OH), ee 100%。旧 NMR (CD3OD，400 MHz，TMS = 0):與（S)-對映異構體相同。49.18 (c = 1〇 mg/mL, CH3OH), ee 100%. Old NMR (CD3OD, 400 MHz, TMS = 0): identical to the (S)-enantiomer.

以—步程序類似地獲得以下對映異構純胺鹽酸鹽：自相應醛與手性助劑之縮合開始，立體選擇性格林納加成，其中非對映異構體混合物係藉由再結晶或藉由層析（SFC 或管柱）來拆分且將主要（S，S)·非對映異構體以HC1最終轉化為手性胺。結構 (HC1 鹽）化學名稱 [a]2D° > (10mg/ml) MeOH Ee (手性HPLC) *HNMR (CD3OD, 400 MHz) C-[(S)-C-環丙基-C-(2-氣-苯基)]-甲基胺 +19.61 100 7.31-7.28 (m, 1H), 7.14-7.01 (m, 3H), 3.74 (d, J= 9.6 Hz, 1H), 1.12-1.05 (m, 1H), 0.47-0.42 (m, 1H), 0.29-0.28 (m, 2H), 0.10-0.07 (m, 1H) 〇 ljlH2 C-[(S)-C-環丙基-C-(4-氟-苯基)]-甲基胺 +47.25 98.9 7.50-7.46 (m, 2H), 7.19-7.14 (m, 2H), 3.56 (d,J= 10.0 Hz, 1H), 1.40-1.31 (m, 1H), 0.83-0.76 (m, 145 200906801 1H), 0.67-0.54 (m, 2H), 0.40-0.31 (m, 1H)。 Cl nh9 cyv C-[(S)-C-(2-氯-苯基)_C_ ί哀丙基l·甲基胺 +20.56 100 7.68 (dd, J=7.6 Hz, 1.6 Hz, 1H), 7.52-7.38 (m，3H), 4.12 (d, J= 9.6 Hz, 1H), 1.51-1.42 (m, 1H), 0.86-0.80 (m, 1H), 0.68-0.58 (m, 2H), 0.49-0.41 (m，1H)。 nh2 c，x/v C-[(S)-C-(3-氯-苯基）-C-〗哀丙基l·甲基胺 +54.25 96.9 7.55 (s, 1H), 7.50-7.42 (m, 3H), 3.61 (d,J= 10.0 Hz, 1H), 1.42-1.34 (m, 1H), 0.89-0.83 (m, 1H), 0.74-0.62 (m，2H)。 nh5 C-[(S)-C-(4-氯-苯基)-C-環丙基]-甲基胺 +59.1 96.2 7.47 (s, 4H), 3.60 (d, J = 10.4 Hz, 1H), 1.41-1.34 (m, 1H), 0.86-0.81 (m, 1H), 0.71-0.66 (m, 2H), 0.43-0.39 (m，1H)。 F NH, (S)-1-(2-氟-苯基)_丙基胺 -9.71 100 7.54-7.46 (m, 2H), 7.34-7.22 (m, 2H), 4.49 (dd, J= 9.2 Hz, 6.0 Hz, 1H), 2.13-1.96 (m, 2H), 0.95 (t, J=6.8Hz，3H)。 nh2 (S)-1-(3-氟-苯基)_丙基胺 +13.9 100 7.51-7.46 (m, 1H), 7.27-7.14 (m, 3H), 4.20 (dd,J=9.2 Hz, 6.0 Hz, 1H), 2.07-1.89 (m, 2H), 0.89 (t，《/=7.2Hz，3H)。 NH, (S)-1-(4-氟-苯基)-丙基胺 +14.83 98.7 7.53-7.50 (m, 2H), 7.24-7.19 (m, 2H), 4.21 (dd, J = 9.2 Hz, 5.6 Hz, 1H), 2.13-1.91 (m, 2H), 0.89 (t, 7_2 Hz, 3H)。 (S)-1-(2-氯-苯基)-丙基胺 -1.64 100 7.56-7.38 (m, 4H), 4.73 (dd,/=8.8 Hz, 146 200906801The following enantiomeric pure amine hydrochlorides were similarly obtained in a step-by-step procedure: starting from the condensation of the corresponding aldehyde with a chiral auxiliary, stereoselective Grignard addition, wherein the mixture of diastereomers was Crystallization or resolution by chromatography (SFC or column) and the final (S,S)·diastereomer is finally converted to a chiral amine with HC1. Structure (HC1 salt) Chemical name [a] 2D ° > (10 mg/ml) MeOH Ee (chiral HPLC) *HNMR (CD3OD, 400 MHz) C-[(S)-C-cyclopropyl-C-( 2-Gas-Phenyl)]-Methylamine+19.61 100 7.31-7.28 (m, 1H), 7.14-7.01 (m, 3H), 3.74 (d, J = 9.6 Hz, 1H), 1.12-1.05 (m , 1H), 0.47-0.42 (m, 1H), 0.29-0.28 (m, 2H), 0.10-0.07 (m, 1H) 〇ljlH2 C-[(S)-C-cyclopropyl-C-(4- Fluoro-phenyl)]-methylamine + 47.25 98.9 7.50-7.46 (m, 2H), 7.19-7.14 (m, 2H), 3.56 (d, J = 10.0 Hz, 1H), 1.40-1.31 (m, 1H) ), 0.83-0.76 (m, 145 200906801 1H), 0.67-0.54 (m, 2H), 0.40-0.31 (m, 1H). Cl nh9 cyv C-[(S)-C-(2-chloro-phenyl)_C_ 哀 propyl l-methylamine + 20.56 100 7.68 (dd, J=7.6 Hz, 1.6 Hz, 1H), 7.52- 7.38 (m,3H), 4.12 (d, J= 9.6 Hz, 1H), 1.51-1.42 (m, 1H), 0.86-0.80 (m, 1H), 0.68-0.58 (m, 2H), 0.49-0.41 ( m, 1H). Nh2 c,x/v C-[(S)-C-(3-chloro-phenyl)-C-〗〖 propyl propyl l-methylamine +54.25 96.9 7.55 (s, 1H), 7.50-7.42 (m , 3H), 3.61 (d, J = 10.0 Hz, 1H), 1.42-1.34 (m, 1H), 0.89-0.83 (m, 1H), 0.74-0.62 (m, 2H). Nh5 C-[(S)-C-(4-Chloro-phenyl)-C-cyclopropyl]-methylamine +59.1 96.2 7.47 (s, 4H), 3.60 (d, J = 10.4 Hz, 1H) , 1.41-1.34 (m, 1H), 0.86-0.81 (m, 1H), 0.71-0.66 (m, 2H), 0.43-0.39 (m, 1H). F NH, (S)-1-(2-fluoro-phenyl)-propylamine-9.71 100 7.54-7.46 (m, 2H), 7.34-7.22 (m, 2H), 4.49 (dd, J = 9.2 Hz , 6.0 Hz, 1H), 2.13-1.96 (m, 2H), 0.95 (t, J = 6.8 Hz, 3H). Nh2 (S)-1-(3-fluoro-phenyl)-propylamine +13.9 100 7.51-7.46 (m, 1H), 7.27-7.14 (m, 3H), 4.20 (dd, J=9.2 Hz, 6.0 Hz, 1H), 2.07-1.89 (m, 2H), 0.89 (t, "/= 7.2 Hz, 3H). NH, (S)-1-(4-fluoro-phenyl)-propylamine +12.83 98.7 7.53-7.50 (m, 2H), 7.24-7.19 (m, 2H), 4.21 (dd, J = 9.2 Hz, 5.6 Hz, 1H), 2.13-1.91 (m, 2H), 0.89 (t, 7_2 Hz, 3H). (S)-1-(2-Chloro-phenyl)-propylamine -1.64 100 7.56-7.38 (m, 4H), 4.73 (dd, /=8.8 Hz, 146 200906801

Cl NH, 6.4 Hz, 1H), 2.08-1.96 (m, 2H), 0.92 (t，·/= 7.6 Hz，3H)。 nh2 Ck0^ (S)-l-(3-鼠-苯基)-丙基胺 +14.46 100 7.48-7.35 (m, 4H), 4.17 (dd,/= 9.2 Hz, 6.0 Hz, 1H), 2.06-1.88 (m, 2H), 0.88 (t，《/= 7.2 Hz, 3H)。 NH- (S)· 1-(4-乳苯基)-丙基胺 +14.73 100 7.50-7.47 (m, 2H), 7.44-7.41 (m, 2H), 4.18 (dd,/=9.6 Hz, 6.0 Hz, 1H), 2.07-1.90 (m, 2H), 0.89 (t，7.6 Hz, 3H)。 NH? 〇V (S)-2-曱基-1-苯基-丙基胺 +7.12 100 7.47-7.37 (m, 5H), 3.91 (d, J= 9.2 Hz, 1H), 2.21-2.16 (m, 1H), 1.13 (d, J=6.8 Hz, 3H), 0.78 (d,J = 6.8 Hz, 3H)。 nh2 c-((s)-c_ 環丁基-C-苯基)-曱基胺 +17.57 95.4 7.37-7.31 (m, 5H), 4.12 (d,J= 10.4 Hz, 1H), 2.84-2.75 (m, 1H), 2.21-2.13 (m, 1H), 1.99-1.64 (m, 。 nh2 σχ> c-((s)-c-環戊基-C-苯基)-甲基胺 +6.97 99.2 7.43 (br, 5H), 3.99 (d,J= 10.4 Hz, 1H), 2.46-2.40 (m, 1H), 2.02 (br, 1H), 1.76-1.08(m, 8H)。 nh2 c-[(s)-c-環丁基-C-(3-氟-苯基)]-甲基胺 +19.45 100 7.48-7.44 (m, 1H), 7.24-7.15 (m, 3H), 4.26 (d,/= 10.4 Hz, 1H), 2.87-2.84 (m, 1H), 2.25-2.24 (m, 1H), 2.05-1.76 (m, 5H)。 nh2 c-[(s)-c_ 環丁基-C-(4-亂·苯基)]-甲基胺 +26.98 100 7.45-7.41 (m, 2H), 7.18-7.14 (m, 2H), 4.22 (d，/= 10.6 Hz, 1H), 2.89-2.81 (m, 1H), 2.28-2.21 (m, 147 200906801 100 1H)， 2.05-1.71 (m, 5H)° 7.46-7.34 (m, 5H), 3.92 ；d, J = 9.2 Hz, 1H)， 1.97-1.94 (m， 1H), 1.86-1.83 (m， 2H), 1.68-1.66 (m， 2H), 1.33-1.30 (m， 2H), 1.20-1.11 (m， 3H), 0.91-0.88 (m, 1H)。Cl NH, 6.4 Hz, 1H), 2.08-1.96 (m, 2H), 0.92 (t, ·/= 7.6 Hz, 3H). Nh2 Ck0^(S)-l-(3-murine-phenyl)-propylamine+14.46 100 7.48-7.35 (m, 4H), 4.17 (dd, /= 9.2 Hz, 6.0 Hz, 1H), 2.06- 1.88 (m, 2H), 0.88 (t, "/= 7.2 Hz, 3H). NH-(S)· 1-(4-lactylphenyl)-propylamine +14.73 100 7.50-7.47 (m, 2H), 7.44-7.41 (m, 2H), 4.18 (dd, /=9.6 Hz, 6.0 Hz, 1H), 2.07-1.90 (m, 2H), 0.89 (t, 7.6 Hz, 3H). NH? 〇V (S)-2-mercapto-1-phenyl-propylamine +7.12 100 7.47-7.37 (m, 5H), 3.91 (d, J= 9.2 Hz, 1H), 2.21-2.16 (m , 1H), 1.13 (d, J = 6.8 Hz, 3H), 0.78 (d, J = 6.8 Hz, 3H). Nh2 c-((s)-c_cyclobutyl-C-phenyl)-decylamine +17.57 95.4 7.37-7.31 (m, 5H), 4.12 (d, J = 10.4 Hz, 1H), 2.84-2.75 ( m, 1H), 2.21-2.13 (m, 1H), 1.99-1.64 (m, .nh2 σχ> c-((s)-c-cyclopentyl-C-phenyl)-methylamine +6.97 99.2 7.43 (br, 5H), 3.99 (d, J = 10.4 Hz, 1H), 2.46-2.40 (m, 1H), 2.02 (br, 1H), 1.76-1.08 (m, 8H). nh2 c-[(s) -c-cyclobutyl-C-(3-fluoro-phenyl)]-methylamine+19.45 100 7.48-7.44 (m, 1H), 7.24-7.15 (m, 3H), 4.26 (d, /= 10.4 Hz, 1H), 2.87-2.84 (m, 1H), 2.25-2.24 (m, 1H), 2.05-1.76 (m, 5H). nh2 c-[(s)-c_cyclobutyl-C-(4- Chaotic phenyl)]-methylamine + 26.98 100 7.45-7.41 (m, 2H), 7.18-7.14 (m, 2H), 4.22 (d, /= 10.6 Hz, 1H), 2.89-2.81 (m, 1H ), 2.28-2.21 (m, 147 200906801 100 1H), 2.05-1.71 (m, 5H)° 7.46-7.34 (m, 5H), 3.92 ;d, J = 9.2 Hz, 1H), 1.97-1.94 (m, 1H), 1.86-1.83 (m, 2H), 1.68-1.66 (m, 2H), 1.33-1.30 (m, 2H), 1.20-1.11 (m, 3H), 0.91-0.88 (m, 1H).

nh2 0¾ c-((s)-c-環己基-c-苯基)-甲基胺 +4.8 C-環丁基-C-(2-氟-笨基）_甲基胺。將 1/3 環丁基溴（5.0 g，41 3 ^ J mm〇1)於無水四氫呋喃 (24 mL)中之溶液在回流下與鎂（l u gu咖〇1) -起擾拌。剩餘溶液經15 ^分鐘時期逐滴添加，且在回流下持續攪拌30分鐘。在吖下向所獲得之溶液中逐滴添加於THFU5HU)中之2_氟苯甲腈（12§)。將混合物在代下授拌5·5小時’隨後添加甲醇（3Gml)及蝴氫化鈉（ιΐ3 g)。將反應混合物在環境溫度下攪拌16小時，且濃縮。使殘餘物在氯仿（3 X 1〇〇 mi )與水之間分溶，且將值凋整至1。混合物以氯仿萃取。將水相調整至〇，且以氯仿（3 X 1〇〇 mi)萃取，將經合併之有機層乾燥，蒸發且藉由矽膠管柱層析法（乙酸乙酯/石油醚=i7i )純化產生標題胺（0.45 g，產率 7.9%)。NMR (CD3〇D, 400 MHz) 7.49-7.38 (m，2H)，7.30-7.15 (m，2H)，4.50 (d，J = 10.4 Hz, 148 200906801 1H)，3.00-2.90 (m，1H)，2.29-2.21 (m，1H)，2.09-1.71 (m， 5H)。通式XIX之酸-醯胺的合成：Nh2 03⁄4 c-((s)-c-cyclohexyl-c-phenyl)-methylamine +4.8 C-cyclobutyl-C-(2-fluoro-phenyl)methylamine. A solution of 1/3 cyclobutyl bromide (5.0 g, 41 3 ^ J mm 〇1) in anhydrous tetrahydrofuran (24 mL) was stirred with magnesium (l u gu 〇〇 1) under reflux. The remaining solution was added dropwise over a period of 15 ^ minutes and stirring was continued for 30 minutes under reflux. To the obtained solution, 2-fluorobenzonitrile (12 §) inTHFU5HU) was added dropwise under the armpit. The mixture was mixed for 5 to 5 hours. Then methanol (3 Gml) and sodium hydrogen hydride (ι 3 g) were added. The reaction mixture was stirred at ambient temperature for 16 h and concentrated. The residue was partitioned between chloroform (3 X 1 〇〇 mi ) and water, and the value was reduced to 1. The mixture was extracted with chloroform. The aqueous phase was adjusted to hydrazine and extracted with chloroform (3×1 〇〇mi). The combined organic layers were dried, evaporated and purified by EtOAc EtOAc EtOAc The title amine (0.45 g, yield 7.9%). NMR (CD3〇D, 400 MHz) 7.49-7.38 (m, 2H), 7.30-7.15 (m, 2H), 4.50 (d, J = 10.4 Hz, 148 200906801 1H), 3.00-2.90 (m, 1H), 2.29-2.21 (m, 1H), 2.09-1.71 (m, 5H). Synthesis of acid-decylamine of the general formula XIX:

2，[((S)-1-苯基-丙基胺曱醯基）_甲基]_苯甲酸。將高鄰苯二曱酸酐（810 mg，5 mmol)及（S)-(-)_i-苯基丙基胺（676 mg，5 mmol)於乙腈（15 ml)中之混合物在微波照射下在+1 5 0 °C下加熱1 5分鐘。藉由過據收集白色沈澱物’以庚烧洗蘇且真空乾燥產生標題化合物，產率72% (l_065g)。或者，向高鄰苯二甲酸酐（i6214g，〇」mol ) 於乙腈（100 ml)中之經攪拌溶液中逐滴添加（s)-(—)_ι_笨基丙基胺（13.83 g，0· 102 mol)(放熱反應）且將所獲得之反應混合物回流5分鐘。使其冷卻且將產物如上文所述藉由過濾分離產生23.4g無色固體，產率79%。LC-MS (m/z) 298.5 (MH+) ; tR = 1.1 1。H NMR (5 00 MHz，DMSO-d6): 0·84 (t，J = 7.3 Hz，3H)，1·67 (五重峰，J = 7.3 Hz, 2H), 3.85 (AB 系統之 d，J=15.1 Hz，1H), 3_95 (AB 系統之 d, J = 15.1 Hz, 1H)， 4.66 (q，J=7.6 Hz，1H), 7.2 (未解析 m，1H)，7.25-7.34 (m， 5H), 7.45 (t, J=7.3 Hz, 1H), 7.8 (d, J=7.8 Hz, 1H), 8.39 (br. d, J=7.7 Hz，1H, NH) 〇 149 200906801 以下化合物係分別自相應通式χνιπ之高鄰苯二甲酸酐及通式XI之胺類似地獲得。反應通常係在室溫下進行且將產物藉由萃取或過濾分離且未經進一步純化用於隨後步驟中。2, [((S)-1-Phenyl-propylaminoindolyl)-methyl]-benzoic acid. a mixture of high phthalic anhydride (810 mg, 5 mmol) and (S)-(-)-i-phenylpropylamine (676 mg, 5 mmol) in acetonitrile (15 ml) under microwave irradiation Heat at +1 50 °C for 15 minutes. The title compound was obtained by soaking a white precipitate, which was then washed with <RTI ID=0.0>> Alternatively, (s)-(-)_ι_ stupylpropylamine (13.83 g, 0) is added dropwise to a stirred solution of high phthalic anhydride (i6214g, 〇"mol) in acetonitrile (100 ml). • 102 mol) (exothermic reaction) and the resulting reaction mixture was refluxed for 5 minutes. It was allowed to cool and the product was isolated by filtration to give 23.4 g of a colourless solid. LC-MS (m/z) 495 (MH+); H NMR (5 00 MHz, DMSO-d6): 0·84 (t, J = 7.3 Hz, 3H), 1·67 (five-peak, J = 7.3 Hz, 2H), 3.85 (d system, d, J =15.1 Hz, 1H), 3_95 (d, J = 15.1 Hz, 1H for AB system), 4.66 (q, J = 7.6 Hz, 1H), 7.2 (unresolved m, 1H), 7.25-7.34 (m, 5H) ), 7.45 (t, J=7.3 Hz, 1H), 7.8 (d, J=7.8 Hz, 1H), 8.39 (br. d, J=7.7 Hz, 1H, NH) 〇149 200906801 The following compounds are respectively corresponding The high phthalic anhydride of the formula ννιπ and the amine of the formula XI are obtained analogously. The reaction is usually carried out at room temperature and the product is isolated by extraction or filtration and used in the subsequent step without further purification.

2-({[(S)-環丙基-(3-氟-苯基）-甲基]-胺甲醢基卜曱基）-6-氟-苯甲酸。 LC-MS (m/z) 346_2 (MH+); tR = 1.14。NMR (500 MHz, DMSO-d6): 0.35 (m，1H)，0.39 (m, 1H)，0.5 (m，2H)，1.12 (m， 1H)，3_68 & 3.74 (AB 系統之兩個 d，J= 15.2 Hz，2H，CH2)， 4.25 (t, J= 8.5 Hz, 1H), 7.05 (dt, J=2.2, 8.05 Hz, 1H), 7.13 (d, ( J- 8.1 Hz, 1H), 7.16-7.21 (m, 2H), 7.35 (m, 1H), 7.42 (m, 1H), 8.66 (d，J= 8.2 Hz, 1H，NH)，13.44 (br.，C02H)。2-({[(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-amine-mercaptopurinyl)-6-fluoro-benzoic acid. LC-MS (m/z) 346 (MH+); NMR (500 MHz, DMSO-d6): 0.35 (m, 1H), 0.39 (m, 1H), 0.5 (m, 2H), 1.12 (m, 1H), 3_68 & 3.74 (the two d of the AB system, J= 15.2 Hz, 2H, CH2), 4.25 (t, J= 8.5 Hz, 1H), 7.05 (dt, J=2.2, 8.05 Hz, 1H), 7.13 (d, ( J- 8.1 Hz, 1H), 7.16 -7.21 (m, 2H), 7.35 (m, 1H), 7.42 (m, 1H), 8.66 (d, J = 8.2 Hz, 1H, NH), 13.44 (br., C02H).

2-氣-6-[((S)-i-苯基-丙基胺曱醯基)-甲基]苯曱酸。 150 200906801 LC-MS (m/z) 3 32.2 (MH+); tR = 1·19。4 NMR (500 MHz， DMSO-d6): 0.84 (t，J=7.3 Hz, 3H)，1·68 (五重峰，J=7.3 Hz， 2H), 3.54 & 3·61 (AB 系統之兩個 d，J=15.3 Hz，2H，CH2)， 4.67 (q, J = 7.5 Hz, 1H), 7.19-7.4 (m, 8H), 8.48 (d, J=8.3 Hz, 1H，NH), 13.64 (br·，C02H)。2-Ga-6-[((S)-i-phenyl-propylaminoindolyl)-methyl]benzoic acid. </ RTI> </ RTI> <RTIgt; Heavy peak, J=7.3 Hz, 2H), 3.54 & 3.61 (two d of the AB system, J=15.3 Hz, 2H, CH2), 4.67 (q, J = 7.5 Hz, 1H), 7.19-7.4 (m, 8H), 8.48 (d, J = 8.3 Hz, 1H, NH), 13.64 (br·, C02H).

2-氟-6-[((S)-l-苯基-丙基胺甲醯基）-甲基]_苯曱酸。 LC-MS (m/z) 316.3 (MH+); tR = 1.13。4 NMR (5 00 MHz， CDC13): 0.79 (t，7.4 Hz，3H), 1.76 (五重峰之 d，2H，Et 之非對映異構 CH2)，3.64 (s，2H，CH2)，4.75 (q，J= 7.7 Hz， 1H), 7.04 (t, J=8.5 Hz, 1H), 7.08 (d, J=7.7 Hz, 1H), 7.17-7.23 l (重疊 m，3H)，7.24-7.28 (重疊 m，2H)，7.32 (m，1H)，7.45 (br d, J= 8.1 Hz, 1H, NH). 8.48 (d, J=8.3 Hz, 1H, NH), 11.14 (br., co2h)。2-Fluoro-6-[((S)-l-phenyl-propylaminemethanyl)-methyl]-benzoic acid. LC-MS (m/z) 316.3 (MH+); tR = 1.13. 4 NMR (5 00 MHz, CDC13): 0.79 (t, 7.4 Hz, 3H), 1.76 (D of the five-fold peak, 2H, Et Isomer CH2), 3.64 (s, 2H, CH2), 4.75 (q, J = 7.7 Hz, 1H), 7.04 (t, J = 8.5 Hz, 1H), 7.08 (d, J = 7.7 Hz, 1H) , 7.17-7.23 l (overlapping m, 3H), 7.24-7.28 (overlap m, 2H), 7.32 (m, 1H), 7.45 (br d, J = 8.1 Hz, 1H, NH). 8.48 (d, J= 8.3 Hz, 1H, NH), 11.14 (br., co2h).

151 200906801 2-氯-6-({[(S)-環丙基-(3-氟-苯基）-甲基]-胺甲醯基}-甲基）-苯曱酸。151 200906801 2-Chloro-6-({[(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-aminemethanyl}-methyl)-benzoic acid.

2-{[((S)-環丙基-苯基-甲基）-胺曱醯基]-甲基}-6-氟-苯曱酸。 LC-MS (m/z) 328·4 (MH+) ; tR = 1.12。2-{[((S)-cyclopropyl-phenyl-methyl)-amine fluorenyl]-methyl}-6-fluoro-benzoic acid. LC-MS (m/z) 328.

2-({[(S)-環丁基-(3-氟-苯基）-甲基]-胺甲醯基}-曱基）- 6-氟-苯甲酸。 LC-MS (m/z) 360.2 (MH+) ; tR = 1·31。2-({[(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-aminemethylmercapto}-indenyl)-6-fluoro-benzoic acid. LC-MS (m/z) 360.2 (MH+);

152 200906801 2-({[(S)-環丙基-(3-氟-苯基）-曱基]-胺甲醯基}-曱基）- 4,6-二氟-苯甲酸。152 200906801 2-({[(S)-Cyclopropyl-(3-fluoro-phenyl)-indenyl]-amine-methylmethyl}-indenyl)-4,6-difluoro-benzoic acid.

2-({[(8)-環丙基-(3-氟-苯基）-甲基]-胺甲醯基}-甲基）-3,6-二氟-苯甲酸。2-({[(8)-cyclopropyl-(3-fluoro-phenyl)-methyl]-aminemethylmercapto}-methyl)-3,6-difluoro-benzoic acid.

2-[((S)-：l-苯基-丙基胺曱醯基）-甲基]-6-三氟甲基-苯甲 LC-MS (m/z) 366·4 (MH+) ; tR = 1‘24。通式XXIII化合物之合成：2-[((S)-:l-phenyl-propylaminoindolyl)-methyl]-6-trifluoromethyl-benzene-LC-MS (m/z) 366·4 (MH+) tR = 1'24. Synthesis of a compound of the formula XXIII:

4-乙酸基- 3- ((S)-l-苯基-丙基胺基）-異色細 _ 1 -晒。 153 200906801 將2-[((S)-l-苯基-丙基胺甲醯基）-甲基]-苯甲酸（i〇 g)、乙酸酐（50 ml)及N，N-二曱基胺基。比咬（1〇〇 mg) 之混合物在溫和回流（Tmax = +124°C)下加熱7分鐘且在 + 50°C下真空蒸發產生呈黃褐色固體狀之標題化合物（ii.i g，藉由 NMR 之純度 98%)。LC-MS (m/z) 322·3 (MH+) ; tR =1.72° !H NMR (500 MHz, DMSO-d6): 0.89 (t5 J=7.2 Hz, 3H), 1.86-1.97 (m, 2H), 2.56 (s, 3H), 4.95 (q, 7.1 Hz, 1H, CH- f NH)，7.26 (t，J=7.5 Hz，1H)，7.29 (未解析 m，1H)，7.36-7.41 (未解析 m.，3H)，7.71 (t，J=7.5 Hz，1H)，7.75 (d，J=8.3 Hz， 1H), 7.98 (d, J=7.8 Hz, 1H), 11.53 (d, J=7.6 Hz, 1H, NH)° 13C APT NMR (125 MHz, DMSO-d6, 5(DMSO-d6)-39.87 ppm): 10.68 (CH3), 30.0 (CH2), 31.57 (CH3), 57.01 (CH), 92.44 (C), 114.88 (C), 124.2 (CH), (CH), 124.26 (CH), 126.65 (CH), 127.8 (CH), 129.05 (CH), 129.93 (CH), 135.71 (CH), 138.68 (C), 141.86 (C), 158.51 (C), 160.55 (C), 194.82 (C, MeCD.)。4-Acetyl 3-((S)-l-phenyl-propylamino)-heterochromatic _ 1 - drying. 153 200906801 2-[((S)-l-Phenyl-propylaminemethanyl)-methyl]-benzoic acid (i〇g), acetic anhydride (50 ml) and N,N-didecyl Amine. The title compound (ii.ig) was obtained as a yellow-brown solid (yield: y. The purity of NMR was 98%). LC-MS (m/z) 322·3 (MH+); tR = 1.72° & NMR (500 MHz, DMSO-d6): 0.89 (t5 J=7.2 Hz, 3H), 1.86-1.97 (m, 2H) , 2.56 (s, 3H), 4.95 (q, 7.1 Hz, 1H, CH- f NH), 7.26 (t, J = 7.5 Hz, 1H), 7.29 (unresolved m, 1H), 7.36-7.41 (unresolved m., 3H), 7.71 (t, J = 7.5 Hz, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H), 11.53 (d, J = 7.6 Hz , 1H, NH)° 13C APT NMR (125 MHz, DMSO-d6, 5(DMSO-d6)-39.87 ppm): 10.68 (CH3), 30.0 (CH2), 31.57 (CH3), 57.01 (CH), 92.44 ( C), 114.88 (C), 124.2 (CH), (CH), 124.26 (CH), 126.65 (CH), 127.8 (CH), 129.05 (CH), 129.93 (CH), 135.71 (CH), 138.68 (C ), 141.86 (C), 158.51 (C), 160.55 (C), 194.82 (C, MeCD.).

4-乙醯基-8 -氯-3-((S)-l -苯基-丙基胺基）-異色婦-i- 將2-氮-6-[((S)_l-苯基-丙基胺曱酿基）-曱基]-苯曱酸 (11.4 g)及乙酸酐（50 ml)在103°C下加熱60分鐘且蒸發產生12.45 g褐色油狀物（根據4 NMR純度約95%)。 154 2009068014-Ethyl-8-chloro-3-((S)-l-phenyl-propylamino)-isochromo-i- 2-A-6-[((S)-l-phenyl- Propylamine oxime)-mercapto]-benzoic acid (11.4 g) and acetic anhydride (50 ml) were heated at 103 ° C for 60 minutes and evaporated to give abr. %). 154 200906801

LC-MS (m/z) 35 5.2 (MH+) ; tR = 1·82。在冷卻（乾冰_ Et〇H 浴）及過濾後藉由再結晶（來自3 0 ml熱MeCN之9 g )製備分析純樣本，產生呈淺黃色固體狀之標題化合物（4.41 g)° LC-MS (m/z) 355.2 (MH+) ； tR = 1.82〇 !H NMR (500 MHz, DMSO-d6): 0.88 (t, J=7.4 Hz, 3H), 1.92 (m, 2H), 2.5 (s, 3H), 4.92 (q, J = 7.3 Hz, 1H, CH-NH), 7.27-7.33 (m, 2H), 7.39 (d (未解析 m)，J= 4.3 Hz, 4H)，7.59-7.66 (m, 2H), 11.11 (d， J=7.8 Hz, 1H, NH)。 f'LC-MS (m/z) 35 5.2 (MH+); An analytically pure sample was prepared by recrystallization (9 g of hot MeCN from EtOAc). (m/z) 355.2 (MH+) ; tR = 1.82 〇!H NMR (500 MHz, DMSO-d6): 0.88 (t, J = 7.4 Hz, 3H), 1.92 (m, 2H), 2.5 (s, 3H ), 4.92 (q, J = 7.3 Hz, 1H, CH-NH), 7.27-7.33 (m, 2H), 7.39 (d (unresolved m), J=4.3 Hz, 4H), 7.59-7.66 (m, 2H), 11.11 (d, J = 7.8 Hz, 1H, NH). f'

4-乙醯基-3_{[(S)-環丙基-(3-氟-苯基）-甲基]-胺基}-8-氟-異色烯-1-嗣。將2-({[(S)-環丙基-(3 -氟-苯基）-甲基]-胺甲醢基}_甲基）-6-氟-苯曱酸（12.92 g，37.41 mmol )與乙酸酐（100 mL， 1 mol )之混合物在+65°C下授拌20小時且真空蒸發（65°C， 1 0毫巴’ 2小時）產生呈褐色黏稠油狀物之標題化合物，其未經純化用於隨後步驟（14.3 0 g，產率1 〇3.5%，根據1Η NMR 純度 95°/。）。LC-MS (m/z) 370.1 (MH+) ; tR = 1.65。# NMR (500 MHz, DMSO-d6): 0.45-0.59 (m, 3H), 0.64 (m, 1H), 1.41 (m, 1H), 2.53 (s，3H)，4.3 6 (t (未解析 dd)，1H)，7.03 (dd, J = 8.3，10.7 Hz，1H)，7.12 (dt，J = 1.9, 8 5Hz，1H), 7 27 (d, J=10.2 Hz, 1H), 7.3 (d, J=7.8 Hz, 1H), 7.42 (q, J = 7.8 Hz, 1H), 155 200906801 7.53 (d, 8.5 Hz, 1H), 7.7 (m, 1H), 11.3 (d, J=7.3 Hz, 1H, NH)。4-Ethyl 3-({(())-cyclopropyl-(3-fluoro-phenyl)-methyl]-amino}-8-fluoro-isochromene-1-indole. 2-({[(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-aminecarbazinyl}-methyl)-6-fluoro-benzoic acid (12.92 g, 37.41 mmol And a mixture of acetic anhydride (100 mL, 1 mol) at rt. It was used in the subsequent step without purification (14.3 g, yield 1 〇 3.5%, purity according to 1 NMR, 95 °/). LC-MS (m/z). # NMR (500 MHz, DMSO-d6): 0.45-0.59 (m, 3H), 0.64 (m, 1H), 1.41 (m, 1H), 2.53 (s, 3H), 4.3 6 (t (unresolved dd) , 1H), 7.03 (dd, J = 8.3, 10.7 Hz, 1H), 7.12 (dt, J = 1.9, 8 5Hz, 1H), 7 27 (d, J = 10.2 Hz, 1H), 7.3 (d, J =7.8 Hz, 1H), 7.42 (q, J = 7.8 Hz, 1H), 155 200906801 7.53 (d, 8.5 Hz, 1H), 7.7 (m, 1H), 11.3 (d, J=7.3 Hz, 1H, NH ).

4-乙醯基-3-{[(S)-環丁基-(3-氟-苯基）-甲基]-胺基卜8_ 氟-異色浠-1-酮。 LC-MS (m/z) 384.4 (MH+) ; tR = 1_82。4-Ethyl-3-([(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amino)- 8-fluoro-isochroman-1-one. LC-MS (m/z) 384.4 (MH+);

(2 -側氣基-。比洛咬-1 _基）_乙酸。將 2-〇比 η各 α定酮（2.66 ml，34 mmol )及 NaH(油中 60%， L25 g，31_3 mmol)於TIIF ( 75 ml)中之混合物攪拌直至 V止氣體析出（30分鐘）。添加2-溴乙酸第三丁酯（4.45 nU， 0 mmol)且在至溫下撥掉隔夜，接著在水（200^1)與乙酸乙酯（ 200 m〇之間分溶產生中間物2_(側氧基_吡咯啶_ 1-基）-乙酸第三丁酯（5 8 g)。將其溶解於乙酸（4〇 ^1) 及濃HC1水溶液（6 ml )中，觀測到氣體析出。在室溫下攪拌2小時後，將其蒸發且自曱苯/乙醇再結晶產生2 58 g 才不題化合物（產率 60% )。〖H NMR (500 MHz, DMSO-d6): 1.95 (五重峰，j= 7 7 Hz，2H)，2.24 (t，J= 8>1 Hz，2Η)，3·38 (m，與 H2〇重疊（3.35 ppm)，2H)，3·91 (s, 2H)，12.77 (br·，1H)。 156 200906801(2 - side gas base -. Bilo bite - 1 - base) - acetic acid. A mixture of 2-indole η each α-butanone (2.66 ml, 34 mmol) and NaH (60% in oil, L25 g, 31_3 mmol) in TIIF (75 ml) was stirred until V gas evolution (30 min) . Add 2-bromoacetic acid tert-butyl ester (4.45 nU, 0 mmol) and dial overnight at ambient temperature, then dilute between water (200^1) and ethyl acetate (200 m〇 to give intermediate 2_(( The side oxy-pyrrolidin-1-yl-acetic acid tert-butyl ester (58 g) was dissolved in acetic acid (4 〇^1) and concentrated HCl aqueous solution (6 ml), and gas evolution was observed. After stirring at room temperature for 2 hours, it was evaporated and recrystallized from benzene/ethanol to give 2 58 g of compound (yield 60%). H NMR (500 MHz, DMSO-d6): 1.95 Peak, j = 7 7 Hz, 2H), 2.24 (t, J = 8 > 1 Hz, 2 Η), 3·38 (m, overlap with H2 ( (3.35 ppm), 2H), 3·91 (s, 2H ), 12.77 (br·, 1H). 156 200906801

氟側氧基苯基_两基胺基）_ih_異色烯_4_基]-2·側氧基_乙基卜吡咯啶_2_酮。向2_側氧基-吡咯啶_1_基-乙酸（丨56 g，1〇 9 mm〇1) 於1，2-二氯乙烷（40 ml)中之溶液中添加乙二醯氣（〇95 ml，10.9 mm〇1)及DMF ( i滴），觀測到氣體析出。在室溫下攪拌1小時後，添加2_氟_6_[((8)_1_苯基_丙基胺甲醯基）-曱基]-笨曱酸（1.56g，4.95 mmol)、三乙胺（2.1 ml， 14.9 mmol )及dmAP ( 85 mg，0· 1當量）且在室溫下授拌隔夜。使其在〇·2 M HC1水溶液（100 ml)-鹽水（100 ml) 混合物與乙酸乙酯（250 ml )之間分溶，以水洗滌且蒸發產生1.8 9 g粗標題化合物，其未經進一步純化用於隨後步驟中。 4 NMR (500 MHz, DMSO-d6,所選共振）：4.51 & 4.58 (AB 系統之兩個 d，J=16.3 Hz，N-CH2-CO)，4.99 (q，J= 7.5 Hz, 1H, CH-NH)，11.31 (d, J= 7.9 Hz，1H, NH)。Fluoroside phenyl phenyl 2-diylamino) _ih_heterochromene _4_yl]-2. oxo-ethylpyrrolidin-2-one. To the solution of 2_side oxy-pyrrolidin-1-yl-acetic acid (丨56 g, 1〇9 mm〇1) in 1,2-dichloroethane (40 ml) was added with ethylene dioxane ( 〇95 ml, 10.9 mm 〇1) and DMF (i drop), gas evolution was observed. After stirring at room temperature for 1 hour, 2_fluoro_6_[((8)_1_phenyl-propylaminemethanyl)-indenyl]-moleic acid (1.56 g, 4.95 mmol), triethyl Amine (2.1 ml, 14.9 mmol) and dmAP (85 mg, 0.1 eq.) were stirred overnight at room temperature. This was partitioned between EtOAc EtOAc (EtOAc) (EtOAc (EtOAc) Purification was used in the subsequent steps. 4 NMR (500 MHz, DMSO-d6, selected resonance): 4.51 & 4.58 (two d of the AB system, J = 16.3 Hz, N-CH2-CO), 4.99 (q, J = 7.5 Hz, 1H, CH-NH), 11.31 (d, J = 7.9 Hz, 1H, NH).

157 200906801 1-[2-(3-{[(8)-環丙基-(3_氟_苯基;)_甲基]_胺基卜8_氟-1_ 側氧基-1H-異色烯-4-基）-2-側氧基_乙基]-吡咯啶_2-酮。類似地製備標題化合物且藉由si〇2急驟層析法純化。 LC-MS (m/z) 453.3 (MH+) ; tR = 1.48。157 200906801 1-[2-(3-{[(8)-Cyclopropyl-(3-fluoro-phenyl))-methyl]-aminophenyl 8_fluoro-1_ oxo-1H-isochromene 4-yl)-2-yloxy-ethyl]-pyrrolidine-2-one. The title compound was prepared in a similar manner and purified by EtOAc EtOAc. LC-MS (m/z) 453 (MH+);

l-(2-{3-[((S)-環丙基-苯基-曱基胺基]·^氟—卜側氧基 -1H-異色稀-4-基}-2-側氧基-乙基）比u各唆_2-酮。類似地製備標題化合物。LC-MS (m/z) 435.3 (MH+) ; tR =1.43 。L-(2-{3-[((S)-cyclopropyl-phenyl-fluorenylamino)]-fluoro-b-oxy-1H-isochroman-4-yl}-2-yloxy The title compound was prepared in a similar manner to EtOAc (m/z).

4-乙醯基-3-[((S)-環丙基-苯基-甲基）_胺基]_8_氟·異色烯-1 -酿I。 LC-MS (m/z) 352.6 (MH+); tR = 1_62。4 NMR (500 MHz， DMSO-d6): 0.48 (m, 2H), 0.54 (m, 1H), 0.64 (m, 1H), 1.39 (m, 1H), 2.53 (s，3H)，4.39 (t (未解析 dd)，1H)，7.04 (dd，J = 8.2, 10.8 Hz, 1H), 7.3 (t, J=7.3 Hz, 1H), 7.39 (t, J=7.6 Hz, 2H), 7.43 (d, J=7.3 Hz, 2H), 7.53 (d, 8.5 Hz, 1H), 7.7 (m, 1H), 11.39 (d，J=7.5 Hz, 1H, NH)。 158 200906801 通式调化合物水解為通式χχν化合物4-Ethyl benzyl-3-[((S)-cyclopropyl-phenyl-methyl)-amino]_8_fluoro·isochromene-1 - Brewing I. LC-MS (m/z) 352.6 (MH+); s.sup.ssssssssssssssssssssssssssssssssssss (m, 1H), 2.53 (s, 3H), 4.39 (t (unresolved dd), 1H), 7.04 (dd, J = 8.2, 10.8 Hz, 1H), 7.3 (t, J=7.3 Hz, 1H) , 7.39 (t, J=7.6 Hz, 2H), 7.43 (d, J=7.3 Hz, 2H), 7.53 (d, 8.5 Hz, 1H), 7.7 (m, 1H), 11.39 (d, J=7.5 Hz , 1H, NH). 158 200906801 Hydrolysis of a compound of the formula to a compound of the formula χχν

2-(l-{[(S)-% 丙基 _(3_ t t u 1軋-本基）_曱基]-胺甲醯基卜2_侧氧基-丙基）-6-氟-笨甲酸。丨2側將 4-乙酿基- 搭 -a. U0)-%丙基_(3_氟_苯基）_甲 8-氟-2-苯并哌喃-^酮（丨』胺基}- 明I 14.30 g，38·72麵〇1)溶解於四吱口南（5 0 mL )與甲酿τ、知（50 mL)之混合物中且在攪拌下置於冰/水浴槽中。添加Na〇H 巾丨m，_…且持續授拌1小時。移除冷卻浴槽且使混合物在i小時期間溫至室溫（20t)。將反應混合物倒入冰水混合物（2〇〇g + 2〇〇 ml )中，隨後緩慢添加2 M HCi水溶液（2〇〇)且以乙酸乙Sa ( 200 mL)萃取，以飽和NaC1水溶液洗滌，乾燥 (NaJO4 )，過濾且蒸發產生呈淺褐色泡沫狀之標題化合物（14.65 g，產率97.7%)。粗產物未經進一步純化用於隨後步驟中。LC-MS (m/z) 388.3 (MH+) ; tR = 1.2. NMR (500 MHz，DMSO-d6)··互變異構體與非對映異構體之混合物。類似地製備以下化合物： 159 2009068012-(l-{[(S)-% propyl-(3_ttu 1-roll-based)-indenyl]-amine-mercaptopurin 2_sideoxy-propyl)-6-fluoro-abdominic acid .丨2 side will be 4-ethyl aryl----. U0)-% propyl-(3_fluoro-phenyl)-methyl 8-fluoro-2-benzopipen- ketone (丨胺 amino group) - Ming I 14.30 g, 38·72 face 〇 1) Dissolved in a mixture of Sishaokou South (50 mL) and yoghurt τ, zhi (50 mL) and placed in an ice/water bath with stirring. Add Na〇H towel 丨m, _... and continue to mix for 1 hour. The cooling bath was removed and the mixture was allowed to warm to room temperature (20t) during 1 hour. The reaction mixture was poured into an ice-water mixture (2 〇〇g + 2 〇〇ml), then 2 M aqueous EtOAc (2 EtOAc) was slowly added and extracted with ethyl acetate (200 mL) The title compound (14.65 g, yield 97.7%) was obtained eluted The crude product was used in the subsequent step without further purification. LC-MS (m/z) 388.3 (MH+); t.sup.ssssssssssssssssssssssssssssss The following compounds were prepared similarly: 159 200906801

2 -氣-6 - [ 2 -側乳基-3 - ( 2 -側乳基-π比°各α定-1 -基）-l-((S)-l- 苯基-丙基胺曱醯基）-丙基]-苯甲酸。2- gas-6 - [2-sialyl-based 3-(2-mercapto-pyrano-π ratio)-l-((S)-l-phenyl-propylamine oxime Mercapto)-propyl]-benzoic acid.

2-[l-{[(S)-環丙基-(3-氟-苯基）-曱基]-胺甲醯基}-2-側氧基-3-(2-側氧基-°比洛π定-1 -基）-丙基]-6 -亂-苯甲酸。 LC-MS (m/z) 471.4 (ΜΗ+) ; tR = 1.17。2-[l-{[(S)-cyclopropyl-(3-fluoro-phenyl)-indolyl]-aminecarbazinyl}-2-oxo-3-(2- oxo-° Bilo 1,3-decate-1-yl)-propyl]-6-disorganized-benzoic acid. LC-MS (m/z) 471.4 (?+);

2-(l-{[(S)-i哀丁基-(3 -乱-苯基）-甲基]-胺曱酿基}-2 -側氧基-丙基）-6 -氣-苯甲酸。 LC-MS (m/z) 402.2 (MH+) ; tR = 1.36。通式XXIV及XXV化合物之合成：如上文針對通式 160 200906801 ΧΧΙΠ化合物所述類似地但在較高溫度下（1 50°C，15分鐘）獲得通式χχιν化合物，且其一般水解為通式XXV化合物而不進行分離及表徵，因此下文中僅給出化合物XXIV之兩個實例。2-(l-{[(S)-i butyl butyl-(3-disorgano-phenyl)-methyl]-amine oxime}-2-sideoxy-propyl)-6-gas-benzene Formic acid. LC-MS (m/z) 4021. (MH+); Synthesis of compounds of the general formula XXIV and XXV: a compound of the formula χχιν is obtained analogously to the above formula 160 200906801 oxime compound but at a higher temperature (1 50 ° C, 15 minutes), and is generally hydrolyzed to the formula The XXV compound was not isolated and characterized, so only two examples of compound XXIV are given below.

3-甲基-1-側氧基-1Η-異色烯-4-羧酸（（S)-l-苯基-丙基）- 醯胺。藉由Si02急驟層析法純化標題化合物。LC-MS (m/z) 3 22.1 (MH+) ； tR = 1.27 〇 ]H NMR (500 MHz, CDC13): 1.03 (t, J=7.3 Hz, 3H)，1.91-2.06 (複雜 m，2H，CH2)，2.19 (s，3H)， 5.11 (q, J=7.8 Hz, 1H), 7.06 (br. d, J=8.3 Hz, 1H, NH), 7.22-7.33 (m, 3H), 7.36-7.43 (m, 4H), 7.54 (t, J= 7.6 Hz, 1H), 7.95 (d，J= 7.8 Hz，1H)。W NMR (500 MHz, DMSO-d6): 0.92 (t, J= 7.3 Hz, 3H), 1.76 (m, 2H), 2.18 (s, 3H), 4.93 (q, J=8.3 Hz, 1H), 7.21-7.41 (m, 6H), 7.59 (t, J=7.7 Hz, 1H), 7.82 (t, J=7.2 Hz, 1H), 8.17 (d, J=7.8 Hz, 1H), 9.1 (br. d, J=8.4 Hz, 1H, NH)。 161 2009068013-Methyl-1-oxooxy-1 quinone-isochromene-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine. The title compound was purified by flash chromatography on EtOAc. LC-MS (m/z) 3 22.1 (MH+); t,,,,,,,,,,, ), 2.19 (s, 3H), 5.11 (q, J = 7.8 Hz, 1H), 7.06 (br. d, J = 8.3 Hz, 1H, NH), 7.22-7.33 (m, 3H), 7.36-7.43 ( m, 4H), 7.54 (t, J = 7.6 Hz, 1H), 7.95 (d, J = 7.8 Hz, 1H). W NMR (500 MHz, DMSO-d6): 0.92 (t, J = 7.3 Hz, 3H), 1.76 (m, 2H), 2.18 (s, 3H), 4.93 (q, J = 8.3 Hz, 1H), 7.21 -7.41 (m, 6H), 7.59 (t, J=7.7 Hz, 1H), 7.82 (t, J=7.2 Hz, 1H), 8.17 (d, J=7.8 Hz, 1H), 9.1 (br. d, J = 8.4 Hz, 1H, NH). 161 200906801

6,8-二氟-3-甲基-1-侧氧基-111-異色稀_4_羧酸[(8)-環丙基- (3·•氣-苯基）-甲基]-酿胺。6,8-Difluoro-3-methyl-1-oxo-111-isochromic _4_carboxylic acid [(8)-cyclopropyl-(3·•gas-phenyl)-methyl]- Amine amine.

藉由Si〇2急驟層析法純化標題化合物。[e-MS (m/z) 388.4 (MH+) ; tR = 1.39 °The title compound was purified by flash chromatography eluting with EtOAc. [e-MS (m/z) 388.4 (MH+) ; tR = 1.39 °

2-[2-側氧基-1-((8)-1-苯基_丙基胺曱醯基）_丁基]_苯甲酸。2-[2-Sideoxy-1-((8)-1-phenyl-propylaminoindolyl)-butyl]-benzoic acid.

將2-[((S)-l-苯基-丙基胺曱醯基）_甲基]_苯甲酸（4〇9 mg，1.38 mmol)、丙酸酐（1〇 ml)與 4_N，N_二曱基胺基匕定（1 5 mg )之ί&封混合物在微波照射下在1 $ 〇。〇下加熱 2〇分鐘且在1M HC1 ( 50 ml)與乙酸乙酯（1〇〇 ml)之間分溶。有機層以飽和NaHC〇3水溶液（2 χ 5〇以）及鹽水洗滌且真空濃縮。向所獲得之殘餘物中添加甲醇（25 ml )、四氯咬喃（25 ml)及2MNaOH水溶液（5〇如）且在室溫下攪拌1小時。將有機揮發物真空移除且將pH值以3mhci 水溶液調整至i。粗標題產物（495 mg)藉由以乙酸乙酯 162 200906801 (150 ml)萃取分離且未經進一步純化用於隨後步驟中。ιΗ NMR (500 MHz, DMSO-d6):互變異構體與非對映異構體之混合物。類似地獲得以下化合物：2-[((S)-l-phenyl-propylaminoindolyl)-methyl]-benzoic acid (4〇9 mg, 1.38 mmol), propionic anhydride (1 〇ml) and 4_N,N_ The dimethyl hydrazide group (1 5 mg) of ί & seal mixture under microwave irradiation at 1 $ 〇. Heat underarm for 2 〇 minutes and dissolve between 1 M HCl (50 ml) and ethyl acetate (1 〇〇 ml). The organic layer was washed with aq. EtOAc (EtOAc m. Methanol (25 ml), tetrachloromethane (25 ml) and 2M aqueous NaOH (5 g) were added to the obtained residue and stirred at room temperature for 1 hour. The organic volatiles were removed in vacuo and the pH was adjusted to i with aq. The crude title product (495 mg) was isolated eluting with ethyl acetate 162 200906801 (150 ml) and used in the next step without further purification. Η NMR (500 MHz, DMSO-d6): a mixture of tautomers and diastereomers. The following compounds were obtained similarly:

2-氟-6-[2-侧氧基-1-((S)-1-苯基-丙基胺甲醢基）_丙基]_ 苯曱酸。 LC-MS (m/z) 358_4 (MH+) ; tR = 1.17。2-Fluoro-6-[2-o-oxy-1-((S)-1-phenyl-propylaminemethanyl)-propyl]-benzoic acid. LC-MS (m/z) 358. (MH+);

2-U-{[(S)-環丙基-(3-氟-苯基）-甲基]-胺甲醯基}_2_側氧基-丙基）-4,6 -二氣-苯曱酸。 LC-MS (m/z) 406.7 (MH+) ; tR = 1_3。 163 2009068012-U-{[(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-aminecarbamyl}_2_sideoxy-propyl)-4,6-di-benzene-benzene Tannic acid. LC-MS (m/z) 406.7 (MH+); 163 200906801

2-(1-{[(s)-環丙基-(3-氟-苯基）_甲基]_胺甲醯基}-2-側氧基-丙基）-3,6-二氟-苯甲酸。 LC-MS (m/z) 406.0 (MH+) ; tR = 〇_72 (方法 B)。 f .2-(1-{[(s)-cyclopropyl-(3-fluoro-phenyl)-methyl]-aminecarbamyl}-2-oxo-propyl)-3,6-difluoro -benzoic acid. LC-MS (m/z) 406.0 (MH+); tR = 〇 _ 72 (Method B). f.

2-[2-側氧基-1-((8)-1-苯基-丙基胺曱醯基）-丙基]·6· 氟甲基-苯曱酸。標題化合物直接用於隨後步驟。 02-[2-Sideoxy-1-((8)-1-phenyl-propylaminoindenyl)-propyl]·6·fluoromethyl-benzoic acid. The title compound was used directly in the next step. 0

1-第三丁基·哌啶-4-酮。根據所述程序製備標題化合物：J.S. Amato，J.Y.L Chung, R-J- Cvetovich, X. Gong, M. McLaughlin, R.A Reamer J. 〇rg. Chem. 2005, 70，1930。 164 2009068011-tert-butyl-piperidin-4-one. The title compound was prepared according to the procedure: J. S. Amato, J. Y. L Chung, R-J-Cvetovich, X. Gong, M. McLaughlin, R. A Reamer J. 〇rg. Chem. 2005, 70, 1930. 164 200906801

(i-第三丁基-亞哌啶_4_基）_乙酸乙酯。將1-第三丁基·派唆_4__ ( 4 59 g，Μ 6匪〇1)及（三苯基亞鱗si基）乙酸乙酯（1G3g，23 6 _g1)於甲苯（⑽ mL)中之混合物在回流下在氮氣下㈣μ小時且真空蒗 f 發。殘餘物藉切膠管柱層析法（石㈣/三乙胺=100/1') 純化產生 5 · 1 g 呈潘甚洛收& 久κ色油狀物之標題化合物，產率 76.5%。 +(i-T-butyl-piperidinyl-4-yl)-ethyl acetate. 1-1-tert-butyl·Panthene_4__ (4 59 g, Μ 6匪〇1) and (triphenyl sulfenyl si) ethyl acetate (1G3g, 23 6 _g1) in toluene ((10) mL) The mixture was refluxed under nitrogen for four hours and vacuum was applied. The residue was purified by EtOAc EtOAc EtOAc (EtOAc) +

(1-第三丁基-哌啶_4_基）_乙酸乙酯。向(1_第三丁基-亞…-基)-乙酸乙醋（5」g，227 _〇υ於乙醇（5〇叫中之溶液中添加i〇%pd/c(〇6g 且將混合物在氫氣氛（42 psi )下在 # —丄^ P ; P在裱境溫度下攪拌14小牯。稭由過濾移除催化劑，且將濟液@ 耵德及濃縮產生標題（4.03 g，產率78%)，其直接用於隨後步驟中。(1-tert-Butyl-piperidine-4-yl)-ethyl acetate. To (1_t-butyl-sub-...-yl)-acetic acid ethyl acetate (5"g, 227 _ 〇υ in ethanol (5 添加之 solution added i 〇 % pd / c (〇 6g and the mixture Under a hydrogen atmosphere (42 psi), the mixture was stirred at ambient temperature for 14 hours. The catalyst was removed by filtration, and the title was obtained by filtration and the title was obtained (4.03 g, yield 78%), which is used directly in the subsequent steps.

N- ho2c (1-第三丁基-哌啶_4_基）_乙酸。向NaOH於水/乙醇（v/v = 4〇/1〇，5〇⑷中之中添加。-第三丁基-旅咬-4-基)_乙酸乙醋（4〇3 §，”8 165 200906801 溫下攪拌隔夜。添加1 N HC1水溶將揮發物真空蒸發，殘餘物以甲醇 mmol )且將混合物在室液以將pH值調整為5。 (30 mL )稀釋’ 藉由過㈣除不溶性無機鹽。將慮液濃縮且藉由石夕膠管柱層析法（CH2Cl2/Me〇H = 2〇/1至5/ι) Λ化產生0.7 g呈淺灰色粉末狀之標題化合物。1h (彻 MHz, DMSO-d6): 3.15-3.08 (br m, 2H), 2.3〇 (br t, j = Π.2N-ho2c (1-tert-butyl-piperidine-4-yl)-acetic acid. Add NaOH to water/ethanol (v/v = 4〇/1〇, 5〇(4). -T-butyl-Brigade-4-yl)-acetic acid ethyl vinegar (4〇3 §,”8 165 200906801 Stir under temperature overnight. Add 1 N HCl in water to evaporate the volatiles in vacuo, the residue is taken in methanol (methanol) and the mixture is taken to room temperature to adjust pH to 5. (30 mL) diluted by (4) by insoluble The title compound was obtained as a light gray powder. MHz, DMSO-d6): 3.15-3.08 (br m, 2H), 2.3 〇 (br t, j = Π.2

Hz，2H)，2.0 5 (d，J = 6 4 7η、λ η λ 0.4 Hz, 2H), 1.71-1.68 (m, 3H), 1.30- 1.27 (m, 2H)，1.10 (s，9h)。Hz, 2H), 2.0 5 (d, J = 6 4 7η, λ η λ 0.4 Hz, 2H), 1.71-1.68 (m, 3H), 1.30- 1.27 (m, 2H), 1.10 (s, 9h).

2-(1-第三丁基-哌啶_4_基）_小笨基-乙醯胺。向（1-第二丁基-哌啶_4_基）_ 乙酸（672 3 37 、苯胺（0.32 nU，3.5 _0〇及 H〇Bt ( 568 mg，4 2 _〇1) 於DMF ( 20 ml )中之混合物中添加EDC ( 8〇5叫，η mmol)。將其在室溫下攪拌2小時且在水爪1)與乙 S夂乙酉日（2GG mi )之間分溶。有機相以Q 5 N Na〇H水溶液 (2 X 50 ml)及鹽水（3 x 5〇 ml)洗滌，乾燥（MgS〇j 且真空濃縮。殘餘物藉由急驟層析法（Si〇2,梯度庚烷-乙西义乙S曰）純化產生250 mg標題化合物。iH NMR (5〇〇 MHz, DMSO-d6): 1.07 (s, 9H), 1.32 (br. 2U), 1.81 (br. d, 2H), 1.89 (m, 1H), 2.11 (br. t, 2H), 2.25 (d5 2H), 3.03 (br. d, 2H), 7.1 (t, 1H), 7.24 (br., 1H), 7.31 (t, 2H), 7.52 (d, 2H) 〇 166 200906801 本發明化合物實施例12-(1-Tert-butyl-piperidine-4-yl)-p-styl-acetamide. To (1-tert-butyl-piperidine-4-yl)-acetic acid (672 3 37, aniline (0.32 nU, 3.5 _0 〇 and H〇Bt ( 568 mg, 4 2 〇 1 ) in DMF ( 20 ml EDC (8〇5, η mmol) was added to the mixture. It was stirred at room temperature for 2 hours and dissolved between the water claw 1) and the acetonitrile day (2GG mi ). Wash with Q 5 N Na〇H aqueous solution (2×50 ml) and brine (3×5 〇ml), dry (MgS 〇j and concentrated in vacuo. Purification of 250 mg of the title compound, iH NMR (5 〇〇 MHz, DMSO-d6): 1.07 (s, 9H), 1.32 (br. 2U), 1.81 (br. d, 2H), 1.89 (m, 1H), 2.11 (br. t, 2H), 2.25 (d5 2H), 3.03 (br. d, 2H), 7.1 (t, 1H), 7.24 (br., 1H), 7.31 (t, 2H), 7.52 (d, 2H) 〇166 200906801 Compound of the present invention Example 1

la 3-甲基-1-側氧基-2_苯基-丨头二氫-異喹啉-肛羧酸 ((s)-l-苯基-丙基）_醯胺。將3-甲基-1-側氧基_2_苯基-12-二氳-異喹啉-4-羧酸 (212 mg ’ 0.76 mmol)於 S0C12 (1.5 ml)及二曱基甲醯胺（約5 μ!^ )中之溶液在回流下加熱5分鐘。真空移除揮發物產生228 mg呈淺褐色固體狀之相應醯氣。將一部分酿氯（110 mg ’ 〇·37 mmol)溶解於 ι，2-二氯乙烷（2 ml) 中且添加（S)-(--)-1-苯基丙基胺（150 pL，1.1 mmol)。將所獲得之懸浮液振盪5分鐘，以丨，2_二氣乙烷（1〇 ml)稀釋’以1M HC1水溶液（3 x 5 ml)及水（5 ml )洗滌。將有機相倒入Si〇2 ( 5 §)中’以1，2-二氣乙烷（50 ml)稀釋且將產物以I:1乙酸乙酯-庚烷溶離產生140 mg無色結曰曰口體產率95%。或者，在另一輪中，使反應混合物在 2M HC1與庚烷（10 ml)之間分溶且藉由過濾使產物自所獲得之兩相系統分離。 167 200906801 LC-MS (m/z) 397.1 (MH+); tR = 1.44。4 NMR (500 MHz， CDC13): 1.0 (t, 3H), 1.93 (m, 5H), 5.16 (q, 1H), 6.7 (d, 1H), 7.07 (d, 2H), 7.31 (m, 1H), 7.36 (d, 4H), 7.4-7.5 (m, 5H), 7.63 (未解析 t，1H)，8.31 (d，1H)。自相應酸及胺類似地獲得以下化合物且藉由製備型 LC-MS純化：La 3-methyl-1-oxo-2-phenyl-indole dihydro-isoquinoline-anionic carboxylic acid ((s)-l-phenyl-propyl)-decylamine. 3-Methyl-1-oxo-2-phenyl-2-pyrene-isoquinoline-4-carboxylic acid (212 mg '0.76 mmol) in S0C12 (1.5 ml) and dimercaptocaramine The solution (about 5 μ!^) was heated under reflux for 5 minutes. The volatiles were removed in vacuo to yield 228 mg of the corresponding helium as a light brown solid. A portion of the brewed chlorine (110 mg '〇·37 mmol) was dissolved in ι,2-dichloroethane (2 ml) and (S)-(--)-1-phenylpropylamine (150 pL, 1.1 mmol). The obtained suspension was shaken for 5 minutes, and washed with hydrazine, 2 - dioxaethane (1 〇 ml) diluted with 1M aqueous HCl (3 x 5 ml) and water (5 ml). The organic phase was poured into Si〇2 (5 §) and diluted with 1,2-dioxaethane (50 ml) and the product was dissolved in 1:1 ethyl acetate-heptane to give a colorless sapon. The body productivity was 95%. Alternatively, in another round, the reaction mixture was partitioned between 2M HCl and heptane (10 ml) and the product was separated from the obtained two-phase system by filtration. 167 200906801 LC-MS (m/z) 397.1 (MH+); tR = 1.44. 4 NMR (500 MHz, CDC13): 1.0 (t, 3H), 1.93 (m, 5H), 5.16 (q, 1H), 6.7 (d, 1H), 7.07 (d, 2H), 7.31 (m, 1H), 7.36 (d, 4H), 7.4-7.5 (m, 5H), 7.63 (unresolved t, 1H), 8.31 (d, 1H) ). The following compounds were obtained analogously from the corresponding acids and amines and purified by preparative LC-MS:

1 b 3，6 -二曱基-1 -側氧基-2 -苯基-1,2-二鼠-異喧淋-4 -竣酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 41 1.3 (MH+) ; tR = 0.8 (方法 B)。 \1 b 3,6-dimercapto-1 -p-oxy-2-phenyl-1,2-di-oxo-isoindole-4-decanoic acid ((S)-l-phenyl-propyl)- Guanamine. LC-MS (m/z) 41 1.3 (MH+); \

lc 7 -氯-3-曱基-1-側乳基-2-苯基-1，2-二鼠-異啥嚇*-4-緩 168 200906801 酸（（s)-i-苯基-丙基）-醯胺。 LC-MS (m/z) 43 1.3 (MH+) ; tR = 0·86 (方法 B)。Lc 7 -Chloro-3-indolyl-1-ylidery-2-phenyl-1,2-dimur-isoindole *-4-slow 168 200906801 Acid ((s)-i-phenyl-prop Base) - guanamine. LC-MS (m/z) 43 1.3 (MH+); tR = 0·86 (Method B).

Id 7-溴-3-曱基-1-側氧基-2-苯基-1,2-二氳-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 475.1 (MH+，79Br) ; tR = 0·87 (方法 B)。Id 7-bromo-3-indol-1-yloxy-2-phenyl-1,2-diindole-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)- Guanamine. LC-MS (m/z) 475.1 (MH+, 79Br); tR = 0·87 (Method B).

le 6 -氣-3-曱基-1-側氧基-2-苯基-1，2_二氮-異啥琳-4-缓酸苯基-丙基）-醯胺。 LC-MS (m/z) 415_5 (MH+) ; tR = 0_80 (方法 B)。 169 200906801Le 6 - gas-3-mercapto-1-yloxy-2-phenyl-1,2-diaza-isoindolin-4-o-phenyl-propyl)-guanamine. LC-MS (m/z) 415_5 (MH+); tR = 0_80 (method B). 169 200906801

If 3,5-二甲基-1-侧氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-驢胺。 LC-MS (m/z) 41 1·3 (MH+) ; tR = 0.84 (方法 B)。If 3,5-Dimethyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-oxime amine. LC-MS (m/z) 41 1·3 (MH+); tR = 0.84 (Method B).

1 g 7 -氣-3-甲基-1-側氧基-2-苯基-1，2-二氮-異喧琳-4 -缓酸（（S)-l-苯基-丙基）-酸胺。 LC-MS (m/z) 415.4 (MH+) ; tR = 1.49。 170 2009068011 g 7-gas-3-methyl-1-oxo-2-phenyl-1,2-diaza-isoindolin-4-sodium acid ((S)-l-phenyl-propyl) - Acid amine. LC-MS (m/z) 415.4 (MH+); 170 200906801

lh 3,7-二曱基-1-側乳基-2-苯基-1，2-二氮-異喧琳-4-缓酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 411_4 (MH+) ; tR = 1.5。Lh 3,7-dimercapto-1-yl-lacyl-2-phenyl-1,2-diaza-isoindolin-4-o-acid ((S)-l-phenyl-propyl)-醯amine. LC-MS (m/z) 411_4 (MH+);

li 8 -氯-3-曱基-1-側乳基-2-苯基-1,2-二氮-異喧嚇 - 4 -叛酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 431.4 (MH+) ; tR = 1.54。 171 200906801Li 8 -Chloro-3-indol-1-yl-lactyl-2-phenyl-1,2-diaza-isoindole- 4 - tacrotic acid ((S)-l-phenyl-propyl)- Guanamine. LC-MS (m/z) 436 (MH+); 171 200906801

lj 3,8-二曱基-1-側乳基-2-苯基-1,2-二氮-異啥琳-4-叛酸（（S)-l-苯基-丙基）-S盘胺。 LC-MS (m/z) 41 1.4 (MH+) ; tR = 1.5。4 NMR (2 5 0 MHz， DMSO-d6, T=343K): 0.91 (t, 3H), 1·78 (重疊 s，3H), 1.79 (重疊 m, 1H), 2.75 (s, 3H)，4.94 (q，1H), 7.15-7.27 (m, 5H), 7.27-7.39 (m, 4H), 7.41-7.58 (m，4H)，8.67 (d, 1H)。Lj 3,8-dimercapto-1-yl-lacyl-2-phenyl-1,2-diaza-isoindolin-4-deoxalate ((S)-l-phenyl-propyl)-S Pot amine. LC-MS (m/z) 41 1.4 (MH+); t,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, ), 1.79 (overlapping m, 1H), 2.75 (s, 3H), 4.94 (q, 1H), 7.15-7.27 (m, 5H), 7.27-7.39 (m, 4H), 7.41-7.58 (m, 4H) , 8.67 (d, 1H).

lk 2-(2 -氣-苯基）-3 -甲基-1-側氧基-1,2-二鼠-異嗤琳-4 -羧酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 415.5 (MH+) ; tR = 1.49。 172 200906801Lk 2-(2- gas-phenyl)-3-methyl-1-oxo-1,2-di-oxo-isoindolin-4-carboxylic acid ((S)-l-phenyl-propyl ) - guanamine. LC-MS (m/z) 415.5 (MH+); 172 200906801

11 3-曱基-1-側氧基-2-鄰甲苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 411.5 (MH+) ; tR = 1.5。11 3-Mercapto-1-yloxy-2-o-tolyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine. LC-MS (m/z) 411.5 (MH+);

lm 2-(2-氯-苯基）-3-甲基-1-側氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 431.2 (MH+) ; tR = 1.51。 173 200906801Lm 2-(2-Chloro-phenyl)-3-methyl-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl ) - guanamine. LC-MS (m/z) 4321. (MH+); 173 200906801

In 2-(2，6-二氣-苯基）-3 -甲基-1-側乳基-1，2·二氮-異啥〆琳-4 -竣酸（（S)-l_苯基-丙基）-酿胺。 LC-MS (m/z) 433.4 (MH+) ; tR = 1.54。In 2-(2,6-dioxa-phenyl)-3-methyl-1-flavoryl-1,2·diaza-isoindolin-4-decanoic acid ((S)-l-benzene Base-propyl)-bristamine. LC-MS (m/z) 433.4 (MH+);

lo 2-(3 -氣-苯基）-3 -曱基-1-側乳基-1，2 -二氮-異喧琳-4 -竣酸（（S)-l-苯基-丙基）-驢胺。 LC-MS (m/z) 415_1 (MH+) ; tR = 1.48。 174 200906801Lo 2-(3- gas-phenyl)-3-mercapto-1-latyl-1,2-diaza-isoindolin-4-decanoic acid ((S)-l-phenyl-propyl ) - guanamine. LC-MS (m/z) 415 (MH+); 174 200906801

lp 3-曱基-1-側氧基-2-間甲苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/ζ) 411·5 (MH+) ; tR = 1.53。Lp 3-mercapto-1-yloxy-2-m-tolyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine. LC-MS (m/ζ) 411·5 (MH+);

lq 2-(3-氯-苯基）-3-甲基-1-側氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 431.2 (MH+) ; tR = 1.57。 175 200906801Lq 2-(3-Chloro-phenyl)-3-methyl-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl ) - guanamine. LC-MS (m/z) 4321. (MH+); 175 200906801

lr 3 -甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸 ((S)-環丙基··苯基-甲基）-醯胺。 LC-MS (m/z) 409.4 (MH+); tR = 1.43。W NMR (250 MHz, DMSO-d6, T=343K): 0.45 (m, 2H), 0.56 (m, 2H), 1.25 (m, 1H), 1.88 (s, 3H), 4.51 (t, 1H), 7.21-7.37 (m, 5H), 7.42-7.59 (m, 7H)，7.7 (dt，1H)，8.21 (dd，1H), 8.89 (d，1H)。Lr 3 -Methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-cyclopropyl··phenyl-methyl)-醯amine. LC-MS (m/z) 409.4 (MH+); W NMR (250 MHz, DMSO-d6, T = 343 K): 0.45 (m, 2H), 0.56 (m, 2H), 1.25 (m, 1H), 1.88 (s, 3H), 4.51 (t, 1H), 7.21-7.37 (m, 5H), 7.42-7.59 (m, 7H), 7.7 (dt, 1H), 8.21 (dd, 1H), 8.89 (d, 1H).

Is 3-甲基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸 [(S)-J哀丙基- (3 -乱-苯基）-甲基]-酿胺。 LC-MS (m/z) 427.1 (MH+); tR = 1_48。4 NMR (250 MHz, DMSO-d65 T=343K): 0.48 (m, 2H), 0.57 (m, 2H), 1.24 (m, 1H), 1.89 (s, 3H), 4.51 (t, 1H), 7.05 (m, 1H), 7.21-7.31 (m, 176 200906801 4H), 7.33-7.6 (m, 6H), 7.7 (dt, 1H), 8.21 (dd, 1H), 8.94 (d, 1H)。Is 3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-J propyl-(3-disorgano-phenyl) -Methyl]-bristamine. LC-MS (m/z) 427.1 (MH+); t,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, ), 1.89 (s, 3H), 4.51 (t, 1H), 7.05 (m, 1H), 7.21-7.31 (m, 176 200906801 4H), 7.33-7.6 (m, 6H), 7.7 (dt, 1H), 8.21 (dd, 1H), 8.94 (d, 1H).

It 8-氯-3-甲基-1-側氧基-2-苯基-1,2-二氳-異喹啉-4-羧酸[(S)-J哀丙基- (3 -氣-苯基）-甲基]-酸胺。 LC-MS (m/z) 461.6 (MH+); tR = 1.51。NMR (250 MHz, DMSO-d6, T=343K): 0.48 (m, 2H), 0.58 (m, 2H), 1.27 (m, 1H), 1.87 (s, 3H), 4.5 (t, 1H), 7.06 (m, 1H), 7.21-7.32 (m, 4H), 7.32-7.45 (m, 2H), 7.45-7.66 (m, 5H)，8.95 (d，1H)。It 8-chloro-3-methyl-1-oxo-2-phenyl-1,2-diindole-isoquinoline-4-carboxylic acid [(S)-J propyl propyl- (3- gas -Phenyl)-methyl]-acid amine. LC-MS (m/z) 461.6 (MH+); NMR (250 MHz, DMSO-d6, T=343K): 0.48 (m, 2H), 0.58 (m, 2H), 1.27 (m, 1H), 1.87 (s, 3H), 4.5 (t, 1H), 7.06 (m, 1H), 7.21-7.32 (m, 4H), 7.32-7.45 (m, 2H), 7.45-7.66 (m, 5H), 8.95 (d, 1H).

laa 2-(3-甲氧基-苯基）-3-甲基-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 426.7 (MH+) ; tR = 1.43。 177 200906801Laa 2-(3-methoxy-phenyl)-3-methyl-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl- Propyl)-guanamine. LC-MS (m/z) 422 (MH+); 177 200906801

lab 2-(4-曱氧基-苯基）-3-甲基-1-側氧基-1,2-二氫-異啥琳-4-竣酸（（S)-l-苯基-丙基）-酸胺。 LC-MS (m/ζ) 427·0 (MH+) ; tR = 1.43。气Lab 2-(4-decyloxy-phenyl)-3-methyl-1-oxooxy-1,2-dihydro-isoindolin-4-indole ((S)-l-phenyl- Propyl)-acid amine. LC-MS (m/?) 427. (MH+); gas

lac 2-(4-氟-苯基）-3-甲基-Μ則氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺。 I LC-MS (m/z) 415.0 (MH+) ； tR = 1.43 °Lac 2-(4-Fluoro-phenyl)-3-methyl-oxime oxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl) - guanamine. I LC-MS (m/z) 415.0 (MH+) ; tR = 1.43 °

lad 2-(4-乳-苯基）-3 -甲基-1-側氧基-1，2-二氮-異喧琳-4-羧酸（（S)-l-苯基-丙基）-醯胺。 178 200906801 LC-MS (m/z) 431.1 (MH+) ; tR = 1.54。Lad 2-(4-lacyl-phenyl)-3-methyl-1-oxo-1,2-diaza-isoindolin-4-carboxylic acid ((S)-l-phenyl-propyl ) - guanamine. 178 200906801 LC-MS (m/z) 431.1 (MH+);

1 a e 3 -甲基-1 -側氧基-2-對甲苯基-1，2-二鼠-異啥琳-4 -羧酸（（S)-l-苯基-丙基）-醯.胺。 LC-MS (m/z) 411·2 (MH+) ; tR = 1.51 〇1 ae 3 -Methyl-1 -yloxy-2-p-tolyl-1,2-dimur-isoindolin-4 -carboxylic acid ((S)-l-phenyl-propyl)-oxime. amine. LC-MS (m/z) 411·2 (MH+) ; tR = 1.51 〇

FF

laf 2-(3·曱氧基-苯基）-3 -曱基-1-側氧基-1，2-二氮-異啥嚇^-4 -魏酸[(S)-J哀丙基- (3 -鼠-苯基）-甲基]-酿胺。 LC-MS (m/z) 457_0 (MH+) ; tR = 1.47。Laf 2-(3·decyloxy-phenyl)-3-indolyl-1-yloxy-1,2-diaza-isoindole^-4-treaic acid [(S)-J propyl - (3 - murine-phenyl)-methyl]-bristamine. LC-MS (m/z) 457. (MH+);

FF

lag 2-(4 -甲氧基-苯基）-3 -曱基-1-側氧基-1，2-二氫·異 179 200906801 喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基卜醯胺。 LC-MS (m/z) 457.1 (MH+) ; tR = 1.46。Lag 2-(4-methoxy-phenyl)-3-indolyl-1-yloxy-1,2-dihydro-iso-179 200906801 Quinoline-4-carboxylic acid [(S)-cyclopropyl -(3-Fluoro-phenyl)-methyldoxime. LC-MS (m/z) 457.1 (MH+);

lah 2-(4-氟-苯基）-3-甲基-1-側氧基-1,2-二氳-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺。 LC-MS (m/z) 445.6 (MH+) ; tR = 1.48。Lah 2-(4-Fluoro-phenyl)-3-methyl-1-oxo-1,2-diindole-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3- Fluoro-phenyl)-methyl]-guanamine. LC-MS (m/z) 495 (MH+);

FF

lai 2-(4-氯-苯基）-3-甲基-1-側氧基-1，2-二氫-異喹啉-4-緩酸[(S)-環丙基- (3 -氟-苯基）·曱基]-酿胺。 LC-MS (m/z) 461.3 (MH+) ; tR = 1.57。Lai 2-(4-Chloro-phenyl)-3-methyl-1-oxooxy-1,2-dihydro-isoquinoline-4-hypoacid [(S)-cyclopropyl-(3- Fluoro-phenyl) fluorenyl]-bristamine. LC-MS (m/z) 4621. (MH+);

FF

180 200906801 laj 3 -曱基-1-側氧基-2-對甲苯基-1，2-二氫-異喧咐_4-羧酸[(S)-環丙基-(3-氟-苯基）-曱基]•酿胺。 LC-MS (m/z) 440_9 (MH+) ; tR = 1.54 0180 200906801 laj 3 - Mercapto-1-yloxy-2-p-tolyl-1,2-dihydro-isoindole 4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-benzene Base) - mercapto) LC-MS (m/z) 440_9 (MH+) ; tR = 1.54 0

lak 2-(2-甲氧基-苯基）-3 -甲基-1-側氧基_1，2-二氫-異哇嘛-4-叛酸（（S)-l -苯基-丙基）-酿胺。 LC-MS (m/z) 427.0 (MH+) ; tR = 1.39。Lak 2-(2-methoxy-phenyl)-3-methyl-1-oxooxyl-1,2-dihydro-isowa-4-pyreic acid ((S)-l-phenyl- Propyl)-bristamine. LC-MS (m/z) 427.0 (MH+);

lal 2-(2-曱氧基-苯基）-3-甲基d —侧氧基4,2-二氫-異喹咏-4-叛酸[(S)-環丙基- (3 -氟-苯基）_甲基]_酿胺。 LC-MS (m/z) 457.4 (MH+) ; tR = 1.43 〇Lal 2-(2-decyloxy-phenyl)-3-methyld-p-oxy 4,2-dihydro-isoquinoline-4-retadiol [(S)-cyclopropyl-(3- Fluoro-phenyl)-methyl]-bristamine. LC-MS (m/z) 457.4 (MH+); tR = 1.43 〇

181 200906801 1 a m 3 -甲基-8 -石肖基-1 -側乳基-2 -苯基-1，2 -二鼠-異啥嚇·-4-羧酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 442.4 (MH+) ; tR = 1.46。181 200906801 1 am 3 -Methyl-8 - Shishaji-1 -Lactyl-2-phenyl-1,2-di-oxo-isoindole-4-carboxylic acid ((S)-l-phenyl- Propyl)-guanamine. LC-MS (m/z) 442.4 (MH+);

f ' 1 a π 3 -甲基-8 -石肖基-1 -側氣基-2 -苯基-1，2-二鼠-異嗤琳-4 -叛酸[(S)-J哀丙基- (3 -氣-苯基）-甲基]-酿胺。 LC-MS (m/z) 442.4 (MH+) ; tR = 1.46。f ' 1 a π 3 -Methyl-8 -Shishaoji-1 -Side-based 2-phenyl-1,2-di-iso-indiyl-4 - tacrotic acid [(S)-J propyl- (3-Gas-phenyl)-methyl]-bristamine. LC-MS (m/z) 442.4 (MH+);

lao 8-曱氧基-3-甲基-1-側氧基-2-苯基-1,2-二氫-異喹琳-4-叛酸（（S)-l-苯基-丙基）-酿胺。 LC-MS (m/z) 427.1 (MH+) ; tR = 1.32。Lao 8-decyloxy-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinolin-4-reactive acid ((S)-l-phenyl-propyl ) - Amine. LC-MS (m/z) 427.1 (MH+);

182 200906801 lap 8-甲氧基-3-曱基-1-側氧基_2_笨 + I '1,2-二氫-異喹琳-4-緩酸[(S)-環丙基-(3 -氟-苯基）_甲基]_酿胺 LC-MS (m/z) 457.4 (MH+) ; tR = ι·36 〇182 200906801 lap 8-methoxy-3-mercapto-1-yloxy_2_stupid + I '1,2-dihydro-isoquinolin-4-hygroic acid [(S)-cyclopropyl- (3-Fluoro-phenyl)-methyl]-bristamine LC-MS (m/z) 457.4 (MH+) ; tR = ι·36 〇

，2'二氫-異啥琳- laq 8-胺基-3-甲基-1-側氧基苯基 4-羧酸（（S)-l-苯基-丙基）-醯胺。向3-曱基-8-硝基-1-側氧基-2-笨10 , 二氫-異喹啉-4- 羧酸（（S)-l-苯基-丙基）_醯胺（lam , 1 〇，0.023 mmol) 於四虱吱喃（0.15 mi)中之經授拌溶液中添加2m hci水溶液（0.12 m卜 0.25 mmoi)及 Zn 粉（45 mg，〇 69 _〇ι)。 3〇分鐘後，將混合物過濾且在乙酸乙酯（4以丨）與飽和2' Dihydro-isoindole-laq 8-amino-3-methyl-1-oxophenylphenyl 4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine. To 3-mercapto-8-nitro-1-oxo-2-phenyl 10, dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine Lam, 1 〇, 0.023 mmol) A 2 m hci aqueous solution (0.12 m 0.25 mm oi) and Zn powder (45 mg, 〇69 _〇ι) were added to the mixed solution in tetrahydrofuran (0.15 mi). After 3 minutes, the mixture was filtered and saturated with ethyl acetate (4 EtOAc)

NaHC03水溶液（2 ml )，接著鹽水（3 ml )之間分溶。將有機溶液乾燥（MgS 04 )且蒸發產生5 _ 9 mg標題化合物（產率 70%)。LC-MS (m/z) 412.4 (MH+) ; tR = 1.37。A solution of NaHC03 in water (2 ml) followed by brine (3 ml). The organic solution was dried (MgS04) and evaporated to give 5~9 mg of the title compound (yield 70%). LC-MS (m/z) 4121. (MH+);

183 200906801 lar 8-氰基-3-曱基-^側氧基_2_苯基-丨，2_二氫-異喹啉_ 4 -緩酸（（S)-l-苯基-丙基）_醯胺。 LC-MS (m/z) 422.1 (MH+) ； tR = 1.37 ° 根據一般程序獲得以下化合物：在室溫下將DMF ( 0.5 ml)中之通式IX之相應酸（〇〇4 mm〇1)及通式XI之胺 (0_06 mmol)在 Et3N ( 3 當量）、EDC ( 1.5 當量）及 HOBT (1.5當量）存在下攪拌隔夜，隨後在乙酸乙酯（2nil)與〇·5 M NaOH ( 1 ml)之間分溶且經受si〇2急驟層析法。 las lat 化學名稱結構 8-氣-3-曱基-1-側氧基苯基_ 12-二氫-異喹啉-4-羧酸[(S)-l-(4_氯-苯基)-丙基]-醯胺183 200906801 lar 8-cyano-3-indolyl-^-oxy 2-1-phenyl-indole, 2-dihydro-isoquinoline _ 4 - slow acid ((S)-l-phenyl-propyl ) _ guanamine. </ RTI> <RTIgt And the amine of formula XI (0_06 mmol) was stirred overnight in the presence of Et3N (3 eq.), EDC (1.5 eq.) and HOBT (1.5 eq.), followed by ethyl acetate (2 nil) and 〇·5 M NaOH (1 ml) Diluted between and subjected to si〇2 flash chromatography. Las lat chemical name structure 8- gas-3-mercapto-1-yloxyphenyl_12-dihydro-isoquinoline-4-carboxylic acid [(S)-l-(4-chloro-phenyl) -propyl]-nonylamine

tR MW m/z (min) (MH+) 1.63 465.4 465.4tR MW m/z (min) (MH+) 1.63 465.4 465.4

8-氯-3-曱基-1-側氧基-2-苯基-1，2-二氫-異喹啉_4_羧酸[⑻—μ (4_氟-苯基)-丙基]-醯胺8-Chloro-3-indol-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(8)-μ(4-fluoro-phenyl)-propyl ]-guanamine

1.52 448.9 449.3 lau 8-氯-3-曱基-1-側氧基-2-苯基-1，2'二氫-異喹啉-4-羧酸[(S)-1 -(2-氟-苯基)-丙基]-醯胺1.52 448.9 449.3 lau 8-chloro-3-indol-1-yloxy-2-phenyl-1,2'dihydro-isoquinoline-4-carboxylic acid [(S)-1 -(2-fluoro -phenyl)-propyl]-guanamine

1.52 448.9 449.4 lav 8-氣-3-曱基-1-側氧基-2-苯基-—氮-異喧嚇>-4-缓酸[(S)-l-(3-氯-苯基)_丙基]-醯胺1.52 448.9 449.4 lav 8-gas-3-mercapto-1-yloxy-2-phenyl--nitrogen-isoteryin >-4-sodium acid [(S)-l-(3-chloro-benzene Base)-propyl]-guanamine

1.62 465.4 465.3 184 200906801 law 8-氣-3-甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸[⑻-(3-氮··苯基)-ί衷丙基-甲基]-酸胺1.62 465.4 465.3 184 200906801 law 8-Gas-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(8)-(3-nitrogen·· Phenyl)- 衷 propyl-methyl]-acid amine

1.64 477.4 477.3 lax lay1.64 477.4 477.3 lax lay

8-氣-3-甲基-1-侧乳基-2-苯基-1，2-二氫-異喹啉-4-羧酸[⑸-(4-氣-本基)-¾丙基-甲基]-酿胺 8-氯!-3-甲基-1-側氧基-2-苯基_ 1,2-二氫-異喹啉-4-羧酸[⑻-1 -(3-氟-苯基)-丙基]-S藍胺8-Gas-3-methyl-1-flavoryl-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(5)-(4-Gas-yl)-3⁄4 propyl -methyl]-bristamine 8-chloro!-3-methyl-1-oxo-2-phenyl-1 1,2-dihydro-isoquinoline-4-carboxylic acid [(8)-1 -(3 -fluoro-phenyl)-propyl]-S leucine

1.64 477.4 477.4 1.53 448.9 449.3 laz 8-氯-3-甲基-1-側氧基-2-苯基-1，2-二氳-異喹啉-4-羧酸((S)-2-曱基-1-苯基-丙基)-醯胺1.64 477.4 477.4 1.53 448.9 449.3 laz 8-chloro-3-methyl-1-oxo-2-phenyl-1,2-di-p-isoquinoline-4-carboxylic acid ((S)-2-indole -1-phenyl-propyl)-guanamine

1.59 444.96 445.7 lba1.59 444.96 445.7 lba

lbb 8-氣-3-甲基-1-側氧基-2-苯基- 1.2- 二氫-異喹啉-4-羧酸[⑶-環丙基-(4-氟-苯基)-甲基]-醯胺 8-氣-3-曱基-1-側氧基-2-苯基_ 1.2- 二氫-異喹啉-4-羧酸[(8)-1-(2-氯-苯基)-丙基]-S篮胺Lbb 8-gas-3-methyl-1-oxo-2-phenyl-1.2-dihydro-isoquinoline-4-carboxylic acid [(3)-cyclopropyl-(4-fluoro-phenyl)- Methyl]-nonylamine 8-gas-3-mercapto-1-yloxy-2-phenyl-1.2-dihydro-isoquinoline-4-carboxylic acid [(8)-1-(2-chloro -phenyl)-propyl]-S basket amine

1.61 465.4 465.3 1.53 460.9 461.5 lbc 8-氯-3-曱基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-環戊基-苯基-甲基)-醢胺1.61 465.4 465.3 1.53 460.9 461.5 lbc 8-chloro-3-indol-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-cyclopentyl -phenyl-methyl)-guanamine

1.72 470.99 471.8 185 200906801 lbd lbe lbf1.72 470.99 471.8 185 200906801 lbd lbe lbf

8-鼠-3-甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸[⑻-(2-鼠-苯基)-¾丙基-甲基]-酸胺 8-氣-3-甲基-1-側氧基-2-苯基_ 1，2-二氫-異喹啉-4-羧酸[(S)-壞丙基-(2-鼠-苯基)-甲基]-酿胺 8-氯-3-甲基-1-侧氧基-2-苯基-1,2-二氳-異喹啉-4-羧酸((S)-環己基-笨基-甲基)-醯胺8-murro-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(8)-(2-mur-phenyl)-3⁄4 propyl -methyl]-acid amine 8-gas-3-methyl-1-oxo-2-phenyl-1 1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-d-propyl -(2-mur-phenyl)-methyl]-bristamine 8-chloro-3-methyl-1-oxo-2-phenyl-1,2-di-p-isoquinoline-4-carboxylate Acid ((S)-cyclohexyl-phenyl-methyl)-guanamine

1.6 477.4 477.21.6 477.4 477.2

1.6 460.9 461.6 1.8 485.0 485.41.6 460.9 461.6 1.8 485.0 485.4

Ibg 8-氮-3-曱基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-環丙基-苯基-甲基)-醯胺Ibg 8-azin-3-indol-1-oneoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-cyclopropyl-phenyl-methyl )-guanamine

1.5 442.9 443.5 lbh1.5 442.9 443.5 lbh

8-氣-3-甲基-1-側乳基-2-苯基-1,2_二氫-異喹啉-4-羧酸[(S)-環丁基-(3-氟-苯基)-甲基]-酸胺8-ox-3-methyl-1-flavoryl-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclobutyl-(3-fluoro-benzene) Methyl]-acid amine

1.65 474.96 475.5 lbi 8-氯-3-甲基-1-側乳基-2-苯基-1,2-二氫-異喹啉-4-羧酸[⑸-環丁基-(4-氣-苯基)-甲基]-酸胺1.65 474.96 475.5 lbi 8-chloro-3-methyl-1-flavoryl-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(5)-cyclobutyl-(4- gas -phenyl)-methyl]-acid amine

1.64 474.96 475.5 186 200906801 1.52 460.9 461.51.64 474.96 475.5 186 200906801 1.52 460.9 461.5

NHNH

8-氯-3-甲基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸[(R)-環丙基-(3-氟-苯基)-甲基]-醯胺 lbn 8-氯-3-甲基-1-側氧基-2-苯基- p 1.61 456.97 457.3 1,2-二氫-異喹啉-4-羧酸(⑸環 ΟγΝΗ 丁基-苯基·甲基)-酿胺 lb〇 8-氯-3-甲基-1-側氧基-2-苯基- 1.64 474.96 475.4 1，2-二氫-異喹啉-4-羧酸[環丁 ΟγΝΗ 基-(2- it-苯基)-曱基]-驢胺 9¾8-Chloro-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(R)-cyclopropyl-(3-fluoro-benzene) Base)-methyl]-guanamine lbn 8-chloro-3-methyl-1-oxo-2-phenyl-p 1.61 456.97 457.3 1,2-dihydro-isoquinoline-4-carboxylic acid ( (5) Ογγ butyl-phenyl·methyl)-bristamine lb〇8-chloro-3-methyl-1-oxo-2-phenyl- 1.64 474.96 475.4 1,2-dihydro-isoquinoline 4-carboxylic acid [cyclobutanyl γ-yl-(2- it-phenyl)-fluorenyl]-nonylamine 93⁄4

實施例2 :中間物之製備Example 2: Preparation of intermediates

3-溴甲基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸 ((S)-l-苯基-丙基）-酿胺。向 CaC03 (500 mg，5 mmol)及 3-曱基-1-侧氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺（115 187 200906801 mg ’ 0.29 mm〇1)於1，2-二氣乙烷（5 ml)中之懸浮液中添加溴（600 mg ’ 3.75 mm〇i)。將所獲得之混合物在+33。〇下超音波處理2小時，以1，2-二氣乙烷（20 ml )稀釋且倒入石夕膠管柱（5 g )中。將過量溴以丨，2_二氣乙烷溶離且將產物以1:1乙酸乙酯-庚烷溶離產生135 mg褐色固體。將其 /合解於乙酸乙醋（〇 5 ml )中且以庚烷（2〇 ^1 )沈澱產生 1〇〇mg 黃褐色固體。產率 72%。LC-MS (m/z) 475.2 (MH+， 7 93-Bromomethyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-bristamine. To CaC03 (500 mg, 5 mmol) and 3-mercapto-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl -propyl)-decylamine (115 187 200906801 mg '0.29 mm 〇1) bromo (600 mg ' 3.75 mm 〇i) was added to a suspension of 1,2-dioxaethane (5 ml). The mixture obtained was at +33. Subginger Ultrasonic treatment for 2 hours, diluted with 1,2-dioxaethane (20 ml) and poured into a Shixi rubber column (5 g). Excess bromine was dissolved in hydrazine, 2_diethane, and the product was dissolved in 1:1 ethyl acetate-heptane to yield 135 mg of brown solid. This was combined with ethyl acetate (5 ml) and precipitated with heptane (2 〇 ^1) to yield 1 〇〇mg of a tan solid. The yield was 72%. LC-MS (m/z) 475.2 (MH+, 7 9

Br) ; tR = 1.59。ifj NMR (500 MHz，DMSO-d6，兩種互變旋轉異構體之混合物）：0.95 (br, 3H，CH3), 1.74 and 1.82 (兩個未解析 m，2 χ iH，CH2)，4.0 (未解析 m，1H，CH2Br)，4.21 and 4.35 (兩個未解析 m，2 x 〇 5H，CH2Br)，4 97 (q，m，CH)， 7.1 (br, 0.5H), 7.24 (br, 0.5H), 7.28-7.21 (br m, 11.5H), 7.89 (br, 0.5H)，8.25 (br, 1H), 9.28 (d，1H, NH)。類似地獲得以下化合物：Br) ; tR = 1.59. Ifj NMR (500 MHz, DMSO-d6, a mixture of two tautomeric rotamers): 0.95 (br, 3H, CH3), 1.74 and 1.82 (two unresolved m, 2 χ iH, CH2), 4.0 ( Unresolved m,1H,CH2Br), 4.21 and 4.35 (two unresolved m, 2 x 〇5H, CH2Br), 4 97 (q, m, CH), 7.1 (br, 0.5H), 7.24 (br, 0.5 H), 7.28-7.21 (br m, 11.5H), 7.89 (br, 0.5H), 8.25 (br, 1H), 9.28 (d, 1H, NH). The following compounds were obtained similarly:

3 ->臭曱基-8-氯-1-側氧基-2-苯基-1，2-二氮-異喧琳-4-叛酸（（S)-l-苯基-丙基）-酿胺。粗產物未經進一步純化用於隨後步驟中。LC-MS (m/z) 188 200906801 511.3 (MH+，79Br) ; tR = 1_68 〇3 -> skunkyl-8-chloro-1-oxo-2-phenyl-1,2-diaza-isoindolin-4-deoxalate ((S)-l-phenyl-propyl ) - Amine. The crude product was used in the next step without further purification. LC-MS (m/z) 188 200906801 511.3 (MH+,79Br) ; tR = 1_68 〇

3-溴甲基-2-(2-氟-苯基）_i_側氧基-i，2-二叛酸（（S)-l -苯基-丙基）_醯胺。粗產物未經進一步純化用於隨後步驟中 493.3 (MH+，79Br) ; tR = 162。 -氮-異喧琳_ 4 -〇 LC-MS (m/z)3-Bromomethyl-2-(2-fluoro-phenyl)_i_ pendant oxy-i,2-di-oroxic acid ((S)-l-phenyl-propyl)-decylamine. The crude product was used in the next step without further purification of 493.3 (MH+, 79Br); tR = 162. -Nitrogen-isophthalene _ 4 -〇 LC-MS (m/z)

3 _溴曱基_ 1 -側氧基-2-鄰曱苯基-1,2-二酸（（S)-l-苯基-丙基）_醯胺。粗產物未經進一步純化用於隨後步驟中 489.3 (MHV9Br) ; tR=1_65。 -異01琳-4-羧 LC-MS (m/z) 189 2009068013 _Bromoindolyl-1 1-sided oxy-2-o-indolephenyl-1,2-diacid ((S)-l-phenyl-propyl)-decylamine. The crude product was used in the next step without further purification of 489.3 (MHV9Br); tR = 1 to 65. -iso 01琳-4-carboxyl LC-MS (m/z) 189 200906801

3-溴甲基-2-(3-氟-苯基）-1-側氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 493.5 (MH+，79Br) ; tR = 0.80 (方法 B)。3-bromomethyl-2-(3-fluoro-phenyl)-1-oxooxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl ) - guanamine. LC-MS (m/z) 493.5 (MH+, 79Br); tR = 0.80 (Method B).

i. 3->臭曱基-2-(3-氣-苯基）-1-側氧基-1，2-二氮-異喧淋-4-繞酸（（S)-l-笨基-丙基）胺。 LC-MS (m/ζ) 511·5 (ΜΗ+，81Br) ; tR = 0.84 (方法 Β)。 190 200906801i. 3-> skunkyl-2-(3-a-phenyl)-1-oxooxy-1,2-diaza-isoindole-4-oxo acid ((S)-l-stupid Base-propyl)amine. LC-MS (m/ζ) 511·5 (ΜΗ+, 81Br); tR = 0.84 (method Β). 190 200906801

3-溴甲基-1-側氧基-2-間甲苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 489.2 (MH+, 79Br) ; tR = 0.86 (方法 B)。3-Bromomethyl-1-oxo-2-m-tolyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine. LC-MS (m/z) 489.2 (MH+, 79Br);

3-溴曱基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸 [0¾丙基- (3 -鼠-苯基）-曱基]-酿胺。 LC-MS (m/z) 505.1 (MH+) ; tR = 1.62。3-bromomethyl-1-acetoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [03⁄4 propyl-(3-n-phenyl-phenyl)-indenyl]- Amine amine. LC-MS (m/z) 505.1 (MH+);

191 200906801 3-溴曱基-2-(3 -曱氧基-苯基）-卜側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺。產物藉由Si02急驟層析法（梯度庚烷-乙酸乙酯）純化且直接用於隨後步驟中。191 200906801 3-Bromomethyl-2-(3-indenyloxy)-p-oxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl -propyl)-guanamine. The product was purified by EtOAc flash chromatography ( gradient heptane-ethyl acetate) and used directly in the next step.

3-溴甲基-2-(4-曱氧基-苯基）_1_側氧基-丨，2_二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）·醯胺。產物藉由Si〇2急驟層析法（梯度庚烷-乙酸乙酯）純化。LC-MS (m/z) 505.1 & 507.2 (MH+) ; tR = 1.52。3-bromomethyl-2-(4-decyloxy-phenyl)_1_sideoxy-oxime, 2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propane Base) · guanamine. The product was purified by flash chromatography ( gradient heptane-ethyl acetate). LC-MS (m/z) 505.1 &

3-溴甲基-2-(4-氟-苯基）-1-侧氧基4,2-二氫-異喹啉_4_ 羧酸（（S)-l-苯基-丙基）-醯胺。產物藉由Si〇2急驟層析法（梯度庚炫-乙酸乙酯）純化。LC-MS (m/z) 493.3 & 495.3 (MH+) ; tR 二 1.54。 192 2009068013-bromomethyl-2-(4-fluoro-phenyl)-1-yloxy 4,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)- Guanamine. The product was purified by flash chromatography on EtOAc ( gradient EtOAc-EtOAc). LC-MS (m/z) 493.3 & 495.3 (MH+); 192 200906801

3 ->臭甲基- 2- (4 -氣-苯基）-1-側氧基-1，2-羧酸（（S)-l-苯基-丙基）-醯胺。3-> Stinylmethyl-2-(4- gas-phenyl)-1-oxooxy-1,2-carboxylic acid ((S)-l-phenyl-propyl)-decylamine.

LC-MS (m/z) 509.2 & 511.1 (MH+) ； tRLC-MS (m/z) 509.2 & 511.1 (MH+); tR

3 - >臭甲基-8 -亂-1 -側乳基-2 -苯基-1，2 -二酸[(S)-i^丙基- (3 -氣-苯基）-曱基]-酿胺。3 - > stinky methyl-8 - chaotic-1 - flavonyl-2 -phenyl-1,2-diacid [(S)-i^propyl-(3- gas-phenyl)-fluorenyl ]--Amine.

LC-MS (m/z) 539.1 & 541.4 (MH+) ; tRLC-MS (m/z) 539.1 & 541.4 (MH+) ; tR

3 ->臭甲基-8-氣-1-側氧基-2-苯基-1,2 -二酸（（S)-l-本基-丙基）-龜胺。3-> Stinylmethyl-8-gas-1-oxo-2-phenyl-1,2-diacid ((S)-l-benyl-propyl)-monamine.

LC-MS (m/z) 493.3 & 495.2 (MH+) ; tR 氫-異啥琳-4-1_63。 -異喹琳-4-羧 1.69。 -異喹琳-4-羧 1.52。 193 200906801LC-MS (m/z) 493.3 & 495.2 (MH+); <EMI> - Isoquinolin-4-carboxyl 1.69. - Isoquinolin-4-carboxyl 1.52. 193 200906801

3-漠甲基-8-氟-1-侧氧基-2-苯基-1，2-二氫-異啥琳叛酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺。 LC-MS (m/z) 523.5 & 525.6 (MH+) ; tR = 1.56。本發明化合物3-Methylmethyl-8-fluoro-1-oxo-2-phenyl-1,2-dihydro-isoindole retinoic acid [(S)-cyclopropyl-(3-fluoro-phenyl) -Methyl]-nonylamine. LC-MS (m/z) (495). Compound of the invention

2a 3-二甲基胺基甲基-i_側氧基_2_苯基_丨，2_二氫-異喹琳-4-缓酸（（S)-l-苯基-丙基）_醯胺。將3-溴甲基-1-側氧基_2-苯基4,2-二氫_異喹啉_4_羧酸 ((S)_1-苯基-丙基）-醯胺（70 mg，〇147 mm〇1)與二甲基胺 (1ml無水乙醇中33%溶液，過量）之混合物保持於5〇t>c 下歷時丨0分鐘且接著真空蒸發。將殘餘物溶解於甲醇中且穿過sex陽離子交換管柱（1 g, RS〇3H形式）。將未填充之雜男以甲醇/合離且將產物以甲醇中4Μ ΝΗ〗溶離產生 194 200906801 53 mg無色玻璃狀固體。將其進一步藉由si02急驟層析法 (5 g，梯度1，2-二氣乙烷—1，2-二氯乙烷中1〇%乙酸乙酯）純化產生45 mg無色固體。產率70%。LC-MS (m/z) 440.1 (MH+) ； tR = 0.88 ° Ή NMR (250 MHz, DMSO-d6, T = 333 K): 0.92 (t，2H)，1.83 (兩個重疊 m，2H), 1.66 (s，6H)，2.96 and 3.08 (CHAHBN 之兩個 d，2H)，4_96 (q，1H), 7.19-7.56 (m， 12H)，7_68 (t, 1H), 8.21 (d，1H)，8.75 (d，1H)。2a 3-dimethylaminomethyl-i-sideoxy-2_phenyl-indole, 2-dihydro-isoquinolin-4-acid ((S)-l-phenyl-propyl) _ guanamine. 3-Bromomethyl-1-oxo-2-phenyl 4,2-dihydro-isoquinoline-4-carboxylic acid ((S)_1-phenyl-propyl)-decylamine (70 mg A mixture of 〇147 mm〇1) and dimethylamine (33% solution in 1 ml absolute ethanol, excess) was kept at 5 °t >c for 分钟0 min and then evaporated in vacuo. The residue was dissolved in methanol and passed through a s cation exchange column (1 g, RS 〇 3H form). The unfilled male was dissolved in methanol/isolated and the product was dissolved in methanol to give 194 200906801 53 mg of a colorless glassy solid. It was further purified by flash chromatography (5 g, gradient EtOAc, EtOAc (EtOAc) The yield was 70%. LC-MS (m/z) 440.1 (MH+), NMR (250), NMR (250 MHz, DMSO-d6, T = 333 K): 0.92 (t, 2H), 1.83 (two overlapping m, 2H), 1.66 (s,6H), 2.96 and 3.08 (two d, 2H of CHAHBN), 4_96 (q, 1H), 7.19-7.56 (m, 12H), 7_68 (t, 1H), 8.21 (d, 1H), 8.75 (d, 1H).

2b 3-甲基胺基曱基側氧基_2_苯基-U2_二氫-異喹啉_ 4-羧酸（（S)-l-苯基-丙基）_醯胺。將3-漠曱基-1-側氧基_2-苯基- i，2-二氫-異啥琳_4_緩酸 ((S)-l-本基-丙基）_醢胺（4.7 mg，0.01 mmol )與甲基胺（1 ml四氫吱喃中2M溶液，過量）之混合物保持於環境溫度下歷時20分鐘且接著真空蒸發。產物未經進一步純化用於生物測試中。LC-MS (m/z) 426.3 (MH+) ; tR = 0.85。在％境溫度下自相應3 -溴·曱基衍生物及1.2 - 5莫耳當 S之適當赌族或芳族一級或二級胺於溶劑四氫吱喃中類似地製備以下3-胺基甲基衍生物。反應係藉由LC-MS監測。 195 200906801 — 在若干狀況下，使用較長反應時間或將反應混合物加熱至 5 0°C及/或添加二異丙基乙基胺（2當量）作為鹼。將反應混合物蒸發之後，藉由分析型LC-MS偵測，化合物具有足夠純度；否則進行藉由SCX管柱或藉由製備型LC-MS進行進一步純化。來自實施例2之化合物之列表化學名稱 tR(min) MW m/z (MH+) f 2c 3-乙基胺基甲基-1-側氧基-2- 045 439.6 440.6 苯基-1,2-二氮-異嗤琳-4-叛酸（方法b) ((S)-l-苯基-丙基)-醯胺 2d 3-環丙基胺基甲基-1-側氧基-0.49 451.6 452.1 2-苯基-1,2-二鼠-異嗤琳-4-叛（方法b) 酸((S)-1 -苯基-丙基)-醯胺 2e 3-[(環丙基甲基-胺基)-曱基]-0.51 465.6 466.4 1-側氧基-2-苯基-1,2-二氫-異（方法b) 喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 2f 3-(3,6-二氫-2H-吡啶-1-基曱 0.99 基)-1 -側乳基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基 -丙基)-醯胺 477.6 478.1 2g 3-[4-(2-甲氧基-苯基)-哌畊-1.14 1-基曱基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 586.7 587.5 2h 3-[4-(4-氟-苯基)-哌啡-1-基 1.35 574.7 575.6 196 200906801 2i 甲基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-酿胺 3-(4-甲醯基-哌啡-1-基甲基)- 1.12 508.6 509.3 2j 1_側乳基-2-苯基-1,2-二風-異 π奎琳-4-竣酸((S)-1 -苯基-丙基)-醯胺 4-[ 1 -側氧基-2-苯基-4-( 1 -苯基 1.33 552.7 553.7 r 2k -丙基胺甲醯基)-1,2-二氫-異喹啉-3-基甲基]-哌啡-1-羧酸乙酯 3_(4_甲基-哌啡-1-基甲基)-1- 0.87 494.6 495.7 21 側氧基-2-苯基-1,2-二鼠-異喧琳-4-竣酸((S)-l-苯基-丙基)_ 醯胺 1_ 側氧基-2-苯基-3-(l，3,4,9- 1.27 566.7 567.7 # ' 2m 四氮_β_叶淋_2-基曱基)-l，2_ 二氮-異喧嚇-4-叛酸((S)-l-苯基-丙基)-S篮胺 1-側氧基-2-苯基-3-哌啡-1- 0.86 480.6 481.2 2n 基曱基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-酿胺 3-(3-甲基-哌啡-1-基曱基)-1- 0.88 494.6 495.7 2o 側氧基-2-苯基-1,2-二氯-異哇嚇·_4-竣酸((S)-l-苯基-丙基)_ 醯胺 3-(3,5-二甲基-哌啡-1-基甲 0.9 508.7 509.3 基)-1-側氧基-2-苯基-1,2-二 200906801 氫-異喹啉-4-羧酸((S)-l-苯基 -丙基)-醯胺 2p 3-(4-苯曱基-娘啡-1-基曱基)-1 -側乳基·2·苯基· 1，2-二氮·異喧嚇 -4-竣酸((S)-1 -苯基-丙基)-醯胺 1.02 570.7 571.5 2q 1 -側氧基-3-[4-(2·側氧基-2·吼洛。定-1 -基-乙基)-娘明:-1 -基曱基]-2-苯基-1，2-二氣-異喧琳-4-竣酸((S)-l-苯基-丙基) 醯胺 0.92 591.8 592.4 2r 3-嗎福林-4-基曱基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4_羧酸((S)-l-苯基-丙基)-驢胺 1.08 481.6 482.2 2s 3-(2,6-二甲基-嗎福林-4-基甲基)小側氧基-2-苯基-1，2-二氮-異喧琳-4-叛酸((S)-l-苯基 -丙基)-驢胺 1.21 509.6 510.2 ( 2t 1-側氧基-2-苯基-3-硫代嗎福林-4-基曱基-1，2-二鼠-異啥琳 -4-羧酸((S)小苯基-丙基)-醯胺 1.22 497.7 498.8 2u 3-(1，4-二氧雜-8-氮雜-螺[4_5] 癸-8-基曱基)·1-側氧基-2-苯基-1，2-二氯-異喧琳-4-魏酸 ((S)-l-苯基-丙基)-酸胺 1.01 537.7 538.4 2v 1-側乳基-2-苯基-3-旅。定_1-基 1 479.6 480.3 甲基-1，2-二氫-異喹啉-4-羧酸 200906801 ((s)-i-苯基-丙基)-醯胺 2w 3-(2-曱基-哌啶-1-基曱基)-1-側氧基_2-苯基-1，2-二氮-異喧琳-4-竣酸((S)-l-苯基-丙基)_ 醯胺 1.07 493.6 494.4 2x 3-(2,6-二曱基-哌啶-1-基甲基)-1 -側氧基-2-苯基-1,2-二氮-異啥>^木-4-叛酸((S)-l-苯基 -丙基)-酿胺 1.09 507.7 508.4 2y 3-(2-羥基曱基-哌啶-1-基甲基)小側氧基-2-苯基-1,2-二氮-異啥淋_4_竣酸((S)-l-苯基 -丙基)-醯胺 0.93 509.6 510.3 2z 1 -[ 1 -側氧基-2-苯基-4-( 1 -苯基 -丙基胺甲酿基)-1,2-二氮-異喹啉-3-基曱基]-哌啶-3-羧酸乙酯 1.14 551.7 552.4 2aa 3-(3-甲基-哌啶-1-基甲基)-1-側氧基-2-苯基-1，2-二氫-異喹嚇>-4-魏酸((S)-l-苯基-丙基)* 醯胺 1.09 493.6 494.5 2ab 3-(4-羥基-哌啶-1-基甲基)-1-側氧基-2-苯基-1,2-二風-異喧啉-4-羧酸((S)-l-苯基-丙基)- 醯胺 0.83 495.6 496.5 2ac 1_側氧基-2-苯基-3-(4-苯基- 1.27 555.7 556.5 略°定-1-基曱基)-l，2-二氣-異啥嚇 -4-繞酸((S)-1 -苯基-丙 199 200906801 基)-醯胺 2ad 1-[1-側乳基-2-苯基-4-(1-苯基 -丙基胺甲醯基)-1,2-二氳-異啥淋-3-基甲基]-α底D定-4-叛酸乙酯 1.11 551.7 552.5 2ae 3-(4-甲基-哌啶-1-基甲基)-1-側乳基-2-苯基-1,2-二氮-異啥嚇·_4-竣酸((S)-l-苯基-丙基)_ 酸胺 1.1 493.6 494.6 2af 1-側氧基-2-苯基-3-(4-°比°定-2-基-旅明^1-基甲基)-1,2-二氣_ 異唾琳-4-竣酸((S)-l-苯基-丙基)-醯胺 0.97 557.7 558.4 2ag 3-(八氮查嚇 1-基甲基)-1-側氧基-2-苯基-1,2-二氮-異喧琳 -4-竣酸((S)-l-苯基-丙基)-酿胺 1.18 533.7 534.4 2ah 3-氮雑環庚烷-1-基曱基-1-側乳基-2-苯基-1,2-二氮-異唾嚇 -4-羧酸((S)-1-苯基-丙基)-醯胺 1.08 493.6 494.6 2ai 3-(3-羥基-哌啶-1-基甲基)-1-側氧基-2-苯基-1,2-二鼠-異喧淋-4-竣酸((S)-l-苯基-丙基)·* 醯胺 0.88 495.6 496.5 2aj 3-[4-(2,4-二曱基-苯基)-哌啡- 1.45 584.8 585.5 1_基甲基]-I-側氧基·2-苯基-1,2-二氫-異喹啉斗羧酸(⑻- 200 200906801 1-苯基-丙基)-醯胺 2ak 3-[4-(3,4-二甲基-苯基)-哌啡-1-基甲基]-1-側氧基-2-苯基_ 1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-酿胺 1.29 584.8 585.6 2al 3-(4-二甲基胺基-哌啶-1-基甲基)-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基 -丙基)-醯胺 0.81 522.7 523.5 2am 3-[4-(2,5-二甲基-苯基)-哌畊-1-基甲基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-1-本基-丙基)-酸胺 1.47 584.8 585.6 2an 3-[4_(2_氟-苯基)-哌啡-1-基甲基]-1 -側乳基-2-苯基-1，2_ 二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 1.42 574.7 575.4 2ao 3_[4_(3_曱氧基-苯基)_哌畊_ 1-基甲基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-酸胺 1.32 586.7 587.3 2ap 1-側氧基-2-苯基-3-(4-間曱苯基底[井-1-基甲基)-i，2-二氯_ 異喧琳-4-竣酸((S)-l-苯基-丙基)-醯胺 1.33 570.7 571.7 2aq 3-[4_(4·甲氧基-苯基)-哌畊- 1.11 586.7 587.6 1-基曱基]-1-側氧基-2-苯基-1,2_二氫-異喹啉-4-羧酸((S)- 201 200906801 2ar 1-苯基-丙基)-醯胺 l-側氧基-3_(4-苯乙基-哌明 1.09 584.8 585.5 2as 1-基曱基)-2-苯基-1,2-二里^ 異啥淋-4-竣酸((S)-l-苯基-丙基)-醯胺卜側氧基-^-苯基^-^-^密咬-之- 1.18 558.7 559.3 f 2at V 基-哌明:小基曱基)_；1，2-二氳-異喧琳-4-竣酸((S)-l-苯基-丙基)-醯胺 3-[4_(2-亂基-苯基)-旅胡^1- 1.43 581.7 582.7 2au 基曱基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 3-[4-(4-氯-苯基)-哌明M-基 1.54 591.2 591.3 2av 甲基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 3-((18,311,511)-3-羥基-8-氮雜- 0.88 521.7 522.7 I \ " 2aw 雙環[3.2.1]辛-8-基甲基)-1-側氧基-2-苯基-1,2-二氮-異喧琳 -4-羧酸((S)-l-苯基-丙基)-醯胺 3-(4-乙醯基-旅啡-1-基甲基)- 1.07 522.6 523.5 2ax 1_側氧基-2-苯基-1,2-二鼠-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 3-(4-甲基-[1，4]二氮雑環庚烷 0.89 508.7 509.2 -1-基曱基)-1-側氧基-2-苯基- 202 200906801 * 1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 2ay 3-(4-乙基-旅呼基曱基)-1-側氧基_2_苯基-1，2-二氫-異喹琳-4-魏酸((S)-l-苯基-丙基) 醯胺 0.89 508.7 509.2 2az r 3-((2S，6R)-2,6-二甲基·嗎福林-4-基曱基)-1-側氧基-2-苯基-1，2·二氮-異啥淋-4·緩酸 ((S)· 1 苯基-丙基)酿胺 1.21 509.6 510.2 2ba 3-[4-(2,4-二氟-苯基)-哌啡-1-基甲基]-1 -側氧i基-2-苯基_ 1，2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 1.48 592.7 593.6 2bb 3-[4-(3-二曱基胺基-丙基)-旅明基曱基]-1-側氧基-2-苯基-1，2-二氫-異喹啉_4_羧酸 ((S)-l·苯基-丙基)-酸胺 0.76 565.8 566.7 2bc .·；· - 3-(4-異丙基-娘明^1-基甲基)_ 1-側氧基-2-苯基-1，2-二鼠-異喧琳·4·魏酸((S)-1 _苯基-丙基)-醯胺 0.91 522.7 523.5 2bd 3-(3-氮雜-雙環[3.2.2]壬-3-基曱基)-1 -側氧基-2-苯基-1，2_ 二氫-異喹啉-4-羧酸(⑸小苯基-丙基)-醯胺 1.21 519.7 520.4 2be 3-(4-ί哀戍基·娘明^l·基曱基)_ 1-側氧基-2-苯基-1，2-二鼠_異 0.98 548.7 549.6 200906801 2bf 〇奎嚇· -4-竣酸((S)-1 -苯基-丙基)-醯胺 3-[1,4']聯哌啶-Γ-基曱基-1-側 0.86 562.8 563.2 2bg 氧基-2-苯基-1,2-二氮-異啥嚇· -4-羧酸((S)-1 -苯基-丙基)-醯胺 3-(3,4-二氫-1H-異喹啉-2-基 1.22 527.7 528.7 ί ' \, 2bh 甲基)-1 -側氧基-2-苯基-1，2_ 二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-感胺 3-[4-(2-二甲基胺基-乙基)-旅 0.74 551.7 552.5 2bi 啡-1-基甲基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸 ((S)-l-苯基-丙基)-醯胺 3-(4-羥基曱基-哌啶-1-基甲 0.86 509.6 510.3 2bj 基)-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸((S)-l-苯基 -丙基)-醯胺 1-側乳基-2-苯基-3-[4-(四鼠· 1.16 578.7 579.9 2bk 呋喃_2_羰基)-哌啡-1-基甲基]-1,2-二氫_異喹啉-4-羧酸 ((S)-l-苯基-丙基)-酿胺 3-(4-異丁基底啡-1-基曱基)- 0.98 536.7 537.4 2bl 1_側氧基-2-苯基-1,2-二鼠-異喧琳-<4-竣酸((S)-1 -苯基-丙基)-醯胺 3-[4_(2_甲氧基-乙基)-哌畊- 0.91 538.7 539.6 1-基甲基]-1-侧氧基-2-苯基- 204 200906801 1，2-二氮-異嗤琳-4-魏酸((S)-1-本基-丙基)-1盘胺 2bm 2bn f 2bo 2bp 2bq 2br 2bs 3-[4-(2-嗎福林-4-基-乙基)-旅啡-1-基甲基]-1-側氧基_2_苯基-1，2-二氫·異喹啉-4-羧酸 ((8)-1-苯基-丙基)-1盘胺 0.75 593.8 594.7 3-(1,3-二氳-異吲哚-2-基曱基)-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基 -丙基)-酿胺 1.16 513.6 514.8 3-[4-(1-甲基-哌啶-4-基)-哌啡-1-基曱基]-1-側氧基-2-苯基-1,2-二氫-異喧琳-4-叛酸 ((S)-l-苯基-丙基)-酸胺 0.72 577.8 578.5 1 -側氧基-2-苯基-3-[4-(2-哌啶 -1-基-乙基)-哌啡-1-基甲基]-1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 0.75 591.8 592.5 1-側氧基-2-苯基-3-[4-(2-α比洛 α定-1-基-乙基)-旅明^1-基甲基]-1,2-二鼠-異啥琳-4-叛酸 ((S)-l-苯基-丙基)-酿胺 0.74 577.8 578.4 3-(4-二甲基胺甲醯基甲基-哌啡-1-基曱基)-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸 ((S)-l-苯基-丙基)-醯胺 0.89 565.7 566.6 3-(八氳比啶并[1,2-a]吡啡-2-基曱基)-1-側氧基-2-苯基- 0.93 534.7 535.4 205 200906801 1,2-二氫-異喹啉-4-羧酸(⑸-1-苯基-丙基)-醯胺 2bt 3-(4-曱醯基-[1,4]二氮雑環庚烧-1-基甲基)-1-側氧基-2-苯基-1，2-二氳-異喹啉-4-羧酸 ((S)-l-苯基-丙基)-酿胺 0.94 522.6 523.6 2bu 3-[4-(4-氰基-苯基)-哌啡-1-基甲基]-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸((S)- 1.46 581.7 582.6 f 1-苯基-丙基)-酿胺 2bv 1-側氧基-2-苯基-3-(4-吡啶-4-基曱基-哌啡-1-基曱基)-1,2_ 二氮-異喧嚇>-4-叛酸((S)-l-苯基-丙基)-醯胺 0.77 571.7 572.4 2bw 1_側氧基-2-苯基-3-[4-(3-°比咯啶-1-基-丙基)-哌啡-1-基曱基]-1,2-二氫-異喹啉-4-羧酸 ((8)-1-苯基-丙基)-3&胺 0.75 591.8 592.6 , 2bx i 1-側氧基-2-苯基-3-(4-吡啶-2-基曱基-哌畊-1-基曱基)-u-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 0.93 571.7 572.5 2by 3-(4-乙磺醯基-哌啡-1-基曱基)-1 -側乳基-2-苯基-1，2-二氮-異喧琳-4-叛酸((S)-l-苯基 -丙基)-醯胺 1.38 572.7 573.7 2bz 3_(4_第二丁基-哌啡-1-基曱 0.96 536.7 537.4 基)-1-側氧基-2-苯基-1,2-二 206 200906801 風-異喧琳_4_叛酸((S)-l-苯基 -丙基)-醯胺 2ca 3-[4-(l-乙基-丙基)-0底明^1-基曱基]_ 1 -侧乳基-2-苯基_ 1，2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-酸胺 1.01 550.7 551.8 2cb f 3-[4-(2-氣基-乙基)-旅明：_1_ 基曱基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-S盘胺 0.9 533.7 534.4 2cc 3-(4-曱磺醯基-哌啡-1-基曱基)-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基 -丙基)-醯胺 1.31 558.7 559.2 2cd {1-[1-侧氧基-2-苯基-4-(1-苯基-丙基胺甲醯基)-1,2-二氫-異啥嚇-3-基曱基]-α底咬-4-基}-乙酸乙酯 1.12 565.7 566.7 i' 2ce 3-[4_(3_氟-苯基)-哌啡-1-基曱基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 1.48 574.7 575.5 2cf 1-側氧基-2-苯基-3-((S)-3-苯基-旅。定-1-基甲基)-1,2-二鼠_ 異喧嚇·_4-竣酸((S)-l-苯基-丙基)-醯胺 1.27 555.7 556.5 2cg 1 -側氧基-2-苯基-3 - [4-0匕咯 °定-1-幾基)-旅明^1-基甲基]- 1.11 577.7 578.6 207 200906801 1，2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 2ch 3-[4-(嗎福林-4-羰基)-哌啡-1-基甲基]-1-側氧基-2-苯基-1,2_二氳·異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 1.04 593.7 594.7 2d 3-(4-曱氧基-哌啶-1-基甲基)-1-側氧基_2-苯基-1，2-二氮-異啥♦ -4-竣酸((S)-1 -苯基-丙 0.98 509.6 510.2 f 基)-醯胺 2cj 3-(4'-羥基-3'，4',5',6'-四氫-2Ή-[3,4f]聯吼啶-Γ-基曱基)-l-側氧基-2-苯基-1,2-二氮-異喧嚇 -4-羧酸((S)-1 -苯基-丙基)-醯胺 0.71 572.7 573.8 2ck ι· 3-(4-羥基-3,4,5,6-四氫-2H-[4,4']聯吼啶-1-基甲基)-1-側氧基-2-苯基-1,2-二氮-異11 奎淋 -4-叛酸((S)-l-苯基-丙基)-酿胺 0.71 572.7 573.8 2d 3-(3H-螺[異苯并呋喃-1,4’-哌 α定]-I1-基甲基)-1-側氧基-2-苯基-1,2-二氮-異啥琳-4-竣.酸 ((S)-l-苯基-丙基)-醯胺 1.25 583.7 584.5 2cm 3-(4-經基-4-甲基-旅咬-1-基 0.91 509.6 510.1 曱基)-1 -側氧基-2·苯基-1，2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 208 200906801 2cn 3- (六氫-螺[苯并[1，3]二腭唑-2,4·-哌啶]-Γ-基曱基)-1-側氧基-2-苯基-1,2-二氮-異哇'琳_ 4- 竣酸((S)-1 -苯基-丙基)-酿胺 1.27 591.7 592.5 2co 1-側氧基-2-苯基-3-(3,4,5,6-四氫-2H-[4,4']聯吡啶-1-基甲基)-1,2-二氮-異啥嚇·_4-叛酸 ((S)-l-苯基-丙基)-酿胺 0.71 556.7 557.4 f 2cp 3-[4-(2-二甲基胺基-乙基>哌啶-1-基甲基H-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸 ((S)-l-苯基-丙基)-酿胺 0.68 550.7 551.4 2cq 3-(4-二曱基胺磺醯基-哌明：-1-基甲基)-1-側氣基-2-苯基_ 1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 1.43 587.7 588.3 2cr i 3- (1,1-二侧氧基-硫代嗎福林- 4- 基甲基)-l-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 1.29 529.7 530.3 2cs 1-側氧基-2-苯基-3-(2-吡啶-2-基甲基-哌啶-1-基甲基)-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-酿胺 1.05 570.7 571.6 2ct 3-(2-嗎福林-4-基曱基-旅〇定_ 1-基甲基)-1-側氧基-2-苯基-U-二氫-異喹啉-4-羧酸((S)- 1.08 578.8 579.8 209 200906801 2cu 2cv f 2cw 2cx 2cy 2cz 2da 1-苯基-丙基)-醯胺 3-(4-呋喃并[3,2-φ比啶-4-基-哌啡-1-基甲基)-1-側氧基_2_ 笨基-1,2-二氮-異喧琳-4-叛酸 ((S)-1 -笨基-丙基)-S篮胺 1.01 597.7 598.5 3-(4-環丙基甲基-哌啡-1-基曱基)-1 -側乳基-2-苯基-1，2_ 二氳-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 0.95 534.7 535.3 3-[4-(2-嗎福林-4-基-乙基)-旅啶-1-基曱基]-1-側氧基-2-苯基-1,2-二氮-異喧琳-4-竣酸 ((S)-l-苯基-丙基胺 0.69 592.8 593.5 1-側氧基-2-苯基-3-(4-嘧啶-2-基-[1，4]二氮雑環庚烷-1-基曱基)-1，2-二氮-異啥嚇>-4-叛酸 ((S)-l-苯基-丙基)-酿胺 1.05 572.7 573.5 3-(4-曱基-6,7-二氳-4H-噻吩并[3,2-小比啶-5-基甲基)-1-側氧基-2-苯基-1,2-二氯-異喧嚇 -4-羧酸((S)-l-苯基-丙基)-醯胺 1.23 547.7 548.5 3-[1,4]二氮雑環庚烷-1-基曱基-1-側氧jS_2-苯基-1,2-二氮 -異喧琳_4_竣酸((S)-1 -本基_ 丙基)-醯胺 0.89 494.6 495.7 3-((2S,5R)-2,5-二曱基-哌啡-1-基甲基>1-側氧基-2-苯基- 0.92 508.7 509.2 210 200906801 1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 2db 2dc f \ 2dd 2de f 2df2b 3-Methylaminoindenyloxy-2_phenyl-U2_dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine. 3-(indolyl-1-oxo-2-phenyl-i,2-dihydro-isoindole_4_hypoacid ((S)-l-n-propyl-propyl)-decylamine A mixture of 4.7 mg, 0.01 mmol) and methylamine (2 ml solution in 1 mL tetrahydrofuran, excess) was maintained at ambient temperature for 20 min and then evaporated in vacuo. The product was used in a biological test without further purification. LC-MS (m/z) 426.3 (MH+); The following 3-amino group was prepared similarly in the solvent tetrahydrofuran from the corresponding 3-bromo-indenyl derivative and the appropriate gamma or aromatic primary or secondary amine of 1.2-5 moles S at % ambient temperature. Methyl derivative. The reaction was monitored by LC-MS. 195 200906801 - In some cases, a longer reaction time is used or the reaction mixture is heated to 50 ° C and / or diisopropylethylamine (2 equivalents) is added as a base. After evaporation of the reaction mixture, the compound was of sufficient purity by analytical LC-MS; otherwise it was further purified by SCX column or by preparative LC-MS. List of compounds from Example 2 Chemical name tR(min) MW m/z (MH+) f 2c 3-ethylaminomethyl-1-o-oxy-2-045 439.6 440.6 Phenyl-1,2- Diazo-isoindolin-4-deoxy acid (method b) ((S)-l-phenyl-propyl)-guanamine 2d 3-cyclopropylaminomethyl-1-oxo-0.49 451.6 452.1 2-Phenyl-1,2-dimur-isoindole-4-repod (Method b) Acid ((S)-1 -Phenyl-propyl)-decylamine 2e 3-[(cyclopropyl A) -Amino)-indenyl]-0.51 465.6 466.4 1-Phenoxy-2-phenyl-1,2-dihydro-iso (Method b) Quinoline-4-carboxylic acid ((S)-l- Phenyl-propyl)-nonylamine 2f 3-(3,6-dihydro-2H-pyridin-1-ylindole 0.99 yl)-1 -yllacyl-2-phenyl-1,2-dihydro- Isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 477.6 478.1 2g 3-[4-(2-methoxy-phenyl)-piped-1.14 1-yl Mercapto]-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 586.7 587.5 2h 3 -[4-(4-Fluoro-phenyl)-piperidin-1-yl 1.35 574.7 575.6 196 200906801 2i Methyl]-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline 4-carboxylic acid ((S)-l-phenyl-propyl)-bristamine 3-(4-methylindolyl-piperidin-1-ylmethyl)- 1.12 508.6 509.3 2j 1_Sidelacyl-2-phenyl-1,2-diphos-iso-π-quine-4-indole ((S)-1 -phenyl-propyl)-decylamine 4-[ 1 -Sideoxy-2-phenyl-4-(1-phenyl1.33 552.7 553.7 r 2k-propylaminecarbamimidyl)-1,2-dihydro-isoquinolin-3-ylmethyl]-peri Ethyl-1-carboxylic acid ethyl ester 3-(4-methyl-piperidin-1-ylmethyl)-1-0.87 494.6 495.7 21 oxo-2-phenyl-1,2-di-iso-iso-lin -4-decanoic acid ((S)-l-phenyl-propyl)_ decylamine 1_ oxo-2-phenyl-3-(l,3,4,9- 1.27 566.7 567.7 # ' 2m tetranitrogen _β_叶淋_2-ylindenyl)-l,2_diaza-isoindole-4-oxo acid ((S)-l-phenyl-propyl)-S basket amine 1-sideoxy- 2-phenyl-3-piperidin-1-0.86 480.6 481.2 2n decyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)- Amine 3-(3-methyl-piperidin-1-ylindenyl)-1- 0.88 494.6 495.7 2o oxo-2-phenyl-1,2-dichloro-isowa scare_4-decanoic acid ( (S)-l-phenyl-propyl)- decyl 3-(3,5-dimethyl-piperidin-1-ylmethyl 0.9 508.7 509.3 base)-1-nonoxy-2-phenyl- 1,2-二200906801 Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2p 3-(4-benzoinyl-indenyl-1-ylindenyl )-1 - side lactyl · 2 · phenyl 1,2-diaza-isoindole-4-indic acid ((S)-1 -phenyl-propyl)-decylamine 1.02 570.7 571.5 2q 1 - oxo-3-[4-(2· side Oxy-2. Ding-1 -yl-ethyl)-Niangming:-1 -ylindenyl]-2-phenyl-1,2-diqi-isoindolin-4-indole ((S)-l-phenyl -propyl) decylamine 0.92 591.8 592.4 2r 3-ofoline-4-ylmercapto-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid (( S)-l-phenyl-propyl)-decylamine 1.08 481.6 482.2 2s 3-(2,6-dimethyl-norfosin-4-ylmethyl) small pendant oxy-2-phenyl-1 ,2-diaza-isoindolin-4-deoxalate ((S)-l-phenyl-propyl)-decylamine 1.21 509.6 510.2 ( 2t 1-sided oxy-2-phenyl-3-thio福福林-4- mercapto-1,2-di-oxo-isoindolin-4-carboxylic acid ((S) small phenyl-propyl)-decylamine 1.22 497.7 498.8 2u 3-(1,4- Dioxa-8-aza-spiro[4_5]non-8-ylindenyl)-l-oxy-2-phenyl-1,2-dichloro-isoindolin-4-weilic acid (( S)-l-phenyl-propyl)-acid amine 1.01 537.7 538.4 2v 1-sided lactyl-2-phenyl-3-brid. 1-1-yl 1 479.6 480.3 methyl-1,2-dihydro -isoquinoline-4-carboxylic acid 200906801 ((s)-i-phenyl-propyl)-nonylamine 2w 3-(2-mercapto-piperidin-1-ylindenyl)-1-yloxy _2-phenyl-1,2-diaza-isoindolin-4-indole ((S)-l-phenyl-propyl)_decylamine 1.07 493.6 494.4 2x 3-(2,6-dioxin Base-piperidin-1- Methyl)-1 -p-oxy-2-phenyl-1,2-diaza-isoindole>^wood-4-teric acid ((S)-l-phenyl-propyl)-bristamine 1.09 507.7 508.4 2y 3-(2-hydroxyindolyl-piperidin-1-ylmethyl) small pendant oxy-2-phenyl-1,2-diaza-isoindole _4_decanoic acid ((S) -l-phenyl-propyl)-decylamine 0.93 509.6 510.3 2z 1 -[ 1 -Sideoxy-2-phenyl-4-( 1 -phenyl-propylamine)--1,2- Ethyl diazo-isoquinolin-3-ylindenyl]-piperidine-3-carboxylate 1.14 551.7 552.4 2aa 3-(3-methyl-piperidin-1-ylmethyl)-1-yloxy -2-phenyl-1,2-dihydro-isoquine >-4-weilic acid ((S)-l-phenyl-propyl)* decylamine 1.09 493.6 494.5 2ab 3-(4-hydroxy- Piperidin-1-ylmethyl)-1-oxo-2-phenyl-1,2-diphos-isoindoline-4-carboxylic acid ((S)-l-phenyl-propyl)- Indoleamine 0.83 495.6 496.5 2ac 1_Sideoxy-2-phenyl-3-(4-phenyl- 1.27 555.7 556.5 succinyl-1-ylindenyl)-l,2-di-gas-iso-stimulus- 4-acid ((S)-1 -phenyl-propene 199 200906801 base)-decylamine 2ad 1-[1-flavoryl-2-phenyl-4-(1-phenyl-propylaminecarboxamidine) 1,1,2-diindole-isoindole-3-ylmethyl]-α-end D-decaline acid ethyl ester 1.11 551.7 552.5 2ae 3-(4-methyl-piperidin-1-yl ))-1-Lactyl-2-phenyl-1,2-diaza-isoindole _4-decanoic acid ((S)-l-phenyl-propyl)-acid amine 1.1 493.6 494.6 2af 1 - oxo-2-phenyl-3-(4-° ratio 1,4-butyl-tumamine-1-ylmethyl)-1,2-digas _ isosalin-4-decanoic acid ( (S)-l-phenyl-propyl)-nonylamine 0.97 557.7 558.4 2ag 3-(octanitrogen-staining 1-ylmethyl)-1-oxo-2-phenyl-1,2-diazo -isoindolin-4-decanoic acid ((S)-l-phenyl-propyl)-nitramine 1.18 533.7 534.4 2ah 3-azepidineheptan-1-ylindenyl-1-flavoryl-2 -Phenyl-1,2-diaza-iso-s-trione-4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 1.08 493.6 494.6 2ai 3-(3-hydroxy-piperidine-1 -ylmethyl)-1-oxo-2-phenyl-1,2-di-oxo-isoindole-4-decanoic acid ((S)-l-phenyl-propyl)·* decylamine 0.88 495.6 496.5 2aj 3-[4-(2,4-Dimercapto-phenyl)-piperidin- 1.45 584.8 585.5 1_ylmethyl]-I-sideoxy·2-phenyl-1,2-di Hydrogen-isoquinoline carboxylic acid ((8)-200 200906801 1-phenyl-propyl)-guanamine 2ak 3-[4-(3,4-dimethyl-phenyl)-piperidin-1-yl 1-yloxy-2-phenyl- 1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-bristamine 1.29 584.8 585.6 2al 3 -(4-dimethylamino-peline -1-ylmethyl)-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.81 522.7 523.5 2am 3-[4-(2,5-Dimethyl-phenyl)-piped-1-ylmethyl]-1-oxo-2-phenyl-1,2-dihydro- Isoquinoline-4-carboxylic acid ((S)-1-n-propyl-propyl)-acid amine 1.47 584.8 585.6 2an 3-[4_(2-fluoro-phenyl)-piperidin-1-ylmethyl] -1 - flavonyl-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 1.42 574.7 575.4 2ao 3_[4_( 3_decyloxy-phenyl)_piperidin-1-ylmethyl]-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S) -1-phenyl-propyl)-acid amine 1.32 586.7 587.3 2ap 1-sided oxy-2-phenyl-3-(4-m-phenylene phenyl [well-1-ylmethyl)-i,2- Dichloro-isoindolin-4-decanoic acid ((S)-l-phenyl-propyl)-decylamine 1.33 570.7 571.7 2aq 3-[4_(4·methoxy-phenyl)-piped- 1.11 586.7 587.6 1-Ginyl]-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-201 200906801 2ar 1-phenyl-propyl - indoleamine l-sideoxy-3_(4-phenethyl-peipamine 1.09 584.8 585.5 2as 1-ylindenyl)-2-phenyl-1,2-dili^isoindole-4-竣Acid ((S)-l-phenyl-propyl - 醯卜侧侧 - - - 苯基 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1.琳-4-decanoic acid ((S)-l-phenyl-propyl)-decylamine 3-[4_(2-ranyl-phenyl)-Brigade ^1 1.43 581.7 582.7 2au thiol]- 1-Phenoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 3-[4-(4- Chloro-phenyl)-pepirin M-group 1.54 591.2 591.3 2av methyl]-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)- L-phenyl-propyl)-nonylamine 3-((18,311,511)-3-hydroxy-8-aza-0.88 521.7 522.7 I \ " 2aw bicyclo[3.2.1]oct-8-ylmethyl)- 1-Phenoxy-2-phenyl-1,2-diaza-isoindolin-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 3-(4-ethyl fluorenyl) -Norphine-1-ylmethyl)- 1.07 522.6 523.5 2ax 1_Sideoxy-2-phenyl-1,2-dimur-isoquinoline-4-carboxylic acid ((S)-l-phenyl -propyl)-decylamine 3-(4-methyl-[1,4]diazepineecycloheptane 0.89 508.7 509.2 -1-ylindenyl)-1-yloxy-2-phenyl- 202 200906801 * 1,2-Dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 2ay 3-(4-ethyl-beckoyl)-1- Sideoxy_2_phenyl-1,2- Hydrogen-isoquinoline-4-weilic acid ((S)-l-phenyl-propyl) decylamine 0.89 508.7 509.2 2az r 3-((2S,6R)-2,6-dimethyl·forfolin 4--4-mercapto)-1-oxooxy-2-phenyl-1,2.diazepine-isoindole-4-sodium acid ((S)·1 phenyl-propyl)-bristamine 1.21 509.6 510.2 2ba 3-[4-(2,4-Difluoro-phenyl)-piperidin-1-ylmethyl]-1 -oxyxyl-2-yl-1,2-dihydro-isoquine Porphyrin-4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 1.48 592.7 593.6 2bb 3-[4-(3-Didecylamino-propyl)-blindyl fluorenyl]- 1-Phenoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l·phenyl-propyl)-acid amine 0.76 565.8 566.7 2bc .·; - 3-(4-Isopropyl-Numamine-1-ylmethyl)_ 1-oxo-2-phenyl-1,2-dimur-isoindolin·4·Wereic acid ((S) -1 _phenyl-propyl)-nonylamine 0.91 522.7 523.5 2bd 3-(3-Aza-bicyclo[3.2.2]indol-3-ylindenyl)-1 -p-oxy-2-phenyl- 1,2_Dihydro-isoquinoline-4-carboxylic acid ((5) small phenyl-propyl)-decylamine 1.21 519.7 520.4 2be 3-(4-ί戍戍基·娘明^l·基曱基)_ 1-Sideoxy-2-phenyl-1,2-di-mouse-iso-0.98 548.7 549.6 200906801 2bf 〇奎吓·-4- decanoic acid ((S)-1 -phenyl-propane )-decylamine 3-[1,4']bipiperidin-fluorenyl-mercapto-1-one side 0.86 562.8 563.2 2bg oxy-2-phenyl-1,2-diaza-isoindole -4 -carboxylic acid ((S)-1 -phenyl-propyl)-decylamine 3-(3,4-dihydro-1H-isoquinolin-2-yl1.22 527.7 528.7 ί ' \, 2bh methyl)- 1-Sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-sensitive amine 3-[4-(2-di Methylamino-ethyl)-Break 0.74 551.7 552.5 2bi phenyl-1-ylmethyl]-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ( (S)-l-Phenyl-propyl)-nonylamine 3-(4-hydroxyindolyl-piperidin-1-ylmethyl 0.86 509.6 510.3 2bj-yl)-1-oxo-2-phenyl-1 ,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 1-flavoryl-2-phenyl-3-[4-(four mice 1.16 578.7 579.9 2bk furan_2-carbonyl)-piperidin-1-ylmethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)- Amine 3-(4-isobutyl phenylephthyl-1-ylindenyl)-0.98 536.7 537.4 2bl 1_Sideoxy-2-phenyl-1,2-di-oxo-isoindole-<4-竣Acid ((S)-1 -phenyl-propyl)-nonylamine 3-[4_(2-methoxy-ethyl)-piped-0.91 538.7 539.6 1-ylmethyl]-1-yloxy -2-phenyl- 204 200906 801 1,2-diaza-isoindolin-4-weilic acid ((S)-1-benyl-propyl)-1-paneamine 2bm 2bn f 2bo 2bp 2bq 2br 2bs 3-[4-(2-? Forint-4-yl-ethyl)-branoid-1-ylmethyl]-1-yloxy-2-phenyl-1,2-dihydroisoquinoline-4-carboxylic acid (8 )-1-phenyl-propyl)-1-padamine 0.75 593.8 594.7 3-(1,3-dioxin-isoindol-2-ylindenyl)-1-oxo-2-phenyl-1 ,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-bristamine 1.16 513.6 514.8 3-[4-(1-methyl-piperidin-4-yl )-piperidin-1-ylindenyl]-1-oxo-2-phenyl-1,2-dihydro-isoindolin-4-deoxalate ((S)-l-phenyl-propyl )-acid amine 0.72 577.8 578.5 1 -Sideoxy-2-phenyl-3-[4-(2-piperidin-1-yl-ethyl)-piperidin-1-ylmethyl]-1,2 -Dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 0.75 591.8 592.5 1-Sideoxy-2-phenyl-3-[4-(2-比比洛α定-1-yl-ethyl)-Belling^1-ylmethyl]-1,2-dimur-isoindolin-4-deoxy acid ((S)-l-phenyl-prop Base)-Tainamine 0.74 577.8 578.4 3-(4-Dimethylaminocarbamimidomethyl-piperidin-1-ylindenyl)-1-yloxy-2-phenyl-1,2-dihydro -isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.89 565.7 566.6 3-( Indolepyrido[1,2-a]pyridin-2-ylindenyl)-1-oxo-2-phenyl-0.93 534.7 535.4 205 200906801 1,2-Dihydro-isoquinoline-4- Carboxylic acid ((5)-1-phenyl-propyl)-nonylamine 2bt 3-(4-mercapto-[1,4]diazepinecycloheptan-1-ylmethyl)-1-yloxy -2-phenyl-1,2-dioxa-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-bristamine 0.94 522.6 523.6 2bu 3-[4-(4-cyanide -Phenyl)-piperidin-1-ylmethyl]-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)- 1.46 581.7 582.6 f 1-phenyl-propyl)-bristamine 2bv 1-sided oxy-2-phenyl-3-(4-pyridin-4-ylindenyl-piperidin-1-ylindenyl)-1,2_ Diazo-isoindole >-4-reaction acid ((S)-l-phenyl-propyl)-decylamine 0.77 571.7 572.4 2bw 1_sideoxy-2-phenyl-3-[4-( 3-°pyrrolidin-1-yl-propyl)-piperidin-1-ylmercapto]-1,2-dihydro-isoquinoline-4-carboxylic acid ((8)-1-phenyl- Propyl)-3&amine 0.75 591.8 592.6 , 2bx i 1-sided oxy-2-phenyl-3-(4-pyridin-2-ylindenyl-piped-1-ylindenyl)-u-di Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.93 571.7 572.5 2by 3-(4-ethanesulfonyl-piperidin-1-ylindenyl)- 1 - flavonyl-2-phenyl-1,2-di -isoterein-4-deoxy acid ((S)-l-phenyl-propyl)-decylamine 1.38 572.7 573.7 2bz 3_(4_t-butyl-piperidin-1-ylindole 0.96 536.7 537.4 base) -1-Sideoxy-2-phenyl-1,2-di 206 200906801 Wind-isoteryline_4_Resin ((S)-l-phenyl-propyl)-guanamine 2ca 3-[4 -(l-ethyl-propyl)-0 succinyl-1-ylindenyl]_ 1 -salyl-2-phenyl-1,dihydro-isoquinoline-4-carboxylic acid (( S)-1-phenyl-propyl)-acid amine 1.01 550.7 551.8 2cb f 3-[4-(2-Alkyl-ethyl)-Belling:_1_ylmercapto]-1-lateraloxy-2 -phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-S-padamine 0.9 533.7 534.4 2cc 3-(4-oxasulfonyl- Piperidin-1-ylindenyl)-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)- Indoleamine 1.31 558.7 559.2 2cd {1-[1-Sideoxy-2-phenyl-4-(1-phenyl-propylaminemethanyl)-1,2-dihydro-isoindole-3-曱基基--α bottom bit-4-yl}-ethyl acetate 1.12 565.7 566.7 i' 2ce 3-[4_(3_fluoro-phenyl)-piperidin-1-ylindenyl]-1-side oxygen Benzyl-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 1.48 574.7 575.5 2cf 1-sideoxy-2- Phenyl-3-((S)-3-phenyl- trip. Ding-1-ylmethyl)-1,2-di-mouse _isostimulated _4-decanoic acid ((S)-l-phenyl-propyl)-decylamine 1.27 555.7 556.5 2cg 1 -sideoxy- 2-phenyl-3 - [4-0 匕 ° -1- -1- yl) - 旅明 ^ 1- yl methyl] - 1.11 577.7 578.6 207 200906801 1,2-dihydro-isoquinoline -4- Carboxylic acid ((S)-1-phenyl-propyl)-nonylamine 2ch 3-[4-(norfosin-4-carbonyl)-piperidin-1-ylmethyl]-1-yloxy- 2-phenyl-1,2-diindole-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 1.04 593.7 594.7 2d 3-(4-decyloxy-peripipeline Pyridin-1-ylmethyl)-1-oxooxy-2-phenyl-1,2-diaza-isoindole -4-pyruic acid ((S)-1 -phenyl-propanoid 0.98 509.6 510.2 f -) guanamine 2cj 3-(4'-hydroxy-3',4',5',6'-tetrahydro-2Ή-[3,4f]biacridine-fluorenyl-fluorenyl)-l-side Oxy-2-phenyl-1,2-diaza-isoindole-4-carboxylic acid ((S)-1 -phenyl-propyl)-decylamine 0.71 572.7 573.8 2ck ι· 3-(4- Hydroxy-3,4,5,6-tetrahydro-2H-[4,4']biazin-1-ylmethyl)-1-yloxy-2-phenyl-1,2-diaza- Iso 11 quinolate-4-repulsive acid ((S)-l-phenyl-propyl)-nitramine 0.71 572.7 573.8 2d 3-(3H-spiro[isobenzofuran-1,4'-piperidin] -I1-ylmethyl)-1-yloxy-2-phenyl-1,2-diaza-啥琳-4-竣.Acid ((S)-l-phenyl-propyl)-decylamine 1.25 583.7 584.5 2cm 3-(4-Pyano-4-methyl-Bigbit-1-one 0.91 509.6 510.1 Mercapto)-1 -yloxy-2·phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 208 200906801 2cn 3 - (hexahydro-spiro[benzo[1,3]dioxazole-2,4·-piperidinyl]-fluorenyl)-l-oxy-2-phenyl-1,2-di Nitrogen-isow'lin_ 4- decanoic acid ((S)-1 -phenyl-propyl)-bristamine 1.27 591.7 592.5 2co 1-sided oxy-2-phenyl-3-(3,4,5 ,6-tetrahydro-2H-[4,4']bipyridin-1-ylmethyl)-1,2-diaza-isoindole _4-rebel ((S)-l-phenyl-prop Base)-Tainamine 0.71 556.7 557.4 f 2cp 3-[4-(2-Dimethylamino-ethyl)piperidin-1-ylmethyl H-sideoxy-2-phenyl-1,2 -Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nitramine 0.68 550.7 551.4 2cq 3-(4-didecylamine sulfonyl-pemamine: -1 -ylmethyl)-1-ylidene-2-phenyl-1,dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 1.43 587.7 588.3 2cr i 3-(1,1-di-oxy-thio-rhofolin-4-ylmethyl)-l-oxo-2-phenyl-1,2-dihydro-isoquinoline- 4-carboxylic acid ((S)-1-phenyl-propyl)-fluorene 1.29 529.7 530.3 2cs 1-Sideoxy-2-phenyl-3-(2-pyridin-2-ylmethyl-piperidin-1-ylmethyl)-1,2-dihydro-isoquinoline-4 -carboxylic acid ((S)-l-phenyl-propyl)-bristamine 1.05 570.7 571.6 2ct 3-(2-ofofolin-4-ylindenyl- lycopene-1-ylmethyl)-1 -Phenoxy-2-phenyl-U-dihydro-isoquinoline-4-carboxylic acid ((S)-1.08 578.8 579.8 209 200906801 2cu 2cv f 2cw 2cx 2cy 2cz 2da 1-phenyl-propyl)- Indole 3-(4-furo[3,2-φ-pyridin-4-yl-piperidin-1-ylmethyl)-1-yloxy-2_ phenyl-1,2-diaza-iso喧琳-4-Repulsive acid ((S)-1 - strepyl-propyl)-S basket amine 1.01 597.7 598.5 3-(4-cyclopropylmethyl-piperidin-1-ylindenyl)-1 - Lacto-2-phenyl-1,2-diindole-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.95 534.7 535.3 3-[4-(2-福福林-4-yl-ethyl)-brazidin-1-ylindenyl]-1-yloxy-2-phenyl-1,2-diaza-isoindolin-4-indole (( S)-l-phenyl-propylamine 0.69 592.8 593.5 1-Sideoxy-2-phenyl-3-(4-pyrimidin-2-yl-[1,4]diazepinee-heptane-1-曱 ))-1,2-diaza-isointimidation>-4-reaction acid ((S)-l-phenyl-propyl)-bristamine 1.05 572.7 573.5 3-(4-mercapto-6 ,7-diindole-4H-thiazide And [3,2-micropyridin-5-ylmethyl)-1-oxo-2-phenyl-1,2-dichloro-isoindole-4-carboxylic acid ((S)-l- Phenyl-propyl)-nonylamine 1.23 547.7 548.5 3-[1,4]diazepineheptan-1-ylindenyl-1-oxo-xS_2-phenyl-1,2-diaza-isoindole Lin_4_capric acid ((S)-1 -benyl-propyl)-decylamine 0.89 494.6 495.7 3-((2S,5R)-2,5-dimercapto-piperidin-1-ylmethyl > 1-Sideoxy-2-phenyl-0.92 508.7 509.2 210 200906801 1,2-Dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 2db 2dc f \ 2dd 2de f 2df

K 2dg 2dh 3-((S)-3-甲基-哌啡-1-基甲基)-1 ·側乳基-2-苯基-1，2·二氮-異啥琳冰魏酸((S)-l-苯基 -丙基)-驢胺 0.88 494.6 495.7 3-((R)-3-甲基-哌啡-1·基曱基)-1 -側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸(⑸小苯基 -丙基)-驢胺 0.88 494.6 495.7 3-[3·(3_氯-苯基)-哌啡小基甲基]-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸(⑶小苯基-丙基)-酿胺 1.11 591.2 591.4 3-[4-(1Η-吲哚-4-基)哌明Μ-基甲基]-1-側氧基-2-苯基_ 1，2-二氫-異喹啉冰羧酸((S)-1_苯基-丙基)-醯胺 1.1 595.7 596.6 1-側氧基冬(3-側氧基-哌啡-1-基甲基)-2-苯基·1，2-二鼠_ 異喧琳-4-魏酸((S)-l-苯基-丙基酸胺 1.09 494.6 495.7 3-[4·(1Η-吲哚 _5_ 基)-哌明M-基甲基]-1 -側氧基-2-苯基_ 1，2-二氮-異喧淋-4-幾酸((8)_ 1-苯基-丙基)-醯胺 1.04 595.7 596.7 3-(6,9-二氮雜-螺[4.5]癸-9-基甲基)_ 1 -側氧基-2-苯基-1，2- 0.97 534.7 535.3 211 200906801 二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 2dm V.. 2di 2dj 2dk 2dl 2dn 2do 3-(1,4-二氮雜-螺[5.5]十一-4-基甲基)-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-酸胺 1.01 548.7 549.7 3-(3-異丙基-哌明基甲基)-1-側氧1基-2-苯基-1,2-二氮-異口查嚇· -4-竣酸((S)-l-苯基-丙基)-醯胺 0.96 522.7 523.5 3-(3,3-二甲基-哌啡-1-基甲基)-1-側氧基-2-苯基-1,2-二虱-異啥琳_4_缓酸((S)-l-苯基 -丙基)-醯胺 0.9 508.7 509.2 3-[3-(4-氟-苯基)-哌啡-1-基甲基]-1-側氧基-2-苯基-1,2-二氫-異喹啉斗羧酸((S)-l-苯基-丙基)-醯胺 1.05 574.7 575.4 1-側氧基-2-苯基-3-(3-對甲苯基-哌啡-1-基甲基)-1，2_二氳-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 1.08 570.7 571.7 4- [ 1 -側氧基-2-苯基-4-( 1 -苯基 -丙基胺曱酿基)-1,2-二氣-異喹啉-3-基曱基]-哌啡-1-羧酸第三丁酯 1.49 580.7 581.9 3-(4-曱基胺甲醯基甲基-哌明^1-基曱基)-1-側乳基-2-苯 0.86 551.7 552.9 212 200906801 基-1，2-二氫-異喹啉-4-羧酸 ((8)-1-苯基-丙基)-隨胺 2dp 8-氯-3-二曱基胺基甲基-1-侧氧基-2-苯基-1，2-二氮-異喧琳 -4-羧酸((S)-1 -苯基-丙基)-醯胺 0.95 474.0 474.6 2dr 3-¾戊基胺基甲基-1-側氧基-2-苯基-1,2-二鼠-異啥琳-4-竣酸((S)-l-苯基-丙基)-醯胺 1.03 479.6 480.4 2ds 3-¾己基胺基曱基-1-側氧基_ 2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-1 -苯基-丙基)-醯胺 1.1 493.6 494.4 2dt 3_{[(2-經基-乙基)-曱基-胺基]-甲基}_1_側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 0.84 469.6 470.6 2du 3-咪唑-1-基曱基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸 ((S)-l-苯基-丙基)-釀胺 0.86 462.6 463.4 2dv 3-(2-曱基-咪唑-1-基甲基)-1-倒乳基-2-苯基-1,2-二氮-異唾琳-4-竣酸((S)-l-苯基-丙基)_ 醯胺 0.88 476.6 477.3 2dw 3-(4-曱基-咪唑-1-基曱基)-1-側氧基-2-苯基-1,2-二氫-異喹琳-4-竣酸((S)-l-苯基丙基)_ 醯胺 0.89 476.6 477.3 2dx 3-(2,5-二風比洛-1-基甲基)- 0.92 463.6 464.5 213 200906801 I-側乳基·2-苯基-1，2-二氮-異 σ奎嚇· -4·竣酸((S)-1 -苯基-丙基)-醯胺 2dy 3-(2,5-二甲基-2,5-二氫-吡咯-l-基曱基)-M則氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸(⑸-1-苯基-丙基)-醯胺 1.06 491.6 492.4 2dz 1 -側乳基-2-苯基-3 -α比略^定-1 基甲基-1，2-二氮-異喧琳-4-緩酸((S)-l-笨基-丙基)-酸胺 0.92 465.6 466.3 2ea 1-側氧基-2-苯基-3 -(嗟°坐-2-基胺基曱基)-1，2-二氯-異啥琳-4-竣酸((S)-l-苯基丙基)_ 酸胺 0.88 494.6 495.6 2eb I-側乳基-2-苯基-3-(^^-4-基胺基曱基)-1，2-二鼠-異喧啉-4-羧酸((S)-l-苯基-丙基)- 醯胺 0.85 489.6 490.4 2ec 3-(弟二丁基胺基-甲基)-1-側氧基-2-苯基·1，2-二氮-異啥琳 -4-羧酸((S)-l·苯基-丙基)-醯胺 1 467.6 468.7 2ed 3-[(2-說基-1，1_二甲基-乙基胺基)_甲基]-1-側氧基-2-苯基 -1，2-二氫-異喹啉-4-羧酸((S)· 1-苯基-丙基)-醯胺 0.91 483.6 484.3 2ee 3-(異丙基胺基-甲基)小側氧基-2-苯基-1，2-二氯-異啥嚇*- 0.93 453.6 454.3 214 200906801 4-羧酸((S)-l-苯基-丙基)-醯胺 2ef 3-[(2-輕基-1-曱基-乙基胺基)-甲基]-1 -側氧基-2-苯基-1，2-二氮-異喧淋-4-竣酸((S)-l-苯基-丙基)-醯胺 0.86 469.6 470.5 2eg 3-[(1-每基甲基-丙基胺基)-曱基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基 -丙基：)-醯胺 0.92 483.6 484.4 2eh 3-[(2,2-二曱基-丙基胺基)-曱基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基 -丙基> 醯胺 1.13 481.6 482.2 2ei 1 -側氧基-2-苯基-3-丙-2-炔基胺基甲基-1,2-二氮-異啥琳-4_ 羧酸((S)-l-苯基-丙基)-醯胺 0.95 449.6 450.2 2ej 3-細丙基胺基甲基-1-側乳基_ 2-苯基-1，2-二氮-異哇嚇>-4-叛酸((S)-l-苯基-丙基)-醯胺 0.94 451.6 452.4 2ek 3-[(甲基-丙-2-炔基-胺基)-甲基]-1 -側乳基-2-苯基-1,2-二鼠_異啥琳-4-叛酸((S)-l-苯基 -丙基)-醯胺 1.22 463.6 464.5 2el 3-二烯丙基胺基曱基-1-側氧 1.19 491.6 492.4 基-2-苯基-1，2-二氮-異喧淋-4-羧酸((S)-l-苯基-丙基)-醯胺 215 200906801 2em 3-二乙基胺基甲基-1-側氧基-2-苯基-1，2-二鼠·異喧琳-4-繞酸((S)-l-苯基-丙基)-醯胺 0.98 467.6 468.5 2en 3-[(異丙基-甲基-胺基)-甲基]_ 1_側乳基苯基-1，2-二氮-異喹啉-4-羧酸((S)小苯基·丙基)-醯胺 0.96 467.6 468.7 2eo [(⑻基-1·曱基·乙基胺基)-甲基]_1·侧乳基-2-苯基_ 0.86 469.6 470.5 f \ 1 >二氫-異喹啉-4-羧酸(⑶-1-苯基-丙基)-酸胺 2ep 3-[((R)-2-經基-1-曱基-乙基胺基)-甲基]-1-側氧基-2-苯基_ 1，2-二氫-異喧琳-4_魏酸((8)-1-苯基_丙基)-醯胺 0.87 469.6 470.5 2eq c 3-{[(2-甲氧基-乙基)-甲基-月安基]-曱基}'-1-側乳基-2-苯基_ I，2-二氫-異喹啉-4-羧酸((S)-1 -苯基-丙基)-酸胺 0.96 483.6 484.4 \ 2er 3-((R)-3-羥基-吼咯啶-1-基甲基)-1 -側氧基-2·苯基-1，2-二氮-異喧你-4-缓酸((S)-l-苯基 -丙基)-醯胺 0.85 481.6 482.3 2es 3-((S)-3-羥基-吼咯啶-1-基甲基)-1·側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸((S)-l-苯基 -丙基)-醯胺 0.84 481.6 482.3 2et 3-[(環戊基-甲基-胺基)-甲基]- 1.09 493.6 494.5 216 200906801 1-側乳基-2-苯基-1，2-二鼠-異喧淋·4-竣酸((S)_l -苯基-丙基)-醯胺 2eu 3-{[(2-羥基-1-甲基-乙基)-甲基-胺基]-甲基}-l-側乳基-2_ 苯基-1，2-二氮-異啥嚇*-4-竣酸 ((S)-l-苯基-丙基)-醯胺 0.89 483.6 484.4 2ev [乙基-(2-輕基-乙基)-胺基]-甲基}-1-側氧基-2·苯基_ 0.89 483.6 484.4 / 1，2-二氫-異喹啉-4-羧酸(⑸-1-苯基-丙基)-酿胺 2ew 3-[(乙基-曱基-胺基)-曱基]-1_ 側氧基-2-苯基-1，2-二氫-異喹嚇^-4-叛酸((S)-l-苯基-丙基)_ 醯胺 0.92 453.6 454.4 lex 3-¾ 丁基胺基甲基-1-側氧基_ 2-苯基-1，2-二氫·異喹啉-4-羧酸((S)-l-苯基-丙基)·醯胺 0.98 465.6 466.4 , 2ey \ 3- 四氫吖唉-1-基曱基-1-側氧基-2-苯基-1，2-二氮-異喧淋 4- 叛酸((S)-l-苯基·丙基)-酿胺 0.86 451.6 452.3 2ez \(4-第三丁基-哌明基甲基)-1-側氧基-2-苯基-1，2-二氮-異喧琳-4-竣酸((S)-l_苯基 -丙基)-醯胺 0.91 536.7 537.3 2fa 3_[4·(2_ ||望基-乙基) σ底-1- 0.86 524.7 525.6 基甲基]側氧基-2-苯基- 217 200906801 * 1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-酿胺 2fb 3- {4-[2-(2-|^ι 基-乙氧基)-乙基]-哌明M-基甲基}-1-侧氧基-2-苯基-1,2-二星1 -異喧嚇 _ 4- 羧酸((S)-l-苯基-丙基)-醯胺 0.86 568.7 569.6 2fc f % 3- [4-(3-氯-5-三氟甲基比啶-2-基)-»底啡-1-基曱基]-1-側氧基-2-苯基-1,2-二風-異哇'琳_ 4- 羧酸((S)-l-苯基-丙基)-醯胺 1.77 660.1 660.8 lid 3-[4-(3,5-二氯-吡啶-4-基)-哌啡-1-基甲基]-1-側氧基-2_苯基-1,2-二氮-異啥琳-4-叛酸 ((S)-l-苯基-丙基)-酿胺 1.45 626.6 626.5 2fe r i 4-[1-側氧基-2-苯基-4-((S)-l-苯基-丙基胺甲酿基)-1，2-二氫-異喹啉-3-基甲基]-哌啡-1-羧酸苯甲酯 1.57 614.7 615.4 2ff 3-[4-(3-嗎福林-4-基-丙基)-旅畊-1-基甲基]-1-側氧基-2-苯基-1,2-二氮-異σ奎琳-4-叛酸 ((S)-l-苯基-丙基)-醯胺 0.74 607.8 609.0 2fg 1-側氧基-2-苯基-3-[4-(3-哌啶 -1-基-丙基)-旅0^-1-基甲基]-1，2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-臨胺 0.76 605.8 607.1 200906801 ：2fh 3_[4_(4,6-二甲氧基-嘧啶-2-基曱基)-哌啡-1-基甲基]-1-侧氧基-2-苯基-1,2-二氯-異喧琳 -4-羧酸((S)-l-苯基-丙基)-醯胺 1.05 632.8 633.9 2fi 3-[4-(3-羥基-丙基)-哌明M-基甲基]-1 •側氣基-2-苯基_ 1,2-二氫-異喹啉-4-羧酸(⑶-1-苯基-丙基)-3盛胺 0.86 538.7 539.4 r 2fj 3-[4-(2,3-二羥基-丙基)-哌啡-1-基甲基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 0.84 554.7 555.7 2fk (2-側氧基-2- {4- [ 1 -側氧基-2-苯基-4-( 1 -苯基-丙基胺甲酿基)-1,2-二鼠-異喧嚇>-3-基曱基]-制井-l-基}-乙基)-胺基甲酸第三丁酯 1.39 637.8 638.5 3-[4-(1Η-吲唑-5-基)-哌啡-1-基曱基]-1 -側乳基-2-苯基-1,2-二氫-異喹啉-4-羧酸(⑸-1-苯基-丙基)-醯胺 0.99 596.7 597.7 2fm 1-側氧基-2-笨基-3-(4-喹啉-6-基-旅明^1-基甲基)-1,2-二氮_ 異σ奎琳-4-竣酸((S)-l-苯基-丙基)-醯胺 0.95 607.8 608.7 2fn 3-[4-(6,7-二甲氧基-喹唑啉-4-基基甲基]-1-側乳 1.06 668.8 669.3 219 200906801 2fo 基-2-苯基-1，2-二氮-異喧琳-4-羧酸((S)-l-苯基-丙基)-醯胺 4-{4-[1-側氧基-2-苯基-4-(1- 1.09 663.9 664.8 2fp 苯基-丙基胺曱醯基)-1,2-二氫-異喹啉-3-基甲基]-哌啡-1-基}-哌啶-1-羧酸第三丁酯 3-{4-[2-(4-氣-苯氧基)-乙基]- 1.19 635.2 635.9 f \ 2fq 旅明Μ-基甲基}-1-側氧基-2-苯基-1,2-二鼠-異嗤嚇·_4-叛酸 ((S)-l-苯基-丙基)-酸胺 {4-[1-側氧基-2-苯基-4-(1-苯 1.08 594.8 595.9 2fr 基-丙基胺曱酿基)-1,2-二鼠-異喹啉-3-基曱基]-哌啡-l-基}-乙酸第三丁酯 1-側氧基-2-苯基-3-[4-(3,3,3_ 0.96 592.7 593.6 2fs 三氟羥基-丙基)-哌明M-基曱基]_1，2_二風-異喧嚇·-4-羧酸((S)-l-苯基-丙基)-醯胺 3-[4-(2-羥基-丙基)-哌啡-1- 0.86 538.7 539.5 2fu 基曱基]-1-側乳基-2-苯基_ 1，2-二鼠-異啥淋-4-竣酸((8)_ 1-苯基-丙基)-醯胺 3-[4-(4-胺基-6,7-二曱氧基-喹 1.03 683.8 684.7 唑啉_2_基)-哌啡-1-基甲基]-1_側氧基-2-苯基-1,2-二鼠-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 220 200906801 2fv 2fw 2fx 2fy 2fz 2ga (2-{4-[l-側乳基-2-苯基-4-(1- 1.06 苯基-丙基胺甲醯基)-1,2-二氳-異喹啉-3-基甲基]-哌明=-1-基}-乙基)-胺基甲酸第三丁酯 1-側氧基-3-{4-[2-(2-側氧基-0.85 咪唑啶-1-基)-乙基]-哌啡-1-基甲基}-2-苯基-1,2-二氫-異啥琳-4-棱酸((S)-1 -苯基-丙基)-醯胺 3-{4-[(4,6-二甲氧基-嘧啶-2- L21 基)-苯基-甲基]底明^-1-基甲基} -1 -側乳基-2-苯基-1,2-二氫-異啥淋_4_竣酸((S)-l-苯基 -丙基)-酸胺 3-(4-苯并[1,2,5]噻二唑-4-基-} .48 哌啡小基曱基)-1-側氧基_2_ 苯基-1,2-二氮-異喧淋-4-叛酸 ((S)-l-笨基-丙基)-酿胺 3-[4-(2,3-二氫-苯并[1,4]二腭 1.2 畊_5_基)-哌啡-1-基曱基]-1-側氧基-2-苯基-1,2-二氫-異喹琳-4-竣酸((S)-l-苯基-丙基)_ 醯胺 3-[4-(4-甲基-喹啉2-基)-哌啡 1>15 -1-基曱基]-1-側氧基-2-苯基-1,2-二氳-異喹啉-4-羧酸(⑸-1-苯基-丙基)-酿胺 623.8 592.7 708.9 614.8 614.7 621.8 624.5 593.7 709.4 615.4 615.3 622.7 221 200906801 2gb 1- 側氧基-2-苯基-3-[4-(ntbn定- 2- 基胺曱醯基甲基)-哌明^1-基曱基]-1,2-二氫-異喹啉-4-缓酸((S)-1 -苯基-丙基)-S盘胺 0.93 614.7 615.4 2gc 3-[4-(6-氯-3-侧氧基-3,4-二氫 -m-苯并[1，4]聘畊-8-基)-哌啡-1-基甲基]-1-側氧基-2-苯基-1,2-二氫-異喹琳-4-叛酸 ((S)-l-苯基-丙基)-醯胺 1.21 662.2 662.8 r 2gd 3-(4-胺曱醯基甲基-哌啡-l-基曱基)-l-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 0.85 537.7 538.5 2ge 3-(4-經基-4-苯基-旅咬-1-基甲基)-1 -側氧基-2-苯基-1，2_ 二氫-異喹啉-4-羧酸(⑸-1 -苯基-丙基)-醯胺 1.12 571.7 572.6 2gf i 3-[4-(4-氯-苯基)-4-羥基-哌啶 -1-基甲基]-1-側氣基-2-苯基_ 1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 1.23 606.2 606.8 2gg Η1 -側氧基-2-苯基-4-( 1 -苯基 -丙基胺甲醯基)-1,2-二氫-異喹啉-3-基甲基]-哌啶-4-羧酸 0.9 523.6 524.5 2gh 3-(4-氣基-4-苯基-旅β定-1-基 1.59 580.7 581.9 甲基)-1 -側氧基·2-苯基-1，2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-S蓝胺 222 200906801 2gi 3-(4-苯甲基-4-羥基-哌啶-1-基曱基)-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸(⑸-1-苯基-丙基)-醯胺 1.16 585.7 586.0 2gj H1-側氧基-2-苯基-4-(1-苯基 -丙基胺甲醯基)-1,2-二氫異喹啉-3-基甲基]-4-苯基-哌啶-4-羧酸乙酯 1.35 627.8 628.5 2gk f \ 1-側乳基-2-笨基-3-[4-(苯基_ 丙醯基-胺基)-哌啶小基甲基]-1，2-二氫-異啥琳-4-缓酸 ((S)-l-苯基-丙基)-酿胺 1.17 626.8 627.6 2gl 甲基-{1-[1-側氧基-2-苯基-4-(1-苯基-丙基胺甲酷基)-1，2_ 二氮_異嗤嚇^3_基甲基]-略σ定· 4-基}•胺基曱酸第三丁酯 1.25 608.8 609.8 2gm f. k 1-側氧基-2-苯基-3-[4-(2-α比洛 °定-1-基-乙基)-派°定-1 -基甲基]-1，2-二氣-異啥琳-4-魏酸 ((S)-l-苯基-丙基)-醯胺 0.72 576.8 577.5 2gn 3-{4-[5-(4-氟-苯基)-[1，3,4]聘二。坐-2-基]-娘淀-1-基甲基}-1-側氧基-2-苯基-1，2-二氮-異喹啉冰羧酸((S)-l -苯基-丙基)-酸胺 1.22 641.7 642.3 2go 1-側氧基-2-苯基-3-[4·(3-°比13定冰基-[I，2,4]腭二唑-5-基)-哌啶-1-基曱基]-1，2-二氳-異喹 0.96 624.7 625.5 223 200906801 2gp 2gq 2gr 2gsK 2dg 2dh 3-((S)-3-methyl-piperidin-1-ylmethyl)-1 · galactyl-2-phenyl-1,2.diazepine-isoindole icylic acid ( (S)-l-phenyl-propyl)-decylamine 0.88 494.6 495.7 3-((R)-3-methyl-piperidin-1·ylindenyl)-1 -oxy-2-phenyl -1,2-dihydro-isoquinoline-4-carboxylic acid ((5) small phenyl-propyl)-decylamine 0.88 494.6 495.7 3-[3·(3_Chloro-phenyl)-piperidinyl -1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((3) small phenyl-propyl)-nitramine 1.11 591.2 591.4 3-[4-( 1Η-吲哚-4-yl)pepirin-ylmethyl]-1-oxo-2-phenyl-1 1,2-dihydro-isoquinoline glacial carboxylic acid ((S)-1_benzene --propyl)-nonylamine 1.1 595.7 596.6 1-sided oxy-tung (3-o-oxy-piperidin-1-ylmethyl)-2-phenyl·1,2-di-rat 喧4-Weyric acid ((S)-l-phenyl-propyl acid amine 1.09 494.6 495.7 3-[4·(1Η-吲哚_5_yl)-pemamine M-ylmethyl]-1 -oxyl -2-phenyl_ 1,2-diaza-isoindole-4-carboxylic acid ((8)_ 1-phenyl-propyl)-decylamine 1.04 595.7 596.7 3-(6,9-diaza -spiro[4.5]dec-9-ylmethyl)_ 1 -p-oxy-2-phenyl-1,2-0.97 534.7 535.3 211 200906801 Dihydro-isoquinoline-4-carboxylic acid ((S)- L-benzene -propyl)-guanamine 2dm V.. 2di 2dj 2dk 2dl 2dn 2do 3-(1,4-diaza-spiro[5.5]undec-4-ylmethyl)-1-yloxy-2- Phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-acid amine 1.01 548.7 549.7 3-(3-isopropyl-peminylmethyl )-1-Lideoxy-1-yl-2-phenyl-1,2-diaza-iso-portal terrorism--4-decanoic acid ((S)-l-phenyl-propyl)-decylamine 0.96 522.7 523.5 3-(3,3-Dimethyl-piperidin-1-ylmethyl)-1-oxooxy-2-phenyl-1,2-diindole-isoindole_4_-acid ((S) )-l-phenyl-propyl)-nonylamine 0.9 508.7 509.2 3-[3-(4-Fluoro-phenyl)-piperidin-1-ylmethyl]-1-oxo-2-phenyl -1,2-dihydro-isoquinoline carboxylic acid ((S)-l-phenyl-propyl)-decylamine 1.05 574.7 575.4 1-sided oxy-2-phenyl-3-(3-pair Tolyl-piperidin-1-ylmethyl)-1,2-diindole-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 1.08 570.7 571.7 4- [ 1-oxo-2-phenyl-4-(1-phenyl-propylamine oxime)-1,2-dioxa-isoquinolin-3-ylindenyl]-piperidin-1- Tert-butyl carboxylic acid 1.49 580.7 581.9 3-(4-decylamine-mercaptomethyl-pepirinyl-1-ylindenyl)-1-ylidery-2-benzene 0.86 551.7 552.9 212 200906801 Base-1 , 2-two Hydrogen-isoquinoline-4-carboxylic acid ((8)-1-phenyl-propyl)-amine 2dp 8-chloro-3-didecylaminomethyl-1-oxo-2-benzene 1,2-diaza-isoindolin-4-carboxylic acid ((S)-1 -phenyl-propyl)-decylamine 0.95 474.0 474.6 2dr 3-3⁄4 pentylaminomethyl-1- side Oxy-2-phenyl-1,2-dimur-isoindolin-4-decanoic acid ((S)-l-phenyl-propyl)-decylamine 1.03 479.6 480.4 2ds 3-3⁄4 hexylamino hydrazine -1--1-oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 1.1 493.6 494.4 2dt 3_{ [(2-Phenyl-ethyl)-fluorenyl-amino]-methyl}_1_sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S )-1-phenyl-propyl)-decylamine 0.84 469.6 470.6 2du 3-imidazol-1-ylindenyl-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4 -carboxylic acid ((S)-l-phenyl-propyl)-bristamine 0.86 462.6 463.4 2dv 3-(2-mercapto-imidazol-1-ylmethyl)-1-p-lacyl-2-phenyl -1,2-diaza-isosalin-4-decanoic acid ((S)-l-phenyl-propyl)_decylamine 0.88 476.6 477.3 2dw 3-(4-mercapto-imidazol-1-ylindole ))-1-oxo-2-phenyl-1,2-dihydro-isoquinolin-4-indole ((S)-l-phenylpropyl)-decylamine 0.89 476.6 477.3 2dx 3- (2,5-two wind ratio -1-ylmethyl)- 0.92 463.6 464.5 213 200906801 I-side lactyl·2-phenyl-1,2-diaza-iso-sigma quino--4·nonanoic acid ((S)-1 -phenyl group -propyl)-guanamine 2dy 3-(2,5-dimethyl-2,5-dihydro-pyrrole-l-ylindenyl)-M-oxy-2-phenyl-1,2-di Hydrogen-isoquinoline-4-carboxylic acid ((5)-1-phenyl-propyl)-decylamine 1.06 491.6 492.4 2dz 1 - flavonyl-2-phenyl-3 -α ratio slightly -1 -1 Base-1,2-diaza-isoindolin-4-o-acid ((S)-l-styl-propyl)-acid amine 0.92 465.6 466.3 2ea 1-sideoxy-2-phenyl-3 - (嗟°坐-2-ylamino fluorenyl)-1,2-dichloro-isoindolyl-4-decanoic acid ((S)-l-phenylpropyl)-acid amine 0.88 494.6 495.6 2eb I- Lacto-2-phenyl-3-(^^-4-ylaminoindenyl)-1,2-dioxa-isoindoline-4-carboxylic acid ((S)-l-phenyl-propionate Base)-decylamine 0.85 489.6 490.4 2ec 3-(dibutylamino-methyl)-1-oxooxy-2-phenyl·1,2-diaza-isoindolin-4-carboxylic acid ( (S)-l·Phenyl-propyl)-guanamine 1 467.6 468.7 2ed 3-[(2-Indolyl-1,1-dimethyl-ethylamino)-methyl]-1-yloxy Benzyl-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)· 1-phenyl-propyl)-decylamine 0.91 483.6 484.3 2ee 3-(isopropylamine -Methyl) small pendant oxy-2-phenyl-1,2-dichloro-isoindole *- 0.93 453.6 454.3 214 200906801 4-carboxylic acid ((S)-l-phenyl-propyl)-醯Amine 2ef 3-[(2-Lightyl-1-indenyl-ethylamino)-methyl]-1 -p-oxy-2-phenyl-1,2-diaza-isoindole-4- Capric acid ((S)-l-phenyl-propyl)-decylamine 0.86 469.6 470.5 2eg 3-[(1-perylmethyl-propylamino)-indenyl]-1-yloxy-2 -phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl:)-decylamine 0.92 483.6 484.4 2eh 3-[(2,2-dioxin) -propylamino)-indenyl]-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl > Indoleamine 1.13 481.6 482.2 2ei 1 -Phenoxy-2-phenyl-3-prop-2-ynylaminomethyl-1,2-diaza-isoindolin-4_carboxylic acid ((S) -l-phenyl-propyl)-nonylamine 0.95 449.6 450.2 2ej 3-pyridylaminomethyl-1-flankyl-2-phenyl-1,2-diaza-isowa scary-- 4-Resin ((S)-l-phenyl-propyl)-decylamine 0.94 451.6 452.4 2ek 3-[(Methyl-prop-2-ynyl-amino)-methyl]-1 - colostrum Benzyl-2-phenyl-1,2-dimur _isoindolin-4-teric acid ((S)-l-phenyl-propyl)-decylamine 1.22 463.6 464.5 2el 3-diallyl Base fluorenyl-1-side oxygen 1.19 491.6 492.4 yl-2-phenyl-1,2-diaza-isoindole-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 215 200906801 2em 3-Diethylaminomethyl-1-indolyl-2-phenyl-1,2-dioxa-isoindole-4-ruthenic acid ((S)-l-phenyl-propyl )-decylamine 0.98 467.6 468.5 2en 3-[(isopropyl-methyl-amino)-methyl]_ 1_ flavonylphenyl-1,2-diaza-isoquinoline-4-carboxylic acid ((S)Phenylphenyl)-decylamine 0.96 467.6 468.7 2eo [((8)yl-1·indolylethylamino)-methyl]_1·Lactyl-2-phenyl_ 0.86 469.6 470.5 f \ 1 > dihydro-isoquinoline-4-carboxylic acid ((3)-1-phenyl-propyl)-acid amine 2ep 3-[((R)-2-yl-1-yl-yl- Ethylamino)-methyl]-1-oxo-2-phenyl-1 1,2-dihydro-isoindolene-4_weilic acid ((8)-1-phenyl-propyl)- Indoleamine 0.87 469.6 470.5 2eq c 3-{[(2-methoxy-ethyl)-methyl-rhoal]-mercapto}'-1-flank-2-phenyl_ I,2- Dihydro-isoquinoline-4-carboxylic acid ((S)-1 -phenyl-propyl)-acid amine 0.96 483.6 484.4 \ 2er 3-((R)-3-hydroxy-indolyl-1-yl Methyl)-1 -Sideoxy-2.Phenyl-1,2-diaza-isoindole -4-butyric acid ((S)-l-phenyl-propyl)-decylamine 0.85 481.6 482.3 2es 3-((S)-3-Hydroxy-indolyl-1-ylmethyl)-1·Sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylate Acid ((S)-l-phenyl-propyl)-decylamine 0.84 481.6 482.3 2et 3-[(cyclopentyl-methyl-amino)-methyl]- 1.09 493.6 494.5 216 200906801 1-sided emulsion -2-phenyl-1,2-di-oxo-isoindole·4-decanoic acid ((S)_l-phenyl-propyl)-guanamine 2-sub 3-{[(2-hydroxy-1-methyl) -ethyl)-methyl-amino]-methyl}-l-flavoryl-2_phenyl-1,2-diaza-isoindole*-4-decanoic acid ((S)-l-benzene --propyl)-decylamine 0.89 483.6 484.4 2ev [ethyl-(2-light-ethyl)-amino]-methyl}-1- oxo-2 phenyl _ 0.89 483.6 484.4 / 1 ,2-dihydro-isoquinoline-4-carboxylic acid ((5)-1-phenyl-propyl)-bristamine 2ew 3-[(ethyl-indolyl-amino)-indenyl]-1_ side oxygen Benzyl-2-phenyl-1,2-dihydro-isoquine-inferior-4-deoxy acid ((S)-l-phenyl-propyl)_ decylamine 0.92 453.6 454.4 lex 3-3⁄4 butylamino Methyl-1-oxooxy-2-phenyl-1,2-dihydroisoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)·decylamine 0.98 465.6 466.4 , 2ey \ 3- Tetrahydroindole-1-ylmercapto-1-yloxy-2-phenyl-1,2-diaza-isoindole 4-colic acid ((S)- L-phenyl·propyl)-bristamine 0.86 451.6 452.3 2ez \(4-Terbutyl-Pepylmethyl)-1-oxo-2-phenyl-1,2-diaza-isoindole琳-4-竣酸((S)-l_phenyl-propyl)-decylamine 0.91 536.7 537.3 2fa 3_[4·(2_ ||望基-ethyl) σ底-1- 0.86 524.7 525.6 Side oxy-2-phenyl-217 200906801 * 1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-bristamine 2fb 3- {4 -[2-(2-|^ι-ethoxy)-ethyl]-pepirin M-ylmethyl}-1-oxo-2-phenyl-1,2-dioxa-1-isoindole _ _ 4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.86 568.7 569.6 2fc f % 3- [4-(3-chloro-5-trifluoromethylpyridin-2-yl) )-»Desphedo-1-ylindenyl]-1-yloxy-2-phenyl-1,2-dipho-iso Wahlin_ 4-carboxylic acid ((S)-l-phenyl- Propyl)-nonylamine 1.77 660.1 660.8 lid 3-[4-(3,5-Dichloro-pyridin-4-yl)-piperidin-1-ylmethyl]-1-yloxy-2-phenyl -1,2-diaza-isoindolin-4-deoxalate ((S)-l-phenyl-propyl)-nitramine 1.45 626.6 626.5 2fe ri 4-[1- oxo-2-phenyl 4-((S)-l-phenyl-propylamine methyl-)-1,2-dihydro-isoquinolin-3-ylmethyl]-piperidin-1-carboxylic acid benzyl ester 1.57 614.7 615.4 2ff 3-[ 4-(3-ofofolin-4-yl-propyl)-bred-1-ylmethyl]-1-oxooxy-2-phenyl-1,2-diaza-iso-sigridine- 4-Resin ((S)-l-phenyl-propyl)-decylamine 0.74 607.8 609.0 2fg 1-sided oxy-2-phenyl-3-[4-(3-piperidin-1-yl- Propyl)-branches 0^-1-ylmethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-amine 0.76 605.8 607.1 200906801 :2fh 3_[4_(4,6-Dimethoxy-pyrimidin-2-ylindenyl)-piperidin-1-ylmethyl]-1-yloxy-2-phenyl-1,2-di Chloro-isoindol-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 1.05 632.8 633.9 2fi 3-[4-(3-hydroxy-propyl)-pemmin M-yl Base]-1 •triazin-2-phenyl_ 1,2-dihydro-isoquinoline-4-carboxylic acid ((3)-1-phenyl-propyl)-3-amine 0.86 538.7 539.4 r 2fj 3 -[4-(2,3-dihydroxy-propyl)-piperidin-1-ylmethyl]-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4- Carboxylic acid ((S)-1-phenyl-propyl)-decylamine 0.84 554.7 555.7 2fk (2-Sideoxy-2-{4-[1-Pentyloxy-2-phenyl-4-(1) -Phenyl-propylamine-branched)-1,2-di-mouse-isostimulus>-3-ylindenyl]-well-l-yl}-ethyl)-carbamic acid tert-butyl Ester 1.39 637.8 638.5 3-[4-(1Η-indazol-5-yl)-peripipeline -1-ylindenyl]-1 -s-mercapto-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((5)-1-phenyl-propyl)-decylamine 0.99 596.7 597.7 2fm 1-Sideoxy-2-peptidyl-3-(4-quinolin-6-yl-tumamine^1-ylmethyl)-1,2-diaza_iso-sigretin-4-竣Acid ((S)-l-phenyl-propyl)-decylamine 0.95 607.8 608.7 2fn 3-[4-(6,7-Dimethoxy-quinazolin-4-ylmethyl)-1- Colostrum 1.06 668.8 669.3 219 200906801 2fo -2-phenyl-1,2-diaza-isoindolyl-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 4-{4 -[1-Sideoxy-2-phenyl-4-(1-.09 663.9 664.8 2fp phenyl-propylamine decyl)-1,2-dihydro-isoquinolin-3-ylmethyl] -piperidin-1-yl}-piperidine-1-carboxylic acid tert-butyl ester 3-{4-[2-(4-a-phenoxy)-ethyl]- 1.19 635.2 635.9 f \ 2fq Μ-ylmethyl}-1-oxo-2-phenyl-1,2-dimur-isoindole·_4-retadic acid ((S)-l-phenyl-propyl)-acid amine { 4-[1-Sideoxy-2-phenyl-4-(1-benzene 1.08 594.8 595.9 2fr-propylamine oxime)-1,2-di-r-isoquinolin-3-ylfluorenyl ]-Pentyl-l-yl}-acetic acid tert-butyl ester 1-sided oxy-2-phenyl-3-[4-(3,3,3-0.96 592.7 593.6 2fs trifluorohydroxy-propyl)-per明M-基曱基]_1,2_ Wind-isoindole-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 3-[4-(2-hydroxy-propyl)-piperidin-1-0.86 538.7 539.5 2fu曱 ] ] -1- 侧侧 -2- -2- -1- -1- -1- -1- -1- -1- -1- -1- -1- -1- -1- [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ 4-(4-Amino-6,7-dimethoxy-quinoline 1.03 683.8 684.7 oxazoline-2-yl)-piperidin-1-ylmethyl]-1_sideoxy-2-phenyl- 1,2-di-rho-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 220 200906801 2fv 2fw 2fx 2fy 2fz 2ga (2-{4-[l-side milk Benzyl-2-phenyl-4-(1-1.06 phenyl-propylaminemethanyl)-1,2-dioxa-isoquinolin-3-ylmethyl]-piperidine=-1-yl} -ethyl)-carbamic acid tert-butyl ester 1-tertiaryoxy-3-{4-[2-(2-o-oxy-0.85 imidazolidin-1-yl)-ethyl]-piperidin-1 -ylmethyl}-2-phenyl-1,2-dihydro-isoindolyl-4-aryl acid ((S)-1 -phenyl-propyl)-nonylamine 3-{4-[(4 ,6-dimethoxy-pyrimidin-2- L21 yl)-phenyl-methyl] decyl -1-ylmethyl} -1 - flavonyl-2-phenyl-1,2-dihydro -isoindole _4_decanoic acid ((S)-l-phenyl-propyl)-acid amine 3-(4-benzo[1,2,5]thiadiazol-4-yl-}.48 Piperidinyl fluorenyl)-1-yloxy_2_phenyl-1,2-diaza-isoindole-4-deoxy acid ((S)-l- stupid -propyl)-bristamine 3-[4-(2,3-dihydro-benzo[1,4]dioxin 1.2 tillage_5_yl)-piperidin-1-ylindenyl]-1- side Oxy-2-phenyl-1,2-dihydro-isoquinolin-4-indole ((S)-l-phenyl-propyl)-decylamine 3-[4-(4-methyl- Quinoline 2-yl)-piperidin 1 >15 -1-ylindenyl]-1-oxo-2-phenyl-1,2-diindole-isoquinoline-4-carboxylic acid ((5)-1 -Phenyl-propyl)-chiral amine 623.8 592.7 708.9 614.8 614.7 621.8 624.5 593.7 709.4 615.4 615.3 622.7 221 200906801 2gb 1-sided oxy-2-phenyl-3-[4-(ntbn- 2-aminoamine oxime Mercaptomethyl)-pepirin^1-ylindenyl-1,2-dihydro-isoquinoline-4-hypoacid ((S)-1 -phenyl-propyl)-S-padamine 0.93 614.7 615.4 2gc 3-[4-(6-Chloro-3-oxo-3,4-dihydro-m-benzo[1,4] hired-8-yl)-piperidin-1-ylmethyl ]-1-Sideoxy-2-phenyl-1,2-dihydro-isoquinolin-4-reactive acid ((S)-l-phenyl-propyl)-decylamine 1.21 662.2 662.8 r 2gd 3 -(4-Aminylmethyl-piperidin-l-ylindenyl)-l-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S )-1-phenyl-propyl)-nonylamine 0.85 537.7 538.5 2ge 3-(4-pyridyl-4-phenyl-bunken-1-ylmethyl)-1-oxo-2-phenyl -1,2_ Dihydro-isoquinoline-4-carboxylic acid ((5)-1 - Base-propyl)-nonylamine 1.12 571.7 572.6 2gf i 3-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-ylmethyl]-1-ylidene-2-benzene Base-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 1.23 606.2 606.8 2gg Η1 - oxo-2-phenyl-4- (1-Phenyl-propylaminemethanyl)-1,2-dihydro-isoquinolin-3-ylmethyl]-piperidine-4-carboxylic acid 0.9 523.6 524.5 2gh 3-(4-gas group -4-Phenyl-Big-Butyl-1-yl 1.59 580.7 581.9 Methyl)-1 -Phenyloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S) -l-phenyl-propyl)-S leucine 222 200906801 2gi 3-(4-Benzyl-4-hydroxy-piperidin-1-ylindenyl)-1-yloxy-2-phenyl- 1,2-Dihydro-isoquinoline-4-carboxylic acid ((5)-1-phenyl-propyl)-decylamine 1.16 585.7 586.0 2gj H1-Sideoxy-2-phenyl-4-(1-benzene Ethyl-propylamine-mercapto)-1,2-dihydroisoquinolin-3-ylmethyl]-4-phenyl-piperidine-4-carboxylic acid ethyl ester 1.35 627.8 628.5 2gk f \ 1-side Lacto-2-phenyl-3-[4-(phenyl-propionyl-amino)-piperidinemethyl]-1,2-dihydro-isoindol-4-acid (( S)-l-phenyl-propyl)-bristamine 1.17 626.8 627.6 2gl methyl-{1-[1-o-oxy-2-phenyl-4-(1-phenyl-propylamine) Base)-1,2_diaza-isoindole^3_ylmethyl]-slightly sigma·4-yl}•aminobutyric acid tert-butyl ester 1.25 608.8 609.8 2gm f. k 1-sideoxy- 2-Phenyl-3-[4-(2-αBilozol-1-yl-ethyl)-pyridine-1 -ylmethyl]-1,2-digas-isoindole-4 -Weyric acid ((S)-l-phenyl-propyl)-decylamine 0.72 576.8 577.5 2gn 3-{4-[5-(4-fluoro-phenyl)-[1,3,4] employed two. Sodium-2-yl]-Nandyl-1-ylmethyl}-1-oxo-2-phenyl-1,2-diaza-isoquinoline glacial carboxylic acid ((S)-l-phenyl -propyl)-acid amine 1.22 641.7 642.3 2go 1-sided oxy-2-phenyl-3-[4·(3-° ratio 13 icylic acid-[I,2,4] oxadiazole-5- Base)-piperidin-1-ylindenyl-1,2-dioxa-isoquine 0.96 624.7 625.5 223 200906801 2gp 2gq 2gr 2gs

i K 2gt 2gu 啉-4-羧酸((S)-l-苯基-丙基)- 醯胺 1 -側氧基-2-苯基-3-[4-(3- ° 比 1.04 啡 _2_ 基-[I，2,4]腭二唑-5-基)-旅。定-1-基甲基]-1,2-二風-異唾淋-4-棱酸((S)-1 -苯基-丙基)-醯胺 1-側氧基-2-苯基-3-[4-(3-。比啶丨.04 -4-基-[1,2,4]腭二唑-5-基)-哌啶-1-基甲基]-1,2-二氳-異喹啉-4-羧酸((S)-l-苯基-丙基)- 醯胺 3-(4’-羥基-3’,4',5’，6’-四氫-2’：《- 0.83 [2,4·]聯吡啶-Γ-基曱基)-1-側氧基-2-苯基-1，2-二氯-異哇琳 -4-羧酸((S)-l-苯基-丙基)-醯胺 3 -(螺[異二氳苯并哌喃-1,4'- 1.24 °底0定]-1'-基曱基)-1-側氧基-2-苯基-1，2-二氳-異喹啉-4-羧酸 ((S)-l-苯基-丙基)-醯胺 3-[4-羥基-4-(3-甲氧基-苯基)-U3 旅0定-1-基甲基]-1-側乳基_2_ 苯基-1,2-二鼠-異啥嚇·_4-竣酸 ((S)-l-苯基-丙基)-醯胺 3-[4-(3-風-苯基)-4-經基-旅。定 1.23 -1-基甲基]-1-側氧1基-2-苯基_ 1,2-二氫-異喹啉-4-羧酸((S)- 625.7 624.7 572.7 597.8 601.7 606.2 626.5 625.5 573.5 598.6 602.4 606.8 224 200906801 2gv 2gw 2gx 2gyi K 2gt 2gu porphyrin-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 1 - oxo-2-phenyl-3-[4-(3- ° ratio 1.04 _ 2_Base-[I,2,4]oxadiazol-5-yl)-Brigade. Ding-1-ylmethyl]-1,2-diphos-iso-salt-4-pyrimidic acid ((S)-1 -phenyl-propyl)-nonylamine 1- oxo-2-phenyl -3-[4-(3-.pyridinium.04-4-yl-[1,2,4]oxadiazol-5-yl)-piperidin-1-ylmethyl]-1,2- Diterpene-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 3-(4'-hydroxy-3',4',5',6'-tetrahydro- 2': "-0.83 [2,4·]bipyridyl-fluorenyl-fluorenyl)-1-yloxy-2-phenyl-1,2-dichloro-isowolin-4-carboxylic acid (( S)-l-phenyl-propyl)-guanamine 3 -(spiro[iso-bifluorenylbenzopyran-1,4'- 1.24 ° base]-1'-ylindenyl)-1- side Oxy-2-phenyl-1,2-dioxa-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 3-[4-hydroxy-4-(3 -Methoxy-phenyl)-U3 旅0定-1-ylmethyl]-1-flavoryl 2_1 phenyl-1,2-di-mouse-isostimulated _4-decanoic acid ((S) -l-Phenyl-propyl)-guanamine 3-[4-(3-Wino-phenyl)-4-yl--Brigade. 1.23 -1-ylmethyl]-1-oxooxyl-2-yl-1- 1,2-dihydro-isoquinoline-4-carboxylic acid ((S)- 625.7 624.7 572.7 597.8 601.7 606.2 626.5 625.5 573.5 598.6 602.4 606.8 224 200906801 2gv 2gw 2gx 2gy

2ha 1-苯基-丙基)-醯胺 3- (6-氯-3H-螺[異苯并呋喃-丨.36 1，4’-哌啶]-Γ-基曱基)-1-侧氧基-2-苯基-1,2-二氮-異喧琳_ 4- 羧酸((S)-l-苯基-丙基)-醯胺 3-(4- {[4-氯-3-(4-氟-苯基)-茚-i .36 1-基]-曱基-胺基}-旅。定-1-基甲基)-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸(⑸-1 -苯基-丙基)-酿胺 3-(1-乙醯基-螺[吲哚啉-3,4'- us 0底咬]-1'-基曱基)-1-側氧基-2_ 苯基-1,2-二氣-異啥琳-4-竣酸 ((S)-l-苯基-丙基)-酿胺 3- (1-乙醯基-5-氟-螺[。引嗓啉-1.2 3,4’-哌啶]-Γ-基甲基)-1-側氧基-2-苯基-1,2-二鼠-異啥琳_ 4- 羧酸((S)-l-苯基-丙基)-醯胺卜側氧基-3-(4-侧氧基-1-苯基 1.15 -1,3,8-三氮雜-螺[4.5]癸-8-基甲基)-2-苯基-1,2-二氮-異喧啦>-4-竣酸((S)-l-苯基-丙基)_ 醯胺 3-(4-乙酿基胺基-π底咬-1-基曱 0.83 基)-1 -側氧基-2-苯基-1,2-二氳-異喹啉-4-羧酸((S)-l-苯基 618.2 753.4 624.8 642.8 625.8 536.7 618.4 753.4 625.6 643.4 626.6 537.4 225 200906801 2hb 2hc 2hd 2he 2hf 2hg 2hh -丙基)-醯胺 1 -側氧基-3.-(1-側氧基-2,8-二 0.85 氮雜-螺[4.5]癸-8-基甲基)-2-苯基-1,2-二氫-異喹啉-4-羧酸 ((S)-l-苯基-丙基)-酿胺 3-[4-經基-4-(3-二氟甲基-苯 1.29 基)-旅。定-1-基曱基]-1-側氧基 -2-米基-1,2-二鼠-異喧嚇 -4-羧酸((S)-1 -苯基-丙基)-醯胺 1 -側氧基-2-苯基-3-(4-三氟甲 1.3 基-°底。定-1-基甲基)-1,2-二氮_ 異啥嚇·_4-竣酸((S)-l-苯基-丙基)-醯胺 3-[4-(4-曱基-哌啡-1-羰基)-〇.7 娘°定-1-基曱基]-1-側氧基-2_ 苯基-1,2-二鼠-異喧琳-4-叛酸 ((S)-l-苯基-丙基)-酿胺 3-(5-異丙基-3H-螺[異苯并呋丨.48 喃-1,4’-哌啶]-Γ-基甲基)-1-側氧基-2-苯基-1,2-二氮-異π奎'^木 -4-羧酸((S)-1 -苯基-丙基)-醯胺 3- [4-(乙酸基-甲基-胺基)-4-苯 1.13 基-旅°定-1-基曱基]-1-側氧基_ 2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 4- { 1-[1-側氣基-2-苯基-4-(1- 1.03 苯基-丙基胺甲酿基)-1,2-二 548.7 549.7 639.7 547.6 605.8 625.8 626.8 663.9 640.3 548.4 607.0 626.6 627.7 664.7 226 200906801 氳-異喹啉-3-基曱基]-哌啶-4-基}-旅啡-1-羧酸第三丁酯 2hi (2-{l-[l-側氧基-2-苯基-4-(1-苯基-丙基胺甲醯基)-l，2-二氫-異啥琳-3-基甲基]-0辰0定-4-基}-乙基)-胺基甲酸第三丁酯 1.19 622.8 623.5 2hj 3-(4-曱基胺基-4-苯基底。定_ 1-基曱基)-1-侧氧基-2-苯基_ 1，2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 1.01 584.8 585.5 2hk 3-(4-乙酿基胺基-4-苯基-旅〇定 -1 -基甲基)-1 -側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-酿胺 1.06 612.8 613.3 2hl 3-[4-乙酿基胺基-4-(3-氣-苯基)-旅0定-1-基甲基]-1-側氧基 -2-苯基-1,2-二鼠-異喧嚇· -4_ 羧酸((S)-l-苯基-丙基)-醯胺 1.06 630.8 631.5 2hm 1-側氧基-3-[4-(4-側氧基-哌 π定-1-祿基)-旅0定-1-基甲基]-2_ 本基-1,2-二鼠-異啥嚇>-4-缓酸 ((S)-l-苯基-丙基)-醯胺 0.89 604.7 605.3 2hn 3-[4,4']聯哌啶-1-基甲基-1-側氧基-2-苯基-1,2-二鼠-異喧嚇· -4-竣酸((S)-l -苯基-丙基)-酿胺 0.7 562.8 563.2 2ho 側氧基-2-苯基-4-(1-苯基-丙基胺曱酿基)-1,2-二氮- 1.15 594.8 595.8 227 200906801 2hp 2hq 2hr 2hs \ 2ht 2hu 異喹啉-3-基甲基]-哌啶-4-基}-胺基甲酸第三丁酯 3-[1,4']聯哌啶-Γ-基甲基-1-侧 0.95 氧基-2-苯基-1,2-二氮-異啥琳 -4-叛酸[J哀丙基-(3-鼠-苯基)_ 甲基]-醯胺 1-側氧基-3_(4_苯乙基-0底明^ 1.15 1-基曱基)-2-苯基-1,2-二氫-異》奎嘛-4-竣酸[ί哀丙基-(3-氣-苯基)-甲基]-醯胺 3-(4-異丙基-哌胡基甲基)-0.97 1-側氧基-2-苯基-1,2-二氮-異啥琳-4-叛酸[ί哀丙基-(3-氣-苯基)-甲基]-醯胺 3-[4-(2-嗎福林-4-基-乙基)-派 0.81 畊-1-基甲基]-1-側氧基_2_苯基-1，2-二氫-異喹啉-4-羧酸 [壞丙基-(3-1-苯基)-甲基]-酸胺 3-[4-(1-曱基-派π定-4-基)-0底〇_78 啡-1-基甲基]-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸 [玉哀丙基-(3-氣-苯基)-甲基]-酸胺 1-側氧基-2-苯基-3-[4-(2-哌啶 0.82 -1-基-乙基)-«底$-1-基甲基]-1,2-二氮-異啥淋-4-叛酸[J哀丙基-(3-氟-苯基)-甲基]-酿胺 592.8 614.8 552.7 623.8 607.8 621.8 593.5 615.5 553.8 624.6 608.9 622.6 228 200906801 ；2hv 1-側氧基-2-苯基-3-[4-(2-°比咯啶-1-基-乙基)-哌啡-1-基甲基]-1,2-二氯-異喧琳-4-魏酸 [環丙基-(3-氟-苯基)-甲基]-醯胺 0.8 607.8 608.8 2hw 1 -側氧基-2-苯基-3-(4-吡啶-4-基曱基-哌啡-1-基曱基)-1,2-二鼠-異啥琳-4-叛酸[環丙基_ (3_氟-苯基)-曱基]_酿胺 0.84 601.7 602.6 f 2hx \ 3-(4-羥基-3,4,5,6-四氫-211-基甲基)-1-側氧基-2-苯基-1,2-二鼠-異喧琳 -4-叛酸[壞丙基-(3-氟-苯基)_ 甲基]-醯胺 0.77 602.7 603.7 2hy 3_[4_(2-嗎福林-4-基-乙基)-派啶-1-基曱基]-1-側氧基-2-苯基-1,2-二鼠-異喧嚇 -4-叛酸 [環丙基-(3-苯基)-甲基]-酸 0.75 622.8 623.7 i \ 胺 2hz 3-[4-羥基-4-(3-曱氧基-苯基)-哌啶-1-基甲基]-1-側氧基-2-苯基-1，2-二鼠-異哇琳-4-竣酸 [環丙基-(3-敗-苯基)-甲基]-醯胺 1.17 631.7 632.6 2ia 3-[4-(乙醯基-甲基-胺基)-4-苯基-派。定-1-基甲基]-1-側乳基- 1.18 656.8 657.8 2-笨基-1，2-二鼠-異喧琳-4-缓酸[壞丙基-(3-氣-苯基)-甲基]- 229 200906801 酸胺 2ib 2-(2-氟-苯基)-1-側氧基-3-(4-苯乙基·哌啡小基曱基)-l，2-二鼠-異喧琳-4-竣酸((S)-1 -苯基-丙基)-醯胺 1.12 602.8 603.8 2ic 2-(2-氣-苯基)-3-(4-異丙基-派明^1-基曱基)-1-側氣基-1，2· 二氳-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 0.96 540.7 541.7 2id 3-[1，4]聯哌啶-Γ-基曱基-2-(2-氟-苯基)-1-側氧基-1，2-二氮-異啥琳-4-竣酸((S)-1 -苯基 -丙基)-醯胺 1 580.7 581.7 2ie 2-(2-鼠-苯基)-3-[4-(2-嗎福林_ 4-基-乙基)-派明^1-基甲基]_ 1-側氧基·1，2-二氫-異喹啉-4-羧酸((S)-l_苯基-丙基)-醯胺 0.82 611.8 612.5 2if 2-(2-氟-苯基)-3-[4-(1-曱基-哌啶斗基)·哌啡-1-基甲基]-1-側氧基-1，2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-驢胺 0.76 595.8 596.8 2ig 2-(2-亂-苯基)-1·側乳基娘 °定 -1 - 基- 乙基)-派 -1 -基曱基]-1，2-二氳-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 0.81 609.8 610.5 2ih 2-(2-氣-苯基)-1-側氧基-3-[4-(2-°比洛^定-1-基-乙基)-娘呼[:-1-基甲基]-1，2-二氮-異喧琳- 0.8 595.8 596.7 230 200906801 - 4-羧酸((S)-l-苯基丙基)-醯胺 2ii 2-(2-鼠-苯基)-1-侧氧基-3-(4-吡啶-4-基甲基-哌啡-1-基甲基)-1,2-二氫-異喹啉-4-羧酸 ((S)-l-苯基-丙基)-醯胺 0.84 589.7 590.4 2ij 2-(2-氟-苯基）-3-(4- 每基-3,4,5,6-四氫-2H-[4,4丨]聯吡啶_ 1-基甲基)-1_側氧基-1，2-二氮 0.85 590.7 591.3 f \ -異啥淋_4_棱酸((S)-1 -苯基_ 丙基)-醯胺 2ik 2-(2-氣-苯基)-3-[4-(2-嗎福林_ 4-基-乙基)-旅。定-1-基曱基]-1_ 側氧基-1，2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 0.76 610.8 611.7 2il 2-(2-氣-苯基)-3-[4-|^i 基-4-(3_ 曱氧基-苯基)-哌啶-1-基甲基]-1-側氧基-1,2-二氫-異喹 1.21 619.7 620.3 c 琳-4-竣酸((S)-l-苯基-丙基)_ V,·' 醯胺 2im 3-[4-(2-嗎福林-4-基-乙基)-旅畊-1-基曱基]-1-側氧基-2-鄰甲苯基-1,2-二氯-異啥琳-4-叛酸((S)-l-苯基-丙基)-酿胺 0.82 607.8 608.8 2in 1-側氧基-3-[4-(2-哌啶-1-基-乙基)-哌啡-1-基曱基]-2-鄰甲苯基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 0.81 605.8 606.9 231 200906801 2io 1-側氧基-3-(4-。比啶-4-基曱基 -哌啡-1-基甲基)_2_鄰甲苯基 -1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 0.84 585.7 586.4 2ip 2-(3-氟-苯基)-1-側氧基-3-(4-笨乙基-派明^1-基甲基)-1，2_ 二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-酿胺 1.13 602.8 603.8 2iq 2-(3-鼠-苯基)-3-(4-異丙基-旅明基曱基)-1-側氧基-1，2_ 二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-感胺 0.96 540.7 541.3 2ir 3-[1，4’]聯哌啶-Γ-基甲基-2-(3-亂-苯基)-1-侧氧基-1,2-二氳-異喹啉-4-羧酸((S)-l-苯基 -丙基)-醯胺 0.98 580.7 581.8 2is 2-(3-鼠-苯基)-3-[4-(2-嗎福林_ 4-基-乙基)-哌啡-1-基甲基]-1-側乳基-1，2-二氫-異喧嚇·_4_ 羧酸((S)-1 -苯基-丙基)-醯胺 0.81 611.8 612.6 2it 2-(3-氣-苯基)-3-[4-(1-曱基-旅啶_4_基)-哌啡-1-基曱基]-1-側氧基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-1篮胺 0.75 595.8 596.8 2iu 2-(3-氟-苯基)-1-側氧基-3-[4- 0.8 609.8 610.7 (2-略°定-1 -基-乙基)-娘-1-基甲基]-1，2-二氫-異喹啉-4-羧酸((S)-l-苯基·丙基)-醯胺 232 200906801 . 2iv 2-(3-鼠-苯基)-1-側氧基-3-[4-(2σfcb洛σ定l_基-乙基)-娘明:-1-基曱基]-1，2-二氮·異喧琳-4-羧酸((S)-l -笨基-丙基)-醯胺 0.79 595.8 596.8 2iw 2-(3-鼠-苯基)-1-側乳基-3-(4_ 吡啶-4-基曱基-哌明M-基曱基)-1，2-二氳-異啥琳-4-羧酸 ((S)-l-苯基-丙基)-醯胺 0.83 589.7 590.2 2ix 2-(3-氣-苯基)·3-[4·(2-嗎福林-4-基-乙基)-娘。定-1-基甲基]-1_ 側氧基-1，2-二氫-異喹啉-4-羧酸((S)-l-苯基丙基)-醯胺 0.73 610.8 611.6 2iy 2-(3-亂-苯基)-3-[4-輕·基-4-(3_ 曱氧基-本基)_ 0辰α定 1-基甲基]-1-側氧基-1，2-二鼠-異喧啦-4-竣酸((S)-l-苯基-丙基) 醯胺 1.18 619.7 620.7 2iz 3-[4-(乙酿基-曱基-胺基)-4-苯基-派π定_ι_基甲基]-2-(3-氣-苯基)-1_側氧基-1，2-二氫-異喹琳-4-繞酉曼((S)-l -苯基-丙基)_ 醯胺 1.2 644.8 645.7 2ja 2-(3 -氮-苯基)-1 -側乳基-3·(4_ 苯乙基-哌啡-1-基甲基)-1> 二鼠-異哇琳-4-繞酸((S)-l-苯基-丙基)-醯胺 1.17 619.2 619.4 2jb 2-(3-氣-苯基)-3-(4-異丙基-娘 1 557.1 557.5 233 200906801 畊-1-基甲基)-1-側氧基-1，2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 2jc 3-[1,4]聯哌啶-1'-基甲基-2-(3-氣-苯基)-1-側氧基-1,2-二氮-異σ奎琳_4_棱酸((S)-l-苯基 -丙基)-酿胺 1.04 597.2 597.8 2jd /' \ 2-(3 -乳-苯基)-3 - [4_(2_嗎福林_ 4-基-乙基)-哌啡-1-基甲基]-1-側氧基-1,2-二氮-異唾琳-4-羧酸((S)-l-苯基-丙基)-醯胺 0.86 628.2 628.6 2je 2-(3-氯-苯基)-3-[4-(1-甲基-哌啶-4-基)-哌啡-1-基曱基]-1-側氧基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醢胺 0.79 612.2 612.2 2jf 翁 2-(3-氣-苯基)-1-侧氧基-3-[4-(2-哌啶-l-基-乙基)-哌啡-l-基甲基]-1,2-二氫-異喹啉-4-羧酸((S)-1 -苯基-丙基)-醯胺 0.84 626.2 626.7 K 2jg 2-(3-氯-苯基)-1-側氧基-3-[4-(2-吡咯啶-l-基-乙基)-哌啡-1-基甲基]-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 0.83 612.2 612.4 2jh 2-(3-氣-苯基)-1-側氣基-3-(4_ 吡啶-4-基f基-哌啡-1-基曱基)-1,2-二氮-異喧琳-4-缓酸 ((S)-l-苯基-丙基)-S篮胺 0.88 606.2 606.1 200906801 • 2ji 2-(3-氯-苯基)-3-[4-(2-嗎福林-4-基-乙基)-哌啶-1 -基甲基]-1 -側氧基-1，2-二氳-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 0.78 627.2 627.4 2jj 2-(3-氯-苯基)-3-[4-羥基-4-(3-甲氧基-苯基)-^π定-1-基曱基]-1-側氧基-1,2-二氳-異喹琳-4-竣酸((S)-l-苯基-丙基)· 醯胺 1.23 636.2 636.7 f. 2jk 3-[4-(乙醯基-甲基-胺基)-4-苯基-旅°定-1-基甲基]-2-(3-氯-苯基)-1-側氧基-1,2-二鼠-異喧琳-4·-棱酸((S)-l-苯基-丙基)_ 醯胺 1.26 661.2 662.0 2jl 1_側氧基-3-(4-苯乙基底明^ 1-基曱基)-2-間曱苯基-1，2-二氳-異喹啉-4-羧酸((S)-l-苯基 -丙基)-醯胺 1.15 598.8 599.6 , 2jm \ 3-[1，4’]聯哌啶-Γ-基曱基-1-側氧基-2-間甲苯基-1,2-二氣-異啥淋-4-竣酸((S)-1 -苯基-丙基)-醯胺 0.96 576.8 577.5 2jn 3-[4-(2-嗎福林-4-基-乙基)-哌啡-1-基曱基]-1-側氧基_2_間甲苯基-1,2-二氮-異唾琳-4-叛酸((s)-i-苯基-丙基)-醯胺 0.83 607.8 609.0 2jo 3-[4-(1-甲基-哌啶-4-基)-哌啡-1-基甲基]-1-側氧基_2_間 0.78 591.8 592.6 235 200906801 曱苯基-1，2-二氮·異啥琳-4-竣酸((S)-l-苯基·丙基)-醯胺 2jp 1-側氧基-3-[4-(2-哌啶-1-基-乙基)-哌明^1-基甲基]-2-間曱苯基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-酿胺 0.83 605.8 607.1 2jq 1-側氧基-3-[4-(2-吼咯啶-1-基 -乙基)-哌啡-1-基甲基]-2-間甲苯基-1,2-二氮-異喧琳-4-叛 0.81 591.8 592.6 f 酸((S)-l-苯基-丙基)-酿胺 2jr 1-側氧基-3-(4-°比啶-4-基甲基 -哌啡-1-基甲基)-2-間甲苯基 -1,2-二氫-異喹啉-4-羧酸((S)-1-苯基-丙基)-醯胺 0.85 585.7 586.0 2js 3-[4-(2-嗎福林-4-基-乙基)-旅咬-1 -基甲基]-1 -側乳基-2-間曱苯基-1，2-二氫-異喹啉-4-羧酸((S)-l-笨基-丙基)-酿胺 0.73 606.8 608.1 , 2Jt 3-[4-羥基-4-(3-甲氧基-苯基)-旅σ定-1-基甲基]-1-側氣基-2_ 間甲苯基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醢胺 1.18 615.8 616.3 2ju 3-[4-(乙醯基-甲基-胺基)-4-苯 1.19 640.8 641.7 基-派。定-1-基甲基]-1-側乳基-2-間曱苯基-1，2_二氮-異喧琳_ 4-羧酸((S)-l-苯基-丙基)·醯胺 236 200906801 來自實施例2之化合物之列表，續 2ka 2kb 化學名稱 tR MW (min) 3-(4-第三丁基-哌啡-1-基甲 1.06 601.2 基)-8-氣-1-侧氧基-2-苯基-1，2_ 二氫-異喹啉-4-羧酸[(S)-環丙基-(3-亂-苯基)-甲基]-酿胺 8-氯-3-(4-異丙基-哌啡-1-基 1.01 557.1 m/z (MH+) 601.5 557.52ha 1-phenyl-propyl)-nonylamine 3-(6-chloro-3H-spiro[isobenzofuran-oxime.36 1,4'-piperidinyl]-fluorenyl-hydrazino)-1- side Oxy-2-phenyl-1,2-diaza-isoindole_ 4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 3-(4-{[4-chloro- 3-(4-Fluoro-phenyl)-indole-i.36 1-yl]-indenyl-amino}-Ben. Ding-1-ylmethyl)-1-yloxy-2-phenyl- 1,2-dihydro-isoquinoline-4-carboxylic acid ((5)-1 -phenyl-propyl)-bristamine 3-(1-ethylindenyl-spiro[porphyrin-3,4'-us 0 bottom biting]-1'-ylindenyl)-1-yloxy-2_phenyl-1,2-diqi-isoindolyl-4-decanoic acid ((S)-l-phenyl-propyl )--Amine 3-(1-Ethyl-5-fluoro-spiro[.pyroline-1.2 3,4'-piperidinyl]-indolyl-methyl)-1-oxo-2-benzene Base-1,2-di-oxo-isoindole_ 4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine-side oxy-3-(4-o-oxy-1-benzene 1.15 -1,3,8-triaza-spiro[4.5]dec-8-ylmethyl)-2-phenyl-1,2-diaza-isoindole>-4-decanoic acid (( S)-l-phenyl-propyl)- decyl 3-(4-ethylhydroamino-π bottom-1-one oxime 0.83 yl)-1 - oxo-2-phenyl-1, 2-Di-indole-isoquinoline-4-carboxylic acid ((S)-l-phenyl 618.2 753.4 624.8 642.8 625.8 536.7 618.4 753.4 625.6 643.4 626.6 537.4 225 2009 06801 2hb 2hc 2hd 2he 2hf 2hg 2hh -propyl)-guanamine 1 - pendantoxy-3.-(1-sidedoxy-2,8-di0.85 aza-spiro[4.5]癸-8-yl 2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-bristamine 3-[4-pyridin-4-( 3-Difluoromethyl-benzene 1.29 base)-Brigade. Ding-1-ylindenyl]-1-yloxy-2-myl-1,2-dimur-isoxan-4-carboxylic acid ((S)-1 -phenyl-propyl)-indole Amine 1 - pendant oxy-2-phenyl-3-(4-trifluoromethyl 1.3 yl- decyl.-1-ylmethyl)-1,2-diaza _isoindole _4-decanoic acid ((S)-l-phenyl-propyl)-guanamine 3-[4-(4-indolyl-piperidin-1-carbonyl)-〇.7 娘定-1--1-indenyl]-1 -Sideoxy-2_phenyl-1,2-dimur-isoindolin-4-deoxy acid ((S)-l-phenyl-propyl)-bristamine 3-(5-isopropyl-3H - snail [isobenzofurazan. 48 -1-1,4'-piperidine]-fluorenyl-methyl)-1- oxo-2-phenyl-1,2-diaza-iso-π-quine ^木-4-carboxylic acid ((S)-1 -phenyl-propyl)-decylamine 3- [4-(acetoxy-methyl-amino)-4-benzene 1.13 base-Brigade-1 -ylindolyl]-1-sideoxy_2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 4- { 1-[1-Silicon-2-phenyl-4-(1-1.03 phenyl-propylamine)- 1,2-di 548.7 549.7 639.7 547.6 605.8 625.8 626.8 663.9 640.3 548.4 607.0 626.6 627.7 664.7 226 200906801 氲-Isoquinolin-3-ylmercapto]-piperidin-4-yl}-Bergic-l-carboxylic acid tert-butyl ester 2hi (2-{l-[l-sideoxy-2 -Phenyl-4-(1-phenyl-propylaminemethanyl)-l,2-di -isoindol-3-ylmethyl]-0 butyl-4-yl}-ethyl)-amino carboxylic acid tert-butyl ester 1.19 622.8 623.5 2hj 3-(4-decylamino-4-benzene Benzyl.-1-ylhydrazino)-1-yloxy-2-phenyl-1,dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl) - decylamine 1.01 584.8 585.5 2hk 3-(4-Ethylamino-4-phenyl-julidine-1 -ylmethyl)-1-oxo-2-phenyl-1,2-di Hydrogen-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-bristamine 1.06 612.8 613.3 2hl 3-[4-Ethylamino-4-(3- gas-phenyl) )-Brigade 0-l-yl-methyl]-1-oxo-oxy-2-phenyl-1,2-di-miso-isoxan--4_carboxylic acid ((S)-l-phenyl-propionate Base)-decylamine 1.06 630.8 631.5 2hm 1-Sideoxy-3-[4-(4-Sideoxy-piperidine-1-l-yl)-Bud 0-yl-1-ylmethyl]-2_ Base-1,2-di-mouse-isostimulation>-4-sodium sulphate ((S)-l-phenyl-propyl)-decylamine 0.89 604.7 605.3 2hn 3-[4,4']bipiperidine -1-ylmethyl-1-oxo-2-phenyl-1,2-dimur-isoindole -4-decanoic acid ((S)-l-phenyl-propyl)-nitramine 0.7 562.8 563.2 2ho oxo-2-phenyl-4-(1-phenyl-propylamine oxime)-1,2-diaza-1.15 594.8 595.8 227 200906801 2hp 2hq 2hr 2hs \ 2ht 2hu Benzyl-3-ylmethyl]-piperidin-4-yl}-carbamic acid tert-butyl 3-[1,4']bipiperidin-fluorenyl-methyl-1-side 0.95 oxy- 2-phenyl-1,2-diaza-isoindolin-4-deoxalic acid [J singyl-(3-mur-phenyl)-methyl]-nonylamine 1-sideoxy-3_(4 _Phenylethyl-Ethylamine^ 1.15 1-ylmercapto)-2-phenyl-1,2-dihydro-iso-"Quie-4-pyruic acid] [ί-propyl-(3- gas-benzene -Methyl]-nonylamine 3-(4-isopropyl-pipeholylmethyl)-0.97 1-oxo-2-phenyl-1,2-diaza-isoindole-4-deoxy [ί propyl-(3- gas-phenyl)-methyl]-nonylamine 3-[4-(2-morphine-4-yl-ethyl)-pie 0.81 cultivating-1-ylmethyl ]-1-Sideoxy_2_Phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [d-propyl-(3-1-phenyl)-methyl]-acid amine 3- [4-(1-indolyl-pyridin-4-yl)-0-indenyl-78-phenyl-1-ylmethyl]-1-yloxy-2-phenyl-1,2-dihydro- Isoquinoline-4-carboxylic acid [玉莉propyl-(3-a-phenyl)-methyl]-acid amine 1-sided oxy-2-phenyl-3-[4-(2-piperidine) 0.82 -1-yl-ethyl)-«bottom $-1-ylmethyl]-1,2-diaza-isoindole-4-deoxy acid [J propyl-(3-fluoro-phenyl) -Methyl]-bristamine 592.8 614.8 552.7 623.8 607.8 621.8 593.5 615.5 553.8 624.6 608.9 622.6 228 20090 6801 ; 2hv 1-sided oxy-2-phenyl-3-[4-(2-°-pyrrolidin-1-yl-ethyl)-piperidin-1-ylmethyl]-1,2-di Chloro-isoindolin-4-weilic acid [cyclopropyl-(3-fluoro-phenyl)-methyl]-decylamine 0.8 607.8 608.8 2hw 1 - oxo-2-phenyl-3-(4- Pyridin-4-ylindenyl-piperidin-1-ylindenyl-1,2-di-oxo-isoindolin-4-derivative [cyclopropyl-(3-fluoro-phenyl)-indenyl] _ Brewing amine 0.84 601.7 602.6 f 2hx \ 3-(4-hydroxy-3,4,5,6-tetrahydro-211-ylmethyl)-1-oxo-2-phenyl-1,2-di Rat-isoindolin-4-retinic acid [d-propyl-(3-fluoro-phenyl)-methyl]-decylamine 0.77 602.7 603.7 2hy 3_[4_(2-folinin-4-yl-ethyl )-Phenidin-1-ylindenyl-1-one-oxy-2-phenyl-1,2-dimur-isoindole-4-treazone [cyclopropyl-(3-phenyl)- Methyl]-acid 0.75 622.8 623.7 i \amine 2hz 3-[4-hydroxy-4-(3-indolyl-phenyl)-piperidin-1-ylmethyl]-1-yloxy-2- Phenyl-1,2-di-molybdenum-isowalin-4-decanoic acid [cyclopropyl-(3-f-phenyl)-methyl]-nonylamine 1.17 631.7 632.6 2ia 3-[4-(ethylidene) Base-methyl-amino)-4-phenyl-pie. Ding-1-ylmethyl]-1-flavoryl- 1.18 656.8 657.8 2-phenyl-1,2-di-oxo-isoindolin-4-hypoacid [d-propyl-(3- gas-phenyl) )-Methyl]- 229 200906801 Acid amine 2ib 2-(2-Fluoro-phenyl)-1-oxo-3-(4-phenethyl·piperidinyl)-l,2-di Mouse-isoindolin-4-decanoic acid ((S)-1 -phenyl-propyl)-nonylamine 1.12 602.8 603.8 2ic 2-(2- gas-phenyl)-3-(4-isopropyl-明明^1-基曱基)-1-lateral gas group-1,2·diindole-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.96 540.7 541.7 2id 3-[1,4]bipiperidinyl-fluorenyl-2-yl-2-(2-fluoro-phenyl)-1-yloxy-1,2-diaza-isoindolin-4-indole ((S)-1 -Phenyl-propyl)-decylamine 1 580.7 581.7 2ie 2-(2-Ran-phenyl)-3-[4-(2-isofolin-4-yl-ethyl) -Phenamine ^1-ylmethyl]_ 1-sidedoxy·1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.82 611.8 612.5 2if 2-(2-Fluoro-phenyl)-3-[4-(1-indolyl-piperidinyl)·piperidin-1-ylmethyl]-1-yloxy-1,2- Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.76 595.8 596.8 2ig 2-(2- disordered-phenyl)-1· side-milk -1 -yl-ethyl)-pie-1-ylindenyl-1 2-Di-indole-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.81 609.8 610.5 2ih 2-(2-Ga-phenyl)-1-yloxy- 3-[4-(2-°Biluol-1-yl-ethyl)-Nianghu [:-1-ylmethyl]-1,2-diaza-isoindole- 0.8 595.8 596.7 230 200906801 - 4-carboxylic acid ((S)-l-phenylpropyl)-guanamine 2ii 2-(2-mur-phenyl)-1-oxo-3-(4-pyridin-4-ylmethyl) -piperidin-1-ylmethyl)-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.84 589.7 590.4 2ij 2-(2 -fluoro-phenyl)-3-(4- per-3,4,5,6-tetrahydro-2H-[4,4丨]bipyridyl-1-ylmethyl)-1_sideoxy- 1,2-diaza 0.85 590.7 591.3 f \ -isoindole _4_clear acid ((S)-1 -phenyl-propyl)-guanidine 2ik 2-(2-gas-phenyl)-3- [4-(2-Folinin-4-yl-ethyl)-Brigade. Ding-1-ylindenyl]-1_ oxo-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.76 610.8 611.7 2il 2 -(2-Gas-phenyl)-3-[4-|^iyl-4-(3-hydroxy-phenyl)-piperidin-1-ylmethyl]-1-oxoyl-1, 2-Dihydro-isoquine 1.21 619.7 620.3 c lin-4-decanoic acid ((S)-l-phenyl-propyl)_ V,·' guanamine 2im 3-[4-(2- hollyline- 4-yl-ethyl)-branched-1-ylindenyl-1-one-oxy-2-o-tolyl-1,2-dichloro-isoindolin-4-deoxalate ((S)- L-phenyl-propyl)-bristamine 0.82 607.8 608.8 2in 1-sided oxy-3-[4-(2-piperidin-1-yl-ethyl)-piperidin-1-ylindenyl]- 2-o-tolyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.81 605.8 606.9 231 200906801 2io 1-sideoxy-3 -(4-.pyridin-4-ylindolyl-piperidin-1-ylmethyl)_2-o-tolyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1 -Phenyl-propyl)-nonylamine 0.84 585.7 586.4 2ip 2-(3-Fluoro-phenyl)-1-oxooxy-3-(4-p-ethyl-pyramine-1-ylmethyl)- 1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nitramine 1.13 602.8 603.8 2iq 2-(3-mur-phenyl)-3-(4- Isopropyl-bromobenzyl)-1-oxooxy-1 2_ Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-sensitive amine 0.96 540.7 541.3 2ir 3-[1,4']bipiperidinyl-fluorenyl-methyl- 2-(3-dis-phenyl)-1-oxooxy-1,2-dioxa-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.98 580.7 581.8 2is 2-(3-Mosin-phenyl)-3-[4-(2-isofolin-4-yl-ethyl)-piperidin-1-ylmethyl]-1-flavoryl-1 ,2-dihydro-isoindole·_4_carboxylic acid ((S)-1 -phenyl-propyl)-decylamine 0.81 611.8 612.6 2it 2-(3- gas-phenyl)-3-[4-( 1-indolyl-Bistidine-4-yl-piperidin-1-ylindenyl]-1-yloxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l -Phenyl-propyl)-1 basket amine 0.75 595.8 596.8 2iu 2-(3-Fluoro-phenyl)-1-oxooxy-3-[4-0.8 609.8 610.7 (2-slightly definite-1 -yl) -ethyl)-fanny-1-ylmethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 232 200906801 . 2iv 2 -(3-mur-phenyl)-1-oxooxy-3-[4-(2σfcb 洛σ定l_yl-ethyl)-Numing:-1-ylindenyl]-1,2-di Nitrogen isoindolin-4-carboxylic acid ((S)-l-styl-propyl)-decylamine 0.79 595.8 596.8 2iw 2-(3-mur-phenyl)-1-flavoryl-3-( 4_ Pyridin-4-ylindenyl-pemamine M-ylindenyl-1,2-diindole-isoindole-4 -carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.83 589.7 590.2 2ix 2-(3- gas-phenyl)·3-[4·(2-ofofolin-4-yl- Ethyl) - mother. Dec-1-ylmethyl]-1_ oxo-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenylpropyl)-decylamine 0.73 610.8 611.6 2iy 2- (3-dis-phenyl)-3-[4-light-yl-4-(3-decyloxy-benyl)- 0-methyl-1,3-methyl--1-yloxy-1,2 - squirrel-isoindole-4-decanoic acid ((S)-l-phenyl-propyl) decylamine 1.18 619.7 620.7 2iz 3-[4-(ethyl aryl-fluorenyl-amino)-4- Phenyl-pyridine πι_ylmethyl]-2-(3-a-phenyl)-1_ oxo-1,2-dihydro-isoquine-4-cyclone (S) )-l-phenyl-propyl)-decylamine 1.2 644.8 645.7 2ja 2-(3-nitro-phenyl)-1 - flavonyl-3·(4_phenethyl-piperidin-1-ylmethyl) )-1> Di-myrazine-isowalin-4-acid ((S)-l-phenyl-propyl)-decylamine 1.17 619.2 619.4 2jb 2-(3-gas-phenyl)-3-(4 -Isopropyl-Niang 1 557.1 557.5 233 200906801 Till-1-ylmethyl)-1-oxooxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl -propyl)-nonylamine 2jc 3-[1,4]bipiperidin-1'-ylmethyl-2-(3-a-phenyl)-1-yloxy-1,2-diaza- Σσ奎琳_4_       福福林_ 4-yl-ethyl)-piperidin-1-yl ]-1-Sideoxy-1,2-diaza-isosalin-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.86 628.2 628.6 2je 2-(3-chloro- Phenyl)-3-[4-(1-methyl-piperidin-4-yl)-piperidin-1-ylindenyl]-1-yloxy-1,2-dihydro-isoquinoline- 4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.79 612.2 612.2 2jf Weng 2-(3- gas-phenyl)-1-yloxy-3-[4-(2- Piperidine-l-yl-ethyl)-piperidin-l-ylmethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1 -phenyl-propyl)- Indoleamine 0.84 626.2 626.7 K 2jg 2-(3-Chloro-phenyl)-1-oxo-3-[4-(2-pyrrolidinyl-l-yl-ethyl)-piperidin-1-yl 1,1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.83 612.2 612.4 2jh 2-(3-gas-phenyl)-1 -Side-based 3-(4-pyridin-4-ylf-phenyl-phenyl- cyano-1-yl)-1,2-diaza-isoindolyl-4-acid ((S)-l-benzene --propyl)-S basket amine 0.88 606.2 606.1 200906801 • 2ji 2-(3-chloro-phenyl)-3-[4-(2-norfosin-4-yl-ethyl)-piperidine-1 -ylmethyl]-1 -p-oxy-1,2-dioxa-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.78 627.2 627.4 2jj 2-( 3-Chloro-phenyl)-3-[4-hydroxy-4-(3-methoxy-phenyl)-^π-dec-1-ylindenyl]-1-yloxy -1,2-dioxa-isoquinoline-4-decanoic acid ((S)-l-phenyl-propyl)·decylamine 1.23 636.2 636.7 f. 2jk 3-[4-(ethenyl-methyl -amino)-4-phenyl-branched-l-ylmethyl]-2-(3-chloro-phenyl)-1-yloxy-1,2-dimur-isoindole-4 ·-Chromic acid ((S)-l-phenyl-propyl)_ decylamine 1.26 661.2 662.0 2jl 1_Sideoxy-3-(4-phenethyldiamine^-1-ylindenyl)-2-inter Phenylphenyl-1,2-dioxa-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 1.15 598.8 599.6 , 2jm \ 3-[1,4'] Piperidine-fluorenyl-mercapto-1-yloxy-2-m-tolyl-1,2-dioxa-isoindole-4-decanoic acid ((S)-1 -phenyl-propyl)- Indoleamine 0.96 576.8 577.5 2jn 3-[4-(2-Folinin-4-yl-ethyl)-piperidin-1-ylindenyl]-1-yloxy-2_m-tolyl-1, 2-Diazin-isosalin-4-Resin ((s)-i-phenyl-propyl)-decylamine 0.83 607.8 609.0 2jo 3-[4-(1-methyl-piperidin-4-yl) )-piperidin-1-ylmethyl]-1-sideoxy-2_ between 0.78 591.8 592.6 235 200906801 Phenylphenyl-1,2-diaza-isoindolin-4-indole ((S)- L-phenyl-propyl)-nonylamine 2jp 1-p-oxy-3-[4-(2-piperidin-1-yl-ethyl)-piperidine-l-ylmethyl]-2-inter Phenylphenyl-1,2-dihydro-isoquinoline-4- Acid ((S)-l-phenyl-propyl)-bristamine 0.83 605.8 607.1 2jq 1-sided oxy-3-[4-(2-indolyl-1-yl-ethyl)-piperidin- 1-ylmethyl]-2-m-tolyl-1,2-diaza-isoindole-4-rebel 0.81 591.8 592.6 f acid ((S)-l-phenyl-propyl)-bristamine 2jr 1 -Sideoxy-3-(4-°pyridin-4-ylmethyl-piperidin-1-ylmethyl)-2-m-tolyl-1,2-dihydro-isoquinoline-4-carboxylate Acid ((S)-1-phenyl-propyl)-decylamine 0.85 585.7 586.0 2js 3-[4-(2-Wufolin-4-yl-ethyl)-Bucking-1 -ylmethyl] -1 - flavonyl-2-m-phenylphenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-styl-propyl)-nitramine 0.73 606.8 608.1 , 2Jt 3-[4-Hydroxy-4-(3-methoxy-phenyl)-birthidine-1-ylmethyl]-1-indolyl-2_m-tolyl-1,2-dihydro-iso Quinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 1.18 615.8 616.3 2ju 3-[4-(ethenyl-methyl-amino)-4-benzene 1.19 640.8 641.7 Base-pai. Ding-1-ylmethyl]-1-salyl-2-indenylphenyl-1,2-dinitro-isoindolyl-4-carboxylic acid ((S)-l-phenyl-propyl) Indoleamine 236 200906801 List of compounds from Example 2, continued 2ka 2kb Chemical name tR MW (min) 3-(4-Terbutyl-piperidin-1-ylmethyl 1.06 601.2 base)-8-gas- 1-Phenoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-dis-phenyl)-methyl]-bristamine 8 -Chloro-3-(4-isopropyl-piperidin-1-yl 1.01 557.1 m/z (MH+) 601.5 557.5

2kc 曱基)-1 -侧氧基-2-苯基-1,2-二風τ異π奎琳_4_缓酸((S)-l-苯基_ 丙基)-醯胺 571.7 8-氣-3-(4-異丁基-哌啡-1-基 1.07 571.2 \ 2kd 曱基)-1-側氧基-2-苯基-1,2-二鼠-異喧琳_4_竣酸((S)-l-本基_ 丙基)-醯胺 8-氯-3-(八氫-吡啶并[1,2-a]吡 1.03 569.1 明1 _2-基曱基)-1 -側氣基_2_苯 569.6 基-1，2-二氫-異喹啉-4-羧酸 ((S)-1-苯基-丙基)-酿胺 2ke 607.9 8-氯-3-(4-羥基-3,4,5,6-四氫-0.8 607.2 2H- [4,4']聯吡啶-1 -基曱基)-1 -側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸((S)-1 -苯基-丙基)- 醯胺 237 200906801 2kf 8_氯-3-(4-環丙基曱基-哌啡-1 -基甲基)-1 -側乳基-2-苯基_ 1，2-二氫-異喹啉-4-羧酸((S)-l- 苯基-丙基)-醯胺 1.04 569.1 569.8 2kg 8-氣-3-[4-(2-嗎福林-4-基-乙基)-aj^a定-1-基曱基]-1-側氧基_ 2-苯基-1,2-二氳-異喹啉-4-羧酸((S)-l-苯基-丙基)-酿胺 0.75 627.2 627.4 2kh 8-氮-3-[1，4]二鼠雜壞庚烧-1-基曱基-1-側氧基-2-苯基-1,2-二氳-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 0.98 529.1 529.3 2ki 8_氯-3_((S)-3-甲基-哌啡-1-基曱基)-1-側乳基-2-苯基-1,2-二氫-異π奎淋_4-竣酸((S)-l-笨基_ 丙基)-醯胺 0.98 529.1 529.2 2kj 8-氯-3-咪唑-1-基甲基-1-側氧基-2-苯基-1,2-二氮-異啥淋-4_ 羧酸((S)-l-苯基-丙基)-醯胺 0.92 497.0 497.4 2kk 8-氯-3-(4-甲基-咪唑-1-基曱基)-1-側乳基-2-苯基-1,2-二氮 -異哇淋_4_竣酸((S)-l-苯基-丙基)-醯胺 0.97 511.0 511.3 2kl 3-(第三丁基胺基-甲基)-8-氯- 1.06 502.1 502.5 238 200906801 1-側乳基_2-苯基-1，2-二風-異啥琳-4·魏酸((S)-l-苯基-丙基)-醯胺 2km 2kn / 2ko 2kp i \. 2kq 2kr 8-氣-3-(異丙基胺基-甲基)-1-側氧基-2-苯基-1,2-二鼠-異啥啉-4-羧酸((S)-1 -苯基-丙基)- 酸胺 1 488.0 488.6 8-氯-3-[4-羥基-4-(3-甲氧基-苯基)-哌啶-1-基曱基]-1-侧氧基-2-本基-1,2-二氮-異喧琳-4_ 羧酸((S)-1 -苯基-丙基)-醯胺 1.2 636.2 636.8 3-(4-第三丁基-哌啡-1-基甲基)-8-氣-1-側氧基-2-苯基-1，2_ 二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 1.03 571.2 571.4 3-苯并咪唑-1-基甲基-1-側氧基-2-苯基-1,2-二氮-異啥琳-4-缓酸((S)-l-苯基-丙基)-酿胺 1.02 512.6 513.3 側氧基-2-苯基-3-α比。坐-1-基甲基-1,2-二氫-異喹啉-4-羧酸 ((S)-l-笨基-丙基)-酸胺 1.54 462.6 463.4 3-(4-甲基-吡唑-1-基甲基)-1- 1.65 476.6 477.3 側氧基-2-苯基-1，2-二氯-異喧啉-4-羧酸((S)-l-苯基-丙基)- 239 200906801 酸胺 2ks 1-側氧基-2-苯基-3-[l，2,3]三 1.23 唑-1 -基曱基-1,2-二氫-異喹啉-4-竣酸((S)-l-苯基-丙基)-酿胺 2kt 2-(3-曱氧基-苯基)-1-側氧基-0.82 3-(4-吡啶-4-基曱基-哌啡-1-基曱基)-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 2ku 2-(4-曱氧基-苯基)-3-[4-(2-嗎 0.8 福林-4-基-乙基)-σ底明^1-基甲基]-1-側氧基-U-二氫-異喹啉 -4-竣酸((S)-l-苯基-丙基)-酿胺 2kv 2-(4-氟-苯基)-1-側氧基-3-(4- 1.13 苯乙基-哌啡-1-基甲基)-1,2-二鼠異σ奎琳-4-竣酸((S)-l-苯基-丙基)-醯胺 2kw 2-(4-氟-苯基)-3-(4-異丙基-哌 0.95 啡-1-基曱基H-側氧基-U-二風-異η奎琳-4-叛酸((S)-l-苯基_ 丙基)-醯胺 2kx 3-[1,4']聯哌啶-Γ-基甲基-2-(4- 0.98 氟-苯基)小側氧基-1,2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙 463.5 464.4 601.7 623.8 602.8 540.7 580.7 602.7 624.5 603.8 541.7 581.9 240 200906801 2ky 2kz 21a 21b / 21c 21d 基)-醯胺 2-(4-氟-苯基)-3-[4-(2-嗎福林-0.79 4-基-乙基)-π底[井-1-基曱基]-1_ 侧氧基-1,2-二氫-異喧琳-4-叛酸((S)-l-苯基-丙基)-醯胺 2-(4-氟-苯基)-3-[4-(1-曱基-哌 0.74 π定-4-基)-0底明^1-基甲基]-1-侧氧基-1,2-二氫-異喧琳-4-叛酸 ((S)-l-苯基-丙基)-醯胺 2-(4-氟-苯基)-1-側氧基-3-[4- 0.78 (2-0比略唆]-基-乙基基甲基]-1，2-二氫-異啥琳-4-缓酸((S)-l-苯基-丙基)-醯胺 2-(4-氟-苯基)-3-[4-羥基-4-(3- 1.18 曱氧基-苯基)-哌啶-1-基曱基]-1 -側氧基-1，2-二氮-異喧咐· _4_羧酸(⑸-1 -苯基-丙基)-醯胺 2-(4-氣-苯基)-1-側氧基-3-(4- 1.17 苯乙基-旅明^1-基甲基)-1，2_ 二氮_異啥淋-4-竣酸((S)-l-本基-丙基)-酿胺 2-(4-氯-苯基)-3-(4-異丙基-哌 0.99 〇#-1-基曱基)-；H則氧基-1,2-二 611.8 612.6 595.8 595.8 619.7 619.2 557.1 596.8 596.7 620.4 619.3 557.4 241 200906801 氫-異喧琳_4-叛酸((S)-l-苯基-丙基)-醯胺 21e 3-[1,4’]聯哌啶-Γ-基甲基-2-(4-氣-苯基)-1-側乳基-1,2-二鼠_ 異喹啉-4-羧酸(⑻小苯基-丙基)-醯胺 1.04 597.2 597.8 21f f \ 2-(4-氣-苯基)-3 - [4-(2-嗎福林_ 4-基-乙基)-哌啡-1-基甲基]-1-側氧基-1，2-二氮-異唾琳-4-叛酸((S)-l-苯基-丙基)-醯胺 0.85 628.2 628.6 21g 2-(4-氣-苯基)-3-[4-(1-曱基-π辰啶-4-基)-旅[井-1-基甲基Η-側乳基-1,2-二氮-異哇琳-4-竣酸 ((S)-l-苯基-丙基)-酿胺 0.77 612.2 612.3 21h / _ 2-(4-氣-苯基)-1-側氧基-3-[4-(2_哌啶-1 -基-乙基)-哌啡-1 -基甲基]-1,2-二氫-異喹啉-4-羧酸 ((S)-l-苯基-丙基)-酸胺 0.84 626.2 626.8 21i 2-(4-氯-苯基)-1-侧氧基-3-[4· (2-°比咯啶-1 -基-乙基)-哌啡-1 -基甲基]-1，2-二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-醯胺 0.81 612.2 612.6 21j H4-第三丁基-哌啡-1-基甲基)_8_鼠-1-側乳基-2-苯基-1,2- 0.96 554.7 555.7 200906801 21k 二氫-異喹啉-4-羧酸((S)-l-苯基-丙基)-酿胺 8-氯-3-環丙基胺基曱基-1-側 0_61 486.0 486.4 211 f \ 21m 氧基-2-苯基-1,2-二氫-異喹啉-(方法B) 4-缓酸((S)-l-苯基-丙基)-酸胺 3-(4-第三丁基-哌啡-1-基甲 0_98 584.7 基)-8-氣-1-側氧基-2-苯基-1,2- 二氫-異喹啉-4-羧酸[(S)-環丙基-(3-鼠-苯基)-甲基]-酿胺 8_氟-1-側氧基_2_苯基_3_哌啡 0.89 528.6 -1 -基甲基-1,2-二氳-異喹啉-4- 585.5 529.4 21n 21o 羧酸[⑸-環丙基-(3-1-苯基)-曱基]-醯胺（*) 8-氣-1-側氧基-3-(3-側乳基-π比 1.14 528.6 唑啶-1-基曱基)-2-苯基-1,2-二氫-異啥琳_4_竣酸[(S)-^丙基_ (3-氟-苯基)-甲基]-醯胺 8-氟-1 -側氧基-3-(3-側氧基-哌 1.13 542.6 Q^-l-基甲基)-2-苯基-1,2-二氮 528.8 543.5 _異啥琳_4_叛酸[(S)-壞丙基-(3-貌-苯基)-甲基]-醯胺 (*):將1-(第三丁氧基羰基）哌畊用作胺且BOC-基團在隨後步驟中在室溫下藉由***及甲醇（1:1)中之2MHC1 移除。 243 200906801 實施例32kc fluorenyl)-1 - oxo-2-phenyl-1,2-dipho τ iso π quinine _4_caustic acid ((S)-l-phenyl-propyl)-decylamine 571.7 8 -gas-3-(4-isobutyl-piperidin-1-yl 1.07 571.2 \ 2kd fluorenyl)-1-yloxy-2-phenyl-1,2-dimur-isoindole_4_ Capric acid ((S)-l-benyl-propyl)-guanamine 8-chloro-3-(octahydro-pyrido[1,2-a]pyrazole 1.03 569.1 Ming 1 _2-ylindenyl)-1 - side gas group 2_benzene 569.6 yl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-nitramine 2ke 607.9 8-chloro-3- (4-hydroxy-3,4,5,6-tetrahydro-0.8 607.2 2H-[4,4']bipyridin-1-ylindenyl)-1 -p-oxy-2-phenyl-1,2 -Dihydro-isoquinoline-4-carboxylic acid ((S)-1 -phenyl-propyl)-decylamine 237 200906801 2kf 8_chloro-3-(4-cyclopropylindenyl-piperidin-1 -ylmethyl)-1 -yllacyl-2-phenyl- 1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 1.04 569.1 569.8 2kg 8-ox-3-[4-(2-)-Folin-4-yl-ethyl)-aj^a-1,4-ylindenyl]-1-yloxy_2-phenyl-1 ,2-diindole-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-bristamine 0.75 627.2 627.4 2kh 8-nitro-3-[1,4] Ethyl-1-ylindol-1-yloxy-2-phenyl-1,2-diindole-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.98 529.1 529.3 2ki 8_chloro-3_((S)-3-methyl-piperidin-1-ylindenyl)-1-ylidery -2-phenyl-1,2-dihydro-iso-π-quinone_4-decanoic acid ((S)-l-styl-propyl)-decylamine 0.98 529.1 529.2 2kj 8-chloro-3-imidazole- 1-ylmethyl-1-oxo-2-phenyl-1,2-diaza-isoindole-4_carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.92 497.0 497.4 2kk 8-chloro-3-(4-methyl-imidazol-1-ylindenyl)-1-y-lacyl-2-phenyl-1,2-diaza-iso-wrap _4_decanoic acid (( S)-l-phenyl-propyl)-nonylamine 0.97 511.0 511.3 2kl 3-(t-butylamino-methyl)-8-chloro-1.06 502.1 502.5 238 200906801 1-sided lactyl-2-benzene Base-1,2-two wind-isoterpene-4·wei acid ((S)-l-phenyl-propyl)-guanamine 2km 2kn / 2ko 2kp i \. 2kq 2kr 8-gas-3-( Isopropylamino-methyl)-1-oxo-2-phenyl-1,2-dimur-isoindoline-4-carboxylic acid ((S)-1 -phenyl-propyl)- Acid amine 1 488.0 488.6 8-chloro-3-[4-hydroxy-4-(3-methoxy-phenyl)-piperidin-1-ylindenyl]-1-nonoxy-2-benyl- 1,2-diaza-isoindolin-4_carboxylic acid ((S)-1 -phenyl-propyl)-decylamine 1.2 636.2 636.8 3-(4-tert-butyl-piperidin-1-yl Base)-8-gas-1-side oxygen -2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 1.03 571.2 571.4 3-benzimidazol-1-ylmethyl -1-Sideoxy-2-phenyl-1,2-diaza-isoindolin-4-o-acid ((S)-l-phenyl-propyl)-bristamine 1.02 512.6 513.3 side oxy- 2-phenyl-3-α ratio. -1-ylmethyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-styl-propyl)-acid amine 1.54 462.6 463.4 3-(4-methyl- Pyrazol-1-ylmethyl)-1- 1.65 476.6 477.3 oxo-2-phenyl-1,2-dichloro-isoindoline-4-carboxylic acid ((S)-l-phenyl-propane Base)- 239 200906801 Acid amine 2ks 1-sided oxy-2-phenyl-3-[l,2,3]tri- 1.23 azole-1 -ylmercapto-1,2-dihydro-isoquinoline-4 -capric acid ((S)-l-phenyl-propyl)-bristamine 2kt 2-(3-decyloxy-phenyl)-1-yloxy-0.82 3-(4-pyridin-4-yl Mercapto-piperidin-1-ylindenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ku 2-(4-曱oxy-phenyl)-3-[4-(2-?0.8 phenylene-4-yl-ethyl)-σ 明 ^ 1--ylmethyl]-1-yloxy-U-dihydrogen -isoquinoline-4-decanoic acid ((S)-l-phenyl-propyl)-bristamine 2kv 2-(4-fluoro-phenyl)-1-yloxy-3-(4- 1.13 benzene Ethyl-piperidin-1-ylmethyl)-1,2-dimurium σ 奎竣竣竣 ( ((S)-l-phenyl-propyl)-decylamine 2kw 2-(4- Fluoro-phenyl)-3-(4-isopropyl-piperazine 0.95-phenyl-1-ylindenyl H-sideoxy-U-two-wind-iso-η-quine-4-deoxy acid ((S)-l -Phenyl-propyl)-nonylamine 2kx 3-[1,4']bipiperidinyl-fluorenyl-methyl-2-(4-0.98 fluoro-phenyl) small pendant oxy -1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propane 463.5 464.4 601.7 623.8 602.8 540.7 580.7 602.7 624.5 603.8 541.7 581.9 240 200906801 2ky 2kz 21a 21b / 21c 21d base) -nonylamine 2-(4-fluoro-phenyl)-3-[4-(2-ofoline-0.79 4-yl-ethyl)-π-[[-1-ylindenyl]-1_ side oxygen 1,2-dihydro-isoindolin-4-deoxalate ((S)-l-phenyl-propyl)-nonylamine 2-(4-fluoro-phenyl)-3-[4-( 1-fluorenyl-piperazine 0.74 π-1,4-yl)-0- phenoxy-l-ylmethyl]-1-yloxy-1,2-dihydro-isoindole-4-deoxy acid ((S )-l-phenyl-propyl)-nonylamine 2-(4-fluoro-phenyl)-1-yloxy-3-[4-0.78 (2-0 ratio 唆)-yl-ethyl group Methyl]-1,2-dihydro-isoindolin-4-o-acid ((S)-l-phenyl-propyl)-nonylamine 2-(4-fluoro-phenyl)-3-[4 -hydroxy-4-(3- 1.18 decyloxy-phenyl)-piperidin-1-ylindenyl]-1 -trioxy-1,2-diaza-isoindole·_4_carboxylic acid ((5) -1 -Phenyl-propyl)-nonylamine 2-(4-Gas-phenyl)-1-oxooxy-3-(4- 1.17 phenethyl-Briamine^1-ylmethyl)-1 , 2_ Diazo-isoindole-4-decanoic acid ((S)-l-benyl-propyl)-bristamine 2-(4-chloro-phenyl)-3-(4-isopropyl-piperidin 0.99 〇#-1-ylindenyl)-;H-oxyl-1,2-two 611.8 612.6 595.8 595.8 619.7 619.2 557.1 596.8 596.7 620.4 619.3 557.4 241 200906801 Hydrogen-isoindole_4-repulsive ((S)-l-phenyl-propyl)-nonylamine 21e 3-[1,4']bipiperidinium-indole -ylmethyl-2-(4-a-phenyl)-1-flavoryl-1,2-di-mo-isoquinoline-4-carboxylic acid ((8) small phenyl-propyl)-decylamine 1.04 597.2 597.8 21f f \ 2-(4-Gas-phenyl)-3 - [4-(2-Walfolin-4-yl-ethyl)-piperidin-1-ylmethyl]-1-side oxygen Base-1,2-diaza-isosalin-4-deoxalate ((S)-l-phenyl-propyl)-decylamine 0.85 628.2 628.6 21g 2-(4-gas-phenyl)-3- [4-(1-indolyl-π- suldin-4-yl)-Brigade [well-1-ylmethylhydrazine-siallacyl-1,2-diaza-isovallin-4-decanoic acid (( S)-l-phenyl-propyl)-nitramine 0.77 612.2 612.3 21h / _ 2-(4- gas-phenyl)-1-oxo-3-[4-(2-piperidin-1 - Base-ethyl)-piperidin-1 -ylmethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-acid amine 0.84 626.2 626.8 21i 2-(4-Chloro-phenyl)-1-oxooxy-3-[4·(2-°-pyridin-1-yl-ethyl)-piperidin-1-ylmethyl]-1 ,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 0.81 612.2 612.6 21j H4-tert-butyl-piperidin-1-ylmethyl) _8_murine-1-flank-2-phenyl-1 , 2- 0.96 554.7 555.7 200906801 21k Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-bristamine 8-chloro-3-cyclopropylamino fluorenyl-1 - side 0_61 486.0 486.4 211 f \ 21m oxy-2-phenyl-1,2-dihydro-isoquinoline-(method B) 4-acid ((S)-l-phenyl-propyl)- Acid amine 3-(4-t-butyl-piperidin-1-ylmethyl 0-98 584.7-yl)-8-a-1-1-oxo-2-phenyl-1,2-dihydro-isoquinoline- 4-carboxylic acid [(S)-cyclopropyl-(3-mur-phenyl)-methyl]-bristamine 8_fluoro-1-oxooxy-2_phenyl_3_piperidin 0.89 528.6 - 1 -ylmethyl-1,2-dioxa-isoquinoline-4- 585.5 529.4 21n 21o carboxylic acid [(5)-cyclopropyl-(3-1-phenyl)-fluorenyl]-decylamine (*) 8-gas-1-oxooxy-3-(3-flavoryl-π ratio 1.14 528.6 oxazin-1-ylindenyl)-2-phenyl-1,2-dihydro-isoindole _4 _Citrate [(S)-(propyl)-(3-fluoro-phenyl)-methyl]-nonylamine 8-fluoro-1-oxo-3-(3-oxo-peline 1.13 542.6 Q ^-l-ylmethyl)-2-phenyl-1,2-diaza 528.8 543.5 _isoindene _4_ tacrolein [(S)- propyl-(3-pheno-phenyl)- Base]-decylamine (*): 1-(Tertibutoxycarbonyl) piperazine is used as the amine and the BOC- group is in the subsequent step at room temperature by diethyl ether and methanol (1:1). 2MHC1 In addition. 243 200906801 Example 3

f 3 31~側氧基-3-(2-側氧基-吡咯啶-1_基甲基）_2_苯芙_ 1 2 _ — & 土 ’ 虱~異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺。向2~。比n各啶酮（〇·1 ml)於四氫呋喃（2 ml)中之溶中、、号^力知 η'、σ氧化鈉（20 mg，礦物油中60%分散液）。將反應混合物在不班,扣、衣境溫度下攪拌直至氣體析出停止，接著添加3 _ 漠曱裏_ 1 .f 3 31~Sideoxy-3-(2-o-oxy-pyrrolidin-1_ylmethyl)_2_phenylfu_ 1 2 _ — & soil '虱~isoquinoline-4-carboxylic acid ( (S)-l-Phenyl-propyl)-guanamine. To 2~. It is soluble in tetrahydrofuran (2 ml) than n-hexanone (〇1 ml), and η', σ-sodium oxide (20 mg, 60% dispersion in mineral oil). The reaction mixture was stirred at the temperature of the unloaded, buckled and clothing conditions until the gas evolution stopped, and then 3 _ 曱曱 _ 1 was added.

土則氧基-2-苯基_1，2-二氫-異喹琳_4-羧酸（（S)-1_苯基丙基酿胺（30 mg)。30分鐘後，添加乙酸（〇.〇5 mi) 且真空移除揮發物。產物藉由si〇2急驟層析法（5 g，丨，2_ 一氯乙燒接著梯度庚烷中50%至100%乙酸乙酯）純化產生17111经白色固體。產率56%。1^-；^8(111/7) 480.5 (1^11+); tR = 1·21 。類似地獲得以下化合物： ’ 244 200906801则氧基 oxy-2-phenyl-1,2-dihydro-isoquinolin-4-carboxylic acid ((S)-1 phenylpropyl urethane (30 mg). After 30 minutes, acetic acid was added ( 〇.〇5 mi) and the volatiles were removed in vacuo. The product was purified by flash chromatography (5 g, EtOAc, EtOAc (EtOAc) The yield was 56%. 1^-;^8(111/7) 480.5 (1^11+); tR=1·21. The following compound was obtained similarly: ' 244 200906801

3b 8 -氣-1-側氧基- 3- (2 -側氧基-D比洛π定_ι_基曱基）_2_苯基-1,2-二氫-異啥淋-4-幾酸（（S)-l -苯基-丙基）-醯胺。 LC-MS (m/z) 514.7 (MH+) ; tR = 1_33 〇中間物之合成3b 8 -gas-1-sideoxy- 3- (2-o-oxy-D piroxicam _ι_yl fluorenyl)_2_phenyl-1,2-dihydro-isoindole-4- A few acids ((S)-l-phenyl-propyl)-guanamine. LC-MS (m/z) 514.7 (MH+); tR = 1_33 合成 Synthesis of intermediates

3-側氧基-吡唑啶-1-羧酸第三丁酯。向 3-°比啥咬酿| 鹽酸鹽（55.3 mg，0.45 mmol )、Na2C03 (133 mg，1.24 mol )、水（0.5 ml )與二腭烧（〇·054 ml ) 之混合物中添加二_烷（0.16 ml )中之BOC-酐（101 mg， 0.46 mmol )且在室溫下攪拌隔夜。將其過濾，蒸發且未經進一步純化用於隨後步驟中。1H NMR (500 MHz，DMSO-d6): 1.4 (s，9H)，2.32 (t，J=9 Hz，2H)，3.6 (t，J=9 Hz，2H)。 245 2009068013-tertiary oxy-pyrazolidine-1-carboxylic acid tert-butyl ester. Add to the mixture of 3-° ratio bite | hydrochloride (55.3 mg, 0.45 mmol), Na2C03 (133 mg, 1.24 mol), water (0.5 ml) and diterpene (〇·054 ml) BOC-anhydride (101 mg, 0.46 mmol) in hexane (0.16 ml) was stirred at room temperature overnight. It was filtered, evaporated and used in the next step without further purification. 1H NMR (500 MHz, DMSO-d6): 1.4 (s, 9H), 2.32 (t, J = 9 Hz, 2H), 3.6 (t, J = 9 Hz, 2H). 245 200906801

3c 1-側氧基-2-苯基-3-(1Η-[1，2,4]三。坐-3-基硫烷基曱基）-1,2-二氫-異啥淋-4-致酸（（S)-l-笨基-丙基）-酿胺。 LC-MS (m/z) 496.6 (MH+) ; tR = 0.64 (方法 B)。3c 1-Phenoxy-2-phenyl-3-(1Η-[1,2,4]tris(ytyl-3-ylsulfanylalkyl)-1,2-dihydro-isoindole-4 - Acidic ((S)-l-styl-propyl)-bristamine. LC-MS (m/z) 496.6 (MH+);

3d 8-氯-1-側氧基-3-(2-側氧基-吡咯啶-卜基甲基）-2-苯基-1,2-二氫-異喹琳-4-羧酸[(S)-環丙基-(3-氟-苯基）_甲基]- 醯胺。 LC-MS (m/z) 544.3 (MH+); tR = 1.39。W NMR (250 MHz, 7〇°C, DMSO-d6): 0.4-0.64 (m, 4H), 1.28 (m, 1H), 1.74 (m, 2H), 1-97 (m, 2H), 2.89 (br, 1H), 3.06 (H20), 4.02-4.14 (br, 2H), 4.51 (t, J=8.6 Hz, 1H), 7.08 (dt, 1H), 7.2-7.3 (m, 4H), 7.37-7.7 (m, 7H)，9.07 (d, J=8.1 Hz, 1H，NH)。 246 2009068013d 8-Chloro-1-oxo-3-(2-oxo-pyrrolidinyl-p-methyl)-2-phenyl-1,2-dihydro-isoquinolin-4-carboxylic acid [ (S)-Cyclopropyl-(3-fluoro-phenyl)-methyl]-guanamine. LC-MS (m/z) 495 (MH+); W NMR (250 MHz, 7 ° C, DMSO-d6): 0.4-0.64 (m, 4H), 1.28 (m, 1H), 1.74 (m, 2H), 1-97 (m, 2H), 2.89 ( Br, 1H), 3.06 (H20), 4.02-4.14 (br, 2H), 4.51 (t, J=8.6 Hz, 1H), 7.08 (dt, 1H), 7.2-7.3 (m, 4H), 7.37-7.7 (m, 7H), 9.07 (d, J = 8.1 Hz, 1H, NH). 246 200906801

3e 8-氟-1-側氧基-3-(2-侧氧基-吡咯啶-1-基甲基）-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醢胺。 LC-MS (m/z) 498.8 (MH+) ; tR = 1.23, tR = 0_68 (方法 B)。’H NMR (250 MHz，70。(：，DMSO-d6): 0.93 (t，J=7.3 Hz, 3H)，1.66-2.0 (m，6H)，2.84 (br t，1H)，3·01 (重疊之 H20 信號），3.98-4.08 (br, 2H)，4·97 (t, J=7.6 Hz，1H)，7.2-7.54 (m, 12 H), 7.69 (m, 1H), 8.77 (d，J = 7.9 Hz，1H，NH)。3e 8-fluoro-1-oxooxy-3-(2-o-oxy-pyrrolidin-1-ylmethyl)-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-Phenyl-propyl)-guanamine. LC-MS (m/z) 498.8 (MH+); tR = 1.23, tR = 0_68 (Method B). 'H NMR (250 MHz, 70. (:, DMSO-d6): 0.93 (t, J = 7.3 Hz, 3H), 1.66-2.0 (m, 6H), 2.84 (br t, 1H), 3·01 ( Overlapping H20 signals), 3.98-4.08 (br, 2H), 4·97 (t, J=7.6 Hz, 1H), 7.2-7.54 (m, 12 H), 7.69 (m, 1H), 8.77 (d, J = 7.9 Hz, 1H, NH).

3f 8-氣-1 -側氧基-3-(2-側氧基-σ比嘻11 定-1-基曱基）-2 -本基-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]- 醯胺。 LC-MS (m/z) 528.7 (MH+); tR = 1.29, tR = 0.7 (方法 B)。 Ή NMR (250 MHz, 80°C, DMSO-d6): 0.37-0.62 (m, 4H), 1.25 (m, 1H), 1.71 (五重峰，J=7.5 Hz, 2H), 1.94 (t, J=7.9 Hz, 2H)， 2.85 (br, 2H), 2.94 (H20), 4.05 (br, 2H), 4.5 (t, J=8.6 Hz, 1H), 7.04 (m, 1H), 7.17-7.32 (m, 5H), 7.32-7.52 (m, 5H), 7.7 (m, 247 200906801 -1H), 8.97 (d, J=8.1 Hz, 1H, NH) °3f 8-gas-1 -oxooxy-3-(2-olyoxy-σ 嘻11-decyl-1-ylindenyl)-2 -benyl-1,2-dihydro-isoquinoline-4 -carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-guanamine. LC-MS (m/z) 528.7 (MH+); t. NMR NMR (250 MHz, 80 ° C, DMSO-d6): 0.37-0.62 (m, 4H), 1.25 (m, 1H), 1.71 (five-peak, J=7.5 Hz, 2H), 1.94 (t, J =7.9 Hz, 2H), 2.85 (br, 2H), 2.94 (H20), 4.05 (br, 2H), 4.5 (t, J=8.6 Hz, 1H), 7.04 (m, 1H), 7.17-7.32 (m , 5H), 7.32-7.52 (m, 5H), 7.7 (m, 247 200906801 -1H), 8.97 (d, J=8.1 Hz, 1H, NH) °

3g 8 -氟-1-側乳基_3_(5_側氧基_n比唾。定_1_基甲基苯基-1,2-二氫-異喹啉_4_羧酸[(s)_環丙基_(3_氟_苯基）甲基]_ 醯胺。將3-側氧基-吡唑啶_；!_羧酸第三丁酯用於藉由NaH促進之偶合反應中。將所獲得之中間物2_(4_{[(s)_環丙基兴弘氟-苯基）-甲基]-胺甲醯基卜8_氟_丨_側氧基_2_苯基4,2 —二氫_ 異喹啉-3-基甲基）·3_側氧基_吡唑啶_丨_ BOC-基團在室溫下以㈣—甲醇（1:1)t之/Μ—=之歷時30分鐘且將標題化合物藉由製備型lc趟純化。 LC-MS (m/z) 529.3 (MH+) ; tR = 1.15 〇3g 8 -fluoro-1-saltyl _3_(5_sideoxy_n is more than salivary. 1-1 ylmethylphenyl-1,2-dihydro-isoquinoline _4-carboxylic acid [( s)_cyclopropyl-(3-fluoro-phenyl)methyl]-decylamine. 3-tert-oxy-pyrazolidine_;!-carboxylic acid tert-butyl ester for coupling by NaH promotion In the reaction, the obtained intermediate 2_(4_{[(s)_cyclopropyl Xinghong fluoro-phenyl)-methyl]-amine mercapto phenyl 8_fluoro_丨_sideoxy_2_ Phenyl 4,2-dihydro-isoquinolin-3-ylmethyl)·3_sideoxy_pyrazolidine_丨_ BOC- group at room temperature with (tetra)-methanol (1:1)t / Μ - = for 30 minutes and the title compound was purified by preparative lc. LC-MS (m/z) 529.3 (MH+); tR = 1.15 〇

°底啡-1-基甲基）-2-苯基 -(3-氟-苯基）-甲基;|_醯 3h 8-氟-1-側氧基_3-(2_側氧基_ -1,2-二氫-異喹啉-4-羧酸[(s)-環丙基 248 200906801 -胺。自2-側氧基_4_(第三丁氧基羰基）哌畊隨後移除B〇c 基團’類似地製備標題化合物。Lc_MS (m/z) 543.6 (MH+); (r = 0·84 〇°Desin-1-ylmethyl)-2-phenyl-(3-fluoro-phenyl)-methyl;|_醯3h 8-fluoro-1-yloxy_3-(2_sideoxy _-1,2-Dihydro-isoquinoline-4-carboxylic acid [(s)-cyclopropyl 248 200906801 -amine. From 2-sided oxy-4_(t-butoxycarbonyl) piperene The title compound was prepared analogously except for the B〇c group. Lc_MS (m/z) 543.6 (MH+); (r = 0·84 〇

FF

8-氟-1-側氧基_3_(2_側氧基_哌啶-丨_基甲基）_2•苯基_ 1，2-二氫-異喹啉_4_羧酸[(s)_環丙基_(3_氟-苯基）_甲基]_醯胺。自哌啶酮類似地製備標題化合物。LC-MS (m/z) Μ2·5 (MH+) ; tR = 1.35。 / 1. 實施例48-fluoro-1-oxooxy_3_(2_sideoxy-piperidine-hydrazinylmethyl)_2•phenyl-1,2-dihydro-isoquinoline_4_carboxylic acid [(s )_cyclopropyl-(3-fluoro-phenyl)-methyl]-decylamine. The title compound was prepared analogously from piperidone. LC-MS (m/z) Μ 2·5 (MH+); tR = 1.35. / 1. Example 4

4a 3-氰基甲基-1-側氧基_2_苯基-l，2-二氫-異喹啉-4-羧 249 200906801 . 酸（（s)-i-苯基-丙基）_醯胺。向3-溴曱基小侧氧基_2_苯基]，2_二氫_異啥琳_4_幾酸 ((s)-i-苯基-丙基）-醯胺（83 mg，〇 174 mm〇1)於 thf ( ml’無水）及DMF (1.5 ml，無水）中之溶液中添加氰化鈉（83 mg，過量）。5分鐘後，將所獲得之懸浮液倒入水 (50 ml)中，隨後添加庚烷（2〇 ml)。粗產物藉由過濾分離且藉由Si〇2急驟層析法（5g ’ 1:1 ea-庚烷）純化產生50 mg 無色固體，產率 68%。LC-MS (m/z) 422.4 (MH+) ; tR = f 1.39 〇 Ή NMR (250 MHz, DMSO-d6, T = 343 K): 0.94 (t, 3H), 1.78及1.85 (ABX4之兩個重疊五重峰，2H，Et之ch2)，3.45 及 3.54 (AB 之兩個 d，2H，CH2CN)，4.98 (q，1H), 7.22-7.44 (m, 8H), 7.53-7.64 (m, 4H), 7.72 (dt, 1H), 8.25 (dd, 1H), 9.05 (d，1H)。4a 3-cyanomethyl-1-oxo-2-phenyl-l,2-dihydro-isoquinoline-4-carboxy 249 200906801 . Acid ((s)-i-phenyl-propyl) _ guanamine. To 3-bromoindole small side oxy-2-phenyl], 2_dihydro-isoindolyl-4-acid ((s)-i-phenyl-propyl)-decylamine (83 mg, 〇 174 mm 〇 1) Sodium cyanide (83 mg, excess) was added to a solution of thf (ml 'anhydrous) and DMF (1.5 ml, anhydrous). After 5 minutes, the obtained suspension was poured into water (50 ml), followed by the addition of heptane (2 〇 ml). The crude product was isolated by filtration and purified by EtOAc EtOAc (EtOAc) LC-MS (m/z) 422.4 (MH+); tR = f 1.39 NMR (250 MHz, DMSO-d6, T = 343 K): 0.94 (t, 3H), 1.78 and 1.85 (two overlaps of ABX4) Wufeng, 2H, Et ch2), 3.45 and 3.54 (two d, 2H, CH2CN of AB), 4.98 (q, 1H), 7.22-7.44 (m, 8H), 7.53-7.64 (m, 4H) , 7.72 (dt, 1H), 8.25 (dd, 1H), 9.05 (d, 1H).

4b 8-氯-3-氰基曱基-i_側氧基_2-苯基-1,2-二氫-異喹啉 -4-羧酸[(S)-環丙基-(3-氟-苯基）-曱基]-醢胺。 LC-MS (m/z) 486.5 (MH+) ; tR = 1.81。實施例5 250 2009068014b 8-chloro-3-cyanoindolyl-i_sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3- Fluoro-phenyl)-mercapto]-guanamine. LC-MS (m/z) 486.5 (MH+); Example 5 250 200906801

5a 3-甲基-1-側氧基_2_苯基-1ϊ2_二氫-異喹啉_4_竣酸 Ν’，Ν'-二苯基-肼。將3-甲基-1-侧氧基_2·苯基_1，2_二氫-異唾琳-4-幾基氯 (合成係在上文實施例la中描述）（25 mg，0.08 mm〇1) 及1，1-一本基肼鹽酸鹽（56 mg，0.25 mmol )於1，2-二氣乙烷（1 ml)中之混合物在微波照射下在i40°c下加熱2〇分鐘。真空移除揮發物且產物藉由製備型LC-MS純化產生 14 mg 無色固體。LC-MS (m/z) 446.7 (MH+) ; tR = 1.58。 α5a 3-Methyl-1-oxooxy-2_phenyl-1ϊ2_dihydro-isoquinoline_4_decanoic acid Ν', Ν'-diphenyl-fluorene. 3-Methyl-1-oxo-2-phenyl-1,2-dihydro-isosalin-4-yl chloride (synthesis is described in Example la above) (25 mg, 0.08 Mixture of mm〇1) and 1,1-one hydrazinium hydrochloride (56 mg, 0.25 mmol) in 1,2-diethane (1 ml) under microwave irradiation at i40 °c 2 Minutes. The volatiles were removed in vacuo and the product was purified by preparative LC-MS to afford &lt LC-MS (m/z) 446.7 (MH+); α

II

3_曱基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸N，-苯基-肼。[740-170]3_Mercapto-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid N,-phenyl-indole. [740-170]

類似地製備標題化合物。LC-MS (m/z) 370.2 (MH+) ; tR 251 200906801 :吐 i5。4 NMR (5〇〇 MHz，DMS0_d6): 2 〇1 (s，3h)，6 % ⑴ 1H), 6.83 (d, 2H), 7.2 (t, 2H), 7.33 (br5 2H), 7.5-7.62 (m, 5H) 7-83 (t, 1H), 8.11 (br, 1H), 8.24 (d, 1H), i〇.33 m) oThe title compound was prepared analogously. LC-MS (m/z) 370.2 (MH+); tR 251 200906801: sp. i5. 4 NMR (5 〇〇 MHz, DMS0_d6): 2 〇1 (s, 3h), 6% (1) 1H), 6.83 (d, 2H), 7.2 (t, 2H), 7.33 (br5 2H), 7.5-7.62 (m, 5H) 7-83 (t, 1H), 8.11 (br, 1H), 8.24 (d, 1H), i〇. 33 m) o

5b N’ —（3-甲基-1·側氧基-2_笨基-1，2-二氫-異喹啉·‘ 幾基）-Ν-苯基-肼缓酸曱酯。將3-曱基小側氧基_2_苯基—a二氯_異㈣_4_㈣ Ν，-苯基-肼（5a，490 mg ’ i .3匪〇1 )及氯甲酸曱酉旨（〇 6 w， 8mm〇1)。於U2•二氯乙烧（1〇ml)中之混合物在微波照射下在100°c下加熱10分鐘。真空移除揮發物且產物藉由急驟層析法（Si〇2 ’梯度庚烷_ i: 1乙酸乙酯/庚烷）純化產生 1.225b N' - (3-methyl-1. oxo-2 - phenyl-1,2-dihydro-isoquinoline ' hexyl)-fluorene-phenyl- hydrazide. 3-mercapto-small-oxyl-2-phenyl-a-dichloro-iso(tetra)-4-(tetra)pyrene,-phenyl-indole (5a, 490 mg 'i.3匪〇1) and chloroformic acid (〇6) w, 8mm〇1). The mixture in U2 • dichloroethene (1 〇 ml) was heated at 100 ° C for 10 minutes under microwave irradiation. The volatiles were removed in vacuo and the product was purified by flash chromatography (Si </RTI> <RTI ID=0.0>

190 mg 固體。LC-MS (m/z) 428.8 (MH+) ; tR 實施例6190 mg solid. LC-MS (m/z) 428.8 (MH+); tR Example 6

252 200906801 6a 2'(3,4_二氯-苯基）-3 -甲基-1-側氧基-1，2-二氫—異啉-4-羧酸（（s)-；!-苯基-丙基）_醯胺。將4-乙醯基•苯基_丙基胺基）_異色烯_丨_鲖（6〇 mg)及3,4-二氯苯胺（ 250 mg)於乙腈（〇.5 mi)中合物在微波照射下在16(rc下加熱15分鐘。使反應混合物在2M HC1 (3 ml)與乙酸乙酯（3 ml)之間分溶。使有機溶液吸附於Si〇2 ( 600 mg )上且以梯度庚烷_乙酸乙酯進 ( 行Sl〇2 ( 20 g)急驟層析產生22 mg呈白色固體狀之標題化合物。LC-MS (m/z) 465.4 & 467.4 (MH+) ; tR = 1 63。自通式XXIII之相應化合物及通式VI之適當苯胺類似地獲得以下化合物：252 200906801 6a 2'(3,4-Dichloro-phenyl)-3-methyl-1-oxo-1,2-dihydro-isoline-4-carboxylic acid ((s)-;!- Phenyl-propyl)-decylamine. 4-Ethyl phenyl-propylamino)-isochromene_丨_鲖(6〇mg) and 3,4-dichloroaniline (250mg) in acetonitrile (〇.5 mi) The mixture was heated at 16 (rc) for 15 minutes under microwave irradiation. The reaction mixture was partitioned between 2M EtOAc (3 ml) and ethyl acetate (3 ml). The title compound was obtained as a white solid. mjjjjjjjjjjjjjjjjjjjjjj 1 63. The following compounds were obtained analogously from the corresponding compounds of the formula XXIII and the appropriate anilines of the formula VI:

異喹啉-4-羧酸 8-氯-3-甲基-1-側氧基-2-苯基-1，2-二氫_ ((S)-l-苯基-丙基）_醯胺（li)。在實施例1 i中描述標題化合物及其替代製備方法Isoquinoline-4-carboxylic acid 8-chloro-3-methyl-1-oxo-2-phenyl-1,2-dihydro-((S)-l-phenyl-propyl)_醯Amine (li). The title compound and its alternative preparation method are described in Example 1 i

253 200906801 6b 8 -氟-1-側氧基- 3- (2-侧氧基- nitB各咬-1-基甲基）-2 -苯基-1,2-二氫-異喹啉-4-羧酸（（S)-環丙基-苯基-曱基）-醯胺。 LC-MS (m/z) 510.3 (MH+) ; tR = 1.25。253 200906801 6b 8 -Fluoro-1-oxooxy-3-(2-o-oxy-nitB each -1-ylmethyl)-2-phenyl-1,2-dihydro-isoquinoline-4 - Carboxylic acid ((S)-cyclopropyl-phenyl-indenyl)-guanamine. LC-MS (m/z) 510.3 (MH+);

6c 8-氟-3-曱基-1-侧氧基-2-苯基-1,2-二氮-異喹啉-4-羧酸（（S)-環丙基-苯基-甲基）-醯胺。 LC-MS (m/z) 427.3 (MH+) ; tR = 1.39。實施例76c 8-fluoro-3-indol-1-yloxy-2-phenyl-1,2-diaza-isoquinoline-4-carboxylic acid ((S)-cyclopropyl-phenyl-methyl ) - guanamine. LC-MS (m/z) 427.3 (MH+); Example 7

7a 3-乙基-1-側氧基_2_苯基_ι，2·二氫-異喹啉_4_羧酸 ((S)-l-苯基-丙基）_酸胺。將2-[2-側氧基-l_((S)-l-苯基-丙基胺甲醯基丁基]_苯甲酸（82 mg，〇.2 mmol)及苯胺（〇_3 ml，3.3 mmol)於乙腈（〇_3 ml)中之密封混合物在微波照射下在+16〇〇c下加熱10分鐘。使混合物在乙酸乙酯（2〇 ml)與3M hci 254 200906801 C 2 X 10 ml)與殘餘物藉由急驟水溶液（2 χ 8 ml ) '飽和NaHC03水溶液鹽水之間分溶’乾燥（MgS04 )且蒸發。層析法（Si〇2，梯度庚烷-乙酸乙酯）純化產生32 mg標題化合物。LC-MS (m/z) 411.5 (MH+)·，tR= ;ι·48。lHNMR(500 MHz，DMSO-d6):兩種滞轉異構體之混合物。藉由使通式XXV化合物與通式VI之適當苯胺縮合類似地獲得以下化合物：7a 3-Ethyl-1-oxooxy-2_phenyl_ι,2·dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-acid amine. 2-[2-Sideoxy-l_((S)-l-phenyl-propylaminecarbamimidyl]-benzoic acid (82 mg, 〇. 2 mmol) and aniline (〇_3 ml, 3.3 mmol) of the sealed mixture in acetonitrile (〇_3 ml) was heated under microwave irradiation for 10 minutes at +16 ° C. The mixture was made between ethyl acetate (2 mL) and 3M hci 254 200906801 C 2 X 10 Ml) and the residue were separated by aq. (2 χ 8 ml) of a saturated aqueous solution of NaHC03 aqueous solution, dried (MgS04) and evaporated. Chromatography (Si.sub.2, gradient heptane-ethyl acetate) was purified to give the title compound. LC-MS (m/z) 411.5 (MH+)·, tR=; lH NMR (500 MHz, DMSO-d6): a mixture of two abbreviations. The following compounds are obtained by condensing a compound of the formula XXV with an appropriate aniline of the formula VI:

7b 8 -氟-3 -甲基-1-側氧基-2-苯基- i,2_二氫-異喹啉-4-缓酸（（S)-l -苯基-丙基）-酿胺。 LC-MS (m/z) 415.5 (MH+) ; tR = 1.39 〇7b 8 -Fluoro-3-methyl-1-oxo-2-phenyl-i,2-dihydro-isoquinoline-4-hypoacid ((S)-l-phenyl-propyl)- Amine amine. LC-MS (m/z) 415.5 (MH+); tR = 1.39 〇

7c 8 -氟- 2-(3 -氟-苯基）-3 -甲基-1-側氧基_ι，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 433.5 (MH+) ; tR = ι·4ΐ。 255 2009068017c 8 -fluoro-2-(3-fluoro-phenyl)-3-methyl-1-oxooxyl,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-benzene Base-propyl)-guanamine. LC-MS (m/z) 433.5 (MH+); tR = ι·4. 255 200906801

7d 8-氟-2-(4-氟-苯基）-3-甲基-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺。 LC-MS (m/z) 433.6 (MH+) ; tR = 1.4。 f7d 8-Fluoro-2-(4-fluoro-phenyl)-3-methyl-1-oxooxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-benzene Base-propyl)-guanamine. LC-MS (m/z) 433.6 (MH+); f

8-氟-1-側氧基-3-(2-側氧基比咯啶-1-基甲基）-2-苯基-1,2-二氮-異°奎琳-4-棱酸（（S)-l-本基-丙基）-酿胺（3e)。在上文實施例3中描述標題化合物及其替代製備方法。8-Fluoro-1-oxo-3-(2-oxo-oxypyrrolidin-1-ylmethyl)-2-phenyl-1,2-diaza-iso-quineline-4-chelonic acid ((S)-l-N-propyl-propyl)-bristamine (3e). The title compound and its alternative preparation method are described in Example 3 above.

7e 8-氟-3-曱基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧 256 200906801 酸[(S)-環丙基-(3-氟-苯基）-曱基]-醯胺。 LC-MS (m/z) 445.6 (MH+); tR = 1_44。W NMR (250 MHz， 70°C, DMSO-d6): 0.41-0.61 (m, 4H), 1.25 (m, 1H), 1.86 (s, 3H), 4.49 (t, J=8.9 Hz, 1H), 7.04 (m, 1H), 7.13-7.31 (m, 6H), 7.37 (m, 1H), 7.42-7.6 (m, 3H), 7.67 (m, 1H), 8.93 (br d, J = 8.5 Hz, 1H, NH)。7e 8-Fluoro-3-indol-1-oneoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxy 256 200906801 Acid [(S)-cyclopropyl-(3- Fluoro-phenyl)-mercapto]-guanamine. LC-MS (m/z) 445.6 (MH+); W NMR (250 MHz, 70 ° C, DMSO-d6): 0.41-0.61 (m, 4H), 1.25 (m, 1H), 1.86 (s, 3H), 4.49 (t, J = 8.9 Hz, 1H), 7.04 (m, 1H), 7.13-7.31 (m, 6H), 7.37 (m, 1H), 7.42-7.6 (m, 3H), 7.67 (m, 1H), 8.93 (br d, J = 8.5 Hz, 1H , NH).

7f 8-氟-2-(3-氟-苯基）-1 _側氧基_3_(2-側氧基-n比咯啶· 1-基甲基）-1,2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺。藉由製備型矽膠TLC分離標題產物。LC-MS (m/z) 546.4 (MH+) ; tR = 0.71 (方法 B)。7f 8-Fluoro-2-(3-fluoro-phenyl)-1 _ pendantoxy_3_(2-sided oxy-n-pyrrolidin-1-ylmethyl)-1,2-dihydro-iso Quinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-guanamine. The title product was isolated by preparative silica gel TLC. LC-MS (m/z) 546.4 (MH+);

7g 8-氟-2-(4-氟-苯基）_：!_側氧基_3_(2-側氧基-吡咯啶_ 1-基曱基）-1，2-二氫-異喹啉_4_羧酸[(s)_環丙基_(3_氟-苯 257 200906801 基）-甲基]-醯胺。藉由製備型矽膠TLC分離標題產物。LC-MS (m/z) 546.3 (MH+) ; tR = 0.71 (方法 B)。7g 8-fluoro-2-(4-fluoro-phenyl)_:!_sideoxy_3_(2-o-oxy-pyrrolidinyl-1-ylindenyl)-1,2-dihydro-isoquine Porphyrin_4_carboxylic acid [(s)_cyclopropyl_(3_fluoro-benzene 257 200906801 base)-methyl]-guanamine. The title product was isolated by preparative silica gel TLC. LC-MS (m/z) 546.3 (MH+);

FF

7h 8-氟-3-甲基-1-側氧基-2-苯基-1,2-二氳-異喹啉-4-羧酸[(S)-環丁基-(3-氟-苯基）-曱基]-醯胺。 LC-MS (m/z) 459.4 (MH+) ; tR = 1.54。7h 8-Fluoro-3-methyl-1-oxo-2-phenyl-1,2-dioxa-isoquinoline-4-carboxylic acid [(S)-cyclobutyl-(3-fluoro- Phenyl)-mercapto]-guanamine. LC-MS (m/z) 495 (MH+);

FF

7i 8-氟-2-(2-氟-苯基）-3-甲基-1-側氧基-1,2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺。 LC-MS (m/z) 463.3 (MH+) ; tR = 1.46。7i 8-fluoro-2-(2-fluoro-phenyl)-3-methyl-1-oxooxy-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl -(3-Fluoro-phenyl)-methyl]-guanamine. LC-MS (m/z) 463.3 (MH+);

FF

258 200906801 7j 8-氟-2-(3-氟-苯基）-3-曱基-卜側氧基-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-曱基]-醯胺。 LC-MS (m/z) 463.3 (MH+) ; tR = 1.46。258 200906801 7j 8-Fluoro-2-(3-fluoro-phenyl)-3-indolyl-p-oxy-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropane Base-(3-fluoro-phenyl)-indenyl]-guanamine. LC-MS (m/z) 463.3 (MH+);

FF

7k 8-氟-2-(4-氟-苯基）-3-甲基-1-側氧基-1，2-二氫-異喹琳-4-竣酸[(S)-J^丙基- (3 -鼠-苯基）-曱基]-酿胺。 LC-MS (m/z) 463.4 (MH+) ; tR = 1.45。7k 8-fluoro-2-(4-fluoro-phenyl)-3-methyl-1-oxooxy-1,2-dihydro-isoquinolin-4-indole [[S)-J^-propyl Base - (3 - murine-phenyl)-indenyl]-bristamine. LC-MS (m/z) 463.4 (MH+);

FF

71 6,8-二氪-3-曱基-1-側氧基-2-苯基-1，2-二氫-異喹啉· 4-缓酸[(S)-i^丙基- (3 -氣-苯基）-甲基]-酿胺。 LC-MS (m/z) 463.2 (MH+) ; tR = 0·82 (方法 B)。 259 20090680171 6,8-dioxin-3-mercapto-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline·4-sodium acid [(S)-i^propyl- ( 3-Gas-phenyl)-methyl]-bristamine. LC-MS (m/z) 463.2 (MH+); tR = 0. 82 (Method B). 259 200906801

FF

7m 5，8-二氣-3-曱基-1-側氧基· 2 -苯基-1，2-二鼠-異喧琳 -4 -魏酸[(S)-i^丙基- (3 -亂-苯基）-曱基]-酿胺。 LC-MS (m/z) 463.4 (MH+) ; tR = 1.39。7m 5,8-dioxa-3-mercapto-1-yloxy-2-phenyl-1,2-dimur-isoindole-4-weilic acid [(S)-i^propyl- ( 3--disorganized-phenyl)-indenyl]-bristamine. LC-MS (m/z) 463.4 (MH+);

7n 3-甲基-Μ則氧基-2-苯基-8-三氟甲基-1，2-二氳-異喹琳_ 4 •竣酸本基-丙基）-驗胺。 LC-MS (m/z) 465.3 (MH+) ; tR = 1.57。7n 3-Methyl-oxime oxy-2-phenyl-8-trifluoromethyl-1,2-dioxa-isoquinoline _ 4 • decanoic acid benzyl-propyl)-amine. LC-MS (m/z) 465.3 (MH+);

實施例8Example 8

FF

8a 3-(卜第三丁基-哌啶-4-基甲基）·8-氯-1-側氧基-2-苯 260 200906801 - 基-1,2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-曱基]- 酸胺。向2-(1-第三丁基-哌啶-4-基）-N-苯基-乙醯胺（25 0 mg， 0.91 mmol)及 2,6-二甲基0比0定（0.139 ml，1·2 mmol)於 1,2-二氯乙烷（8 ml )中之冷（冰浴）混合物中添加乙二酸氯（0.07 ml，0.8 mmol)且在0°C下授拌15分鐘。添加 2-氯-6-({[(S)-環丙基-(3-氟-苯基）-曱基]-胺甲醯基}-甲基）-苯曱酸（70 mg，0.2 mmol)且將反應混合物在90°C下在 f 密封容器中攪拌15小時。使其在0.5 M NaOH水溶液（40 ml )與乙酸乙酯（200 ml )之間分溶，有機相以水洗滌，乾燥且蒸發。殘餘物藉由急驟層析法（Si02，乙酸乙酯-甲醇）純化產生 19 mg標題化合物。LC-MS (m/z) 600.6 (MH+) ; tR = 1·1。4 NMR (500 MHz, r.t.，DMSO-d6):寬峰信號，兩種滯轉異構體之混合物。用於製備該等化合物之試劑。名稱供應商 CAS編號產品編號乙醯乙酸乙酯 Aldrich 141-97-9 E 964-1 乙醯乙酸甲酯 Aldrich 105-45-3 53,736-5 氫化鈉，礦物油中60%分散液 Aldrich 7646-69-7 45,291-2 漠化銅(I) Aldrich 7787-70-4 21,286-5 2-溴苯甲酸 Janssen Chimica 88-65-3 41066/1 2-溴-4-曱基苯甲酸 Matrix Scientific 7697-27-0 001816 2-溴-6-甲基苯甲酸 Matrix Scientific 90259-31-7 001819 2,5-二溴苯曱酸 ABCR 610-71-9 AVI5077 2-溴-4-氟苯甲酸 Fluorochem 1006-41-3 005470 261 200906801 2-漠-5-氯苯曱酸 ABCR 21739-93-5 AV10103 2->臭-5-氟苯甲酸 Aldrich 394-28-5 56,349-8 2-溴-3-曱基苯甲酸 Fluorochem 53663-39-1 112800 2->臭-5-曱基苯曱酸 Fluorochem 6967-82-4 B2947-E 2-漠_6-氯苯曱酸 Fluorochem 93224-85-2 19332 苯胺 Aldrich 62-53-3 13,293-4 2-氟苯胺 Lancaster 348-54-9 1236 2,6-二氟笨胺 Aldrich 5509-65-9 196614 2-氯苯胺 Aldrich 95-51-2 23300 鄰甲苯胺 Aldrich 95-53-4 18,542-6 3-氟苯胺 Flrochem 372-19-0 1438 3-氯苯胺 Fluka 108-42-9 23330 間甲苯胺 Aldrich 108-44-1 511218 (S)-(-)-1 -苯基丙基胺 Lancaster 3789-59-1 X16320G0025 C-((S)-C-環丙基-c-苯基)-甲基胺該化合物係根據WO 2〇〇5/014575中所述之程 _ 序製備 C-[(S)-C-環丙基-C-(3-氟-苯基)]-甲該化合物係根據WO 2〇05/014575中所述之程基胺序製備四乙氧基矽烷 Aldrich 78-10-4 236209 I-乙基-3-(3-二甲基胺基丙基)碳化Aldrich 25952-53-8 16,146-2 二亞胺鹽酸鹽（EDC) 1-羥基苯并***（HOBT) ABCR 2592-95-2 AV21700 二曱基胺，無水乙醇中之33%溶Fluka 124-40-3 38950 液曱基胺，THF中之2M溶液 Aldrich 74-89-5 42,646-6 2-吡咯啶酮 Aldrich 616-45-5 240338 1,1-二苯基肼鹽酸鹽 Aldrich 530-47-2 11,459-6 262 200906801 苯基肼 Aldrich 100-63-0 P2,625-2 氯甲酸甲酯 Aldrich 79-22-1 M35304 氰化鈉 Aldrich 143-33-9 380970 用於製備該等化合物之試劑，續。名稱供應商 CAS編號產品編號高鄰苯二甲酸酐 ABCR 703-59-3 AVI 5538 環丙烷甲醛 Aldrich 1489-69-6 27,221-3 1·>臭-3-氣苯 Aldrich 1073-06-9 B67007 (S)-3-胺基-3-苯基丙猜 Netchem - 331516 3,4-二氯苯胺 Aldrich 95-76-1 56042 2-溴-6-硝基苯甲酸參考1 38876-67-4 - 2-溴-6-甲氧基苯曱酸參考2 31786-45-5 - 2-溴乙酸第三丁酯 Aldrich 5292-43-3 12,426-0 (三苯基亞磷醯基)乙酸乙酯 Aldrich 1099-45-2 C510-6 1-(第三丁氧基羰基)哌啡 Lancaster 57260-71-6 13363 3-吡唑啶酮鹽酸鹽 Acros 1752-88-1 335490050 2-側氧基-4-(第三丁氧基羰基)哌 Aldrich 76003-29-7 64,105-7 畊 2·°底咬酮 Aldrich 675-20-7 V20-9 參考 1.根據所述程序：S.C.Glossop 2007, 7, 981製備化合物。參考 2.根據所述程序：T. Sugaya, Y. Mimura, N. Kato, M. Ikuta，Τ· Mimura 等人.办;ίί/ζαζ··? 1994，73 製備化合物。實施例9 ΝΚ3受體結合檢定膜製備：將穩定表現人類ΝΚ3受體之ΒΗΚ細胞接種於採集培養盤中含有Glut aMax ( 862 mg/1) 、ImM丙酮酸 263 200906801 ' 鈉、1〇%胎牛血清、1%Pen/StreP、l mg/ml G418 之 Dulbeccos MEM培養基中且使其在34〇c下在含有i〇% 之潮.濃氣氛中生長。為增加受體表現，以約9〇0/❶之匯合度採集細胞前24小時，向培養基中添加1 〇 μΜ曲古抑菌素A( trichotatin A)。採集前，用不含肘§2+或Ca2+之pBS洗滌細胞兩次且隨後在每個採集培養盤10 mI PBS中刮除。以15〇〇χ(3離心細胞懸浮液3分鐘，隨後再懸浮於含有2mMMgCl2; 〇.3 mM EDTA 及 1 mM EGTA 之 15 mM Tris Hcl pH 7 5 緩衝液（緩衝液A )中。將細胞懸浮液均質化，且隨後以4〇〇〇〇xg 離心30分鐘。將膜丸粒再懸浮於含有25〇 mM蔗糖之緩衝液A中’等分且儲存於_8〇。〇下。親和力檢定描述：作為基於SPA之競爭結合檢定在含有 120 mM NaCl、3 mM MnCl2、40 pg/ml 枯草桿菌 (bacitracin)、2 pg/ml 糜蛋白酶抑素（chymostatin)、1 pg/mi 磷醯胺素（Phosphoramidon )及4 pg/ml亮抑蛋白酶狀 (Leupeptin)之50 mM Tris pH 7.4檢定緩衝液中進行檢 < 定。將約〇·〇2 nM 125I-NKB與測試化合物混合，隨後添加 4 pg均質化NK3膜製劑及0.025 mg SPA珠粒，總體積為 60 μΐ。隨後在室溫下在攪動下培育檢定培養盤9〇分鐘。以5 00xG離心培養盤1〇分鐘，且在T〇pCounter中每孔叶數5分鐘。包含少於5 °/。所添加之放射性配位體之總結合係使用檢定緩衝液定義’而非特異性結合係在1 μΜ奥沙奈垣存在下定義。非特異性結合占總結合之約5%。 264 200906801 - 數據點係以125l-NKB之特異性結合百分比表示且藉由非線性回歸分析使用Sigmoidal可變斜率曲線擬合測定IC5〇值（引起125Ι-ΝΚΒ特異性結合50%抑制的濃度）。由Cheng Prusoff 等式（Ki = IC5〇/(l+(L/KD)))計算解離常數（心），其中游離放射性配位體L之濃度近似為檢定中添加之ΐ25；[_ ΝΚΒ濃度（約0.02 ηΜ)。由各自以雙份測定進行之三個獨立飽和檢定測定125Ι-ΝΚΒ之KD為0.7 ηΜ。Bmax為約2 pmcl/mg - 本發明化合物一般具有500 ηΜ或更小之Kj值。實際上’许多化合物具有低於1 〇〇 ηΜ直至單個位數值之Ki值。下表顯示對NK3受體之Ki 化合物 IQ ηΜ 實施例2a 180 實施例2bm 8.2 實施例2hs 5.3 實施例2hz 3 實施例3a 72 __實施例5a 55 本發明化合物之更多親和力數據亦參見實施例10之表。貫知例1 0 NK3受體效能（efficacy )及效價（potency ) 檢定將穩定表現人類NK3受體之BHK細胞接種於黑壁透 265 200906801 '明底96孔培養盤（Costar)中之100 μΐ培養基中，旨在檢定當天匯合度為95_100%。根據FLIPR Calcium 4檢定套組（Molecular Devices)進行檢定。檢定當天，移除培養基且以HBSS緩衝液（含有20 mM Hepes之Hanks BSS緩衝液，pH 7.4)洗滌細胞丨次’隨後向細胞中添加1〇〇 μΐ 由鈣檢定試劑溶解於含有2.5 mM丙磺舒（probinicid)之 HBSS緩衝液中所形成之溶液。將培養盤在34。〇、i〇% c〇2 下培育60分鐘，隨後用於FLIPR中以供檢驗螢光性。、在設備中以NKB檢驗一代表性培養盤之劑量反應曲線’其中最初向孔中添加HBSS緩衝液且15分鐘後添加各種濃度之NKB以測定NKB之Ec5〇及Ec85值。用於NKB 之所有化合物培養盤用1%BSA溶液預塗覆且隨後用h2〇洗務3次。將NKB稀釋於含有0.1% BSA之HBSS緩衝液中。對於化合物之效能及效價評估而言，將其在測試前稀 /釋於HBSS緩衝液中。為測試促效活性，添加25 μι經稀 … 釋化合物溶液且將培養盤在FLIPR中分析5分鐘。為測試抬抗活性，如上文所述將培養盤再培育45分鐘，隨後添加25 μΐ EC85濃度之ΝΚΒ (約4 ηΜ)。隨後將培養盤分析 5分鐘，接著結束檢定。測定添加各配位體後螢光性相對於背景之最大增加。使用Sigmoidal可變斜率曲線擬合計异 1匸50值’且使用等式（cIC：50 = IC5〇/(1+(Ec85/Ec50)))測定cICm值’其中NKB之EC85及C5G值係如上文所述測定。在NK3受體效能及效價檢定中表徵之本發明的所有異 266 200906801 喹啉酮為拮抗劑，在相關劑量下未觀測到任何顯著促效活性。表中顯示由本發明化合物獲得之親和力數據（如實施例9所述獲得）及效價數據。實施例9與10之製表值之間的微小差異僅反映已測試一個以上批次且/或一批次已被測試一次以上。親和力效價實例編號 Kj/nM cIC50/nM 2e 330 470 li 41 130 3a 88 270 2r 320 420 2s 200 340 2u 90 96 2ah 290 360 2bg 160 220 2bm 8,8 14 2bn 160 300 2cw 8,4 45 2cz 76 49 2df 340 450 2ec 210 520 2eg 240 610 2es 140 240 2ey 240 480 2fm 33 140 2gt 9,2 22 2hq 10 44 2hs 7,5 21 267 200906801 2hu 6,2 29 2hv 14 35 2hw 8,2 63 2hx 9,3 68 2hy 8,8 63 2hz 4,5 35 2ia 12 100 2iy 17 92 It 27 44 2kh 82 120 2kn 8,7 41 2ko 11 5,6 3d 16 46 21j 18 16 3b 32 47 lbh 21 81 211 7,9 6,3 8a 7 9,9 lbn 23 23 6c 23 24 lbl 470 【圖式簡單說明】 (無）【主要元件符號說明】 (無） 2688a 3-(di-tert-butyl-piperidin-4-ylmethyl)·8-chloro-1-o-oxy-2-benzene 260 200906801 - yl-1,2-dihydro-isoquinoline-4 -carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-indolyl]-acid amine. To 2-(1-tert-butyl-piperidin-4-yl)-N-phenyl-acetamide (25 0 mg, 0.91 mmol) and 2,6-dimethyl 0 to 0 (0.139 ml) , 1. 2 mmol) Add oxalic acid chloride (0.07 ml, 0.8 mmol) to a cold (ice bath) mixture in 1,2-dichloroethane (8 ml) and mix for 15 min at 0 °C . Add 2-chloro-6-({[(S)-cyclopropyl-(3-fluoro-phenyl)-indolyl]-amine-methylhydrazino}-methyl)-benzoic acid (70 mg, 0.2 mmol) The reaction mixture was stirred at 90 ° C for 15 hours in a f-sealed vessel. It was partitioned between 0.5 M aqueous NaOH (40 ml) and ethyl acetate (200 ml). The organic phase was washed with water, dried and evaporated. The residue was purified by flash chromatography (EtOAc,EtOAc) LC-MS (m/z) 600.6 (MH+); </RTI> <RTIgt;</RTI>> NMR (500 MHz, r.t., DMSO-d6): broad peak signal, mixture of two abbreviations. An agent for preparing the compounds. Name Supplier CAS No. Product No. Ethyl Acetate Aldrich 141-97-9 E 964-1 Ethylacetate Aldrich 105-45-3 53,736-5 Sodium hydride, 60% dispersion in mineral oil Aldrich 7646-69 -7 45,291-2 Desert copper (I) Aldrich 7787-70-4 21,286-5 2-bromobenzoic acid Janssen Chimica 88-65-3 41066/1 2-Bromo-4-mercaptobenzoic acid Matrix Scientific 7697-27 -0 001816 2-Bromo-6-methylbenzoic acid Matrix Scientific 90259-31-7 001819 2,5-dibromobenzoic acid ABCR 610-71-9 AVI5077 2-bromo-4-fluorobenzoic acid Fluorochem 1006-41 -3 005470 261 200906801 2-Mos-5-chlorobenzoic acid ABCR 21739-93-5 AV10103 2->Smelly 5-fluorobenzoic acid Aldrich 394-28-5 56,349-8 2-Bromo-3-indenyl Benzoic acid Fluorochem 53663-39-1 112800 2->Smelly-5-mercaptobenzoic acid Fluorochem 6967-82-4 B2947-E 2-Mo _6-chlorobenzoic acid Fluorochem 93224-85-2 19332 Aniline Aldrich 62-53-3 13,293-4 2-Fluoroaniline Lancaster 348-54-9 1236 2,6-Difluoroaminol Aldrich 5509-65-9 196614 2-Chloroaniline Aldrich 95-51-2 23300 o-Toluidine Aldrich 95 -53-4 18,542-6 3-fluoroaniline Flrochem 372-19-0 1438 3-chloroaniline Fluka 108-42-9 23330 m-toluidine Aldrich 108-44-1 511218 (S)-(-)-1 -phenylpropylamine Lancaster 3789-59-1 X16320G0025 C-((S) -C-cyclopropyl-c-phenyl)-methylamine This compound is prepared according to the procedure described in WO 2〇〇5/014575. C-[(S)-C-cyclopropyl-C- (3-Fluoro-phenyl)]-methyl This compound is prepared according to the group amine sequence described in WO 2〇05/014575. Tetraethoxydecane Aldrich 78-10-4 236209 I-ethyl-3-( 3-dimethylaminopropyl)carbonated Aldrich 25952-53-8 16,146-2 Diimine hydrochloride (EDC) 1-hydroxybenzotriazole (HOBT) ABCR 2592-95-2 AV21700 Didecylamine 33% dissolved in absolute ethanol Fluka 124-40-3 38950 liquid decylamine, 2M solution in THF Aldrich 74-89-5 42,646-6 2-pyrrolidone Aldrich 616-45-5 240338 1,1- Diphenylhydrazine hydrochloride Aldrich 530-47-2 11,459-6 262 200906801 Phenylhydrazine Aldrich 100-63-0 P2,625-2 Methyl chloroformate Aldrich 79-22-1 M35304 Sodium cyanide Aldrich 143-33 -9 380970 Reagents for the preparation of these compounds, continued. Name Supplier CAS No. Product No. High Phthalic Anhydride ABCR 703-59-3 AVI 5538 Cyclopropane Formaldehyde Aldrich 1489-69-6 27,221-3 1·>Smelly-3-Phenylbenzene Aldrich 1073-06-9 B67007 (S)-3-Amino-3-phenylpropane Netchem - 331516 3,4-Dichloroaniline Aldrich 95-76-1 56042 2-Bromo-6-nitrobenzoic acid Reference 1 38876-67-4 - 2-Bromo-6-methoxybenzoic acid reference 2 31786-45-5 - 2-bromoacetic acid tert-butyl ester Aldrich 5292-43-3 12,426-0 (triphenylphosphinium) ethyl acetate Aldrich 1099-45-2 C510-6 1-(Tertibutoxycarbonyl) piperidine Lancaster 57260-71-6 13363 3-pyrazolidinone hydrochloride Acros 1752-88-1 335490050 2-sided oxy-4 -(Tertibutoxycarbonyl)piperidinium Aldrich 76003-29-7 64,105-7 Plowing 2·° Bite Ketone Aldrich 675-20-7 V20-9 Reference 1. According to the procedure: SCGlossop 2007, 7, 981 A compound was prepared. Reference 2. According to the procedure: T. Sugaya, Y. Mimura, N. Kato, M. Ikuta, Τ·Mimura et al.; ίί/ζαζ··? 1994, 73 Preparation of compounds. Example 9 ΝΚ3 receptor binding assay membrane preparation: sputum cells stably expressing human ΝΚ3 receptor were seeded in a collection plate containing Glut aMax (862 mg/1), 1 mM pyruvate 263 200906801 'sodium, 1% fetal cattle Serum, 1% Pen/StreP, 1 mg/ml G418 in Dulbeccos MEM medium and allowed to grow at 34 °c in a concentrated atmosphere containing i〇%. To increase receptor expression, cells were harvested at a confluence of approximately 9 〇 0 / 24 24 hours before the addition of 1 〇 μ trichotatin A to the culture medium. Prior to collection, cells were washed twice with pBS without § 2+ or Ca 2+ and then scraped in 10 μl PBS per collection plate. The cell suspension was centrifuged at 15 Torr for 3 minutes, and then resuspended in 15 mM Tris Hcl pH 7 5 buffer (buffer A) containing 2 mM MgCl 2 ; 3 mM EDTA and 1 mM EGTA. The solution was homogenized and subsequently centrifuged at 4 Torr x 30 for 30 minutes. The membrane pellets were resuspended in buffer A containing 25 mM sucrose and aliquoted and stored at _8 Torr. Axillary assay description : As a SPA-based competitive binding assay in 120 mM NaCl, 3 mM MnCl2, 40 pg/ml Bactilracin, 2 pg/ml chymostatin, 1 pg/mi Phosphoramidon (Phosphoramidon) And 4 pg/ml of Leupeptin in 50 mM Tris pH 7.4 assay buffer for assays. Mix approximately 〇·〇2 nM 125I-NKB with the test compound followed by 4 pg homogenization NK3 membrane preparation and 0.025 mg SPA beads in a total volume of 60 μΐ. The assay plate was then incubated for 9 minutes at room temperature with agitation. Centrifuge the plate at 500 rpm for 1 minute, and per well in T〇pCounter The number of leaves is 5 minutes. Contains less than 5 ° / total of the added radioligand Binding lines were defined using assay buffer definitions instead of specific binding lines in the presence of 1 μΜ oxathanol. Non-specific binding accounted for approximately 5% of total binding. 264 200906801 - Data points are specifically bound by 125l-NKB Percentage representation and determination of IC5 〇 value (concentration that causes 125Ι-ΝΚΒ specific binding to 50% inhibition) by non-linear regression analysis using Sigmoidal variable slope curve fitting. By Cheng Prusoff equation (Ki = IC5〇/(l+( L/KD))) Calculate the dissociation constant (heart), wherein the concentration of the free radioligand L is approximately ΐ25 added in the assay; [_ ΝΚΒ concentration (about 0.02 ηΜ). Three of each are determined in duplicate The independent saturation assay determines that the KD of 125 Ι-ΝΚΒ is 0.7 η Μ. Bmax is about 2 pmcl/mg - the compounds of the invention generally have a Kj value of 500 η Μ or less. In fact, 'many compounds have less than 1 〇〇 Μ Μ up to a single position The Ki value of the value. The following table shows the Ki compound IQ η 对 for the NK3 receptor. Example 2a 180 Example 2bm 8.2 Example 2hs 5.3 Example 2hz 3 Example 3a 72 __Example 5a 55 More affinity of the compound of the present invention See also the table of Example 10 for the data. Permeation Example 10 NK3 Receptor Efficacy and Potency Assays BHK cells stably expressing human NK3 receptor were inoculated into 100 μM of Hebijing 265 200906801 'Bottom 96-well culture plate (Costar). In the medium, it is intended to determine the confluence of 95_100% on the day. The assay was performed according to the FLIPR Calcium 4 assay kit (Molecular Devices). On the day of the assay, the medium was removed and the cells were washed with HBSS buffer (Hanks BSS buffer containing 20 mM Hepes, pH 7.4) and then 1 μμ was added to the cells. The calcium assay reagent was dissolved in 2.5 mM propionate. A solution formed in the probinicid HBSS buffer. Place the plate at 34. Incubate for 60 minutes under 〇, i〇% c〇2, and then used in FLIPR for fluorescence detection. The dose response curve of a representative culture plate was examined by NKB in the apparatus. HBSS buffer was initially added to the wells and various concentrations of NKB were added after 15 minutes to determine the Ec5 and Ec85 values of NKB. All compound plates for NKB were pre-coated with 1% BSA solution and subsequently washed 3 times with h2. NKB was diluted in HBSS buffer containing 0.1% BSA. For the efficacy and potency evaluation of the compounds, they were diluted/released into HBSS buffer prior to testing. To test for agonistic activity, 25 μl of the diluted compound solution was added and the plates were analyzed in FLIPR for 5 minutes. To test the anti-activation activity, the plates were incubated for an additional 45 minutes as described above, followed by the addition of 25 μΐ EC85 concentration (about 4 η Μ). The plates were then analyzed for 5 minutes and then the assay was terminated. The maximum increase in fluorescence relative to the background after addition of each ligand was determined. Use the Sigmoidal variable slope curve to fit the difference of 1匸50 value' and determine the cICm value using the equation (cIC:50 = IC5〇/(1+(Ec85/Ec50))) where the EC85 and C5G values of NKB are as above The assay. All of the isochronous 266 200906801 quinolinones of the present invention characterized in the NK3 receptor potency and potency assay were antagonists and no significant efficacious activity was observed at the relevant doses. Affinity data obtained as obtained by the compounds of the invention (obtained as described in Example 9) and titer data are shown in the table. The slight difference between the tabulated values of Examples 9 and 10 only reflects that more than one batch has been tested and/or one batch has been tested more than once. Affinity potency example number Kj/nM cIC50/nM 2e 330 470 li 41 130 3a 88 270 2r 320 420 2s 200 340 2u 90 96 2ah 290 360 2bg 160 220 2bm 8,8 14 2bn 160 300 2cw 8,4 45 2cz 76 49 2df 340 450 2ec 210 520 2eg 240 610 2es 140 240 2ey 240 480 2fm 33 140 2gt 9,2 22 2hq 10 44 2hs 7,5 21 267 200906801 2hu 6,2 29 2hv 14 35 2hw 8,2 63 2hx 9, 3 68 2hy 8,8 63 2hz 4,5 35 2ia 12 100 2iy 17 92 It 27 44 2kh 82 120 2kn 8,7 41 2ko 11 5,6 3d 16 46 21j 18 16 3b 32 47 lbh 21 81 211 7,9 6,3 8a 7 9,9 lbn 23 23 6c 23 24 lbl 470 [Simple description of the diagram] (none) [Description of main component symbols] (none) 268

Claims

200906801 、申請專利範園： 1 · 一種式I化合物200906801, Patent Application Park: 1 · A compound of formula I

,R5 、R6 其中A表示n、CH或CR1 ; i 其中各R1獨立地表示氫、Cw烷基、c2 6烯基、c2-6 炔基、-c(〇)-cl 6 烷基、_C(0)_C2 6 烯基、炔基、 -c(o)-〇-Cl 6 烷基、_c(〇)_〇_c26 烯基、_c(〇) 〇 c26 炔基或苯基，其中該苯基、Ci 6烷基、C26烯基或C2 6炔基視情況經一或多個選自以下基團之取代基取代：齒素、羥基、齒基Cw烷基、硝基、Ci 6烷氧基、及nr2r3 ; 2其中X表示氫、Cl.6院基、c2-6烯基、c2 6炔基、氰基、〇 C(〇)R > -0C(0)NR2R3 , -C(0)-NR2R3 ' - n(r2)c(0)r3、_N(R2)_C_R2R3 或 NR2R3 m 示且有 w個環原子之單環、雙環或三環部分，環原子中之一、者為氮，且其中丨個、2個或3個 β c 兄個頸外環原子可為選自N、Ο 及S之雜原子，且其中該單環、成雙衣或二垓部分可視情況 269 200906801 - 經一或多個取代基w取代’其中w係選自氫、羥基、_ 素、氰基、（ = 0)、-0-(CH2)c-〇-，其中 C 為 2 或 3(螺）、（CH2)d，其中d為5或6(螺）、CV6烷基、C2_6烯基、c26炔基、c， * * 6 烧氧基、-(^(CO-Cu 烧基、-C(0)-C2.6 稀基、-C(〇)-C2.6 块基、-(3(0)-0-(^.6 烧基、-C(0)-0-C2_6 烯基、_c(〇)-〇_c 2-6 炔基、-o-qco-Cw 烷基、-o-c(o)-c2_6 烯基、_0_c(0)_c 2 ·· 6 块基、-C(0)H、COOH;或其中 W 表示式 _(CH2)a-Y-(CH2)b_2 之部分；其中a及b獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、c(0)、0、S、-〇-c(〇)、-C(〇)-〇_、 -NR2-、-NR2-C(〇)-、_C(0)-NH-或 S(〇)2 ; 其中z表示氫、c]_6烷基、NR2R3、氰基或包含4至u 個環原子之單環或稍合雙環部分，環原子中視情況i個、 2個或3個為選自N、〇及s之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群 <的取代基取代._素、氰基、C】.6院基、經基、及烧 k 氧基、吡畊基、苯基、吡啶基、及經鹵素取代之苯基； #其中m m R13_R”中之每一者獨立地表示氫 1-6烧基C2_6稀基、C2_6块基、鹵素、NR2R3、經基、於肖土匸丨^烧氧基〜鹵基匚丨—烧基或經基匚丨^烧基；其m R3獨立地表示氫、Ci 6炫基、u基、C2 6 快基經基Cl-6烧基、鹵基k烧基或苯基；及其醫藥學上可接受之鹽。 2.如申請專利範圍第i項之化合物，其中r4-R8表示 270 200906801 . 氫。 3. 如申請專利範圍第1項之化合物，其中r9_ri2表示氫。 ’ 4. 如申叫專利範圍第1項之化合物’其中表示氫。 5 ·如申凊專利範圍第丨項之化合物，其具有式I， α,. I η κι, R5, R6 wherein A represents n, CH or CR1; i wherein each R1 independently represents hydrogen, Cw alkyl, c2 6 alkenyl, c2-6 alkynyl, -c(〇)-cl 6 alkyl, _C( 0)_C2 6 alkenyl, alkynyl, -c(o)-fluorene-Cl 6 alkyl, _c(〇)_〇_c26 alkenyl, _c(〇) 〇c26 alkynyl or phenyl, wherein the phenyl The Ci 6 alkyl, C26 alkenyl or C 2 6 alkynyl group is optionally substituted with one or more substituents selected from the group consisting of dentate, hydroxyl, dentate Cw alkyl, nitro, Ci 6 alkoxy And nr2r3; 2 wherein X represents hydrogen, Cl.6, K2-6 alkenyl, c2 6 alkynyl, cyano, 〇C(〇)R > -0C(0)NR2R3 , -C(0) -NR2R3 ' - n(r2)c(0)r3, _N(R2)_C_R2R3 or NR2R3 m is a monocyclic, bicyclic or tricyclic moiety having w ring atoms, one of which is nitrogen, and Wherein one, two or three β c brothers and one outer ring atom may be heteroatoms selected from N, Ο and S, and wherein the single ring, double coat or bismuth moiety may be visible 269 200906801 - by one Or a plurality of substituents w substituted with 'where w is selected from the group consisting of hydrogen, hydroxy, _, cyano, (=0), -0-(CH2)c-〇-, wherein C is 2 or 3 (snail) ), (CH2)d, wherein d is 5 or 6 (spiro), CV6 alkyl, C2_6 alkenyl, c26 alkynyl, c, * * 6 alkoxy, -(^(CO-Cu alkyl, -C) (0)-C2.6 dilute group, -C(〇)-C2.6 block group, -(3(0)-0-(^.6 alkyl group, -C(0)-0-C2_6 alkenyl group, _c(〇)-〇_c 2-6 alkynyl, -o-qco-Cw alkyl, -oc(o)-c2_6 alkenyl, _0_c(0)_c 2 ·· 6 block, -C(0) H, COOH; or wherein W represents a moiety of the formula _(CH2)aY-(CH2)b_2; wherein a and b independently represent an integer selected from 〇, 1, 2 and 3; wherein Y represents a bond, c(0 ), 0, S, -〇-c(〇), -C(〇)-〇_, -NR2-, -NR2-C(〇)-, _C(0)-NH- or S(〇)2; Wherein z represents hydrogen, c]-6 alkyl, NR2R3, cyano or a monocyclic or slightly bicyclic moiety containing 4 to u ring atoms, and as the case, i, 2 or 3 are selected from N, 〇 as the ring atom And a hetero atom of s, and wherein the monocyclic or fused bicyclic moiety is optionally substituted with one or more substituents selected from the group consisting of: - cyano, cyano, C. , a thiol group, a phenyl group, a pyridyl group, a phenyl group, a pyridyl group, and a halogen-substituted phenyl group; #其mm R13 Each of _R" independently represents a hydrogen 1-6 alkyl C2_6 dilute group, a C2_6 block group, a halogen, an NR2R3 group, a thiol group, an alkoxy group, a halogen group, or a hydrazine group. a ruthenium group; wherein m R3 independently represents hydrogen, Ci 6 leukoxyl, u-based, C2 6 fast-based thiol-alkyl group, halo-k-alkyl or phenyl; Accept the salt. 2. A compound as claimed in claim i, wherein r4-R8 represents 270 200906801. Hydrogen. 3. A compound as claimed in claim 1 wherein r9_ri2 represents hydrogen. 4. In the case of the compound referred to in paragraph 1 of the patent patent, which represents hydrogen. 5 · A compound of the formula 丨凊, which has the formula I, α,. I η κι

其中Α表示n、ch或CR1 ; 其中各R1獨立地表示氫、Ci0烷基、烷基、 -cw-o-k院基、或苯基，其中該苯基或Ci 6燒基視情況經一或多個選自以下基團之取代基取代H、經基、鹵基Cl-6烷基、硝基、C丨·6烷氧基、及nr2r3 ; 土其中X表示氫、c“6烷基、氰基、-or2' -〇C(〇)取2R3、⑼通f、_n(r2)c(〇)r3、（-n)R ; ⑽N W或NR2R3，或x表示具有4_ i 6個環原子之單^ 雙壤或三環部分，環原子中之-者為氮，且衣、個或3個額外環原子可為選自N、〇及s之雜原子，八r 1個、2 且其 271 200906801 -中該單環、雙環或三環部分可視情況經一或多個取代基w 取代，其中W係選自氫、羥基、齒素、氰基、（=〇)、_〇_ (CH2)c-〇-，其中c為2或3(螺）、（CH2)d，其中4為5或6(螺）、 c,-6 烷基、Cl_6 烷氧基、_c(0)_Ci 6 烷基、_c(〇)_〇_Ci 6 烷基、烷基、-C(〇)H、COOH ;或其中 W 表示式-(CH2)a-Y_(CH2)b-Z 部分；其中a及b獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、C(O)、〇、S、-O-C(O)、_c(0)-0_、 -NR2-、-NR2-C(0)-、-C(0)-NH-或 S(0)2 ; 其中Z表示氫'C,.6烷基、NR2R3、氰基或包含4至12 個環原子之單環或稠合雙環部分，環原子中視情況丨個、 2個或3個為選自N、〇及s之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：_素、氰基、Ci·6烷基、羥基、及Ch烷氧基、吡啡基、苯基、吡啶基、及經鹵素取代之苯基； ( 其中R4-R8、R9-R12& R〗3-R17中之每一者獨立地表示 V 氫、C〗_6烷基、C2-6烯基、C2_6炔基、鹵素、NR2R3、羥基、氰基、硝基' 烷氧基、鹵基Ci_6烷基或羥基Ci 6烷基；其中R2及R3獨立地表示氳、Cl·6烷基、C2 6烯基、^ 6 炔基、羥基Cw烷基、_基Ci 6烷基或苯基；及其醫藥學上可接受之鹽。 6. 如申請專利範圍帛5項之化合物，其中A表示⑶。 7. 如申請專利範圍第6項之化合物，其中ri表示匸烧基。 272 200906801 ' 8·如申請專利範圍第7項之化合物，其中R1表示乙基或環丙基。 9.如申請專利範圍第5_8項中任一項之化合物，其中 X 表不氫、cN6 烷基、氰基、_or2、_〇 c(〇)r2、_〇c(〇)nr2r3、 _C(〇)-NR2R3-、-N(R2)C(〇)R3、_N(R2)_c(〇)Nm nr2r3，其中R2及R3獨立地表示氫、Cm烷基、羥基Cw烷基、 1¾基C1-6院基或苯基。 r 1〇·如申請專利範圍第9項之化合物，其中X表示氫、甲基、或NR2R3，其中R2及R3獨立地表示氳、ci 6烷基、或羥基CV6烷基。 U •如申請專利範圍第10項之化合物，其中R2及R3 獨立地表示氫、環丙基曱基、曱基、乙基或環丙基。 1 2.如申明專利範圍第5_8項中任一項之化合物，其中 X表不具有4-1 6個環原子之單環、雙環或三環部分，環原子中之一者為氮，且其中丨個、2個或3個額外環原子可為選自N、0及S之雜原子，且其中該單環、雙環或三環邛分可視情況經一或多個取代基w取代，其中w係選自氲、羥基、鹵素、氰基、（=〇)、_〇_(CH2)c_〇_，其中c為2 或3(螺）、(CH2)d ’其中d為5或6(螺）、Ci 6烷基、烷氧基、烷基、烷基、_〇_c(〇) Ci6 烧基、-O-C(O)-、-C(〇)H、c〇OH ;或其中 W 表示式 __ (CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自〇、ι、2及3之整數；其中 Y 表示一鍵、c(〇)、〇、s、_〇_c(〇)、、 273 200906801 -NR2-、-NR2-C(0)_、_c(〇) Nh 或 s(〇)2 ; ’、表示氫Cl·6娱:基、NR2R3、氰基或包含4至l2 個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、〇&s之雜原子’且其中該單環或稍合雙壤部分視情況經—或多個選自由以下基團組成之群的取代基取代.由素、氰基、Ci.6烧基、經基、及^ 6燒氧基、吡畊基、$基、吡啶基、及經彘素取代之苯基； f V 其中R及R3獨立地表示氫、Cl—烷基、羥基c丨—烷基、鹵基（^_6烷基或苯基。 13.如申請專利範圍第12項中任一項之化合物，其中 X表不具有5個環原子之單環部分，環原子中之一者為氮，且其中1個、2個或3個額外環原子可為選自N、〇及s 之雜原子’且其中該單環部分可視情況經一或多個取代基 W取代’其巾W係選自氫、經基、画素、氰基、（=〇)、_ (CH2)c-〇- ’ 其中 c & 2 或 3(螺）、（CH2)d，其中 d 為 5 或 6(螺）' 烷基、Ci 6 烷氧基、_c(〇)_Ci_6 烷基、_c(〇>〇_ 16 烷基、-0-C(0)-Ci-6 烷基、-O-C(O)-、-C(0)H、COOH ; 或其中W表示式一(CH2)a-Y-(CH2)b-Z部分；其中a及b獨立地表示選自〇、ι、2及3之整數；其中 Y 表示一鍵、c(〇)、〇、S、_〇_c(〇)、_c(0) 〇、、……弋⑴）-、-C(0)-NH-或 S(0)2 ; 其中Z表示氫、C16烷基、NR2R3、氰基或包含4至12 1固ΐ班 /S 衣’、子之單環或稠合雙環部分，環原子中視情況1個、個或3個為選自Ν、〇 & 5之雜原子，且其中該單環或 274 200906801 .稠合雙％部分視情況經一或多個選自由以下基團組成之群的取代基取代：齒素、氰基、烷基、羥基、及Cl_6烷氧基、吼啡基、苯基、吼。定基、及經函素取代之苯基；其中R及R3獨立地表示氣、Ci.6烧基 '經基Cl 6烧基、_基Cw烧基或苯基。 14·如申租專利範圍第12項中任一項之化合物，其中以示具有6個環原子之單環部分，環原子中之—者為氮，且其中1個、2個或3個額外環原子可為選自n、〇及s 之雜原子，且其中該單環部分可視情況經一或多個取代基 W取代，其中W係選自氫、羥基、鹵素、氰基、（=〇)、\ o-(ch2)c-o-，其中c為2或3(螺）、（CH丄，其中d為5或 6(螺）、烷基、Ci 6 烷氧基、_c(〇)_Ci 6 烷基、_c(〇)_〇_ C,.6 烷基、-O-qcO-Cw 烷基、_0_C(0)_、_c(〇)H、c〇〇H ; 或其中W表示式—(CH2)a_Y_(CH2)b_z部分；其中a及b獨立地表示選自〇、i、2及3之整數；其中 Y 表示一鍵、C(0)、0、s、_〇_c(⑺、_c(〇)_〇、 -NR2-、-NR2-C(0)-、-C(〇)-NH-或 S(0)2 ; 其中Z表示氫、Cl_6烷基、NR2r3、氰基或包含4至i2 個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自n、〇及S之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：鹵素、氰基、c^·6烷基、羥基、及Cl 6燒氧基、°比啡基、苯基、吼。定基、及經鹵素取代之苯基；其中R2及R3獨立地表示氫、C, — 6烷基、羥基Ci 6烧 275 200906801 基、鹵基Ci.6烷基或苯基。 &如中請專利範圍帛12項中任—項之化合物，其中 X表示具有7個環原子之單環部分，環原子中之—者為氮，且其中1個2個或3個額外環原子可為選自Ν、〇及s 之雜原子且其中該單環部分可視情況經一或多個取代基 W取代’其巾w係選自氫、經基、齒素、氰基、(=〇)、_ 0-(CH2)e-0- ’其中e為2或3(螺）、（CH丄其中d為5或 6(螺）<^.6烧基、c2.6稀基、Cw块基、烧氧基、_c(〇)_c“6 烷基 C(o) O-Cy 烷基、_〇_c(〇)_Ci 6 烷基、_c(〇)H、 COOH ;或其中W表示式_(CH2)a_Y (cHA_z部分；其中a及b獨立地表示選自ο」、〕及3之整數；其中 Y 表示一鍵、C(〇)、〇、S、_〇_c(〇)、_c(〇) 〇、 -NR2-、-NR2-C(0)_、_c(〇)_NH 或 s(〇)2 ; 其中Z表示氫、Ci 6烧基、nr2r3、氛基或包含4至Q 個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、〇A 8之雜原子，且其中該單環或稍合雙環部分視情況經__或多個選自由以下基團組成之群的取代基取代：^素、氰基、k烧基、經基、及Ci6燒氧基tt%基、苯基、Dtbn定基、及經函素取代之苯基；其中R2及R3獨立地表示氫、Cw烷基、羥基Ci —烷基、鹵基Cw烷基或苯基。 16.如申凊專利範圍第12項中任一項之化合物，其中 X表示具有8個環原子之單環或雙環部分，環原子中之一者為氮’且其中1個、2個或3個額外環原子可為選自 276 200906801 〇及s之雜原子，且其中該單環或雙環部分可視情況經一或多個取代基w取代，其中w係選自氫、羥基、_素、氛基、（=0)、-〇-(CH2)c-〇-，其中 c 為 2 或 3(螺）、（CH2)d，其中d為5或6(螺）、Cl6烷基、Ci6烷氧基、_c(〇)_Ci6 烷基、-C(0)-〇_Ci 6 烷基、_〇_c(〇)_Ci 6 烷基、_c(〇)H、 C〇〇H ;或其中 W 表示式-(CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自〇、1、2及3之整數； f.. κ 其中 Y 表示一鍵、C(〇)、〇、S、_〇_C(〇)、_c(〇)_〇、 _NR2_、_NR2_C(〇)-、-C(0)-NH-或 S(0)2 ; 其中Z表示氫、Ci·6烷基、Nr2r3、氰基或包含4至個裒原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、〇及s之雜原？，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成的取代基取代：_素、氰基、烧基、經基、及燒氧基…㈣基、苯基、。㈣基、及經❹取代之苯基；① 其中R2及R3獨立地表示氫、Ci 6烧基、經基Cw户基、鹵基CK6烷基或苯基。 A 17·如申請專利範圍第12項中任话夕外人此一只丫任一項之化合物，其中 X表示具有9個環原子之單環 '、 0 # , 次雙衣邠刀，％原子中之〜者為氮，且其中丨個、2個或 Ο S 1U額外％原子可為選自N、 U及b之雜原子，且其中該單户斗、μ τ ^早％或雙環部分可視情或多個取代基W取代，其中w π 」視匱况鉍〜畜其r。、中…係選自氫、羥基、齒素、亂基、（二0)、-〇_(CH2)c_〇_，其 ^ , 「。马 2 或 3(螺其中d為5或6(螺)、Ci6烷山’ 匕1-6院氧基、 277 200906801 烷基、-(:(0)-0-(^.6 烷基、-0-(:(0)-(^.6 烷基、_C(0)H、 COOH ;或其中 w 表示式—(CH2)a_Y_(CH2)b_z 部分；其中a及b獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、C(O)、Ο、S、-O-C(O)、-C(0)-0-、 -NR2-、-NR2-C(〇)-、-C(0)-NH-或 S(0)2 ; 其中Z表示氫、Ci 6烷基、NR2R3、氰基或包含4至12 個環原子之單環或稠合雙環部分，環原子中視情況i個、 r: 2個或3個為選自N、〇及s之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代·· i素、氰基、Ci 6烧基、㈣、及CM境氧基、口比啡基、苯基…比咬基、及經南素取代之苯基；疋其:R2及R3獨立地表示氫、Ci 6燒基、6稀基、k 炔基、輕基（^.6絲、自基Ci6院基或苯基^ 6 18·如申請專利範圍帛12項中任-項之化合物，盆中 X表不具有個環原子之單環或雙環部分，環原子中之— 者為氮’且其令i個、2個或3個額外環原子可為選自N、〇及S之雜原子，且其中該單環或雙環部分可視情況經— =個(取：基W取代’其中w係選自氯、經基、i素、氧基、（=〇)m〇-，其 h 為 2 或 3(螺）、（CH2)d，其中d為5或6(螺）、Ci 6 d 烧基…C(〇)-〇_Ci.6 烧基、_〇 Cl'6 跪基、-crom、 COOH ;或其中W表示式（）H 认（LH2)b_Z部分；其中a及b獨立地表示選自其中 γ表不-鍵、c(〇)、0、s、_0_c(〇)、c(〇) 〇、 278 200906801 • ·ΝΚ2_、-NR2-C(〇)-、-C(0)-NH-或 S(0)2，· 其中Z表示氫、C〗_6烷基、nr2r3、氰基或包含*至η 個環原子之單環或稍合雙環部分，環原子中視情況工個、 2個或3個為選自N、w s之雜原+，且其中該單環或稠合雙環部分視，if況經-或多個選自&以下基團組成之群的取代基取代：鹵素、氰基、Ci δ烷基、羥基、及烷氧基、吡阱基、苯基、吡啶基、及經鹵素取代之苯基；其中R2及R3獨立地表示氫、Cl 6烷基、羥基Cl 6烷基、鹵基C】_6烧基或苯基。 19.如申請專利範圍第1項之化合物，其具有式IbWherein Α represents n, ch or CR1; wherein each R1 independently represents hydrogen, Ci0 alkyl, alkyl, -cw-ok, or phenyl, wherein the phenyl or Ci 6 alkyl group is optionally one or more Substituents selected from the group consisting of H, a trans group, a halo C1-6 alkyl group, a nitro group, a C丨6 alkoxy group, and nr2r3; wherein X represents hydrogen, c "6 alkyl, cyanide Base, -or2' -〇C(〇) takes 2R3, (9) passes f, _n(r2)c(〇)r3, (-n)R; (10) N W or NR2R3, or x represents 4_i 6 ring atoms a single or double-ring or tricyclic moiety, wherein the ring atoms are nitrogen, and the clothes, or three additional ring atoms may be heteroatoms selected from N, 〇 and s, 八r1, 2 and 271 200906801 - The monocyclic, bicyclic or tricyclic moiety may be optionally substituted with one or more substituents w, wherein W is selected from the group consisting of hydrogen, hydroxy, dentate, cyano, (=〇), _〇_ (CH2) C-〇-, wherein c is 2 or 3 (spiro), (CH2)d, wherein 4 is 5 or 6 (spiro), c, -6 alkyl, Cl_6 alkoxy, _c(0)_Ci 6 alkyl , _c(〇)_〇_Ci 6 alkyl, alkyl, -C(〇)H, COOH; or wherein W represents a moiety of the formula -(CH2)a-Y_(CH2)bZ; a and b independently represent an integer selected from 〇, 1, 2, and 3; wherein Y represents a bond, C(O), 〇, S, -OC(O), _c(0)-0_, -NR2-, -NR2-C(0)-, -C(0)-NH- or S(0)2; wherein Z represents hydrogen 'C,.6 alkyl, NR2R3, cyano or a single containing 4 to 12 ring atoms a ring or a fused bicyclic moiety, optionally in the ring atom, 2 or 3 is a hetero atom selected from N, fluorene and s, and wherein the monocyclic or fused bicyclic moiety is optionally selected from one or more Substituted by a group consisting of: _, cyano, Ci. 6 alkyl, hydroxy, and Ch alkoxy, pyranoyl, phenyl, pyridyl, and phenyl substituted by halogen; Wherein each of R4-R8, R9-R12& R-3-R17 independently represents V hydrogen, C -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, NR 2 R 3 , hydroxy, cyano, a nitro 'alkoxy group, a halogenyl Ci_6 alkyl group or a hydroxy Ci 6 alkyl group; wherein R 2 and R 3 independently represent hydrazine, Cl. 6 alkyl group, C 2 6 alkenyl group, ^ 6 alkynyl group, hydroxy C c alkyl group, _ a Ci 6 alkyl or phenyl group; and a pharmaceutically acceptable salt thereof. 6. A compound of the formula 5 And wherein A represents (3). 7. The compound of claim 6 wherein ri represents a sulphur group. 272 200906801 '8. The compound of claim 7, wherein R1 represents an ethyl group or a cyclopropyl group. 9. A compound according to any one of claims 5 to 8, wherein X represents hydrogen, cN6 alkyl, cyano, _or2, _〇c(〇)r2, _〇c(〇)nr2r3, _C(〇 -NR2R3-, -N(R2)C(〇)R3, _N(R2)_c(〇)Nm nr2r3, wherein R2 and R3 independently represent hydrogen, Cm alkyl, hydroxy Cw alkyl, 13⁄4 base C1-6 Hospital base or phenyl. r 1〇. The compound of claim 9, wherein X represents hydrogen, methyl, or NR2R3, wherein R2 and R3 independently represent hydrazine, ci 6 alkyl, or hydroxy CV6 alkyl. U. A compound according to claim 10, wherein R2 and R3 independently represent hydrogen, cyclopropylindenyl, fluorenyl, ethyl or cyclopropyl. The compound of any one of clauses 5 to 8, wherein X represents a monocyclic, bicyclic or tricyclic moiety having 4 to 16 ring atoms, and one of the ring atoms is nitrogen, and wherein The oxime, 2 or 3 additional ring atoms may be heteroatoms selected from N, 0 and S, and wherein the monocyclic, bicyclic or tricyclic oxime may be optionally substituted with one or more substituents w, wherein Is selected from the group consisting of hydrazine, hydroxy, halogen, cyano, (=〇), _〇_(CH2)c_〇_, where c is 2 or 3 (spiro), (CH2)d 'where d is 5 or 6 ( Spiro), Ci 6 alkyl, alkoxy, alkyl, alkyl, _〇_c(〇) Ci6 alkyl, -OC(O)-, -C(〇)H, c〇OH; or The expression __(CH2)aY-(CH2)bZ portion; wherein a and b independently represent an integer selected from 〇, ι, 2, and 3; wherein Y represents a bond, c(〇), 〇, s, _ 〇_c(〇),, 273 200906801 -NR2-, -NR2-C(0)_, _c(〇) Nh or s(〇)2 ; ', denotes hydrogen Cl·6 entertainment: base, NR2R3, cyano Or a monocyclic or fused bicyclic moiety containing 4 to 12 ring atoms, wherein one, two or three of the ring atoms are selected from N, 〇 &s heteroatoms' And wherein the single ring or slightly double soil is partially substituted by a plurality of substituents selected from the group consisting of: a cyano group, a cyano group, a Ci.6 alkyl group, a thiol group, and a An oxy group, a pyridinyl group, a benzyl group, a pyridyl group, and a phenyl group substituted with a halogen; f V wherein R and R3 independently represent hydrogen, Cl—alkyl, hydroxy c丨—alkyl, halo (^_6) A compound according to any one of claims 12, wherein X has no single ring moiety of 5 ring atoms, one of the ring atoms is nitrogen, and one of them, The two or three additional ring atoms may be heteroatoms selected from N, hydrazine and s and wherein the monocyclic moiety may be substituted by one or more substituents W, Pixel, cyano, (=〇), _ (CH2)c-〇- ' where c & 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro)' alkyl, Ci 6 Alkoxy, _c(〇)_Ci_6 alkyl, _c(〇>〇_ 16 alkyl,-0-C(0)-Ci-6 alkyl, -OC(O)-, -C(0)H , COOH; or wherein W represents a formula (CH2)aY-(CH2)bZ moiety; wherein a and b are independently selected from 〇 , integers of ι, 2, and 3; where Y represents a bond, c(〇), 〇, S, _〇_c(〇), _c(0) 〇, , ...弋(1))-, -C(0 -NH- or S(0)2; wherein Z represents hydrogen, C16 alkyl, NR2R3, cyano or a monocyclic or fused bicyclic moiety comprising 4 to 12 1 hydrazine/S coat, a ring atom 1 , 3 or 3 are heteroatoms selected from Ν, 〇 & 5, and wherein the monocyclic ring or 274 200906801. The fused double % moiety is optionally selected from one or more selected from the group consisting of Substituent substituents of the group: dentate, cyano, alkyl, hydroxy, and Cl-6 alkoxy, morphine, phenyl, fluorene. A phenyl group substituted with a base and a cytosine; wherein R and R3 independently represent a gas, a Ci.6 alkyl group, a thiol group, a yl group, a phenyl group or a phenyl group. The compound of any one of the preceding claims, wherein the compound has a single ring moiety having 6 ring atoms, wherein the ring atom is nitrogen, and one, two or three additional The ring atom may be a hetero atom selected from n, fluorene and s, and wherein the monocyclic moiety may be optionally substituted with one or more substituents W, wherein W is selected from the group consisting of hydrogen, hydroxy, halogen, cyano, (=〇 ), \ o-(ch2)co-, wherein c is 2 or 3 (spiro), (CH丄, where d is 5 or 6 (spiro), alkyl, Ci 6 alkoxy, _c(〇)_Ci 6 Alkyl, _c(〇)_〇_C,.6 alkyl, -O-qcO-Cw alkyl, _0_C(0)_, _c(〇)H, c〇〇H; or where W is a formula - ( CH2) a_Y_(CH2)b_z portion; wherein a and b independently represent an integer selected from 〇, i, 2, and 3; wherein Y represents a bond, C(0), 0, s, _〇_c ((7), _c(〇)_〇, -NR2-, -NR2-C(0)-, -C(〇)-NH- or S(0)2; wherein Z represents hydrogen, Cl_6 alkyl, NR2r3, cyano or contains a monocyclic or fused bicyclic moiety of 4 to i2 ring atoms, wherein one, two or three of the ring atoms are heteroatoms selected from n, fluorene and S, and wherein the monocyclic or fused bicyclic ring Substituting at least one or more substituents selected from the group consisting of halogen, cyano, c^.6 alkyl, hydroxy, and C 6 alkoxy, phage, phenyl, And a halogen-substituted phenyl group; wherein R2 and R3 independently represent hydrogen, C,-6 alkyl, hydroxy Ci 6 calcination 275 200906801, halo-Ci.6 alkyl or phenyl. The compound of any one of the 12th patents, wherein X represents a single ring moiety having 7 ring atoms, wherein the ring atom is nitrogen, and one of the 2 or 3 additional ring atoms may be a hetero atom selected from the group consisting of ruthenium, osmium and s and wherein the monocyclic moiety is optionally substituted with one or more substituents W, wherein the towel w is selected from the group consisting of hydrogen, thiol, dentate, cyano, (=〇), _ 0-(CH2)e-0- 'where e is 2 or 3 (spiro), (CH丄 where d is 5 or 6 (spiro) <^.6 alkyl, c2.6 dilute, Cw block , alkoxy, _c(〇)_c"6 alkyl C(o) O-Cy alkyl, _〇_c(〇)_Ci 6 alkyl, _c(〇)H, COOH; or wherein W is a formula _ (CH2)a_Y (cHA_z portion; wherein a and b independently represent an integer selected from ο,, and 3; Y represents a bond, C(〇), 〇, S, _〇_c(〇), _c(〇) 〇, -NR2-, -NR2-C(0)_, _c(〇)_NH or s( 〇) 2 ; wherein Z represents hydrogen, Ci 6 alkyl, nr 2 r 3 , an aryl group or a monocyclic or fused bicyclic moiety containing 4 to Q ring atoms, and optionally 1, 2 or 3 of the ring atoms are selected from the group consisting of a hetero atom of N, 〇A 8 , and wherein the monocyclic or slightly bicyclic moiety is optionally substituted with __ or a plurality of substituents selected from the group consisting of: a cyano group, a cyano group, a k-alkyl group, a phenyl group substituted with a phenyl group, a phenyl group, a Dtbn group, and a conjugated compound; wherein R 2 and R 3 independently represent hydrogen, C c alkyl, hydroxy Ci—alkyl, halo C w alkane Base or phenyl. The compound according to any one of the preceding claims, wherein X represents a monocyclic or bicyclic moiety having 8 ring atoms, one of the ring atoms is nitrogen ' and one, two or three thereof The additional ring atom may be a hetero atom selected from 276 200906801 〇 and s, and wherein the monocyclic or bicyclic moiety may be optionally substituted with one or more substituents w, wherein w is selected from the group consisting of hydrogen, hydroxyl, _ 素, Base, (=0), -〇-(CH2)c-〇-, where c is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), Cl6 alkyl, Ci6 alkoxy Base, _c(〇)_Ci6 alkyl, -C(0)-〇_Ci 6 alkyl, _〇_c(〇)_Ci 6 alkyl, _c(〇)H, C〇〇H; or where W represents a formula -(CH2)aY-(CH2)bZ moiety; wherein a and b independently represent an integer selected from the group consisting of 〇, 1, 2, and 3; f.. κ where Y represents a bond, C(〇), 〇, S , _〇_C(〇), _c(〇)_〇, _NR2_, _NR2_C(〇)-, -C(0)-NH- or S(0)2; wherein Z represents hydrogen, Ci.6 alkyl, Nr2r3, cyano or a monocyclic or fused bicyclic moiety containing 4 to fluorene atoms, wherein 1, 2 or 3 of the ring atoms are selected from the group consisting of N, hydrazine and s original? And wherein the monocyclic or fused bicyclic moiety is optionally substituted with one or more substituents selected from the group consisting of: a cyano group, a cyano group, a decyl group, a thiol group, and an alkoxy group (tetra) group, benzene base,. (d) a phenyl group substituted with a hydrazine; wherein R2 and R3 independently represent hydrogen, a Ci 6 alkyl group, a trans-group Cw group, a halo CK6 alkyl group or a phenyl group. A 17· As in the case of the 12th item of the patent application, any one of the compounds of the present invention, wherein X represents a single ring of 9 ring atoms, 0 #, a double coat, in the % atom The one is nitrogen, and wherein one, two or Ο S 1U additional % atoms may be heteroatoms selected from N, U and b, and wherein the single household bucket, μ τ ^ early % or double ring portion may be Or a plurality of substituents W, wherein w π ” depends on the condition of the animal. , medium ... is selected from the group consisting of hydrogen, hydroxyl, dentate, chaotic, (2), -〇_(CH2)c_〇_, its ^, ". horse 2 or 3 (snail where d is 5 or 6 ( Snail), Ci6 alkane ' 匕 1-6 oxime, 277 200906801 alkyl, -(:(0)-0-(^.6 alkyl,-0-(:(0)-(^.6 alkane a group, _C(0)H, COOH; or wherein w represents a formula -(CH2)a_Y_(CH2)b_z moiety; wherein a and b independently represent an integer selected from 〇, 1, 2, and 3; wherein Y represents a bond , C(O), Ο, S, -OC(O), -C(0)-0-, -NR2-, -NR2-C(〇)-, -C(0)-NH- or S(0 Wherein Z represents hydrogen, Ci 6 alkyl, NR 2 R 3 , cyano or a monocyclic or fused bicyclic moiety containing 4 to 12 ring atoms, as in the case of a ring atom, r: 2 or 3 a hetero atom from N, hydrazine and s, and wherein the monocyclic or fused bicyclic moiety is optionally substituted with one or more substituents selected from the group consisting of: i, cyano, Ci 6 a group, a (4), and a CM oxy group, a phenoxy group, a phenyl group, a phenyl group, and a phenyl group substituted with a ruthenium; 疋: R 2 and R 3 independently represent hydrogen, Ci 6 alkyl, 6 dilute , k alkynyl, light base (^.6 silk, The base of the Ci6 or the phenyl group is a compound of any one of the items in the scope of claim 12, wherein the X in the pot does not have a monocyclic or bicyclic moiety of a ring atom, and the nitrogen in the ring atom is And wherein i, 2 or 3 additional ring atoms may be heteroatoms selected from N, 〇 and S, and wherein the monocyclic or bicyclic moiety may be replaced by -= (take: base W instead of 'where w Is selected from the group consisting of chlorine, thiol, i, oxy, (=〇)m〇-, where h is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), Ci 6 d Burning base...C(〇)-〇_Ci.6 alkyl group, _〇Cl'6 fluorenyl group, -crom, COOH; or wherein W represents a formula ()H recognition (LH2)b_Z portion; wherein a and b are independently The expression is selected from the group consisting of γ, -, c(〇), 0, s, _0_c(〇), c(〇) 〇, 278 200906801 • ·ΝΚ2_, -NR2-C(〇)-, -C(0) -NH- or S(0)2,· wherein Z represents hydrogen, C _6 alkyl, nr2r3, cyano or a monocyclic or slightly bicyclic moiety containing from * to n ring atoms, as the case may be, 2 or 3 are heterogenes selected from N and ws, and wherein the monocyclic or fused bicyclic moiety is viewed as if Substituted with substituents of a plurality of groups selected from the group consisting of: halogen, cyano, Ci δ alkyl, hydroxy, and alkoxy, pyridinyl, phenyl, pyridyl, and halogen Substituted phenyl; wherein R 2 and R 3 independently represent hydrogen, Cl 6 alkyl, hydroxy C 6 alkyl, halo C -6 alkyl or phenyl. 19. A compound according to claim 1 which has the formula Ib

其中A表示N、CH或CR1 ; 其中各R1獨立地表示氫、Ci 6烷基、_c(〇)_Ci 6烷基、 c(o)-〇-cK6烧基、或苯基’其中該苯基、或Ci6烷基視情 ’况經一或多個選自以下基團之取代基取代：鹵素、羥基、鹵基C, _6燒基、確基、c, 6烧氧基、及n w ; 其中W係選自氫、經基、鹵素、氰基、（=〇)、 279 200906801 -(CH2)c-〇-，其中c為2或3(螺）、（CH2)d，其中d為5或6(螺）、 Ci-6 烧基、Cu 院氧基、-C(0)-C〗_6 燒基、6 烧基、-O-qovCu烷基、-C(0)H、COOH :或其中w表示式—(CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自0、1、2及3之整數；其中 Y 表示一鍵、C(O)、Ο、S、-O-C(O)、-C(0)_〇_、 -NR2-、-NR2-C(0)-、-C(0)-NH-或 S(0)2 ; 其中Z表示氫、c^-6烧基、NR2R3、氰基或包含4至12 1 個環原子之單環或稠合雙環部分，環原子中視情況i個、 2個或3個為選自N、〇及S之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：鹵素、氰基、Gw烷基、羥基、及Cm烷氧基、吡啡基、苯基、吡啶基、及經鹵素取代之苯基；其中R2及R3獨立地表示氫、Cl·6烷基、羥基c] 6境基、鹵基CN6烷基或苯基；及其醫藥學上可接受之鹽。 C ： 2〇.如申請專利範圍第19項之化合物，其中A表示CH，且R1表示Cw烷基。 21.如申請專利範圍第2〇項之化合物，其中Rl表示乙基或環丙基。 22，如申請專利範圍第1 9-21項中任一項之化合物，其中 W 表示式—(CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自〇、ι、2及3之整數；其中 Y 表示一鍵、C(O)、Ο、S、-O-C(O)、-C(0)-0-、 280 200906801 -NR2-、-NR2-C(〇)-、-C(0)-NH-或 S(0)2 ; 其中z表示氫、Cw烷基、nr2r3、氰基或包含4至12 個環原子之單環或稠合雙環部分，環原子中視情況i個、 2個或3個為選自N、〇及S之雜原子，且其中該單環或稠合雙％部分視情況經一或多個選自由以下基團組成之群的取代基取代：i素、氰基、Gw烷基、羥基、及烷氧基吡明1基、苯基、吡啶基、及經鹵素取代之苯基；其中R2及R3獨立地表示氫、Gw烷基、羥基CM烷基、_基C,-6烷基或笨基。 23. 如申請專利範圍第22項之化合物，其中γ表示一鍵、C(〇)或s(o)2 ;其中a+b為卜卜之、〗或4;且其中 =表不包含4至12個碳環原子及視情況丨個、2個或3個選自N、〇及s之雜原子之單環或稠合雙環部分，且其中忒早環或雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：鹵素、氰基、Cm烷基、羥基、及 6烧氧基、苯基、，基"比咬基、及經函素取代之苯基。 24. 如申請專利範圍第23項之化合物，其中γ表示一鍵或C(〇)，且a+b為〇、丨、2或3。 25. 如申明專利範圍第22項之化合物，其中z表示視 f月况、座或夕個選自由以下基團組成之群的取代基取代之嗎福林基：齒素、氰基、C“烷基、羥基、及Cl_6烷氧基、苯基、㈣基K基、及經i素取代之苯基。 26. 如巾請專利範圍第25項之化合物，其中該嗎福林基經由氮與W部分之剩餘部分連接。 281 200906801 27. 如申請專利範圍第22項之化合物，其中z表示視情況經一或多個選自由以下基團組成之群的取代基取代之哌啶基：A素、氱基、Ci 6烷基、羥基、及c"烷氧基、苯基、°比啡基、吡啶基、及經鹵素取代之苯基。 28. 如申請專利範圍第27項之化合物，其中該哌啶基經由氮與W部分之剩餘部分連接。 29. 如申請專利範圍第22項之化合物，其中z表示視情況經一或多個選自由以下基團組成之群的取代基取代之比啶基·鹵素、氰基、Ci-6烷基、羥基、及（V6烷氧基、 °比啡基、苯基、°比。^基、及經函素取代之笨基。 30. 如申叫專利範圍第29項之化合物其中該吡啶基係I由β亥比疋基之2、3或4位置與w部分之剩餘部分連 31 ·如申吻專利範圍第22項之化合物，其中Z表示視情況經一或多個選自ώ a 曰由以下基團組成之群的取代基取代之苯基·函素氰基、Ci6烧基、經基、及[Η院氧基、苯基、°比啡基、°比°定基、及經i素取代之苯基。 3 2 ·如申請專利簕囹梦. 車已圍第22項之化合物，其中z表示視情況經一或多個選自A 司由以下基團組成之群的取代基取代之吡咯啶基：函素、氰其土、Cl-6烧基、羥基、及CV6燒氧基、口 t匕啡基、苯基、吨°定其 n /上* 心卷、及經鹵素取代之苯基。 3 3 _如申請專利範圚视園第22項之化合物，其中z表示視情況經一或多個選自ώ ㈡田U下基團組成之群的取代基取代之吲哚基：鹵素、氰基、Γ Cl-6烧基、經基、及Cw烧氧基、 282 200906801 苯基、吡畊基、吡啶基、及經鹵素取代之苯基。 34.如申請專利範圍第33項之化合物，其中該吲嗓琳基係在該吲哚基之4、5、6或7位置與W部分之剩餘部分連接。 35 ·如申請專利範圍第22項之化合物，其中Z表示環戊基。 36.如申請專利範圍第22項之化合物，其中z表示。夫喃并吡咬基。 f 37·如申請專利範圍第22項之化合物，其中z表示四氫咬喃基。 3 8.如申請專利範圍第22項之化合物，其中γ表示— 鍵、C(O)、-C(0)-〇-、C(〇)_NH_、_〇_或 s(〇)2 ; a+b 為〇、 1、2、3或4;且其中z表示氫、CV6烷基、NR2R3或氰基。 39.如申請專利範圍第38項之化合物，其中γ表示— 鍵、c(o)、-c(o)-〇-、C(0)_NH_、_0_或 s(0)2，a+b 為〇、 1、2或3，且其中Z表示氫、曱基、乙基、_N(CH3)2、氰 ( 基、異丙基、異丁基、或第三丁基。 40·如申請專利範圍第19-21項中任一項之化合物，其中％係選自氫、羥基、鹵素、氰基、（=0)、-0-(CH2)c-〇、，其中c為2或3(螺）、（CH2)d，其中d為5或6(螺）、CK6境基、Cw 烧氧基、_C(0)_Ci 6 烷基、_c(〇)_〇_Ci 6 烷基 ί 烧基、_c(〇)h、c〇〇H。 41.如申請專利範圍第4〇項之化合物，其中贾係選自 -(CH2)d- ’其中d為5或6(螺），及^ —烷基。 283 200906801 42_如申請專利範圍第1項之化合物，其具有式IcWherein A represents N, CH or CR1; wherein each R1 independently represents hydrogen, Ci6 alkyl, _c(〇)_Ci6 alkyl, c(o)-〇-cK6 alkyl, or phenyl' wherein the phenyl Or a Ci6 alkyl group, as appropriate, substituted with one or more substituents selected from the group consisting of halogen, hydroxy, halo C, -6 alkyl, decyl, c, 6 alkoxy, and nw; W is selected from the group consisting of hydrogen, mercapto, halogen, cyano, (=〇), 279 200906801 -(CH2)c-〇-, where c is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), Ci-6 alkyl, Cu oxy, -C(0)-C _6 alkyl, 6 alkyl, -O-qovCu alkyl, -C(0)H, COOH: or w represents the formula -(CH2)aY-(CH2)bZ moiety; wherein a and b independently represent an integer selected from 0, 1, 2 and 3; wherein Y represents a bond, C(O), Ο, S, - OC(O), -C(0)_〇_, -NR2-, -NR2-C(0)-, -C(0)-NH- or S(0)2; wherein Z represents hydrogen, c^- 6 alkyl, NR2R3, cyano or a monocyclic or fused bicyclic moiety containing 4 to 12 1 ring atoms, wherein, in the ring atom, i, 2 or 3 are heteroatoms selected from N, fluorene and S, And wherein the monocyclic or fused bicyclic moiety is as appropriate Substituted by one or more substituents selected from the group consisting of halogen, cyano, Gw alkyl, hydroxy, and Cm alkoxy, pyrenyl, phenyl, pyridyl, and substituted by halogen Phenyl; wherein R 2 and R 3 independently represent hydrogen, Cl. 6 alkyl, hydroxy c yl, halo CN 6 alkyl or phenyl; and pharmaceutically acceptable salts thereof. C: 2〇. A compound according to claim 19, wherein A represents CH, and R1 represents Cw alkyl. 21. The compound of claim 2, wherein R1 represents ethyl or cyclopropyl. The compound of any one of claims 1-9, wherein W represents a formula -(CH2)aY-(CH2)bZ moiety; wherein a and b independently represent a group selected from 〇, ι, 2, and An integer of 3; wherein Y represents a bond, C(O), Ο, S, -OC(O), -C(0)-0-, 280 200906801 -NR2-, -NR2-C(〇)-, - C(0)-NH- or S(0)2; wherein z represents hydrogen, Cw alkyl, nr2r3, cyano or a monocyclic or fused bicyclic moiety containing from 4 to 12 ring atoms, as in the case of a ring atom , 2 or 3 are heteroatoms selected from the group consisting of N, hydrazine and S, and wherein the monocyclic or fused bis-% moiety is optionally substituted with one or more substituents selected from the group consisting of: i a cyano group, a cyano group, a Gw alkyl group, a hydroxy group, and an alkoxypyrimidinyl group, a phenyl group, a pyridyl group, and a halogen-substituted phenyl group; wherein R2 and R3 independently represent hydrogen, Gw alkyl group, hydroxy CM alkane Base, _ group C, -6 alkyl or stupid. 23. The compound of claim 22, wherein γ represents a bond, C(〇) or s(o)2; wherein a+b is 卜, 或 or 4; and wherein the table does not contain 4 to 12 carbon ring atoms and, as the case may be, 2 or 3 monocyclic or fused bicyclic moieties selected from heteroatoms of N, hydrazine and s, and wherein the fluorene or bicyclic moiety is one or more Substituted by a substituent of the group consisting of halogen, cyano, Cm alkyl, hydroxy, and 6 alkoxy, phenyl, phenyl, and phenyl substituted by a thiol group. 24. The compound of claim 23, wherein γ represents a bond or C(〇), and a+b is 〇, 丨, 2 or 3. 25. A compound according to claim 22, wherein z represents a phenoline group substituted with a substituent selected from the group consisting of dentate, cyano, C" An alkyl group, a hydroxyl group, and a Cl_6 alkoxy group, a phenyl group, a (tetra)yl group, and a phenyl group substituted by an element. 26. A compound of the 25th aspect of the patent, wherein the phenoflavinyl group is via nitrogen The remainder of the W moiety is linked. 281 200906801 27. The compound of claim 22, wherein z represents a piperidinyl group optionally substituted with one or more substituents selected from the group consisting of: A , fluorenyl, Ci 6 alkyl, hydroxy, and c" alkoxy, phenyl, phentyl, pyridyl, and halogen substituted phenyl. 28. A compound of claim 27, wherein The piperidinyl group is attached to the remainder of the W moiety via nitrogen. 29. A compound according to claim 22, wherein z represents a ratio substituted by one or more substituents selected from the group consisting of: Pyridyl, halogen, cyano, Ci-6 alkyl, hydroxy, and (V6 alkoxy , ° ratio of morphyl, phenyl, °. ^ base, and the base substituted by the element. 30. For example, the compound of claim 29, wherein the pyridyl group I is composed of β , the 3 or 4 position and the remainder of the w portion 31. The compound of claim 22, wherein Z represents a substituent selected from the group consisting of one or more selected from the group consisting of ώ a 视a substituted phenyl-functional cyano group, a Ci6 alkyl group, a thiol group, and a [phenylene oxy group, a phenyl group, a phenanthrenyl group, a ° ratio, and a phenyl group substituted by i. 3 2 · Patent application nightmare. The compound of the 22nd item, wherein z represents a pyrrolidinyl group substituted by one or more substituents selected from the group consisting of the following groups: a gram, a cyanide Soil, Cl-6 alkyl, hydroxyl, and CV6 alkoxy, thiophene, phenyl, ton, n / upper * heart roll, and halogen substituted phenyl. 3 3 _ as patent A compound of the 22nd item, wherein z represents a thiol group substituted with one or more substituents selected from the group consisting of ώ(二)田U groups: , cyano, hydrazine, Cl-6 alkyl, thiol, and Cw alkoxy, 282 200906801 phenyl, pyridinyl, pyridyl, and halogen substituted phenyl. 34. Patent Application No. 33 a compound wherein the sulfhydryl group is attached to the remainder of the W moiety at the 4, 5, 6 or 7 position of the thiol group. 35. The compound of claim 22, wherein Z represents a cyclopentyl group. 36. A compound according to claim 22, wherein z represents a compound of the formula 22, wherein z represents a tetrahydrocarbyl group. 3 8. The compound of claim 22, wherein γ represents — bond, C(O), —C(0)-〇-, C(〇)_NH_, _〇_ or s(〇)2; +b is 〇, 1, 2, 3 or 4; and wherein z represents hydrogen, C6 alkyl, NR2R3 or cyano. 39. A compound according to claim 38, wherein γ represents — bond, c(o), —c(o)-〇-, C(0)_NH_, _0_ or s(0)2, a+b Is 〇, 1, 2 or 3, and wherein Z represents hydrogen, fluorenyl, ethyl, _N(CH3)2, cyanide (yl, isopropyl, isobutyl, or tert-butyl. 40) The compound according to any one of items 19 to 21, wherein the % is selected from the group consisting of hydrogen, hydroxy, halogen, cyano, (=0), -0-(CH2)c-〇, wherein c is 2 or 3 ( Spiro), (CH2)d, where d is 5 or 6 (spiro), CK6, Cw alkoxy, _C(0)_Ci 6 alkyl, _c(〇)_〇_Ci 6 alkyl , _c(〇)h, c〇〇H. 41. The compound of claim 4, wherein the family is selected from -(CH2)d- 'where d is 5 or 6 (spiro), and ^ Alkyl. 283 200906801 42_A compound of claim 1 having the formula Ic

其中A表示n、CH或CR1 ; 其中各R1獨立地表示氳、CU6烷基、烷基、 -c(o)_〇_Ci 6烷基、或苯基，其中該苯基、或Ci 6烷基視情況經一或多個選自以下基團之取代基取代：函素、羥基、南基C1-6烷基、硝基、C16烷氧基、及NR2R3 ; 其中W係選自氫、羥基、鹵素、氰基、（=〇)、_〇_ (CH2)c_〇-’其中c為2或3(螺）、（CH2)d，其中d為5或6(螺）、 ci-6 燒基、Cu 烷氧基、_C(;0)_Ci_6 烷基、-C(〇)_〇_Ci 6 烷基、-O-CHCO-Cu 烷基、_C(〇)H、c〇OH ;或其中 w 表示式一(CH2)a_Y-(CH2)b-Z 部分；其中a及b獨立地表示選自〇、〖、2及3之整數；其中 Y 表示一鍵、c(0)、Ο、S、-O-C(o)、-C(0)-0-、 •NR2_、-NR2-C(0)-、-C(〇)-NH-或 S(0)2 ; 其中z表示氫、Ci0烷基、NR2R3、氰基或包含4至丄2 個裱原子之單環或稠合雙環部分，環原子中視情況1個、 284 200906801 2個或3個為選自N、〇及S之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：鹵素、氰基、Cw烷基、羥基、及（^·6貌氧基、α比啡基、苯基、η比咬基 '及經鹵素取代之苯基；其中R2及R3獨立地表示氫、Cu烷基、羥基CK6燒基、鹵基<^_6烷基或笨基；及其醫藥學上可接受之鹽。 43 ·如申請專利範圍第42項之化合物，其中a表示CH，Wherein A represents n, CH or CR1; wherein each R1 independently represents hydrazine, CU6 alkyl, alkyl, -c(o)_〇_Ci 6 alkyl, or phenyl, wherein the phenyl or Ci 6 alkane The base-view condition is substituted with one or more substituents selected from the group consisting of a hydroxyl group, a hydroxyl group, a south group C1-6 alkyl group, a nitro group, a C16 alkoxy group, and NR2R3; wherein the W group is selected from the group consisting of hydrogen and hydroxyl groups. , halogen, cyano, (=〇), _〇_ (CH2)c_〇-' where c is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), ci-6 Alkyl, Cu alkoxy, _C(;0)_Ci_6 alkyl, -C(〇)_〇_Ci 6 alkyl, -O-CHCO-Cu alkyl, _C(〇)H, c〇OH; or Wherein w represents a formula (CH2)a_Y-(CH2)bZ moiety; wherein a and b independently represent an integer selected from the group consisting of 〇, 〖, 2, and 3; wherein Y represents a bond, c(0), Ο, S, -OC(o), -C(0)-0-, •NR2_, -NR2-C(0)-, -C(〇)-NH- or S(0)2; wherein z represents hydrogen, Ci0 alkyl , NR2R3, cyano or a monocyclic or fused bicyclic moiety containing 4 to 2 fluorene atoms, as in the case of a ring atom, 284 200906801 2 or 3 are heteroatoms selected from N, 〇 and S, and Where the single ring or fused The ring moiety is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, Cw alkyl, hydroxy, and (^.6 morphoxy, alpha morphinyl, phenyl, N is more than a thiol group and a halogen-substituted phenyl group; wherein R 2 and R 3 independently represent hydrogen, Cu alkyl group, hydroxy CK 6 alkyl group, halo group < ^ 6 alkyl group or stupid group; and pharmaceutically acceptable thereof Salt. 43. A compound as claimed in claim 42 wherein a represents CH,

且RI表示CK6烷基。 44_如申請專利範圍第43項之化合物，其中Rl表示乙基或環丙基。 45·如申請專利範圍第42-44項中任一項之化合物，其 2 w獨立地表示氫、羥基、苯基、經Ci6烷氧基取代之苯二印底°定基…比咬基、.〇_(CH2)c-〇_ ’其中c為2或3(螺）、或兔】3)2、C“ 烷基、-(CH2)a-C(0)-0_(CH2)b-H，其中 a+b 馬1、2或3 (CH2)--n 〇 ’其中a表示1、2或3。 46·如申請專利範圍第1項之化合物，其具有式1( 285 200906801And RI represents a CK6 alkyl group. 44. A compound according to claim 43, wherein R1 represents an ethyl group or a cyclopropyl group. The compound of any one of claims 42-44, wherein 2 w independently represents hydrogen, a hydroxy group, a phenyl group, a Ci6 alkoxy group substituted by a Ci6 alkoxy group, a bite base. 〇_(CH2)c-〇_ 'where c is 2 or 3 (spiro), or rabbit] 3) 2, C "alkyl, -(CH2)aC(0)-0_(CH2)bH, where a+ b horse 1, 2 or 3 (CH2)--n 〇 'where a represents 1, 2 or 3. 46. The compound of claim 1 has the formula 1 (285 200906801)

[Id] 其中A表示N、CH或CR1 ; 其中各R1獨立地表示氫、CV6烧基、烧基、 -c(o)-〇-Ci 0烷基、或苯基，其中該苯基、或Ci 6烷基視情況經一或多個選自以下基團之取代基取代：鹵素、羥基、 _基CU6烷基、硝基、Cl.6烷氧基、及nr2r3 ; 其中W係選自氫、羥基、鹵素、氰基、（=〇)、-〇_ (CH2)c-〇_，其中c為2或3(螺）、（CH2)d，其中d為5或6(螺）、 Cu 烷基、CV6 烷氧基、-C(〇)_Cl 6 烷基、_c(〇)_〇_Ci 6 烷基、-O-CCCO-Cu 烷基、-C(0)H、COOH ; ，、中R及R3獨立地表示氫、（^_6烧基、羧基Cu烧基、i基（^.6烷基或苯基；其中R9-R12獨立地表示氫或鹵素；及其醫藥學上可接受之鹽。 47.如申請專利範圍第46項之化合物，其中a為CH ; R〗表示CN0烷基；且R9_Ru中之每一者獨立地表示氫或齒素。 286 200906801 48·如申請專利範圍第47項之化合物，其中R1 基或環丙基；且R9_R12中之每一者表示氫。不乙 49_如申請專利範圍第1項之化合物，其具有式I[Id] wherein A represents N, CH or CR1; wherein each R1 independently represents hydrogen, CV6 alkyl, alkyl, -c(o)-〇-Ci0 alkyl, or phenyl, wherein the phenyl, or The Ci 6 alkyl group is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, _yl CU6 alkyl, nitro, Cl.6 alkoxy, and nr2r3; wherein W is selected from hydrogen , hydroxy, halogen, cyano, (=〇), -〇_(CH2)c-〇_, where c is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), Cu Alkyl, CV6 alkoxy, -C(〇)_Cl 6 alkyl, _c(〇)_〇_Ci 6 alkyl, -O-CCCO-Cu alkyl, -C(0)H, COOH ; Wherein R and R3 independently represent hydrogen, (^6 alkyl, carboxyl Cu, i group (^.6 alkyl or phenyl; wherein R9-R12 independently represents hydrogen or halogen; and pharmaceutically acceptable thereof) 47. A compound according to claim 46, wherein a is CH; R represents a CN0 alkyl group; and each of R9_Ru independently represents hydrogen or dentate. 286 200906801 48 · as claimed A compound according to item 47, wherein R1 or cyclopropyl; and each of R9_R12 represents hydrogen. B 49_ scope of the compounds as described in Patent Application, Paragraph 1, having the formula I

[le] 其中A表示n、CH或CR1 ; 其中各R1獨立地表示氫、Ci 6烷基、_c(〇)_Ci 6烷基、 •c(o)-o-u基、或苯基’其“亥苯基、或6燒基視情況經一或多個選自以下基團之取代基取代：_素、羥基、鹵基Cw烷基、硝基、Cl.6烷氧基、及NR2R3 ; 其中W係選自氫、羥基、函素、氰基、（=〇)、_〇_ (CH2)c-0-，其中c為2或3(螺）、（CH2)d，其中d為5或6(螺）、 Cw 烷基、cv6 烷氧基、_c(0)_Ci 6 烷基、_c(〇)_〇_Ci 6 烷基、-0-(:(0)-(^.6 烷基、_C(0)H、COOH ;或其中 w 表示式一(CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、C(C〇、〇、S、-O-C(O)、_c(0)-0-、 NR2、-NR2-C(0)-、_c(〇)-NH-或 S(0)2 ; 287 200906801 其中Z表示氫、c!·6烷基、nr2r3、氰基或包含4至12 個ί哀原子之單壞或稠合雙環部分’環原子中視情況1個 2個或3個為選自Ν、〇及S之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：_素、氰基、Cy烷基、羥基、及Γ 入院氧基比啡基、本基、。比α定基、及經_素取代之苯義· 其中R2及R3獨立地表示氫、Ci_6烷基、羥基Ci 6燒基、函基（^-6烷基或苯基；及其醫藥學上可接受之鹽。 50. 如申請專利範圍第49項之化合物，其中a為，且R1表示Ci_6烷基。 51. 如申請專利範圍第50項之化合物，其中R】表示乙基或環丙基。 ’ 52·如申請專利範圍第1項之化合物，其具有式If[le] wherein A represents n, CH or CR1; wherein each R1 independently represents hydrogen, Ci 6 alkyl, _c(〇)_Ci 6 alkyl, • c(o)-ou, or phenyl 'its The phenyl group or the 6 alkyl group is optionally substituted with one or more substituents selected from the group consisting of: _, hydroxy, halo Cw alkyl, nitro, Cl. 6 alkoxy, and NR 2 R 3 ; Is selected from the group consisting of hydrogen, hydroxyl, hydroxyl, cyano, (=〇), _〇_(CH2)c-0-, where c is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), Cw alkyl, cv6 alkoxy, _c(0)_Ci 6 alkyl, _c(〇)_〇_Ci 6 alkyl,-0-(:(0)-(^.6 alkyl, _C(0)H, COOH; or wherein w represents a formula (CH2)aY-(CH2)bZ moiety; wherein a and b independently represent an integer selected from 〇, 1, 2, and 3; wherein Y represents a bond, C(C〇, 〇, S, -OC(O), _c(0)-0-, NR2, -NR2-C(0)-, _c(〇)-NH- or S(0)2; 287 200906801 Wherein Z represents hydrogen, c!.6 alkyl, nr2r3, cyano or a single or fused bicyclic moiety containing 4 to 12 mourning atoms. One ring or two of the ring atoms are selected from the group consisting of ruthenium, And a hetero atom of S, and wherein the single ring or fused The ring moiety is optionally substituted with one or more substituents selected from the group consisting of _, cyano, Cy alkyl, hydroxy, and oxime, oxy, phenyl, benzyl, benzyl And phenyl-substituted by _-- wherein R 2 and R 3 independently represent hydrogen, Ci-6 alkyl, hydroxy Ci 6 alkyl, functional (^-6 alkyl or phenyl; and pharmaceutically acceptable salts thereof 50. A compound according to claim 49, wherein a is, and R1 represents a Ci_6 alkyl group. 51. A compound according to claim 50, wherein R] represents an ethyl or cyclopropyl group. Such as the compound of claim 1 of the patent scope, which has the formula If

其中A表示n、CH或CR1 ; 其中各R1獨立地表示氫、Ci 0烷基、_c(〇)_c】-6烷基 200906801 .4(0)-0-(^.6烧基、或苯基，其中該苯基、或c16烧基視情況經一或多個選自以下基團之取代基取代：4素、經基、鹵基CV6烷基、硝基' Cw烷氧基、及nr2r3 ; 其中W係選自氫、羥基、鹵素、氰基、（=〇)、_〇_ (CH2)c-0-，其中C為2或3(螺）、（CH2)d，其中d為5或6(螺）、 Ci-6 烧基、CV6 烧氧基、-(:(0)-(^6 烧基、燒基、-O-CCCO-Cu 烷基、-C(0)H、COOH ;或其中 W 表示式-(CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、C(O)、Ο、S、-O-C(O)、_c(0)-0-、 NR2、-NR2-C(0)-、-C(0)-NH-或 S(0)2 ; 其中Z表示氫、（γ6烷基、NR2R3、氰基或包含4至12 個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、0及S之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：鹵素、氰基、Ci·6烷基、羥基、及6烷 £ 、氧基、D比啡基、苯基、°比°定基、及經鹵素取代之苯基；其中R2及R3獨立地表示氫、Cl 6烷基、羥基Gw烷基、鹵基CV6烷基或苯基；及其醫藥學上可接受之鹽。 53·如申请專利範圍第52項之化合物，其中a為CH，且R1表示CN6烷基。 54.如申請專利範圍第53項之化合物，其中Rl表示乙基或環丙基。 289 200906801 55·如申請專利範圍第1項之化合物，其具有式IgWherein A represents n, CH or CR1; wherein each R1 independently represents hydrogen, Ci0 alkyl, _c(〇)_c]-6 alkyl 200906801.4(0)-0-(^.6 alkyl, or benzene a group wherein the phenyl group or the c16 alkyl group is optionally substituted with one or more substituents selected from the group consisting of a 4-membered group, a trans-group, a halo-CV6 alkyl group, a nitro 'Cw alkoxy group, and nr2r3 Wherein W is selected from the group consisting of hydrogen, hydroxy, halogen, cyano, (=〇), _〇_(CH2)c-0-, wherein C is 2 or 3 (spiro), (CH2)d, where d is 5 Or 6 (spiro), Ci-6 alkyl, CV6 alkoxy, -(:(0)-(^6 alkyl, alkyl, -O-CCCO-Cu alkyl, -C(0)H, COOH Or wherein W represents a formula -(CH2)aY-(CH2)bZ moiety; wherein a and b independently represent an integer selected from the group consisting of 〇, 1, 2, and 3; wherein Y represents a bond, C(O), Ο, S, -OC(O), _c(0)-0-, NR2, -NR2-C(0)-, -C(0)-NH- or S(0)2; wherein Z represents hydrogen, (γ6 alkane a group, NR2R3, a cyano group or a monocyclic or fused bicyclic moiety containing 4 to 12 ring atoms, wherein one, two or three of the ring atoms are optionally selected from N, 0 and S, and wherein Monocyclic or fused bicyclic moiety as appropriate by one or more Substituted by substituents of the group consisting of halogen, cyano, Ci.6 alkyl, hydroxy, and 6-alkane, oxy, D-cyano, phenyl, °, and halogen a substituted phenyl group; wherein R 2 and R 3 independently represent hydrogen, Cl 6 alkyl, hydroxy Gw alkyl, halo CV 6 alkyl or phenyl; and pharmaceutically acceptable salts thereof. A compound of the formula 52, wherein a is CH, and R1 represents a CN6 alkyl group. 54. A compound according to claim 53 wherein R1 represents ethyl or cyclopropyl. 289 200906801 55 · as claimed in claim 1 a compound having the formula Ig

其中A表示N、CH或CR1 ; 其中各R1獨立地表示氫、Cw烷基、烷基、 -c(o)-〇-Cl 6烷基、或苯基，其中該苯基、或Ci6烷基視情況經一或多個選自以下基團之取代基取代：_素、羥基、鹵基C】_6烷基、硝基、Cl.6烷氧基、及NR2R3 ; 其中W係選自氫、羥基、鹵素、氰基、（ = 〇)、-〇-(CH2)c-〇-，其中c為2或3(螺）、（CH2)d，其中d為5或6(螺）、 C,-6 烷基、CV6 烷氧基、-CCCO-Cu 烷基、烷基、-O-CCCO-Cu 烷基、-N(R2)-C(0)-R3、-C(〇)H、COOH ; 或其中W表示式-(CH2)a-Y-(CH2)b-Z部分；其中a及b獨立地表示選自0、1、2及3之整數；其中 Y 表示一鍵、C(O)、Ο、S、-〇-C(〇)、-C(0)-0-、 NR2、-NR2-C(0)-、-C(0)-NH-或 S(0)2 ; 其中z表示氫'Cw烷基、NR2R3、氰基或包含4至12 個環原子之單環或稠合雙環部分’環原子中視情況1個、 290 200906801 2個或3個為選自N、0及S之雜原子，且其中該單環咬稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：ii素、氰基、Cw烷基、羥基、及氧基、°比啡基、苯基、°比咬基、及經鹵素取代之苯基；其中R2及R3獨立地表示氫、（V6烷基、羥基Cl 6提基、i基cv6烷基或苯基；及其醫藥學上可接受之鹽。Wherein A represents N, CH or CR1; wherein each R1 independently represents hydrogen, Cw alkyl, alkyl, -c(o)-〇-Cl 6 alkyl, or phenyl, wherein the phenyl or Ci6 alkyl Optionally substituted with one or more substituents selected from the group consisting of: _, hydroxy, halo C -6 alkyl, nitro, Cl. 6 alkoxy, and NR 2 R 3 ; wherein W is selected from hydrogen, Hydroxyl, halogen, cyano, (= 〇), -〇-(CH2)c-〇-, wherein c is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), C, -6 alkyl, CV6 alkoxy, -CCCO-Cu alkyl, alkyl, -O-CCCO-Cu alkyl, -N(R2)-C(0)-R3, -C(〇)H, COOH Or wherein W represents a formula -(CH2)aY-(CH2)bZ moiety; wherein a and b independently represent an integer selected from 0, 1, 2, and 3; wherein Y represents a bond, C(O), Ο, S, -〇-C(〇), -C(0)-0-, NR2, -NR2-C(0)-, -C(0)-NH- or S(0)2; wherein z represents hydrogen' Cw alkyl, NR2R3, cyano or a monocyclic or fused bicyclic moiety containing 4 to 12 ring atoms, as the case may be, 290 200906801 2 or 3 are heteroatoms selected from N, 0 and S And wherein the single ring bite the fused bicyclic moiety as appropriate One or more substituents selected from the group consisting of ii, cyano, Cw alkyl, hydroxy, and oxy, phentyl, phenyl, decyl, and halogen substituted Phenyl; wherein R2 and R3 independently represent hydrogen, (V6 alkyl, hydroxyCl6, i-based cv6 alkyl or phenyl; and pharmaceutically acceptable salts thereof).

56.如申請專利範圍第55項之化合物，其中a為CH，立R1表示CU6烷基。 57_如申請專利範圍第56項之化合物，其中R1表示乙基或環丙基。 58.如申請專利範圍第1項之化合物，其具有式^56. The compound of claim 55, wherein a is CH and R1 represents CU6 alkyl. 57. A compound according to claim 56, wherein R1 represents an ethyl group or a cyclopropyl group. 58. The compound of claim 1, wherein the compound has the formula ^

其中A表示N、ch或CRi ; 其中各R1獨立地表示氯、Ci ό院基、_c(〇)_Ci 6烧基、 _C⑼办cv6烧基、或苯基’其中該苯基或k燒基視情况經-或多個選自以下基團之取代基取代：處素、經基、 291 200906801 : 鹵基Cw烷基、硝基、CV6烷氧基、及NR2R3 ; 其中 W係選自氫、羥基、鹵素、氰基、（ = 〇)、_〇_ (CH2)c-0-，其中C為2或3(螺）、（CH2)d，其中d為5或6(螺）、 Cw烷基、C〗.6烷氧基、-QCO-Cw烷基、-c(〇)-〇-CU6像基' -O-qcO-Cu烷基、-C(0)H、COOH ;或其中W表示式-(CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自0、1、2及3之整數；其中 Y 表示一鍵、C(O)、Ο、S、-O-C(O)、、 NR2、-NR2-C(0)-、-C(0)-NH-或 S(0)2 ; 其中z表示氫、Cw烷基、NR2R3、氰基或包含4至12 個環原子之單環或稠合雙環部分，環原子中視情況i個、 2個或3個為選自N、0及S之雜原子，且其中該單環或稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：鹵素、氰基、Cw烷基、羥基、及q 6烷氧基、吡啡基、苯基、吡啶基、及經鹵素取代之苯基. 其中R2及R3獨立地表示氫、Ci 0烷基、羥基I 6烷基、齒基Ci_6烧基或苯基；及其醫藥學上可接受之鹽。 59.如申請專利範圍第58項之化合物，其中a為ch，且R1表示C!_6烷基。 6〇·如申請專利範圍第57項之化合物，其中R1表示乙基或環丙基。 ' 61.如申請專利範圍第丨項之化合物其具有式I 292 200906801Wherein A represents N, ch or CRi; wherein each R1 independently represents chlorine, Ci ό 院, _c(〇)_Ci 6 alkyl, _C(9) cv6 alkyl, or phenyl 'where the phenyl or k alkyl The case is substituted with or a plurality of substituents selected from the group consisting of: a mesogen, a mesogen, 291 200906801: a halo Cw alkyl group, a nitro group, a CV6 alkoxy group, and NR2R3; wherein the W group is selected from the group consisting of hydrogen and hydroxyl groups. , halogen, cyano, ( = 〇), _〇_ (CH2)c-0-, wherein C is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), Cw alkyl , C 〖.6 alkoxy, -QCO-Cw alkyl, -c(〇)-〇-CU6 like base '-O-qcO-Cu alkyl, -C(0)H, COOH; or where W is a moiety of the formula -(CH2)aY-(CH2)bZ; wherein a and b independently represent an integer selected from 0, 1, 2, and 3; wherein Y represents a bond, C(O), Ο, S, -OC ( O), NR2, -NR2-C(0)-, -C(0)-NH- or S(0)2; wherein z represents hydrogen, Cw alkyl, NR2R3, cyano or contains 4 to 12 rings a monocyclic or fused bicyclic moiety of an atom, wherein, in the ring atom, i, 2 or 3 are heteroatoms selected from N, 0 and S, and wherein the monocyclic or fused bicyclic moiety is optionally one or more One Substituted by a substituent of a group consisting of halogen, cyano, Cw alkyl, hydroxy, and q 6 alkoxy, pyranyl, phenyl, pyridyl, and phenyl substituted by halogen. And R3 independently represents hydrogen, Ci0 alkyl, hydroxyI6 alkyl, dentate Ci-6 alkyl or phenyl; and pharmaceutically acceptable salts thereof. 59. The compound of claim 58 wherein a is ch and R1 represents C!-6 alkyl. 6. A compound according to claim 57, wherein R1 represents an ethyl group or a cyclopropyl group. '61. A compound of the scope of the patent application, having the formula I 292 200906801

1或2 (w) [Ι>] 其中A表示N、CH或CR1 ; 其中各R1獨立地表示氳、C〖.6烷基、-(:(0)-(:,.6烷基、 -C(〇)_〇_Ci J烧基、或苯基，其中該苯基、或Gy烷基視情況經一或多個選自以下基團之取代基取代：_素、羥基、 _基CK6烷基、硝基、Cl.6烷氧基、及NR2R3 ; 其中W係選自氳、羥基、鹵素、氰基、（=〇)、_〇_ (CH2)c_〇·，其中（；為2或3(螺）、（CH2)d，其中d為$或6(螺）、 Ci-6 垸基、Cw 烧氧基、_(：(0)-(^.6 烧基、_(^(〇)-〇-〇ν6 院基、-O-CCC^-Cu 烷基、-C(0)H、COOH ;或其中 X 表示式〜(CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自〇、1、2及3之整數；其中 Y 表示一鍵、C(O)、Ο、S、-〇-c(〇)、_c(〇；)-〇-、 NR2、-NR2-C(0)-、-C(〇)-NH-或 S(0)2 ; 其中Z表示氫、Cu烧基、NR2R3、氰基或包含4至12 個環原子之單環或稠合雙環部分’環原子中視情況丨個、 2個或3個為選自N、〇及S之雜原子，且其中該單環或 293 200906801 稠合雙環部分視情況經一或多個選自由以下基團组成的取代基取代：函素、氰基、h_6烧基、㈣、及Ci6燒氧基、吡畊基、苯基、吡啶基、及經鹵素取代之苯基；其中R及R3獨立地表示氫、Ci_6烷基、羥基Cl 6烷基、齒基CU6烷基或笨基；及其醫藥學上可接受之鹽。 62.如申請專利範圍第61項之化合物，其中a為CH，且R1表示（^_6烷基。 63 _如申請專利範圍第62項之化合物，其中R1表示乙基或環丙基。 64·如申晴專利範圍第1項之化合物，其具有式ij R14 R16^>^A-R1 R17 I1 or 2 (w) [Ι>] wherein A represents N, CH or CR1; wherein each R1 independently represents 氲, C 〖.6 alkyl, -(:(0)-(:, .6 alkyl, - C(〇)_〇_Ci J alkyl, or phenyl, wherein the phenyl or Gy alkyl is optionally substituted with one or more substituents selected from the group consisting of: _, hydroxy, _ ke6 An alkyl group, a nitro group, a Cl. 6 alkoxy group, and NR2R3; wherein W is selected from the group consisting of hydrazine, hydroxy, halogen, cyano, (=〇), _〇_(CH2)c_〇·, wherein 2 or 3 (spiro), (CH2)d, where d is $ or 6 (spiro), Ci-6 thiol, Cw alkoxy, _(:(0)-(^.6 alkyl, _(^ (〇)-〇-〇ν6 院基, -O-CCC^-Cu alkyl, -C(0)H, COOH; or wherein X represents a formula ~(CH2)aY-(CH2)bZ moiety; b independently represents an integer selected from 〇, 1, 2, and 3; wherein Y represents a bond, C(O), Ο, S, -〇-c(〇), _c(〇;)-〇-, NR2 -NR2-C(0)-, -C(〇)-NH- or S(0)2; wherein Z represents hydrogen, Cu alkyl, NR2R3, cyano or a single ring or thick containing 4 to 12 ring atoms In the bicyclic moiety, the ring atoms are optionally one, two or three are heteroatoms selected from N, fluorene and S. And wherein the monocyclic or 293 200906801 fused bicyclic moiety is optionally substituted with one or more substituents selected from the group consisting of a functional group, a cyano group, a h-6 alkyl group, (IV), and a Ci6 alkoxy group, pyridinium a phenyl group, a pyridyl group, and a halogen-substituted phenyl group; wherein R and R3 independently represent hydrogen, Ci-6 alkyl, hydroxyCl 6 alkyl, dentyl CU6 alkyl or stupid; and pharmaceutically acceptable 62. A compound according to claim 61, wherein a is CH, and R1 represents (^_6 alkyl. 63 _ as claimed in claim 62, wherein R1 represents ethyl or cyclopropane 64. A compound according to claim 1 of the Shenqing patent range, which has the formula ij R14 R16^>^A-R1 R17 I

其中A表示n、CH或CR1 ; 其中各R1獨立地表示氫、Cw烷基、-CCCO-CV6烷基、 -C(0)-0-CK6烷基、或苯基，其中該苯基或Cl.6烷基視情況經一或多個選自以下基團之取代基取代：鹵素、經基、 294 200906801 鹵基Cw烷基、硝基、Cl.6烷氧基、及NR2R3 ; 其中X表示氫、Cu烧基、氰基、-OR2、-〇_c(〇)&2、 -〇c(o)nr2r3、_c(0)_nr2r3、-N(R2)c(o)R3、_n(r2) C(0)NR2R3或NR2R3’或X表示具有4-16個環原子之單環、雙環或三環部分，環原子中之一者為氮，且其中1個、2 個或3個額外環原子可為選自N、0及s之雜原子，且其中該單環、雙環或三環部分可視情況經一或多個取代基w ( ν' 取代，其中W係選自氫、羥基、鹵素、氰基、（=〇)、七 (CH2)c-〇-，其中e為2或3(螺）、（CH2)d，其中d為5或6(螺）、 cv6 烷基、Cl_6 烷氧基、_c(0)_Ci 6 烷基、_c(〇)_〇_Cm 烷基、-〇-c(o)-Cl 6烷基、^⑴阳、c〇〇H ;或其中w表示式—(CH2)a-Y_(CH2)b_z 部分；其中a及b獨立地表示選自〇、ι、2及3之整數；其令 Y表示—鍵、c(〇)、〇、S、-ο-e⑼、_c(0)_0… -NR2_、_NR2-C(0)-、-C(0)-NH·或 s(0)2 ; 其中Z表示氫、c"烷基、nrZr3、氰基或包含4至以個環原子之單環或稠合雙環部分，環原子中視情況1個、 2個或3個為選自N、〇及s之雜原子，且其中該單環稠合雙環部分視情況經一或多個選自由以下基團組成之群的取代基取代：顧素、氰基、c“6貌基、經基、及c 氧基、苯基、。比啶其 s . I.6烷比定基、及經齒素取代之苯基；其中R4-r8中之一去矣+占主 13 7 者表不幽素且其餘表示氫；其中之—者表示幽素且其餘表示氫；其中R2及R3獨立地表示氫、 L I丨·6烷基、羥基c丨.6烷 295 200906801 -基、鹵基<^_6烷基或苯基；及其醫藥學上可接受之鹽。 65 _如申請專利範圍第64項之化合物，其中A表示CH ; R1表示乙基或環丙基；Ri4表示鹵素：且以或反8表示鹵素。 66. 如申請專利範圍第65項之化合物，其中X表示經或兩個取代基W取代之I»辰啡基或ΐ-α底。定基，其中該w 為式-(CH2)a-Y_(CH2)b_z部分，其中a及b獨立地表示〇、 - 1、2或3 ; Y表示一鍵、Ο、_NR2-C(0)-;且其中Z表示軋、Cw烷基、哌啶基、嗎福林基、吡啶基、、 1 - 6燒氧基取代之苯基或D比咯啶基。 67. 如申請專利範圍第1項之化合物’其具有式Wherein A represents n, CH or CR1; wherein each R1 independently represents hydrogen, Cw alkyl, -CCCO-CV6 alkyl, -C(0)-0-CK6 alkyl, or phenyl, wherein the phenyl or Cl The .6 alkyl group is optionally substituted with one or more substituents selected from the group consisting of halogen, thiol, 294 200906801 halo Cw alkyl, nitro, Cl. 6 alkoxy, and NR2R3; wherein X represents Hydrogen, Cu alkyl, cyano, -OR2, -〇_c(〇)&2, -〇c(o)nr2r3, _c(0)_nr2r3, -N(R2)c(o)R3, _n( R2) C(0)NR2R3 or NR2R3' or X represents a monocyclic, bicyclic or tricyclic moiety having 4-16 ring atoms, one of the ring atoms being nitrogen, and one, two or three additional The ring atom may be a hetero atom selected from N, 0 and s, and wherein the monocyclic, bicyclic or tricyclic moiety may be optionally substituted with one or more substituents w ( ν ' , wherein W is selected from hydrogen, hydroxy, Halogen, cyano, (=〇), hepta(CH2)c-〇-, wherein e is 2 or 3 (spiro), (CH2)d, where d is 5 or 6 (spiro), cv6 alkyl, Cl_6 alkane Oxy, _c(0)_Ci 6 alkyl, _c(〇)_〇_Cm alkyl, -〇-c(o)-Cl 6 alkyl, ^(1) cation, c〇〇H; or wherein w a formula -(CH2)a-Y_(CH2)b_z moiety; wherein a and b independently represent an integer selected from the group consisting of 〇, ι, 2, and 3; and let Y denote a bond, c(〇), 〇, S, - Ο-e(9), _c(0)_0... -NR2_, _NR2-C(0)-, -C(0)-NH· or s(0)2; wherein Z represents hydrogen, c"alkyl, nrZr3, cyano Or a monocyclic or fused bicyclic moiety containing 4 to a ring atom, wherein 1, 2 or 3 of the ring atoms are heteroatoms selected from N, fluorene and s, and wherein the monocyclic fused bicyclic moiety Optionally substituted with one or more substituents selected from the group consisting of: cyclin, cyano, c "6-formyl, thiol, and c-oxy, phenyl, pyridine. .6 alketidine, and a phenyl substituted by dentate; wherein one of R4-r8 is deuterium + occupies the main 13 7 and the rest represents hydrogen; wherein - represents spectrin and the rest represents hydrogen Wherein R2 and R3 independently represent hydrogen, LI丨.6 alkyl, hydroxy c丨.6 alkane 295 200906801-yl, halo<^6 alkyl or phenyl; and pharmaceutically acceptable salts thereof. 65 _If the compound of claim 64, A represents C H; R1 represents an ethyl group or a cyclopropyl group; Ri4 represents a halogen: and a halogen is represented by an or a trans group. 66. A compound according to claim 65, wherein X represents or is substituted by two substituents W. Morphic or ΐ-α base. a base, wherein w is a moiety of the formula -(CH2)a-Y_(CH2)b_z, wherein a and b independently represent 〇, -1, 2 or 3; Y represents a bond, Ο, _NR2-C(0)- And wherein Z represents a rolling, a Cw alkyl group, a piperidinyl group, a moffolin group, a pyridyl group, a 1-6 alkoxy substituted phenyl group or a D-pyridyl group. 67. If the compound of claim 1 of the patent scope has the formula

5 6 R R R7 R1[lk] 其中R1表示氩、Cw烷基、Cw烯基或c2 6炔基； /、中X表示氫、CK6烷基、c2-6烯基、c2_6炔基或NR2R3，或X表示具有5_9個環原子之單環或雙環部分，環原子中之-者為II ’且其中i個、2個或3個額外環原子可為選 296 200906801 .自N、〇及s之雜原子，且其中該單環或雙環部分可視情況經一或多個取代基w取代，其中w係選自氫、_素、声工基（-〇)、cK6燒基、c2.6細基、c2_6块基、cN6炫氧基，或其中W表示式__(CH2)a_Y_(CH2)b-Z部分；其中a及b獨立地表示選自〇、〗、2及3之整數. 其中Y表示—鍵，且其辛Z表示包含5至6個環原子之單環部分’環原子中視情況1個、2個或3個為選自N、 Ο及S之雜原子，且其中該單環部分視情況經一或多個選自由以下基團組成之群的取代基取代：齒素、。丨6烷基、羥基、及Cy烷氧基；其中R4-R8中之每-者獨立地表示氣或齒素；其中R9-R12中之每-者獨立地表示氫或齒素，其限制條件為R9-RU中之至少—者表示鹵素；其中R13-R17中之每-者獨立地表示氫或鹵素； /.、中R及R獨立地表示氫、Cl 6燒基、c2 6稀基、6 炔基；及其醫藥學上可接受之鹽。 68·如申请專利範圍第67項之化合物，其具有式v 297 2009068015 6 RR R7 R1[lk] wherein R1 represents argon, Cw alkyl, Cwalkenyl or c2 6 alkynyl; /, wherein X represents hydrogen, CK6 alkyl, c2-6 alkenyl, c2-6 alkynyl or NR2R3, or X represents a monocyclic or bicyclic moiety having 5-9 ring atoms, and the one in the ring atom is II ' and wherein i, 2 or 3 additional ring atoms may be selected as 296 200906801. From N, 〇 and s An atom, and wherein the monocyclic or bicyclic moiety is optionally substituted with one or more substituents w, wherein w is selected from the group consisting of hydrogen, _ 素, acene (-〇), cK6 alkyl, c2.6, a c2_6 block group, a cN6 methoxy group, or wherein W represents a moiety of the formula __(CH2)a_Y_(CH2)bZ; wherein a and b independently represent an integer selected from the group consisting of 〇, 〖, 2, and 3. wherein Y represents a — bond And its xin Z represents a monocyclic moiety containing 5 to 6 ring atoms. One, two or three of the ring atoms are optionally heteroatoms selected from N, oxime and S, and wherein the single ring moiety is optionally Substituted by one or more substituents selected from the group consisting of dentate.丨6 alkyl, hydroxy, and Cy alkoxy; wherein each of R4-R8 independently represents a gas or a dentate; wherein each of R9-R12 independently represents hydrogen or dentate, the limiting conditions thereof A halogen is represented by at least one of R9-RU; wherein each of R13-R17 independently represents hydrogen or halogen; wherein R and R independently represent hydrogen, Cl 6 alkyl, c 2 6 diluted, 6 alkynyl; and pharmaceutically acceptable salts thereof. 68. A compound of claim 67, having the formula v 297 200906801

其中R1係選自CV6烷基；其中X係選自氫、CV6烷基或NR2R3，或X表示具有 5-9個環原子之單環或雙環部分，環原子中之一者為氮，且其中1個額外環原子可為選自N之雜原子，且其中該單環或雙環部分可視情況經一或多個取代基W取代，其中W 係選自氫、羥基、（=0)、Cu烷基或其中 W表示式-(CH2)a-Y-(CH2)b-Z 部分；其中a及b獨立地表示選自0、1、2及3之整數；其中Y表示一鍵，且其中Z表示包含5至6個環原子之單環部分，環原子中視情況1個為選自N、0及S之雜原子，且其中該單環部分視情況經一或多個選自由以下基團組成之群的取代基取代：鹵素、Cw烷基、羥基、及Cr 6烷氧基；其中R12表示鹵素； R13-R15各自獨立地表示氫或鹵素；及其醫藥學上可接受之鹽。 200906801 69. 如申請專利範圍第67-68項中任一項之化合物，其中R1表示曱基、乙基、環丙基、環丁基、環戊基或環己基。 70. 如申請專利範圍第69項之化合物，其中X表示Wherein R 1 is selected from C C 6 alkyl; wherein X is selected from hydrogen, C 6 alkyl or NR 2 R 3 , or X represents a monocyclic or bicyclic moiety having 5 to 9 ring atoms, one of which is nitrogen, and wherein 1 additional ring atom may be a hetero atom selected from N, and wherein the monocyclic or bicyclic moiety may be optionally substituted with one or more substituents W, wherein W is selected from the group consisting of hydrogen, hydroxy, (=0), cumane Or wherein W represents a moiety of the formula -(CH2)aY-(CH2)bZ; wherein a and b independently represent an integer selected from 0, 1, 2 and 3; wherein Y represents a bond, and wherein Z represents 5 to a single ring moiety of 6 ring atoms, wherein one ring atom is optionally a hetero atom selected from N, 0 and S, and wherein the monocyclic moiety is optionally substituted by one or more groups selected from the group consisting of: Base substitution: halogen, Cw alkyl, hydroxy, and Cr 6 alkoxy; wherein R12 represents halogen; R13-R15 each independently represent hydrogen or halogen; and a pharmaceutically acceptable salt thereof. The compound of any one of claims 67-68, wherein R1 represents a decyl group, an ethyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group. 70. A compound as claimed in claim 69, wherein X represents

-NR2R3，或氫。 71.如申請專利範圍第70項之化合物，其中X表示-NR2R3, or hydrogen. 71. A compound as claimed in claim 70, wherein X represents

，且其中W表示氫、（=0)、Cw烷基或-(CH2)a- Y-(CH2)b-Z。 72. 如申請專利範圍第71項之化合物，其中W表示氫、甲基、環丙基甲基、異丙基、異丁基、第三丁基、（=0)或-(CH2)a-Y-(CH2)a-Z，其中a+b為2且Z係選自4-嗎福林基、苯基、1 -略咬或1 -。比略咬基。 73. 如申請專利範圍第70項之化合物，其中X表示And wherein W represents hydrogen, (=0), Cw alkyl or -(CH2)a-Y-(CH2)b-Z. 72. A compound according to claim 71, wherein W represents hydrogen, methyl, cyclopropylmethyl, isopropyl, isobutyl, tert-butyl, (=0) or -(CH2)aY- (CH2)aZ, wherein a+b is 2 and the Z system is selected from 4-norlinyl, phenyl, 1-slightly bite or 1-. Than slightly bite. 73. For the compound of claim 70, where X is

W表示氫、羥基、CV6-烷基或-(CH2)a-Y-(CH2)a-Z。 74.如申請專利範圍第73項之化合物，其中W表示氫、 299 200906801 羥基、第三丁基，或a+b為0或2且Z表示4-嗎福林基視情況經（^_6烷氧基取代之苯基或4-哌啶基。 1STW represents hydrogen, hydroxy, CV6-alkyl or -(CH2)a-Y-(CH2)a-Z. 74. The compound of claim 73, wherein W represents hydrogen, 299 200906801 hydroxy, tert-butyl, or a+b is 0 or 2 and Z represents 4-folin base as the case (^_6 alkane) Oxy-substituted phenyl or 4-piperidinyl. 1ST

1或2 75.如申請專利範圍第70項之化合物，其中X表示 (W). 且W表示（=0) 76. 如申請專利範圍第70項之化合物，其中X表示-NR2R3。 f 77. 如申請專利範圍第76項之化合物，其中R2及R3 獨立地表示氫或Ci_6烷基。 7 8.如申請專利範圍第77項之化合物，其中R2表示氫，且R3表示環丙基、異丁基或第三丁基。 79. 如申請專利範圍第70項之化合物，其中X為氫。 80. 如申請專利範圍第1項之化合物，其具有式Ik’’1 or 2 75. The compound of claim 70, wherein X represents (W). and W represents (=0) 76. The compound of claim 70, wherein X represents -NR2R3. f 77. The compound of claim 76, wherein R2 and R3 independently represent hydrogen or Ci-6 alkyl. 7. A compound according to claim 77, wherein R2 represents hydrogen and R3 represents cyclopropyl, isobutyl or tert-butyl. 79. The compound of claim 70, wherein X is hydrogen. 80. The compound of claim 1 having the formula Ik’’

300 200906801 :R14及R15中之兩者表示氫。 8 L如申請專利範圍第80項之化合物，其中該化合物基本上為如式Ik’ ’ ’所述之S對映異構體 R1300 200906801 : Both of R14 and R15 represent hydrogen. 8 L is a compound of claim 80, wherein the compound is substantially the S enantiomer R1 as described in formula Ik''

R 2 Η CR 2 Η C

R12 Ο [Ik"，] 其中R1表示乙基或環丙基；其中R12表示氟或氯；且 R13、R14及R15各自獨立地表示氳、氟或氯，其中R13 R14及R15中之兩者表示氳。 82.如申請專利範圍第1項之化合物，其具有式Id’ 301 2 80 06 9 R1R12 Ο [Ik", wherein R1 represents ethyl or cyclopropyl; wherein R12 represents fluorine or chlorine; and R13, R14 and R15 each independently represent hydrazine, fluorine or chlorine, wherein two of R13 R14 and R15 represent heavy atmosphere. 82. The compound of claim 1, wherein the compound has the formula Id' 301 2 80 06 9 R1

3 ^— R3 ^— R

其中R1表示乙基或環丙基； R12表示鹵素； R13、R14及R15各自獨立地表示氫或鹵素；及其醫藥學上可接受之鹽。 83.如申請專利範圍第1項之化合物，其具有式Id’’Wherein R1 represents an ethyl group or a cyclopropyl group; R12 represents a halogen; and R13, R14 and R15 each independently represent hydrogen or a halogen; and a pharmaceutically acceptable salt thereof. 83. The compound of claim 1, wherein the compound has the formula Id'

[Id"] 其中R1表示乙基或環丙基； R12表示氯或氟； 302 200906801 • R12、R14及R15各自獨立地表示氫、氯或氟，其中R12、 R14及R15中之兩者表示氫；及其醫藥學上可接受之鹽。 84.如申請專利範圍第83項之化合物，其中該化合物基本上為如式Id’ ’ ’所述之S對映異構體[Id"] wherein R1 represents ethyl or cyclopropyl; R12 represents chlorine or fluorine; 302 200906801 • R12, R14 and R15 each independently represent hydrogen, chlorine or fluorine, wherein two of R12, R14 and R15 represent hydrogen And its pharmaceutically acceptable salts. 84. The compound of claim 83, wherein the compound is substantially the S enantiomer of formula Id''

R12 Ο [Id1，，] 其中R1表示乙基或環丙基； R12表示氯或氟； I R12、R14及R15各自獨立地表示氳、氯或氟，其中R12、 R14及R15中之兩者表示氫；及其醫藥學上可接受之鹽。 85. 如申請專利範圍第1項之化合物，其係選自 1 a 3 -曱基-1-側氧基-2 -苯基-1,2 -二氮-異啥琳-4 -竣酸 ((S)-l-苯基-丙基）-醯胺 lb 3,6-二甲基-1-側氧基-2-苯基-1,2-二鼠-異0奎嚇^-4 -叛 303 200906801 . 酸（（s)-i-苯基-丙基）_醯胺 lc 7-氯-3-甲基-1-側氧基-2-苯基-1,2-二氳-異啥琳-4-竣酸（（S)-l-苯基-丙基）-酸胺 Id 7-溴-3 -甲基-1-側氧基-2-苯基-1，2-二氳-異啥琳_4_ 羧酸（（S)-l-苯基-丙基）-醯胺 le 6-氟-3 -甲基-1-側氧基-2-苯基- i，2-二氫-異喹琳_4_羧酸（（S)-l-苯基-丙基）-醯胺 If 3,5-二甲基-卜側氧基-2-苯基_1，2-二氫-異喹啉羧酸（（S)-l-苯基-丙基）-酿胺 lg 7-氟-3 -曱基-1-側氧基-2-苯基-1,2-二氫-異喹啉_4_ 歎酸（（S)-l-苯基-丙基）-酿胺 lh 3,7-二曱基-1-側氧基-2-苯基_1，2-二氫-異喹琳缓酸（（S)-l -苯基-丙基）-酿胺 li 8-氯-3-甲基-1-側氧基-2-苯基_l，2-二氫-異喹啉_4_羧酸（（S)-l-苯基-丙基）-醯胺 lr 3-甲基-1-侧氧基-2-苯基_l52_二氫-異喹啉_4_羧酸 I ((S)-環丙基-苯基-甲基）-醯胺 Is 3-甲基-1-側氧基-2-苯基_1，2-二氫·異喹啉_4_羧酸 [(S)-環丙基-(3-氟-苯基）-甲基]-醯胺 lj 3,8-二甲基-1-側氧基-2-苯基_1，2_二氫-異喹琳_4_羧酸（（S)-l-苯基-丙基）·酸胺 lk 2-(2-氟-苯基）-3-甲基-1-側氧基二氳·異喹啉_4_ 羧酸（（S)-l-苯基-丙基）-醯胺 11 3-甲基-1-側氧基-2-鄰曱苯基-；!，^二氫_異喹啉_4_羧 304 200906801 . 酸（（s)-i-苯基-丙基）_酿胺 lm 2-(2-氣-苯基）_3·曱基-1-側氧基-1,2-二氫-異喹啉_4-叛酸（（S)-l-苯基-丙基）_酿胺 In 2-(2,6-一氟-苯基）-3 -甲基-1-側氧基-1，2-二氫-異唾啉-4-羧酸（（S)-l-苯基-丙基）_醢胺 lo 2-(3 -氟-本基）_3 -甲基-1-側氧基— 1,2-二氯-異喧琳叛酸（（S)-1 -苯基-丙基）_酿胺 lp 3-甲基-1-側氧基_2_間甲苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l -苯基-丙基）-酿胺 lq 2-(3-氯-苯基）-3-甲基-1-側氧基-i，2-二氫-異喹啉_4- 羧·酸（（S)-l -苯基-丙基）-酿胺 It 8-氯-3-曱基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺 2a 3-二甲基胺基曱基-1-侧氧基_2-苯基-丨，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2b 3 -甲基胺基甲基-1 -側氧基-2-苯基-1,2-二氫-異π奎琳_ ί: 4-羧酸（（S)-l-苯基-丙基）-醯胺 2c 3-乙基胺基曱基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2d 3-環丙基胺基甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2e 3-[(環丙基甲基-胺基）-甲基]-1-側氧基-2-苯基-1，2-二氳-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2f 3-(3,6-二氫-2H-吡啶-1·基甲基）-1-側氧基-2-苯基- 305 200906801 .1，2_ —風-異唾嚇·_4 -叛酸（（S)-l -苯基-丙基）-酿胺 2g 3-[4-(2-甲氧基-苯基）-n底啡-1-基甲基]_丨_側氧基_2_ 苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2h 3-[4_(4_氟-苯基）-略啡-1-基甲基]_ι_側氧基_2_苯基_ 1，2-二氫-異喹啉-4-羧酸（（3)-1-笨基-丙基）_醯胺 2i 3-(4-曱醯基-〇底啡-1-基曱基）_1-側氧基_2_苯基_ι,2_ 二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2j 4-[1-側氧基-2-苯基-4-(1-苯基-丙基胺甲醯基）_ι，2_ ' 二氫-異喹啉-3-基曱基]-哌啡-1-羧酸乙酯 2k 3-(4-甲基-哌畊-1-基甲基）-1-側氧基_2_苯基_1>2_二鼠-異喧淋-4-竣酸（（S)-l-苯基-丙基）-酿胺 21 I-側氧基-2-苯基- 3-(l，3,4,9-四氫-β-味琳_2-基甲基）_ l，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2m 1-側氧基_2_苯基_3_哌啡-1_基甲基―；!，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2n 3-(3-甲基-哌畊-1-基曱基）-1-側氧基_2_苯基-^:二 '* 虱-異σ奎琳-4-叛酸（（S)-l-苯基-丙基）-酿胺 2〇 3-(3,5-二甲基-哌啡-1-基甲基）-1-側氧基_2_苯基_ 1,2-二氫-異唾琳-4-缓酸（（S)-l-苯基-丙基）-醯胺 2p 3-(4_苯甲基-哌明^1-基曱基）-1-侧氧基_2-苯基_1，2_ 二氫•異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2q 1-側氧基-3-[4-(2-側氧基-2-吡咯啶-1-基-乙基）_哌畊-1-基甲基]-2-苯基-1,2-二氫-異喹啉-4_羧酸（（8)-1-苯基-丙基）-酿胺 306 200906801 2r 3-嗎福林_4_基曱基_1_側氧基_2 -苯基- i，2-二氫_異嗜啉-4-羧酸（（S)-i_苯基-丙基）_醯胺 2s 3-(2,6-二曱基—嗎福林_4_基曱基）_；!_側氧基苯基_ U2_二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2t 1-側氧基-2-苯基-3-硫代嗎福林-4-基曱基-丨’:^二氣_ 異喧琳-4-羧酸（〇1_苯基-丙基）_醯胺 3-(1，4-二氧雜_8_氮雜-螺[4·5]癸_8_基曱基側氧基-2-苯基_1，2-二氫-異喹啉_4_羧酸（（”_!_苯基_丙基）_醯胺 2v 1-側氧基_2_苯基_3_哌啶基曱基_丨，2_二氫-異喹啉 -4-羧酸（（S)-l-苯基-丙基）_醯胺 2w 3-(2-甲基·哌啶_ι_基甲基）]_側氧基_2_苯基_i，2_二氫-異喹啉-4-羧酸笨基-丙基）_醯胺 2x 3-(2,6-二甲基-哌啶_1_基甲基）_卜側氧基_2_苯基· 1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基·•丙基）_醯胺 2y 3-(2-羥基甲基-哌啶-基甲基）_!_側氧基_2_苯基_ 1，2-二氳-異喹啉_4-羧酸（（S)-l-苯基-丙基醯胺 2z 1-[1-側氧基_2_苯基-4-(1-苯基-丙基胺曱醯基）_丨，2_ 二氫-異喹啉-3-基甲基]-哌啶-3-羧酸乙g旨 2aa 3-(3-甲基-哌啶-1-基甲基側氧基_2•苯基-it: 氫-異喧琳-4-叛酸（（S)-l-苯基-丙基）_醯胺 23匕3-(4-羥基-哌啶-1-基甲基）_1_側氧基_2_苯基_1，2_二氫-異啥琳-4-叛酸（（S)-l -苯基-丙基）_醯胺 2ac 1-側氧基-2-苯基- 3-(4 -苯基-派咬_ι_基甲基）_1，2_二氫-異啥琳-4-叛酸（（S)-l -苯基-丙基）_醯胺 307 200906801 2ad 1-U-側氡基-2-苯基-4-(1-苯基·丙基胺曱醯基）_1，2-一氫-異嗜琳-3-基甲基]底。定_4_羧酸乙酯 2ae 3-(4-甲基-哌啶基甲基卜丨-側氧基_2_苯基-^―二氫-異喹啉-4-羧酸苯基-丙基）_醯胺 2af 1-側氧基_2_苯基_3_(4_吡啶_2_基_哌啡_丨_基甲基 L2-二氫·異喹啉_4-羧酸（（S)-l-苯基-丙基）-醯胺 2ag 3-(八氫-喹啉-丨·基曱基）側氧基_2_苯基-^2-二氫-異喹啉-4-羧酸（（s)-i_苯基-丙基醯胺 n 2ah 3_氮雑環庚烷-1-基甲基-1-側氧基-2-苯基-1，2-二氫 _異喹啉-4-羧酸（(s)-〗·苯基_丙基）·醯胺 2ai 3-(3-羥基-哌啶基曱基側氧基_2_苯基_152_二氫-異喹啉_4_羧酸苯基-丙基）-醯胺 2aj 3-[4-(2,4-二甲基-苯基）_哌啡基甲基]側氧基_ 2-苯基-I，2-二氫-異喹啉_4_羧酸（（yd —苯基-丙基）_醯胺 2ak 3_[4-(3,4_二甲基-苯基）_哌啡-1-基甲基]-1-側氧基-2-苯基-I，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 L 2al 3-(4-二甲基胺基-哌啶-1-基曱基）-1-側氧基_2_苯基 -1,2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）_醯胺 2請3-[4-(2,5·二甲基-苯基）哌啡小基甲基]」_側氧基 -2-苯基-I，2-二氬異喹啉-4-羧酸（(S)-l-苯基-丙基）_醯胺 2an 3·[4_(2·氟-苯基）-〇底啡-1-基甲基]_ι_側氧基_2_苯基 -1，2-二氫-異啥琳_4_叛酸（（S)-l -苯基-丙基）_醯胺 2ao 3-[4-(3_甲氧基-苯基）-哌明：-1_基甲基卜卜側氧基_2_ 苯基-1，2-二氫-異喧琳-4-缓酸（（S)-l-苯基-丙基）_酿胺 308 200906801 2aP 侧氧基-2-苯基- 3-(4 -間甲苯基辰啡_ι_基甲基）_ 1，2-二氫-異嗜琳-4-缓酸（（S )-1-苯基-丙基）-醯胺 2aq 3-[4-(4-甲氧基-苯基）-派啡-1-基甲基]_丨_側氧基_2_ 本基-1，2 - 一風_異啥琳-4 -叛酸（（S)-l -苯基-丙基）_酿胺 2ar 1-側氧基-3-(4-苯乙基-哌畊-1-基甲基）·2_苯基-n 二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2as 1-侧氧基-2·苯基-3-(4_〇密咬_2_基- η底啡基曱基）_ 1，2-二氫-異哇嚇_-4-叛酸（（S)-l-苯基-丙基）-醯胺 Γ 3-[4-(2-氰基-苯基）-哌畊-1-基曱基]_；!_側氧基_2_苯基-1,2-二虱-異啥琳-4-叛酸（（S)-l-苯基-丙基）_酿胺 2au 3-[4_(4_氯-苯基）-0辰啡-1-基甲基]-1-侧氧基_2_苯基 -1，2-二氢-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2av 3-((lS，3R，5R)-3-羥基-8-氮雜-雙環[3.21]辛 _8_ 基甲基）-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（s)-l-苯基 -丙基）-醯胺 2aw 3-(4-乙醯基底明基甲基）-1-側氧基-2-苯基-I 1,2-二氫-異啥琳-4-羧酸苯基-丙基）-醯胺 2ax 3-(4 -甲基-[1，4] 一氮雜環庚烧-1-基甲基）-1-側氧基 -2-苯基-1，2-二氫-異喹啉-4-羧酸（（s)-l_苯基-丙基）-醯胺 2ay 3-(4-乙基-0底啡基曱基）小侧氧基-2-苯基-1，2-二氫-異喹琳-4-缓酸（（s)_1_苯基-丙基）_醯胺 2az 3-((2S,6R)-2,6-一曱基-嗎福林-4-基甲基）-1-側氧基 -2-苯基-1，2-二氫-異喹啉-4-緩酸（(S)-i_苯基-丙基）-醯胺 2ba 3-[4-(2,4-二氟-苯基）_0底畊-1-基甲基]-1-側氧基-2- 309 200906801 -苯基-1，2·二氫-異喹啉_4·羧酸（（s)-i-苯基-丙基）-醯胺 2bb 3-[4-(3-二甲基胺基-丙基）_哌啡_丨_基甲基]側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（s)-l-苯基-丙基醯胺 2bc 3-(4-異丙基-哌畊基甲基）_K側氧基苯基二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）_醯胺 2bd 3-(3-氮雜-雙環[3_2_2]壬-3-基甲基）_ι_側氧基_2_苯基-1，2-二氫·異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2be 3-(4_環戊基-派啡-1-基曱基）_ι_側氧基_2_苯基二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2bf 3-Π〆1]聯哌啶-1·-基甲基側氧基_2_苯基」，2_二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2bg 3-(3,4-二氫-1H-異喹啉-2-基甲基）_ι_側氧基_2_苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）·醯胺 2bh 3-[4_(2·二甲基胺基-乙基）_〇底啡_1_基甲基]側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸苯基-丙基醯胺 2bi 3-(4-羥基甲基-哌啶-1-基曱基）_；!-側氧基_2_苯基_ I，2-二氫-異喹啉_4·羧酸苯基-丙基）_醯胺 2bj 1-側氧基-2-苯基·3-[4-(四氫-π夫喃_2 -幾基）·π底啡_ι_ 基甲基]-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基·丙基）_醯胺 2bk 3-(4-異丁基-哌啡-1-基甲基）-1-側氧基-2_苯基山：二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2bl 3-[4-(2-甲氧基-乙基）-哌畊-1-基甲基]_!_側氧基_2_ 苯基-1，2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）_醯胺 2bm 3-[4-(2-嗎福林-4-基-乙基）-哌畊-1-基甲基]侧 310 200906801 .氧基_2_苯基-1，2·二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）_醯胺 2bn 3-(1，3-二氫-異吲哚_2_基甲基）_丨_側氧基_2•苯基_ 1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基醯胺 2bo 3-[4-(1-曱基-哌啶—‘基卜哌畊-卜基曱基]側氧基 -2-苯基-1，2-二氫-異喹啉_4_羧酸苯基-丙基）_醯胺 2bp 1-侧氧基-2-苯基-3-[4-(2-旅咬_1 -基-乙基）_α底啡基甲基]-1，2-二氫-異喹啉_4-羧酸（（S)-l-苯基-丙基）_醯胺 2bq 1-侧氧基_2_苯基_3_[4_(2_吡咯啶_丨基_乙基）_哌哄_ 1-基甲基]-1，2-二氫-異喹啉_4-羧酸（（S)-l-苯基-丙基）_醯胺 2br 3-(4-二曱基胺甲醯基甲基-哌啡基甲基侧氧基-2-本基-1,2 - 一鼠_異°奎琳-4 -竣酸（（S)-l -苯基-丙基）_酿胺 2bs 3-(八氫-吡啶并[i，2_a]吡啡_2_基曱基側氧基_2_ 苯基-I，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2bt 3-(4-甲醯基-[1，4]二氮雑環庚烷-1-基甲基）_〗_側氧基-2-本基-1，2 - 一氮-異喧琳-4-叛酸（（S)-l -苯基-丙基）_酿胺 2bu 3-[4-(4 -氰基-苯基）-旅明^1-基甲基]-1-側氧基_2_苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2bv 1-側氧基-2-苯基…-(各吡啶-扣基甲基-哌畊-^基甲基）-1，2-二氫-異啥琳-4-叛酸（（S)-l-苯基-丙基）-g盘胺 2bw 1-側氧基-2-苯基-3-[4-(3-吡咯啶-1-基-丙基）_娘啡 -1-基甲基]-1,2-二氫-異啥郝-4-缓酸（（S)-l -苯基-丙基）_酿胺 2 5\1-侧氧基-2-苯基-3-(4-吡啶-2-基甲基-哌啡-1_基甲基）-1，2-二氫-異噎琳-4-叛酸苯基-丙基）-醒胺 311 200906801 _ 2by 3-(4-乙績酿基-旅啡-1-基曱基）-1 -側氧基-2-苯基_ 1.2- 二氫-異啥琳-4-羧酸（（S)-l -苯基-丙基）-醯胺 2bz 3-(4_第二丁基-哌畊-1-基甲基）-1-側氧基-2-苯基_ 1，2-二氫-異啥琳-4-幾酸（（S)-l -苯基-丙基）-醯胺 2ca 3-[4-(1-乙基-丙基辰啡-1-基曱基]-1-側氧基_2_苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）·醯胺 2cb 3-[4-(2-氰基-乙基）-哌啡-1-基曱基]-1-側氧基_2_苯基-1，2-二鼠-異啥淋-4-叛酸（（S)-l -苯基-丙基）_酿胺 2cc 3-(4-曱績醯基-哌啡-1-基甲基）-1-側氧基_2_苯基_ 1.2- 二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2cd 側氧基-2 -苯基- 4-(1-苯基-丙基胺甲醯基）_ 1，2-二風-異哇琳-3-基甲基]-派咬-4-基}-乙酸乙酉旨 2ce 3-[4-(3-氟-苯基）-哌啡-1-基甲基]-i_側氧基_2_苯基 -1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2cf 1-側氧基-2 -苯基- 3- ((S)-3 -苯基-〇底〇定_1_基甲基）_ 1，2-二氫-異喹啉-4-羧酸（（8)-1-苯基-丙基）-醯胺 I 2cg 1-側氧基-2-苯基-3-[4-(吡咯啶-1·羰基）-哌啡-^基曱基]-I，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2ch 3_[4_(嗎福林- 4_|l厌基）-α底啡基甲基]側氧基_2_ 苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2ci 3-(4-甲氧基-哌啶-1-基甲基）·ι·側氧基_2_苯基-丨，）· 二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2cj 3-(4’-羥基 _3’，4'，5’，6’-四氫-2Ή-[3,4，]聯吡啶 4，-基甲基）-1-側氧基-2-苯基-1，2-二氫-異喹琳-4-缓酸（(;§)_1_苯基 312 200906801 .-丙基）-醯胺 2ck 3-(4-羥基 _3,4,5,6-四氫 _2H-[4,4，]聯吡啶基甲基）-1-侧氧基-2-苯基-1，2-二氫-異喹啉_4-羧酸（^丨-苯基_ 丙基）-醯胺 2cl 3-(3H-螺[異苯并呋喃_丨，4，_哌啶卜Γ_基甲基）_卜側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基·丙基）_醯胺 2(：1113-(4-羥基-4-甲基_哌啶_1_基曱基）_1_側氧基_2_苯基-1，2-二氫-異喹啉-4-羧酸（（s)-l-苯基-丙基；)_醯胺 ,’ 2en 3-(六風-螺[苯并[I，3]二聘峻_2,4,_0底〇定]_1,_基曱基）-1-侧氧基-2 -苯基-1，2-二氫-異啥琳-4 -幾酸（（s)-i_苯基_ 丙基）-醯胺 2co 1-側氧基-2-苯基-3-(3,4,5,6-四氫-2H-[4,4，]聯吡啶- 1- 基甲基）-1，2-二氫-異喹啉-4-羧酸（（S)-l_苯基-丙基）_醯胺 2cp 3-[4-(2-二甲基胺基-乙基）_〇底咬·ι_基甲基]側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2cq 3-(4-二曱基胺磺醯基-哌明：_1_基甲基）_；!_側氧基_2_ I，苯基-i，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2cr 3-(1，1-二側氧基-硫代嗎福林-4-基甲基）_1_側氧基· 2- 苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）·醯胺 2cs 1-側氧基-2-苯基- 3- (2-°比0定-2-基甲基-旅唆-丨_基曱基- —氮_異啥淋-4-叛酸（（S)-l-苯基-丙基）-酿胺 2ct 3-(2-嗎福林-4-基甲基-哌啶-1-基曱基）-1_側氧基_2_ 本基- —乳_異啥琳-4-叛酸本基-丙基）_酿胺 2cu 3-(4-呋喃并[3,2-c]吡啶-4-基-哌啡-1-基曱基）_丨_側 313 200906801 -氧基_2_苯基―1，2-二氫_異喹琳-4-缓酸（（S)-l -苯基-丙基）_酿胺 2cv 3-(4-環丙基曱基-哌啡_ι·基曱基）_丨_側氧基_2_苯基 -1，2_ —風-異啥琳-4·叛酸（（S)-l -苯基-丙基）-醯胺 2 c w 3-[4-(2-嗎福林-4-基-乙基）-〇展〇定-1-基甲基]_ι_側氧基-2-苯基-1，2-二氫-異喹啉_4_羧酸（（S)-l-苯基-丙基）_醯胺 2cx 1-側氧基-2-苯基-3-(4-嘧啶-2-基-[1，4]二氮雑環庚火元-1-基甲基）-1，2-二氫-異啥琳-4-叛酸（（S)-l-苯基-丙基）_醯 r... ‘胺 2cy 3-(4 -甲基-6,7-二氫-41^-°塞吩并[3,2-(：]〇比〇定_5-基甲基）-1-侧氧基-2-苯基-1,2-二氫-異啥琳-4-竣酸（（S)-l_苯基_ 丙基）-醯胺 2cz 3-[1，4]二氮雑環庚炫-1-基甲基-1_側氧基_2_苯基_ 1，2-二氫-異喹啉_4_羧酸（（S)-l-苯基-丙基）-醯胺 2da 3-((2S，5R)-2,5-二甲基-〇底啡-1-基甲基）_ι_側氧基· 2 -本基-1，2-二氫-異啥淋-4-缓酸（（S)-l -苯基-丙基）_酿胺 I 2db 3-((S)-3-曱基-哌畊-1-基甲基）-1-側氧基·2_苯基_ 1，2-二氫-異喧淋-4-缓酸（(S)-l-苯基-丙基）-酿胺 2dc 3-((R)-3 -曱基底哄-1-基甲基）-1-侧氧基-2-笨基_ 1,2-二氫-異啥淋-4-羧酸（（S)-l-苯基-丙基）-醯胺 2dd 3-[3-(3-氯-苯基）-哌畊-1-基甲基]-1-侧氧基-2-苯基 -1，2-二氫-異嗤琳-4-叛酸（（S)-l -苯基-丙基）-酿胺 2de 3-[4-(1Η-吲哚-4-基）-哌畊-1-基甲基]-1-側氧基-2-苯基-1，2-二氮-異哇嚇·-4-緩酸（（S)-l-苯基-丙基）_酿胺 314 200906801 2df 1-側氧基_3-(3-側氧基-旅畊-1·基甲基）-2-苯基-l，2-二氫-異喹琳-4-缓酸（（S)-l -苯基-丙基）_醯胺 2dg 3-[4-(1Η-吲哚-5-基）-哌畊-1-基曱基]-1-側氧基_2-苯基-1，2-二氫-異喹淋-4-叛酸（（S)-l-苯基-丙基）_酸胺 2dh 3-(6,9-二氮雜-螺[4·5]癸_9_基甲基）-1_側氧基-2-苯基-I,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2di 3-(1,4-二氮雜-螺[5.5]十一-4-基甲基）-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2dj 3-(3-異丙基-哌明^1-基甲基）-1-侧氧基-2-苯基-1，2-二氫-異°奎琳-4 -叛酸（（S)-l-苯基-丙基）-酿胺 2dk 3-(3,3-二甲基-哌啡-1-基甲基）-1-側氧基-2-苯基- 1.2- 二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2dl 3-[3-(4-氟-苯基）-哌畊-1-基甲基]-1-侧氧基-2-笨基 _1，2-二風-異啥淋-4-缓酸（（S)-l -苯基-丙基）-酿胺 2dm 1-側氧基-2-苯基- 3- (3 -對曱苯基-旅啡-1-基曱基）_ 1.2- 二氮··異p奎嚇>-4 -叛酸（（S)-l-苯基-丙基）-酿胺 I 2dn 4-Π-侧氧基-2-苯基-4-(1-苯基-丙基胺曱醯基）-1，2· 二氫-異喹啉-3-基曱基]-哌畊-1-羧酸第三丁酯 2do 3-(4-曱基胺曱醢基曱基-哌畊-1-基曱基）_1_側氧基 -2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2dp 8-氣-3-二甲基胺基甲基-M則氧基-2-苯基·1，2-二氫 -異啥琳-4 -羧酸（（S)-l -苯基-丙基）_醢胺 2dr 3-環戊基胺基甲基-1-側氧基-2-苯基-1,2-二氫-異啥琳-4-羧酸（（S)-l -苯基-丙基）-酿胺 315 200906801 2ds 3-環己基胺基甲基-側氧基_2_苯基_丨，2_二氫_異喹啉-4-羧酸（（S)-1-苯基-丙基）_醯胺 2dt 3-{[(2-羥基-乙基）_甲基-胺基]_甲基卜卜側氧基_2_ 苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2du 3-咪唑-1-基曱基_；!_側氧基·2_笨基]，2_二氫異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2dv 3-(2-曱基-咪唑-1-基曱基）_；!_侧氧基_2_苯基_丨，2_二氫-異喹啉-4-羧酸（（S)-l·苯基-丙基）_醯胺、 2dw 3·(4_甲基-咪唑―1-基甲基）-1-側氧基-2-苯基-1,2- 二氫-異喹啉-4-羧酸（（S)-l-苯基·丙基）_醯胺 2dx 3-(2,5-二氫-吡咯-1-基甲基）_；[_側氧基_2_苯基— I〗· 二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2dy 3-(2,5-二甲基-2,5-二氫-。比洛_l-基甲基）_1_側氧基_ 2-苯基-l，2-二氫-異喹啉-4-羧酸（（S)-l-苯基·丙基）_醯胺 2dz 1-側氧基-2-苯基-3-°比略〇定-i_基甲基_ι，2_二氫_異喹啉-4-羧酸（（S )-1-苯基-丙基）-醯胺 i 2ea 1-側氧基-2-苯基-3-(噻唑-2-基胺基曱基）_丨，2_二氫_ 異啥1#-々-缓酸（（S)-l -苯基-丙基）-酿胺 2eb 1-侧氧基-2-苯基-3-(嘧啶-4-基胺基曱基）_ι，2_二氫 -異喧琳-4 -缓酸（（S)-l -苯基-丙基）-醯胺 2ec 3-(第三丁基胺基-甲基）側氧基_2_苯基-丨，2_二氫 -異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ed 3-[(2·羥基-1，1-二甲基-乙基胺基）_甲基側氧基_ 2-苯基-1，2·二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基醯胺 316 200906801 2ee 3-(異丙基胺基-曱基）-1-側氧基-2_苯基―丨，二氫_ 異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ef 3-[(2-羥基-1-甲基乙基胺基）-甲基]側氧基_2_苯基-1，2-二氫-異喧琳-4_緩酸（（S)-l-苯基-丙基）_醯胺 2eg 3-[(1-羥基曱基-丙基胺基）-曱基]_丨_侧氧基_2_苯基 -1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基·丙基）_醯胺 2eh 3-[(2,2-二曱基-丙基胺基）-曱基]_1_侧氧基_2_苯基-1，2-二氫-異喹啉-4-羧酸（（8)-1-苯基-丙基）_醯胺 2ei 1-側氧基-2-苯基-3-丙-2-块基胺基甲基_i,2-二氫_ 異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ej 3-烯丙基胺基曱基-1-側氧基_2_苯基-L2-二氫-異啥啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ek 3-[(曱基-丙_2-炔基-胺基）-甲基]側氧基_2_苯基_ 1,2-二氫-異喹啉_4_羧酸（（s)-!·苯基-丙基）_醯胺 2el 3-二烯丙基胺基甲基-i_側氧基_2_苯基-1,2_二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2em 3-二乙基胺基甲基_1_側氧基苯基_1，2_二氫-異喧σ林-4-叛酸（（S)-l-苯基-丙基）_酿胺 2en 3_[(異丙基-甲基-胺基）_甲基]_卜側氧基_2_苯基_ 1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2eo 3-[((S)-2-羥基-1-甲基·乙基胺基曱基^ •側氧基_ 2-苯基-1，2-二氫-異喹啉羧酸（（S)-l-苯基-丙基）_醯胺 2ep 3-[((R)-2-羥基-1_甲基-乙基胺基）_甲基]側氧基_ 2-苯基-1，2-二氫-異喹啉_4_羧酸（（s)-；!-苯基-丙基）_醯胺 317 200906801 2eq 3-{[(2-曱氧基-乙基）-曱基-胺基]•甲基}·^側氧基_ 2-苯基-1，2-二氫-異喧琳-4-叛酸（（S)-l-苯基-丙基）_醯胺 2er 3-((R)-3·羥基--比咯啶-1-基曱基）1側氧基苯基_ 1，2_二氫-異:琳-4-叛酸（（S)-l -苯基-丙基）_酿胺 2es 3-((S)-3-羥基-吡咯啶-1-基甲基）_1_侧氧基_2_苯基_ 1.2- 二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2et 3-[(環戊基-甲基-胺基）-曱基]_丨_側氧基_2_苯基_ 1，2-二虱-異啥淋-4-緩酸（（S)-l -苯基-丙基）_醯胺 2eu 3-{[(2-羥基-1-曱基-乙基）-曱基-胺基曱基卜^側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l·苯基-丙基）_酿胺 2ev 3-{[乙基- (2-經基-乙基）-胺基]-甲基卜1_側氧基_2_ 本基-1,2 - —虱異喧嚇*-4 -叛酸（（S)-l -苯基-丙基）_酿胺 2ew 3-[(乙基-曱基-胺基）-甲基]-l_側氧基-2_苯基二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ex 3-環丁基胺基甲基-1-侧氧基_2·苯基-l，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ey 3-四氫吖唉-1-基甲基-1·側氧基_2·苯基_丨，2·二氫_ 異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ez 3-(4-第三丁基-哌畊-1-基曱基）·！_側氧基·2_苯基· 1.2- 二氫-異喹啉-4-羧酸（（S)-l·苯基-丙基）-醯胺 2fa 3-[4-(2-羥基-乙基）-哌明：-1_基曱基卜丨·側氧基_2·苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2fb 3-{4-[2-(2-羥基-乙氧基）_乙基]-哌明:小基曱基} + 318 200906801 . 側氧基-2 -苯基-1，2-二氫-異啥淋_4 -叛酸（（S)-l -苯基·"丙基）- 醯胺 2fc 3-[4-(3-氯-5-三氟甲基-吡啶-2-基）-哌畊-1-基甲基]-1-侧氧基-2-苯基-i，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2fd 3-[4_(3,5-二氯-吨啶-4-基）-哌畊-1-基曱基]-1-側氧基-2-苯基-1，2-二氫-異喹啉_4_羧酸（（s)-l-笨基-丙基）-醯胺 2fe 4-[1-侧氧基-2-苯基-4-((S)-l-苯基·丙基胺曱醯基）-ί 丨，2-二氫-異01琳-3-基曱基]-旅明"-l-缓酸苯甲酯 2ff 3-[4-(3-嗎福林-4-基-丙基）-娘啡-i_基甲基]-1·側氧基-2-苯基-1，2-二氫-異喧琳-4-缓酸（（S)-l -苯基-丙基）-醯胺 2fg卜側氧基_2_苯基_3-[4-(3·哌啶-1-基-丙基）-哌畊」_ 基甲基]-l，2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）-醯胺 2fh 3-[4_(4,6_二甲氧基-嘲咬_2_基甲基）_〇辰啡-卜基曱基]-1-側氧基-2 -苯基-1,2-二氫-異啥琳-4-叛酸（（s)-l -苯基_ 丙基）-醯胺 L 2fi 3-[4-(3-經基丙基）“底啡-1-基甲基]_ 1_側氧基_2_苯基-1，2-二氫-異喧淋-4-缓酸（（S)-l -苯基-丙基）_醯胺 2fj 3-[4-(2,3-二羥基-丙基）-哌啡-1-基曱基·侧氧基· 2-苯基-1,2-二氫·異喹啉-4-羧酸苯基-丙基）_酿胺 2fk (2-側氧基-2-{4-[l -側氧基-2-苯基- 4-(ι_苯基_丙基胺曱醯基）-1,2-二氫-異喹啉-3-基甲基]_哌啡-j•基卜乙基）_ 胺基甲酸第三丁酯 2fl 3-[4-(1Η-吲唑-5-基）_哌啡_1_基甲基]小側氧基_2_ 319 200906801 苯基-1,2-二氫-異喧淋-4-羧酸（（S)_l-苯基-丙基）-醯胺 2fm 1-侧氧基-2-苯基-3-(4_喹啉_6·基-0底明^1-基甲基）_ 1,2-二氩-異喹琳-4-羧酸（（S)_1_苯基-丙基）-醯胺 2fn 3-[4-(6,7-二甲氧基-喧唑啉-4-基）-哌畊-1-基曱基]_ 1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（(S)-l-笨基-丙基）-醯胺 2fo 4-{4-[1-侧氧基-2_笨基-4-(l -笨基-丙基胺甲醯基）_ 1，2_二氫-異喧琳-3-基甲基]底啡-1-基卜π底。定-1-叛酸第三丁酉旨 2fp 3-{4-[2-(4-氯-苯氧基）·乙基]-哌畊-1-基甲基卜丨_侧氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_酿胺 2fq {4-[1-側氧基-2 -苯基-4-(1-苯基-丙基胺甲酿基）_ 1.2- 二氫-異喹啉-3-基甲基]-哌畊-1-基}-乙酸第三丁酯 2fr 1-側氧基-2-苯基-3-[4-(3,3,3-三氟-2-經基-丙基）_〇底啡-1-基甲基]-1，2-二氫-異喧嚇·_4-缓酸（（S)-l-苯基-丙基）_醯 I 胺 2fs 3-[4-(2-經基-丙基）-派啡-1-基曱基]_ι_側氧基_2_笨基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2fu 3-[4-(4-胺基-6,7-二甲氧基-喧嗤琳_2_基）_〇底啡_ι_ 基甲基]-卜側氧基-2-苯基- l，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2fv (2-{4-[1-側氧基-2-苯基-4-(1-苯基-丙基胺甲醯基）- 1.2- 二氫-異喹啉-3-基甲基]•哌啡-^基卜乙基）_胺基甲酸第 320 200906801 三丁酯 2fw 1-側氧基-3-{4-[2-(2-側氧基-咪唑啶·丨_基）_乙基]_ 哌啡1基曱基苯基_ls2_二氫_異喹淋_4_缓酸（⑻·】·苯基-丙基）-酿胺 2fx 3-{4_[(4,6_二甲氧基_嘧啶_2_基）_苯基-甲基]-哌啡_ 1-基曱基}-1-側氧基-2-苯基_ι，2_二氫_異喹啉_4_羧酸苯基-丙基）-醯胺 2fy 3-(4~笨并[I，2,5]噻二唑_心基_哌啡·卜基甲基）·卜侧氧基-2-苯基_1，2_二氫-異喹啉_4_羧酸（（y—b苯基-丙基）_醯胺 2fz 3-[4-(2’3-二氫-苯并[L4]二腭啡_5_基）哌畊4基曱基]-1-侧氧基-2-苯基-1，2-二氫-異喧琳_4-叛酸（（s)_i_苯基_ 丙基）-醯胺 2ga 3-[4-(4-甲基-喹啉-2-基）-哌畊基甲基卜卜側氧基 -2-苯基-1，2-二氫-異喹啉-4-羧酸（（s)-l-苯基-丙基）_醯胺 2gb 1-側氧基-2-苯基-3-[4-(»比咬-2-基胺甲醯基曱基）_ 哌畊-1-基曱基]-1，2-二氫·異喹啉-4-羧酸（（S)-l-苯基-丙基）_ 醯胺 2gc 3-[4-(6-氯-3-側氧基-3,4-二氫-2H-笨并[1，4]聘啡 _ 8-基）-哌畊-1-基甲基]-1-側氧基-2-苯基-1，2-二氫-異喹啉_4_ 羧酸（（S)-l-苯基-丙基）_醯胺 2gd 3-(4-胺曱醯基甲基-哌啡-1-基甲基）-1-側氧基-2-苯基-1,2-二氫-異啥琳-4-羧酸苯基·丙基）-龜胺 2ge 3-(4-羥基-4-苯基-哌啶-1·基甲基）-1_側氧基-2-苯 321 200906801 . 基_1，2-—風_異啥琳-4-缓酸（（S)-l -苯基-丙基）_酿胺 2gf 3-[4-(4-氣-苯基）-4-羥基-派啶-1 —基甲基]_ι_側氧基 -2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 1-[1-側乳基-2-苯基- 4- (1-苯基-丙基胺甲酿基）-1，2-一氫-異喧琳-3-基甲基]-π底α定-4-叛酸 2gh 3-(4-氰基-4-苯基-哌啶-1-基甲基）_丨-側氧基_2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2gi 3-(4-苯甲基-4-羥基-哌啶-1-基甲基）-i·側氧基-2-苯厂基-1，2-二氫-異喹啉_4_羧酸（（S)-l-苯基-丙基）-醯胺 2gj 1-[1-側氧基-2-苯基-4-(1-苯基-丙基胺甲醯基）-1,2-一虱-異啥嚇基甲基]-4 -苯基- π底咬-4-叛酸乙醋 2gk 1-側氧基-2-苯基-3-[4-(苯基-丙醯基-胺基）-哌啶-卜基甲基]-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2gl曱基-{1-[1-側氧基-2-苯基-4-(1-苯基-丙基胺甲醯基）-1，2-二氫-異喹啉-3-基甲基]-哌啶-4-基}-胺基甲酸第三丁酯、 2gm 1-側氧基·2·苯基-3-[4-(2-吡咯啶-1-基-乙基）-哌啶 _卜基甲基]-1,2-二氫-異喹啉-4-羧酸（(S)-l-笨基-丙基）-醯胺 2gn 3-{4-[5-(4-氟-苯基）-[1,3,4]腭二唑-2-基]-哌啶-1-基甲基}-1-侧氧基-2-笨基-1,2-二氫-異喹啉-4-羧酸（（S)-l-本基-丙基）-酿胺 2g〇 1-側氧基-2-苯基-3-[4-(3-吡啶-4-基-[1，2,4]聘二唑-5-基）-哌啶-1-基曱基]-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基- 丙基）-醯胺 322 200906801 2gp 1-側氧基-2-苯基-3_[4_(3_吡畊_2_基-[i,2,4]聘二唑_ 5-基）-哌啶-1-基甲基]-i，2-二氫_異喹啉_4_羧酸（（8)_丨_苯基_ 丙基）-醯胺 2区9 1-側氧基-2-苯基_3-[4-(3-吡啶-4-基-[1,2,4]_二唑-5-基）-哌啶-1-基甲基]_1,2_二氫_異喹啉_4_羧酸苯基_ 丙基）-醯胺 28圹3-(4’-羥基-3’，4’，5,，6'-四氫-2111-[2,4’]聯吡啶-1|-基曱基）-1-側氧基-2-笨基_1，2_二氫_異喹啉_4_羧酸苯基 -丙基）-S篮胺 2gs 3-(螺[異二氫苯并哌喃]，4，_哌啶]，基甲基）_丨_側氧基-2-苯基-1，2-二氫-異喹啉_4_羧酸（(3)_1_苯基-丙基卜醯胺 2gt 3 [4 &基-4-(3-曱氧基_苯基）_旅。定_卜基甲基]側氧基-2-苯基-1，2-二氫-異喹啉_4_羧酸苯基-丙基醯胺 2gu 3-[4-(3-氯-苯基）_4-羥基-哌啶_丨_基甲基]_丨_側氧基 -2-苯基-1，2-二氫-異喹啉_4_羧酸（（yq —苯基_丙基）_醯胺 2gv 3-(6-氯-3H-螺[異苯并呋喃哌啶]_广基甲基）_ 卜側氧基-2-苯基- l，2-二氫-異喹啉_4_羧酸苯基-丙基）-醯胺 2gw 3-(4-{[4-氯-3-(4-氟-苯基）_茚_卜基]-甲基-胺基}_ 哌啶-1-基曱基）-1_側氧基_2_苯基二氫_異喹啉_4_羧酸 ((S)-l -苯基-丙基）_酿胺 2gx 3-(1-乙醯基-螺卜引哚啉_3,4，_哌啶]·丨，_基甲基）_丨_側 323 200906801 氧基-2-苯基-1，2-二氫-異喹啉_4·羧酸苯基_丙基）_醯胺 2gy 3-(1-乙醯基_5 -氟-螺卜弓卜朵琳_3,4'_〇底咬]_广基甲基）-1-侧氧基-2-苯基- l，2-二氫-異喹琳_4_缓酸（（s)_i_苯基_ 丙基）-醯胺 2gz 1-側氧基-3-(4-侧氧基_1_苯基- 三氮雜·螺[4 5] 癸-8-基曱基）-2-苯基_ι，2·二氫-異喹琳叛酸（（s)-l·苯基_ 丙基）-醯胺 2ha 3-(4-乙醯基胺基-哌啶_丨·基曱基）側氧基_2_苯基 -1，2-二氫-異喹啉_4_羧酸苯基-丙基）_醢胺 2111)1-側氧基-3-(1-側氧基_2,8-二氮雜_螺[4.5]癸_8-基甲基）-2-苯基-1,2-二氳-異喹啉_4_羧酸（（s)-l-苯基-丙基）_醯胺 2hc 3-[4-羥基-4-(3-三氟甲基·苯基）_哌啶基甲基卜卜側氧基-2-苯基-1，2-二氫-異喹啉_4_羧酸（（s)-l-苯基_丙基醒胺 2hd 1-側氧基-2-苯基-3-(4-三氟曱基·哌啶_丨_基甲基 1,2-二氫-異喹啉-4-羧酸（（㈨—丨―苯基_丙基）_醯胺 2he 3-[4-(4-甲基-哌畊-i_羰基）_哌啶_丨_基曱基]_丨_側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-1-苯基-丙基）_醯胺 21^3-(5-異丙基-311-螺[異苯并呋喃_1，4，_哌啶]_1，_基甲基）-1-側氧基-2 -本基-1,2-二氫-異唾琳_4_缓酸（（；§)_卜笨基_ 丙基）-醯胺 2hg 3-[4-(乙醯基-甲基-胺基）_4•苯基·哌啶基甲基]_ 324 200906801 1-側氧基-2-笨基- i，2_二氫-異喹淋_4-叛酸（（s)_i_苯基-丙基）-醯胺 2hh 4-{1-[1-側氡基_2_苯基_4_(1_苯基-丙基胺曱醯基）_ 1，2-二氫-異喹啉-3-基曱基]_哌啶_4-基}-哌啡羧酸第三丁酯 2hi (2-{1-[1-側氧基_2_苯基_4-(1-苯基-丙基胺曱醯基）-1，2 - 一 31-異啥琳-3-基曱基]_〇底〇定-4-基}-乙基）-胺基曱酸第三丁酯 2hj 3-(4-甲基胺基_4_苯基-哌啶-1-基甲基）-1-侧氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2hk 3-(4-乙醯基胺基-4-苯基-哌啶-1-基甲基）-1-側氧基 -2-苯基-1,2-二氫-異喹啉-4-羧酸笨基-丙基）-醯胺 21|丨3-[4-乙醯基胺基-4-(3-氟-苯基）-哌啶-1-基甲基]-1_ 側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2hm 1-侧氧基-3-[4-(4-側氧基-旅°定-1-羰基）-B底咬-卜基甲基]-2-苯基-1,2-二氫-異噎淋_4-缓酸（（S)_1_苯基-丙基）_酸胺 2hn 3-[4,4，]聯旅。定-1_基曱基側氧基本基_1，2- — 氫-異喹啉-4-羧酸（（s)_1_苯基·丙基）_醯胺 2ho {1-[1-側氧基_2·苯基-4_(卜苯基·丙基胺甲酿基）· 1,2-二氫-異喹淋-3-基甲基]-D底啶-4-基卜胺基甲酸第二丁西曰 2hp 3-[1 4·，]聯略0定_1’_基甲基·1_侧氧基·2_本基_1，2_ 一氫-異喹啉-4-羧酸[環丙基-(3_氟-苯基）-曱基]-醯胺 325 200906801 2hq 1-側氧基_3_(4-苯乙基-派明基曱基）_2_苯基-1，2_ 二氫-異啥琳-4-羧酸[環丙基_(3 -氟-苯基）-甲基]-醯胺 2hr 3-(4-異丙基-哌啡-1-基甲基卜1—侧氧基-2-苯基-1，2-二氫-異01琳-4-叛酸[環丙基- (3 -氟-苯基）-曱基]-酿胺 2hs 3-[4-(2-嗎福林_4·基-乙基）-哌啡-1-基曱基]-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸[環丙基-(3 -氟-苯基）-甲基]-酿胺 2ht 3-[4-(卜甲基-哌啶-4-基）-哌畊-1-基曱基]_1_側氧基 -2-苯基-1，2-二氫-異喹啉-4-羧酸[環丙基-(3-氟-苯基）_甲基]-醯胺 2hu 1-侧氣基-2 -苯基-3- [4-(2-0底°定-1-基-乙基）_0底啡_ι_ 基甲基]-I，2-二氳-異喹啉-4-羧酸[環丙基_(3_氟_苯基）_甲基]-醯胺 2hv 1-侧氧基-2_苯基·3_[4-(2-°比咯啶-i_基-乙基）辰啡_ 1-基曱基]-1,2-二氫-異喧琳-4-叛酸[環丙基_(3_氟_苯基）甲基]-醯胺 2hw 1-側氧基_2·苯基-3·(4-吼啶_4-基甲基_π底啡基甲基）-1,2-二氫-異喹啉-4-羧酸[環丙基_(3_氟_笨基甲美]醯胺 2hx 3-(4-羥基-3,4,5,6- r % °足_ 1 -基甲基）-1-側氧基-2-苯基-1，2-二氫-異喹琳_4_羧酴又吃1¾丙基_(3-翁 -苯基）-甲基]-醯胺 2hy 3-[4-(2-嗎福林-4-基-乙基）-哌啶暴甲基]-1-側氣基-2-苯基-I，2·二氫-異喹啉-4-鲮酸[環丙基 — 土鼠-苯基）·甲 326 200906801 基]-醯胺 2hz 3-[4-羥基-4-(3-曱氧基-苯基）-哌啶-1-基甲基]-1-側乳基-2-苯基-1，2 -二鼠-異喧琳-4-叛酸[ί哀丙基- (3 -氣-苯基）_ 甲基]-醯胺 2ia 3-[4-(乙醯基-曱基-胺基）-4-苯基-哌啶-1-基曱基]-1_側氧基-2-苯基-1,2-二氮-異啥琳-4-竣酸[壤丙基- (3 -氣-苯基）-甲基]-醯胺 2ib 2-(2 -氣-苯基）-1-側乳基- 3- (4-苯乙基-旅啡-1 -基甲基）-1，2-二氮-異。奎琳-4-竣酸（（S)-l-苯基-丙基）-酿胺 2ic 2-(2 -亂-苯基）-3-(4-異丙基-α底啡-1-基甲基）-1-側氧基-1，2 -二氮-異啥嚇 - 4 -竣酸（（S)-l -苯基-丙基）-酿胺 2id 3-[1，4']聯哌啶-1’-基曱基-2-(2-氟-苯基）-1-側氧基-1,2-二氮-異喧琳-4-竣酸（（S)-l -苯基-丙基）-酷胺 2ie 2-(2_氟-苯基）-3-[4-(2_嗎福林_4_基-乙基）-哌啡-1-基曱基]-1-側氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2if 2-(2-亂-苯基）-3-[4-(1-甲基-0辰α定-4 -基）-旅明1 -1 -基甲基]-1-側氧基-1,2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）- 醯胺 2ig 2-(2 -氣-本基）-1 -側氣基- 3- [4-(2 -旅°定-1 -基-乙基）_ 哌畊-1-基曱基]-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）- 醯胺 21112-(2-氟-苯基）-1-側氧基-3-[4-(2-吡咯啶-1-基-乙基）-哌畊-1-基甲基]-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙 327 200906801 基）-醯胺 2ii 2-(2 -鼠-苯基）-1-側乳基- 3- (4 -0比σ定-4-基甲基-旅明1 _ 1-基甲基）-1，2-二氫-異喹啉-4-羧酸（（8)-1-苯基-丙基）-醯胺 2ij 2-(2-氟-苯基）-3-(4-羥基-3,4,5,6-四氫-211-[4,4’]聯。比啶-1-基甲基）-1-侧氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ik 2-(2 -氣-笨基）-3-[4-(2-嗎福林-4-基-乙基）-α底。定-1 _ 基甲基]-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基醯胺 2il 2-(2-氟-苯基）-3-[4-羥基-4-(3-曱氧基-苯基）-哌啶-1-基甲基]-卜側氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2im 3-[4-(2-嗎福林-4-基-乙基）_〇底啡-1-基曱基]-1-側氧基-2-鄰甲苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）- 酉&胺 24 1-側氧基-3-[4-(2-哌啶-1-基-乙基）-哌畊-1-基甲基]-2-鄰甲苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）- 醯胺 2io 1-側氧基-3-(4-吡啶-4-基甲基-哌畊-1-基甲基）-2-鄰甲本基-1,2 -二氮-異喧琳-4-竣酸（（S)-l-苯基-丙基）-酸胺 2ip 2-(3 -氣-苯基）-1-側氧基- 3- (4-苯乙基-旅啡-1 -基甲基）-1，2-二氮-異哇琳-4-竣酸（（S)-l -苯基-丙基）-酸胺 2iq 2-(3 -氣-苯基）-3-(4-異丙基-°底啡-1-基甲基）-1-側氧基-1，2-二氫-異喹啉-4-羧酸苯基-丙基）-醯胺 328 200906801 2ir 3-[ 1,4']聯哌啶-1’-基曱基-2-(3-氟-苯基）-1-側氧基-1,2-二氮-異唾嚇 - 4-竣酸（（S)-l-苯基-丙基）-酿胺 2is 2-(3 -亂苯基）-3-[4-(2-嗎福林-4 -基-乙基）-旅明1 -1 _ 基甲基]-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2-(3 -氣-苯基）-3-[4-(1-甲基-〇底0定-4-基）-旅明:-1 -基甲基]-1-側氧基-1，2-二氳-異喹啉-4-羧酸（（S)-l-苯基-丙基）- 醯胺 2iu 2-(3 -氣-苯基）-1-側乳基- 3- [4-(2 -〇底°定-1 -基-乙基）_ 哌啡-1-基甲基]-1，2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）- 酸胺 2iv 2-(3 -鼠-苯基）-1 -側氧基- 3- [4-(2 - 0比洛α定-1 -基-乙基）-哌啡-1-基曱基]-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2iw 2-(3 -氣-苯基）-1-側氧基- 3- (4 -0比0定-4-基甲基-旅明1 _ 1-基曱基）-1，2-二氫-異喹啉-4-羧酸（（8)-1-苯基-丙基）-醯胺 2ix 2-(3 -氣-苯基）-3-[4-(2 -嗎福林-4-基-乙基）-派α定-1 _ 基甲基]-1-側氧基-1,2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）-醯胺 2-(3 -氣-苯基）-3-[4-輕基- 4- (3 -曱氧基-苯基）-旅〇定_ 1- 基曱基]-1-側氧基-1，2-二氳-異喹啉-4-羧酸苯基-丙基）-醯胺 2iz 3-[4-(乙醯基-甲基-胺基）-4-苯基-哌啶-1-基曱基]- 2- (3-氟-苯基）-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯 329 200906801 基-丙基）-醯胺 2ja 2-(3-氯-苯基）-1-側氧基-3-(4-苯乙基-哌啡-1-基甲基）-1,2-二風-異啥淋-4-叛酸（（S)-l-苯基-丙基）-酿胺 2jb 2-(3 -氯-苯基）-3-(4-異丙基-α底啡-1-基曱基）-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2jc 3-[1,4']聯哌啶-Γ-基甲基-2-(3-氯-苯基）-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2jd 2-(3 -鼠-苯基）-3-[4-(2-嗎福林-4-基-乙基）-派啡-1 基曱基]-1-側氧基-1,2-二氳-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2je 2-(3 -乳-苯基）-3-[4-(1-甲基-旅0定-4-基）-旅啡-1 -基曱基]-1-側氧基-1,2-二氳-異喹啉-4-羧酸（(S)-l-苯基-丙基）- 醯胺 2jf 2-(3-氯-苯基）-1-側氧基-3-[4-(2-哌啶-1-基-乙基）-哌明^1-基甲基]-1,2-二氳-異喹啉-4-羧酸（(S)-l-苯基-丙基）· 醯胺 2jg 2-(3 -氮-苯基）-1-側乳基- 3- [4-(2 -σ比略0定-1 -基-乙基）-哌啡-1-基甲基二氳-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2jh 2-(3_氣-苯基）-1-側氧基-3-(4·-。比13定-4·-基曱基-13底明1 _ 1-基甲基）-1,2-二鼠-異啥嚇^-4-叛酸（（S)-l-苯基-丙基）-酿胺 2ji 2-(3 -氣-苯基）-3-[4-(2 -嗎福林-4-基-乙基）-旅。定-1 _ 基甲基]-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 330 200906801 - 2jj 2-(3-氣-苯基）-3-[4-羥基-4-(3-曱氧基-苯基）-哌啶- 1_基甲基]侧氧基_1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基_丙基）-酿胺 2jk 3_[4'(乙醯基-甲基-胺基）-4-苯基-旅啶-1-基曱基]_ 2_(3_氯_苯基）-丨-側氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2』丨1-側氧基-3-(4-苯乙基_哌畊-1_基曱基）_2-間甲苯基· l2-二氫-異喹啉-4-羧酸（（s)-l-苯基-丙基）-醯胺 2jm 3-[1，4']聯哌啶基甲基-i_側氧基_2_間甲苯基_ 1’2 - _虱-異喧淋-4 -叛酸（（S)-l -苯基-丙基）-醯胺 2jn 3-[4-(2 -嗎福林-4-基-乙基）-娘啡-1-基甲基]_ι_側氧基-2-間甲苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_ 酉1胺 2jo 3-[4-(1-甲基-α底。定-4-基）-〇辰啡-1-基甲基]側氧基 -2-間甲苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2jp 1 -側氧基-3-[4-(2- °底咬-1 -基-乙基）· β底啡-1 _基曱基]_2-間甲苯基-ΐ，2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）_ 醯胺 2jq 1-側氧基-3-[4-(2-1〇比11各13定-1-基-乙基）-旅啡-1-基甲基]-2-間曱苯基- i，2-二氫-異喧淋-4-叛酸（(S)-l·苯基·丙基）_ 醯胺 1-側氧基-3-(4-吡啶-4-基甲基-哌啡-1-基甲基）_2·間甲笨基-1,2-二氫-異喹淋-4-羧酸（（S)-l-苯基-丙基）_醯胺 331 200906801 2js 3-[4-(2-嗎福林-4-基-乙基）-哌啶-卜基甲基Μ-側氧基-2 -間甲苯基-1,2-二氳-異喹琳-4-缓酸（(S)_1_笨基-丙基）- 酸胺 2jt 3-[4-羥基-4-(3_甲氧基-苯基V哌咬-1·基甲基]-1_側氧基-2-間曱苯基- I，2-二氫·異喹啉_4-羧酸（(S)_i -笨基-丙基）-酿胺 2ju 3-[4-(乙醯基_曱基-胺基）-4-苯基_0底0定-1-基甲基]-1-側氧基-2-間甲苯基-1，2_二氫-異喹啉-4_羧酸（（S)-l-笨基- { 丙基）-醢胺 3a 1-側氧基-3-(2-側氧基-啦咯啶-l_基曱基）_2_笨基_ 1,2-二氫-異嗜淋_4_缓酸（（S)-l -苯基-丙基）_酿胺 3b 8-氯-卜側氧基-3_(2·側氧基-吡咯啶基甲基）_2•笨基- I，2·二氫-異啥嚇·_4_緩酸（（S)-l -苯基-丙基）_酿胺 4a 3-氰基甲基-1-側氧基-2-苯基-1，2-二氫_異喹啉_4羧酸（（S)-l-苯基-丙基）_醯胺 5a 3-曱基-1-側氧基-2-苯基-1，2·二氳-異喹啉_4_羧酸 ί Ν，Ν-二苯基-肼 5b Ν，-(3-甲基-1-侧氧基-2-苯基-1，2-二氫-異喹啉_4_羰基）-Ν-苯基-肼羧酸甲酯 laa 2-(3-甲氧基-苯基）-3-甲基-1_側氧基2_二氫異。奎琳-4-羧酸（（S)-l -苯基-丙基）-醯胺 lab 2-(4-甲氧基-苯基）-3-曱基-l_側氧基_152_二氫-異喧琳-4-缓酸（（S)-l -苯基-丙基）_酿胺 lac 2-(4-氟-苯基）_3·甲基側氧基“，之·二氫_異喹啉_ 332 200906801 4-羧酸（（S)-l-笨基-丙基）-醯胺 lad 2-(4-氯-苯基）-3-甲基-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-笨基-丙基）-醯胺 lae 3-甲基-1-側氧基-2-對甲苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 laf 2-(3-甲氧基-苯基）-3-甲基-1-側氧基-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺 lag 2-(4-曱氧基-苯基）-3-曱基-1-側氧基-1,2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-曱基]-醯胺 lah 2-(4-氟-笨基）-3-甲基-1-侧氧基-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺 lai 2-(4-氣-苯基）-3-曱基-1-側氧基-1,2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺 laj 3-曱基-1-側氧基-2-對甲苯基-1,2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-曱基]-醯胺 lak 2-(2-曱氧基-苯基）-3-甲基-i_側氧基-1,2-二氫-異〇奎淋-4-叛酸（（S)-l -苯基-丙基）-酿胺 lal 2-(2 -甲氧基-苯基）-3 -甲基-1-側氧基-1，2-二氫-異唾啉-4-羧酸[(S)-環丙基-(3-氟-苯基）_曱基;醯胺 lam 3 -甲基-8-石肖基-1-側氧基_2-苯基-1，2-二氫-異喧琳-4 -叛酸（（S)_l_苯基-丙基）_酿胺 lan 3-甲基-8-硝基-1-侧氧基_2·苯基-1,2-二氫-異喹啉-4-羧酸[(S)_環丙基-(3 -氟·苯基）-甲基]-醢胺 lao 8 -曱氧基-3 -甲基-1-側氧基_2_苯基·ι，2_二氫異喹 333 200906801 琳-4-缓酸（（S)-l-苯基-丙基）_醯胺 lap 8-甲氧基-3-甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺 laq 8-胺基-3-甲基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸苯基-丙基）_醯胺 lar 8-氰基-3-甲基-1-側氧基_2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 las 8-氯-3-甲基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-缓酸[(S)-l-(4 -氯-苯基）-丙基]-酿胺 lat 8-氣-3-曱基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-叛酸[(S)-l-(4 -氟-苯基）-丙基]-醯胺 lau 8-氯-3-甲基-1-側氧基-2-苯基-l，2-二氫-異喹啉-4-缓酸[(S)-l-(2 -貌-苯基）-丙基]-酿胺 lav 8-氯-3-甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-叛酸[(S)-l-(3 -氯-苯基）-丙基]-醯胺 law 8-氯-3-甲基-1-側氧基-2-苯基-1，2-二氳-異喹啉-4-k J 羧酸[(s)-(3·氯-苯基）-環丙基·曱基]-醯胺 lax 8-氣-3-甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸[(S)-(4-氯-笨基）_環丙基-曱基]_醯胺 lay 8 -氟-3-甲基-1-側氧基-2-苯基-1，2-二氫-異喧琳- 4-羧酸[(S)-1-(3-氟-苯基）-丙基]-醯胺 laz 8-氣·3_甲基-1-側氧基_2·苯基-1,2-二氫-異喹啉·4-羧酸（（S)-2-甲基_丨_苯基-丙基）_醯胺 lba 8-氯_3_甲基-1-側氧基-2·苯基-1,2-二氫-異喹啉-4- 334 200906801 缓酸[(S)-環丙基-(4-氟-苯基）_甲基]-醯胺 lbb 8-氯-3-曱基-1-側氧基_2-苯基-1，2-二氫-異喹啉-4-叛酸[(S)-l-(2 -氯-苯基）-丙基]-醯胺 lbc 8-氯-3-甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉-4-羧酸（（S)-環戊基-苯基-曱基）-醯胺 lbd 8-氯-3-甲基-1-側氧基_2_苯基-1，2-二氫-異喹啉-4-叛酸[(S)-(2 -氯-苯基）-環丙基-甲基]_醯胺 lbe 8-氣-3-曱基-1-側氧基-2-苯基-1,2-二氫-異喹啉-4-叛酸[(S)-環丙基- (2 -氟-苯基）-甲基]_醯胺 lbf 8-氯-3-甲基-1-側氧基-2-苯基-1，2-二氫-異啥琳- 4-羧酸（（S)-環己基-苯基-曱基）-醯胺 Ibg 8-氯-3-甲基-1-側氧基-2-苯基_1，2_二氫-異喹啉-4-羧酸（（S)-環丙基-苯基-甲基）-醯胺 lbh 8-氯-3-甲基-1-側氧基-2-笨基-1,2-二氫-異喹啉-4-羧酸[(S)-環丁基-(3-氟-苯基）-甲基]-醢胺 lbi 8-氯-3-甲基-1-側氧基-2-苯基- l，2-二氫-異喧淋- 4-羧酸[(S)-環丁基-(4-氟-苯基）-曱基]-醯胺 Ibl 8 -氯-3-甲基-1-側氧基-2-苯基-1,2-二氫-異喹琳- 4-羧酸[(R)-環丙基-(3-氟-苯基）-曱基]-醯胺 lbn 8-氯-3-曱基-1-側氧基-2-苯基·1，2-二氫-異喹啉-4· 羧酸（（S)環丁基-苯基·甲基）-醯胺 lbo 8 -氯-3-甲基-1-側氧基-2-苯基·ι，2·二氫-異喹琳- 4-羧酸[環丁基-(2-氟-苯基）-甲基]-醯胺 2ka 3-(4_第三丁基-哌啡-1-基甲基）_8_氯-丨_側氧基_2_ 335 200906801 苯基-1,2-二氫-異喹啉-4-羧酸[(s)-環丙基-(3-氟-苯基）-曱基]-S盘胺 2kb 8-氯-3-(4-異丙基-哌畊_丨_基甲基）_丨·側氧基_2-苯基-1，2-二氫·異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2kc 8-氯-3-(4-異丁基-哌啡-；[_基甲基）_丨_側氧基苯基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基醯胺 2kd 8-氣_3_(八氫-吡啶并[i，2_a]吡啡_2_基甲基η-側氧基-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2ke 8-氯-3-(4-羥基-3,4,5,6-四氫-2H-[4,4']聯吡啶-1-基甲基）-1-側氧基-2-苯基-1，2-二氫-異喹琳_4_缓酸（（S)-l-苯基 -丙基）-醯胺 2kf 8-氯-3-(4-環丙基曱基-哌啡_ι_基曱基）_卜側氧基_2_ 苯基-1，2-二氫-異喹啉-4-羧酸（（s)-!·苯基-丙基）_醯胺 2kg 8-氯-3-[4-(2-嗎福林_4_基-乙基）_哌啶基甲基]_ 1 -側氧基-2-苯基-1,2-二氫-異喧琳-4-缓酸（(s)_i _苯基-丙基）-醯胺 2kh 8-氣-3-[1，4]二氮雑環庚烧-i_基曱基側氧基_2_ 苯基-1，2-二氫-異喹啉-4-羧酸苯基-丙基）·醯胺 2ki δ-氯-3_((S)-3 -甲基-哌啡_1_基曱基）_卜側氧基_2_苯基_1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醢胺 2kj 8-氯-3-咪唑-1-基曱基_1_側氧基_2_苯基。，孓二氫_ 異喧琳-4-致酸（（S)-l -苯基-丙基）-酿胺 2kk 8-氯-3-(4-甲基-味唑-1-基甲基）_^側氧基_2_苯基_ 1，2 -—虱-異啥琳-4-缓酸（（S)-l -苯基-丙基）_醯胺 336 200906801 2kl 3-(第三丁基胺基-甲基）-8-氯-1-侧氧基_2-苯基-1，2-二氯-異喧淋-4-叛酸（（S)-l -苯基-丙基）-酿胺 2km 8 -氯- 3-(異丙基胺基-甲基）-1-側氧基-2 -苯基_ι,2_ -一鼠-異啥琳-4-叛酸（（S)-l-苯基-丙基）-§篮胺 2kn 8-氣-3-[4 -經基-4-(3 -甲氧基·苯基）旅。定_1_基甲基]-1-側氧基-2-苯基-1,2-二氫-異噎琳-4-缓酸（（s)-i-苯基_ 丙基）-醯胺 2ko 3-(4-第三丁基-哌啡-1-基曱基）_8_氣-丨_側氧基_2_ 苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2kp 3-苯并咪唑-1-基甲基_1_側氧基_2_苯基_丨，2_二氫_ 異啥琳-4-叛酸（（S)-l -苯基-丙基）_醯胺 2kq 1-側氧基-2-苯基-3-°比唑-1-基甲基-丨，2_二氫-異喧啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 2kr 3-(4-甲基-吼唑-1-基甲基）_卜侧氧基_2_苯基一，二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2ks 1-側氧基_2_苯基_3-[1，2,3]***_1_基甲基dj·二氫 ϋ -異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2kt 2 (3 -〒氧基_本基）_ι_側氧基- 基甲基_ 哌畊-1-基甲基）_1，2_二氫-異喹啉_4_羧酸苯基-丙基）_ 醯胺 2ku 2-(4 -甲氧基_苯基）_3_[4_(2_嗎福林_心基-乙基）_0底啡-1 -基甲基]-1 -側氧基-1，2-二氫-異啥琳_4_叛酸（（s)_i _苯基 -丙基）-醯胺 2kv 2-(4-氟-苯基）_卜侧氧基_3_(4_苯乙基―哌畊-卜基甲 337 200906801 基）-l，2-—鼠-異喧琳-4-叛酸（（S)-l-苯基-丙基）_酿胺 2kw 2-(4_氟-苯基）-3-(4-異丙基-哌啡-1-基甲基）-1_側氧基-1，2 - 一虱-異喧琳-4-缓酸（（S)-l-苯基-丙基）_酿胺 2kx 3-[1，4’]聯哌啶-1’-基甲基-2-(4-氟-苯基）-1-側氧基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_醯胺 2ky 2-(4-氟-苯基）-3-[4-(2-嗎福林-4-基-乙基）-哌畊-1-基曱基]-1-侧氧基-1，2-二氫-異喹啉-4-羧酸（(S)-l -苯基·丙基）-醯胺 2kz 2-(4-氟-苯基）-3-[4-(1-曱基-〇底咬-4-基）-〇底啡-1-基曱基]-1-側氧基-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）_ 酿胺 21a 2-(4-氟-苯基）-1-側氧基-3- [4-(2_〇比d各咬-1-基-乙基）-D底畊-1-基甲基]-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-酸胺 21b 2-(4-氟-苯基）-3-[4-羥基-4-(3-曱氧基-苯基）-哌啶_ 1-基曱基]-1-侧氧基-1，2-二氫-異喹啉_4_羧酸（（S)-l-苯基-丙基）-醯胺 21c 2-(4 -亂-苯基）-1-側氧基_3_(4_苯乙基- η底啡-1-基曱基）-1,2-二氫-異喹啉-4-羧酸（（s)-l-苯基-丙基）_醯胺 21d 2-(4-氣-苯基）-3-(4-異丙基底啡-1-基曱基）-1_側氧基-1，2-二氫-異喹啉-4-羧酸（（s)-i-苯基-丙基）_醯胺 21e 3-[1，4’]聯哌啶-i’_基甲基_2_(4_氣-苯基）側氧基· 1，2-二氫-異喹啉_4_羧酸（（s)-i-苯基-丙基）_醯胺 21f 2-(4 -氯-苯基）-3-[4-(2-嗎福林-4-基-乙基）-〇底啡-i_ 338 200906801 基曱基]-1-侧氧基-1,2-二氫-異喹琳-4-羧酸（（s)-l -苯基-丙基）-醯胺 21g 2-(4-氣-本基）·3-[4-(1-曱基-旅〇定-4-基）-〇底啡_1_基曱基]-1-側氧基-1,2-二氫-異喹琳_4_叛酸（⑻小苯基-丙基）_ 醯胺 21h 2-(4-氯-苯基）_1_侧氧基_3_[4_(2-哌啶_1_基_乙基）_ 派啡-1-基曱基]-1,2-二氫-異喹啉_4_羧酸（⑻—卜苯基-丙基）一醯胺 21i 2-(4-乳-本基）-]_-側氧基_3-[4-(2-°比略· u定-1-基-乙基）-哌畊-1-基曱基]-1，2-二氫-異喹啉-4-羧酸（(S)-l-苯基-丙基）-醯胺 21j 3-(4-第三丁基-哌畊-1-基曱基）_8_氟-丨·側氧基_2•苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 21k 8-氯-3-環丙基胺基甲基-1-側氧基-2-苯基-1，2-二氫 -異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 211 3-(4-第三丁基-哌畊-1-基曱基）-8-氟-1-側氧基_2_笨基-1，2-二氫-異喧淋-4-叛酸[(S)-環丙基- (3 -氟-苯基）·甲基]_ 醯胺 2lm 8-氟-1-側氧基_2_苯基哌啡-1_基甲基-I，2-二氫· 異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺 21η 8-氟-1-側氧基-3-(3-側氧基-吡唑啶-1-基曱基）-2-苯基-1，2-二氳-異喹啉-4-羧酸[(s)_環丙基_(3-氟·苯基）-甲基]-醯胺 21〇 8 -氟-1-側氧基- 3-(3-側乳基-α底哄-1-基甲基）-2 -苯基 339 200906801 -1,2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺 3c 1-側氧基-2-苯基-3-(1Η-[1，2,4]***-3-基硫烷基甲基）-1，2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 3 d 8 -氣-1 -側氧基-3 - (2 -側氧基-π比洛α定-1 -基曱基）-2 -笨基-1，2-二氫-異喹啉-4_羧酸[(8)-環丙基-(3-氟-苯基）-曱基μ 酸胺 3e 8-氟-1-側氧基-3-(2-側氧基-吡咯啶-1-基曱基）-2-苯基-1,2-二氫-異喹啉-4-羧酸（（S)-l-苯基-丙基）-醯胺 3f 8-氟-1-側氧基-3-(2-側氧基比咯啶-1-基甲基）-2-苯基-1,2-二氫-異喹啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]- 醯胺 3g 8-氟-1-側氧基-3-(5-側氧基-吡唑啶-1-基甲基）-2-苯基-1,2-二氫-異喹啉-4_羧酸[(S)-環丙基-(3-氟-苯基）-曱基]- 醯胺 3h 8-氟-1-側氧基-3-(2-側氧基-哌畊-1-基甲基）-2-苯基 -1,2-二氫-異喧琳-4-叛酸[(S)-環丙基- (3 -氟-苯基）-曱基]-酿胺 3i 8-氟-1-側氧基-3-(2-側氧基-哌啶-1-基甲基）-2-苯基-1，2-二氫-異啥琳-4-缓酸[(S)-環丙基-(3 -氟-苯基）-曱基]-醯胺 4b 8-氯-3-氰基甲基-1-側氧基-2-苯基-1，2-二氫-異喹啉 -4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]·醯胺 6a 2-(3,4-二氯-苯基）-3-甲基-1-側氧基-1，2-二氫-異喹 340 200906801 琳-4-叛酸（（S)-l -苯基-丙基）_g篮胺 6b 8-氟-1-側氧基-3-(2-側氧基-吡咯啶-1-基曱基）-2-苯基-1，2-二氫-異喹啉-4-羧酸（（s)-環丙基-苯基-甲基）-醯胺 6c 8-氟-3-曱基-1-側氧基_2_苯基-l，2-二氳-異喹啉-4-羧酸（（S)-環丙基-苯基-甲基）_醯胺 7a 3 -乙基-1-側氧基_2·苯基- i，2-二氫-異喹啉-4-羧酸 ((S)-l-苯基-丙基）-醯胺 7b 8-氟-3 -甲基-1-側氧基_2_苯基-1,2-二氫-異喹啉_4-羧酸（（S)-l-苯基-丙基）_醯胺 7c 8-氟-2-(3-氟-苯基）_3_甲基側氧基4,2_二氫_異喹淋-4-叛酸（（S)-l-苯基-丙基）_醯胺 7d 8-氟-2-(4-氟-苯基）_3_曱基_；!_側氧基_1>2_二氫_異喹琳-4-緩酸（（S)-l -苯基-丙基）_醯胺 8-氟-3-甲基-i_側氧基_2_苯基-1〗·二氫-異喹啉_4_羧酸[(S)-環丙基-(3-氟·苯基）_曱基]_醯胺 7f 8-氟-2-(3-氟-苯基）_丨_側氧基_3_(2_側氧基_吡咯啶_ 1-基甲基）-1，2-二氫-異喹啉_4_羧酸[(s)_環丙基_(3氟-苯基）-甲基]-醯胺 7g 8-氟-2-(4-氟-苯基）_丨_側氧基_3_(2_側氧基_D比咯啶- 1-基甲基）-1，2-二氯-異喹啉-4_羧酸[(s)_環丙基_(3_氟-苯基）-甲基]-醯胺 7h 8-氟-3-甲基小側氧基_2_苯基a，二氫_異喹啉_4_ 羧酸[(S)-環丁基-(3-氟·苯基甲基]_醯胺 7ι 8-1-2-(2-氟_苯基）_3_曱基_1_侧氡基_1,2_二氫_異喹 341 200906801 琳-4-叛酸[(S)-環丙基- (3 -氟-苯基）-甲基]-醯胺 7j 8 -氟- 2-(3 -氟·苯基）-3 -甲基-1-側氧基_1，2-二氫-異喧啉-4-羧酸[(S)-環丙基-(3-氟-苯基）-甲基]-醯胺 7k 8 -氟-2- (4-戴-苯基）-3 -曱基-1-側氧基- i，2-二氫-異啥啉_4_羧酸[(S)-環丙基-(3-氟-笨基）-曱基]_醯胺 71 6,8-二氟-3-曱基-1-側氧基-2-笨基-1，2-二氫-異啥淋_ 4 -缓酸[(S)-環丙基- (3 -氟-苯基）-甲基]-酿胺 7m 5,8-二氟-3-曱基-1-側氧基-2-苯基-i，2-二氫-異喹啉 -4 -叛酸[(S)-環丙基- (3 -氟-苯基）-甲基]-酿胺 7n 3 -甲基-1-侧氧基-2-苯基-8-三氟甲基- i，2-二氫-異喹啉_4_羧酸（（S)-l-苯基-丙基）-醯胺 8a 3-(1-第三丁基-哌啶-4-基甲基）_8_氯側氧基_2_苯基-1，2-二氫-異喹啉-4-羧酸[(S)-環丙基_(3_氟-苯基）_曱基]_ 醯胺；及此專化合物中之任一者的醫藥學上可接受之鹽。 86_如申請專利範圍第n、19_21、42_44、46 68、和 L 80-85項中任一項之化合物，其係用於治療。 87. —種治療選自以下疾病之疾病的方法，精神病丨精神***症；類精神***症（schiz〇phren〇f〇rm dis〇rder); ***情感性障礙（schiz〇affective dis〇rder );妄想症 (deluSi〇nal diS0rder);暫時性精神病 disorder) ·，共享型精神病（如㈣psych〇dc ；歸因於一般醫學狀況之精神病；物質或藥物引發之精神病 (古柯鹼、酒精、***等）；類精神***人格異常 342 200906801 (schizoid personality disorder );精神***型人格異常 (schizoptypal personality disorder) •’ 與重度憂繫症有關之精神病或精神***症；雙極性情感疾患、阿茲海默氏症 (Alzheimer’s disease )或帕金森氏症（parkins〇n,sR12 Ο [Id1,,] wherein R1 represents ethyl or cyclopropyl; R12 represents chloro or fluoro; I R12, R14 and R15 each independently represent hydrazine, chloro or fluoro, wherein two of R12, R14 and R15 represent Hydrogen; and pharmaceutically acceptable salts thereof. 85. A compound according to claim 1 which is selected from the group consisting of 1 a 3 -mercapto-1-o-oxy-2-phenyl-1,2-diazo-isoindole-4-decanoic acid ((S) )-l-phenyl-propyl)-guanamine lb 3,6-dimethyl-1-oxo-2-phenyl-1,2-dimur-iso-zero quinques ^-4 - rebellion 303 200906801 . Acid ((s)-i-phenyl-propyl)-decylamine lc 7-chloro-3-methyl-1-oxo-2-phenyl-1,2-dioxime-isoindole-4 - citric acid ((S)-l-phenyl-propyl)-acid amine Id 7-bromo-3 -methyl-1-oxo-2-phenyl-1,2-diindole-isoindole _4_ Carboxylic acid ((S)-l-phenyl-propyl)-decylamine le 6-fluoro-3-methyl-1-oxo-2-phenyl-i,2-dihydro-isoquine Lin_4_carboxylic acid ((S)-l-phenyl-propyl)-guanamine If 3,5-dimethyl-b-oxy-2-phenyl-1,2-dihydro-isoquine Porphyrincarboxylic acid ((S)-l-phenyl-propyl)-bristamine lg 7-fluoro-3-mercapto-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline _4_ succinic acid ((S)-l-phenyl-propyl)-bristamine lh 3,7-dimercapto-1-yloxy-2-phenyl-1,2-dihydro-isoquine Acid ((S)-l-phenyl-propyl)-bristamine li 8-chloro-3-methyl-1-oxo-2-phenyl-l,2-dihydro-isoquinoline 4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine lr 3-methyl-1-oxo-2-phenyl_l52_dihydro-isoquinoline_4_carboxylic acid I ((S)-cyclopropyl-phenyl-methyl)-nonylamine Is 3-methyl-1-oxo-2-phenyl-1,2-dihydroisoquinoline_4_carboxylate Acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-guanamine Lj 3,8-Dimethyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline_4_carboxylic acid ((S)-l-phenyl-propyl)·acid Alk lk 2-(2-fluoro-phenyl)-3-methyl-1-oxooxyindole·isoquinoline_4_carboxylic acid ((S)-l-phenyl-propyl)-decylamine 11 3-Methyl-1-oxo-2-indenylphenyl-;!,^Dihydro-isoquinoline_4_carboxyl 304 200906801 . Acid ((s)-i-phenyl-propyl)-bristamine lm 2-(2-Gas-phenyl)_3. Mercapto-1-yloxy-1,2-dihydro-isoquinoline 4-Resin ((S)-l-phenyl-propyl)-bristamine In 2-(2,6-fluoro-phenyl)-3-methyl-1-oxo-1,2- Dihydro-isosporphyrin-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine lo 2-(3-fluoro-benyl)_3-methyl-1-oxo- 1 ,2-Dichloro-isoindole riboic acid ((S)-1 -phenyl-propyl)-bristamine lp 3-methyl-1-oxooxy-2_m-tolyl-1,2-di Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-bristamine lq 2-(3-chloro-phenyl)-3-methyl-1-oxo-i ,2-dihydro-isoquinoline_4-carboxy-acid ((S)-l-phenyl-propyl)-bristamine It 8-chloro-3-indolyl-1-yloxy-2-benzene 1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-nonylamine 2a 3-dimethylamino hydrazine 1-yloxy 2 phenyl-indole, 2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2b 3 -methylamine Methyl-1 -p-oxy-2-phenyl-1,2-dihydro-iso-π-quineline_ 4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2c 3-ethylaminomercapto-1-yloxy-2-phenyl-1 ,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2d 3-cyclopropylaminomethyl-1-oxooxy-2-benzene Base-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2e 3-[(cyclopropylmethyl-amino)-methyl ]-1-Sideoxy-2-phenyl-1,2-dioxa-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2f 3-(3, 6-Dihydro-2H-pyridine-1·ylmethyl)-1-oxo-2-phenyl- 305 200906801 . 1,2_-wind-isostimulation·_4 - tacrotic acid ((S)-l-phenyl-propyl)-bristamine 2g 3-[4-(2-methoxy-phenyl)-n-form -1-ylmethyl]_丨_sideoxy_2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2h 3-[4_(4_Fluoro-phenyl)-Ltyphthyl-1-ylmethyl]_ι_sideoxy_2_phenyl_ 1,2-dihydro-isoquinoline-4-carboxylic acid (( 3)-1-phenyl-propyl)-guanamine 2i 3-(4-mercapto-indenyl-1-ylindenyl)_1-sideoxy_2_phenyl_ι,2_ dihydrogen -isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2j 4-[1-o-oxy-2-phenyl-4-(1-phenyl-propyl) Aminomethyl hydrazino)_ι,2_ 'Dihydro-isoquinolin-3-ylindenyl]-piperidin-1-carboxylic acid ethyl ester 2k 3-(4-methyl-pipedino-1-ylmethyl) -1-Sideoxy_2_phenyl_1>2_two-isoindole-4-decanoic acid ((S)-l-phenyl-propyl)-bristamine 21 I-sideoxy- 2-Phenyl-3-(l,3,4,9-tetrahydro-β-flaxy-2-ylmethyl)- l,2-dihydro-isoquinoline-4-carboxylic acid ((S) -l-phenyl-propyl)-guanamine 2m 1-sided oxy-2_phenyl_3_piperidin-1 ylmethyl-;,,2-dihydro-isoquinoline-4-carboxylate Acid ((S)-l-phenyl-propyl)-nonylamine 2n 3-(3-A -Peptin-1-ylindenyl)-1-yloxy-2-phenyl--:di-**虱-iso-σ-quine-4-derivative ((S)-l-phenyl-propyl )--Amine 2〇3-(3,5-dimethyl-piperidin-1-ylmethyl)-1-oxooxy-2_phenyl_ 1,2-dihydro-isosalazine-4 - slow acid ((S)-l-phenyl-propyl)-nonylamine 2p 3-(4-phenylmethyl-pemidine)-ylindenyl-1-oneoxy-2-phenyl_ 1,2_ Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2q 1-sided oxy-3-[4-(2- oxo-2 -pyrrolidin-1-yl-ethyl)-piperidin-1-ylmethyl]-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((8)-1-benzene Base-propyl)-bristamine 306 200906801 2r 3-ofoline _4_ylmercapto_1_sideoxy-2-phenyl-i,2-dihydro-iso-p-dioxo-4-carboxylic acid ( (S)-i_phenyl-propyl)-decylamine 2s 3-(2,6-dimercapto-mflin _4_ylindenyl)_;!_sideoxyphenyl_U2_2 Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2t 1-sided oxy-2-phenyl-3-thiofenofin-4-ylindole基-丨':^二气_ Isophthalene-4-carboxylic acid (〇1_phenyl-propyl)_decylamine 3-(1,4-dioxa-8-aza-spiro[4· 5]癸_8_ylindolyloxy-2-phenyl_1,2- Hydrogen-isoquinoline_4_carboxylic acid (("_!_phenyl-propyl)-decylamine 2v 1-sideoxy-2_phenyl_3_piperidinyl fluorenyl 丨, 2_2 Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2w 3-(2-methyl-piperidinyl-yl-methyl)]-side oxy group 2_phenyl_i,2_dihydro-isoquinoline-4-carboxylic acid, strepyl-propyl)-nonylamine 2x 3-(2,6-dimethyl-piperidinyl-1-ylmethyl) _Polyoxy 2_phenyl· 1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl·•propyl)_decylamine 2y 3-(2-hydroxyl Methyl-piperidinyl-methyl)_!_Sideoxy_2_Phenyl-1,2-diindole-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propylhydrazine Amine 2z 1-[1-Sideoxy_2-phenyl-4-(1-phenyl-propylaminoindenyl)-indole, 2-dihydro-isoquinolin-3-ylmethyl]-peri Acridine-3-carboxylic acid, ethyl g, 2aa 3-(3-methyl-piperidin-1-ylmethyloxy-2, phenyl-it: hydrogen-isoindene-4-deoxy acid ((S) )-l-phenyl-propyl)-nonylamine 23匕3-(4-hydroxy-piperidin-1-ylmethyl)_1_sideoxy-2_phenyl_1,2_dihydro-iso啥琳-4-Repulsive acid ((S)-l-phenyl-propyl)-decylamine 2ac 1-sided oxy-2-phenyl- 3-(4-phenyl-pyro-_ι_基甲Base)_1,2_dihydro-啥琳-4-Repulsive acid ((S)-l-phenyl-propyl)_decylamine 307 200906801 2ad 1-U- side fluorenyl-2-phenyl-4-(1-phenyl-propylamine Indenyl)_1,2-monohydro-isoindol-3-ylmethyl] bottom. _4_Carboxylic acid ethyl ester 2ae 3-(4-methyl-piperidinylmethyldoxime-sideoxy-2_phenyl-^-dihydro-isoquinoline-4-carboxylic acid phenyl- Propyl)-nonylamine 2af 1-sideoxy-2_phenyl_3_(4_pyridine_2_yl-piperidinyl-methyl-L2-dihydro-isoquinoline-4-carboxylic acid ( (S)-l-phenyl-propyl)-nonylamine 2ag 3-(octahydro-quinoline-indole-ylhydrazino) sideoxy-2_phenyl-^2-dihydro-isoquinoline- 4-carboxylic acid ((s)-i-phenyl-propyl decylamine n 2ah 3 -azacycloheptan-1-ylmethyl-1-yloxy-2-phenyl-1,2-di Hydrogen_isoquinoline-4-carboxylic acid ((s)-〗-phenyl-propyl)·guanidine 2ai 3-(3-hydroxy-piperidinylfluorenyl sideoxy_2_phenyl_152_ Dihydro-isoquinoline-4-carboxylic acid phenyl-propyl)-nonylamine 2aj 3-[4-(2,4-dimethyl-phenyl)-piperidinylmethyl] pendant oxy-2 -phenyl-I,2-dihydro-isoquinoline-4-carboxylic acid ((yd-phenyl-propyl)-decylamine 2ak 3_[4-(3,4-dimethyl-phenyl)_ Piperidin-1-ylmethyl]-1-oxo-2-phenyl-I,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)_ Indoleamine L 2al 3-(4-dimethylamino-piperidin-1-ylindenyl)-1-oxooxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylate Acid ((S)- l-Phenyl-propyl)-decylamine 2 Please 3-[4-(2,5·dimethyl-phenyl)piperidinylmethyl]"-oxy-2-phenyl-I, 2-Di-argon isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2an 3·[4_(2·fluoro-phenyl)-dethiophene-1-yl group Base]_ι_Sideoxy_2_Phenyl-1,2-dihydro-isoindole_4_Resin ((S)-l-phenyl-propyl)-decylamine 2ao 3-[4- (3_Methoxy-phenyl)-pemamine: -1 -ylmethylbubu sideoxy_2_phenyl-1,2-dihydro-isoindolyl-4-hypoacid ((S)- l-Phenyl-propyl)_Taolin 308 200906801 2aP Side Oxyl-2-phenyl-3-(4-m-tolylthyl cyano-methyl)- 1,2-dihydro-iso- Lin-4-acid ((S)-1-phenyl-propyl)-guanamine 2aq 3-[4-(4-methoxy-phenyl)-parphin-1-ylmethyl]_丨_Sideoxy_2_Benyl-1,2 - I wind _isoindene-4 - tacrotic acid ((S)-l-phenyl-propyl)-nitramine 2ar 1-sideoxy-3-( 4-phenethyl-piperidin-1-ylmethyl)·2_phenyl-n dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2as 1-sided oxy-2·phenyl-3-(4_〇密咬_2_yl- η phenyl thiol ))_ 1,2-dihydro-iso Wah _-4- oxo acid (( S)-l-phenyl- ))- amidoxime 3-[4-(2-cyano-phenyl)-piped-1-ylindenyl]_;!_sideoxy_2_phenyl-1,2-diindole- Isoindolin-4-reaction acid ((S)-l-phenyl-propyl)_bristamine 2au 3-[4_(4-chloro-phenyl)-0 henyl-1-ylmethyl]-1 -Sideoxy_2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2av 3-((lS,3R, 5R)-3-hydroxy-8-aza-bicyclo[3. 21]octyl-8-ylmethyl)-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-l-phenyl-propyl)- Indole 2aw 3-(4-ethylhydrazine-based Benylmethyl)-1-oxo-2-phenyl-I 1,2-dihydro-isoindol-4-carboxylic acid phenyl-propyl)- Indole 2ax 3-(4-methyl-[1,4]-azepan-1-ylmethyl)-1-oxo-2-phenyl-1,2-dihydro-isoquine Porphyrin-4-carboxylic acid ((s)-l-phenyl-propyl)-decylamine 2ay 3-(4-ethyl-0- phenyl-cyanoguanidino)-small-oxy-2-phenyl-1, 2-Dihydro-isoquinoline-4-buffer acid ((s)_1_phenyl-propyl)-decylamine 2az 3-((2S,6R)-2,6-monodecyl-moffolin- 4-ylmethyl)-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-hypoacid ((S)-i-phenyl-propyl)-decylamine 2ba 3-[4-(2,4-Difluoro-phenyl)-enosyl-1-ylmethyl]-1-yloxy-2- 309 200906801 -Phenyl-1,2·dihydro-isoquine Porphyrin_4·carboxylic acid ((s)-i-phenyl-propyl)-guanamine 2bb 3-[4-(3-dimethylamino-propyl)-piperidinyl-yl-methyl] Phenoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-l-phenyl-propyl decylamine 2bc 3-(4-isopropyl-piperidin Methyl)_K side oxyphenyl Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2bd 3-(3-aza-bicyclo[3_2_2]indol-3-ylmethyl)_ι_ side Oxy-2_phenyl-1,2-dihydroisoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2be 3-(4_cyclopentyl-pie Phenyl-1-ylindenyl)_ι_sideoxy-2_phenyldihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2bf 3-Π〆 1]bipiperidin-1·-ylmethyl sideoxy_2_phenyl", 2_dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-醯Amine 2bg 3-(3,4-dihydro-1H-isoquinolin-2-ylmethyl)_ι_sideoxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)·decylamine 2bh 3-[4_(2·Dimethylamino-ethyl)-dethiophene-1-ylmethyl] sideoxy-2- Phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid phenyl-propyl decylamine 2bi 3-(4-hydroxymethyl-piperidin-1-ylindenyl)_;!- side oxygen Base_2_phenyl_I,2-dihydro-isoquinoline_4·carboxylic acid phenyl-propyl)-decylamine 2bj 1-sideoxy-2-phenyl·3-[4-(four Hydrogen-π-propan-2-yl-yl)·π-derhenyl-ιι-methyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl·propyl) _ guanamine 2bk 3- (4-isobutyl-piperidin-1-ylmethyl)-1-yloxy-2_phenylene: dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propane Base)-nonylamine 2bl 3-[4-(2-methoxy-ethyl)-pipedino-1-ylmethyl]_!_sideoxy_2_phenyl-1,2-dihydro-iso Quinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2bm 3-[4-(2-isofolin-4-yl-ethyl)-pitricin-1-yl Methyl] side 310 200906801 . Oxy-2_phenyl-1,2·dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2bn 3-(1,3-dihydro- Isoindole_2_ylmethyl)_丨_sideoxy_2•phenyl_ 1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propylhydrazine Amine 2bo 3-[4-(1-indolyl-piperidine-' kebidine-peptidyl) oxo-2-phenyl-1,2-dihydro-isoquinoline _4_carboxylate Acid phenyl-propyl)-nonylamine 2 bp 1-sided oxy-2-phenyl-3-[4-(2-Bist _1-yl-ethyl)-α- phenyl-methyl]-1, 2-Dihydro-isoquinoline 4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2bq 1-sideoxy-2_phenyl_3_[4_(2_pyrrolidine_ Mercapto-ethyl)-piperidinyl-1-ylmethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2br 3 -(4-didecylaminemethylmercaptomethyl-piperidinylmethyloxy-2-benzol-1,2 - a murine _iso- cylin-4 -nonanoic acid ((S)-l -phenyl-propyl)-bristamine 2bs 3-(octahydro-pyrido[i,2_a]pyridin-2-ylindenyloxy-2_phenyl-I,2-dihydro-isoquinoline 4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2bt 3-(4-carbamimido-[1,4]diazepine cycloheptan-1-ylmethyl)_ __Sideoxy-2-ben 1,2-N-nitrogen-isoindolin-4-teric acid ((S)-l-phenyl-propyl)-bristamine 2bu 3-[4-(4-cyano-phenyl)-branche ^^1-ylmethyl]-1-oxooxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-oxime Amine 2bv 1-tert-oxy-2-phenyl...-(each pyridine-carboxymethyl-piperidin-ylmethyl)-1,2-dihydro-isoindole-4-deoxy acid ((S )-l-phenyl-propyl)-g-padamine 2bw 1-tertiaryoxy-2-phenyl-3-[4-(3-pyrrolidin-1-yl-propyl)-Nantine-1- Methyl]-1,2-dihydro-isoindole HA-4-acid ((S)-l-phenyl-propyl)-bristamine 2 5\1-sideoxy-2-phenyl- 3-(4-Pyridin-2-ylmethyl-piperidin-1-ylmethyl)-1,2-dihydro-isoindole-4-deoxyp-phenyl-propyl)- awake amine 311 200906801 _ 2by 3-(4-B-branched-bromide-1-ylindenyl)-1 -yloxy-2-phenyl_ 1. 2-Dihydro-isoindolin-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2bz 3-(4_t-butyl-piperidin-1-ylmethyl)- 1-Phenoxy-2-phenyl-1,2-dihydro-isoindolyl-4-acid ((S)-l-phenyl-propyl)-decylamine 2ca 3-[4-(1 -ethyl-propyl morphine-1-ylindenyl]-1-oxooxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-benzene Base-propyl)·guanamine 2cb 3-[4-(2-cyano-ethyl)-piperidin-1-ylindenyl]-1-yloxy-2-phenyl-1,2-di Rat-isoindole-4-deoxy acid ((S)-l-phenyl-propyl)_bristamine 2cc 3-(4-曱醯-yl-piperidin-1-ylmethyl)-1- side Oxy-2_phenyl_ 1. 2-Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2cd oxo-2-phenyl- 4-(1-phenyl-propylamine Methyl sulfonyl) _ 1,2-diphos-isowalin-3-ylmethyl]-pyrene-4-yl}-acetic acid acetaminophen 2ce 3-[4-(3-fluoro-phenyl)-per Phenyl-1-ylmethyl]-i_sideoxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)_醯Amine 2cf 1-sided oxy-2 -phenyl-3-((S)-3-phenyl-indole decyl-1-ylmethyl)-1,2-dihydro-isoquinoline-4- Carboxylic acid ((8)-1-phenyl-propyl)-nonylamine I 2cg 1-tertiaryoxy-2-phenyl-3-[4-(pyrrolidin-1.carbonyl)-piperidin-yl Mercapto]-I,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ch 3_[4_(fifolin- 4_|l ano) -α-Desphthyridylmethyl] sideoxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ci 3- (4-methoxy-piperidin-1-ylmethyl)·ι·sideoxy_2_phenyl-indole,)·Dihydro-isoquinoline-4-carboxylic acid ((S)-l- Phenyl-propyl)-nonylamine 2cj 3-(4'-hydroxy-3',4',5',6'-tetrahydro-2indole-[3,4,]bipyridyl 4,-ylmethyl) -1-sided oxy-2-benzene 1,2-dihydro - isoquinolin acid buffer Lin -4- ((; §) _1_ phenyl 312,200,906,801. -propyl)-guanamine 2ck 3-(4-hydroxy-3,4,5,6-tetrahydro-2H-[4,4,]bipyridylmethyl)-1-oxo-2-benzene Base-1,2-dihydro-isoquinoline-4-carboxylic acid (^丨-phenyl-propyl)-guanamine 2cl 3-(3H-spiro[isobenzofuran-丨,4,_piperidine Dioxanyl-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2 (:1113-(4-hydroxy-4-methyl-piperidinyl-1-ylindenyl)_1_sideoxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ( (s)-l-phenyl-propyl;) 醯 guanamine, ' 2en 3- (six wind-snail [benzo[I,3] two junjun_2,4,_0 bottom set]_1,_曱 ))-1-yloxy-2-phenyl-1,2-dihydro-isoindolin-4-acid ((s)-i-phenyl-propyl)-guanamine 2co 1- Oxyloxy-2-phenyl-3-(3,4,5,6-tetrahydro-2H-[4,4,]bipyridyl-1-ylmethyl)-1,2-dihydro-isoquine Porphyrin-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2cp 3-[4-(2-dimethylamino-ethyl)_〇 bottom bite·ι_ylmethyl Side oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2cq 3-(4-didecyl) Aminesulfonyl-pepirin: _1_ylmethyl)_;!_ Oxy-2_1, phenyl-i,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2cr 3-(1,1-two side Oxy-thiomorphin-4-ylmethyl)_1_sideoxy·2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl -propyl)·decylamine 2cs 1-sided oxy-2-phenyl-3-(2-° ratio 0-but-2-ylmethyl-tv-唆-yl- fluorenyl--nitrogen-isoindole -4-Resin ((S)-l-phenyl-propyl)-bristamine 2ct 3-(2-ofolin-4-ylmethyl-piperidin-1-ylindenyl)-1_ side Oxy-2_benyl--milk-isoindolin-4-deoxy-acid benzyl-propyl)-bristamine 2cu 3-(4-furo[3,2-c]pyridin-4-yl-piperidine -1-ylindenyl)_丨_ side 313 200906801 -oxy_2_phenyl-1,2-dihydro-isoquinolin-4-acid ((S)-l-phenyl-propyl) _ Brewed amine 2cv 3-(4-cyclopropyl decyl-piperidinyl)-p-yloxy-2-phenyl-1,2_-wind-iso-lin-4 ((S)-l-phenyl-propyl)-guanamine 2 cw 3-[4-(2-norfosin-4-yl-ethyl)-indole decyl-1-ylmethyl]_ι _Sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2cx 1- oxo-2- benzene -3-(4-pyrimidin-2-yl-[1,4]diazepinecycloheptan-1-ylmethyl)-1,2-dihydro-isoindolin-4-deacid ((S )-l-phenyl-propyl)_醯r. . . 'Amine 2cy 3-(4-methyl-6,7-dihydro-41^-°epeno[3,2-(:]〇〇定_5-ylmethyl)-1-yloxy -2-phenyl-1,2-dihydro-isoindolin-4-indole ((S)-l-phenyl-propyl)-guanamine 2cz 3-[1,4]diazepine Hyun-1-ylmethyl-1_sideoxy-2_phenyl_ 1,2-dihydro-isoquinoline_4_carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2da 3-((2S,5R)-2,5-Dimethyl-indenyl-1-ylmethyl)_ι_ oxy 2 -benyl-1,2-dihydro-isoindole- 4-acidic acid ((S)-l-phenyl-propyl)-bristamine I 2db 3-((S)-3-indolyl-piperidin-1-ylmethyl)-1-yloxy 2_Phenyl-1,2-dihydro-isoindole-4-butyric acid ((S)-l-phenyl-propyl)-bristamine 2dc 3-((R)-3 -曱 base 哄- 1-ylmethyl)-1-o-oxy-2-phenyl-1,2-dihydro-isoindole-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2dd 3-[3-(3-Chloro-phenyl)-piped-1-ylmethyl]-1-oxo-2-phenyl-1,2-dihydro-isoindole-4-deoxasylate ((S)-l-phenyl-propyl)-bristamine 2de 3-[4-(1Η-吲哚-4-yl)-piped-1-ylmethyl]-1-yloxy-2 -Phenyl-1,2-diaza-isowa scare-4-butyric acid ((S)-l-phenyl-propyl)-bristamine 314 200906801 2df 1-Sideoxy_3-(3-Sideoxy-Brigine-1·ylmethyl)-2-phenyl-l,2-dihydro-isoquinolin-4-acid ((S )-l-phenyl-propyl)-guanamine 2dg 3-[4-(1Η-吲哚-5-yl)-piped-1-ylindenyl]-1-sideoxy-2-phenyl -1,2-dihydro-isoquino-4-deoxasy ((S)-l-phenyl-propyl)-acid amine 2dh 3-(6,9-diaza-spiro[4·5]癸_9_ylmethyl)-1_p-oxy-2-phenyl-I,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-醯Amine 2di 3-(1,4-diaza-spiro[5. 5]undec-4-ylmethyl)-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl )_醯amine 2dj 3-(3-isopropyl-pepirin-1-ylmethyl)-1-oxo-2-phenyl-1,2-dihydro-iso-quine-4 - rebellion Acid ((S)-l-phenyl-propyl)-bristamine 2dk 3-(3,3-dimethyl-piperidin-1-ylmethyl)-1-oxo-2-phenyl- 1. 2-Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2dl 3-[3-(4-fluoro-phenyl)-piped-1-yl Methyl]-1-oxo-2-phenyl-1,2-diphos-isoindole-4-hypoacid ((S)-l-phenyl-propyl)-bristamine 2dm 1-side Oxy-2-phenyl-3-(3-p-phenylene-branoid-1-ylindenyl)_ 1. 2-Dinitro--iso-p-quine >-4 - tacrotic acid ((S)-l-phenyl-propyl)-bristamine I 2dn 4-Π-sideoxy-2-phenyl-4- (1-phenyl-propylaminoindenyl)-1,2·dihydro-isoquinolin-3-ylindenyl]-piperidine-1-carboxylic acid tert-butyl ester 2do 3-(4-曱Amidyl fluorenyl-piperidin-1-ylindenyl)_1_sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l- Phenyl-propyl)-nonylamine 2dp 8-gas-3-dimethylaminomethyl-M-oxy-2-phenyl·1,2-dihydro-isoindolin-4carboxylic acid (S)-l-phenyl-propyl)-guanamine 2dr 3-cyclopentylaminomethyl-1-oxo-2-phenyl-1,2-dihydro-isoindole-4- Carboxylic acid ((S)-l-phenyl-propyl)-bristamine 315 200906801 2ds 3-Cyclohexylaminomethyl-tertiaryoxy_2_phenyl-indole, 2-dihydro-isoquinoline- 4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 2dt 3-{[(2-hydroxy-ethyl)-methyl-amino]-methylbubsideoxy_2_ Phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2du 3-imidazole-1-ylindenyl _; 2·笨基基], 2_Dihydroisoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2dv 3-(2-indenyl- Zin-1-ylindenyl)_;!_sideoxy_2_phenyl-indole, 2_dihydro-isoquinoline-4-carboxylic acid ((S)-l·phenyl-propyl)_ Indoleamine, 2dw 3·(4-methyl-imidazolium-1-ylmethyl)-1-oxooxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S )-l-phenyl·propyl)-decylamine 2dx 3-(2,5-dihydro-pyrrol-1-ylmethyl)_;[_sideoxy_2_phenyl-I]·dihydrogen -isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2dy 3-(2,5-dimethyl-2,5-dihydro-.bilo_l- Methyl)_1_sideoxy_2-phenyl-l,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2dz 1-side Oxy-2-phenyl-3-° ratio slightly --i_ylmethyl_ι,2_dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl) - indoleamine i 2ea 1-pivaloxy-2-phenyl-3-(thiazol-2-ylaminoindenyl)-indole, 2_dihydro-isoindole 1#-々-slow acid ((S) -l-phenyl-propyl)-bristamine 2eb 1-sided oxy-2-phenyl-3-(pyrimidin-4-ylaminoindenyl)_ι,2_dihydro-isoindole-4 Acid ((S)-l-phenyl-propyl)-decylamine 2ec 3-(Tertiary butylamino-methyl) pendant oxy-2_phenyl-indole, 2_dihydro-isoquine Porphyrin-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2ed 3-[(2.hydroxy-1,1-dimethyl-ethylamino)-methyl-oxyl-2-phenyl- 1,2·Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl decylamine 316 200906801 2ee 3-(isopropylamino-indenyl)-1-yloxy -2_phenyl-indole, dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ef 3-[(2-hydroxy-1-methylethyl) Amino)-methyl] sideoxy-2_phenyl-1,2-dihydro-isoindolene-4_sodium acid ((S)-l-phenyl-propyl)-decylamine 2eg 3- [(1-hydroxyindolyl-propylamino)-indenyl]_丨_sideoxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l -Phenyl-propyl)-nonylamine 2eh 3-[(2,2-dimercapto-propylamino)-indenyl]_1_sideoxy-2_phenyl-1,2-dihydro- Isoquinoline-4-carboxylic acid ((8)-1-phenyl-propyl)-decylamine 2ei 1-sided oxy-2-phenyl-3-propan-2-ylaminomethyl-i ,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2ej 3-allylamino fluorenyl-1-yloxy_2_benzene -L2-dihydro-isoindoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ek 3-[(indolyl-prop-2-enyl-amino)- methyl] Oxy-2_phenyl_ 1,2-dihydro-isoquinoline_4_carboxylic acid ((s)-!·phenyl-propyl)-decylamine 2el 3-diallylaminomethyl -i_Sideoxy_2_Phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2em 3-diethylamine Methyl-1_1-oxyphenyl_1,2-dihydro-isoindole sigma-4-deoxalate ((S)-l-phenyl-propyl)-bristamine 2en 3_[(isopropyl --methyl-amino)-methyl]-di-oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl ) 醯 2 2o 3-[((S)-2-hydroxy-1-methylethylethyl fluorenyl) • oxo _ 2-phenyl-1,2-dihydro-isoquinoline carboxylic acid Acid ((S)-l-phenyl-propyl)-decylamine 2ep 3-[((R)-2-hydroxy-1_methyl-ethylamino)-methyl]-oxyl_ 2- Phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-;!-phenyl-propyl)_decylamine 317 200906801 2eq 3-{[(2-decyloxy-B ))-fluorenyl-amino]•methyl}·^ sideoxy_2-phenyl-1,2-dihydro-isoindole-4-deoxalate ((S)-l-phenyl-propenyl Base) 醯醯 2er 3-((R)-3·hydroxy--pyrrolidin-1-ylindenyl) 1 side oxyphenyl _ 1,2_dihydro-iso: lin-4-indole ((S)-l - Yl-propyl) - amine _ stuffed 2es 3 - ((S) -3- hydroxy - pyrrolidin-l-ylmethyl) phenyl _ _1_ _2_-oxo-1. 2-Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2et 3-[(cyclopentyl-methyl-amino)-indenyl]-丨_Sideoxy_2_Phenyl-1,2-diindole-isoindole-4-acidic acid ((S)-l-phenyl-propyl)-decylamine 2eu 3-{[(2-hydroxyl -1-fluorenyl-ethyl)-fluorenyl-amino-hydrazinyl-p-oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l· Phenyl-propyl)-bristamine 2ev 3-{[ethyl-(2-trans-ethyl)-amino]-methyl b 1_sideoxy_2_bens-1,2 - —虱Iso-stimulate *-4 - tacrotic acid ((S)-l-phenyl-propyl)_bristamine 2ew 3-[(ethyl-indolyl-amino)-methyl]-l_sideoxy- 2_Phenyldihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2ex 3-cyclobutylaminomethyl-1-epoxy 2· Phenyl-l,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ey 3-tetrahydroindol-1-ylmethyl-1 Sideoxy_2·phenyl-indole, 2·dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2ez 3-(4-t-butyl -Peptin-1-ylindenyl)·! _ sideoxy · 2 phenyl · 1. 2-Dihydro-isoquinoline-4-carboxylic acid ((S)-l·phenyl-propyl)-decylamine 2fa 3-[4-(2-hydroxy-ethyl)-pemamine:-1_曱曱丨丨侧侧侧 _2 _2 _2 · · · · · · · ( ( { { { { { { { { { { { { { { { { { { { { { { 4-[2-(2-Hydroxy-ethoxy)-ethyl]-pemamine: small fluorenyl} + 318 200906801 . Oxyoxy-2 -phenyl-1,2-dihydro-isoindole _4 - tacrotic acid ((S)-l-phenyl·"propyl)-nonylamine 2fc 3-[4-(3 -chloro-5-trifluoromethyl-pyridin-2-yl)-pipedino-1-ylmethyl]-1-oxo-2-phenyl-i,2-dihydro-isoquinoline-4 -carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2fd 3-[4_(3,5-dichloro-oxaridin-4-yl)-piped-1-ylindenyl]- 1-Phenoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-l-styl-propyl)-guanamine 2fe 4-[1- side oxygen Benzyl-2-phenyl-4-((S)-l-phenyl-propylamine fluorenyl)-ί 丨,2-dihydro-iso 01-lin-3-yl fluorenyl]-Brigade" -l-hypo-benzoic acid ester 2ff 3-[4-(3-norfosin-4-yl-propyl)-ninnyl-i-ylmethyl]-1. oxo-2-phenyl- 1,2-dihydro-isoindolin-4-o-acid ((S)-l-phenyl-propyl)-nonylamine 2fg oxime oxy-2_phenyl_3-[4-(3· Piperidin-1-yl-propyl)-piperidin"-ylmethyl]-l,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-oxime Amine 2fh 3-[4_(4,6-dimethoxy-branchone_2_ylmethyl)_〇辰啡-卜基曱基]-1-lateral oxy-2 -phenyl-1,2 -Dihydro-isoindolin-4-deoxalate ((s)-l-phenyl-propyl)-nonylamine L 2fi 3 -[4-(3-Phenylpropyl)"-endo-yl-1-ylmethyl]_ 1_sideoxy-2_phenyl-1,2-dihydro-isoindole-4-acid ( (S)-l-phenyl-propyl)-decylamine 2fj 3-[4-(2,3-dihydroxy-propyl)-piperidin-1-ylindenyl·peroxy-2-phenyl -1,2-dihydro-isoquinoline-4-carboxylic acid phenyl-propyl)-bristamine 2fk (2-o-oxy-2-{4-[l-sideoxy-2-phenyl- 4-(ι_phenyl-propylaminoindenyl)-1,2-dihydro-isoquinolin-3-ylmethyl]-piperidin-j• kibethyl)-tert-butyl carbamic acid 2fl 3-[4-(1Η-oxazol-5-yl)-piperidinyl-1-ylmethyl]small oxy-2_ 319 200906801 Phenyl-1,2-dihydro-isoindole-4- Carboxylic acid ((S)_l-phenyl-propyl)-nonylamine 2fm 1-sided oxy-2-phenyl-3-(4-quinoline-6(yl)-carbomethoxyl-ylmethyl )_ 1,2-Di-argon-isoquinolin-4-carboxylic acid ((S)_1_phenyl-propyl)-nonylamine 2fn 3-[4-(6,7-dimethoxy-carbazole啉-4-yl)-piperidin-1-ylindenyl] 1- 1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l- Stupid-propyl)-guanamine 2fo 4-{4-[1-o-oxy-2-phenyl]-4-(l-phenyl-propylaminomethyl)- 1,2-dihydro- Isoindolin-3-ylmethyl]-endo--1-yl b . -1--1-Resin 3D 3- 2fp 3-{4-[2-(4-Chloro-phenoxy)·ethyl]-Peptin-1-yl-methyl oxime _ sideoxy-2- Phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-bristamine 2fq {4-[1- oxo-2-phenyl- 4-(1-phenyl-propylamine methyl)_1 2-Dihydro-isoquinolin-3-ylmethyl]-pipedino-1-yl}-acetic acid tert-butyl ester 2fr 1-sided oxy-2-phenyl-3-[4-(3,3 , 3-trifluoro-2-yl-propyl)-dethiophenan-1-ylmethyl]-1,2-dihydro-isoindole _4-acidic acid ((S)-l-phenyl -propyl)_醯I Amine 2fs 3-[4-(2-P-propyl-propyl)-pyridin-1-ylindenyl]_ι_sideoxy-2_styl-1,2-dihydro -isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2fu 3-[4-(4-amino-6,7-dimethoxy-喧嗤琳_ 2_基)_〇底啡_ι_ylmethyl]-b-oxy-2-phenyl-l,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl- Propyl)-nonylamine 2fv (2-{4-[1-o-oxy-2-phenyl-4-(1-phenyl-propylaminecarbamyl)- 1. 2-Dihydro-isoquinolin-3-ylmethyl]•piperidin-^-kibethyl)-aminocarboxylic acid 320th 200906801 Tributyl ester 2fw 1-sideoxy-3-{4-[2-(2 - side oxy-imidazolidinyl hydrazinyl) ethyl] _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - Stearic amine 2fx 3-{4_[(4,6-dimethoxy-pyrimidin-2-yl)-phenyl-methyl]-piperidin-1-ylindenyl}-1-sideoxy-2 -phenyl_ι,2_dihydro-isoquinoline_4_carboxylic acid phenyl-propyl)-guanamine 2fy 3-(4~ stupid [I,2,5]thiadiazole_cardiac_ Piperyl bromide methyl)·b-oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((y-bphenyl-propyl)-decylamine 2fz 3 -[4-(2'3-dihydro-benzo[L4]di- stilbene _5_yl) piperene 4 mercapto]-1-yloxy-2-phenyl-1,2-dihydro -isoteryline_4-rebel acid ((s)_i_phenyl-propyl)-guanamine 2ga 3-[4-(4-methyl-quinolin-2-yl)-pipedyl methyl b Bi-oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-l-phenyl-propyl)-decylamine 2gb 1-sideoxy-2- Phenyl-3-[4-(»Bist-2-ylaminocarbamoyl)-piperidin-1-ylindenyl]-1,2-dihydroisoquinoline-4-carboxylate ((S)-l-phenyl-propyl)_ decylamine 2gc 3-[4-(6-chloro-3-indolyl-3,4-dihydro-2H-stupid [1,4] Phenyl-8-yl)-piped-1-ylmethyl]-1-oxo-2-phenyl-1,2-dihydro-isoquinoline_4_carboxylic acid ((S)-l-benzene Base-propyl)-guanamine 2gd 3-(4-Amidinomethyl-piperidin-1-ylmethyl)-1-oxo-2-phenyl-1,2-dihydro-iso啥琳-4-carboxylic acid phenyl propyl)-chatoline 2ge 3-(4-hydroxy-4-phenyl-piperidin-1·ylmethyl)-1_sideoxy-2-benzene 321 200906801 . Base_1,2--wind_isoindene-4-low acid ((S)-l-phenyl-propyl)_bristamine 2gf 3-[4-(4-gas-phenyl)-4- Hydroxy-p-pyridin-1 -ylmethyl]_ι_ oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl) -Acetamine 1-[1-Lactyl-2-phenyl-4-(1-phenyl-propylamine)-l,2-monohydro-isoindol-3-ylmethyl] -π底α定-4-Toxaic acid 2gh 3-(4-cyano-4-phenyl-piperidin-1-ylmethyl)_丨-sideoxy-2-phenyl-1,2-di Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2gi 3-(4-benzyl-4-hydroxy-piperidin-1-ylmethyl)- i.Sideoxy-2-Benzene-based-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2gj 1-[1- side Oxy-2-phenyl-4-(1-phenyl-propylaminemethanyl)-1,2-indolyl-isoindole methyl]-4-phenyl-π bottom bite-4- 2gk 1-Phenoxy-2-phenyl-3-[4-(phenyl-propionyl-amino)-piperidine-buylmethyl]-1,2-dihydro-iso Quinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2gl fluorenyl-{1-[1-o-oxy-2-phenyl-4-(1-phenyl- Propylamine-methyl)-1,2-dihydro-isoquinolin-3-ylmethyl]-peri -4-yl}-aminocarboxylic acid tert-butyl ester, 2gm 1-o-oxy-2-phenyl-3-[4-(2-pyrrolidin-1-yl-ethyl)-piperidine Methyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-styl-propyl)-nonylamine 2gn 3-{4-[5-(4-fluoro-benzene -[1,3,4]oxadiazol-2-yl]-piperidin-1-ylmethyl}-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline 4-carboxylic acid ((S)-l-benyl-propyl)-bristamine 2g〇1-sideoxy-2-phenyl-3-[4-(3-pyridin-4-yl-[1 , 2,4] hired oxazol-5-yl)-piperidin-1-ylindenyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propane ))- guanamine 322 200906801 2gp 1-sided oxy-2-phenyl-3_[4_(3_pyridine_2_yl-[i,2,4] oxadiazole-5-yl)-piperidine -1-ylmethyl]-i,2-dihydro-isoquinoline-4-carboxylic acid ((8)_丨_phenyl-propyl)-decylamine 2 region 9 1-sided oxy-2- Phenyl-3-[4-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)-piperidin-1-ylmethyl]_1,2-dihydro-iso Quinoline_4_carboxylic acid phenyl-propyl)-nonylamine 28圹3-(4'-hydroxy-3',4',5,6'-tetrahydro-2111-[2,4'] Pyridine-1|-ylindenyl-1-oneoxy-2-phenyl-1,2-dihydro-isoquinoline_4-carboxylic acid phenyl-propyl)-S basket Amine 2gs 3-(spiro[isodihydrobenzopyran], 4,-piperidinyl],ylmethyl)-indole_p-oxy-2-phenyl-1,2-dihydro-isoquinoline 4-carboxylic acid ((3)_1_phenyl-propyl oxime 2gt 3 [4 & -4-(3-decyloxy-phenyl)_ brig. _ 卜甲基 methyl methyl] side oxy-2-phenyl-1,2-dihydro-isoquinoline _4-carboxylic acid phenyl-propyl decylamine 2gu 3-[4-(3-chloro-benzene _4-hydroxy-piperidine 丨基 ylmethyl] 丨侧侧 -2- -2- -2- -2- -2- -2- -2- 侧侧侧侧侧侧 ( ( ( ( ( 2) valine 2gv 3-(6-chloro-3H-spiro[isobenzofuranylpiperidine]-benzylmethyl)_b-oxy-2-phenyl-l,2-dihydro-isoquine Porphyrin_4_carboxylic acid phenyl-propyl)-guanamine 2gw 3-(4-{[4-chloro-3-(4-fluoro-phenyl)-indolyl]-methyl-amino} _ piperidin-1-ylindenyl)-1_sideoxy-2_phenyldihydro-isoquinoline_4_carboxylic acid ((S)-l-phenyl-propyl)_bristamine 2gx 3 -(1-Ethyl-pyridyl porphyrin_3,4,- piperidine]·丨,_ylmethyl)_丨_ side 323 200906801 oxy-2-phenyl-1,2-dihydro -isoquinoline_4·carboxylic acid phenyl-propyl)-decylamine 2gy 3-(1-ethylindenyl_5-fluoro-spirobendole _3,4'_ bottom bite]_广Methyl)-1-oxo-2-phenyl- l,2-dihydro-isoquinoline_4_saucy acid ((s)_i_phenyl-propyl)-guanamine 2gz 1-side Oxy-3-(4-oxo-1-phenyl-triaza-spiro[4 5] fluoren-8-ylindenyl)-2-phenyl_ι,2·dihydro-isoquine Oreic acid ((s)-l·phenyl-propyl)-guanamine 2ha 3-(4-ethylhydrazinyl-piperidinylhydrazinyl) sideoxy-2_phenyl-1, 2-Dihydro-isoquinoline_4_carboxylic acid phenyl-propyl)-decylamine 2111) 1-tertiaryoxy-3-(1-sideoxy-2,8-diaza-spiro[4 . 5] 癸_8-ylmethyl)-2-phenyl-1,2-dioxa-isoquinoline_4_carboxylic acid ((s)-l-phenyl-propyl)-decylamine 2hc 3- [4-Hydroxy-4-(3-trifluoromethylphenyl)-piperidinylmethylbubu-p-oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-l-phenyl-propyl amide amine 2hd 1-sided oxy-2-phenyl-3-(4-trifluoromethyl piperidine hydrazinylmethyl 1,2-dihydro -isoquinoline-4-carboxylic acid (((9)-fluorene-phenyl-propyl)-decylamine 2he 3-[4-(4-methyl-piped-i-carbonyl)-piperidine-yl)曱基]_丨_Sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-1-phenyl-propyl)-decylamine 21^3- (5-isopropyl-311-spiro[isobenzofuran_1,4,-piperidinyl]_1,-ylmethyl)-1-yloxy-2-propenyl-1,2-dihydro- Isotope _4_slow acid ((;§)_卜基基_propyl)-guanamine 2hg 3-[4-(ethinyl-methyl-amino)_4•phenyl·piperidinyl Base]_ 324 200906801 1-Sideoxy-2-phenyl-i,2-dihydro-isoquinoline_4-Resin ((s)_i_phenyl-propyl)-nonylamine 2hh 4-{ 1-[1-A side fluorenyl-2-phenylyl_4_(1-phenyl-propylaminoindenyl)-1,2-dihydro-isoquinolin-3-ylindenyl]-piperidine 4-base} - piperidine carboxylic acid tert-butyl ester 2hi (2-{1-[1-o-oxy-2-phenyl-4-(1-phenyl-propylamine fluorenyl)-1,2-31 -isoindol-3-ylindenyl]_〇底〇定-4-yl}-ethyl)-amino decanoic acid tert-butyl ester 2hj 3-(4-methylamino-4-phenyl) Piperidin-1-ylmethyl)-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)- Indole 2hk 3-(4-Ethylamino-4-phenyl-piperidin-1-ylmethyl)-1-oxo-2-phenyl-1,2-dihydro-isoquinoline 4-carboxylic acid phenyl-propyl)-nonylamine 21|丨3-[4-ethylhydrazino-4-(3-fluoro-phenyl)-piperidin-1-ylmethyl]-1_ Sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2hm 1-sided oxy-3-[ 4-(4-Sideoxy-Break-But-1-carbonyl)-B-Bite-Betylmethyl]-2-phenyl-1,2-dihydro-isoindole _4-acidic acid (( S)_1_phenyl-propyl)-acid amine 2hn 3-[4,4,] 联旅. 定-1_yl fluorenyl side oxy-based group 1,2-hydro-isoquinoline -4- Carboxylic acid ((s)_1_phenyl·propyl)-decylamine 2ho {1-[1-Sideoxy_2·Phenyl-4_(Phenylpropylamine)] 1,2 -dihydro-isoquinolin-3-ylmethyl]-D -4- benzylamine dibutyl oxime 2 hp 3-[1 4 ·,] _ 0 _1 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ -isoquinoline-4-carboxylic acid [cyclopropyl-(3-fluoro-phenyl)-indolyl]-decylamine 325 200906801 2hq 1-sided oxy_3_(4-phenethyl-phenantyl fluorenyl) _2_Phenyl-1,2_dihydro-isoindolin-4-carboxylic acid [cyclopropyl-(3-fluoro-phenyl)-methyl]-guanamine 2hr 3-(4-isopropyl- Piperidin-1-ylmethyldi-l-oxy-2-phenyl-1,2-dihydro-iso- 01-lin-t-acid [cyclopropyl-(3-fluoro-phenyl)-indole 2]-branched amine 2hs 3-[4-(2-isofolin-4-yl-ethyl)-piperidin-1-ylindenyl]-1-yloxy-2-phenyl-1,2 -Dihydro-isoquinoline-4-carboxylic acid [cyclopropyl-(3-fluoro-phenyl)-methyl]-bristamine 2ht 3-[4-(b-methyl-piperidin-4-yl)-peri Plung-1-ylindenyl]_1_sideoxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [cyclopropyl-(3-fluoro-phenyl)-methyl ]-decylamine 2hu 1-sided gas-based 2-phenyl-3-[4-(2-0-decyl-1-yl-ethyl)-enosylphinyl-methyl-I-2- Diterpene-isoquinoline-4-carboxylic acid [cyclopropyl-(3-fluoro-phenyl)-methyl]-nonylamine 2hv 1-sideoxy-2_phenyl·3_[4-(2- °Byridine-i_based-B )) kenyl -1- 1-mercapto]-1,2-dihydro-isoindolin-4-deoxalate [cyclopropyl-(3-fluoro-phenyl)methyl]-nonylamine 2hw 1-side Oxy-2·phenyl-3·(4-Acridine-4-ylmethyl_π-endophthylmethyl)-1,2-dihydro-isoquinoline-4-carboxylic acid [cyclopropyl_ (3_Fluorine) Amidoxime 2hx 3-(4-hydroxy-3,4,5,6-r % ° _ 1 -ylmethyl)-1-oxo-2-phenyl -1,2-dihydro-isoquinoline _4_carboxyindole and eat 13⁄4 propyl _(3-ion-phenyl)-methyl]-nonylamine 2hy 3-[4-(2- porphyrin- 4-yl-ethyl)-piperidinyl methyl]-1-flamo-2-phenyl-I,2·dihydro-isoquinoline-4-decanoic acid [cyclopropyl-borine-benzene Base)·甲326 200906801 base]-nonylamine 2hz 3-[4-hydroxy-4-(3-indolyl-phenyl)-piperidin-1-ylmethyl]-1-ylidery-2- Phenyl-1,2-di-iso-iso-lin-4-deoxy acid [[ 哀 propyl-(3- gas-phenyl)_methyl]-nonylamine 2ia 3-[4-(ethenyl- Mercapto-amino)-4-phenyl-piperidin-1-ylindenyl]-1_sideoxy-2-phenyl-1,2-diaza-isoindolyl-4-decanoic acid Propyl-(3- gas-phenyl)-methyl]-nonylamine 2ib 2-(2- gas-phenyl)-1-flavoryl 3-(4-phenylethyl-branol-1 Methyl)-1,2-di -different.奎琳-4- decanoic acid ((S)-l-phenyl-propyl)-bristamine 2ic 2-(2-disorgano-phenyl)-3-(4-isopropyl-α-parphin-1- Methyl)-1-oxooxy-1,2-diaza-isoindole- 4 -decanoic acid ((S)-l-phenyl-propyl)-bristamine 2id 3-[1,4' Bipiperidin-1'-ylmercapto-2-(2-fluoro-phenyl)-1-oxooxy-1,2-diaza-isoindolin-4-indole ((S)-l -Phenyl-propyl)-carbamide 2ie 2-(2-fluoro-phenyl)-3-[4-(2_ofofolin-4-yl-ethyl)-piperidin-1-ylindenyl ]-1-Sideoxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2if 2-(2-chaotic-phenyl) -3-[4-(1-methyl-0 Chen α-1,4-yl)-Budamine 1 -1 -ylmethyl]-1-yloxy-1,2-dihydro-isoquinoline- 4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2ig 2-(2- gas-benyl)-1 - side gas group - 3- [4-(2 - 旅定定- 1-(ethyl-ethyl)_piperidin-1-ylindenyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 21112 -(2-fluoro-phenyl)-1-oxooxy-3-[4-(2-pyrrolidin-1-yl-ethyl)-piped-1-ylmethyl]-1,2-di Hydrogen-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl 327 200906801 base)-guanamine 2ii 2-(2 - rat- Phenyl)-1-flankyl-3-(4-0-butyridine-4-ylmethyl-Briamine 1 -1-ylmethyl)-1,2-dihydro-isoquinoline-4- Carboxylic acid ((8)-1-phenyl-propyl)-decylamine 2ij 2-(2-fluoro-phenyl)-3-(4-hydroxy-3,4,5,6-tetrahydro-211- [4,4']-bipyridin-1-ylmethyl)-1-oxooxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propane Base) - guanamine 2ik 2-(2- gas-stupyl)-3-[4-(2-norfosin-4-yl-ethyl)-α base. Ding-1 _ ylmethyl]-1-yloxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl decylamine 2il 2-(2- Fluoro-phenyl)-3-[4-hydroxy-4-(3-decyloxy-phenyl)-piperidin-1-ylmethyl]-b-oxy-1,2-dihydro-isoquine Porphyrin-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2im 3-[4-(2-isofolin-4-yl-ethyl)-dethiophenan-1-yl Mercapto]-1-oxo-2-o-tolyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)- hydrazine & amine 24 1-Phenoxy-3-[4-(2-piperidin-1-yl-ethyl)-piped-1-ylmethyl]-2-o-tolyl-1,2-dihydro-isoquine Porphyrin-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2io 1-sided oxy-3-(4-pyridin-4-ylmethyl-piped-1-ylmethyl )-2-o-methyl-based-1,2-diaza-isoindolyl-4-decanoic acid ((S)-l-phenyl-propyl)-acid amine 2ip 2-(3- gas-phenyl --1-Alkyloxy-3-(4-phenethyl-benzol-1 -ylmethyl)-1,2-diaza-isovallin-4-decanoic acid ((S)-l-benzene --propyl)-acid amine 2iq 2-(3- gas-phenyl)-3-(4-isopropyl-["-end- phenyl-1-ylmethyl)-1- oxo-1,2- Dihydro-isoquinoline-4-carboxylic acid phenyl-propyl)-decylamine 328 200906 801 2ir 3-[ 1,4']bipiperidin-1'-ylmercapto-2-(3-fluoro-phenyl)-1-yloxy-1,2-diaza-iso-scarred- 4 - citric acid ((S)-l-phenyl-propyl)-nitramine 2is 2-(3-disorganophenyl)-3-[4-(2-norfosin-4-yl-ethyl)-旅明1 -1 _ ylmethyl]-1-yloxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2- (3-Gas-phenyl)-3-[4-(1-methyl-indoledidecyl-4-yl)-Luming:-1 -ylmethyl]-1-yloxy-1,2 - Diterpene-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2iu 2-(3- gas-phenyl)-1-flavoryl- 3- [4 -(2 - 〇 ° ° -1 -yl-ethyl)_piperidin-1-ylmethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-benzene Base-propyl)-acid amine 2iv 2-(3-murine-phenyl)-1 -trioxy-3-[4-(2-0-pyrrolidine-1 -yl-ethyl)-piperidine -1-ylindenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2iw 2-(3- gas-phenyl) -1-Sideoxy-3-(4-0-butoxy-4-ylmethyl-Budamine-1-1-ylindenyl)-1,2-dihydro-isoquinoline-4-carboxylic acid ( (8)-1-phenyl-propyl)-guanamine 2ix 2-(3- gas-phenyl)-3-[4-(2-norfolin-4-yl- ))-派α定-1 _ ylmethyl]-1-yloxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-醯Amine 2-(3- gas-phenyl)-3-[4-lightyl-4-(3-methoxy-phenyl)- lycopene-1-1-ylindolyl]-1-sideoxy- 1,2-dioxin-isoquinoline-4-carboxylic acid phenyl-propyl)-nonylamine 2iz 3-[4-(ethylidene-methyl-amino)-4-phenyl-piperidine- 1-ylindenyl]- 2-(3-fluoro-phenyl)-1-oxooxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-benzene 329 200906801 -propyl)-guanamine 2ja 2-(3-chloro-phenyl)-1-oxo-3-(4-phenethyl-piperidin-1-ylmethyl)-1,2-di wind -isoindole-4-deoxy acid ((S)-l-phenyl-propyl)-bristamine 2jb 2-(3-chloro-phenyl)-3-(4-isopropyl-α-parothin - 1-ylindenyl-1-one-oxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2jc 3-[1, 4']bipiperidin-fluorenyl-methyl-2-(3-chloro-phenyl)-1-yloxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)- L-phenyl-propyl)-guanamine 2jd 2-(3 -mur-phenyl)-3-[4-(2-norfosin-4-yl-ethyl)-parphin-1 fluorenyl ]-1-Sideoxy-1,2-diindole-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propane -) guanamine 2je 2-(3-milo-phenyl)-3-[4-(1-methyl-Bud 0--4-yl)-linphine-1-ylindenyl]-1- side Oxy-1,2-dioxa-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2jf 2-(3-chloro-phenyl)-1-side oxygen 3-[4-(2-piperidin-1-yl-ethyl)-piperidin-1-ylmethyl]-1,2-dioxa-isoquinoline-4-carboxylic acid ((S) -l-phenyl-propyl)·guanamine 2jg 2-(3-aza-phenyl)-1-flavoryl- 3- [4-(2 -σ ratio slightly 0-dec-1-yl-ethyl )-piperidin-1-ylmethyldifluorene-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine 2jh 2-(3_-phenyl-phenyl)-1 - pendant oxy-3-(4·-. Thirteen -1 -4 - fluorenyl-13 - 1 - 1 -ylmethyl)-1,2-di-mouse-isoindole--4-oxo acid ((S)-l-phenyl-prop Base)-bristamine 2ji 2-(3- gas-phenyl)-3-[4-(2-norfosin-4-yl-ethyl)-br.定-1 _ ylmethyl]-1-yloxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 330 200906801 - 2jj 2-(3-Gas-phenyl)-3-[4-hydroxy-4-(3-decyloxy-phenyl)-piperidine-1-ylmethyl] oxo-1,2-dihydro -isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-bristamine 2jk 3_[4'(ethinyl-methyl-amino)-4-phenyl-brazidine- 1-ylindenyl]_ 2_(3-chloro-phenyl)-fluorene-tertiaryoxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl )-decylamine 2 丨1-l-oxy-3-(4-phenethyl-piperidin-1_ylindenyl)_2-m-tolyl·l2-dihydro-isoquinoline-4-carboxylic acid ((s)-l-phenyl-propyl)-guanamine 2jm 3-[1,4']bipiperidinylmethyl-i_sideoxy-2_m-tolyl_1'2 - _虱-isoindole-4 - tacrotic acid ((S)-l-phenyl-propyl)-decylamine 2jn 3-[4-(2-norfolin-4-yl-ethyl)-ninnin-1 -ylmethyl]_ι_sideoxy-2-m-tolyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)_ 酉1 amine 2jo 3-[4-(1-methyl-α- bottom. 1,4-yl)-indolyl-1-ylmethyl]-oxo-2-m-tolyl-1,2-dihydro-isoquine Porphyrin-4-carboxylic acid ((S)-l-benzene --propyl) 醯醯 2jp 1 - oxo-3-[4-(2- ° 咬 -1 -1 -yl-ethyl)·β-deoxyphage-1 _ylindenyl]_2-m-tolyl - hydrazine, 2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)_ decylamine 2jq 1-sided oxy-3-[4-(2-1 〇 ratio 11 each 13-den-1-yl-ethyl)-branoid-1-ylmethyl]-2-m-phenylene-i,2-dihydro-isoindole-4-deacid ((S)- l·Phenyl·propyl)_ decyl 1-l-oxy-3-(4-pyridin-4-ylmethyl-piperidin-1-ylmethyl)_2·metamethyl-1,2- Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 331 200906801 2js 3-[4-(2-TMFolin-4-yl-ethyl)- Piperidine-bylmethylhydrazine-tertiaryoxy-2-m-tolyl-1,2-dioxa-isoquinolin-4-acid ((S)_1_styl-propyl)-acid amine 2jt 3-[4-Hydroxy-4-(3-methoxy-phenyl V piperidin-1ylmethyl)-1_ oxo-2-indenylphenyl-I,2-dihydro-iso Quinoline _4-carboxylic acid ((S)_i-stupyl-propyl)-bristamine 2ju 3-[4-(ethylindolyl-mercapto-amino)-4-phenyl-# 1-ylmethyl]-1-o-oxo-2-m-tolyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-styl-{propyl)-醢Amine 3a 1-sideoxy-3-(2- Oxyl-la-rrolidine-l-ylindenyl)_2_stupyl-1,2-dihydro-isoxanthine_4_jut acid ((S)-l-phenyl-propyl)-nitramine 3b 8-Chloro-bromo-oxy-3_(2·sideoxy-pyrrolidinylmethyl)_2• Stupid-I,2·Dihydro-isoindole·_4_slow acid ((S)-l -phenyl-propyl)-bristamine 4a 3-cyanomethyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4carboxylic acid ((S)-l- Phenyl-propyl)-nonylamine 5a 3-mercapto-1-yloxy-2-phenyl-1,2·diindole-isoquinoline_4_carboxylic acid Ν Ν, Ν-diphenyl-肼5b Ν,-(3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-ylcarbonyl)-fluorene-phenyl-indolecarboxylic acid methyl ester laa 2 -(3-Methoxy-phenyl)-3-methyl-1_sideoxy 2_dihydroiso.奎琳-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine lab 2-(4-methoxy-phenyl)-3-indolyl-l_sideoxy_152_ Dihydro-isoindolin-4-o-acid ((S)-l-phenyl-propyl)-bristamine lac 2-(4-fluoro-phenyl)_3.methyl-oxyl", two Hydrogen_isoquinoline_ 332 200906801 4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine lad 2-(4-chloro-phenyl)-3-methyl-1-yloxy -1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-styl-propyl)-nonylamine lae 3-methyl-1-oxo-2-p-tolyl- 1,2-Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-guanamine laf 2-(3-methoxy-phenyl)-3-methyl- 1-Phenoxy-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-decylamine lag 2-(4 -decyloxy-phenyl)-3-indolyl-1-yloxy-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-benzene) Base)-fluorenyl]-guanamine lah 2-(4-fluoro-phenyl)-3-methyl-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid [(S )-cyclopropyl-(3-fluoro-phenyl)-methyl]-nonylamine lai 2-(4- gas-phenyl)-3-indol-1-yloxy-1,2-dihydro -isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl) -methyl]-nonylamine laj 3-mercapto-1-yloxy-2-p-tolyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-( 3-fluoro-phenyl)-indolyl]-nonylamine lak 2-(2-decyloxy-phenyl)-3-methyl-i-sideoxy-1,2-dihydro-isoindole -4-Resin ((S)-l-phenyl-propyl)-bristamine lal 2-(2-methoxy-phenyl)-3-methyl-1-oxo-1,2- Dihydro-isosporphyrin-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-fluorenyl; decylamine lam 3 -methyl-8-stone succinyl-1-yloxy 2-phenyl-1,2-dihydro-isoindolene-4 - tacrotic acid ((S)_l_phenyl-propyl)-bristamine lan 3-methyl-8-nitro-1-side oxygen Base_2·phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluorophenyl)-methyl]-guanamine lao 8 -曱Oxy-3-methyl-1-oxooxy-2_phenyl·ι,2-dihydroisoquine 333 200906801 Lin-4-acid ((S)-l-phenyl-propyl)_醯Amine lap 8-methoxy-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3 -fluoro-phenyl)-methyl]-nonylamine laq 8-amino-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid Phenyl-propyl)-guanamine lar 8-cyano-3-methyl -1-Sideoxy_2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine las 8-chloro-3- Methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-hypoacid [(S)-l-(4-chloro-phenyl)-propyl]- Amine lat 8-gas-3-mercapto-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4-deconazole [(S)-l-(4-fluoro-benzene ))-propyl]-guanamine lau 8-chloro-3-methyl-1-oxo-2-phenyl-l,2-dihydro-isoquinoline-4-hypoacid [(S)- 1-(2-Iso-phenyl)-propyl]-bristamine lav 8-chloro-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4 - tacrotic acid [(S)-l-(3-chloro-phenyl)-propyl]-decylamine law 8-chloro-3-methyl-1-oxo-2-phenyl-1,2- Diterpene-isoquinoline-4-k J carboxylic acid [(s)-(3·chloro-phenyl)-cyclopropyl·indolyl]-decylamine lax 8-gas-3-methyl-1-side Oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-(4-chloro-phenyl)-cyclopropyl-indenyl]-decylamine lay 8 - Fluoro-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoindole- 4-carboxylic acid [(S)-1-(3-fluoro-phenyl)-propane Base]-nonylamine laz 8-gas·3-methyl-1-oxooxy-2·phenyl-1,2-dihydro-isoquinoline·4-carboxylic acid ((S)-2-methyl _丨_phenyl-propyl _ 醯amine lba 8-chloro_3_methyl-1-oxo-2 phenyl-1,2-dihydro-isoquinoline-4- 334 200906801 酸酸[(S)-cyclopropyl- (4-fluoro-phenyl)-methyl]-nonylamine lbb 8-chloro-3-indolyl-1-yloxy-2-phenyl-1,2-dihydro-isoquinoline-4- rebel Acid [(S)-l-(2-chloro-phenyl)-propyl]-nonylamine lbc 8-chloro-3-methyl-1-oxo-2-phenyl-1,2-dihydro -isoquinoline-4-carboxylic acid ((S)-cyclopentyl-phenyl-fluorenyl)-guanamine lbd 8-chloro-3-methyl-1-oxo-2-phenyl-1, 2-Dihydro-isoquinoline-4-deoxalate [(S)-(2-chloro-phenyl)-cyclopropyl-methyl]-decylamine lbe 8-gas-3-mercapto-1-one Oxy-2-phenyl-1,2-dihydro-isoquinoline-4-deoxalate [(S)-cyclopropyl-(2-fluoro-phenyl)-methyl]-decylamine lbf 8- Chloro-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoindole- 4-carboxylic acid ((S)-cyclohexyl-phenyl-fluorenyl)-decylamine Ibg 8-chloro-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-cyclopropyl-phenyl-methyl )-guanamine lbh 8-chloro-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclobutyl-( 3-fluoro-phenyl)-methyl]-nonylamine lbi 8-chloro-3-methyl-1-oxo-2-phenyl - l,2-Dihydro-isoindole- 4-carboxylic acid [(S)-cyclobutyl-(4-fluoro-phenyl)-indenyl]-decylamine Ibl 8 -chloro-3-methyl- 1-Phenoxy-2-phenyl-1,2-dihydro-isoquinolin-4-carboxylic acid [(R)-cyclopropyl-(3-fluoro-phenyl)-indenyl]-decylamine Lbn 8-chloro-3-indol-1-yloxy-2-phenyl·1,2-dihydro-isoquinoline-4·carboxylic acid ((S)cyclobutyl-phenyl·methyl) - guanamine lbo 8 -chloro-3-methyl-1-oxo-2-phenyl·ι,2·dihydro-isoquine- 4-carboxylic acid [cyclobutyl-(2-fluoro-benzene) Base)-methyl]-nonylamine 2ka 3-(4_t-butyl-piperidin-1-ylmethyl)_8_chloro-indole_sideoxy_2_ 335 200906801 Phenyl-1,2-di Hydrogen-isoquinoline-4-carboxylic acid [(s)-cyclopropyl-(3-fluoro-phenyl)-indenyl]-S-panamine 2 kb 8-chloro-3-(4-isopropyl-piperidin Plough_丨_ylmethyl)_丨·sideoxy-2-phenyl-1,2-dihydroisoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)_醯Amine 2kc 8-chloro-3-(4-isobutyl-piperidin-;[_ylmethyl)-indolyloxyl-1,2-dihydro-isoquinoline-4-carboxylic acid ( (S)-l-phenyl-propyl decylamine 2kd 8-gas _3_(octahydro-pyrido[i,2_a]pyridin-2-ylmethylη-sideoxy-2-phenyl-1 ,2-dihydro-isoquinoline-4-carboxylic acid ( S)-l-phenyl-propyl)-nonylamine 2ke 8-chloro-3-(4-hydroxy-3,4,5,6-tetrahydro-2H-[4,4']bipyridine-1- Methyl)-1-oxo-oxy-2-phenyl-1,2-dihydro-isoquinoline_4_jujubilic acid ((S)-l-phenyl-propyl)-nonylamine 2kf 8- Chloro-3-(4-cyclopropylindenyl-piperidinyl)-p-oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s )-!·Phenyl-propyl)-guanamine 2kg 8-chloro-3-[4-(2-isofolin-4-yl-ethyl)-piperidinylmethyl]- 1 -sideoxy -2-phenyl-1,2-dihydro-isoindolin-4-o-acid ((s)_i_phenyl-propyl)-guanamine 2kh 8-gas-3-[1,4]diazepine Anthracycline-i_yl fluorenyl side oxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid phenyl-propyl)·guanidine 2ki δ-chloro-3_(( S)-3-Methyl-piperidin-1-ylindenyl)-b-oxy-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l- Phenyl-propyl)-guanamine 2kj 8-chloro-3-imidazol-1-ylindolyl_1_sideoxy_2_phenyl. , 孓 dihydrogen _ isoindolin-4-acid ((S)-l-phenyl-propyl)-bristamine 2kk 8-chloro-3-(4-methyl-azizol-1-ylmethyl ) _^ side oxy 2 _ phenyl _ 1,2 - 虱啥啥 -4- -4- 缓缓 ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( Tributylamino-methyl)-8-chloro-1-oxo-2-phenyl-1,2-dichloro-isoindole-4-deoxy acid ((S)-l-phenyl- Propyl)-bristamine 2km 8 -Chloro-3-(isopropylamino-methyl)-1-l-oxy-2 -phenyl-ι, 2_ - a murine-isoindolin-4-deoxy ((S)-l-Phenyl-propyl)- </ RTI> </ RTI> <RTIgt; </ RTI> </ RTI> <RTIgt; _1_1_ylmethyl]-1-oxooxy-2-phenyl-1,2-dihydro-isoindolin-4-o-acid ((s)-i-phenyl-propyl)-醯Amine 2ko 3-(4-t-butyl-piperidin-1-ylindenyl)_8_qi-indole_sideoxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2kp 3-benzimidazol-1-ylmethyl_1_sideoxy_2_phenyl-indole, 2_dihydro-isoline -4-Resin ((S)-l-phenyl-propyl)-decylamine 2kq 1-sided oxy-2-phenyl-3-pyrazole-1-ylmethyl-oxime, 2_two Hydrogen-isoporphyrin-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2kr 3-(4-methyl-oxazol-1-ylmethyl)-b-oxyl 2-phenyl-, dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ks 1-sideoxy-2_phenyl_3-[1, 2,3]triazol-1-ylmethyl dj.indoline-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2kt 2 (3-methoxyl) _本基)_ι_Sideoxy-ylmethyl-piperidin-1-ylmethyl)_1,2-dihydro-isoquinoline_4-carboxylic acid phenyl-propyl)_ decylamine 2ku 2- (4-methoxy-phenyl)_3_[4_(2_ofofolin_cardiyl-ethyl)--0-phenyl-l-ylmethyl]-1 -oxy-1,2-dihydro-异啥琳_4_ Acid ((s)_i _phenyl-propyl)-nonylamine 2kv 2-(4-fluoro-phenyl)_b-oxyl_3_(4-phenylethyl-piperidin-buki 337 200906801 )-l,2--murine-isoindolin-4-teric acid ((S)-l-phenyl-propyl)_bristamine 2kw 2-(4-fluoro-phenyl)-3-(4- Isopropyl-piperidin-1-ylmethyl)-1_sideoxy-1,2-indolyl-isoindolin-4-o-acid ((S)-l-phenyl-propyl) Amine 2kx 3-[1,4']bipiperidin-1'-ylmethyl-2-(4-fluoro-phenyl)-1-yloxy-1,2-dihydro-isoquinoline-4 -carboxylic acid ((S)-l-phenyl-propyl)-decylamine 2ky 2-(4-fluoro-phenyl)-3-[4-(2-folinin-4-yl-ethyl) -piped-1-ylindenyl]-1-oxooxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 2kz 2 -(4-fluoro-phenyl)-3-[4-(1-indolyl-indenyl-4-yl)-indenyl-1-ylindenyl]-1-yloxy-1,2 -Dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)_ tyrosine 21a 2-(4-fluoro-phenyl)-1- oxo-3- [4 -(2_〇 d d each bite-1-yl-ethyl)-D-derived-1-ylmethyl]-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l -phenyl-propyl)-acid amine 21b 2-(4-fluoro-phenyl)-3-[4-hydroxy 4-(3-decyloxy-phenyl)-piperidine-1-ylindolyl-1-oneoxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)- L-phenyl-propyl)-nonylamine 21c 2-(4-disorgano-phenyl)-1-oxooxy_3_(4-phenylethyl- η-phenyl- -1-ylindenyl)-1, 2-Dihydro-isoquinoline-4-carboxylic acid ((s)-l-phenyl-propyl)-decylamine 21d 2-(4-Ga-phenyl)-3-(4-isopropyl basal -1-ylindenyl)-1_sideoxy-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-i-phenyl-propyl)-decylamine 21e 3-[1 , 4']bipiperidin-i'-ylmethyl_2_(4_gas-phenyl) pendant oxy- 1,2-dihydro-isoquinoline _4-carboxylic acid ((s)-i- Phenyl-propyl)-nonylamine 21f 2-(4-chloro-phenyl)-3-[4-(2-ofoline-4-yl-ethyl)-demethyl- _ _ _ _ _ _ 1-yloxy-1,2-dihydro-isoquinolin-4-carboxylic acid ((s)-l-phenyl-propyl)-guanamine 21g 2-(4-gas-benyl ··3-[4-(1-Indolyl-Budidine-4-yl)-demethyl- phenyl-1-ylhydrazino]-1-yloxy-1,2-dihydro-isoquinoline_ 4_oleic acid ((8) small phenyl-propyl)_ decylamine 21h 2-(4-chloro-phenyl)_1_sideoxy_3_[4_(2-piperidin-1-yl-ethyl)_ Phenyl-1-ylindenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((8)-Phenyl-propyl) monodecylamine 21i 2-(4-lactyl-yl)-]_-sideoxy_3-[4-(2-° 比略·u定-1-yl -ethyl)-pipedino-1-ylindenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-nonylamine 21j 3-( 4-t-butyl-piperidin-1-ylindenyl)_8-fluoro-indole-sideoxy-2•phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S) -l-phenyl-propyl)-nonylamine 21k 8-chloro-3-cyclopropylaminomethyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4 -carboxylic acid ((S)-l-phenyl-propyl)-decylamine 211 3-(4-t-butyl-piperidin-1-ylindenyl)-8-fluoro-1-yloxy_ 2_Stupid-1,2-dihydro-isoindole-4-teric acid [(S)-cyclopropyl-(3-fluoro-phenyl)·methyl]_ guanamine 2lm 8-fluoro-1 -Sideoxy_2_phenylpiperidin-1_ylmethyl-I,2-dihydroiso-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl) -methyl]-nonylamine 21η 8-fluoro-1-oxo-3-(3-olyl-pyrazolidin-1-ylindenyl)-2-phenyl-1,2-diindole- Isoquinoline-4-carboxylic acid [(s)-cyclopropyl-(3-fluoro-phenyl)-methyl]-nonylamine 21〇8-fluoro-1-yloxy- 3-(3-side Lacto-α-based 哄-1-ylmethyl)-2-phenyl 339 200906801 - 1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-nonylamine 3c 1-sided oxy-2-phenyl -3-(1Η-[1,2,4]triazol-3-ylsulfanylmethyl)-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl -propyl)-guanamine 3 d 8 - gas-1 - pendant oxy-3 - (2-o-oxy-π pyloryl-l-ylindenyl)-2 - stupid-1,2- Dihydro-isoquinoline-4_carboxylic acid [(8)-cyclopropyl-(3-fluoro-phenyl)-indolyl acid amine 3e 8-fluoro-1-yloxy-3-(2- Oxyloxy-pyrrolidin-1-ylindenyl)-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 3f 8-fluoro-1-oxooxy-3-(2-oxo-oxypyrrolidin-1-ylmethyl)-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-guanamine 3g 8-fluoro-1-oxo-3- (5-side oxy-pyrazolidine-1- Methyl)-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-fluorenyl]-decylamine 3h 8-fluoro-1-oxo-3-(2-oxo-piperidin-1-ylmethyl)-2-phenyl-1,2-dihydro-isoindole-4-deoxy acid [ (S)-cyclopropyl-(3-fluoro-phenyl)-indenyl]-bristamine 3i 8-fluoro-1-indolyl-3-(2-sideoxy -piperidin-1-ylmethyl)-2-phenyl-1,2-dihydro-isoindolyl-4-acid acid [(S)-cyclopropyl-(3-fluoro-phenyl)-fluorene ]]-decylamine 4b 8-chloro-3-cyanomethyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropane Base-(3-fluoro-phenyl)-methyl]-decylamine 6a 2-(3,4-dichloro-phenyl)-3-methyl-1-oxo-1,2-dihydro- Isoquine 340 200906801 Lin-4-Resin ((S)-l-phenyl-propyl)_g basketamine 6b 8-fluoro-1-oxo-3- (2-o-oxy-pyrrolidine-1 -ylindenyl)-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((s)-cyclopropyl-phenyl-methyl)-nonylamine 6c 8-fluoro-3 -mercapto-1-latoxy-2-phenyl-l,2-di-p-isoquinoline-4-carboxylic acid ((S)-cyclopropyl-phenyl-methyl)-decylamine 7a 3 -ethyl-1-oxooxy-2·phenyl-i,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 7b 8-fluoro -3 -Methyl-1-oxooxy-2_phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-decylamine 7c 8 -Fluoro-2-(3-fluoro-phenyl)_3_methyl-oxyl 4,2-dihydro-isoquino-4-deoxalate ((S)-l-phenyl-propyl)_醯Amine 7d 8-fluoro-2-(4-fluoro-phenyl)_3_fluorenyl _; _1>2_Dihydro-isoquinolin-4-acid ((S)-l-phenyl-propyl)-decylamine 8-fluoro-3-methyl-i_sideoxy_2_phenyl -1〗·Dihydro-isoquinoline_4_carboxylic acid [(S)-cyclopropyl-(3-fluorophenyl)-indenyl]-decylamine 7f 8-fluoro-2-(3-fluoro -phenyl)_丨_sideoxy_3_(2_sideoxy-pyrrolidinyl-1-ylmethyl)-1,2-dihydro-isoquinoline_4_carboxylic acid [(s)_ ring Propyl-(3fluoro-phenyl)-methyl]-nonylamine 7g 8-fluoro-2-(4-fluoro-phenyl)-indole_sideoxy_3_(2_sideoxy_D ratio Acridine-1-ylmethyl)-1,2-dichloro-isoquinoline-4-carboxylic acid [(s)-cyclopropyl-(3-fluoro-phenyl)-methyl]-nonylamine 7h 8 -Fluoro-3-methyl small sideoxy 2 -phenyl a, dihydro-isoquinoline 4 -carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenylmethyl)-decylamine 7ι 8-1-2-(2-Fluoro-phenyl)_3_indolyl_1_ side fluorenyl_1,2_dihydro-isoquino 341 200906801 Lin-4-Texic acid [(S)-Cyclopropyl -(3-Fluoro-phenyl)-methyl]-nonylamine 7j 8 -fluoro-2-(3-fluorophenyl)-3-methyl-1-oxo-1,2-dihydro -isoporphyrin-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-nonylamine 7k 8 -fluoro-2-(4-dai-phenyl)-3 -mercapto-1-latoxy-i,2-dihydro-isoindoline_4_carboxylic acid [(S) -cyclopropyl-(3-fluoro-phenyl)-indenyl]-decylamine 71 6,8-difluoro-3-indolyl-1-yloxy-2-phenyl-1,2-dihydro -isoindole _ 4 - slow acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-bristamine 7m 5,8-difluoro-3-indolyl-1-side oxygen Benzyl-2-phenyl-i,2-dihydro-isoquinoline-4-derivative [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-nitramine 7n 3 - A -1-la-oxy-2-phenyl-8-trifluoromethyl-i,2-dihydro-isoquinoline-4-carboxylic acid ((S)-l-phenyl-propyl)-oxime Amine 8a 3-(1-tert-butyl-piperidin-4-ylmethyl)_8-chloro-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid [( S)-cyclopropyl-(3-fluoro-phenyl)-indenyl]-guanamine; and a pharmaceutically acceptable salt of any of the compounds. 86. A compound according to any one of claims n, 19_21, 42_44, 46 68, and L 80-85, which is for use in therapy. 87. a method for treating a disease selected from the group consisting of psychiatric schizophrenia; schizophrenia (schiz〇phren〇f〇rm dis〇rder); schiz〇affective dis〇rder; paranoia (deluSi〇nal diS0rder); temporary psychosis disorder), shared psychosis (such as (d) psych〇dc; psychosis attributed to general medical conditions; substance or drug-induced psychosis (***e, alcohol, amphetamine, etc.); Schizophrenia personality disorder 342 200906801 (schizoid personality disorder); schizoptypal personality disorder • 'psychiatric or schizophrenia associated with severe anxiety; bipolar affective disorder, Alzheimer's disease (Alzheimer's) Disease ) or Parkinson's disease (parkins〇n, s

disease );重度憂鬱症；一般性焦慮症；雙極性情感疾患 (維持治療、復發預防及穩定化）；躁狂（mania);輕症餘狂（hypomania);認知障礙；ADHD ;肥胖症；食慾降低，阿知海默氏症；帕金森氏症；疼痛；驚厥；咳漱；哮喘；氣道過度反應；微血管過敏；支氣管收縮；慢性阻塞 I"生肺病，尿失禁；腸炎；及發炎性腸病，該方法包含向有需要之患者投予治療有效量之如申請專利範圍第1 _85項中任一項之化合物。 88.如申請專利範圍帛87項之方法，其中該疾病為精神***症。 89_如申請專利範圍第88項之方法，其中該治療包含治療精神***症之正性、負性及/或認知症狀。 90. 如申請專利範圍第88項或第89項之方法，其另外包含相伴或相繼投予治療有效量之選自由以下各物組成之列表的化合物·· D2拮抗劑、D2部分促效劑、ρ〇Ει〇拮抗劑、shTm拮抗劑、5_町6拮抗劑及KCNQ4括抗劑。 91. 如申請專利範圍第M、19-21、42-44、46_68、和 80-85項t任—項之化合物，其係用於治療選自以下疾病之疾病：精神病；精神***症；類精神***症；***情感性障礙；妄想症；暫時性精神病；共享型精神病；歸^ 343 200906801 一般醫學狀況之精袖、法· < _>·、# 精柙病，物質或藥物引發之精神病（古驗、酒精、安非他侖：ί · +s lt、丄 u 户他咿寻），類精神***人格異常裂型人格異常：與重度憂誉症有關之精神病或精神分; 症，雙極性情感疾患、阿兹海默氏症或帕金森氏症；重^ 反鬱症’—叙性焦慮症；雙極性情感疾患（維持治療發預防及穩定化）；躁狂；輕症躁狂；認知障礙；八卿. 肥胖症；食您降低；阿茲海默氏症；帕金森氏m 馬厥，咳漱，哮喘；氣道過度反應；微血管過敏；支氣收縮；慢性阻塞性肺病；尿失禁；腸炎；及發炎性腸病。 92·如申凊專利範圍第91項之化合物，其中該疾病為精神***症。取馬精神刀表症之正性、負性及/或認知症狀。 :-：如申請專利範圍第“85項中任一項之化合物之用途，其係用於製造治療選自以下疾病之疾病的醫藥品：精神病；精神***症；類精神***症；***情感性障礙；妄想症，·暫時性精神病；共享型精神病’·歸因於一般醫學狀況之精神病，·物質或藥㈣發之精神病（古柯驗、酒精、***等）’·類精神***人格異常；精神***型人格異常，與重度憂鬱症有關之精神病或精神***症；雙極性情感疾患、阿兹海默氏症或帕金森氏症；重度憂營症· 二:慮症；雙極性情感疾患（维持治療、復發預防及 ;;，餘狂；輕症躁狂；認知障礙；ADHD;肥胖症； “ 阿兹海默氏症；帕金森氏症；疼痛；驚厥；咳 344 200906801 漱’哮喘；氣道過度反應；微▲管過敏；支氣管收縮；，声性阻塞性肺病；尿失禁；腸炎；及發炎性腸病。 95·如申請專利範圍第93項之用途，其中該疾病為精神***症。 96·如申請專利範圍第95項之用途，其中該疾病為精神***症之正性、負性及/或認知症狀。 97. 如申請專利範圍第95項或第96項之用途，其中該製造進一步包含使用選自由以下各物組成之列表的化合物：D2拮抗劑、〇2部分促效劑、PDE10拮抗劑、5_HT 2 A 拮抗劑、5-ΗΤ6拮抗劑及KCNQ4拮抗劑。 98. —種醫藥組合物，其包含如申請專利範圍第丨_85 項中任一項之化合物及一或多種醫藥學上可接受之載劑或賦形劑。 99. 如申請專利範圍第98項之組合物，該組合物另外包含選自由以下各物組成之列表的化合物：D2拮抗劑、D2 部分促效劑、PDE10拮抗劑、5-HT2a拮抗劑、5-HT6拮抗劑及KCNQ4拮抗劑。 10 0 · —種套組，其包含如申請專利範圍第1 _ 8 5項中任一項之化合物以及選自由以下各物組成之列表的化合物： D2拮抗劑、D2部分促效劑、PDE10拮抗劑、5-HT2A持抗劑、5-HT6拮抗劑及KCNQ4拮抗劑。十一、圖式： (無） 345Severe depression; general anxiety disorder; bipolar affective disorder (maintenance therapy, relapse prevention and stabilization); mania; hypomania; cognitive impairment; ADHD; obesity; appetite Hypo, Alzheimer's disease; Parkinson's disease; pain; convulsions; cough; asthma; airway hyperreactivity; microvascular hypersensitivity; bronchoconstriction; chronic obstruction I" lung disease, urinary incontinence; enteritis; and inflammatory bowel disease, The method comprises administering to a patient in need thereof a therapeutically effective amount of a compound according to any one of claims 1 to 85. 88. The method of claim 87, wherein the disease is schizophrenia. 89. The method of claim 88, wherein the treatment comprises treating positive, negative, and/or cognitive symptoms of schizophrenia. 90. The method of claim 88, or claim 89, further comprising administering a therapeutically effective amount of a compound selected from the list consisting of: a D2 antagonist, a D2 partial agonist, ρ〇Ει〇 antagonist, shTm antagonist, 5_cho 6 antagonist and KCNQ4 antagonist. 91. A compound according to the scope of claims M, 19-21, 42-44, 46_68, and 80-85, which is used to treat a disease selected from the group consisting of: psychosis; schizophrenia; Schizophrenia; schizophrenia; paranoia; temporary psychosis; shared psychiatric disease; 343 200906801 General medical condition, sleeves, law, <_>·,#精柙病, substance or drug-induced psychosis (Ancient examination, alcohol, amphetamine: ί · +s lt, 丄u household he is looking for), schizophrenic personality abnormal personality abnormality: mental illness or mental division related to severe anxiety; Polar affective disorder, Alzheimer's disease or Parkinson's disease; heavy ^ anti-depressant' - narrative anxiety; bipolar emotional disorder (maintenance treatment prevention and stabilization); mania; mild mania; cognition Obstacles; 八卿. Obesity; eating you lower; Alzheimer's disease; Parkinson's m horse, cough, asthma; airway overreaction; microvascular allergy; bronchial contraction; chronic obstructive pulmonary disease; urinary incontinence; Enteritis; and inflammatory bowel . 92. The compound of claim 91, wherein the disease is schizophrenia. Take the positive, negative and/or cognitive symptoms of a psychiatric knife. :-: The use of a compound according to any one of the above-mentioned patents, which is for the manufacture of a medicament for the treatment of a disease selected from the group consisting of psychosis; schizophrenia; schizophrenia; Disorder; paranoia, temporary psychosis; shared psychiatric disease's mental illness attributed to general medical conditions, substance or medicine (4) mental illness (coca test, alcohol, amphetamine, etc.)' schizophrenia personality abnormality; Schizophrematic personality abnormalities, psychosis or schizophrenia associated with severe depression; bipolar affective disorder, Alzheimer's disease or Parkinson's disease; severe sorrow syndrome · two: considerations; bipolar affective disorder ( Maintenance treatment, recurrence prevention and;;, madness; mild mania; cognitive impairment; ADHD; obesity; "Alzheimer's disease; Parkinson's disease; pain; convulsions; cough 344 200906801 漱 'asthma; airway Overreaction; micro-▲ tube allergy; bronchoconstriction;, acoustic obstructive pulmonary disease; urinary incontinence; enteritis; and inflammatory bowel disease. 95. If the application of patent scope 93, The disease is schizophrenia. 96. The use of claim 95, wherein the disease is a positive, negative and/or cognitive symptom of schizophrenia. 97. The use of 96, wherein the manufacturing further comprises using a compound selected from the group consisting of a D2 antagonist, a quinone 2 agonist, a PDE10 antagonist, a 5_HT 2 A antagonist, a 5-ΗΤ6 antagonist, and KCNQ4 A pharmaceutical composition comprising a compound according to any one of claims _85 and one or more pharmaceutically acceptable carriers or excipients. The composition of claim 98, further comprising a compound selected from the group consisting of a D2 antagonist, a D2 partial agonist, a PDE10 antagonist, a 5-HT2a antagonist, a 5-HT6 antagonist, and KCNQ4 antagonist. A group comprising a compound according to any one of claims 1 to 8 and a compound selected from the group consisting of: D2 antagonist, D2 partial efficacious Agent, PDE10 Antagonist, 5-HT2A antagonist holders, 5-HT6 antagonists and KCNQ4 antagonists XI, FIG formula: (None) 345