TW201109028A

TW201109028A - HCV protease inhibitors

Info

Publication number: TW201109028A
Application number: TW98131053A
Authority: TW
Inventors: Chen-Fu Liu; Kuang-Yuan Lee; Pei-Chin Cheng; Yo-Chin Liu; Pin Lo; Kuo-Feng Tseng; Chih-Ming Chen; Richard Chi-Hsin King; Chu-Chung Lin
Original assignee: Taigen Biotechnology Co Ltd
Priority date: 2009-09-15
Filing date: 2009-09-15
Publication date: 2011-03-16
Also published as: TWI429450B

Abstract

This invention relates to macrocyclic compounds of formula (I) shown in the specification. These compounds can be used to treat hepatitis C virus infection.

Description

201109028 六、發明說明： c發明戶斤属之技術領域3 本發明係有關於丙型肝炎病毒蛋白酶抑制劑。201109028 VI. Description of the invention: c Inventive technology field 3 The present invention relates to hepatitis C virus protease inhibitors.

H ^tr才支4标J 發明背景丙型肝炎病毒(HCV)是一種(+)有義的單鏈RNA病毒 ((+)-sense single-stranded RNA) ’ 也是主要引起非甲型、非乙型肝炎的致病因數。HCV感染是威脅人類健康的問題。例如參見WO 05/007681 ; WO 89/04669; EP 381216; Alberti 等人的J. Hepatology, 31(增刊 1)，17-24 (1999) ; Alter, J. Hepatology, 31(增刊 1)，88-91 (1999);以及Lavanchy，J. Viral 肝炎，6, 35-47 (1999)。由HCV感染引起的肝炎因為病毒快速突變和避開固有的免疫反應而很難治療。目前僅有的抗-HCV治療劑是幹擾素-α，幹擾素-α/病毒唑組合，以及PEG化的（pegylated)幹擾素-α。但是，發現幹擾素_α或幹擾素_α/病毒唑組合的持續響應率<50%，而且病人會很大程度地受到這些治療劑的副反應影響。例如參見Walker，DDT，4, 518-529 (1999); Weiland，FEMS Microbial. Rev·，14, 279-288 (1994);以及 WO 02/18369。因此，人們仍然需要開發更有效、更易接受的抗HCV藥物。病毒複製所需的HCV蛋白酶包含約3000個氨基酸。它包括核殼體蛋白（C)、包膜蛋白（E1和E2)、以及一些非結構蛋白（NS2, NS3, NS4a，NS5a和NS5b)。 201109028 N S 3蛋白具有絲氨酸蛋白酶活性，被認為是病毒複製和感染所必需。這一點通過黃熱病毒NS3蛋白酶的變異降低病毒感染性、以及HCV NS3蛋白酶活性位點的變異完全抑制了黑猩猩模型中的HCV感染這些現象得以證明。例如參見 Chamber等人的Proc. Natl. Acad· Sci_ USA 87，8898-8902 (1990)以及Rice等人的J. Virol. 74(4) 2046-51 (2000)。另外，發現所述HCV NS3蛋白酶能夠在NS3/NS4a，NS4a/NS4b， NS4b/NS5a，NS5a/NS5b連接點促進蛋白質水解。因此認為 HCV NS3絲氨酸蛋白酶對於病毒複製過程中四種病毒蛋白質的產生有關。例如參見US 2003/0207861。因此，所述 HCV NS3蛋白酶是用來治療HCV感染的一個吸引人的靶標。可能的NS3 HCV蛋白酶抑制劑可以在以下文獻中找到：WO 02/18369，WO 00/09558, WO 00/09543，WO 99/64442, WO 99/07733, WO 99/07734, WO 99/50230, WO 98/46630, WO 98/17679, WO 97/43310, US 5,990,276, Dunsdon等人的，Biorg. Med. Chem. Lett. 10，1571-1579 (2000) ; Llinas-Brunet等人的Biorg. Med. Chem. Lett. 10, 2267-2270 (2000);以及S. LaPlante等人的Biorg· Med. Chem. Lett. 10, 2271-2274 (2000)。【發明内容】發明概要本發明是基於以下出人意料的發現，即某些大環化合物能夠阻斷NS3-4A蛋白酶活性，降低HCVRNA水準，抑制對其他抑制劑对受的HCV蛋白酶突變體，並且在血循環中 201109028 的半衣期延長。在一個方面，本發明涉及下面式⑴的化合物：H ^tr才支四标J Background of the invention Hepatitis C virus (HCV) is a (+) sense single-stranded RNA ((+)-sense single-stranded RNA) ' also mainly causes non-A, non-B The causative factor of hepatitis. HCV infection is a problem that threatens human health. See, for example, WO 05/007681; WO 89/04669; EP 381216; Alberti et al, J. Hepatology, 31 (Supp. 1), 17-24 (1999); Alter, J. Hepatology, 31 (Supp. 1), 88- 91 (1999); and Lavanchy, J. Viral Hepatitis, 6, 35-47 (1999). Hepatitis caused by HCV infection is difficult to treat because of rapid mutation of the virus and avoidance of an innate immune response. The only anti-HCV therapeutics currently available are interferon-alpha, interferon-alpha/ribavirin combinations, and pegylated interferon-alpha. However, the sustained response rate of the interferon-α or interferon-α/ribavirin combination was found to be < 50%, and the patient was greatly affected by the side effects of these therapeutic agents. See, for example, Walker, DDT, 4, 518-529 (1999); Weiland, FEMS Microbial. Rev., 14, 279-288 (1994); and WO 02/18369. Therefore, there is still a need to develop more effective and acceptable anti-HCV drugs. The HCV protease required for viral replication contains approximately 3000 amino acids. It includes nucleocapsid protein (C), envelope proteins (E1 and E2), and some non-structural proteins (NS2, NS3, NS4a, NS5a and NS5b). 201109028 N S 3 protein has serine protease activity and is considered essential for viral replication and infection. This is evidenced by the fact that the mutation of the yellow fever virus NS3 protease reduces viral infectivity and that the variation of the active site of the HCV NS3 protease completely inhibits HCV infection in the chimpanzee model. See, for example, Chamber et al., Proc. Natl. Acad. Sci. USA 87, 8898-8902 (1990) and Rice et al, J. Virol. 74(4) 2046-51 (2000). In addition, the HCV NS3 protease was found to promote proteolysis at the NS3/NS4a, NS4a/NS4b, NS4b/NS5a, NS5a/NS5b junctions. Therefore, HCV NS3 serine protease is thought to be involved in the production of four viral proteins during viral replication. See, for example, US 2003/0207861. Therefore, the HCV NS3 protease is an attractive target for the treatment of HCV infection. Possible NS3 HCV protease inhibitors can be found in WO 02/18369, WO 00/09558, WO 00/09543, WO 99/64442, WO 99/07733, WO 99/07734, WO 99/50230, WO 98/46630, WO 98/17679, WO 97/43310, US 5,990,276, Dunsdon et al, Biorg. Med. Chem. Lett. 10, 1571-1579 (2000); Llinas-Brunet et al. Biorg. Med. Chem Lett. 10, 2267-2270 (2000); and S. LaPlante et al., Biorg. Med. Chem. Lett. 10, 2271-2274 (2000). SUMMARY OF THE INVENTION The present invention is based on the surprising discovery that certain macrocyclic compounds are capable of blocking NS3-4A protease activity, reducing HCV RNA levels, inhibiting HCV protease mutants against other inhibitors, and in circulating blood. The half-length of the 201109028 is extended. In one aspect, the invention relates to compounds of formula (1):

烷基、cM〇雜環烷基、芳基、雜芳基、_Z R或_nh_z_r ;其中R是Η，或者是選自以下的部分：Ci 6烷基、環烷基、 CM{)雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：函素、硝基、氰基、氨基、 Cl.6炫•基Ci.6院乳基、C2_6煉基、C2·6块基、芳基或雜芳其； Z 是 χ(〇)-、-c(o)o-、-c(o)c(o)〇_、-C(0)C(0)NH_、 -C(0)NR’-、-OC(S)-、-C(S)NR，-或-C(NH)〇_，R，是H、Ci 6 烷基、Cwo環烷基、雜環烷基、芳基或雜芳基；R2是H，或者是選自以下的部分：Cw烷基、C3_1Q環烷基、C| |()雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或二取代：iS素、硝基、氰基、氨基、C16烷基、6 烷氧基、C2·6烯基、C2-6炔基、芳基或雜芳基；A*N或cH ; u 是-Ο、-NH-、-NH(CO)-、-NHS(O).或-NHS〇2_ ; w 是 -(CH2)m_ NH(CH2)n-、-(CH2)nNH-、-〇(CH2)n·、_(cH2)n〇-、 -S(CH2)n-、-(CH2)nS-、-S(O)-、-SO(CH2)n-、-(CH2)nS(0)-、 -S〇2(CH2)n-或-(CH2)nS〇2- ’ m疋 1，2 或3，n；^〇，i 或 2 ; x是 201109028 -〇- 、 -S- 、-NH-或-OCH2-;Alkyl, cM〇heterocycloalkyl, aryl, heteroaryl, _Z R or _nh_z_r; wherein R is deuterium or a moiety selected from the group consisting of Ci 6 alkyl, cycloalkyl, CM{) heterocycle An alkyl group, an aryl group and a heteroaryl group, each of which is optionally monosubstituted, disubstituted or trisubstituted by a substituent: a cyclin, a nitro group, a cyano group, an amino group, a Cl. , C2_6 refining group, C2·6 block group, aryl group or heteroaryl; Z is χ(〇)-, -c(o)o-, -c(o)c(o)〇_, -C(0 C(0)NH_, -C(0)NR'-, -OC(S)-, -C(S)NR,- or -C(NH)〇_, R, is H, Ci 6 alkyl, Cwo cycloalkyl, heterocycloalkyl, aryl or heteroaryl; R2 is H, or is selected from the group consisting of Cw alkyl, C3_1Q cycloalkyl, C| |()heterocycloalkyl, aryl And a heteroaryl group, each of which is optionally monosubstituted, disubstituted or disubstituted by the following substituents: iS, nitro, cyano, amino, C16 alkyl, 6 alkoxy, C2·6 alkenyl, C2- 6 alkynyl, aryl or heteroaryl; A*N or cH; u is -Ο, -NH-, -NH(CO)-, -NHS(O). or -NHS〇2_ ; w is -(CH2 M_ NH(CH2)n-, -(CH2)nNH-, -〇(CH2)n·, _(cH2)n〇-, -S(CH2)n-, -(CH 2) nS-, -S(O)-, -SO(CH2)n-, -(CH2)nS(0)-, -S〇2(CH2)n- or -(CH2)nS〇2- 'm疋1,2 or 3,n;^〇,i or 2; x is 201109028 -〇-, -S-, -NH- or -OCH2-;

其中，v和τ各自獨立地是_CH_n 八丨和八2各自獨立地是選自以下的部分：c4_10環烷基、c M〇雜環烧基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：鹵素、硝基、氰基、氨基、c 1 -6 烷基、Cm烷氧基、C2·6稀基、C2·6块基、芳基或雜芳基，或者任選與〇3-|〇環烧基、CM〇雜環烧基、芳基或雜芳基稠合；且Ri是Η、函素、硝基、钪基或氨基，或者是選自以下的部分：Ci_6燒基、C!.6烧氧基、C2-6稀基、C2-6炔基、（〕3-10環燒基、Cmq雜環炫基、芳基和雜芳基，所述C|.6烧基、〇：|_6烷氧基、C2-6烯基和C2·6炔基各自任選被以下取代基單取代、二取代或三取代：li素、硝基、氰基、氨基、Cm烷基、C.M 炫*氧基、€2.6婦基、[2-6块基、匚3.1。環烧基、〇1.1()雜環.炫(基、芳基或雜芳基，C3_l()環烷基、CM()雜環烷基、芳基和雜芳基各自任選被以下取代基單取代、二取代或三取代：鹵素、硝基、氰基 '氨基、Cm烷基、Cw烷氧基、C2-6烯基、C2-6 块基、C3.l0環烷基、CNI()雜環烷基、芳基或雜芳基，或者任選與C3_l()環烷基、CM()雜環烷基、芳基或雜芳基稠合；二疋早鍵或雙鍵。變量U，W，X和Z指定的基團是二價基團。上面所示的 6 201109028 各基團的取向與變量在該結構式中所示的取向相同。以變量U指定-NHSO-基團為例，如該結構式所示，是插在C=〇和R2之間。該-NHS(O)-基團的N原子與C=0相連，S原子與 R2相連。另一個例子是變量Z指定的-C(0)0-插在NH和R之間（即，-NH-Z-R)。-C(0)0-中的C原子與NH相連，Ο原子與 R相連。參見式(I)，化合物的亞組特徵為，RiS-NH-Z-R，其中， Z 是-C(O)-、-C(0)0-、-C(0)C(0)0-或-C(0)C(0)NH- ; R2 '4 >VCH3 是△或△ ; X是Ο ; A是CH ; w是-CH2CH2-、-OCH2-、 -SCH2-或-SOCH〗-，U是-NHS〇2- ; 是雙鍵；或者γ是Wherein v and τ are each independently _CH_n octagonal and octa 2 are each independently selected from the group consisting of c4_10 cycloalkyl, c M 〇heterocyclic alkyl, aryl and heteroaryl, each of which is optional Monosubstituted, disubstituted or trisubstituted by the following substituents: halogen, nitro, cyano, amino, c 1 -6 alkyl, Cm alkoxy, C2·6, C2.6, aryl or a heteroaryl group, or optionally fused to a fluorene 3-? anthracene group, a CM hydrazine heterocyclic group, an aryl group or a heteroaryl group; and Ri is an anthracene, a cycline, a nitro group, a fluorenyl group or an amino group, or Is selected from the following: Ci_6 alkyl, C!.6 alkoxy, C2-6 dilute, C2-6 alkynyl, () 3-10 cycloalkyl, Cmq heterocyclic, aryl and hetero An aryl group, the C|.6 alkyl group, a hydrazine: |6 alkoxy group, a C2-6 alkenyl group and a C2. 6 alkynyl group are each optionally monosubstituted, disubstituted or trisubstituted by the following substituents: Nitro, cyano, amino, Cm alkyl, CM methoxy*, €2.6, [2-6, 匚3.1. Cycloalkyl, oxime 1.1 () heterocycle. Hyun (aryl, aryl) Or a heteroaryl group, each of a C3_l() cycloalkyl group, a CM()heterocycloalkyl group, an aryl group and a heteroaryl group, optionally taken as follows Mono-, di- or tri-substituted: halogen, nitro, cyano 'amino, Cm alkyl, Cw alkoxy, C2-6 alkenyl, C2-6 block, C3.10 cycloalkyl, CNI ( a heterocycloalkyl, aryl or heteroaryl group, or optionally fused to a C3_l() cycloalkyl, CM()heterocycloalkyl, aryl or heteroaryl; diterpene early or double bond. The groups designated by U, W, X and Z are divalent groups. The orientation of each group of 6 201109028 shown above is the same as the orientation shown in the formula. The -NHSO- group is specified by the variable U. For example, as shown in the structural formula, it is inserted between C=〇 and R2. The N atom of the -NHS(O)- group is connected to C=0, and the S atom is connected to R2. Another example is a variable. Z-specified -C(0)0- is interposed between NH and R (ie, -NH-ZR). The C atom in -C(0)0- is connected to NH, and the deuterium atom is connected to R. I), the subgroup of compounds is characterized by RiS-NH-ZR, where Z is -C(O)-, -C(0)0-, -C(0)C(0)0- or -C( 0) C(0)NH- ; R2 '4 > VCH3 is Δ or Δ; X is Ο; A is CH; w is -CH2CH2-, -OCH2-, -SCH2- or -SOCH--, U is - NHS〇2- ; is a double bond; or γ is

Riv ’其中的T是CH或N ; Ri是任選被鹵素、氨基、Ck烧基或Cl-6烧氧基取代的苯基或η塞唑基 (thioazolyl); Rb氏“，Riv>Rv各自獨立地是η、鹵素、硝-基、氰基、氨基、Ck烷基、C,·6烷氧基、c2_6烯基或C2.6炔基，或者是選自以下的部分：C3_1()環烷基、〇11()雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：_素、硝基、氰基、氨基、Ci 6院基、Ci 6院氧基、CM稀基、C2·6炔基、芳基或雜芳基，或者任選與環院基、CM〇雜環烧基、芳基或雜芳基稠合。心的例子是 -NH-C(0)0-t-Bu、-NH-C(0)0-環戊基^0_NH_c(〇x喃基。該化合物的另一個亞組特徵如下，γ是 201109028Riv 'wherein T is CH or N; Ri is phenyl or thioazolyl optionally substituted by halogen, amino, Ck alkyl or Cl-6 alkoxy; Rb's, Riv&R;Rv Independently η, halogen, nitrate-based, cyano, amino, Ck alkyl, C, 6 alkoxy, c2_6 alkenyl or C2.6 alkynyl, or a moiety selected from the group consisting of C3_1() Alkyl, indenyl 11 ()heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: _, nitro, cyano, amino, Ci 6 a thiol group, a Ci 6 alkoxy group, a CM dilute group, a C2·6 alkynyl group, an aryl group or a heteroaryl group, or optionally fused to a ring-based group, a CM fluorene heterocyclic group, an aryl group or a heteroaryl group. Examples are -NH-C(0)0-t-Bu, -NH-C(0)0-cyclopentyl^0_NH_c(〇xyl. Another subgroup of the compound is characterized as follows, γ is 201109028

RiiRii

RiiiRiii

或or

RhRh

Riv 〜丨 Rv ，其中，Ri，Rii，Riii，Riv，R>Rvi各自獨立地是H、鹵素、石肖基、氰基、氨基、C|_6烧基、Ci.6炫·氧基、C2-6稀基、炔基、c3.1()環烷基、CM(，雜環烷基、芳基或雜芳基、環烷基、雜環烷基、芳基和雜芳基各自任選被以下取代基單取代、二取代或三取代：鹵素、硝基、氰基、氨基、C1_6烷基、 C|_6烧氧基、C2·6烤基、C2·6快基、芳基或雜芳基；並任選與 C3-10環坑基、Cl· 10雜環烧基、芳基或雜芳基稠合。在上面的化合物中，Ri可以是例如以下： 201109028Riv~丨Rv, wherein Ri, Rii, Riii, Riv, R> Rvi are each independently H, halogen, schlossyl, cyano, amino, C|_6 alkyl, Ci.6 methoxy, C2-6 A dilute group, an alkynyl group, a c3.1()cycloalkyl group, a CM(,heterocycloalkyl group, an aryl group or a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group are each optionally selected Substituted monosubstituted, disubstituted or trisubstituted: halogen, nitro, cyano, amino, C1-6 alkyl, C|-6 alkoxy, C2-6 alkyl, C2.6 fast radical, aryl or heteroaryl And optionally fused to a C3-10 ring pit group, a Cl.10 heterocycloalkyl group, an aryl group or a heteroaryl group. Among the above compounds, Ri may be, for example, the following: 201109028

(CH2)n(CH2)n

其中，n為1或2。本發明化合物還具有的特徵是，二是單鍵，R2是Where n is 1 or 2. The compounds of the invention also have the feature that the second is a single bond and R2 is

，或^是-H、-OH、C1-6烷基、C,_6烷氧基、（：3-10環烷基、Cmq雜環烷基、芳基或雜芳基，或-Z-R。術語“烷基”表示飽和的直鏈或支鏈烴基部分，如-CH3 或-CH(CH3)2。術語“烷氧基”表示-CKCk烷基）基團。術語 “烯基”表示包含至少一個雙鍵的直鏈或支鏈烴基部分，例如-CH=CH-CH3。術語“炔基”表示包含至少一個三鍵的直鏈或支鏈烴基部分，例如-OC-CH3。術語“環烷基”表示飽和環狀烴基部分，例如環己基。術語“環烯基”表示包含至少一個雙鍵的非芳族的環狀烴基部分。術語“雜環烷基”表示具有至少一個環雜原子（如N，0或S)的飽和環狀部分，例如 4 -四氫吡喃基。術語“雜環烯基”表示具有至少一個環雜原子 (如Ν, Ο或S)和至少一個環雙鍵的非芳族的環狀部分，例如吡喃基。術語“芳基”表示具有一個或多個芳族環的烴基部分。芳基部分的例子包括：苯基(Ph)、亞苯基、萘基、亞萘基、芘基、蒽基和菲基。術語“雜芳基”表示包含一個或多個具有至少一個雜原子（例如N, 0或S)的芳環的部分。雜芳 201109028 基部分的例子包括呋喃基、亞呋喃基、芴基、吡嚷基、喧吩基、噁唑基、咪唑基、噻唑基、吡啶基、嘧啶基、啥唾淋基、啥琳基、異喹琳基和吲β朵基。術語“氨基，，表示、 -NtHCk烷基）或-Νβκ烷基)2的基團。除非另外特別指出，本文所述的烷基、烯基、炔基、環烷基、環烯基、雜環烷基、雜環烯基、芳基和雜芳基包括取代的和未取代的部分。環烷基、環烯基、雜環烷基、雜環烯基、芳基和雜芳基上可能的取代基包括但不限於： q-Ch)烧基' c2-c1()稀基、c2-c10 炔基、c3-c2〇環烷基、C3_C2〇環烯基、C|-C2〇雜環燒基、crC2〇雜環稀基、C|-C1Q；j^氧基、芳基、芳氧基、雜芳基、雜芳氧基、氨基、crc1Q院基氨基、 crC2〇二烷基氨基、芳基氨基、二芳基氨基、CrC|〇烷基氨磺醯基、芳基氨磺醯基、C1„C1G烷基亞氨基、芳基亞氨基、 (^-(:1()烷基磺基亞氨基、芳基磺基亞氨基、羥基、鹵素、疏代、CrCl()烷硫基、芳硫基、CrC|G烷基磺酿基、芳基磺醯基、醯基氨基、氨基醯基、氨基硫代醯基、脒基、胍基、脲基'氰基、硝基、亞硝基、疊氮基、醯基、硫代醯基、醯氧基、羧基和羧酸酯基。另一方面，烷基，烯基或炔基上的取代基包括上述所有取代基，但是C1_CI()烷基除外。環烷基、環烯基、雜環烷基、雜環烯基、芳基和雜芳基還可以相互稠合。下面列出了本發明的281種示例性的化合物。 10 201109028, or ^ is -H, -OH, C1-6 alkyl, C, -6 alkoxy, (: 3-10 cycloalkyl, Cmq heterocycloalkyl, aryl or heteroaryl, or -ZR. "Alkyl" means a saturated straight or branched hydrocarbyl moiety such as -CH3 or -CH(CH3)2. The term "alkoxy" denotes a -CKCkalkyl) group. The term "alkenyl" denotes a straight or branched hydrocarbyl moiety containing at least one double bond, such as -CH=CH-CH3. The term "alkynyl" means a straight or branched hydrocarbyl moiety containing at least one triple bond, such as -OC-CH3. The term "cycloalkyl" denotes a saturated cyclic hydrocarbyl moiety, such as cyclohexyl. The term "cycloalkenyl" denotes a non-aromatic cyclic hydrocarbyl moiety containing at least one double bond. The term "heterocycloalkyl" denotes a saturated cyclic moiety having at least one ring heteroatom (e.g., N, 0 or S), such as 4-tetrahydropyranyl. The term "heterocyclenyl" denotes a non-aromatic cyclic moiety having at least one ring heteroatom (e.g., fluorene, fluorene or S) and at least one ring double bond, such as a pyranyl group. The term "aryl" means a hydrocarbon moiety having one or more aromatic rings. Examples of the aryl moiety include phenyl (Ph), phenylene, naphthyl, naphthylene, anthracenyl, fluorenyl and phenanthryl. The term "heteroaryl" means a moiety comprising one or more aromatic rings having at least one hetero atom (e.g., N, 0 or S). Examples of the heteroaryl 201109028 base moiety include furyl, furanyl, fluorenyl, pyridyl, porphinyl, oxazolyl, imidazolyl, thiazolyl, pyridyl, pyrimidinyl, sulfhydryl, sulfinyl , isoquinolinyl and 吲β-based. The group "amino," means -NtHCk alkyl) or -Νβκalkyl) 2 Unless otherwise specifically indicated, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, hetero Cycloalkyl, heterocycloalkenyl, aryl and heteroaryl groups include substituted and unsubstituted moieties. Possible for cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl groups. Substituents include, but are not limited to: q-Ch) alkyl group c2-c1(), c2-c10 alkynyl, c3-c2 anthracenyl, C3_C2 anthracenyl, C|-C2 anthracene Anthracene, crC2 fluorene heterocyclic, C|-C1Q; j^oxy, aryl, aryloxy, heteroaryl, heteroaryloxy, amino, crc1Q, alkylamino, crC2〇dialkylamino, Arylamino, diarylamino, CrC|decylalkylsulfonyl, arylsulfamoyl, C1 „C1G alkylimino, arylimino, (^-(:1()alkyl sulfonate Imino, arylsulfoimino, hydroxy, halogen, halogenated, CrCl() alkylthio, arylthio, CrC|G alkylsulfonic acid, arylsulfonyl, decylamino, aminoguanidine Base, aminothiononyl, fluorenyl, fluorenyl, ureido'cyano a nitro group, a nitroso group, an azido group, a fluorenyl group, a thioindenyl group, a decyloxy group, a carboxyl group, and a carboxylate group. On the other hand, a substituent on an alkyl group, an alkenyl group or an alkynyl group includes all of the above substitutions. a group, except for a C1_CI() alkyl group. The cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl groups may also be fused to each other. 281 examples of the invention are listed below. Sex compounds. 10 201109028

化合物3Compound 3

化合物10Compound 10

化合物11Compound 11

化合物15 11 tjtl： 201109028Compound 15 11 tjtl: 201109028

化合物20Compound 20

化合物29Compound 29

化合物27Compound 27

12 20110902812 201109028

化合物45 13 201109028Compound 45 13 201109028

化合物50Compound 50

化合物51 化合物49Compound 51 compound 49

FF

化合物60 14 201109028Compound 60 14 201109028

化合物62Compound 62

化合物63Compound 63

化合物64Compound 64

化合物65Compound 65

化合物66Compound 66

化合物67Compound 67

化合物68Compound 68

化合物69Compound 69

化合物73Compound 73

化合物75 15 201109028Compound 75 15 201109028

化合物84Compound 84

化合物87Compound 87

16 20110902816 201109028

化合物99Compound 99

化合物101Compound 101

17 20110902817 201109028

化合物109Compound 109

化合物107Compound 107

化合物110Compound 110

化合物118 化合物119Compound 118 Compound 119

化合物117Compound 117

化合物120 201109028Compound 120 201109028

化合物121Compound 121

化合物122Compound 122

^νΗΛ^νΗΛ

化合物127Compound 127

>>

化合物131 化合物129Compound 131 Compound 129

化合物130Compound 130

19 20110902819 201109028

化合物141Compound 141

20 20110902820 201109028

化合物157Compound 157

化合物152Compound 152

化合物162Compound 162

21 20110902821 201109028

22 20110902822 201109028

化合物194Compound 194

化合物195 23 201109028Compound 195 23 201109028

γΝ 化合物199Ν Ν compound 199

"iNHOCS"iNHOCS

化合物201Compound 201

化合物202Compound 202

化合物203Compound 203

化合物204Compound 204

24 20110902824 201109028

》slv》slv

σΎΎΎ

,Κ, Κ

化合物218Compound 218

化合物223Compound 223

化合物222Compound 222

化合物225 25 201109028Compound 225 25 201109028

化合物239Compound 239

化合物237Compound 237

化合物240 26 201109028Compound 240 26 201109028

化合物242Compound 242

&&

化合物245Compound 245

σ 丫化合物249σ 丫 compound 249

V νκΛ〇〇V νκΛ〇〇

m^TVm^TV

化合物252Compound 252

27 20110902827 201109028

化合物257Compound 257

FF

化合物263Compound 263

V° 化合物269 彳丫:V° Compound 269 彳丫:

化合物272Compound 272

28 20110902828 201109028

化合物275Compound 275

化合物276Compound 276

另一方面，本發明涉及一種治療HCV感染的方法，該方法包括給予需要的病人有效量的上面式（I)的化合物。又一方面，本發明涉及一種用來治療HCV感染的藥物組合物。該組合物包含有效量的至少一種式(I)的化合物和藥學上可接受的載體。可以包含HCV生命週期中除HCV NS3蛋白酶以外的靶標的抑制劑，如NS5B聚合酶，NS5A, NS4B或p7。這類抑制劑的例子包括但不限於：N-[3-(l-環丁基曱基 -4-經基-2-氧代-1,2-二鼠-喧琳-3-基)-1，1-二氧代-1,4-二氮 29 201109028 -116-苯並[1,2,4]噻二嗪-7-基]-曱磺醯胺(W004041818)，反 -1，2-二-4-[(苯基乙醯基比咯烷-2-(S)-羰基）氨基]-苯基乙烯 (W00401413)和 1-氨基金剛炫^Amentadine, Griffin, 2004, J· Gen· Virol· 85: p451)。藥物組合物還可包含免疫調節劑或第二抗病毒劑。免疫調節劑指能介導免疫應答的活性試劑》免疫調節劑的例子包括但不限於，Nov-205(諾瓦勒斯治療劑公司（Novelos Therapeutics Inc.)，W002076490)和 IMO-2125(伊達拉藥物公司（Idera Pharmaceuticals Inc·)， W005001055)。抗病毒劑指能殺滅病毒或抑制病毒複製的活性試劑。抗病毒劑的例子包括但不限於：病毒唑、利巴米定(ribamidin)、幹擾素-a, Peg化幹擾素以及HCV蛋白酶抑制劑，例如2-(2-{2-環己基-2-[〇b嗪-2-羰基)-氨基]-乙醯基氨基}-3,3-二甲基-丁醯基)-八氫-環戊[c]吡咯-1·羧酸（1-環丙基氨基草酿基-丁基），醯胺（Telaprevir，頂尖藥物公司 (Vertex Pharmaceuticals lnc·)，WO02018369)，3-[2-(3-叔丁基-脲基)-3,3-二曱基-丁醯基]-6,6-二曱基-3··氮雜二環[3.1.0] 己烷-2-羧酸(2-氨基甲醯基-1-環丁基甲基-2-氧代-乙基)-醯胺（Boceprevir，先靈堡研究機構（Schering-Plough Research Institute)，WO03062265)和4-氟-1,3-二氫-異吲哚-2-羧酸 14-叔丁氧基羰基氨基-4-環丙磺醯基氨基羰基-2,15-二氧代 -3，16-二氮雜三環[14.3.0.04,6]十九碳-.7-烯-18-基酯 (ITMN-】91，InterMune Inc.，US2005/0267018)。該組合物在治療HCV感染或者製造用於該治療的藥物中的應用也屬於本發明範圍之内。下面對本發明的一個或多個實施方式進行了詳細描 30 201109028 述。由說明書和申請專利範圍可以顯而易見地看出本發明的其它特徵、目標和優點。【實方包方式j 較佳實施例之詳細說明本發明的化合物可以通過本領域眾所周知的方法由可商購的原料製備。例如，可以通過下面的歷幻所示的路徑合成本發明的化合物：二歷程1In another aspect, the invention relates to a method of treating an HCV infection, the method comprising administering to a patient in need thereof an effective amount of a compound of formula (I) above. In still another aspect, the invention relates to a pharmaceutical composition for treating an HCV infection. The composition comprises an effective amount of at least one compound of formula (I) and a pharmaceutically acceptable carrier. Inhibitors of targets other than the HCV NS3 protease in the HCV life cycle, such as NS5B polymerase, NS5A, NS4B or p7, may be included. Examples of such inhibitors include, but are not limited to, N-[3-(l-cyclobutylindolyl-4-yl-2-oxo-1,2-dimur-indolyl-3-yl)- 1,1-dioxo-1,4-diazo 29 201109028 -116-benzo[1,2,4]thiadiazin-7-yl]-indolesulfonamide (W004041818), anti-1,2 -Di-4-[(phenylethenylpyrrolidine-2-(S)-carbonyl)amino]-phenylethene (W00401413) and 1-amino-gumamine^Amentadine, Griffin, 2004, J. Gen· Virol 85: p451). The pharmaceutical composition may also comprise an immunomodulatory agent or a second antiviral agent. An immunomodulator refers to an active agent capable of mediating an immune response. Examples of immunomodulators include, but are not limited to, Nov-205 (Novelos Therapeutics Inc., W002076490) and IMO-2125 (Idala) Drug Company (Idera Pharmaceuticals Inc.), W005001055). An antiviral agent refers to an active agent that kills a virus or inhibits viral replication. Examples of antiviral agents include, but are not limited to, ribavirin, ribamidin, interferon-a, Pegylated interferon, and HCV protease inhibitors, such as 2-(2-{2-cyclohexyl-2- [〇bazine-2-carbonyl)-amino]-ethionylamino}-3,3-dimethyl-butanyl)-octahydro-cyclopenta[c]pyrrole-1·carboxylic acid (1-cyclopropyl) Aminoglycol-butyl), guanamine (Telaprevir, top pharmaceutical company (Vertex Pharmaceuticals lnc.), WO02018369), 3-[2-(3-tert-butyl-ureido)-3,3-didecyl -Butyl]-6,6-dimercapto-3.-azabicyclo[3.1.0]hexane-2-carboxylic acid (2-carbamoyl-1-cyclobutylmethyl-2-oxo- Ethyl)-decylamine (Boceprevir, Schering-Plough Research Institute, WO03062265) and 4-fluoro-1,3-dihydro-isoindole-2-carboxylic acid 14-tert-butoxy Carbonylamino-4-cyclopropanesulfonylaminocarbonyl-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]dodecyl-.7-ene-18-yl ester (ITMN-] 91, InterMune Inc., US 2005/0267018). The use of the composition in the treatment of HCV infection or in the manufacture of a medicament for use in such a treatment is also within the scope of the invention. One or more embodiments of the present invention are described in detail below. Other features, objects, and advantages of the invention will be apparent from the description and appended claims. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The compounds of the present invention can be prepared from commercially available starting materials by methods well known in the art. For example, the compounds of the invention can be synthesized by the path shown in the following illusion:

31 201109028 如歷程1所示，多環化合物⑴首先與^^_(叔丁氧基羰基)-L-脯氨酸(ii)偶聯，然後進行甲基化，形成中間體(丨丨丨）。中間體(m)進行去保護反應，除去N_丁氧基羰基，形成N_ 遊離化合物(iv)，其與羧酸(v)偶聯，形成中間體(vi)。通過水解中間體(vi)，得到酸(vii)，該酸與胺化合物(viy)偶聯，制得具有兩個烯基端基的吼咯烷化合物(ix)。中間體(ix)在格拉布催化劑存在下進行烯烴置換反應，獲得所需的大環化合物（X)〇大環類似物（xi)的雙鍵可以在pd_c存在下進—步氫化，獲得飽和-大環化合物(X丨）。以下歷程2和3顯示兩種本發明化合物的備選合成路線。歷程231 201109028 As shown in Process 1, the polycyclic compound (1) is first coupled with ^^_(tert-butoxycarbonyl)-L-valine (ii) and then methylated to form an intermediate (丨丨丨) . The intermediate (m) is subjected to a deprotection reaction to remove the N-butoxycarbonyl group to form the N-free compound (iv) which is coupled with the carboxylic acid (v) to form the intermediate (vi). By hydrolyzing the intermediate (vi), an acid (vii) is obtained which is coupled with an amine compound (viy) to obtain a pyrrolidine compound (ix) having two alkenyl end groups. The intermediate (ix) is subjected to an olefin displacement reaction in the presence of a groude catalyst to obtain the desired macrocyclic compound (X). The double bond of the macrocyclic analog (xi) can be further hydrogenated in the presence of pd_c to obtain saturation. Macrocyclic compound (X丨). The following Schemes 2 and 3 show alternative synthetic routes for the two compounds of the invention. History 2

32 201109028 歷程332 201109028 History 3

上述方法還包括在歷程1-3中具體描述的步驟之之後進行的步驟，以添加或去除合適的保護基團，茫夠合成所需的化合物。此外，不同合成步驟可以以備^ 的順序或次序進行，以獲得所需的化合物。用於合成式（丨)可應用的化合物的合成化學轉化和保護基團方法（保言蔓#。1 R. 機保護)是本領域已知的，包括例如以下文獻所述的那些： Larock, Comprehensive Organic Transformations(综合有 #允人 VCH 出版社（1989); T.W. Greene 和 P.G.M. WutsThe above process also includes the steps carried out after the steps specifically described in Schemes 1-3 to add or remove suitable protecting groups to synthesize the desired compound. In addition, the different synthetic steps can be carried out in the order or sequence to obtain the desired compound. Synthetic chemical transformation and protecting group methods for the synthesis of (丨) applicable compounds (Baoyan ‧1 R. machine protection) are known in the art and include, for example, those described in the following literature: Larock, Comprehensive Organic Transformations (combined with #允人VCH Press (1989); TW Greene and PGM Wuts

Protective Groups in Organic Synthesis(有機合成中的保士蔓基風）’第二版’約翰威力和薩孫出版社(John Wiley and 33 201109028Protective Groups in Organic Synthesis 'Second Edition' John Power and Sasun Press (John Wiley and 33 201109028

Sons)(1991); L. Fieser和 M. Fieser，Sons) (1991); L. Fieser and M. Fieser,

Reagents for Organic Synthesis(有機合成中的費氏和費氏試 #9，約翰威力和薩孫出版社（1994);以及L. Paquette著的 Encyclopedia of Reagents for Organic Synthesis(用於有機合竑的試#/全幻，約翰威力和薩孫出版社（1995)，以及其隨後的版本。下面實施例1 ·281詳細描述了化合物1 -281的實際製備方式。本文所述的化合物包含非芳族的雙鍵和不對稱中心。因此，所述化合物可以是多種外消旋體和外消旋混合物，簡單對映體，單獨非對映體’非對映體混合物，互變異構體’以及順-異構體或反-異構體形式。可以預期所有這些異構體形式。例如，上面所示結構式⑴的化合物可以具有以下立體化學構型（II):Reagents for Organic Synthesis (Fahrenheit and Fei's Test #9 in Organic Synthesis, John Power and Sasun Press (1994); and Encyclopedia of Reagents for Organic Synthesis by L. Paquette (Test for Organic Compounds # / Full Magic, John Power and Sasun Press (1995), and subsequent editions. The following is a detailed description of the actual preparation of compound 1-281. The compounds described herein contain non-aromatic doubles. Bonds and asymmetric centers. Thus, the compounds can be a variety of racemates and racemic mixtures, simple enantiomers, individual diastereomeric 'diastereomeric mixtures, tautomers' and cis-iso In the form of a conformation or a trans-isomer. All such isomeric forms are contemplated. For example, the compound of formula (1) shown above may have the following stereochemical configuration (II):

上述化合物包括化合物本身，如果適用，包括其鹽，前藥和溶劑化物。例如鹽可由陰離子和結構式⑴的化合物上的正電荷基團（如氨基)形成。合適的陰離子包括：氣離子、溴離子、硫酸根離子、硝酸根離子、磷酸根離子、擰 34 201109028 檬酸根離子、曱磺酸根離子、三氟乙酸根離子、乙酸根離子、蘋果酸根離子、曱苯確酸根離子、酒石酸根離子、富馬酸根離子、谷氨酸根離子、葡糖醛酸根離子、乳酸根離子、戍二酸根離子和馬來酸根離子。類似地’鹽也可以由陽離子和結構式(I)的化合物上的負電荷基團（如敌酸根）形成。合適的陽離子包括鈉離子、鉀離子、鎂離子、鈣離子和錄陽離子，如四曱基錢離子。結構式(I)的化合物還包括含季氮原子的那些鹽。前藥的例子包括酯類和其他藥學上可接受的衍生物，這些前藥在給予病人後能夠提供結構式 ⑴的活性化合物。溶劑化物指在結構式（I)的活性化合物和藥學上可接受的溶劑之間形成的配合物。藥學上可接受的溶劑的例子包括水，乙醇，異丙醇，乙酸乙酯，乙酸和乙醇胺。本發明範圍之内的一種治療HCV感染的方法是通過給予病人有效量的一種或多種結構式(I)的化合物。術語“治療的”或‘‘治療”表示給予感染了 HCV、表現出感染HCV的症狀、或者易受HCV感染的對象所述化合物，以獲得治療效果，例如治癒、緩解、改變、影響、改善或防止HCV感染、感染HCV的症狀、或者易受HCV感染的傾向。術語“有效量” 表示使得被治療的對象獲得治療效果所需的本發明活性化合物的量。本領域技術人員應當認識到，有效劑量可根據所治療的疾病種類、給藥途徑、所用賦形劑、以及可能並行採用的其它治療而改變。本發明的化合物可以以有效水準長時間保留在血循環 35 201109028 中。因此，這些化合物可以每天一次給予有效量以提供治療效果。為了實施本發明的方法，包含一種或多種本發明化合物的組合物可以胃腸外給藥、口服給藥、鼻内給藥、直腸給藥、局部給藥或含服。術語“胃腸外”表示皮下注射，皮内注射，靜脈注射，肌内注射，關節内注射，動脈内注射，滑膜内注射，胸骨内注射，鞘内注射，傷口注射或顱内注射，以及任何合適的注射技術。無菌可注射組合物可以是位於無毒的胃腸外可接受的稀釋劑或溶劑中的溶液或懸浮液，例如在1,3 - 丁二醇中的溶液。可採用的可接受的媒介物和溶劑為甘露醇，水，林格溶液和等滲氯化鈉溶液。另外，通常使用非揮發性油作為溶劑或懸浮介質（例如合成的單甘油酯或二甘油酯）。脂肪酸，例如油酸及其甘油醋衍生物可用來製備可注射製劑，例如可使用藥學上可接受的天然油類，例如橄欖油或蓖麻油，特別是它們的聚氧基乙烯化形式。這些油溶液或懸浮液還可包含長鏈醇稀釋劑或懸浮劑，羧甲基纖維素或類似的分散劑。其它常用的表面活性劑，例如吐溫(Tween)或司盤（Span)或通常用於生產藥學上可接受的固體、液體或者其它劑型的其它類似的乳化劑或生物利用度促進劑，也可用來配製藥物組合物。用於口服給藥的組合物可以是任何可以接受的口服劑型，包括膠囊、片劑、乳液和水懸浮液、分散體和溶液。對於片劑，常用的載體包括乳糖和玉米澱粉。通常還可加 36 201109028 入潤滑劑，例如硬脂酸鎂。對於膠囊形式的口服給藥，可用的豨釋劑包括乳糖和乾燥的玉米澱粉。當水懸浮液或乳液口服給藥時’可以將活性成分懸浮或溶解在與乳化劑或懸浮劑合併的油相中。如果需要’可以加入某些甜味劑、香料或著色劑。可以根據藥物製劑領域眾所周知的技術製備鼻噴霧劑或吸入組合物。例如，可使用苄醇或其它合適的防腐劑、提高生物利用度的吸收促進劑、氟代烴、和/或本領域已知的其它增溶劑或分散劑，將這樣的組合物製成在鹽水中的溶液° 包含-種或多種本發明的活性化合物的組合物還可以成栓劑的形式’用於直腸給藥。所述藥物組合物中的載體必須是“可以接受，，的，即與組合物的活性成分相容(優選能夠使活性成分穩定化），且= 會對被治療賴象造成不鄉響。可以將—種❹種增溶劑作為絲遞送本發明的活性化合物的藥物賦形劑。其它載體的例子包括膠體氧切、硬麟鎂、纖維素、月桂二硫酸納和D&C# 10黃。土本發明的化合物可以與第二抗HCV試劑一起用來治 HCV，這些第二抗HCV試劑包括例如在Hcv生命週期中卜 HCV NS3蛋白酶以外的乾標的抑制劑 '免疫調節劑和其二抗病毒試劑。本發明的化合物和第二抗Hcv試劑可以同施用給藥或在不同時間給藥。對於同時給藥，可以將二試劑混合形成單-藥丸’或者單獨製成藥丸。兩種試劑^ 37 201109028 自以一定的量服用，使得它們的總量為熟練技術人員認可的治療HCV的有效量。可以通過體外試驗（參見實施例282和283)初步篩選上述本發明化合物在治療HCV感染方面的效力，然後通過動物試驗和臨床試驗確定。其他方法對本領域的普通技術人員而言也是顯而易見的。下面的實施例僅僅是說明性的，並不以任何方式對說明書的其它部分構成限制。我們相信，本領域的技術人員基於本文的描述，無需另外的工作便可最完整程度地利用本發明。本文引用的所有出版物的全文全部以引用的方式納入本文作為參考。實施例1 : 合成{4-環丙績酿基氨基叛基-2,15-二氧代-18-[2-(4-二氟曱基-苯基)-苯並[4,5]呋喃並[3,2-d]嘧啶-4-基氧基:丨-3,16-二氮雜三環[14.3.0.04,6]十九烷-14-基}-氨基甲酸環戊酯（化合物1) 化合物1-3首先由可商購的1-叔丁氧基羰基氨基-2-乙烯基-環丙烷羧酸乙酯通過以下所示路線製備：The above compounds include the compound itself, if applicable, including its salts, prodrugs and solvates. For example, the salt may be formed of an anion and a positively charged group (e.g., an amino group) on the compound of formula (1). Suitable anions include: gas ion, bromide ion, sulfate ion, nitrate ion, phosphate ion, screw 34 201109028 citrate ion, sulfonate ion, trifluoroacetate ion, acetate ion, malate ion, strontium Benzoate ion, tartrate ion, fumarate ion, glutamate ion, glucuronide ion, lactate ion, sebacate ion and maleate ion. Similarly, the salt may also be formed from a cation and a negatively charged group (e.g., a diacidate) on the compound of formula (I). Suitable cations include sodium ions, potassium ions, magnesium ions, calcium ions, and cations such as tetradecyl hydroxy ions. The compounds of formula (I) also include those containing a quaternary nitrogen atom. Examples of prodrugs include esters and other pharmaceutically acceptable derivatives which, upon administration to a patient, provide the active compound of formula (1). Solvate refers to a complex formed between the active compound of formula (I) and a pharmaceutically acceptable solvent. Examples of pharmaceutically acceptable solvents include water, ethanol, isopropanol, ethyl acetate, acetic acid and ethanolamine. One method of treating HCV infection within the scope of the present invention is by administering to a patient an effective amount of one or more compounds of formula (I). The term "therapeutic" or "treatment" means the administration of a compound to a subject infected with HCV, exhibiting symptoms of HCV infection, or susceptible to HCV infection, to achieve a therapeutic effect, such as healing, ameliorating, altering, affecting, ameliorating or Prevention of HCV infection, symptoms of HCV infection, or a predisposition to HCV infection. The term "effective amount" means the amount of active compound of the invention required to achieve a therapeutic effect in a subject being treated. Those skilled in the art will recognize that effective The dosage may vary depending on the type of disease being treated, the route of administration, the excipients employed, and other treatments which may be employed in parallel. The compounds of the present invention may remain in the blood circulation 35 201109028 at an effective level for a long time. Therefore, these compounds may An effective amount is administered once a day to provide a therapeutic effect. In order to practice the methods of the invention, compositions comprising one or more compounds of the invention may be administered parenterally, orally, intranasally, rectally, topically or Contains the service. The term "parenteral" means subcutaneous injection, intradermal injection, intravenous Injection, intramuscular injection, intra-articular injection, intra-arterial injection, intrasynovial injection, intrasternal injection, intrathecal injection, wound injection or intracranial injection, and any suitable injection technique. Sterile injectable composition can be located in non-toxic a solution or suspension in a parenterally acceptable diluent or solvent, for example, in 1,3-butanediol. Acceptable vehicles and solvents that may be employed are mannitol, water, Ringer's solution and Isotonic sodium chloride solution. In addition, non-volatile oils are usually used as a solvent or suspension medium (for example, synthetic monoglycerides or diglycerides). Fatty acids, such as oleic acid and its glycerin derivatives, can be used to prepare injectable preparations. For example, pharmaceutically acceptable natural oils such as olive oil or castor oil, especially in their polyoxyethylated form, may be employed. These oil solutions or suspensions may also contain a long-chain alcohol diluent or suspending agent, carboxy Methylcellulose or similar dispersing agents. Other commonly used surfactants, such as Tween or Span, or commonly used to produce pharmaceutically acceptable solids, Other similar emulsifiers or bioavailability enhancers for body or other dosage forms may also be used to formulate pharmaceutical compositions. Compositions for oral administration may be in any acceptable oral dosage form including capsules, tablets, lotions and Aqueous suspensions, dispersions and solutions. For tablets, commonly used carriers include lactose and corn starch. It is usually also possible to add 36 201109028 to a lubricant such as magnesium stearate. For oral administration in capsule form, available release The agent comprises lactose and dried corn starch. When the aqueous suspension or emulsion is administered orally, the active ingredient can be suspended or dissolved in the oil phase combined with the emulsifier or suspending agent. If desired, certain sweeteners can be added. , perfume or colorant. Nasal sprays or inhalation compositions can be prepared according to techniques well known in the art of pharmaceutical formulation. For example, benzyl alcohol or other suitable preservatives, absorption enhancers that increase bioavailability, fluorohydrocarbons, and / or other solubilizing or dispersing agents known in the art, such compositions are prepared as solutions in saline. The compositions of the various active compounds of the invention may also be administered in the form of a suppository' for rectal administration. The carrier in the pharmaceutical composition must be "acceptable, that is, compatible with the active ingredients of the composition (preferably capable of stabilizing the active ingredient), and = will cause a discomfort to the treated subject. A pharmaceutical excipient that delivers the active compound of the present invention as a silk. Examples of other carriers include colloidal oxygen, hard magnesium, cellulose, sodium lauryl sulfate, and D&C#10 yellow. The compounds of the invention can be used to treat HCV with a second anti-HCV agent, including, for example, a dry-labeled inhibitor of the HCV NS3 protease in the Hcv life cycle, an immunomodulator and a second antiviral agent. The compound of the present invention and the second anti-Hcv agent may be administered as the same or at different times. For simultaneous administration, the two agents may be mixed to form a single-pill or separately into a pill. Two reagents ^ 37 201109028 They are administered in a quantity such that their total amount is an effective amount for the treatment of HCV as recognized by the skilled artisan. Initial screening can be performed by in vitro assays (see Examples 282 and 283). The efficacy of the compounds of the invention in the treatment of HCV infection is then determined by animal and clinical trials. Other methods will be apparent to those of ordinary skill in the art. The following examples are illustrative only and are not intended in any way. The other parts of the specification constitute limitations. It is believed that those skilled in the art, based on the description herein, may use the present invention to the fullest extent without additional work. The entire disclosure of all publications cited herein is hereby incorporated by reference in its entirety Reference Example 1: Synthesis of {4-cyclopropanediaminocarbamicin-2,15-dioxo-18-[2-(4-difluoroindolyl-phenyl)-benzo[4,5 Furano[3,2-d]pyrimidin-4-yloxy:indole-3,16-diazatricyclo[14.3.0.04,6]nonadecane-14-yl}-carbamic acid cyclopentyl ester (Compound 1) Compound 1-3 was first prepared from the commercially available ethyl 1-tert-butoxycarbonylamino-2-vinyl-cyclopropanecarboxylate by the following route:

HATU,DIPEA, DBU DMAP, CH2CI2HATU, DIPEA, DBU DMAP, CH2CI2

38 201109028 向1-叔丁氧基羰基氨基-2-乙烯基_環丙烷羧酸乙酯 (0.34克，1_3毫摩爾）在THF(5毫升)和甲醇(5毫升）的溶液中加入1^〇11(0.13克’5.3毫摩爾）水的懸浮液。室溫攪拌過夜後’用10% HC1(2毫升)使反應猝滅，真空下去除溶劑。產生的固體粉末用水（10毫升）洗滌，得到化合物μΐ(〇.27克， 90%) ° MS m/z 249.9(M++23) ； !H NMR(CDC13) δ 10.35(brs, 1H), 5.84-5.71(m, 1H), 5.29(d, J = 17.4 Hz, 1H), 5.12(d, J = 10.2 Hz, 1H), 2.23-2.14(m, 1H), 1.87-1.65(m, 1H), 1.58-1.41 (m, 1H)，1.43(s，9H)。於室溫攪拌化合物I-l(0_52克，2.3毫摩爾）、2-(lH-7-氮雜苯並三。坐-1-基)-l，l，3,3-四曱基腺陽離子(uronium)六氟 -填酸鹽曱銨(methanaminium)(HATU，1.74克，4.6毫摩爾）和4-二甲基氨基°比〇定（1.39克，11.6毫摩爾）在(1^2〇!12(40毫升) 中的溶液，隨後在15分鐘内緩慢加入環丙烷磺醯胺（0.57 克，4.7毫摩爾）、二異丙基乙胺（1.81毫升，14_0毫摩爾）和 1,8-二氮雜二環[5,4,0]十一碳-7-烯（1.80克，11·7毫摩爾）。於室溫攪拌反應混合物過夜之後，真空下去除溶劑。殘餘物通過矽膠柱色譜純化，得到化合物1-2(0.51克，66%)。 MS m/z 353.1(M++23) ； !H NMR(CDC13) δ 9.75(brs, 1H), 5.64-5.51(m, 1H), 5.30(d, J = 17.4 H), 5.l6(d, J = 10.2 Hz, 1H), 2.95-2.89(m, 1H), 2.19-2.10(m, 1H), 1.93-1.88(m, 1H), 1.47(s, 9H), 1.46-1.38(m, 1H), 1.32-1.23(m, 2H), 1.15-1.00 (m，2H)。在室溫下向化合物1-2(0.50克，1.5毫摩爾）在MeOH(8 39 201109028 毫升）中的溶液加入SOC12(0.26克，2.2毫摩爾）。反應混合物回流1小時之後，真空除去MeOH和S0C12。殘餘物用戊烷磨碎，過濾得到米白色固體中間體1-3(0.32克，91%)。MS m/z (M++l) ； 'H NMR(CD3COD) δ 5.77-5.65(m, 1Η), 5.43(d, J = 17.4 Hz, 1H), 5.32(d, J = 10.2 Hz, 1H), 3.06-2.97(m, 1H), 2.45(dd, J = 17.4 Hz, J = 7.8, 1H), 2.16(dd, J = 8.0 Hz, J = 7.8 Hz, 1H), 1.75(dd, J = 10.1 Hz, J = 7.8 Hz, 1H), 1.32-0.86 (m, 4H) 〇化合物1通過以下路線製備： 40 20110902838 201109028 To a solution of ethyl 1-tert-butoxycarbonylamino-2-vinyl-cyclopropanecarboxylate (0.34 g, 1-3 mmol) in THF (5 mL) A suspension of 11 (0.13 g '5.3 mmol) of water. After stirring overnight at room temperature, the reaction was quenched with 10% EtOAc (2 mL). The resulting solid powder was washed with water (10 ml) to give compound EtOAc (m.sup.27 g, 90%), MS m/z 249.9 (M++23); NMR (CDC13) δ 10.35 (brs, 1H), 5.84-5.71(m, 1H), 5.29(d, J = 17.4 Hz, 1H), 5.12(d, J = 10.2 Hz, 1H), 2.23-2.14(m, 1H), 1.87-1.65(m, 1H) , 1.58-1.41 (m, 1H), 1.43 (s, 9H). Stir compound Il (0-52 g, 2.3 mmol), 2-(lH-7-azabenzotriene.sodium-1-yl)-l,l,3,3-tetradecyl gland cation (uronium) at room temperature Hexafluoro-salt ammonium methanaminium (HATU, 1.74 g, 4.6 mmol) and 4-dimethylamino group (1.39 g, 11.6 mmol) at (1^2〇!12 ( The solution in 40 ml), followed by the slow addition of cyclopropanesulfonamide (0.57 g, 4.7 mmol), diisopropylethylamine (1.81 ml, 14_0 mmol) and 1,8-diaza in 15 minutes. Bicyclo[5,4,0]undec-7-ene (1.80 g, 11.7 mmol). After stirring the reaction mixture at rt overnight, solvent was evaporated in vacuo. Compound 1-2 (0.51 g, 66%) MS m/z 353.1 (M++23); NMR (CDC13) δ 9.75 (brs, 1H), 5.64-5.51 (m, 1H), 5.30 (d) , J = 17.4 H), 5.l6(d, J = 10.2 Hz, 1H), 2.95-2.89(m, 1H), 2.19-2.10(m, 1H), 1.93-1.88(m, 1H), 1.47( s, 9H), 1.46-1.38 (m, 1H), 1.32-1.23 (m, 2H), 1.15-1.00 (m, 2H). Compound 1-2 (0.50 g, 1.5 mmol) at room temperature In MeOH (8 39 201109028 ml) The solution was added to EtOAc (EtOAc (EtOAc) (EtOAc). MS m/z (M++l); 'H NMR (CD3COD) δ 5.77-5.65 (m, 1 Η), 5.43 (d, J = 17.4 Hz, 1H), 5.32 (d, J = 10.2 Hz, 1H ), 3.06-2.97(m, 1H), 2.45(dd, J = 17.4 Hz, J = 7.8, 1H), 2.16(dd, J = 8.0 Hz, J = 7.8 Hz, 1H), 1.75(dd, J = 10.1 Hz, J = 7.8 Hz, 1H), 1.32-0.86 (m, 4H) 〇 Compound 1 was prepared by the following route: 40 201109028

HATU. HOBt, NNM CH2C12HATU. HOBt, NNM CH2C12

MlMl

H：,PdCH:, PdC

MeOHMeOH

於〇°C攪拌3-氨基-笨並呋喃-2-羧酸醯胺（1.00克，5.7毫摩爾）和吡啶（1毫升，12.26毫摩爾）在THF(25毫升）中的溶液 10分鐘。向形成的溶液中緩慢加入4-三氟曱基-苯甲醯氣 41 201109028 (1·48克，7.1毫摩爾）。然後將溫度升高至室溫，攪拌混合物 12小時。減壓下除去溶劑之後，收集形成的固體，用水洗滌，空氣乾燥後得到 1-4(1.92克，96.0%)。MS: m/z 349.0 (M++1) 〇 1-4(1.92克，5.5毫摩_)和2\\3〇玫13毫升)在玢011(25 毫升）的懸浮液於85°C加熱12小時。冷卻之後，將混合物酸化’然後除去EtOH。收集形成的固體，過濾，用水洗滌，乾燥後獲得 1-5(1.71 克，95.0%)。MS m/z 331(M++1)。將1-5(1.71克，5.2毫摩爾）和過量磷醯氣(POCl3)的溶液回流2小時。冷卻並且完全濃縮之後，混合物用二氯甲烷和 10%氫氧化鈉萃取。有機層用MgS04乾燥，濃縮，用CH2C12 和正己烷結晶，得到化合物1-6(1.49克，82%) = MS m/z 348.8, 350.9(M+-H) ； Ή NMR(CDC13) δ 8.70(d, 2Η), 8.34(d, 1H), 7·82·7_75(ητ，4H)，7.57(ddd，1H)。 0°C，向Boc-反-4-羥基-L-脯氨酸(0.53克，2.3毫摩_) 在DMSO(25毫升）的懸浮液中加入t-BuOK(0.82克，5.1毫摩爾）。使該混合物溫熱至室溫並攪拌1小時後，與】0°C緩慢加入化合物丨-6(0.81克，2.3毫摩爾）。繼續攪拌過夜。加入碘曱烷（1·02克，6.9毫摩爾）’室溫下再搅拌反應混合物30 分鐘。反應混合物用10% HC1水溶液中和至pH為6-7，並用二氣甲烷進行萃取。有機層用MgS04乾燥，真空蒸發，並通過矽膠柱層析純化，得到化合物1-7( 1.12克，86%)。MS m/z 557.8(M++1) ； 'H NMR(CDC13) δ 8.63(d, 2Η), 8.28(d, 1H), 7.80-7.74(m, 2H), 7.70(d, 2H), 7.51(ddd, 1H) 〇 42 201109028 室溫，向化合物m3克，2.0毫摩爾）在Me〇H(2〇毫升)溶液中加入克，9.8毫摩爾。將反應混合物回心小時’除去Me〇H和S〇Cl2。殘餘物用戊院研碎。將懸浮液過濾’得到為米白色固體的化合物87克，95%)。 MS m/z 458·1(Μ++1)。至酿，向HATU(1.12克’ 3_〇毫摩爾）、卜經基苯並*** (HOBT，〇.41克’ 3.0毫摩爾）、工，別克，i 9毫摩爾）和2· 叔丁氧基羰基氨基-壬-8-烯酸（1.21克，19毫摩爾）在 CH2C12(40毫升）的溶液中加入N-甲基嗎啉(NMM，丨〇2克， 9_9毫摩爾）。攪拌過夜後，該化合物真空條件下濃縮。殘餘物通過碎膠柱色谱純化’得到化合物Ι_9(ι·〇3克，73%)。 MS m/z 711.3(Μ++1)。室溫，向化合物1-9(1.01克，1.4毫摩爾）在丁册(2〇毫升) 的溶液中加入〇.5M LiOH(5.7毫升，2.9毫摩爾）。攪拌過夜後，反應混合物用丨〇% HC1進行中和至pH < 7，並與真空進行濃縮。形成的殘餘物過濾並用水洗滌，得到化合物 1-10(0.91 克，92%)。MS: m/z 697·3(Μ++1)。室溫，將ΝΜΜ(0.12克，1.2毫摩爾）加入到化合物 1-3(0.28克 ’ 0.4毫摩爾）、HATU(0.31 克，0.8毫摩爾）、ΗΟΒΤ (0.08克，〇·6毫摩爾）和化合物1-10(0.〇9克，0.4毫摩爾）在 CH2Cl2(l〇毫升）的溶液中。攪拌過夜後，反應混合物在真空條件下濃縮。殘餘物通過矽膠柱色譜純化，得到化合物 1-11(0.10克，85%)°MSm/z921.3(M++l); HNMWCDCh) δ 10.24(8, 1Η), 8.61(d, 2H), 8.26(d, 1H), 7.77(d, 2H), 7.73- 43 201109028 7.64(m, 2H), 7.54-7.47(m, 1H), 7.11(s, 1H), 6.19(d, 1H), 5.88-5.70(m, 2H), 5.38-5.25(m, 2H), 5.16(d, 1H), 5.00-4.90 (m, 2H), 4.60(dd, 1H), 4.88-4.34(m, 2H), 4.18-4.10(m, 1H), 2.98-2.89(m, 1H), 2.68(dd, 2H), 2.18-1.96(m? 6H), 1.50-1.32 (m，7H)，1.28(s，9H)，1.09-1.25(m，2H)。室溫，在N2氣氛下向化合物M丨（0.10克，0.11毫摩爾）在毫升）的溶液中加入霍維達-格拉布 (Hoveyda-Grubbs)二代(35毫克，0.056毫摩爾）。然後，於40 C授拌反應混合物24小時，進行易位環化（metathesis cyclization)。將反應猝滅，反應混合物通過柱層析純化，得到化合物1-12(30毫克，31%)。MS: m/z 893.3(M++1) ; lH NMR(CDC13) δ 10.39(s，1H)，8.59(d，2H)，8.21(d，1H)，7.77 (d, 2H), 7.69-7.57(m, 2H), 7.46(dd, 1H), 7.20(s, 1H), 6.12(s, 1H), 5.69(q, 1H), 5.12(d, 1H), 4.97(dd, 1H), 4.81-4.68(m, 2H), 4.28-4.07(m, 2H), 2.96-2.49(m, 3H), 2.30(q, 1H), 1.96-1.12(m, 14H), 1.08(s, 9H), 0.96-0.82(m, 2H) ° 室溫，在A氣氛下向化合物142(30毫克，0.034毫摩晴）在MeOH(l〇毫升）的溶液中加入5%pd-C(5毫克）。然後，在室溫、壓力60 psi ’氫氣氛下攪拌反應混合物4小時。將反應混合物過濾並通過柱層析純化，得到化合物1(16.5毫克’ 55%)°MS: m/z 895.3(M++1); 'H NMR(CDC13) δ 10.79(s, 1H), 8.57(d, 2H), 8.21(d, 1H), 7.75(d, 2H), 7.64(m, 2H), 7.46(d, 1H), 7.11(s, 1H), 6.11(s> ih), 5.29(d, 1H), 4.72(m, 2H), 4.38(m, 2H), 4.12(m, 1H), 3.〇2-2.58(m, 3H), 1.98-0.86(m, 44 201109028 29H)。實施例2-141 :化合物2-141的合成化合物2-141各自按照與實施例1所述類似的方式製備。化合物2: MS: m/z 883.3(M++1) ; NMR(CDC13) δ 10.51(s, 1H), 8.53(d, 2H), 8.16(d, 1H), 7.73(d, 2H), 7.62(m, 2H), 7.22(m, 2H), 6.07(s, 1H), 5.23(d, 1H), 4.77(dd, 1H), 4.49(d, 1H), 4.35(m, 1H), 4.13(m, 1H), 3.02-2.57(m, 3H), 1.99-0.91(m, 30H)。化合物 3: MS: m/z 823.2(M++1) ; ’H NMR(CDC13) δ 10.38(s, 1H), 8.53(d, 2H), 8.16(d, 1H), 7.73(d, 2H), 7.61(m, 2H), 7.41(m, 2H), 6.13(m, 2H), 5.69(q, 1H), 4.98(dd, 1H), 4.78(m, 1H), 4.55(m, 1H), 4.42(m, 1H), 4.19(m, 1H), 2.89(m, 1H), 2.78(m, 2H), 2.52(m, 1H), 2.23(q, 1H), 1.96-0.84(m, 15H)，1.90(s，3H)。化合物4: MS: m/z 882.3(M++1) ; 4 NMR(CDC13) δ 10.47(s, 1H), 8.64(d, 1H), 8.52(m, 3H), 7.70(d, 2H), 7.44(dd, 1H), 6.07(s, 1H), 5.63(q, 1H), 5.01-4.73(m, 3H), 4.07-4.01(m, 2H), 2.90-2.22(m, 4H), 1.97-1.09(m, 17H), 0.94(s, 9H), 0.90-0.88(m，1H)。化合物 5: MS: m/z 840.2(M++1) ; ’H NMR(CDC13) δ 10.42(s, 1H), 8.64-8.47(m, 4H), 7.80(d, 2H), 7.50-7.27(m, 2H), 6.15(s, 1H), 5.69(q, 1H), 5.23(d, 1H), 5.02(dd, 1H), 4.84(dd, 1H), 4.53(d, 1H), 4.25-4.ll(m, 2H), 3.32(s, 3H), 45 201109028 2.93- 2.15(m，4H)，1.92-0.83(m，16H)。化合物 6: MS: m/z 824.2(M++1) ; 4 NMR(CDC13) δ 10.48(s, 1H), 8.63(d, 1H), 8.62-8.48(m, 3H), 7.78(d, 2H), 7.44_7.4〇(m> ih), 6.16-6.14(m, 2H), 5.73(q, 1H), 5.04(dd, 1H)，4.85(dd，1H)，4.55(s，1H), 4.51(s，1H), 4.15(d，1H), 2.93- 2.89(m, 2H), 2.77-2.22(m, 3H), 1.95-1.85(m, IK), 1.79(s，3H), 1.76-0.83(m，]5H)。化合物 7: MS: m/z 839.2(M++1);NMR(C:DC13) δ 10.39(s, 1H), 8.46(d, 2H), 8.15(d, 1H), 7.71(d, 2H), 7.62-7.37(m, 3H)5 7.16(s, 1H), 6.08(s, 1H), 5.71(q, 1H), 5.25(d, 1H), 4.96(dd, 1H), 4.75(dd, 1H), 4.44(d, 1H), 4.35-4.09(m, 2H), 3.34(s, 3H), 2.96-2.71(m, 2H), 2.57(brs, 1H), 2.28(q, 1H)，2.08-0.87(m, 16H)。化合物 8: MS: m/z 849.3(M++1) ; 'H NMR(CDC13) δ 10.54(s, 1H), 8.45(d, 2H), 8.06(d, 1H), 7.71(d, 2H), 7.57(m, 3H), 7.35(s, 1H), 6.28(d, 1H), 6.04(s, 1H), 5.71(q, 1H), 4.96(dd, 1H), 4.67(dd, 1H), 4.47(d, 1H), 4.45(brs, 1H), 4.11(m, 1H), 2.92-2.45(m, 4H), 2.32(q, 1H), 1.96-0.84(m, 20H)。化合物9: MS: m/z 880.3(M++1) ; 4 NMR(CDC13) δ 10.45(s, 1H), 8.40(d, 2H), 8.14(s, 1H), 7.97(d, 1H), 7.64(d, 2H), 7.48-7.41(m, 2H), 7.25-7.20(m, 1H), 5.96(s, 1H), 5.63(q, 1H), 4.92-4.86(m, 2H), 4.77(d, 1H), 4.44(s, 1H), 4.20(dd, 1H), 4.03(dd, 1H), 2.90-2.84(m, 2H), 2.80-2.63(m, 1H), 46 201109028 2.38-2.32(m, 1H), 1.98-1.02(m, 15H), 0.91(s, 9H), 0.90-.086 (m, 1H)。化合物 10: MS: m/z 911·2(Μ++1) ; *H NMR(CDC13) δ 10.23(s, 1H), 8.54(d, 2H), 7.87-7.80(m, 1H), 7.71(d, 2H), 7.56(dd, 1H), 7.33-7.20(m, 1H), 6.88(s, 1H), 6.13(s, 1H), 5.65(q, 1H), 5.07-4.94(m, 2H), 4.69(dd, 1H), 4.57(d, 1H), 4.43-4.38(m, 1H), 4.24-4.01(m, 2H), 2.91-2.80(m, 2H), 2.74 (s, 3H), 2.65-2.63(m, 1H), 2.60-2.41(m, 1H), 2.22(q, 1H), 1.98-0.86(m，20H)。化合物 11: MS: m/z 907.3(M++1)。化合物 12: MS: m/z 923·3(Μ++1) ; NMR(CDC13) δ 10.42(s, 1H), 8.57(d, 2H), 8.06(d, 1H), 7.76(d, 2H), 7.51(s, 1H), 7.14-6.93(m, 2H), 6.13(s, 1H), 5.80-5.60(m, 1H), 5.31(d, 1H), 4.97-4.83(m, 2H), 4.79(dd, 1H), 4.64-4.04(m, 3H), 3.88(s, 3H), 2.94-2_43(m, 3H), 2.36-0.86(m, 25H)。化合物 13: MS: m/z 852.3(M++1) ; ’H NMR(CDC13) δ 10.68(s, 1H), 8.38(d, 2H), 7.95(d, 1H), 7.72-7.58(m, 3H), 7.47(d, 2H), 7.24-7.19(m, 1H), 6.01(s, 1H), 5.69(q, 1H), 4.94(dd, 1H), 4.78(dd, 1H), 4.70(d, 1H), 4.46(d, 1H), 4.22- 3.98(m, 2H), 2.97-2.80(m, 2H), 2.57(s, 6H), 2.67-2.41(m, 1H), 2.23(q, 1H), 1.85-0.84(m，16H)。化合物 14: MS: m/z 766·2(Μ++1) ; ’H NMR(CDC13) δ 10.30(s, 1H), 8.62(m, 2H), 8.24(m, 1H), 7.77(d, 2H), 7.67(m, 2H), 7.48(m, 1H), 6.90(s, 1H), 6.18(s, 1H), 5.72(q, 1H), 47 201109028 4.98(dd, 1H), 4.65(dd, 1H), 4.24(m, 1H), 4.05(m, 1H), 2.92 (m, 1H), 2.76(m, 2H), 2.58-2.28(m, 4H), 1.94-1.05(m, 13H), 0.97-0.86(m, 2H)。化合物 15: MS: m/z 893.3(M++1);NMR(CDC13) δ 10.33(s, 1H), 8.88(s, 1H), 8.68(d, 1H), 8.26(d, 1H), 7.80-7.65(m, 4H), 7.35-7.26(m, 1H), 6.98(d, 1H), 6.20(d, 1H), 5.71(q, 1H), 5.18(d, 1H), 5.00(dd, 1H), 4.77(dd, 1H), 4.64(d, 1H), 4.46(s, 1H), 4.25(dd, 1H), 4.15(dd, 1H), 2.92-2.28(m, 4H)，2.17-0.82(m，24H)。化合物 16: MS: m/z 877.3(M++1) ; 4 NMR(C:DC13) δ 10.40(s, 1H), 8.45(d, 2H), 8.04(d, 1H), 7.62(d, 2H), 7.58-7.50(m, 2H), 7.44(s, 1H), 7.35(dd, 1H), 6.02(s, 1H), 5.95(d, 1H), 5.63(q, 1H), 4.81(dd, 1H), 4.70(dd, 1H), 4.49(d, 1H), 4.42-4.38(m, 1H), 4.04(dd, 1H), 2.90-2.20(m, 6H), 1.96-0.83 (m, 23H) » 化合物 17: MS: m/z 907.3(M++1) ; 4 NMR(CDC13) δ 10.42(s, 1H), 8.73(s, 1H), 8.62(d, 1H), 7.96(s, 1H), 7.71(d, 1H), 7.64(dd, 1H), 7.59-7.25(m, 3H), 6.11(s, 1H), 5.62(q, 1H), 5.21(d, 1H), 4.99(dd, 1H), 4.79(dd, 1H), 4.61(d, 1H), 4.52(s, 1H), 4.25-4.10(m, 2H), 2.95-2.51(m, 3H), 2.47(s ,3H), 2.31(q，]H), 2.03-0_91(m，24H)。化合物 18: MS: m/z 767.2(M++1) ; NMR(CDC13) δ 10.38(s, 1H), 8.49(d, 2H), 8.15(d, 1H), 7.77(d, 2H), 7.64-7.58(m, 2H), 7.41-7.32(m, 1H), 7.29(s, 1H), 6.08(s, 1H), 48 201109028 5.78(q, 1H), 5.08(dd, 1H), 4.66(dd, 1H), 4.42(d, 1H), 4.09-4.06(m, 1H), 3.85-3.62(m, 4H), 2.93-2.45(m, 4H), 2.04-0.87 (m, 13H)。化合物 19: MS: m/z 899·3(Μ++1) ; ’Η NMR(CDC13) δ 10.28(s, 1H), 8.51(d, 2H), 7.80(dd, 1H), 7.70(d, 2H), 7.51-7.42(m, 1H), 7.37-7.23(m, 1H), 6.97(s, 1H), 6.06(s, 1H), 5.63(q, 1H), 4.96-4.85(m, 2H), 4.75-4.63(m, 2H), 4.09-4.02 (m, 2H)，2.93-2.43(m, 4H)，2.21(q，1H)，1.96-0.76(m, 24H)。化合物20: MS: m/z 895.3(M++1) ; 4 NMR(CDC13) δ 10.42(s, 1H), 8.43(d, 2H), 7.81(s, 1H), 7.67(d, 2H), 7.51(s, 1H), 7.35-7.28(m, 2H), 5.92(s, 1H), 5.57(q, 1H), 5.19(d, 1H), 4.88-4.61(m, 3H), 4.14-4.00(m, 2H), 2.83-2.41(m, 4H), 2.38(s, 3H), 2.24(q, 1H), 1.96-1.16(m, 15H),1.05(s, 9H), 0.97-0.78(m，1H)。化合物21: MS: m/z 923·3(Μ++1) ; 'H NMR(CDC13) δ 10.33(s, 1H), 8.50(d, 2H), 7.67(d, 2H), 7.59(s, 1H), 7.41(d, 1H), 7.34(s, 1H), 7.16(d, 1H), 6.06(s, 1H), 5.64(q, 1H), 5.23(d, 1H), 4.94(dd, 1H), 4.87(dd, 1H), 4.58-4.42(m, 2H), 4.30-4.02(m, 2H), 3.84(s, 3H), 2.88-2.44(m, 4H), 2.21(q, 1H), 1.84-0.78(m, 23H)。化合物22: MS: m/z 752.2(M++1) ; 4 NMR(CDC13) δ 10.76(s, 1H), 8.61(d, 2H), 8.25(m, 1H), 7.79(d, 2H), 7.67(d, 2H), 7.52(m, 1H), 6.70(s, 1H), 6.19(s, 1H), 5.69(q, 1H), 5.08(m, 1H), 4.65(dd, 1H), 4.23(dd, 1H), 4.02(m, 1H), 49 201109028 3.05-1.98(m，7H)，1.96-0.82(m, 13H)。化合物23: MS: m/z 907·3(Μ++1) ; if! NMR(CDC13) δ 10.40(s, 1H), 8.56(d, 2H), 8.08(d, 1H), 7.73(d, 2H), 7.29(s, 1H), 7.26-7.20(m, 2H), 6.13(s, 1H), 5.71(q, 1H), 5.22(d, 1H), 4.95(dd, 1H), 4.82-4.73(m, 1H), 4.63-4.51(m, 1H), 4.33-4.06 (m, 2H), 2.96-2.51(m, 4H), 2.53(s, 3H), 2.24(q, 1H), 1.96-0.94(m, 24H)。化合物24: MS: m/z 916.3(M++1) ; 4 NMR(CDC13) δ 10.37(s, 1H), 8.48(d, 2H), 8.08(s, 1H), 7.68(d, 2H), 7.50-7.37(m, 3H), 6.01(s, 1H), 5.59(q, 1H), 5.13(d, 1H), 4.83(dd, 1H), 4.74-4.63(m, 2H), 4.15(dd, 1H), 4.05(d, 1H), 2.94-2.41 (m, 4H), 2.21(q, 1H), 1.89-1.14(m, 14H), 1.03(s, 9H), 0.96-0.85(m，1H)。化合物25: MS: m/z 923.3(M++1)。化合物26: MS: m/z 923.3(M++1) ; 4 NMR(CDC13) δ 1035(s, 1H), 8.50(d, 2H), 7.69(d, 2H), 7.52(dd, 1H), 7.40(s, 1H), 7.12(d, 1H), 6.75(d, 1H), 6.05(s, 1H), 5.63(q, 1H), 5.27(d, 1H), 4.97-4.83(ms 1H), 4.75(dd, 1H), 4.42(brs, 1H), 4.28-4.08(m, 2H), 4.08(s, 3H), 2.91-2.38(m, 4H), 2.23(q, 1H), 1.96-0.82(m, 24H)。化合物27: MS: m/z 894_3(M++1) ;「H NMR(CDC13) δ 10.38(s，】H)，8.47(d，2H)，8.08(d,lH)，7.62(d，2:H)，7.58-7.54(m, 2H), 7.40-7.33(m, 1H), 7.3 l(s, 1H), 6.07(s, 1H), 5.63(q, 1H), 4.95(dd, 1H), 4.83(d, 1H), 4.87(dd, 1H), 4.58(d, 50 201109028 1H), 4.31-4.19(m, 1H), 4.09(dd, 1H), 3.40-3.32(m, 4H), 3.01-2.41(m，8H), 2.19(q, 1H)，1.92-0.83(m, 15H)。化合物28: MS: m/z 878·3(Μ++1) ; ’H NMR(CDC13) δ 10.56(s, 1H), 8.41(d, 2H), 8.02(d, 1H), 7.74(s, 1H), 7.68(d, 2H), 7.53-7.47(m, 2H), 7.35-7.32(m, 1H), 6.01(s, 1H), 5.62(q, 1H), 4.90(dd, 1H), 4.78(dd, 1H), 4.59-4.43(m, 2H), 4.35-4.25 (m, 1H), 4.05(dd, 1H), 3.61-3.49(m, 1H), 3.01-2.45(m, 8H), 2.21(q, 1H)，1.85-0.83(m，18H)。化合物29: MS: m/z 909·3(Μ++1) ; 4 NMR(CDC13) δ 10.27(s, 1H), 8.53(d, 2H), 8.16(d, 1H), 7.67(d, 2H), 7.64-7.43(m, 4H), 6.03(s, 1H), 5.61(q, 1H), 5.22-5.19(m, 1H), 4.87(dd, 1H), 4.66(dd, 1H), 4.57(d, 1H), 4.19-4.01(m, 3H), 3.71-3.42(m, 4H), 3.19-2.97(m, 2H), 2.91-2.43(m, 4H), 2.20(q, 1H)，1.95-0.81(m，17H)。化合物30: MS: m/z 906.3(M++1) ; !H NMR(CDC13) δ 10.18(s, 1H), 8.62(d, 2H), 8.25(d, 1H), 7.78(d, 2H), 7.70-7.61(m, 2H), 7.55-7.46(m, 1H), 7.01(1H), 6.18(1H), 5.71(q, 1H), 5.12(d, 1H), 5.02(dd, 1H), 4.77(dd, 1H), 4.64(d, 1H), 4.53-4.43(lH), 4.31-4.18(m, 2H), , 2.83-2.44(m, 3H), 2.28(q, 1H)，1.95-1.22(m, 23H), 0.83(s，3H)。化合物31: MS: m/z 907.3(M++1);丨11 NMR(CDC13) δ 10.39(s, 1H), 8.57(d, 2H), 8.05(d, 1H), 7.77(d, 2H), 7.42-7.26(m, 3H), 6.15(s, 1H), 5.69(q, 1H), 5.29(d, 1H), 4.96(dd, 1H), 4.78(dd, 1H), 4.63-4.56(m, 1H), 4.40-4.13(m, 3H), 51 201109028 2.91-2.64(m, 3H), 2.62(s, 3H), 2.56-2.22(m, 2H), 1.89-0.96 (m，23H)。化合物32: MS: m/z 895.2(M++1) ; rH NMR(CDC13) δ 10.45(s, 1H), 8.60(d, 2H), 8.22(d, 1H), 7.55(d, 2H), 7.67-7.60(m, 2H), 7.45(dd, 1H), 7.20(s, 1H), 6.12(s, IH), 5.65(q, 1H), 5.13(d, 1H), 4.97(dd, 1H), 4.81-4.71(m, 2H), 4.14-4.10 (m, 2H), 2.82-2.45(m, 3H), 2.27(q, 1H), 1.97-1.21(m, 14H), 1.08(s, 9H), 0.89-0.80(m，4H)。化合物33: MS: m/z 853.3(M++1) ; NMR(CDC13) δ 10.22(s, 1H), 8.58(s, 1H), 8.48(d, 2H), 8.08(d, 1H), 7.57(d, 2H), 7.53-7.44(m, 2H), 7.39-7.26(m, 1H), 6.05(s, 1H), 5.65(q, 1H), 5.21(d, 1H), 4.95(dd, 1H), 4.82(dd, 1H), 4.40(d, 1H), 4.21-4.03(m, 2H), 3.27(s, 3H), 2.81-2.40(m, 3H), 2.22(q, 1H), 1.95-l_20(m，15H)，0.81(s, 3H)。化合物34: MS: m/z 923.3(M++1);丨14 NMR(CDC13) δ 10.17(s, 1H), 8.61(d, 2H), 8.25(d, 1H), 7.80(d, 2H), 7.65-7.50(m, 2H), 7.41(dd, 1H), 6.97(s, 1H), 6.18(s, 1H), 5.72(q, 1H), 5.15(d, 1H), 5.05(dd, 1H), 4.77(dd, 1H), 4.65(d, 1H), 4.29-4.10(m5 2H), 3.78-3.52(m, 2H), 3.23-3.03(m, 2H), 2.79-2.85(ms 2H), 2.56(brs, 1H), 2.27(q, 1H), 1.98-1.19(m, 20H), 0.88(s，3H)。化合物35: MS: m/z 894·2(Μ++1) ; NMR(CDC13) δ 10.45(s, 1H), 8.47(d, 2H), 8.12(s, 1H), 8.05(d, 1H), 7.70(d, 2H), 7.53-7.46(m, 2H), 7.31-7.22(m, 1H), 6.03(s, 1H), 5.70(q, 52 201109028 1H), 5.03-4.84(m, 4H), 4.24(d, 1H), 2.95-2.47(m, 3H), 2.38(q，1H), 1.94-1.ll(m, 25H)，0.85(s, 3H)。化合物36: MS: m/z 889.3(M++1) ; ’H NMR(CDC13) δ 10.26(s, 1H), 8.47(d, 2H), 8.07(d, 1H), 7.65(d, 2H), 7.57(s, 1H), 7.55-7.42(m, 2H), 7.38-7.27(m, 2H), 6.82(d, 1H), 6.62(d, 1H), 5.63(dd, 1H), 6.15(s, 1H), 5.63(q, 1H), 4.92(dd, 1H), 4.74-4.59(m, 2H), 4.42(d, 1H), 4.17(dd, 1H), 2.79-2.42 (m，3H), 2.23(q，1H), 1.95-1.05(m，15H)，0.76(s, 3H)。化合物37: MS: m/z 837·3(Μ++1) ; 4 NMR(CDC13) δ 10.16(s, 1H), 8.48(d, 2H), 8.11(d, 1H), 7.69(d, 2H), 7.58(d, 2H), 7.36(dd, 1H), 7.17(s, 1H), 6.15(s, 1H), 6.04(d, 1H), 5.64(q, 1H), 4.94(dd, 1H), 4.67(dd, 1H), 4.47(dd, 1H), 4.41(d, 1H), 4.12(dd, 1H), 2.78-2.68(m, 1H), 2.43(brs, 1H), 2.22(q, 1H)，1.98-1.64(m, 7H)，1.53-l.ll(m，12H), 0.78(s, 3H)。化合物38: MS: m/z 863·3(Μ++1) ; 4 NMR(CDC13) δ 10.52(s, 1H), 8.38(d, 2H), 7.92(d, 1H), 7.88(s, 1H), 7.65(d, 2H), 7.58-7.52(m, 2H), 7.35-7.21(m, 1H), 6.19(d, 1H), 5.92(s, 1H), 5.71(q, 1H), 5.01(dd, 1H), 4.81(dd, 1H), 4.62(d, 1H), 4.37(brs, 1H), 4.11-4.01(m, 1H), 2.98-2.87(m, 1H), 2.74-2.52 (m, 2H), 2.33(q, 1H), 1.98-1.19(m, 16H), 0.88(s, 3H), 0.68-0.41(m，4H)。化合物39: MS: m/z 908.3(M++1) ; 4 NMR(CDC13) δ 10.26(s, 1H), 8.48(d, 2H), 8.15(d, 1H), 7.67(d, 2H), 7.57-7.46(m, 2H), 7.39-7.35(m, 2H), 6.07(s, 1H), 5.62(q, 1H), s 53 201109028 4.98-4.86(m, 2H), 4.77(dd, 1H), 4.58(d, 1H), 4.02(dd, 1H), 3.38-3.24(m, 4H), 2.99-2.81(m, 4H), 2.82-2.42(m, 3H), 2.19 (q，1H), 1.88-1.04(m，15H)，0.92-0.72(m，4H)。化合物40: MS: m/z 866.3(M++1);丨H NMR(CDC13) δ 10.51(s, 1H), 8.37(d, 2H), 7.91(d, 1H), 7.69(s, 1H), 7.61(d, 2H), 7.53-7.42(m, 2H), 7.23-7.14(m, 1H), 6.01(s, 1H), 5.67(q, 1H), 4.94(dd, 1H), 4.72(dd, 1H), 4.61(d, 1H), 4.43(d, 1H), 4.30-4.02(m, 2H), 2.94-2.60(m, 3H), 2.57(s, 6H), 2.20(q, 1H), 1.80-l_15(m，]5H)，0.77(s，3H)。化合物4】：MS: m/z 892.3(M'+1) ; 4 NMR(CDC13) δ 10.40(s, 1H), 8.51(d, 2H), 8.16(d, 1H), 7.85(d, 2H), 7.65(s, 1H), 7.58(d, 1H), 7.41-7.37(m, 1H), 6.14(s, 1H), 5.59(q, 1H), 4.99(dd, 1H), 4.80(dd, 1H), 4.62(d, 1H), 4.57(d, 1H)? 4.45-4.37(m, 1H), 4.17(dd, 1H), 3.75-3.65(m, 2H), 3.60-3.48 (m, 2H)，2.80-2.45(m，3H)，2.24(q, 1H)，1.89-1.41(m，20H)，0.8(s， 3H)。化合物42: MS: m/z 907.3(M++1) ; NMR(CDC13) δ 10.20(s, 1H), 8.43(d, 2H), 8.10(d, 1H), 7.65(d, 2H), 7.60-7.55(m, 2H), 7.39-7.35(m, 1H), 7.25(s, 1H), 6.05(s, 1H), 5.98(d, 1H), 5.66(q, 1H), 4.93(dd, 1H), 4.72(dd, 1H), 4.52-4.42(m, 2H), 4.08(dd, 1H), 3.78-3.60(m, 2H), 3.21-3.11(m, 2H)，3.81-2.43(br，3H), 2.19-2.05(m, 2H), l_85-1.09(m, 19H)， 0.77(s，3H)。化合物43: MS: m/z 890.3(M++1) ; NMR(CDC13) δ 54 201109028 10.16(s, 1H), 8.55(d, 2H), 8.21(d, 1H), 8.14(s, 1H), 7.68(d, 2H), 7.58-7.41(m, 4H), 7.21(s, 1H), 6.40(s, 1H), 6.18(s, 1H), 5.63(q, 1H), 4.95(dd, 1H), 4.78-4.62(m, 2H), 4.44(d, 1H), 4.16(dd, 1H), 2.69-2.44(m, 3H), 2.24(q, 1H), 1.98-1.15(m, 15H), 0.79(s，3H)。化合物44: MS: m/z 879.3(M++1) ; W NMR(CDC13) δ 10.22(s, 1H), 8.59(d, 2H), 8.22(d, 1H), 7.76(d, 2H), 7.75-7.60(m, 2H), 7.48-7.42(m, 1H), 7.17(s, 1H), 6.20(s, 1H), 6.16(d, 1H), 5.71(q, 1H), 5.02(dd, 1H), 4.77(dd, 1H), 4.60-4.52(m, 2H), 4.20(dd, 1H), 2.79-2.45(m, 3H), 2.21(q, 1H), 1.96-1.07(m，15H), 1.03(s，9H), 0.82(s, 3H)。化合物45: MS: m/z 933_3(M++1) ; NMR(CDC13) δ 10.22(s, 1H), 8.56(d, 2H), 8.19(d, 1H), 7.88(d, 2H), 7.69-7.42(m, 3H), 7.19(s, 1H), 6.81-6.62(m, 4H), 6.11(s, 1H), 5.68 (q, 1H), 5.00(dd, 1H), 4.77(dd, 1H), 4.55(d, 2H), 4.41-4.12 (m, 2H), 2.82-2.42(m, 3H), 2.28(q, 1H), 2.01-l.ll(m, 15H), 0.83(s，1H)。化合物46: MS: m/z 891.3(M++1);丨11 NMR(CDC13) δ 10.34(s, 1H), 8.35(d, 2H), 7.94(d, 1H), 7.66(s, 1H), 7.62(d, 2H), 7.54-7.46(m, 2H), 7.22(dd, 1H), 5.93-5.84(m, 2H), 5.61(q, 1H), 4.92(dd, 1H), 4.87(dd, 1H), 4.58(d, 1H), 4.41-4.36(m, 1H), 4.04(dd, 1H), 2.82-2.75(m, 1H), 2.65-2.50(m, 2H)，2.24(q，1H)，1.80-1.00(m, 24H)，0.81(s，3H)。化合物47: MS: m/z 867_3(M++1) ; iH NMR(CDC13) δ 55 201109028 l〇.35(s, 1H), 8.54(d, 2H), 8.18(d, 1H), 7.86(d, 1H), 7.66(d, 2H)，7.6](m，2H)，7.46(m，2H), 6.13(s，1H)，5.67(q，ΠΙ), 4.94(dd, 1H), 4.77(m, 1H), 4.61(m, 1H), 4.40(d, 1H), 4.20(m, 1H), 3.72(s, 3H), 2.91(m, 1H), 2.72-2.39(m, 3H), 2.25(q, 1H), 1.96-0.82(m，15H)。化合物48: MS: m/z 908.2(M++1) ; ’H NMR(CDC13) δ 10.28(s, 1H), 8.44(d, 1H), 8.23(d, 1H), 7.67(m, 3H), 7.52(m, 1H), 7.07(s, 1H), 6.04(s, 1H), 5.68(q, 1H), 5.12(d, 1H), 4.98(dd, 】H)，4.79-4.68(m, 2H)，4.34(s, 1H), 4.20(dd，1H)， 4.00(m, 1H), 2.95(s, 3H), 2.93(m, 1H), 2.72(m, 2H), 2.52(m, 1H)，2.26(q，1H)，1.94-0.82(23H)。化合物49: MS: m/z 920·2(Μ++1)。化合物50: MS: m/z 806.2(M++1) ; rH NMR(CDC13) δ 10.47(s, 1H), 8.77-8.53(ra, 2H), 8.19(d, 1H), 8.13(d, 1H), 7.73(s, 1H), 7.53-7.30(m, 2H), 7.26-7.18(m, 1H), 6.07(s, 1H), 5.70-5.40(m, 2H), 4.98-4.61(m, 2H), 4.40-4.03(m, 3H), 3.47 (s, 3H), 2.95-2.90(m, 1H), 2.87-2.50(m, 3H), 2.20(dd, 1H), 2.10-1.86(m，3H), 1.61-1.08(m，11H)，0.96(m，1H)。化合物51: MS: m/z 822.3, 824.3(M++1); iHNMRXCDCh) δ 10.42(s, 1H), 8.69-8.44(m, 3H), 8.34(d, 2H), 7.65(s, 1H), 7.42-7.30(m, 3H), 6.04(s, 1H), 5.70-5.45(m, 2H), 4.91-4.63 (m, 2H), 4.35-4.03(m, 3H), 3.42(s, 3H), 2.84(s, 1H), 2.72-2.50(m, 3H)，2.22(dd，1H)，2.19(m，3H), 1.54-0.78(m，11H卜化合物52: MS: m/z 774.2(M++1) ; 4 NMR(CDC13) δ 56 201109028 10.33(s, 1H), 8.65-8.58(m, 1H), 8.46(d, 1H), 8.18(d, 1H), 8.06(d, 1H), 7.46-7.38(m,3H), 7.19-7.11(m, 1H), 6.13(s, 1H), 6.04(d, 1H), 5.66(dd, 1H), 5.27-5.08(m, 1H), 5.07-4.67(m, 2H), 4.52-4.39(m, 2H), 4.13-4.09(m, 1H), 3.62-3.60(m, 1H), 2_95-2.10(m，4H), 1.98(s，3H), 1.90-0.81(m, 14H)。化合物53: MS: m/z 825.3(M++1)。化合物54: MS: m/z 805.3, 807.3(M++1); h NMR(CDC13) δ 10.46(s, 1H), 8.28-8.19(m, 1H), 7.98(s, 1H), 7.88-7.85(m, 1H), 7.63-7.39(m, 6H), 6.07(s, 1H), 5.67-5.46(m, 2H), 4.96-4.79(m, 2H), 4.41-4.09(m, 3H), 3.37(s, 3H), 2.97-0.88 (m, 20H)。化合物55: MS: m/z 789.2(M++1) ; NMR(CDC13) δ 10.61(s, 1H), 8.49(s, 1H), 8.39-8.24(m, 2H), 8.05-7.94(m, 2H), 7.56-7.04(m, 5H), 5.90(s, 1H), 5.47(br, 1H), 4.93-4.69 (br, 2H), 4.40-4.07(m, 3H), 3.46(s, 1H), 3.23(s, 3H), 2.91-2.07(m, 11H), 1-99-1.54(m, 4H), 1.32-0.81(m, 5H)。化合物56: MS: m/z 839.3, 843_3(M++1); 〗HNMR(CDC13) δ 10.27(s, 1H), 8.24(d, 1H), 7.89(d, 1H), 7.63(d, 1H), 7.56(s, 1H), 7.52-7.40(m, 2H), 7.14(brs, 1H), 6.08(s, 1H), 5.69(q, 1H), 5.30(brs, 1H), 4.97(dd, 1H), 4.74(dd, 1H), 4.46(d, 1H), 4.40-4.22(m, 1H), 4.13-4.08(m, 1H), 3.36(s, 3H), 2.99-2.05 (m，5H), l_90-1.10(m，15H), 0.99-0.88(m, 1H)。化合物57: MS: m/z 827·2(Μ++1) ; NMR(CDC13) δ 10.17(s, 1H), 8.42(d, 2H), 7.84(d, 1H), 7.49-7.41(m, 4H), 57 201109028 7.28(m, 1H), 7.13(brs, 1H), 6.16(s, 1H), 5.63(q, 1H), 4.95(m, 1H), 4.70(dd, 1H), 4.63(m, 1H), 4.31-4.11(m, 2H), 2.97-2.70 (m，3H), 2.50-1.06(m，17H)，0.91(m5lH)。化合物58: MS: m/z 803.3(M++1)。化合物59: MS: m/z 789·2(Μ++1) ; NMR(CDC13) δ 10.39(s, 1H), 8.53-8.41(m, 3H), 7.81(d, 1H), 7.59-7.42(m, 4H), 7.26(m, 1H), 7.18(s, 1H), 6.17(s, 1H), 5.17(q, 1H), 5.28(dd, 1H), 4.95(dd, 1H), 4.75(m, 1H), 4.43(d, 1H), 4.38-4.04(m, 2H), 3.40(s, 3H), 2.96-2.67(m, 3H), 2.60-2.41 (m，1H)，2.37-2.22(m，1H)，1.99-0.85(m, 14H)。化合物60: MS: m/z 773.2(M*>1) ; 'H NMR(CDC13) δ 10.33(s, 1H), 8.46(d, 2H), 7.88-7.84(m, 1H), 7.60-7.50(m, 4H), 7.35-7.17(m, 1H), 6.20(s, 1H), 6.08(d, 1H), 5.72(q, 1H), 4.98(dd, 1H), 4.72(dd, 1H), 4.56(m, 1H), 4.41(d, 1H), 4.21(m, 1H), 2.94-2.90(m, 1H), 2.80-2.77(m, 1H), 2.55-2.52(m, 1H), 2.23(q, 1H), 1.98-1.90(m, 1H), 1.84(s, 3H), 1.80-0.80(m, 16H)。化合物61: MS: m/z 845.3(M++1) ; NMR(CDC13) δ 10.41(s, 1H), 8.34(d, 2H), 7.84(d, 1H), 7.53-7.44(m, 1H), 7.40-7.33(m, 3H), 7.19(s, 1H), 6.14(s, 1H), 5.71(q, 1H), 5.15 (d, 1H), 4.98(dd, 1H), 4.89~4.80(m, 2H), 4.25-4.19(m, 2H), 2.95-2.90(m, 1H), 2.88-2.42(m, 3H), 2.44(s, 3H), 2.29 (m, 1H)，1.98-1.20(m，14H)，1.1 l(s, 9H)，1.00-0.87(1H)。化合物62: MS: m/z 841.2(M++1) ; h NMR(CDC13) δ 58 201109028 10.21(s, 1H), 8.35(d, 2H), 7.89(d, 1H), 7.60-7.57(m, 1H), 7.33(d, 2H), 7.17(d, 1H), 7.05(s, 1H), 6.22(s, 1H), 5.68(q, 1H), 4.97(dd, 1H), 4.77-4.64(m, 2H), 4.33-4.17(m, 2H), 2.93-2.74(m, 3H), 2.44(s, 3H), 2.21(m, 1H), 1.95-0.91(m, 17H)。化合物63: MS: m/z 903.3 ; 905.3(M++1); h NMR(CDC13) δ 10.18(s, 1H), 8.45(d, 2H), 8.23(d, 1H), 7.64(m, 2H), 7.49(d, 3H), 7.01(s, 1H), 6.17(s, 1H), 5.72(q, 1H), 5.13(d, 1H), 4.99(dd, 1H), 4.77(dd, 1H), 4.58(d, 1H), 4.53(brs, 1H), 4.27(m, 1H), 4.14(m, 1H), 2.83-2.44(m, 3H), 2.27(q, 1H), 1.95-1.22(m，23H)，0.83(s, 3H)。化合物64: MS: m/z 787.3(M++1);】H NMR(CDC13) δ 10.45(s, 1H), 8.25(d, 2H), 7.75(d, 1H), 7.67(s, 1H), 7.53-7.52(m, 1H), 7.26(d, 2H), 6.29(d, 1H), 6.19(s, 1H), 5.67(q, 1H), 4.94(dd, 1H), 4.75(dd, 1H), 4.52(brs, 1H), 4.42(d, 1H), 4.10-4.18(m, 1H), 2.89-2.50(m, 3H), 2.43(s, 3H), 2.35-2.20 (m，1H)，1.98-1.85(m, 1H), 1.82(s, 3H)，1.62-0.81(m，16H)。化合物65: MS: m/z 803.2(M++1) ; h NMR(CDC13) δ 10.46(s, 1H), 8.30(d, 1H), 8.17(d, 2H), 7.63(d, 1H), 7.55(s, 1H), 7.45-7.41(m, 1H), 7.25-7.20(m, 2H), 5.97(s, 1H), 5.65-5.59(m, 1H), 5.36(d, 1H), 4.91-4.87(m, 1H), 4.73(dd, 1H), 4.37-4.05(m, 3H), 3.30(s, 3H), 2.84-2.47(m, 3H), 2.38(s, 3H), 2.40-2.16(m, 1H)，1.90-0.87(m, 16H)。化合物66: MS: m/z 871.3(M++1) ; ’H NMR(CDC13) δ 59 201109028 10.42(s, 1H), 8.19-8.02(m, ：2H), 7.93(s, 1H), 7.67(s, 1H), 7.47-7.26(m, 3H), 6.05(s, 1H), 5.62(q, 1H), 5.34(d, 1H), 4.96- 4.42(m, 4H), 4.36-4.10(m, 2H), 2.95-2.90(m, 1H), 2.77(s, 3H), 2.76-2.48(m, 3H), 2.35(s, 3H), 2.30-0.87(m, 24H)。化合物67: MS: m/z 875.3(M++1)。化合物68: TG-2379: MS: m/z 871.3(M++1) ; 4 NMR (CDC13) δ 10.33(s, 1H), 8.34(d, 2H), 7.85(d, 1H), 7.73(s, 1H), 7.54-7.46(m, 1H), 7.38-7.22(m, 3H), 6.12(s, 1H), 5.65(q, 1H), 5.35(d, 1H), 4.93(dd, 1H), 4.78(dd, 1H), 4.62-4.50(m, 2H), 4.32-4.08(m, 2H), 2.81-2.42(m, 3H), 2.40(s, 3H), 2.2.6(q, 1H), 1.93-1.l](m, 23H)，0.80(s，3H)。化合物69: MS: m/z 861.3(M++1)。化合物70: MS: m/z 857.2(M++1) ; 4 NMR(CDC13) δ 10.23(s, 1H), 8.09(s, H), 8.05(s, 1H), 7.96(dd, 1H), 7.58(dd, 1H), 7.47-7.19(m, 3H), 7.06(d, 1H), 6.21(s, 1H), 5.69(q, 1H), 4.95(dd, 1H), 4.81-4.60(m, 2H), 4.35-4.17(m, 2H), 3.94(s, 3H)，2.92-2.41(m, 3H), 2.23(q, 1H)，1.92-0.82(m, 17H)。化合物7]: MS: m/z 8]9.2(Mf+l) ; NMR(CDC13) δ 10.36(s，1H), 8.01-7.81(m, 3H)，7.71(d，1H)，7.34-7.22(m， 3H), 6.96(d, IH), 6.01(s, 1H), 5.61(q, 1H), 5.27(dd, 1H), 4.90(dd, 1H), 4.69(dd, 1H), 4.38(d, 1H), 4.22-4.03(m, 2H), 3.87(s, 3H)S 3.28(s, 3H), 2.86-2.42(m, 3H), 2.20(q, 1H), 1.97- 0.88(m, 16H)。 60 201109028 化合物72: MS: m/z 861.3(M++1) ; ’H NMR(CDC13) δ 10.38(s, 1H)，8.10-7.98(m, 2H)，7.86(d，1H)，7.54-7.22(m, 3H), 7.20(s, 1H), 7.06(d, 1H), 6.10(s, 1H), 5.70(q, 1H), 5.29(d, 1H), 4.97(dd, 1H), 4.79-4.67(m, 2H), 4.18-4.04(m, 2H), 3.94(s, 3H), 2.95-2.57(m, 3H), 2.28(q, 1H), 1.91-0.87(m, 25H)。化合物73: MS: m/z 803.2(M++1) ; 4 NMR(CDC13) δ 10.37(s, 1H), 8.12-8.96(m, 2H), 7.85(d, 1H), 7.56-7.26(m, 4H), 7.05(d, 1H), 6.19-6.15(m, 2H), 5.71(q, 1H), 4.96(dd, 1H), 4.74(s, 1H), 4.53-4.42(m, 2H), 4.19(d, 1H), 3.93(s, 3H), 2.91-2.20(m，4H), 2.10-0.82(m，19H)。化合物74: MS: m/z 861·3(Μ++1) ; ’H NMR(CDC13) δ 10.42(s, 1H), 8.39(d, 2H), 7.81(d, 1H), 7.50-7.26(m, 3H), 7.00(d, 2H), 6.05(s, 1H), 5.65(q, 1H), 5.21(d, 1H), 4.95(dd, 1H), 4.84(dd, 1H), 4.68(d, 1H), 4.21-4.07(m, 2H), 3.90(s, 3H), 2.90-2.45(m, 4H), 2.22(q, 1H), 1.98-1.20(m，14H), 1.13(s, 9H)，0.99-0.84(m, 1H)。化合物75: MS: m/z 887.3(M++1) ; ’H NMR(CDC13) δ 10.33(s, 1H), 8.38(d, 2H), 7.82(d, 1H), 7.61(s, 1H), 7.59-7.43(m, 1H), 7.35-7.20(m, 1H), 7.01(d, 2H), 6.07(s, 1H), 5.68(q, 1H), 5.42(d, 1H), 4.98(dd, 1H), 4.75(dd, 1H), 4.58(s, 1H), 4.38-4.13(m, 3H), 3.88(s, 3H), 2.86(br, 2H), 2.59-2.11 (m, 2H), 1.96-1.20(m, 22H), 0.92-0.78(m，4H)。化合物76: MS: m/z 903.3, 905.3(M++1)。 61 201109028 化合物77: MS: m/z 887.3(M++1)。化合物78: MS: m/z 883.4(M++1);丨]·! NMR(CDC13) δ 10.19(s, 1H), 8.46(d, 2H), 8.25(d, 1H), 7.62(m, 2H), 7.46(m, 1H), 7.04((1, 2H), 6.96(s, 1H), 6.19(s, 1H), 5.73(q, 1H), 5.15 (d, 1H), 5.02(dd, 1H), 4.77(m, 1H), 4.58(m, 2H), 4.30(m, 1H), 4.15(m, 3H), 2.79(m, 2H), 2.54(m, 1H), 2.26(q, 1H), 1.92-0_83(m，26H)，0_83(s, 3H)。化合物79: MS: m/z 869_4(M++1) ; 4 NMR(CDC13) δ 10.36(s, 1H), 8.44(d, 2H), 8.24(d, 1H), 7.60(m, 2H), 7.44(m, 1H), 7.04(s, 1H), 7.00(d, ：2H), 6.16(s, 1H), 5.71(q, 1H), 5.21(d, 1H), 4.97(dd, 1H), 4.74(m, 1H), 4.57(m, 2H), 4.30(m, 1H), 4.15(m, 3H), 2.91(m, 1H), 2.75(m, 2H), 2.56(m, 1H), 2.26(q, 1H)，1.92-0.83(m，26H)。化合物80: MS: m/z 883·4(Μ++1) ; ’H NMR(CDC13) δ 10.42(s，1H), 8_43(d，2H), 8.23(d, 1H)，7.61-7.39(m, 4H)， 7.03(d, 2H), 6.18(s, 1H), 5.71(q, 1H), 5.30(d, 1H), 4.96(dd, 1H), 4.79-4.57(m, 4H), 4.41-4.22(m, 1H), 4.15-4.08(m, 1H), 2.96-2.67(m, 3H), 2.57-2.42(m, 1H), 2.25(q, 1H), 1.98-0.87 (m, 29H)。化合物81: MS: m/z 897.4(M++1);丨11 NMR(CDC13) δ 10.31(s, 1H), 8.42(d, 2H), 8.21(d, 1H), 7.57-7.25(m, 4H), 7.02(d, 2H), 6.14(s, 1H), 5.67-5.64(m, 1H), 5.40(d, 1H), 5.03-4.93(m, 1H), 4.79-4.54(m, 4H), 4.39-4.12(m, 2H), 2.77-2.72(m, 2H), 2.54(br, 1H), 2.26(q, 1H), 2.03-1.24(m, 29H), 62 201109028 0.80(s，3H)。化合物82: MS: m/z 915.2(M++1) ; ’H NMR(CDC13) δ 10.29(s, 1H), 8.38(d, 2H), 7.74(d, 1H), 7.57-7.24(m, 3H), 7.27(d, 2H), 6.14(s, 1H), 5.66(q, 1H), 5.32(d, 1H), 4.98(dd, 1H), 4.76(dd, 1H), 4.71-4.48(m, 3H), 4.39-4.08(m, 2H), 2.85-2.42(m, 3H), 2.31(q, 1H), 2.03-1.24(m, 29H), 0.80(s, 3H)。化合物83: MS: m/z 901_2(M++1) ; 4 NMR(CDC13) δ 10.42(s, 1H), 8.46(d, 2H), 7.82(d, 1H), 7.54(dd, 1H), 7.42(s, 1H), 7.32(m, 1H), 6.98(d, 2H), 6.14(s, 1H), 5.65(q, 1H), 5.33(d, 1H), 4.97(dd, 1H), 4.76(dd, 1H), 4.71-4.50(m, 3H), 4.41-4.08(m, 2H), 2.93-2.42(m, 4H), 2.31(q, 1H), 2.03-0.80 (m, 29H)。化合物84: MS: m/z 885.3(M++1) ; W NMR(CDC13) δ 10.26(s, 1H), 8.42(d, 2H), 8.23(d, 1H), 7.58(m, 2H), 7.44(dd, 1H), 7.22(s, 1H), 7.01(d, 2H), 6.17(s, 1H), 5.67(q, 1H), 5.16(d, 1H), 4.98(dd, 1H), 4.75(dd, 1H), 4.62(m, 2H), 4.38-4.08(m, 2H), 2.80-2.42(m, 3H), 2.32(q, 1H), 1.96-1.20(m, 21H), 1.13(s, 9H), 0.81(m, 3H)。化合物85: MS: m/z 923.2(M++1)。化合物86: MS: m/z 883_2(M++1);丨!·！ NMR(CDC13) δ 10.41(s, 1H), 8.19(d, 1H), 8.06(d, 1H), 7.95(s, 1H), 7.61-7.41(m, 4H), 6.92(d, 1H), 6.12(s, 1H), 6.04(s, 2H), 5.67(q, 1H), 5.35(d, 1H), 4.97(dd, 1H), 4.77(dd, 1H), 4.58(d, 1H), 63 201109028 4.36-4.11(m, 2H), 2.85-2.43(m, 3H), 2.27(q, 1H), 1.98-1.21 (m，24H)，0.81(s，3H)。化合物87: MS: m/z 869·2(Μ++1) ; 4 NMR(CDC13) δ 10.36(s, 1H), 8.17(d, 1H), 7.97(d, 1H), 7.88(s, 1H), 7.58-7.32(m, 4H), 6.85(d, 1H), 6.02(s, 1H), 5.98(s, 2H), 5.59(q, 1H), 5.37(d, 1H), 4.87(d, 1H), 4.68(dd, 1H), 4.52-4.02(m, 3H)，2-90-2.38(m，4H)，2.23(q, 1H), 1.91-0.88(m, 24H)。化合物88: MS: m/z 868.5(M++1)。化合物89: MS: m/z 882.5(M++1)。化合物90: MS: m/z 910.3(M++1) ; NMR(CDC13) δ 10.32(s, 1H), 8.34(d, 2H), 8.22(d, 1H), 7.61-7.43(m, 3H), 7.44(dd, 1H), 6.76(d, 2H), 6.l4(s, 1H), 5.62(q, 1H), 5.39(d, 1H), 4.96(dd, 1H), 4.72(dd, 1H), 4.63(brs, 1H), 4.55(d, 1H), 4.41-4.〇4(m, 2H), 3.42(q, 4H), 2.80-2.42(m, 3H), 2.32(q, 1H)，1.98-1.17(m，29H), 0.83(s, 3H)。化合物91: MS: m/z 896·3(Μ++1) ; !Η NMR(CDC13) δ 10.46(s, 1H), 8.33(d, 2H), 8.21(d, 1H), 7.62-7.43(m, 3H), 7.43(dd, 1H), 6.77(d, 2H), 6.13(s, 1H), 5.65(q, 1H), 5.39(d, 1H), 4.93(dd, 1H), 4.73(dd, 1H), 4.64(brs, 1H), 4.53(d, 1H), 4.43-4.05(m, 2H), 3.43(q, 4H), 2.94-2.42(m, 4H), 2.29(q, 1H)，2.14-0.83(m, 29H)。化合物92: MS: m/z 901.4, 903·4(Μ++1); 4 NMR(CDC13) δ 10.40(s, 1H), 8.36(d, 2H), 8.23(s, 1H), 7.58-7.26(m, 5H), 6.15(s, 1H), 5.65(q, 1H), 5.19(d, 1H), 4.96(dd, 1H), 4.77(dd, 64 201109028 1H), 4.62-4.52(m, 2H), 4.33-4.08(m, 2H), 3.01-2.42(m, 5H), 2.25(q, 1H), l_96-0.89(m，29H)。化合物93: MS: m/z 915.4, 917·4(Μ++1);丨11 NMR(CDC13) δ 10.27(s, 1H), 8.38(d, 2H), 8.22(s, 1H), 7.59-7.34(m, 5H), 6.13(s, 1H), 5.70(q, 1H), 5.29(d, 1H), 4.98(dd, 1H), 4.78(dd, 1H), 4.62-4.55(m, 2H), 4.35-4.08(m, 2H), 3.04-2.96(m, 1H), 2.80-2.43(m, 3H), 2.25(q, 1H), 1.97-1.20(m, 29H), 0.81(s, 3H)。化合物94: MS: m/z 867_4(M++1)。化合物95: MS: m/z 881.3(M++1) ; 4 NMR(CDC13) δ 10.31(s, 1H), 8.41(d, 2H), 8.22(d, 1H), 7.63-7.21(m, 4H), 7.20(d, 2H), 6.16(s, 1H), 5.65(q, 1H), 5.38(d, 1H), 4.94(dd, 1H), 4.80(dd, 1H), 4.65-4.56(m, 2H), 4.38-4.12(m, 2H), 3.08-2.92(m, 1H), 2.83-2.67(m， 2H)， 2.59-2.41(m, 1H), 2.25(q, 1H)，1.98-1.08(，m，28H)，0-95-0.86(m，4H)。化合物96: MS: m/z 881_4(M++1) ; 4 NMR(CDC13) δ 10.47(s, 1H), 8.40(d, 2H), 8.23(d, 1H), 7.76(s, 1H), 7.62-7.41(m, 5H), 6.13(s, 1H), 5.65(q, 1H), 5.33(d, 1H), 5.03-4.87 (m, 2H), 4.78(dd, 1H), 4.57(d, 1H), 4.38-4.04(m, 2H), 2.95-2.43(m, 4H), 2.21(q, 1H), 2.01-1.37(m, 20H), 1.33(s, 9H), 1.21-0.86(m，3H)。化合物97: MS: m/z 895.4(M++1);NMR(CDC13) δ 10.30(s, 1H), 8.40(d, 2H), 8.23(d, 1H), 7.59-7.43(m, 5H), 6.98(d, 1H), 6.16(s, 1H), 5.65(q, 1H), 5.41(d, 1H), 4.98(dd, s 65 201109028 1H), 4.79(q, 1H), 4.62-4.52(m, 1H), 4.36-4.09(m, 3H), 2.75 (brs, 2H), 2.59-2.56(m, 1H), 2.28(q, 1H), 1.91-1.18(m, 31H), 0.89-0.78(m, 4H)。化合物98: MS: m/z 869·4(Μ++1) ; NMR(CDC13) δ 10.41(s, 1H), 8.42(d, 2H), 8.23(d, 1H), 7.62-7.43(m, 5H), 7.44(dd, IH), 6.17(s, 1H), 5.64(q, 1H), 5.17(d, 1H), 4.97(dd, 1H), 4.77-4.63(m, 2H), 4.21-4.10(m, 2H), 2.94-2.55(m, 4H), 2.27(q, 1H), 1.891.15(m, 23H), 1.10(s, 9H), 0.98-0.87(m, 1H)。化合物99: MS: m/z 925·4(Μ++1) ; NMR(CDC13) δ 10.28(s, 1H), 8.37(d, 2H), 8.03(d, 1H), 7.50(d, 2H), 7.48(s, 1H), 7.01-6.92(m, 2H), 6.13(s, 1H), 5.65(q, 1H), 5.39(d, 1H), 4.98(dd, 1H), 4.88(dd, 1H), 4.64(s, 1H), 4.53(d, 1H), 4.41-4.23(m, 1H), 4.19-4.1 l(m, 1H), 3.88(s, 3H), 2.78-2.42(m, 3H)，2.26(q, 1H)，2.04-1.18(m，31H), 0.89-0.78(m, 4H)。化合物 100: MS: m/z 925.4(M++1) ; W NMR(CDC13> δ 10.23(s, 1H), 8.35(d, 2H), 7.77(d, 1H), 7.48(d, 2H), 7.38-7.22(m, 1H), 7.04-6.81(m, 2H), 6.16(s, 1H), 5.68(q, 1H), 5.21(d, 1H), 4.99(dd, 1H), 4.78(dd, 1H), 4.57(d, 1H), 4.22-4.03(m, 3H), 4.00(s, 3H), 2.80-2.43(m, 3H), 2.3 l(q, 1H), 1.96-1.20(m, 31H), 0.95-().78(m, 4H)。化合物 101: MS: m/z 827.3(M++1)。化合物 102: MS: m/z 897·4(Μ++1) ; 4 NMR(CDC13) δ 10.30(s, 1H), 8.39(d, 2H), 8.20(d, 1H), 7.59-7.37(m, 5H), 66 201109028 7.14(s, 1H), 6.04(s, 1H), 5.61(q, 1H), 5.21(d, 1H), 4.87(dd, 1H), 4.77(dd, 1H), 4.57(d, 1H), 4.19-4.07(m, 4H), 3.67-3.42 (m，2H)，3.17-2.40(m，6H)，2.20(q，1H), 1.93-0_78(m, 27H)。化合物 103: MS: m/z 866.3(M++1) ; NMR(CDC13) δ 10.45(s, 1H), 8.31(d, 2H), 8.12(d, 1H), 7.51-7.42(m, 5H), 7.32- 7.25(m, 1H), 6.09(s, 1H), 5.61(q, 1H), 4.90(dd, 1H), 4.81(dd, 1H), 4.59(d, 1H), 4.50-4.36(m, 2H), 4.13(dd, 1H), 3.69-3.27(m, 3H), 3.10(brs, 4H), 2.90-2.41(m, 4H), 2.19(q, 1H), 1.98-0.78(m, 25H)。化合物 104: MS: m/z 811·3(Μ++1) ; 'H NMR(CDC13) δ 10.38(s, 1H), 8.38(d, 2H), 8.19(d, 1H), 7.60-7.31(m, 5H), 7.32- 7.25(m, 1H), 6.15(s, 1H), 5.65(q, 1H), 4.88(dd, 1H), 4.70(dd, 1H), 4.57(dd, 1H), 4.40(d, 1H), 4.21-4.05(m, 2H), 2.95-2.41(m, 4H), 2.22(q, 1H), 2.01(s, 3H), 1.98-0.79(m, 24H)。化合物 105: MS: m/z 868·4(Μ++1);NMR(CDC13) δ 10.57(s, 1H), 8.37(d, 2H), 8.15(d, 1H), 8.09(s, 1H), 7.58-7.51(m, 4H), 7.27(dd, 1H), 6.09(s, 1H), 5.61(q, 1H), 4.98-4.79(m, 4H), 4.44(s, 1H), 4.10(dd, 1H), 3.79-3.68(m, 2H), 2.92-2.45(m，4H)，2.24(q，1H), 1.98-0.88(m, 32H)。化合物 106: MS: m/z 882.4(M++1) ; 4 NMR(CDC13) δ 10.37(s, 1H), 8.35(d, 2H), 8.16(d, 1H), 7.56-7.48(m, 2H), 7.42(d, 2H), 7.36-7.33(m, 1H), 7.30(s, 1H), 6.09(s, 1H), 5.63(q, 1H), 4.97-4.86(m, 2H), 4.76(dd, 1H), 4.58(d, 1H), 67 201109028 4.28-4.1 l(m, 2H), 3.39-3.25(m, 4H), 3.01-2.82(m, 5H), 2.75-2.44(m，2H)，2.16(q，1H)，1.95-0.76(m，25H)。化合物 107: MS: m/z 863_3(M++1) ; 4 NMR(CDC13) δ 10.34(s, 1H), 8.33(d, 2H), 8.32(d, 1H), 7.59-7.40(m, 6H), 7.37(s, 1H), 6.81(d, 1H), 6.65(d, 1H), 6.25(s, 1H), 6.13(s, 1H), 5.62(q, 1H), 4.87(dd, 1H), 4.69-4.52(m, 2H), 4,42(d, 1H), 4.18(dd，1H)，2.95-2.40(m，4H)，2.24-0.78(m, 25H)。化合物 108: MS: m/z 840.4(M++1);卞1 NMR(CDC13) δ 10.67(s, 1H), 8.32(d, 2H), 8.19(d, 1H), 7.77(s, 1H), 7.58-7.44(m, 4H), 7.34-7.25(m, 1H), 6.14(s, 1H), 5.77(q, 1H), 4.98(dd, 1H), 4.78-4.71(m, 2H), 4.44(d, 1H), 4.29(brs, 1H), 4.11-4.05(m, 1H), 2.96-2.72(m, 2H), 2.64(s, 6H), 2.41(br, 1H)，2_20(q, 1H), 1.96-0.78(m, 25H)。化合物 109: MS: m/z 837.4(M++1) ;「H NMR(CDC13) δ 10.49(s, 1H), 8.35-8.25(m, 3H), 7.71(s, 1H), 7.55-7.41(m, 4H), 7.26(s5 1H), 6.19(d, 1H), 6.01(s, 1H), 5.63(q, 1H), 4.88(dd, 1H), 4.71(brs, 1H), 4.56(d, 1H), 4.39(brs, 1H), 4.06(d, 1H), 2.81-2.45(m, 4H), 2.23(q, 1H), 1.99-1.64(m, 4H)，1.58-0.77(m, 21H), 0.51(brs，4H)。化合物 1]0: MS: m/z 865·4(Μ++1) ; W NMR(CDC13) δ 10.39(s, 1H), 8.29(d, 2H), 8.15(d, 1H), 7.56-7.42(m, 5H), 7.36-7.24(m, 1H), 6.05(s, 1H), 5.98(d, 1H), 5.64(q, 1H), 4.87 (dd, 1H), 4.69(dd, 1H), 4.55(d, 1H), 4.42(dd, 1H), 4.04(dd, 1H), 2.81-2.05(m, 5H), 1.95-1.71(m, 4H), 1.57-0.76 (m, 68 201109028 29H)。化合物 111: MS: m/z 881·4(Μ++1) ; 'H NMR(CDC13) δ 10.29(s, 1Η), 8.33(d, 2H), 8.30(s, 1H), 7.58-7.41(m, 4H), 7.39(dd, 1H), 7.22(s, 1H), 6.10(s, 1H), 5.98(d, 1H), 5.62(q, 1H), 4.91(dd, 1H), 4.68(dd, 1H), 4.46-4.40(m, 2H), 4.05(dd, 1H), 3.79-3.62(m, 2H), 3.21-3.09(m, 2H), 2.88-2.40(m, 3H), 2.22-1.72(m，6H), 1.47-0.78(m, 25H)。化合物 112: MS: m/z 864.3(M++1) ; A NMR(CDC13) δ 10.29(s, 1H), 8.38(d, 2H), 8.23(d, 1H), 8.09(s, 1H), 7.57-7.45(m, 5H), 7.41(dd, 1H), 7.28(s, 1H), 6.42(s, 1H), 6.15(s, 1H), 5.62(q, 1H), 4.86(dd, 1H), 4.75-4.66(m, 2H), 4.49(d, 1H), 4.17(dd, 1H), 2.83-2.43(m, 3H), 2.25(q, 1H), 1.99-0.78 (m, 25H)。化合物 113: MS: m/z 853·4(Μ++1) ; ’H NMR(CDC13) δ 10.34(s, 1H), 8.36(d, 2H), 8.30(d, 1H), 7.62-7.46(m, 4H), 7.41-7.36(m, 1H), 7.17(s, 1H), 6.19(s, 1H), 6.17(d, 1H), 5.68(q, 1H), 4.92(dd, 1H), 4.73(dd, 1H), 4.58-4.43(m, 2H), 4.19(dd, 1H), 2.89-2.43(m, 3H), 2.22(q, 1H), 1.99-1.82(m, 6H), 1.59-0.83(m，28H)。化合物 114: MS: m/z 907.3(M++1) ; 'H NMR(CDC13) δ 10.30(s, 1H), 8.39(d, 2H), 8.21(d, 1H), 7.56(dd, 1H), 7.48(d, 2H), 7.40(dd, 1H), 7.24(s, 1H), 7.18(d, 2H), 7.03(d, 2H), 6.92(s, 1H), 6.06(s, 1H), 5.74(d, 1H), 5.61(q, 1H), 4.87(dd, 1H), 4.70(dd, 1H), 4.42(d, 1H), 4.31(dd, 1H), 4.08(dd, 1H), 69 5 201109028 2.84-2.79(m, 1H), 2.65-2.43(m, 2H), 2.23(q, 1H), 1.88-1.62 (m, 6H)，1.49-0.78(m，19H)。化合物 115: MS: m/z 895.4(M++1) ; ’H NMR(CDC13) δ 10.42(s，lH)，8.40(d，2H)，8.01(s，lH)，7.55(d，2H),7.46-7.32(m, 3H), 6.13(s, 1H), 5.61(q, 1H), 5.32(brs, 1H), 5.01-4.87(m, 1H), 4.89(dd, 1H), 4.62-4.55(m, 2H), 4.34-4.08 (m, 2H), 2.94-2.55(m, 4H), 2.50(s, 3H), 2.23(q, 1H), 1.95-1.10(m, 32H)。化合物 1]6: MS: m/z 9()9.4(M++1) ; !H NMR(CDC13) δ 10.29(s, ΓΗ), 8.40(d, 2H), 8.01(s, 1H), 7.55(d, 2H), 7.47-7.26(m, 3H)5 6.14(s, 1H), 5.69(q, 1H), 5.37(d, 1H), 4.99(dd, 1H), 4.78(dd, 1H), 4.60(d, 1H), 4.40-4.05(m, 3H), 2.80-2.51 (m, 3H), 2.50(s, 3H), 2.29(q, 1H), 1.98-1.12(m, 32H), 0.82.(s, 3H)。化合物 117: MS: m/z 855.2(M++1) ; rH NMR(CDC13) δ 10.08(s, 1H), 8.22(d, 2H), 8.03(d, 2H), 7.44-7.18(m, 3H), 7.26-7.17(m, 1H), 7.13(d, 1H), 6.12(s, 1H), 5.65(q, 1H), 4.89(dd, 1H), 4.77(dd, 1H), 4.49(d, 1H), 4.42-4.36(m, 1H), 4.13(dd, 1H), 3.16(s, 1H), 2.84-2.46(m, 4H), 2.16(q, 1H), 1.95-0.77(m，31H)。化合物 1]8: MS: m/z 895·4(Μ++1)。化合物 1】9: MS: m/z 895.4(M++1)。化合物 120: MS: m/z 840·2(Μ++1) ; 4 NMR(CDC13) δ 10.26(s, 1H), 8.38(d, 2H), 8.20(d, 1H), 8.00(d, 1H), 7.61- 70 201109028 7.54(m, 2H), 7.50(d, 2H), 7.41-7.35(m, 1H), 7.15(s, 1H), 6.72(d, 1H), 6.10(d, 1H), 5.63(q, 1H), 5.27(d, 1H), 4.89(dd, 1H), 4.68(dd, 1H), 4.51-4.42(m, 2H), 4.12(dd, 1H), 2.84-2.43 (m，4H)，2.22(q，1H)，1.98-0.84(m，24H)。化合物 121: MS: m/z 829.3(M++1)。化合物 122: MS: m/z 833.3(M++1)。化合物 123: MS: m/z 821.3(M++1) ; NMR(CDC13) δ 10.27(s, 1H), 7.90(dd, 1H), 7.60(s, 1H), 7.27(dd, 1H), 7.32-7.20(m, 2H), 6.91(s, 1H), 6.53(dd, 1H), 6.03(s, 1H), 5.64(q, 1H), 4.98-4.89(m, 2H), 4.71-4.58(m, 2H), 4.14-4.03 (m, 2H), 2.86-2.80(m, 1H), 2.67-2.40(m, 2H), 2.22(q, 1H), 1.98-1.10 (m，15H), 1.05(s，9H)，0.98-0.82(m, 1H)。化合物 124: MS: m/z 779·2(Μ++1) ; NMR(CDC13) δ 10.31(s, 1H), 7.93(dd, 1H), 7.70(s, 1H), 7.65-7.55(dd, 1H), 7.41-7.26(m, 2H), 7.04(s, 1H), 6.61(s, 1H), 6.15(s, 1H), 5.72(q, 1H), 5.37(d, 1H), 5.01-4.91(m, 1H), 4.77(dd, 1H), 4.46(d, 1H), 4.37-4.09(m, 2H), 3.36(s, 3H), 2.92-2.53(m, 3H), 2.23(q，1H)，1.99-0.86(m，16H)。化合物 125: MS: m/z 817_2(M++1) ; 'H NMR(CDC13) δ 10.28(s, 1H), 7.98(d, 1H), 7.66(s, 1H), 7.60(dd, 1H), 7.40-7.09(m, 3H), 6.11(s, 1H), 6.60(s, 1H), 6.17(s, 1H), 5.72(q, 1H), 4.99(dd, 1H), 4.76-4.67(m, 2H), 4.31-4.18(m, 2H), 2.91-2.75(m，2H), 2.45(br，1H), 2.22-0.84(m，17H)。化合物 126: MS: m/z 763·2(Μ++1) ; 4 NMR(CDC13) δ 71 201109028 10.29(s, 1H), 7.81(dd, 1H), 7.60(s, 1H), 7.52(dd, 1H), 7.35-7.18(m, 3H), 6.52(d, 1H), 6.13-6.01(m, 2H), 5.61(q, 1H), 4.83(dd, 1H), 4.62(dd, 1H), 4.45(dd, 1H), 4.38(d, 1H), 4.17(dd, 1H), 2.85-2.79(m, 1H), 2.67(d, 1H), 2.41(m, 1H), 2.21-0.84(m, 20H)。化合物 127: MS: m/z 821·3(Μ++1) ; NMR(CDC13) δ 10.37(s, 1H), 8.15(s, 1H), 7.79(d, 1H), 7.45-7.42(m, 3H), 7.35-7.25(m, 1H), 7.01(s, IH), 5.89(s, 1H), 5.54(q, 1H), 5.19(d, 1H), 4.85(dd, 1H), 4.67(dd, 1H), 4.54(d, 1H), 4.20(dd, 1H), 4.04(d, 1H), 2.91-2.44(m, 3H), 2.24(q, 1H), 2.01-1.ll(m, 15H)，1.06(s，9H)，0.83-0.78(m，1H)。化合物 128: MS: m/z 833.3(M++1) ; rH NMR(CDC13) δ 10.37(s, 1H), 8.07(d, 1H), 7.56-7.22(m, 5H), 6.89(d, 1H), 5.96(s, 1H), 5.57-5.49(m, 1H), 5.21-5.17(m, 1H), 4.96-4.83 (m, 1H), 4.72(dd, 1H), 4.67(d, 1H), 4.18-4.03(m, 2H), 2.90-2.79(m, 1H), 2.69(s, 3H), 2.64-2.46(m, 2H), 2.22(q, 1H), 1.97-1.04(m, 15H), 1.04(s，9H), 0.96-0.87(m, 1H)。化合物 129: MS: m/z 836.3(M++1) ; NMR(CDC13) δ 10.29(s, 1H), 7.88(d, 1H), 7.53-7.50(m, 1H), 7.49(dd, 1H), 7.19(s, 1H), 6.65(s, 1H), 6.04(s, 1H), 5.70-5.50(m, IH), 5.12-4.48(m, 4H), 4.19-3.98(m, 2H), 2.95-2.58(m, 3H), 2.48(s, 3H)S 2.32-2.12(m, 1H), 1.97-1.18(m, 15H), 1.00(s, 9H)，0.98-0.86(m, 1H)。化合物 130: MS: m/z 832.2(M++1);NMR(CDC13) δ 72 201109028 10.20(s, 1H), 7.84(dd, 1H), 7.52(dd, 1H), 7.39(, 1H), 7.38-7.26(m, 2H), 6.62(s, 1H), 6.05(s, 1H), 5.60(q, 1H), 4.83(dd, 1H), 4.67(dd, 1H), 4.55(dd, 1H), 4.36(d, 1H), 4.08(dd, 1H), 2.81-2.50(m, 3H), 2.48(s, 3H), 2.45-2.37(m, 1H), 2.18(q, 1H), 1.99-0_87(m, 15H)。化合物 131: MS: m/z 888.3(M++1) ; NMR(CDC13) δ 10.36(s, 1H), 8.23(d, 1H), 7.41(s, 1H), 7.30(m, 2H), 7.11(s, 1H), 6.16(s, 1H), 5.68(q, 1H), 5.23(d, 1H), 4.98(dd, 1H), 4.75(brs, 1H), 4.54(d, 1H), 4.36-4.11(m, 3H), 3.39-3.27(m, 1H), 2.96-2.63(m, 3H), 2.54(s, 3H), 2.25(q, 1H), 1.89-0.93(m, 30H)。化合物 132: MS: m/z 888.3(M++1) ; ’H NMR(CDC13) δ 10.24(s, 1H), 8.37(d, 1H), 7.74-7.51(m, 2H), 7.48-7.42(m, 1H), 7.22(s, 1H), 7.12(s, 1H), 6.17(s, 1H), 5.70(q, 1H), 5.28 (d, 1H), 4.99(dd, 1H), 4.76(dd, 1H), 4.58(d, 1H), 4.52(brs, 1H), 4.35-4.16(m, 2H), 3.40-3.35(m, 1H), 2.79-2.43 (m, 3H), 2.25(q, 1H)，1.95-1.23(m, 29H)，0.87-0.76(m, 3H)。化合物 133: MS: m/z 887·3(Μ++1) ; 4 NMR(CDC13) δ 10.37(s, 1H), 8.59(s, 1H), 8.22(d, 1H), 7.81(d, 1H), 7.58-7.42(m, 3H), 6.95-6.89(m, 2H), 6.09(s, 1H), 5.68(q, 1H), 5.32(d, 1H), 4.99(m, 1H), 4.74(m, 1H), 4.54(d, 1H), 4.39-4.22(m, 1H), 4.14-4.11(m, 1H), 2.90(m, 1H), 2.78(m, 2H), 2.55(m, 1H), 2.27(q, 1H), 1.90-1.10(m, 21H), 1.45(s, 9H), 0_94-0.83(m，2H)。 73 201109028 化合物 134: MS: m/z 901.3(M++1);】H NMR(CDC13) δ 10.21(s,lH)，8.8.51(s，lH)，8.23(d，lH)，7.81(d，lH)，7.59-7.43(m, 3H), 7.13(s, 1H), 6.90(d, 1H), 6.09(s, 1H), 5.68(q, 1H), 5.22(d, 1H), 4.99(dd, 1H), 4.76(m, IH), 4.55(d, 1H), 4 39-4.22(m, 1H), 4.14-4.1 l(m, 1H), 2.78(m, 2H), 2.55(m, 1H)，2_27(q，1H)，1.90-0_83(m，23H), 1.46(s，9H)。化合物 135: MS: m/z 888.3(M++1)。化合物 136: MS: m/z 902.3(M++1)。化合物 137: MS: m/z 899.4(M++1)。化合物 138: MS: m/z 885.3(M++1) ; 4 NMR(CDC13) δ 10.36(s, 1H), 8.17(d, 1H), 7.58(m, 2H), 7.42-7.33(m, 2H), 6.63(m, 1H), 6.07(s, 1H)} 5.67(q, 1H), 5.29(d, 1H), 4.97(dd, 1H), 4.77(m, 1H), 4.57(m, 1H), 4.42-4.03(m, 3H), 2.89(m, 1H), 2.75(m, 5H), 2.52(m, 1H), 2.27(q, 1H), 1.91-0.82(m, 32H)。化合物 139: MS: m/z 803.3(M++1)。化合物 140: MS: m/z 817.3(M++1)。化合物 14L MS: m/z 831.3(M++1) ; 4 NMR(CDC13) δ 10.33(s, 1H), 8.05(s, 1H), 7.56-7.48(m, 3H), 6.06(s, 1H), 5.62(q, 1H), 5.15(dd, 1H), 4.91(dd, 1H), 4.75(dd, 1H), 4.59(d, 1H), 4.35-4.02(m, 3H), 2.96-2.88(m, 1H), 2.74-2.65(m, 2H), 2.53(s，3H)，2.24(q，1H)，1.96-0.89(m, 24H)。實施例142和143 : 合成[4-¾丙績酿基氣基幾基-2,15-二乳代-18-(2-苯基_ 74 201109028 苯並[4,5]呋喃並[3，2-b]吼啶-4-基氧基）-3，16-二氮雜三環 [14.3·0·04,6]十九碳-7-烯-14-基]-氨基甲酸叔丁酯（化合物 142) 和[4-環丙績醯基氨基幾基-2,15-二氧代-18-(2-笨基-笨並[4,5]吱喃並[3,2-b]吼咬-4-基氧基）_316_二氮雜三環 [14.3.0.04,6]十九碳-7-稀-14-基]-氨基甲酸環戊酯（化合物 143) 化合物I42和I43通過以下合成路線製備： 75 201109028A solution of 3-amino-p-furanfuran-2-carboxylic acid decylamine (1.00 g, 5.7 mmol) and pyridine (1 mL, 12.26 mmol) in THF (25 mL) was stirred for 10 min. To the resulting solution was slowly added 4-trifluorodecyl-benzhydrazene 41 201109028 (1·48 g, 7.1 mmol). The temperature was then raised to room temperature and the mixture was stirred for 12 hours. After removing the solvent under reduced pressure, the solid formed was collected, washed with water and dried to give 1-4 (1.92 g, 96.0%). MS: m/z 349.0 (M++1) 〇 1-4 (1.92 g, 5.5 mmol) and 2\\3 〇 13 13 ml) in a suspension of 玢 011 (25 ml) at 85 ° C 12 hours. After cooling, the mixture was acidified and then EtOH was removed. The solid which formed was collected, filtered, washed with water and dried to give 1-5 (1.71 g, 95.0%). MS m/z 331 (M++1). A solution of 1-5 (1.71 g, 5.2 mmol) and excess phosphorus argon (POCl3) was refluxed for 2 hours. After cooling and complete concentration, the mixture was extracted with dichloromethane and 10% sodium hydroxide. The organic layer was dried with EtOAc (EtOAc) (EtOAc) (HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH , 2Η), 8.34(d, 1H), 7·82·7_75(ητ, 4H), 7.57 (ddd, 1H). To a suspension of Boc-trans-4-hydroxy-L-proline (0.53 g, 2.3 mmol) in DMSO (25 mL) was added t-BuOK (0.82 g, 5.1 mmol). After the mixture was allowed to warm to room temperature and stirred for 1 hour, the compound oxime-6 (0.81 g, 2.3 mmol) was slowly added to 0 °C. Continue stirring overnight. Iodine (1. 02 g, 6.9 mmol) was added. The reaction mixture was further stirred at room temperature for 30 minutes. The reaction mixture was neutralized to a pH of 6-7 with a 10% aqueous HCl solution and extracted with di-methane. The organic layer was dried with EtOAc (EtOAc m.) MS m/z 557.8 (M++1); 'H NMR (CDC13) δ 8.63 (d, 2 Η), 8.28 (d, 1H), 7.80-7.74 (m, 2H), 7.70 (d, 2H), 7.51 (ddd, 1H) 〇42 201109028 </RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; The reaction mixture was returned to the hour to remove Me〇H and S〇Cl2. The residue was ground with a pen. The suspension was filtered to give a compound (yield: 87 g, 95%). MS m/z 458·1 (Μ++1). To the brew, to HATU (1.12 g '3_〇 mmol), p-benzotriazole (HOBT, 41.41 g '3.0 mmol), work, Buick, i 9 mmol) and 2 · tert-butoxy N-methylmorpholine (NMM, 2 g, 9-9 mmol) was added to a solution of carbonylamino-indole-8-enoic acid (1.21 g, 19 mmol) in CH2C12 (40 mL). After stirring overnight, the compound was concentrated under vacuum. The residue was purified by column chromatography eluted to afford compound </RTI> -9 (m. MS m/z 711.3 (Μ++1). To a solution of compound 1-9 (1.01 g, 1.4 mmol) in EtOAc (2 mL), EtOAc. After stirring overnight, the reaction mixture was neutralized to pH with 丨〇% HCl. < 7, and concentrated with vacuum. The resulting residue is filtered and washed with water to give compound 1-10 (0. 91 grams, 92%). MS: m/z 697·3 (Μ++1). At room temperature, it will be ΝΜΜ (0. 12 grams, 1. 2 mmol) is added to compound 1-3 (0. 28 grams ’ 0. 4 mmol), HATU (0. 31 grams, 0. 8 mmol), ΗΟΒΤ (0. 08 g, 〇·6 mmol) and compound 1-10 (0. 〇 9 grams, 0. 4 mmol) in a solution of CH2Cl2 (10 mL). After stirring overnight, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography to give compound 1-11 (0. 10 grams, 85%) ° MSm / z921. 3(M++l); HNMWCDCh) δ 10. 24 (8, 1Η), 8. 61(d, 2H), 8. 26(d, 1H), 7. 77(d, 2H), 7. 73- 43 201109028 7. 64(m, 2H), 7. 54-7. 47(m, 1H), 7. 11(s, 1H), 6. 19(d, 1H), 5. 88-5. 70 (m, 2H), 5. 38-5. 25(m, 2H), 5. 16(d, 1H), 5. 00-4. 90 (m, 2H), 4. 60 (dd, 1H), 4. 88-4. 34(m, 2H), 4. 18-4. 10 (m, 1H), 2. 98-2. 89 (m, 1H), 2. 68 (dd, 2H), 2. 18-1. 96 (m? 6H), 1. 50-1. 32 (m, 7H), 1. 28(s,9H), 1. 09-1. 25 (m, 2H). At room temperature, under the N2 atmosphere to the compound M 丨 (0. 10 grams, 0. 11 mmol) Add the Hoveyda-Grubbs II (35 mg, 0.) solution in milliliters). 056 mmol). Then, the reaction mixture was stirred at 40 C for 24 hours to carry out metathesis cyclization. The reaction was quenched and the reaction mixture was purified mpjjjjjjj MS: m/z 893. 3(M++1) ; lH NMR(CDC13) δ 10. 39(s,1H), 8. 59(d, 2H), 8. 21 (d, 1H), 7. 77 (d, 2H), 7. 69-7. 57(m, 2H), 7. 46 (dd, 1H), 7. 20(s, 1H), 6. 12(s, 1H), 5. 69(q, 1H), 5. 12(d, 1H), 4. 97 (dd, 1H), 4. 81-4. 68(m, 2H), 4. 28-4. 07(m, 2H), 2. 96-2. 49(m, 3H), 2. 30(q, 1H), 1. 96-1. 12(m, 14H), 1. 08(s, 9H), 0. 96-0. 82 (m, 2H) ° room temperature, under the A atmosphere to the compound 142 (30 mg, 0. 034 mmol.) 5% pd-C (5 mg) was added to a solution of MeOH (1 mL). Then, the reaction mixture was stirred at room temperature under a hydrogen pressure of 60 psi' for 4 hours. The reaction mixture was filtered and purified by column chromatography to give Compound 1 (16. 5 mg ' 55%) ° MS: m/z 895. 3(M++1); 'H NMR(CDC13) δ 10. 79(s, 1H), 8. 57(d, 2H), 8. 21(d, 1H), 7. 75(d, 2H), 7. 64(m, 2H), 7. 46(d, 1H), 7. 11(s, 1H), 6. 11(s> ih), 5. 29(d, 1H), 4. 72(m, 2H), 4. 38(m, 2H), 4. 12 (m, 1H), 3. 〇 2-2. 58(m, 3H), 1. 98-0. 86 (m, 44 201109028 29H). Example 2-141: Synthesis of Compound 2-141 Compound 2-141 was each prepared in a similar manner to that described in Example 1. Compound 2: MS: m/z 883. 3(M++1) ; NMR(CDC13) δ 10. 51(s, 1H), 8. 53(d, 2H), 8. 16(d, 1H), 7. 73(d, 2H), 7. 62(m, 2H), 7. 22(m, 2H), 6. 07(s, 1H), 5. 23(d, 1H), 4. 77 (dd, 1H), 4. 49(d, 1H), 4. 35 (m, 1H), 4. 13(m, 1H), 3. 02-2. 57(m, 3H), 1. 99-0. 91 (m, 30H). Compound 3: MS: m/z 823. 2(M++1) ; 'H NMR(CDC13) δ 10. 38(s, 1H), 8. 53(d, 2H), 8. 16(d, 1H), 7. 73(d, 2H), 7. 61(m, 2H), 7. 41(m, 2H), 6. 13(m, 2H), 5. 69(q, 1H), 4. 98 (dd, 1H), 4. 78(m, 1H), 4. 55 (m, 1H), 4. 42 (m, 1H), 4. 19 (m, 1H), 2. 89 (m, 1H), 2. 78(m, 2H), 2. 52(m, 1H), 2. 23(q, 1H), 1. 96-0. 84 (m, 15H), 1. 90 (s, 3H). Compound 4: MS: m/z 882. 3(M++1) ; 4 NMR(CDC13) δ 10. 47(s, 1H), 8. 64(d, 1H), 8. 52(m, 3H), 7. 70(d, 2H), 7. 44 (dd, 1H), 6. 07(s, 1H), 5. 63(q, 1H), 5. 01-4. 73(m, 3H), 4. 07-4. 01(m, 2H), 2. 90-2. 22(m, 4H), 1. 97-1. 09(m, 17H), 0. 94(s, 9H), 0. 90-0. 88 (m, 1H). Compound 5: MS: m/z 840. 2(M++1) ; 'H NMR(CDC13) δ 10. 42(s, 1H), 8. 64-8. 47(m, 4H), 7. 80(d, 2H), 7. 50-7. 27(m, 2H), 6. 15(s, 1H), 5. 69(q, 1H), 5. 23(d, 1H), 5. 02(dd, 1H), 4. 84 (dd, 1H), 4. 53(d, 1H), 4. 25-4. Ll(m, 2H), 3. 32(s, 3H), 45 201109028 2. 93- 2. 15 (m, 4H), 1. 92-0. 83 (m, 16H). Compound 6: MS: m/z 824. 2(M++1) ; 4 NMR(CDC13) δ 10. 48(s, 1H), 8. 63(d, 1H), 8. 62-8. 48(m, 3H), 7. 78(d, 2H), 7. 44_7. 4〇(m> ih), 6. 16-6. 14(m, 2H), 5. 73(q, 1H), 5. 04 (dd, 1H), 4. 85 (dd, 1H), 4. 55(s,1H), 4. 51(s,1H), 4. 15(d,1H), 2. 93- 2. 89(m, 2H), 2. 77-2. 22 (m, 3H), 1. 95-1. 85(m, IK), 1. 79(s,3H), 1. 76-0. 83 (m,] 5H). Compound 7: MS: m/z 839. 2 (M++1); NMR (C: DC13) δ 10. 39(s, 1H), 8. 46(d, 2H), 8. 15(d, 1H), 7. 71(d, 2H), 7. 62-7. 37(m, 3H)5 7. 16(s, 1H), 6. 08(s, 1H), 5. 71(q, 1H), 5. 25(d, 1H), 4. 96 (dd, 1H), 4. 75 (dd, 1H), 4. 44(d, 1H), 4. 35-4. 09(m, 2H), 3. 34(s, 3H), 2. 96-2. 71(m, 2H), 2. 57(brs, 1H), 2. 28(q, 1H), 2. 08-0. 87 (m, 16H). Compound 8: MS: m/z 849. 3(M++1) ; 'H NMR(CDC13) δ 10. 54(s, 1H), 8. 45(d, 2H), 8. 06(d, 1H), 7. 71(d, 2H), 7. 57(m, 3H), 7. 35(s, 1H), 6. 28(d, 1H), 6. 04(s, 1H), 5. 71(q, 1H), 4. 96 (dd, 1H), 4. 67(dd, 1H), 4. 47(d, 1H), 4. 45(brs, 1H), 4. 11 (m, 1H), 2. 92-2. 45 (m, 4H), 2. 32(q, 1H), 1. 96-0. 84 (m, 20H). Compound 9: MS: m/z 880. 3(M++1) ; 4 NMR(CDC13) δ 10. 45(s, 1H), 8. 40(d, 2H), 8. 14(s, 1H), 7. 97(d, 1H), 7. 64(d, 2H), 7. 48-7. 41(m, 2H), 7. 25-7. 20 (m, 1H), 5. 96(s, 1H), 5. 63(q, 1H), 4. 92-4. 86(m, 2H), 4. 77(d, 1H), 4. 44(s, 1H), 4. 20 (dd, 1H), 4. 03(dd, 1H), 2. 90-2. 84(m, 2H), 2. 80-2. 63(m, 1H), 46 201109028 2. 38-2. 32(m, 1H), 1. 98-1. 02(m, 15H), 0. 91(s, 9H), 0. 90-. 086 (m, 1H). Compound 10: MS: m/z 911·2 (Μ++1); *H NMR (CDC13) δ 10. 23(s, 1H), 8. 54(d, 2H), 7. 87-7. 80 (m, 1H), 7. 71(d, 2H), 7. 56(dd, 1H), 7. 33-7. 20 (m, 1H), 6. 88(s, 1H), 6. 13(s, 1H), 5. 65(q, 1H), 5. 07-4. 94(m, 2H), 4. 69 (dd, 1H), 4. 57(d, 1H), 4. 43-4. 38(m, 1H), 4. 24-4. 01(m, 2H), 2. 91-2. 80 (m, 2H), 2. 74 (s, 3H), 2. 65-2. 63(m, 1H), 2. 60-2. 41 (m, 1H), 2. 22(q, 1H), 1. 98-0. 86 (m, 20H). Compound 11: MS: m/z 907. 3 (M++1). Compound 12: MS: m/z 923·3 (Μ++1); NMR (CDC13) δ 10. 42(s, 1H), 8. 57(d, 2H), 8. 06(d, 1H), 7. 76(d, 2H), 7. 51(s, 1H), 7. 14-6. 93(m, 2H), 6. 13(s, 1H), 5. 80-5. 60 (m, 1H), 5. 31(d, 1H), 4. 97-4. 83(m, 2H), 4. 79 (dd, 1H), 4. 64-4. 04(m, 3H), 3. 88(s, 3H), 2. 94-2_43(m, 3H), 2. 36-0. 86 (m, 25H). Compound 13: MS: m/z 852. 3(M++1) ; 'H NMR(CDC13) δ 10. 68(s, 1H), 8. 38(d, 2H), 7. 95(d, 1H), 7. 72-7. 58(m, 3H), 7. 47(d, 2H), 7. 24-7. 19(m, 1H), 6. 01(s, 1H), 5. 69(q, 1H), 4. 94 (dd, 1H), 4. 78(dd, 1H), 4. 70(d, 1H), 4. 46(d, 1H), 4. 22- 3. 98(m, 2H), 2. 97-2. 80 (m, 2H), 2. 57(s, 6H), 2. 67-2. 41 (m, 1H), 2. 23(q, 1H), 1. 85-0. 84 (m, 16H). Compound 14: MS: m/z 766·2 (Μ++1); 'H NMR (CDC13) δ 10. 30(s, 1H), 8. 62 (m, 2H), 8. 24(m, 1H), 7. 77(d, 2H), 7. 67(m, 2H), 7. 48 (m, 1H), 6. 90(s, 1H), 6. 18(s, 1H), 5. 72(q, 1H), 47 201109028 4. 98 (dd, 1H), 4. 65 (dd, 1H), 4. 24(m, 1H), 4. 05(m, 1H), 2. 92 (m, 1H), 2. 76(m, 2H), 2. 58-2. 28(m, 4H), 1. 94-1. 05(m, 13H), 0. 97-0. 86 (m, 2H). Compound 15: MS: m/z 893. 3 (M++1); NMR (CDC13) δ 10. 33(s, 1H), 8. 88(s, 1H), 8. 68(d, 1H), 8. 26(d, 1H), 7. 80-7. 65 (m, 4H), 7. 35-7. 26(m, 1H), 6. 98(d, 1H), 6. 20(d, 1H), 5. 71(q, 1H), 5. 18(d, 1H), 5. 00 (dd, 1H), 4. 77 (dd, 1H), 4. 64(d, 1H), 4. 46(s, 1H), 4. 25(dd, 1H), 4. 15(dd, 1H), 2. 92-2. 28(m, 4H), 2. 17-0. 82 (m, 24H). Compound 16: MS: m/z 877. 3(M++1) ; 4 NMR(C:DC13) δ 10. 40(s, 1H), 8. 45(d, 2H), 8. 04(d, 1H), 7. 62(d, 2H), 7. 58-7. 50 (m, 2H), 7. 44(s, 1H), 7. 35 (dd, 1H), 6. 02(s, 1H), 5. 95(d, 1H), 5. 63(q, 1H), 4. 81 (dd, 1H), 4. 70 (dd, 1H), 4. 49(d, 1H), 4. 42-4. 38(m, 1H), 4. 04(dd, 1H), 2. 90-2. 20(m, 6H), 1. 96-0. 83 (m, 23H) » Compound 17: MS: m/z 907. 3(M++1) ; 4 NMR(CDC13) δ 10. 42(s, 1H), 8. 73(s, 1H), 8. 62(d, 1H), 7. 96(s, 1H), 7. 71(d, 1H), 7. 64 (dd, 1H), 7. 59-7. 25(m, 3H), 6. 11(s, 1H), 5. 62(q, 1H), 5. 21(d, 1H), 4. 99(dd, 1H), 4. 79 (dd, 1H), 4. 61(d, 1H), 4. 52(s, 1H), 4. 25-4. 10(m, 2H), 2. 95-2. 51(m, 3H), 2. 47(s , 3H), 2. 31(q,]H), 2. 03-0_91 (m, 24H). Compound 18: MS: m/z 767. 2(M++1) ; NMR(CDC13) δ 10. 38(s, 1H), 8. 49(d, 2H), 8. 15(d, 1H), 7. 77(d, 2H), 7. 64-7. 58(m, 2H), 7. 41-7. 32(m, 1H), 7. 29(s, 1H), 6. 08(s, 1H), 48 201109028 5. 78(q, 1H), 5. 08(dd, 1H), 4. 66(dd, 1H), 4. 42(d, 1H), 4. 09-4. 06(m, 1H), 3. 85-3. 62 (m, 4H), 2. 93-2. 45 (m, 4H), 2. 04-0. 87 (m, 13H). Compound 19: MS: m/z 899·3 (Μ++1); Η NMR (CDC13) δ 10. 28(s, 1H), 8. 51(d, 2H), 7. 80 (dd, 1H), 7. 70(d, 2H), 7. 51-7. 42(m, 1H), 7. 37-7. 23(m, 1H), 6. 97(s, 1H), 6. 06(s, 1H), 5. 63(q, 1H), 4. 96-4. 85(m, 2H), 4. 75-4. 63(m, 2H), 4. 09-4. 02 (m, 2H), 2. 93-2. 43(m, 4H), 2. 21(q,1H), 1. 96-0. 76 (m, 24H). Compound 20: MS: m/z 895. 3(M++1) ; 4 NMR(CDC13) δ 10. 42(s, 1H), 8. 43(d, 2H), 7. 81(s, 1H), 7. 67(d, 2H), 7. 51(s, 1H), 7. 35-7. 28(m, 2H), 5. 92(s, 1H), 5. 57(q, 1H), 5. 19(d, 1H), 4. 88-4. 61(m, 3H), 4. 14-4. 00 (m, 2H), 2. 83-2. 41 (m, 4H), 2. 38(s, 3H), 2. 24(q, 1H), 1. 96-1. 16 (m, 15H), 1. 05(s, 9H), 0. 97-0. 78 (m, 1H). Compound 21: MS: m/z 923·3 (Μ++1); 'H NMR (CDC13) δ 10. 33(s, 1H), 8. 50(d, 2H), 7. 67(d, 2H), 7. 59(s, 1H), 7. 41(d, 1H), 7. 34(s, 1H), 7. 16(d, 1H), 6. 06(s, 1H), 5. 64(q, 1H), 5. 23(d, 1H), 4. 94 (dd, 1H), 4. 87 (dd, 1H), 4. 58-4. 42 (m, 2H), 4. 30-4. 02(m, 2H), 3. 84(s, 3H), 2. 88-2. 44(m, 4H), 2. 21(q, 1H), 1. 84-0. 78 (m, 23H). Compound 22: MS: m/z 752. 2(M++1) ; 4 NMR(CDC13) δ 10. 76(s, 1H), 8. 61(d, 2H), 8. 25(m, 1H), 7. 79(d, 2H), 7. 67(d, 2H), 7. 52(m, 1H), 6. 70(s, 1H), 6. 19(s, 1H), 5. 69(q, 1H), 5. 08(m, 1H), 4. 65 (dd, 1H), 4. 23(dd, 1H), 4. 02(m, 1H), 49 201109028 3. 05-1. 98 (m, 7H), 1. 96-0. 82 (m, 13H). Compound 23: MS: m/z 907·3 (Μ++1); if! NMR (CDC13) δ 10. 40(s, 1H), 8. 56(d, 2H), 8. 08(d, 1H), 7. 73(d, 2H), 7. 29(s, 1H), 7. 26-7. 20(m, 2H), 6. 13(s, 1H), 5. 71(q, 1H), 5. 22(d, 1H), 4. 95 (dd, 1H), 4. 82-4. 73 (m, 1H), 4. 63-4. 51(m, 1H), 4. 33-4. 06 (m, 2H), 2. 96-2. 51(m, 4H), 2. 53(s, 3H), 2. 24(q, 1H), 1. 96-0. 94 (m, 24H). Compound 24: MS: m/z 916. 3(M++1) ; 4 NMR(CDC13) δ 10. 37(s, 1H), 8. 48(d, 2H), 8. 08(s, 1H), 7. 68(d, 2H), 7. 50-7. 37(m, 3H), 6. 01(s, 1H), 5. 59(q, 1H), 5. 13(d, 1H), 4. 83 (dd, 1H), 4. 74-4. 63(m, 2H), 4. 15(dd, 1H), 4. 05(d, 1H), 2. 94-2. 41 (m, 4H), 2. 21(q, 1H), 1. 89-1. 14(m, 14H), 1. 03(s, 9H), 0. 96-0. 85 (m, 1H). Compound 25: MS: m/z 923. 3 (M++1). Compound 26: MS: m/z 923. 3(M++1) ; 4 NMR(CDC13) δ 1035(s, 1H), 8. 50(d, 2H), 7. 69(d, 2H), 7. 52 (dd, 1H), 7. 40(s, 1H), 7. 12(d, 1H), 6. 75(d, 1H), 6. 05(s, 1H), 5. 63(q, 1H), 5. 27(d, 1H), 4. 97-4. 83 (ms 1H), 4. 75 (dd, 1H), 4. 42 (brs, 1H), 4. 28-4. 08(m, 2H), 4. 08(s, 3H), 2. 91-2. 38(m, 4H), 2. 23(q, 1H), 1. 96-0. 82 (m, 24H). Compound 27: MS: m/z 894_3 (M++1); "H NMR (CDC13) δ 10. 38(s,]H), 8. 47(d, 2H), 8. 08(d,lH), 7. 62 (d, 2: H), 7. 58-7. 54(m, 2H), 7. 40-7. 33(m, 1H), 7. 3 l(s, 1H), 6. 07(s, 1H), 5. 63(q, 1H), 4. 95 (dd, 1H), 4. 83(d, 1H), 4. 87 (dd, 1H), 4. 58(d, 50 201109028 1H), 4. 31-4. 19(m, 1H), 4. 09(dd, 1H), 3. 40-3. 32(m, 4H), 3. 01-2. 41 (m, 8H), 2. 19(q, 1H), 1. 92-0. 83 (m, 15H). Compound 28: MS: m/z 878·3 (Μ++1); 'H NMR (CDC13) δ 10. 56(s, 1H), 8. 41(d, 2H), 8. 02(d, 1H), 7. 74(s, 1H), 7. 68(d, 2H), 7. 53-7. 47(m, 2H), 7. 35-7. 32(m, 1H), 6. 01(s, 1H), 5. 62(q, 1H), 4. 90 (dd, 1H), 4. 78(dd, 1H), 4. 59-4. 43(m, 2H), 4. 35-4. 25 (m, 1H), 4. 05(dd, 1H), 3. 61-3. 49(m, 1H), 3. 01-2. 45 (m, 8H), 2. 21(q, 1H), 1. 85-0. 83 (m, 18H). Compound 29: MS: m/z 909·3 (Μ++1); 4 NMR (CDC13) δ 10. 27(s, 1H), 8. 53(d, 2H), 8. 16(d, 1H), 7. 67(d, 2H), 7. 64-7. 43(m, 4H), 6. 03(s, 1H), 5. 61(q, 1H), 5. 22-5. 19(m, 1H), 4. 87 (dd, 1H), 4. 66(dd, 1H), 4. 57(d, 1H), 4. 19-4. 01(m, 3H), 3. 71-3. 42 (m, 4H), 3. 19-2. 97(m, 2H), 2. 91-2. 43(m, 4H), 2. 20(q, 1H), 1. 95-0. 81 (m, 17H). Compound 30: MS: m/z 906. 3(M++1) ; !H NMR(CDC13) δ 10. 18(s, 1H), 8. 62(d, 2H), 8. 25(d, 1H), 7. 78(d, 2H), 7. 70-7. 61(m, 2H), 7. 55-7. 46(m, 1H), 7. 01(1H), 6. 18(1H), 5. 71(q, 1H), 5. 12(d, 1H), 5. 02(dd, 1H), 4. 77 (dd, 1H), 4. 64(d, 1H), 4. 53-4. 43(lH), 4. 31-4. 18(m, 2H), , 2. 83-2. 44(m, 3H), 2. 28(q, 1H), 1. 95-1. 22(m, 23H), 0. 83 (s, 3H). Compound 31: MS: m/z 907. 3(M++1); 丨11 NMR (CDC13) δ 10. 39(s, 1H), 8. 57(d, 2H), 8. 05(d, 1H), 7. 77(d, 2H), 7. 42-7. 26(m, 3H), 6. 15(s, 1H), 5. 69(q, 1H), 5. 29(d, 1H), 4. 96 (dd, 1H), 4. 78(dd, 1H), 4. 63-4. 56(m, 1H), 4. 40-4. 13(m, 3H), 51 201109028 2. 91-2. 64 (m, 3H), 2. 62(s, 3H), 2. 56-2. 22(m, 2H), 1. 89-0. 96 (m, 23H). Compound 32: MS: m/z 895. 2(M++1) ; rH NMR(CDC13) δ 10. 45(s, 1H), 8. 60(d, 2H), 8. 22(d, 1H), 7. 55(d, 2H), 7. 67-7. 60 (m, 2H), 7. 45 (dd, 1H), 7. 20(s, 1H), 6. 12(s, IH), 5. 65(q, 1H), 5. 13(d, 1H), 4. 97 (dd, 1H), 4. 81-4. 71(m, 2H), 4. 14-4. 10 (m, 2H), 2. 82-2. 45 (m, 3H), 2. 27(q, 1H), 1. 97-1. 21(m, 14H), 1. 08(s, 9H), 0. 89-0. 80 (m, 4H). Compound 33: MS: m/z 853. 3(M++1) ; NMR(CDC13) δ 10. 22(s, 1H), 8. 58(s, 1H), 8. 48(d, 2H), 8. 08(d, 1H), 7. 57(d, 2H), 7. 53-7. 44(m, 2H), 7. 39-7. 26(m, 1H), 6. 05(s, 1H), 5. 65(q, 1H), 5. 21(d, 1H), 4. 95 (dd, 1H), 4. 82 (dd, 1H), 4. 40(d, 1H), 4. 21-4. 03(m, 2H), 3. 27(s, 3H), 2. 81-2. 40 (m, 3H), 2. 22(q, 1H), 1. 95-l_20(m, 15H), 0. 81(s, 3H). Compound 34: MS: m/z 923. 3(M++1); 丨14 NMR(CDC13) δ 10. 17(s, 1H), 8. 61(d, 2H), 8. 25(d, 1H), 7. 80(d, 2H), 7. 65-7. 50 (m, 2H), 7. 41 (dd, 1H), 6. 97(s, 1H), 6. 18(s, 1H), 5. 72(q, 1H), 5. 15(d, 1H), 5. 05(dd, 1H), 4. 77 (dd, 1H), 4. 65(d, 1H), 4. 29-4. 10 (m5 2H), 3. 78-3. 52(m, 2H), 3. 23-3. 03(m, 2H), 2. 79-2. 85 (ms 2H), 2. 56(brs, 1H), 2. 27(q, 1H), 1. 98-1. 19(m, 20H), 0. 88 (s, 3H). Compound 35: MS: m/z 894·2 (Μ++1); NMR (CDC13) δ 10. 45(s, 1H), 8. 47(d, 2H), 8. 12(s, 1H), 8. 05(d, 1H), 7. 70(d, 2H), 7. 53-7. 46(m, 2H), 7. 31-7. 22 (m, 1H), 6. 03(s, 1H), 5. 70(q, 52 201109028 1H), 5. 03-4. 84(m, 4H), 4. 24(d, 1H), 2. 95-2. 47(m, 3H), 2. 38(q,1H), 1. 94-1. Ll(m, 25H), 0. 85(s, 3H). Compound 36: MS: m/z 889. 3(M++1) ; 'H NMR(CDC13) δ 10. 26(s, 1H), 8. 47(d, 2H), 8. 07(d, 1H), 7. 65(d, 2H), 7. 57(s, 1H), 7. 55-7. 42(m, 2H), 7. 38-7. 27(m, 2H), 6. 82(d, 1H), 6. 62(d, 1H), 5. 63(dd, 1H), 6. 15(s, 1H), 5. 63(q, 1H), 4. 92(dd, 1H), 4. 74-4. 59(m, 2H), 4. 42(d, 1H), 4. 17(dd, 1H), 2. 79-2. 42 (m, 3H), 2. 23(q,1H), 1. 95-1. 05(m, 15H), 0. 76(s, 3H). Compound 37: MS: m/z 837·3 (Μ++1); 4 NMR (CDC13) δ 10. 16(s, 1H), 8. 48(d, 2H), 8. 11(d, 1H), 7. 69(d, 2H), 7. 58(d, 2H), 7. 36(dd, 1H), 7. 17(s, 1H), 6. 15(s, 1H), 6. 04(d, 1H), 5. 64(q, 1H), 4. 94 (dd, 1H), 4. 67(dd, 1H), 4. 47 (dd, 1H), 4. 41(d, 1H), 4. 12 (dd, 1H), 2. 78-2. 68 (m, 1H), 2. 43(brs, 1H), 2. 22(q, 1H), 1. 98-1. 64 (m, 7H), 1. 53-l. Ll(m,12H), 0. 78(s, 3H). Compound 38: MS: m/z 863·3 (Μ++1); 4 NMR (CDC13) δ 10. 52(s, 1H), 8. 38(d, 2H), 7. 92(d, 1H), 7. 88(s, 1H), 7. 65(d, 2H), 7. 58-7. 52(m, 2H), 7. 35-7. 21 (m, 1H), 6. 19(d, 1H), 5. 92(s, 1H), 5. 71(q, 1H), 5. 01(dd, 1H), 4. 81 (dd, 1H), 4. 62(d, 1H), 4. 37(brs, 1H), 4. 11-4. 01(m, 1H), 2. 98-2. 87 (m, 1H), 2. 74-2. 52 (m, 2H), 2. 33(q, 1H), 1. 98-1. 19(m, 16H), 0. 88(s, 3H), 0. 68-0. 41 (m, 4H). Compound 39: MS: m/z 908. 3(M++1) ; 4 NMR(CDC13) δ 10. 26(s, 1H), 8. 48(d, 2H), 8. 15(d, 1H), 7. 67(d, 2H), 7. 57-7. 46(m, 2H), 7. 39-7. 35 (m, 2H), 6. 07(s, 1H), 5. 62(q, 1H), s 53 201109028 4. 98-4. 86(m, 2H), 4. 77 (dd, 1H), 4. 58(d, 1H), 4. 02(dd, 1H), 3. 38-3. 24(m, 4H), 2. 99-2. 81(m, 4H), 2. 82-2. 42 (m, 3H), 2. 19 (q, 1H), 1. 88-1. 04(m, 15H), 0. 92-0. 72 (m, 4H). Compound 40: MS: m/z 866. 3(M++1); 丨H NMR(CDC13) δ 10. 51(s, 1H), 8. 37(d, 2H), 7. 91(d, 1H), 7. 69(s, 1H), 7. 61(d, 2H), 7. 53-7. 42(m, 2H), 7. 23-7. 14(m, 1H), 6. 01(s, 1H), 5. 67(q, 1H), 4. 94 (dd, 1H), 4. 72 (dd, 1H), 4. 61(d, 1H), 4. 43(d, 1H), 4. 30-4. 02(m, 2H), 2. 94-2. 60 (m, 3H), 2. 57(s, 6H), 2. 20(q, 1H), 1. 80-l_15(m,]5H),0. 77 (s, 3H). Compound 4]: MS: m/z 892. 3(M'+1) ; 4 NMR(CDC13) δ 10. 40(s, 1H), 8. 51(d, 2H), 8. 16(d, 1H), 7. 85(d, 2H), 7. 65(s, 1H), 7. 58(d, 1H), 7. 41-7. 37(m, 1H), 6. 14(s, 1H), 5. 59(q, 1H), 4. 99(dd, 1H), 4. 80 (dd, 1H), 4. 62(d, 1H), 4. 57(d, 1H)? 4. 45-4. 37(m, 1H), 4. 17(dd, 1H), 3. 75-3. 65(m, 2H), 3. 60-3. 48 (m, 2H), 2. 80-2. 45 (m, 3H), 2. 24(q, 1H), 1. 89-1. 41 (m, 20H), 0. 8(s, 3H). Compound 42: MS: m/z 907. 3(M++1) ; NMR(CDC13) δ 10. 20(s, 1H), 8. 43(d, 2H), 8. 10(d, 1H), 7. 65(d, 2H), 7. 60-7. 55(m, 2H), 7. 39-7. 35 (m, 1H), 7. 25(s, 1H), 6. 05(s, 1H), 5. 98(d, 1H), 5. 66(q, 1H), 4. 93(dd, 1H), 4. 72 (dd, 1H), 4. 52-4. 42 (m, 2H), 4. 08(dd, 1H), 3. 78-3. 60 (m, 2H), 3. 21-3. 11 (m, 2H), 3. 81-2. 43(br,3H), 2. 19-2. 05(m, 2H), l_85-1. 09(m, 19H), 0. 77 (s, 3H). Compound 43: MS: m/z 890. 3(M++1) ; NMR(CDC13) δ 54 201109028 10. 16(s, 1H), 8. 55(d, 2H), 8. 21(d, 1H), 8. 14(s, 1H), 7. 68(d, 2H), 7. 58-7. 41(m, 4H), 7. 21(s, 1H), 6. 40(s, 1H), 6. 18(s, 1H), 5. 63(q, 1H), 4. 95 (dd, 1H), 4. 78-4. 62(m, 2H), 4. 44(d, 1H), 4. 16(dd, 1H), 2. 69-2. 44(m, 3H), 2. 24(q, 1H), 1. 98-1. 15(m, 15H), 0. 79 (s, 3H). Compound 44: MS: m/z 879. 3(M++1) ; W NMR(CDC13) δ 10. 22(s, 1H), 8. 59(d, 2H), 8. 22(d, 1H), 7. 76(d, 2H), 7. 75-7. 60 (m, 2H), 7. 48-7. 42(m, 1H), 7. 17(s, 1H), 6. 20(s, 1H), 6. 16(d, 1H), 5. 71(q, 1H), 5. 02(dd, 1H), 4. 77 (dd, 1H), 4. 60-4. 52(m, 2H), 4. 20 (dd, 1H), 2. 79-2. 45 (m, 3H), 2. 21(q, 1H), 1. 96-1. 07(m, 15H), 1. 03(s,9H), 0. 82 (s, 3H). Compound 45: MS: m/z 933_3 (M++1); NMR (CDC13) δ 10. 22(s, 1H), 8. 56(d, 2H), 8. 19(d, 1H), 7. 88(d, 2H), 7. 69-7. 42(m, 3H), 7. 19(s, 1H), 6. 81-6. 62 (m, 4H), 6. 11(s, 1H), 5. 68 (q, 1H), 5. 00 (dd, 1H), 4. 77 (dd, 1H), 4. 55(d, 2H), 4. 41-4. 12 (m, 2H), 2. 82-2. 42 (m, 3H), 2. 28(q, 1H), 2. 01-l. Ll(m, 15H), 0. 83 (s, 1H). Compound 46: MS: m/z 891. 3(M++1); 丨11 NMR (CDC13) δ 10. 34(s, 1H), 8. 35(d, 2H), 7. 94(d, 1H), 7. 66(s, 1H), 7. 62(d, 2H), 7. 54-7. 46(m, 2H), 7. 22 (dd, 1H), 5. 93-5. 84(m, 2H), 5. 61(q, 1H), 4. 92(dd, 1H), 4. 87 (dd, 1H), 4. 58(d, 1H), 4. 41-4. 36(m, 1H), 4. 04(dd, 1H), 2. 82-2. 75 (m, 1H), 2. 65-2. 50 (m, 2H), 2. 24(q,1H), 1. 80-1. 00 (m, 24H), 0. 81 (s, 3H). Compound 47: MS: m/z 867_3 (M++1); iH NMR (CDC13) δ 55 201109028 l〇. 35(s, 1H), 8. 54(d, 2H), 8. 18(d, 1H), 7. 86(d, 1H), 7. 66(d, 2H), 7. 6] (m, 2H), 7. 46 (m, 2H), 6. 13(s,1H), 5. 67(q,ΠΙ), 4. 94 (dd, 1H), 4. 77(m, 1H), 4. 61 (m, 1H), 4. 40(d, 1H), 4. 20 (m, 1H), 3. 72(s, 3H), 2. 91 (m, 1H), 2. 72-2. 39(m, 3H), 2. 25(q, 1H), 1. 96-0. 82 (m, 15H). Compound 48: MS: m/z 908. 2(M++1) ; 'H NMR(CDC13) δ 10. 28(s, 1H), 8. 44(d, 1H), 8. 23(d, 1H), 7. 67(m, 3H), 7. 52(m, 1H), 7. 07(s, 1H), 6. 04(s, 1H), 5. 68(q, 1H), 5. 12(d, 1H), 4. 98(dd, 】H), 4. 79-4. 68 (m, 2H), 4. 34(s, 1H), 4. 20 (dd, 1H), 4. 00 (m, 1H), 2. 95(s, 3H), 2. 93(m, 1H), 2. 72(m, 2H), 2. 52(m, 1H), 2. 26(q,1H), 1. 94-0. 82 (23H). Compound 49: MS: m/z 920. Compound 50: MS: m/z 806. 2(M++1) ; rH NMR(CDC13) δ 10. 47(s, 1H), 8. 77-8. 53 (ra, 2H), 8. 19(d, 1H), 8. 13(d, 1H), 7. 73(s, 1H), 7. 53-7. 30 (m, 2H), 7. 26-7. 18(m, 1H), 6. 07(s, 1H), 5. 70-5. 40 (m, 2H), 4. 98-4. 61(m, 2H), 4. 40-4. 03(m, 3H), 3. 47 (s, 3H), 2. 95-2. 90 (m, 1H), 2. 87-2. 50 (m, 3H), 2. 20 (dd, 1H), 2. 10-1. 86(m,3H), 1. 61-1. 08(m,11H),0. 96 (m, 1H). Compound 51: MS: m/z 822. 3, 824. 3(M++1); iHNMRXCDCh) δ 10. 42(s, 1H), 8. 69-8. 44 (m, 3H), 8. 34(d, 2H), 7. 65(s, 1H), 7. 42-7. 30 (m, 3H), 6. 04(s, 1H), 5. 70-5. 45 (m, 2H), 4. 91-4. 63 (m, 2H), 4. 35-4. 03(m, 3H), 3. 42(s, 3H), 2. 84(s, 1H), 2. 72-2. 50 (m, 3H), 2. 22 (dd, 1H), 2. 19 (m, 3H), 1. 54-0. 78 (m, 11Hb compound 52: MS: m/z 774. 2(M++1) ; 4 NMR(CDC13) δ 56 201109028 10. 33(s, 1H), 8. 65-8. 58 (m, 1H), 8. 46(d, 1H), 8. 18(d, 1H), 8. 06(d, 1H), 7. 46-7. 38 (m, 3H), 7. 19-7. 11 (m, 1H), 6. 13(s, 1H), 6. 04(d, 1H), 5. 66 (dd, 1H), 5. 27-5. 08(m, 1H), 5. 07-4. 67(m, 2H), 4. 52-4. 39(m, 2H), 4. 13-4. 09(m, 1H), 3. 62-3. 60 (m, 1H), 2_95-2. 10 (m, 4H), 1. 98(s,3H), 1. 90-0. 81 (m, 14H). Compound 53: MS: m/z 825. 3 (M++1). Compound 54: MS: m/z 805. 3, 807. 3(M++1); h NMR(CDC13) δ 10. 46(s, 1H), 8. 28-8. 19(m, 1H), 7. 98(s, 1H), 7. 88-7. 85(m, 1H), 7. 63-7. 39(m, 6H), 6. 07(s, 1H), 5. 67-5. 46(m, 2H), 4. 96-4. 79(m, 2H), 4. 41-4. 09(m, 3H), 3. 37(s, 3H), 2. 97-0. 88 (m, 20H). Compound 55: MS: m/z 789. 2(M++1) ; NMR(CDC13) δ 10. 61(s, 1H), 8. 49(s, 1H), 8. 39-8. 24(m, 2H), 8. 05-7. 94(m, 2H), 7. 56-7. 04(m, 5H), 5. 90(s, 1H), 5. 47(br, 1H), 4. 93-4. 69 (br, 2H), 4. 40-4. 07(m, 3H), 3. 46(s, 1H), 3. 23(s, 3H), 2. 91-2. 07(m, 11H), 1-99-1. 54(m, 4H), 1. 32-0. 81 (m, 5H). Compound 56: MS: m/z 839. 3, 843_3 (M++1); 〗〖HNMR (CDC13) δ 10. 27(s, 1H), 8. 24(d, 1H), 7. 89(d, 1H), 7. 63(d, 1H), 7. 56(s, 1H), 7. 52-7. 40 (m, 2H), 7. 14(brs, 1H), 6. 08(s, 1H), 5. 69(q, 1H), 5. 30 (brs, 1H), 4. 97 (dd, 1H), 4. 74 (dd, 1H), 4. 46(d, 1H), 4. 40-4. 22 (m, 1H), 4. 13-4. 08(m, 1H), 3. 36(s, 3H), 2. 99-2. 05 (m, 5H), l_90-1. 10(m, 15H), 0. 99-0. 88 (m, 1H). Compound 57: MS: m/z 827·2 (Μ++1); NMR (CDC13) δ 10. 17(s, 1H), 8. 42(d, 2H), 7. 84(d, 1H), 7. 49-7. 41(m, 4H), 57 201109028 7. 28(m, 1H), 7. 13(brs, 1H), 6. 16(s, 1H), 5. 63(q, 1H), 4. 95 (m, 1H), 4. 70 (dd, 1H), 4. 63(m, 1H), 4. 31-4. 11 (m, 2H), 2. 97-2. 70 (m, 3H), 2. 50-1. 06 (m, 17H), 0. 91 (m5lH). Compound 58: MS: m/z 803. 3 (M++1). Compound 59: MS: m/z 789·2 (Μ++1); NMR (CDC13) δ 10. 39(s, 1H), 8. 53-8. 41(m, 3H), 7. 81(d, 1H), 7. 59-7. 42(m, 4H), 7. 26(m, 1H), 7. 18(s, 1H), 6. 17(s, 1H), 5. 17(q, 1H), 5. 28(dd, 1H), 4. 95 (dd, 1H), 4. 75 (m, 1H), 4. 43(d, 1H), 4. 38-4. 04(m, 2H), 3. 40(s, 3H), 2. 96-2. 67(m, 3H), 2. 60-2. 41 (m, 1H), 2. 37-2. 22 (m, 1H), 1. 99-0. 85 (m, 14H). Compound 60: MS: m/z 773. 2(M*>1) ; 'H NMR(CDC13) δ 10. 33(s, 1H), 8. 46(d, 2H), 7. 88-7. 84(m, 1H), 7. 60-7. 50 (m, 4H), 7. 35-7. 17(m, 1H), 6. 20(s, 1H), 6. 08(d, 1H), 5. 72(q, 1H), 4. 98 (dd, 1H), 4. 72 (dd, 1H), 4. 56(m, 1H), 4. 41(d, 1H), 4. 21 (m, 1H), 2. 94-2. 90 (m, 1H), 2. 80-2. 77(m, 1H), 2. 55-2. 52(m, 1H), 2. 23(q, 1H), 1. 98-1. 90 (m, 1H), 1. 84(s, 3H), 1. 80-0. 80 (m, 16H). Compound 61: MS: m/z 845. 3(M++1) ; NMR(CDC13) δ 10. 41(s, 1H), 8. 34(d, 2H), 7. 84(d, 1H), 7. 53-7. 44(m, 1H), 7. 40-7. 33(m, 3H), 7. 19(s, 1H), 6. 14(s, 1H), 5. 71(q, 1H), 5. 15 (d, 1H), 4. 98 (dd, 1H), 4. 89~4. 80 (m, 2H), 4. 25-4. 19(m, 2H), 2. 95-2. 90 (m, 1H), 2. 88-2. 42 (m, 3H), 2. 44(s, 3H), 2. 29 (m, 1H), 1. 98-1. 20 (m, 14H), 1. 1 l(s, 9H), 1. 00-0. 87 (1H). Compound 62: MS: m/z 841. 2(M++1) ; h NMR(CDC13) δ 58 201109028 10. 21(s, 1H), 8. 35(d, 2H), 7. 89(d, 1H), 7. 60-7. 57(m, 1H), 7. 33(d, 2H), 7. 17(d, 1H), 7. 05(s, 1H), 6. 22(s, 1H), 5. 68(q, 1H), 4. 97 (dd, 1H), 4. 77-4. 64 (m, 2H), 4. 33-4. 17(m, 2H), 2. 93-2. 74 (m, 3H), 2. 44(s, 3H), 2. 21 (m, 1H), 1. 95-0. 91 (m, 17H). Compound 63: MS: m/z 903. 3; 905. 3(M++1); h NMR(CDC13) δ 10. 18(s, 1H), 8. 45(d, 2H), 8. 23(d, 1H), 7. 64(m, 2H), 7. 49(d, 3H), 7. 01(s, 1H), 6. 17(s, 1H), 5. 72(q, 1H), 5. 13(d, 1H), 4. 99(dd, 1H), 4. 77 (dd, 1H), 4. 58(d, 1H), 4. 53(brs, 1H), 4. 27(m, 1H), 4. 14(m, 1H), 2. 83-2. 44(m, 3H), 2. 27(q, 1H), 1. 95-1. 22 (m, 23H), 0. 83(s, 3H). Compound 64: MS: m/z 787. 3(M++1);]H NMR(CDC13) δ 10. 45(s, 1H), 8. 25(d, 2H), 7. 75(d, 1H), 7. 67(s, 1H), 7. 53-7. 52(m, 1H), 7. 26(d, 2H), 6. 29(d, 1H), 6. 19(s, 1H), 5. 67(q, 1H), 4. 94 (dd, 1H), 4. 75 (dd, 1H), 4. 52(brs, 1H), 4. 42(d, 1H), 4. 10-4. 18(m, 1H), 2. 89-2. 50 (m, 3H), 2. 43(s, 3H), 2. 35-2. 20 (m, 1H), 1. 98-1. 85(m, 1H), 1. 82(s, 3H), 1. 62-0. 81 (m, 16H). Compound 65: MS: m/z 803. 2(M++1) ; h NMR(CDC13) δ 10. 46(s, 1H), 8. 30(d, 1H), 8. 17(d, 2H), 7. 63(d, 1H), 7. 55(s, 1H), 7. 45-7. 41 (m, 1H), 7. 25-7. 20(m, 2H), 5. 97(s, 1H), 5. 65-5. 59(m, 1H), 5. 36(d, 1H), 4. 91-4. 87(m, 1H), 4. 73 (dd, 1H), 4. 37-4. 05(m, 3H), 3. 30(s, 3H), 2. 84-2. 47(m, 3H), 2. 38(s, 3H), 2. 40-2. 16 (m, 1H), 1. 90-0. 87 (m, 16H). Compound 66: MS: m/z 871. 3(M++1) ; 'H NMR(CDC13) δ 59 201109028 10. 42(s, 1H), 8. 19-8. 02(m, :2H), 7. 93(s, 1H), 7. 67(s, 1H), 7. 47-7. 26(m, 3H), 6. 05(s, 1H), 5. 62(q, 1H), 5. 34(d, 1H), 4. 96- 4. 42 (m, 4H), 4. 36-4. 10(m, 2H), 2. 95-2. 90 (m, 1H), 2. 77(s, 3H), 2. 76-2. 48 (m, 3H), 2. 35(s, 3H), 2. 30-0. 87 (m, 24H). Compound 67: MS: m/z 875. 3 (M++1). Compound 68: TG-2379: MS: m/z 871. 3(M++1) ; 4 NMR (CDC13) δ 10. 33(s, 1H), 8. 34(d, 2H), 7. 85(d, 1H), 7. 73(s, 1H), 7. 54-7. 46(m, 1H), 7. 38-7. 22 (m, 3H), 6. 12(s, 1H), 5. 65(q, 1H), 5. 35(d, 1H), 4. 93(dd, 1H), 4. 78(dd, 1H), 4. 62-4. 50 (m, 2H), 4. 32-4. 08(m, 2H), 2. 81-2. 42 (m, 3H), 2. 40(s, 3H), 2. 2. 6(q, 1H), 1. 93-1. l](m, 23H), 0. 80 (s, 3H). Compound 69: MS: m/z 861. 3 (M++1). Compound 70: MS: m/z 857. 2(M++1) ; 4 NMR(CDC13) δ 10. 23(s, 1H), 8. 09(s, H), 8. 05(s, 1H), 7. 96(dd, 1H), 7. 58 (dd, 1H), 7. 47-7. 19(m, 3H), 7. 06(d, 1H), 6. 21(s, 1H), 5. 69(q, 1H), 4. 95 (dd, 1H), 4. 81-4. 60 (m, 2H), 4. 35-4. 17(m, 2H), 3. 94(s, 3H), 2. 92-2. 41 (m, 3H), 2. 23(q, 1H), 1. 92-0. 82 (m, 17H). Compound 7]: MS: m/z 8] 9. 2(Mf+l) ; NMR(CDC13) δ 10. 36(s,1H), 8. 01-7. 81 (m, 3H), 7. 71 (d, 1H), 7. 34-7. 22 (m, 3H), 6. 96(d, IH), 6. 01(s, 1H), 5. 61(q, 1H), 5. 27(dd, 1H), 4. 90 (dd, 1H), 4. 69 (dd, 1H), 4. 38(d, 1H), 4. 22-4. 03(m, 2H), 3. 87(s, 3H)S 3. 28(s, 3H), 2. 86-2. 42 (m, 3H), 2. 20(q, 1H), 1. 97- 0. 88 (m, 16H). 60 201109028 Compound 72: MS: m/z 861. 3(M++1) ; 'H NMR(CDC13) δ 10. 38(s, 1H), 8. 10-7. 98(m, 2H), 7. 86(d,1H), 7. 54-7. 22(m, 3H), 7. 20(s, 1H), 7. 06(d, 1H), 6. 10(s, 1H), 5. 70(q, 1H), 5. 29(d, 1H), 4. 97 (dd, 1H), 4. 79-4. 67(m, 2H), 4. 18-4. 04(m, 2H), 3. 94(s, 3H), 2. 95-2. 57(m, 3H), 2. 28(q, 1H), 1. 91-0. 87 (m, 25H). Compound 73: MS: m/z 803. 2(M++1) ; 4 NMR(CDC13) δ 10. 37(s, 1H), 8. 12-8. 96(m, 2H), 7. 85(d, 1H), 7. 56-7. 26(m, 4H), 7. 05(d, 1H), 6. 19-6. 15(m, 2H), 5. 71(q, 1H), 4. 96 (dd, 1H), 4. 74(s, 1H), 4. 53-4. 42 (m, 2H), 4. 19(d, 1H), 3. 93(s, 3H), 2. 91-2. 20 (m, 4H), 2. 10-0. 82 (m, 19H). Compound 74: MS: m/z 861·3 (Μ++1); 'H NMR (CDC13) δ 10. 42(s, 1H), 8. 39(d, 2H), 7. 81(d, 1H), 7. 50-7. 26(m, 3H), 7. 00(d, 2H), 6. 05(s, 1H), 5. 65(q, 1H), 5. 21(d, 1H), 4. 95 (dd, 1H), 4. 84 (dd, 1H), 4. 68(d, 1H), 4. 21-4. 07(m, 2H), 3. 90(s, 3H), 2. 90-2. 45 (m, 4H), 2. 22(q, 1H), 1. 98-1. 20 (m, 14H), 1. 13(s, 9H), 0. 99-0. 84 (m, 1H). Compound 75: MS: m/z 887. 3(M++1) ; 'H NMR(CDC13) δ 10. 33(s, 1H), 8. 38(d, 2H), 7. 82(d, 1H), 7. 61(s, 1H), 7. 59-7. 43(m, 1H), 7. 35-7. 20 (m, 1H), 7. 01(d, 2H), 6. 07(s, 1H), 5. 68(q, 1H), 5. 42(d, 1H), 4. 98 (dd, 1H), 4. 75 (dd, 1H), 4. 58(s, 1H), 4. 38-4. 13(m, 3H), 3. 88(s, 3H), 2. 86(br, 2H), 2. 59-2. 11 (m, 2H), 1. 96-1. 20(m, 22H), 0. 92-0. 78 (m, 4H). Compound 76: MS: m/z 903. 3, 905. 3 (M++1). 61 201109028 Compound 77: MS: m/z 887. 3 (M++1). Compound 78: MS: m/z 883. 4(M++1);丨]·! NMR(CDC13) δ 10. 19(s, 1H), 8. 46(d, 2H), 8. 25(d, 1H), 7. 62(m, 2H), 7. 46(m, 1H), 7. 04((1, 2H), 6. 96(s, 1H), 6. 19(s, 1H), 5. 73(q, 1H), 5. 15 (d, 1H), 5. 02(dd, 1H), 4. 77(m, 1H), 4. 58(m, 2H), 4. 30 (m, 1H), 4. 15(m, 3H), 2. 79(m, 2H), 2. 54 (m, 1H), 2. 26(q, 1H), 1. 92-0_83 (m, 26H), 0_83 (s, 3H). Compound 79: MS: m/z 869_4 (M++1); 4 NMR (CDC13) δ 10. 36(s, 1H), 8. 44(d, 2H), 8. 24(d, 1H), 7. 60 (m, 2H), 7. 44(m, 1H), 7. 04(s, 1H), 7. 00(d, :2H), 6. 16(s, 1H), 5. 71(q, 1H), 5. 21(d, 1H), 4. 97 (dd, 1H), 4. 74 (m, 1H), 4. 57(m, 2H), 4. 30 (m, 1H), 4. 15(m, 3H), 2. 91 (m, 1H), 2. 75(m, 2H), 2. 56(m, 1H), 2. 26(q, 1H), 1. 92-0. 83 (m, 26H). Compound 80: MS: m/z 883·4 (Μ++1); 'H NMR (CDC13) δ 10. 42(s,1H), 8_43(d,2H), 8. 23(d, 1H), 7. 61-7. 39(m, 4H), 7. 03(d, 2H), 6. 18(s, 1H), 5. 71(q, 1H), 5. 30(d, 1H), 4. 96 (dd, 1H), 4. 79-4. 57(m, 4H), 4. 41-4. 22 (m, 1H), 4. 15-4. 08(m, 1H), 2. 96-2. 67(m, 3H), 2. 57-2. 42 (m, 1H), 2. 25(q, 1H), 1. 98-0. 87 (m, 29H). Compound 81: MS: m/z 897. 4(M++1); 丨11 NMR (CDC13) δ 10. 31(s, 1H), 8. 42(d, 2H), 8. 21(d, 1H), 7. 57-7. 25(m, 4H), 7. 02(d, 2H), 6. 14(s, 1H), 5. 67-5. 64 (m, 1H), 5. 40(d, 1H), 5. 03-4. 93(m, 1H), 4. 79-4. 54(m, 4H), 4. 39-4. 12 (m, 2H), 2. 77-2. 72(m, 2H), 2. 54(br, 1H), 2. 26(q, 1H), 2. 03-1. 24(m, 29H), 62 201109028 0. 80 (s, 3H). Compound 82: MS: m/z 915. 2(M++1) ; 'H NMR(CDC13) δ 10. 29(s, 1H), 8. 38(d, 2H), 7. 74(d, 1H), 7. 57-7. 24(m, 3H), 7. 27(d, 2H), 6. 14(s, 1H), 5. 66(q, 1H), 5. 32(d, 1H), 4. 98 (dd, 1H), 4. 76(dd, 1H), 4. 71-4. 48 (m, 3H), 4. 39-4. 08(m, 2H), 2. 85-2. 42 (m, 3H), 2. 31(q, 1H), 2. 03-1. 24(m, 29H), 0. 80 (s, 3H). Compound 83: MS: m/z 901_2 (M++1); 4 NMR (CDC13) δ 10. 42(s, 1H), 8. 46(d, 2H), 7. 82(d, 1H), 7. 54 (dd, 1H), 7. 42(s, 1H), 7. 32(m, 1H), 6. 98(d, 2H), 6. 14(s, 1H), 5. 65(q, 1H), 5. 33(d, 1H), 4. 97 (dd, 1H), 4. 76(dd, 1H), 4. 71-4. 50 (m, 3H), 4. 41-4. 08(m, 2H), 2. 93-2. 42 (m, 4H), 2. 31(q, 1H), 2. 03-0. 80 (m, 29H). Compound 84: MS: m/z 885. 3(M++1) ; W NMR(CDC13) δ 10. 26(s, 1H), 8. 42(d, 2H), 8. 23(d, 1H), 7. 58(m, 2H), 7. 44 (dd, 1H), 7. 22(s, 1H), 7. 01(d, 2H), 6. 17(s, 1H), 5. 67(q, 1H), 5. 16(d, 1H), 4. 98 (dd, 1H), 4. 75 (dd, 1H), 4. 62(m, 2H), 4. 38-4. 08(m, 2H), 2. 80-2. 42 (m, 3H), 2. 32(q, 1H), 1. 96-1. 20(m, 21H), 1. 13(s, 9H), 0. 81 (m, 3H). Compound 85: MS: m/z 923. 2 (M++1). Compound 86: MS: m/z 883_2 (M++1); 丨!·! NMR (CDC13) δ 10. 41(s, 1H), 8. 19(d, 1H), 8. 06(d, 1H), 7. 95(s, 1H), 7. 61-7. 41 (m, 4H), 6. 92(d, 1H), 6. 12(s, 1H), 6. 04(s, 2H), 5. 67(q, 1H), 5. 35(d, 1H), 4. 97 (dd, 1H), 4. 77 (dd, 1H), 4. 58(d, 1H), 63 201109028 4. 36-4. 11 (m, 2H), 2. 85-2. 43(m, 3H), 2. 27(q, 1H), 1. 98-1. 21 (m, 24H), 0. 81 (s, 3H). Compound 87: MS: m/z 869·2 (Μ++1); 4 NMR (CDC13) δ 10. 36(s, 1H), 8. 17(d, 1H), 7. 97(d, 1H), 7. 88(s, 1H), 7. 58-7. 32(m, 4H), 6. 85(d, 1H), 6. 02(s, 1H), 5. 98(s, 2H), 5. 59(q, 1H), 5. 37(d, 1H), 4. 87(d, 1H), 4. 68 (dd, 1H), 4. 52-4. 02(m, 3H), 2-90-2. 38 (m, 4H), 2. 23(q, 1H), 1. 91-0. 88 (m, 24H). Compound 88: MS: m/z 868. 5 (M++1). Compound 89: MS: m/z 882. 5 (M++1). Compound 90: MS: m/z 910. 3(M++1) ; NMR(CDC13) δ 10. 32(s, 1H), 8. 34(d, 2H), 8. 22(d, 1H), 7. 61-7. 43(m, 3H), 7. 44 (dd, 1H), 6. 76(d, 2H), 6. L4(s, 1H), 5. 62(q, 1H), 5. 39(d, 1H), 4. 96 (dd, 1H), 4. 72 (dd, 1H), 4. 63(brs, 1H), 4. 55(d, 1H), 4. 41-4. 〇4(m, 2H), 3. 42(q, 4H), 2. 80-2. 42 (m, 3H), 2. 32(q, 1H), 1. 98-1. 17(m,29H), 0. 83(s, 3H). Compound 91: MS: m/z 896·3 (Μ++1); !Η NMR (CDC13) δ 10. 46(s, 1H), 8. 33(d, 2H), 8. 21(d, 1H), 7. 62-7. 43(m, 3H), 7. 43(dd, 1H), 6. 77(d, 2H), 6. 13(s, 1H), 5. 65(q, 1H), 5. 39(d, 1H), 4. 93(dd, 1H), 4. 73 (dd, 1H), 4. 64 (brs, 1H), 4. 53(d, 1H), 4. 43-4. 05(m, 2H), 3. 43(q, 4H), 2. 94-2. 42 (m, 4H), 2. 29(q, 1H), 2. 14-0. 83 (m, 29H). Compound 92: MS: m/z 901. 4, 903·4(Μ++1); 4 NMR(CDC13) δ 10. 40(s, 1H), 8. 36(d, 2H), 8. 23(s, 1H), 7. 58-7. 26(m, 5H), 6. 15(s, 1H), 5. 65(q, 1H), 5. 19(d, 1H), 4. 96 (dd, 1H), 4. 77 (dd, 64 201109028 1H), 4. 62-4. 52(m, 2H), 4. 33-4. 08(m, 2H), 3. 01-2. 42 (m, 5H), 2. 25(q, 1H), l_96-0. 89 (m, 29H). Compound 93: MS: m/z 915. 4, 917·4(Μ++1);丨11 NMR(CDC13) δ 10. 27(s, 1H), 8. 38(d, 2H), 8. 22(s, 1H), 7. 59-7. 34(m, 5H), 6. 13(s, 1H), 5. 70(q, 1H), 5. 29(d, 1H), 4. 98 (dd, 1H), 4. 78(dd, 1H), 4. 62-4. 55(m, 2H), 4. 35-4. 08(m, 2H), 3. 04-2. 96(m, 1H), 2. 80-2. 43(m, 3H), 2. 25(q, 1H), 1. 97-1. 20(m, 29H), 0. 81(s, 3H). Compound 94: MS: m/z 867_4 (M++1). Compound 95: MS: m/z 881. 3(M++1) ; 4 NMR(CDC13) δ 10. 31(s, 1H), 8. 41(d, 2H), 8. 22(d, 1H), 7. 63-7. 21(m, 4H), 7. 20(d, 2H), 6. 16(s, 1H), 5. 65(q, 1H), 5. 38(d, 1H), 4. 94 (dd, 1H), 4. 80 (dd, 1H), 4. 65-4. 56(m, 2H), 4. 38-4. 12(m, 2H), 3. 08-2. 92(m, 1H), 2. 83-2. 67(m, 2H), 2. 59-2. 41 (m, 1H), 2. 25(q, 1H), 1. 98-1. 08 (, m, 28H), 0-95-0. 86 (m, 4H). Compound 96: MS: m/z 881_4 (M++1); 4 NMR (CDC13) δ 10. 47(s, 1H), 8. 40(d, 2H), 8. 23(d, 1H), 7. 76(s, 1H), 7. 62-7. 41(m, 5H), 6. 13(s, 1H), 5. 65(q, 1H), 5. 33(d, 1H), 5. 03-4. 87 (m, 2H), 4. 78(dd, 1H), 4. 57(d, 1H), 4. 38-4. 04(m, 2H), 2. 95-2. 43(m, 4H), 2. 21(q, 1H), 2. 01-1. 37(m, 20H), 1. 33(s, 9H), 1. 21-0. 86 (m, 3H). Compound 97: MS: m/z 895. 4 (M++1); NMR (CDC13) δ 10. 30(s, 1H), 8. 40(d, 2H), 8. 23(d, 1H), 7. 59-7. 43(m, 5H), 6. 98(d, 1H), 6. 16(s, 1H), 5. 65(q, 1H), 5. 41(d, 1H), 4. 98 (dd, s 65 201109028 1H), 4. 79(q, 1H), 4. 62-4. 52(m, 1H), 4. 36-4. 09(m, 3H), 2. 75 (brs, 2H), 2. 59-2. 56(m, 1H), 2. 28(q, 1H), 1. 91-1. 18(m, 31H), 0. 89-0. 78 (m, 4H). Compound 98: MS: m/z 869·4 (Μ++1); NMR (CDC13) δ 10. 41(s, 1H), 8. 42(d, 2H), 8. 23(d, 1H), 7. 62-7. 43(m, 5H), 7. 44 (dd, IH), 6. 17(s, 1H), 5. 64(q, 1H), 5. 17(d, 1H), 4. 97 (dd, 1H), 4. 77-4. 63(m, 2H), 4. 21-4. 10(m, 2H), 2. 94-2. 55(m, 4H), 2. 27(q, 1H), 1. 891. 15(m, 23H), 1. 10(s, 9H), 0. 98-0. 87 (m, 1H). Compound 99: MS: m/z 925·4 (Μ++1); NMR (CDC13) δ 10. 28(s, 1H), 8. 37(d, 2H), 8. 03(d, 1H), 7. 50(d, 2H), 7. 48(s, 1H), 7. 01-6. 92(m, 2H), 6. 13(s, 1H), 5. 65(q, 1H), 5. 39(d, 1H), 4. 98 (dd, 1H), 4. 88(dd, 1H), 4. 64(s, 1H), 4. 53(d, 1H), 4. 41-4. 23(m, 1H), 4. 19-4. 1 l(m, 1H), 3. 88(s, 3H), 2. 78-2. 42 (m, 3H), 2. 26(q, 1H), 2. 04-1. 18(m, 31H), 0. 89-0. 78 (m, 4H). Compound 100: MS: m/z 925. 4 (M++1); W NMR (CDC13> δ 10. 23(s, 1H), 8. 35(d, 2H), 7. 77(d, 1H), 7. 48(d, 2H), 7. 38-7. 22(m, 1H), 7. 04-6. 81(m, 2H), 6. 16(s, 1H), 5. 68(q, 1H), 5. 21(d, 1H), 4. 99(dd, 1H), 4. 78(dd, 1H), 4. 57(d, 1H), 4. 22-4. 03(m, 3H), 4. 00(s, 3H), 2. 80-2. 43(m, 3H), 2. 3 l(q, 1H), 1. 96-1. 20(m, 31H), 0. 95-(). 78 (m, 4H). Compound 101: MS: m/z 827. 3 (M++1). Compound 102: MS: m/z 897·4 (Μ++1); 4 NMR (CDC13) δ 10. 30(s, 1H), 8. 39(d, 2H), 8. 20(d, 1H), 7. 59-7. 37(m, 5H), 66 201109028 7. 14(s, 1H), 6. 04(s, 1H), 5. 61(q, 1H), 5. 21(d, 1H), 4. 87 (dd, 1H), 4. 77 (dd, 1H), 4. 57(d, 1H), 4. 19-4. 07(m, 4H), 3. 67-3. 42 (m, 2H), 3. 17-2. 40 (m, 6H), 2. 20(q,1H), 1. 93-0_78 (m, 27H). Compound 103: MS: m/z 866. 3(M++1) ; NMR(CDC13) δ 10. 45(s, 1H), 8. 31(d, 2H), 8. 12(d, 1H), 7. 51-7. 42 (m, 5H), 7. 32- 7. 25(m, 1H), 6. 09(s, 1H), 5. 61(q, 1H), 4. 90 (dd, 1H), 4. 81 (dd, 1H), 4. 59(d, 1H), 4. 50-4. 36(m, 2H), 4. 13(dd, 1H), 3. 69-3. 27(m, 3H), 3. 10(brs, 4H), 2. 90-2. 41 (m, 4H), 2. 19(q, 1H), 1. 98-0. 78 (m, 25H). Compound 104: MS: m/z 811·3 (Μ++1); 'H NMR (CDC13) δ 10. 38(s, 1H), 8. 38(d, 2H), 8. 19(d, 1H), 7. 60-7. 31(m, 5H), 7. 32- 7. 25(m, 1H), 6. 15(s, 1H), 5. 65(q, 1H), 4. 88(dd, 1H), 4. 70 (dd, 1H), 4. 57 (dd, 1H), 4. 40(d, 1H), 4. 21-4. 05(m, 2H), 2. 95-2. 41 (m, 4H), 2. 22(q, 1H), 2. 01(s, 3H), 1. 98-0. 79 (m, 24H). Compound 105: MS: m/z 868·4 (Μ++1); NMR (CDC13) δ 10. 57(s, 1H), 8. 37(d, 2H), 8. 15(d, 1H), 8. 09(s, 1H), 7. 58-7. 51(m, 4H), 7. 27(dd, 1H), 6. 09(s, 1H), 5. 61(q, 1H), 4. 98-4. 79(m, 4H), 4. 44(s, 1H), 4. 10(dd, 1H), 3. 79-3. 68(m, 2H), 2. 92-2. 45 (m, 4H), 2. 24(q,1H), 1. 98-0. 88 (m, 32H). Compound 106: MS: m/z 882. 4(M++1) ; 4 NMR(CDC13) δ 10. 37(s, 1H), 8. 35(d, 2H), 8. 16(d, 1H), 7. 56-7. 48(m, 2H), 7. 42(d, 2H), 7. 36-7. 33(m, 1H), 7. 30(s, 1H), 6. 09(s, 1H), 5. 63(q, 1H), 4. 97-4. 86(m, 2H), 4. 76(dd, 1H), 4. 58(d, 1H), 67 201109028 4. 28-4. 1 l(m, 2H), 3. 39-3. 25(m, 4H), 3. 01-2. 82(m, 5H), 2. 75-2. 44 (m, 2H), 2. 16(q,1H), 1. 95-0. 76 (m, 25H). Compound 107: MS: m/z 863_3 (M++1); 4 NMR (CDC13) δ 10. 34(s, 1H), 8. 33(d, 2H), 8. 32(d, 1H), 7. 59-7. 40 (m, 6H), 7. 37(s, 1H), 6. 81(d, 1H), 6. 65(d, 1H), 6. 25(s, 1H), 6. 13(s, 1H), 5. 62(q, 1H), 4. 87 (dd, 1H), 4. 69-4. 52(m, 2H), 4, 42(d, 1H), 4. 18 (dd, 1H), 2. 95-2. 40 (m, 4H), 2. 24-0. 78 (m, 25H). Compound 108: MS: m/z 840. 4(M++1); 卞1 NMR (CDC13) δ 10. 67(s, 1H), 8. 32(d, 2H), 8. 19(d, 1H), 7. 77(s, 1H), 7. 58-7. 44(m, 4H), 7. 34-7. 25(m, 1H), 6. 14(s, 1H), 5. 77(q, 1H), 4. 98 (dd, 1H), 4. 78-4. 71(m, 2H), 4. 44(d, 1H), 4. 29(brs, 1H), 4. 11-4. 05(m, 1H), 2. 96-2. 72(m, 2H), 2. 64(s, 6H), 2. 41(br, 1H), 2_20(q, 1H), 1. 96-0. 78 (m, 25H). Compound 109: MS: m/z 837. 4(M++1) ; "H NMR(CDC13) δ 10. 49(s, 1H), 8. 35-8. 25(m, 3H), 7. 71(s, 1H), 7. 55-7. 41(m, 4H), 7. 26(s5 1H), 6. 19(d, 1H), 6. 01(s, 1H), 5. 63(q, 1H), 4. 88(dd, 1H), 4. 71(brs, 1H), 4. 56(d, 1H), 4. 39(brs, 1H), 4. 06(d, 1H), 2. 81-2. 45 (m, 4H), 2. 23(q, 1H), 1. 99-1. 64 (m, 4H), 1. 58-0. 77(m, 21H), 0. 51 (brs, 4H). Compound 1]0: MS: m/z 865·4 (Μ++1); W NMR (CDC13) δ 10. 39(s, 1H), 8. 29(d, 2H), 8. 15(d, 1H), 7. 56-7. 42 (m, 5H), 7. 36-7. 24(m, 1H), 6. 05(s, 1H), 5. 98(d, 1H), 5. 64(q, 1H), 4. 87 (dd, 1H), 4. 69 (dd, 1H), 4. 55(d, 1H), 4. 42 (dd, 1H), 4. 04(dd, 1H), 2. 81-2. 05(m, 5H), 1. 95-1. 71(m, 4H), 1. 57-0. 76 (m, 68 201109028 29H). Compound 111: MS: m/z 881·4 (Μ++1); 'H NMR (CDC13) δ 10. 29(s, 1Η), 8. 33(d, 2H), 8. 30(s, 1H), 7. 58-7. 41(m, 4H), 7. 39(dd, 1H), 7. 22(s, 1H), 6. 10(s, 1H), 5. 98(d, 1H), 5. 62(q, 1H), 4. 91 (dd, 1H), 4. 68 (dd, 1H), 4. 46-4. 40 (m, 2H), 4. 05(dd, 1H), 3. 79-3. 62(m, 2H), 3. 21-3. 09(m, 2H), 2. 88-2. 40 (m, 3H), 2. 22-1. 72 (m, 6H), 1. 47-0. 78 (m, 25H). Compound 112: MS: m/z 864. 3(M++1) ; A NMR(CDC13) δ 10. 29(s, 1H), 8. 38(d, 2H), 8. 23(d, 1H), 8. 09(s, 1H), 7. 57-7. 45 (m, 5H), 7. 41 (dd, 1H), 7. 28(s, 1H), 6. 42(s, 1H), 6. 15(s, 1H), 5. 62(q, 1H), 4. 86 (dd, 1H), 4. 75-4. 66(m, 2H), 4. 49(d, 1H), 4. 17(dd, 1H), 2. 83-2. 43(m, 3H), 2. 25(q, 1H), 1. 99-0. 78 (m, 25H). Compound 113: MS: m/z 853·4 (Μ++1); 'H NMR (CDC13) δ 10. 34(s, 1H), 8. 36(d, 2H), 8. 30(d, 1H), 7. 62-7. 46(m, 4H), 7. 41-7. 36(m, 1H), 7. 17(s, 1H), 6. 19(s, 1H), 6. 17(d, 1H), 5. 68(q, 1H), 4. 92(dd, 1H), 4. 73 (dd, 1H), 4. 58-4. 43(m, 2H), 4. 19 (dd, 1H), 2. 89-2. 43(m, 3H), 2. 22(q, 1H), 1. 99-1. 82(m, 6H), 1. 59-0. 83 (m, 28H). Compound 114: MS: m/z 907. 3(M++1) ; 'H NMR(CDC13) δ 10. 30(s, 1H), 8. 39(d, 2H), 8. 21(d, 1H), 7. 56(dd, 1H), 7. 48(d, 2H), 7. 40 (dd, 1H), 7. 24(s, 1H), 7. 18(d, 2H), 7. 03(d, 2H), 6. 92(s, 1H), 6. 06(s, 1H), 5. 74(d, 1H), 5. 61(q, 1H), 4. 87 (dd, 1H), 4. 70 (dd, 1H), 4. 42(d, 1H), 4. 31 (dd, 1H), 4. 08(dd, 1H), 69 5 201109028 2. 84-2. 79(m, 1H), 2. 65-2. 43(m, 2H), 2. 23(q, 1H), 1. 88-1. 62 (m, 6H), 1. 49-0. 78 (m, 19H). Compound 115: MS: m/z 895. 4(M++1) ; 'H NMR(CDC13) δ 10. 42(s,lH), 8. 40 (d, 2H), 8. 01(s,lH), 7. 55(d, 2H), 7. 46-7. 32(m, 3H), 6. 13(s, 1H), 5. 61(q, 1H), 5. 32(brs, 1H), 5. 01-4. 87(m, 1H), 4. 89 (dd, 1H), 4. 62-4. 55(m, 2H), 4. 34-4. 08 (m, 2H), 2. 94-2. 55(m, 4H), 2. 50(s, 3H), 2. 23(q, 1H), 1. 95-1. 10 (m, 32H). Compound 1]6: MS: m/z 9() 9. 4(M++1) ; !H NMR(CDC13) δ 10. 29(s, ΓΗ), 8. 40(d, 2H), 8. 01(s, 1H), 7. 55(d, 2H), 7. 47-7. 26(m, 3H)5 6. 14(s, 1H), 5. 69(q, 1H), 5. 37(d, 1H), 4. 99(dd, 1H), 4. 78(dd, 1H), 4. 60(d, 1H), 4. 40-4. 05(m, 3H), 2. 80-2. 51 (m, 3H), 2. 50(s, 3H), 2. 29(q, 1H), 1. 98-1. 12(m, 32H), 0. 82. (s, 3H). Compound 117: MS: m/z 855. 2(M++1) ; rH NMR(CDC13) δ 10. 08(s, 1H), 8. 22(d, 2H), 8. 03(d, 2H), 7. 44-7. 18(m, 3H), 7. 26-7. 17(m, 1H), 7. 13(d, 1H), 6. 12(s, 1H), 5. 65(q, 1H), 4. 89 (dd, 1H), 4. 77 (dd, 1H), 4. 49(d, 1H), 4. 42-4. 36(m, 1H), 4. 13(dd, 1H), 3. 16(s, 1H), 2. 84-2. 46(m, 4H), 2. 16(q, 1H), 1. 95-0. 77 (m, 31H). Compound 1]8: MS: m/z 895·4 (Μ++1). Compound 1]9: MS: m/z 895. 4 (M++1). Compound 120: MS: m/z 840·2 (Μ++1); 4 NMR (CDC13) δ 10. 26(s, 1H), 8. 38(d, 2H), 8. 20(d, 1H), 8. 00(d, 1H), 7. 61- 70 201109028 7. 54(m, 2H), 7. 50(d, 2H), 7. 41-7. 35 (m, 1H), 7. 15(s, 1H), 6. 72(d, 1H), 6. 10(d, 1H), 5. 63(q, 1H), 5. 27(d, 1H), 4. 89 (dd, 1H), 4. 68 (dd, 1H), 4. 51-4. 42 (m, 2H), 4. 12 (dd, 1H), 2. 84-2. 43 (m, 4H), 2. 22(q,1H), 1. 98-0. 84 (m, 24H). Compound 121: MS: m/z 829. 3 (M++1). Compound 122: MS: m/z 833. 3 (M++1). Compound 123: MS: m/z 821. 3(M++1) ; NMR(CDC13) δ 10. 27(s, 1H), 7. 90 (dd, 1H), 7. 60(s, 1H), 7. 27(dd, 1H), 7. 32-7. 20(m, 2H), 6. 91(s, 1H), 6. 53 (dd, 1H), 6. 03(s, 1H), 5. 64(q, 1H), 4. 98-4. 89(m, 2H), 4. 71-4. 58(m, 2H), 4. 14-4. 03 (m, 2H), 2. 86-2. 80 (m, 1H), 2. 67-2. 40 (m, 2H), 2. 22(q, 1H), 1. 98-1. 10 (m, 15H), 1. 05(s,9H),0. 98-0. 82 (m, 1H). Compound 124: MS: m/z 779·2 (Μ++1); NMR (CDC13) δ 10. 31(s, 1H), 7. 93(dd, 1H), 7. 70(s, 1H), 7. 65-7. 55 (dd, 1H), 7. 41-7. 26(m, 2H), 7. 04(s, 1H), 6. 61(s, 1H), 6. 15(s, 1H), 5. 72(q, 1H), 5. 37(d, 1H), 5. 01-4. 91(m, 1H), 4. 77 (dd, 1H), 4. 46(d, 1H), 4. 37-4. 09(m, 2H), 3. 36(s, 3H), 2. 92-2. 53(m, 3H), 2. 23(q,1H), 1. 99-0. 86 (m, 16H). Compound 125: MS: m/z 817_2 (M++1); 'H NMR (CDC13) δ 10. 28(s, 1H), 7. 98(d, 1H), 7. 66(s, 1H), 7. 60 (dd, 1H), 7. 40-7. 09(m, 3H), 6. 11(s, 1H), 6. 60(s, 1H), 6. 17(s, 1H), 5. 72(q, 1H), 4. 99(dd, 1H), 4. 76-4. 67(m, 2H), 4. 31-4. 18(m, 2H), 2. 91-2. 75 (m, 2H), 2. 45(br,1H), 2. 22-0. 84 (m, 17H). Compound 126: MS: m/z 763·2 (Μ++1); 4 NMR (CDC13) δ 71 201109028 10. 29(s, 1H), 7. 81 (dd, 1H), 7. 60(s, 1H), 7. 52 (dd, 1H), 7. 35-7. 18(m, 3H), 6. 52(d, 1H), 6. 13-6. 01(m, 2H), 5. 61(q, 1H), 4. 83 (dd, 1H), 4. 62 (dd, 1H), 4. 45 (dd, 1H), 4. 38(d, 1H), 4. 17(dd, 1H), 2. 85-2. 79(m, 1H), 2. 67(d, 1H), 2. 41 (m, 1H), 2. 21-0. 84 (m, 20H). Compound 127: MS: m/z 821·3 (Μ++1); NMR (CDC13) δ 10. 37(s, 1H), 8. 15(s, 1H), 7. 79(d, 1H), 7. 45-7. 42(m, 3H), 7. 35-7. 25(m, 1H), 7. 01(s, IH), 5. 89(s, 1H), 5. 54(q, 1H), 5. 19(d, 1H), 4. 85 (dd, 1H), 4. 67(dd, 1H), 4. 54(d, 1H), 4. 20 (dd, 1H), 4. 04(d, 1H), 2. 91-2. 44(m, 3H), 2. 24(q, 1H), 2. 01-1. Ll(m, 15H), 1. 06(s,9H),0. 83-0. 78 (m, 1H). Compound 128: MS: m/z 833. 3(M++1) ; rH NMR(CDC13) δ 10. 37(s, 1H), 8. 07(d, 1H), 7. 56-7. 22(m, 5H), 6. 89(d, 1H), 5. 96(s, 1H), 5. 57-5. 49 (m, 1H), 5. 21-5. 17(m, 1H), 4. 96-4. 83 (m, 1H), 4. 72 (dd, 1H), 4. 67(d, 1H), 4. 18-4. 03(m, 2H), 2. 90-2. 79(m, 1H), 2. 69(s, 3H), 2. 64-2. 46(m, 2H), 2. 22(q, 1H), 1. 97-1. 04(m, 15H), 1. 04(s,9H), 0. 96-0. 87 (m, 1H). Compound 129: MS: m/z 836. 3(M++1) ; NMR(CDC13) δ 10. 29(s, 1H), 7. 88(d, 1H), 7. 53-7. 50 (m, 1H), 7. 49 (dd, 1H), 7. 19(s, 1H), 6. 65(s, 1H), 6. 04(s, 1H), 5. 70-5. 50 (m, IH), 5. 12-4. 48 (m, 4H), 4. 19-3. 98(m, 2H), 2. 95-2. 58(m, 3H), 2. 48(s, 3H)S 2. 32-2. 12(m, 1H), 1. 97-1. 18(m, 15H), 1. 00(s, 9H), 0. 98-0. 86 (m, 1H). Compound 130: MS: m/z 832. 2(M++1); NMR(CDC13) δ 72 201109028 10. 20(s, 1H), 7. 84 (dd, 1H), 7. 52 (dd, 1H), 7. 39(, 1H), 7. 38-7. 26(m, 2H), 6. 62(s, 1H), 6. 05(s, 1H), 5. 60(q, 1H), 4. 83 (dd, 1H), 4. 67(dd, 1H), 4. 55 (dd, 1H), 4. 36(d, 1H), 4. 08 (dd, 1H), 2. 81-2. 50 (m, 3H), 2. 48(s, 3H), 2. 45-2. 37 (m, 1H), 2. 18(q, 1H), 1. 99-0_87 (m, 15H). Compound 131: MS: m/z 888. 3(M++1) ; NMR(CDC13) δ 10. 36(s, 1H), 8. 23(d, 1H), 7. 41(s, 1H), 7. 30 (m, 2H), 7. 11(s, 1H), 6. 16(s, 1H), 5. 68(q, 1H), 5. 23(d, 1H), 4. 98 (dd, 1H), 4. 75(brs, 1H), 4. 54(d, 1H), 4. 36-4. 11(m, 3H), 3. 39-3. 27(m, 1H), 2. 96-2. 63(m, 3H), 2. 54(s, 3H), 2. 25(q, 1H), 1. 89-0. 93 (m, 30H). Compound 132: MS: m/z 888. 3(M++1) ; 'H NMR(CDC13) δ 10. 24(s, 1H), 8. 37(d, 1H), 7. 74-7. 51(m, 2H), 7. 48-7. 42(m, 1H), 7. 22(s, 1H), 7. 12(s, 1H), 6. 17(s, 1H), 5. 70(q, 1H), 5. 28 (d, 1H), 4. 99(dd, 1H), 4. 76(dd, 1H), 4. 58(d, 1H), 4. 52(brs, 1H), 4. 35-4. 16(m, 2H), 3. 40-3. 35 (m, 1H), 2. 79-2. 43 (m, 3H), 2. 25(q, 1H), 1. 95-1. 23(m, 29H), 0. 87-0. 76 (m, 3H). Compound 133: MS: m/z 887·3 (Μ++1); 4 NMR (CDC13) δ 10. 37(s, 1H), 8. 59(s, 1H), 8. 22(d, 1H), 7. 81(d, 1H), 7. 58-7. 42 (m, 3H), 6. 95-6. 89(m, 2H), 6. 09(s, 1H), 5. 68(q, 1H), 5. 32(d, 1H), 4. 99(m, 1H), 4. 74 (m, 1H), 4. 54(d, 1H), 4. 39-4. 22 (m, 1H), 4. 14-4. 11 (m, 1H), 2. 90 (m, 1H), 2. 78(m, 2H), 2. 55 (m, 1H), 2. 27(q, 1H), 1. 90-1. 10(m, 21H), 1. 45(s, 9H), 0_94-0. 83 (m, 2H). 73 201109028 Compound 134: MS: m/z 901. 3(M++1);]H NMR(CDC13) δ 10. 21(s,lH), 8. 8. 51(s,lH), 8. 23(d,lH), 7. 81 (d, lH), 7. 59-7. 43(m, 3H), 7. 13(s, 1H), 6. 90(d, 1H), 6. 09(s, 1H), 5. 68(q, 1H), 5. 22(d, 1H), 4. 99(dd, 1H), 4. 76(m, IH), 4. 55(d, 1H), 4 39-4. 22 (m, 1H), 4. 14-4. 1 l(m, 1H), 2. 78(m, 2H), 2. 55(m, 1H), 2_27(q, 1H), 1. 90-0_83 (m, 23H), 1. 46(s, 9H). Compound 135: MS: m/z 888. 3 (M++1). Compound 136: MS: m/z 902. 3 (M++1). Compound 137: MS: m/z 899. 4 (M++1). Compound 138: MS: m/z 885. 3(M++1) ; 4 NMR(CDC13) δ 10. 36(s, 1H), 8. 17(d, 1H), 7. 58(m, 2H), 7. 42-7. 33(m, 2H), 6. 63(m, 1H), 6. 07(s, 1H)} 5. 67(q, 1H), 5. 29(d, 1H), 4. 97 (dd, 1H), 4. 77(m, 1H), 4. 57(m, 1H), 4. 42-4. 03(m, 3H), 2. 89 (m, 1H), 2. 75 (m, 5H), 2. 52(m, 1H), 2. 27(q, 1H), 1. 91-0. 82 (m, 32H). Compound 139: MS: m/z 803. 3 (M++1). Compound 140: MS: m/z 817. 3 (M++1). Compound 14L MS: m/z 831. 3(M++1) ; 4 NMR(CDC13) δ 10. 33(s, 1H), 8. 05(s, 1H), 7. 56-7. 48 (m, 3H), 6. 06(s, 1H), 5. 62(q, 1H), 5. 15(dd, 1H), 4. 91 (dd, 1H), 4. 75 (dd, 1H), 4. 59(d, 1H), 4. 35-4. 02(m, 3H), 2. 96-2. 88(m, 1H), 2. 74-2. 65 (m, 2H), 2. 53(s,3H), 2. 24(q,1H), 1. 96-0. 89 (m, 24H). Examples 142 and 143: Synthesis of [4-3⁄4 propyl-based aryl-based benzyl-2,15-di-lacto-18-(2-phenyl-74 201109028 benzo[4,5]furo[3, 2-b] acridine-4-yloxy)-3,16-diazatricyclo[14. 3·0·04,6]dodecyl-7-en-14-yl]-carbamic acid tert-butyl ester (Compound 142) and [4-cyclopropionylaminoamino-2,15-dioxo -18-(2-stupyl-stupid [4,5]pyrano[3,2-b] ate-4-yloxy)_316_diazatricyclo[14. 3. 0. 04,6] Nineteen carbon-7-thin-14-yl]-carbamic acid cyclopentyl ester (Compound 143) Compounds I42 and I43 were prepared by the following synthetic route: 75 201109028

76 143 201109028 向2-羥基苄腈（30克，251.6毫摩爾）在乙基甲基酮（32〇毫升）的溶液中加入碳酸钟(69.6克，755.5毫摩爾）。於室溫攪拌30分鐘之後，在形成的混合物中加入氣丙酮（34.95克， 3718毫摩爾）’然後於100°C加熱該溶液過夜。最後，減壓下除去反應溶劑，形成的固體用水和乙喊洗滌後得到76 143 201109028 To a solution of 2-hydroxybenzonitrile (30 g, 251.6 mmol) in ethyl methyl ketone (32 mL) was added a carbonic acid (69.6 g, 755.5 mmol). After stirring at room temperature for 30 minutes, air acetone (34.95 g, 3718 mmol) was added to the resulting mixture, which was then heated at 100 ° C overnight. Finally, the reaction solvent was removed under reduced pressure, and the resulting solid was washed with water and then washed.

1_13(31克’產率：70.3%)。MS: m/z 176.0 (M++1) ; 4 NMR (CDCI3) δ 7.59(d, 1H), 7.46(dd, 1H), 7.41(d, 1H), 7.24 (dd, 出)，2.50(s，3H)。於5-10°C，在恒定攪拌下，向2-乙醯基_3_氨基苯並呋喃1-13(2.17克，12.38毫摩爾）和笨曱醛（1.31克，12·38毫摩爾）的乙醇(30毫升）溶液中逐滴加入氫氧化鈉水溶液(7〇0/〇, 5 毫升）。攪拌過夜之後，亮黃色固體的粗產物懸浮在該反應 '谷液中。過濾固體，收集，並用乙醇重結晶，獲得絲狀針形物 1-14(2.7克，90%)。MS: m/z 264.0(M++1) ; 'H NMR (CDC13) δ 7.83(d, 1H), 7.71(dd, 2H), 7.64(d, 1H), 7.62(d, 1H)» 7.58-7.39(m, 5H), 7.29-7.24(m, 1H), 5.83(ms 2H) ° 將中間體I-M(1.32克，5.0毫摩爾）懸浮於乙酸酐（10毫升）中’並在熱水浴中攪拌。攪拌過夜後，將反應混合物倒入冰·水中。分離並收集懸浮的粗產物，然後用乙醇重結日日，得到I-15(1.52g，90〇/〇)。MS: m/z 306·0(Μ++1);丨H NMR (CDc!3) δ 8.58(d，1Η)，7.91(d，1Η)，7.72(m, 3Η)，7.54-7.44 (功，5H)，7.34.7.7 28(m，1H)，2.35(s, 3H)。將中間體1-15(1.22克’ 4.0毫摩爾）在CHC13(20毫升）的岭液緩慢滴加到溴（〇 72 g 4 5毫摩爾）在CHCb(15毫升）的溶 Λ 77 201109028 液中。攪拌過夜後’該反應混合物用冰水驟冷。將懸浮的固體分離、收集和用乙醇/h2o重結晶，獲得1-16(1·12克’ 60%)。MS: m/z 465.9(M++l) ; 'HNMR(CDC13) δ l〇.22(brs， 1Η), 8.63(d, 1H), 7.61-7.25(m, 8H), 5.92(d, 1H), 5.62(d, 1H), 2.37(s，3H)。向1-16(0.93克，2.0毫摩爾）在丙酮（25毫升）的溶液中加入無水乙酸鉀（0.2克，2.0毫摩爾）。攪拌過夜後，將反應混合物倒入冷水中。將懸浮的固體分離、收集和用乙醇重結晶，得到單溴化物-化合物1-17(0.46克，60%)。MS: m/z 385.9(M++1)； 'HNMR(CDC13) δ 10.50(brs, 1H), 8.54(d, 1H), 8.48(s, 1H)} 7.93(m, 2H), 7.56-7.46(m, 5H), 7.36-7.3l(m,lH), 2.35(s，3H)。化合物Μ7(0·35克，1.0毫摩爾）在乙酸(5毫升)和正磷酸 (5毫升）中回流5小時。將反應混合物冷卻至室溫，倒入冰水中再攪拌30分鐘。將懸浮的固體分離 '收集和用DMF重結晶，得到1-18(0.2克，80%)。1^:111^ 262.0(]^++1)。 1-18(1.0克，3.8毫摩爾）和磷醯氯(？〇(：13)(10毫升）的溶液回流2小時。將該溶液冷卻和完全濃縮之後，產生的殘餘物用10%氫氧化鈉猝滅，用二氣甲烷(20毫升X 3)萃取。收集有機層’用硫酸鈉乾燥，並濃縮。粗產物用CH2C12和正己院重結晶’獲得Ι-19(〇.7克，75%)°MS: m/z 279·9(Μ++1); ，H NMR(CDC13) δ 8.45(d, 1Η), 8.09(d, 2H), 7.84(s, 1H), 7.71-7.64(m, 2H), 7.56-7.47(m, 4H) «= 於〇°C向Boc-反_4-羥基_L-脯氨酸(0.53克，2.3毫摩爾） 78 201109028 在DMSO(10毫升）的懸浮液中加入i_BuONa(0.49克，5_08毫摩爾）。加熱至室溫並搜拌1小時後，於1 〇°C緩慢加入中間體1-19(0.64克’ 2.3毫摩爾）。攪拌該反應混合物4小時’然後用10% HC1水溶液猝滅至pH為6-7。過滤粗固體，用水洗滌，真空乾燥’得到I-20(0.94g，86.3%)。MS: m/z 475.1 (M++l) ； 'H NMR(CDC13) δ 8.27(d5 1Η), 7.97(m, 2H), 7.86-7.76(m,3H), 7.66-7.44(ms 4H), 5.81(s, 1H), 4.47(m, 1H), 4.03-3.89(m，2H)，2-81(m，lH)，2.50(q, 1H)。室溫，向1-20(1.1克’ 2.3毫摩爾）的MeOH(20毫升)溶液中加入8〇0：12(1.17克，9.9毫摩爾）。回流1小時後，真空去除反應溶劑，得到粗化合物1-21，該混合物無需進一步純化即可用於下一步驟。MS: m/z 389.1(M++1)。室溫，向I-21(0_78g，2.0毫摩爾）、2-(1Η-7-氮雜苯並三唑-1-基)-1，1，3,3-四甲基脲陽離子六氟-填酸鹽曱錄(HATU， 1.12克，3.0毫摩爾）、N-羥基苯並***(HOBT，0.4克，3.0 毫摩爾）和2-叔丁氧基羰基氨基-壬-8-烯酸(1.19克，5.2毫摩爾）的CH2C12(20毫升)溶液中加入NMM(1.0克，9.9毫摩爾）》攪拌混合物過夜之後，真空濃縮。殘餘物通過矽膠柱色譜純化，得到化合物 1-22(1.02克，80.7%)。MS: m/z 642.3 (M++l) ； ]H NMR(CDC13) δ 8.24(d, 1H), 8.05(d, 2H), 7.58(m, 2H), 7.56-7.41(m, 4H), 7.28(d, 1H), 5.83-5.76(q, 1H), 5.71(s, 1H), 5.24(d, 1H), 5.01-4.82(m, 2H), 4.76(dd, 1H), 4.75-4.34(m, 2H), 4.03(m, 1H), 3.77(s, 3H), 2.78(m, 1H), 2.36(q, 1H), 2.01(m, 2H), 1.75(m, 1H), 1.54(m, 1H), 1.42(m, 6H), 79 5 201109028 1.31(s，9H)。室溫，向1-22(1.0克，1.6毫摩爾）在THF(20毫升）的溶液中加入0.5 M LiOH(5.7毫升，2.9毫摩爾）。反應混合物攪拌過夜之後’用酸化至pH <7 ’並真空濃縮’得到固體產物，將固體產物過濾並用水洗滌，得到1-23。MS: m/z 628.1(M++1) * 'HNMRCCDCb) δ 8.34(brs, 1H), 8.04(d, 2H), 7.62(m, 2H), 7.60-7.41(m, 4H), 7.28(m, 2H), 5.81-5.72(q, 1H), 5.70(s, 1H), 5.29(d, 1H), 5.00-4.87(m, 3H), 4.48(m, 2H), 4.01(m, 1H), 2.77(m, 2H), 1.98(m, 2H), 1.72(m, 1H), 1.61(m, 1H), 1.44(m，6H)，1.33(s, 9H)。室溫，將NMM(0.12克，1.2毫摩爾）加入到化合物 1-23(0_26克，〇·41 毫摩爾）、HATU(0.31 克 ’ 0_81 毫摩爾）、 HOBT(0.084克，0.61毫摩爾）和環丙烷磺酸（1-氨基-2-乙烯基-環丙烷羰基)-醯胺(0.094克，0.41毫摩爾）在CH2C12(10毫升）的溶液中。攪拌反應混合物過夜之後，真空濃縮。殘餘物通過矽膠柱色譜純化，得到化合物1-24(0.15g，45%)。MS: m/z 804.3(M++1) ； 'H NMR(CDC13) δ 10.22(s, 1H), 8.35(d, 1H), 8.01(d, 2H), 7.59(d, 2H), 7.48-7.30(m, 5H), 7.04(s, 1H), 5.78(m, 3H), 5.35(d, 1H), 5.23(d, 1H), 5.15(d, 1H), 4.93(m, 2H), 4.53(dd, 1H), 4.41-4.30(m, 2H), 4.05(m, 1H), 2.91(m, 1H), 2.61(m, 2H), 2.14(dd, 1H), 2.04(m, 3H), 1.91-L52 (m,3H)，1.45-1.22(18H)，1.21(m，2H)。室溫，在N2下向化合物1-24(100毫克，0.12毫摩爾）在 CH2C12的溶液中加入霍維達-格拉布第二代催化劑（35毫 80 201109028 克，0.056毫摩爾），然後加熱該反應混合物至40°C並授拌24 小時。將反應混合物濃縮並通過柱純化，得到化合物142(30 毫克，31%)°MS: m/z 812.3(M++1); ’HNMR^CDCh) δ 10.29 (s，1H)，8.28(d，lH)，8.04(d，2H)，7.61-7.41(m，7H)，7.00(s， 1H), 5.69(m, 2H), 5.19(d, 1H), 4.97(dd, 1H), 4.67(m, 2H), 4.31(m, 1H), 4.05(m, 1H), 2.89(m, 1H), 2.70(m, 2H), 2.55(m, 1H), 2.29(q, 1H), 1.89-l.ll(m, 13H), 1.19(s, 9H), 0.97-0.86 (m，2H) 0 室溫’向化合物142(0.1克’ 0.14毫摩爾）在CH2Cl2(5毫升）的溶液中加入過量4 N HC1在二°惡院(2毫升）中的溶液。攪拌4小時後，蒸發去除HC1、二噁烷和CH2C12，得到粗化合物1-25 ’該粗化合物無需進一步純化即可用於下一步驟。 MS: m/z 712·3(Μ++1)。將1-25溶解於乙腈(2毫升）中，然後加入飽和NaHC03(l 毫升）。攪拌反應混合物10分鐘。室溫在反應混合物中加入氯甲酸環戊酯(0.02克，0_15毫摩爾）。再攪拌2小時之後，反應混合物用飽和NaHC03猝滅，用CH2C12萃取。殘餘物通過矽膠柱色譜純化，得到化合物143(0.1克，87%)。MS: m/z 824.3(M++1) ； 'H NMR(CDC13) δ 10.26(s, 1Η), 8.29(d,lH), 8.07(d, 2H), 7.62-7.32(m, 7H), 7.00(s, 1H), 5.75(s, 1H), 5.70(q, 1H), 5.22(d, 1H), 4.99(dd, 1H), 4.75(m, 2H), 4.56(d, 1H), 4.32(m, 1H), 4.05(m, 1H), 2.89(m, 1H), 2.70(m, 2H), 2.52(m, 1H)，2.29(q, 1H)，1.91-0.85(m，23H)。 81 201109028 實施例144-253 :化合物M4-253的合成化合物144-253各自按照與實施例142和143中所述類似的方式製備。化合物 144: MS: m/z 7887.3(M++1) ; ^HNNlI^CDCb) δ 10.36(s, 1H), 8.40(s, 1H), 8.21(d,lH), 8.08(dd, 1H), 7.56-7.11(m, 7H), 6.80(s, 1H), 5.63(m, 2H), 4.93(m, 1H), 4.79(m, 1H), 4.31(m, 2H), 4.05(m, 1H), 3.45(s, 3H), 2.87(m, 1H), 2.70(m，2H)，2.52(m, 1H)，2.25(q，1H)，1.91-0.84(m，15H)。化合物 145: MS: m/z 872.3(M++1)。化合物 146: MS: m/z 770.3(M++1) ; 4 NMR(CDC13) δ 10.35(s, 1H), 8.25(d,lH), 8.00(d, 2H), 7.56-7.25(m, 7H), 6.66(s, 1H), 5.69(m, 2H), 5.45(d, 1H), 4.95(dd, 1H), 4.70(m, 1H), 4.40-4.28(m, 2H), 4.05(m, 1H), 3.52(s, 3H), 2.88(m, 1H), 2.70(m, 2H), 2.51(m, 1H), 2.30(q, 1H), 1.87-1.09(m, 13H)，0.97-0.84(m，2H)。化合物 147: MS: m/z 697·2(Μ++1) ; 4 NMR(CDC13) δ 10.37(s, 1H), 8.24(d, 1H), 8.04(d, 2H), 7.56-7.31(m, 8H), 5.63(m, 2H), 4.97(dd, 1H), 4.63(m, 1H), 4.09(m, 1H), 3.96(m, 1H), 2.84(m,lH), 2.62(m, 2H), 2.6-2.03(m, 4H), 1.95-0.84(m, 15H) » 化合物 148: MS: m/z 872·3(Μ++1) ; 'H NMR(CDC13) δ 10.29(s, 1H), 8.09(dd, 1H), 7.69(d, 1H), 7.48-7.14(m, 7H), 5.71(m, 2H), 5.31(d,lH), 4.98(dd, 1H), 4.74(m, 1H), 4.55(d, 1H), 4.36(m, 1H), 4.05(m, 2H), 3.96(s, 3H), 2.89(m, 1H), 82 201109028 2.68(m，2H)，2.52(m, 1H)，2.28(q，1H)，2.00-0.88(m，23H)。化合物 149: MS: m/z 818·2(Μ++1)。化合物 150: MS: m/z 802·2(Μ++1) ; ’H NMR(CDC13) δ 10.23(s, 1H), 8.08(dd, 1H), 7.68(d, 1H), 7.49(d, 1H), 7.39-7.13(m, 6H), 6.10(d, 1H), 5.72(m, 2H), 4.95(dd, 1H), 4.63(m, 2H), 4.17(d, 1H), 4.06(m, 1H), 3.92(s, 3H), 2.89(m, 1H), 2.69(m, 2H), 2.46(m, 1H), 2.26(q, 1H), 1.94-0.86(m, 15H), 1.91(s, 3H)。化合物 151: MS: m/z 854·3(Μ++1) ; ’H NMR(CDC13) δ 10.26(s, 1H), 8.27(d, 1H), 8.03(d, 2H), 7.59(m, 3H), 7.45(dd, 1H), 7.01(d, 2H), 6.88(m, 1H), 5.74(m, 2H), 5.19(d, 1H), 4.96(m, 2H), 4.75(s, 1H), 4.53(d, 1H), 4.32(m, 1H), 4.04(m, 1H), 3.87(s, 3H), 2.89(m, 1H), 2.69(m, 2H), 2.46(m, 1H), 2_27(q，1H), 1.90-1.12(m,21H), 0.92-0.87(m,2H)。化合物 152: MS: m/z 842.3(M++1)。化合物 153: MS: m/z 854.3(M++1) ; h NMR(CDC13) δ 10.31(s, 1H), 8.58(s, 1H), 8.43(m,lH), 7.85(d, 1H), 7.59(m, 2H), 7.37(m, 3H), 7.12(dd, 1H), 7.01(d, 1H), 5.65(m, 2H), 5.31(d, 1H), 4.94(dd, 1H), 4.72(m, 2H), 4.53(d, 1H), 4.37(m, 1H), 4.07(m, 1H), 3.87(s, 3H), 2.88(m,lH), 2.66(m, 2H), 2_50(m，1H)，2.28(q, 1H)，l_88-0_82(m，23H)。化合物 154: MS: m/z 854.3(M++1) ; ’H NMR(CDC13) δ 10.29(s, 1H), 8.50(s, 1H), 8.29(d, 1H), 7.63(s, 1H), 7.56(m, 3H), 7.43(m, 2H), 7.28(m, 1H), 7.11(s, 1H), 6.98(dd,lH), 83 201109028 5.74(s, 1H), 5.69(q, 1H), 5.29(d, 1H), 4.94(dd, 1H), 4.73(m, 1H)，4.57(d，1H), 4.34(m, 1H), 4.04(m, 1H)，3.92(s，3H), 2.88(m, 1H), 2.68(m,2H), 2.51(m, 1H), 2.29(q, 1H), 1.87-0.84(m, 23H)。化合物 155: MS: m/z 842.3(M++1);丨只 NMR(CDC13) δ 10.28(s, 1H), 8.28(d,lH), 7.85(d, 1H), 7.57(m, 2H), 7.40(tn, 3H), 7.14(dd, 1H), 7.01(d, 2H), 5.68(q, 1H), 5.58(s, 1H), 5.19(d, 1H), 4.92(dd, 1H), 4.67(m, 2H), 4.33(m, 1H), 4.03(m, 1H), 3.87(s, 3H), 2.89(m,lH), 2.68(m, 2H), 2.54(m, 1H), 2.28(q, 1H), 1.90-l.ll(m, 13H), 1.21(s, 9H), 0.97-0.87(m, 2H)。化合物 156: MS: m/z 854·3(Μ++1) ; ’H NMR(CDC13) δ 10.24(s, 1H), 8.59(s, 1H), 8.04(m, 2H), 7.84(d, 1H), 7.49-7.28(m, 4H), 7.08(d, 1H), 6.91(s, 1H), 5.72(s, 1H), 5.68(q, 1H), 5.21(d, 1H), 4.97(dd, 1H), 4.71-4.67(m, 2H), 4.56(d, 1H), 4.36(m, 1H), 4.05(s, 3H), 4.04(m, 1H), 2.90(m, 1H), 2.69(m, 2H), 2.54(m, 1H), 2.31(q, 1H), 1.96-1.06(m, 21H), 0.95-0.83(m，2H)。化合物 157: MS: m/z 838·3(Μ++1) ; NMR(CDC13) δ 10.30(s, 1H), 8.59(s, 1H), 8.27(d, 1H), 7.92(d, 2H), 7.57(m, 2H), 7.44(m, 1 H), 7.26-7.17(m, 3H), 5.68(s, 1H), 5.64(q, 1H), 5.37(d, 1H), 4.96(m, 1H), 4.76(m, 1H), 4.67(m, 1H), 4.56(d, 1H), 4.36(m, 1H), 4.04(m, 1H), 2.89(m, 1H), 2.69(m, 2H), 2.53(m, 1H), 2.40(s, 3H), 2.31(q, 1H), 1.94-1.07(m, 21H), 84 201109028 0_95-0.83(m，2H)。化合物 158: MS: m/z 842·3(Μ++1) ; 4 NMR(CDC13) δ 10.31(s, 1H), 8.26(d, 1H), 8.05(m, 2H), 7.58(m, 2H), 7.43(m, 1H), 7.25-7.19(m, 4H), 5.72(s, 1H), 5.68(q, 1H), 5.35(d, 1H), 4.96(dd, 1H), 4.75-4.69(m, 2H), 4.56(d, 1H), 4.36(m, 1H), 4.04(m, 1H), 2.87(m, 1H), 2.67(m, 2H), 2.50(m, 1H), 2.28(q, 1H), 1.91-1.07(m，21H)，0.97-0.84(m, 2H)。化合物 159: MS: m/z 872.3(M++1)。化合物 160: MS: m/z 872.1(M++1) ; NMR(CDC13) δ 10.48(s, 1H), 8.02(m, 2H), 7.68(d, 1H), 7.47(d, 1H), 7.23-7.17(m, 4H), 5.74(m, 2H), 5.68(q, 1H), 5.23(d, 1H), 4.97(dd, 1H), 4.76(s, 1H), 4.67(m, 1H), 4.54(d, 1H), 4.33(m, 1H), 4.04(m, 1H), 3.93(s, 3H), 2.89(m, 1H), 2.67(m, 2H), 2.52(m, 1H)，2.27(q, 1H), 1.92-1.06(m，21H)，0.97-0.84(m，2H)。化合物 161: MS: m/z 860·2(Μ++1) ; NMR(CDC13) δ 10.34(s, 1H), 8.01(m, 2H), 7.67(d, 1H), 7.47(d, 1H), 7.29-7.16(m, 5H), 5.68(m, 2H), 5.23(d, 1H), 4.95(dd, 1H), 4.69-4.63(m, 2H), 4.31(m, 1H), 4.04(m, 1H), 3.92(s, 3H), 2.88(m, 1H), 2.67(m, 2H), 2.54(m, 1H), 2.27(q, 1H), 1.92-0.83(m, 15H)，1.20(s, 9H)。化合物 162: MS: m/z 856·1(Μ++1) ; 4 NMR(CDC13) δ 10.23(s, 1H), 8.03(m, 2H), 7.66(d, 1H), 7.48(d, 1H), 7.32(s, 1H), 7.29-7.15(m, 5H), 5.73(m, 2H), 4.92(dd, 1H), 4.69(m, 2H), 4.31(d, 1H), 4.06(m, 1H), 3.91(s, 3H), 2.85(m, 1H), 85 201109028 2.68(m, 2H), 2.44(m, 1H), 2.20(q, 1H), 1.93-0.83(m, 15H) ·> 化合物 163: MS: m/z 854·2(Μ++1) ; NMR(CDC13) δ 10.30(s, 1H), 8.60(s, 1H), 8.01(m, 2H), 7.68(d, 1H), 7.46(m, 4H), 7.15(m, 2H), 5.71(s, 1H), 5.68(q, 1H), 5.37(d, 1H), 4.96(dd, 1H), 4.67(s, 1H), 4.64(m, 1H), 4.55(d, 1H), 4.36(tn, 1H), 4.03(m, 1H), 3.93(s, 3H), 2.88(m, 1H), 2.68(m, 2H), 2.52(m, 1H), 2.28(q, 1H), 1.94-1.07(m, 21H), 0.97-0.84(m, 2H)。化合物 164: MS: m/z 830.4(M++1) ; 'H NMR(CDC13) δ 10.33(s, 1H), 8.25(d, 1H), 8.04(m, 2H), 7.57(m, 2H), 7.42(m, 1H), 7.25-7.14(m, 4H), 5.68(m, 2H), 5.25(d, 1H), 4.92(dd, 1H), 4.66(m, 2H), 4.32(m, 1H), 4.05(m, 1H), 2.87(m, 1H), 2.68(m, 2H), 2.55(m, 1H), 2.28(q, 1H), 1.91-1.06(m, 13H), 1.20(s,9H)，0.97-0.84(m, 2H)。化合物 165: MS: m/z 868.2(M++1) ; NMR(CDC13) δ 10.29(s, 1H), 8.53(s, 1H), 8.13(d, LH), 7.91(m, 2H), 7.58(m, 1H), 7.19(m, 1H), 7.00(m, 3H), 5.72(s, 1H), 5.68(q, 1H), 5.28(d, 1H), 4.95(dd, 1H), 4.79(s, 1H), 4.68(m, 1H), 4.53(d, 1H), 4.37(m, 1H), 4.05(m, 1H), 3.91(s, 3H), 2.88(m, 1H), 2.66(m, 2H), 2.50(m, 1H), 2.40(s, 3H), 2.25(q, 1H), 1.90-1.06(m, 21H)，0.97-0.83(m, 2H)。化合物 166: MS: m/z 868·3(Μ++1) ; NMR(CDC13) δ 10.30(s, 1H), 8.59(s, 1H), 7.98(m, 2H), 7.71(s, 1H), 7.46(d, 1H), 7.27(m, 2H), 7.15(m, 2H), 5.71(s, 1H), 5.68(q, 1H), 86 201109028 5.29(d, 1H), 4.94(dd, 1H), 4.78(s, 1H), 4.67(m, 1H), 4.54(d, 1H), 4.36(m, 1H), 4.04(m, 1H), 3.93(s, 3H), 2.88(m, 1H), 2.68(m, 2H), 2.53(m, 1H), 2.40(s, 3H), 2.28(q, 1H), 1.92-1.08(m, 21H), 0.97-0.83(m，2H)。化合物 167: MS: m/z 872·4(Μ++1) ; NMR(CDC13) δ 10.29(s, 1H), 8.51(s, 1H), 8.08(d, 1H), 8.01(m, 2H), 7.15(d, 2H), 7.04(m, 3H), 5.73(s, 1H), 5.69(q, 1H), 5.30(d, 1H), 4.95(dd, 1H), 4.79(s, 1H), 4.65(m, 1H), 4.53(d, 1H), 4.37(m, 1H), 4.04(m, 1H), 3.91(s, 3H), 2.88(m, 1H), 2.66(m, 2H), 2.50(m, 1H), 2.28(q, 1H), 1.90-1.05(m, 21H), 0.97-0.83(m, 2H)。化合物 168: MS: m/z 826.4(M++1) ; NMR(CDC13) δ 10.23(s, 1H), 8.28(d, 1H), 7.94(d, 2H), 7.56(m, 2H), 7.42(m, 1H), 7.28(m, 3H), 7.03(s, 1H), 5.68(m, 2H), 5.21(d, 1H), 4.94(dd, 1H), 4.67(m, 2H), 4.32(m, 1H), 4.05(m, 1H), 2.89(m, 1H), 2.68(m, 2H), 2.55(m, 1H), 2.55(s, 3H), 2.35(q, 1H), 1.94-1.07(m，13H), 1.20(s, 9H), 0.97-0.84(m，2H)。化合物 169: MS: m/z 858.3，859·3(Μ++1) ; NMR (CDC13) δ 10.35(s, 1H), 8.58(s, 1H), 8.24(d, 1H), 8.00(d, 2H), 7.57(m, 2H), 7.45(m, 3H), 7.25(s, 1H), 5.71(s, 1H), 5.66(q, 1H), 5.41(d, 1H), 4.96(dd, 1H), 4.75(m, 2H), 4.55(d, 1H), 4.35(m, 1H), 4.04(m, 1H), 2.87(m, 1H), 2.69(m, 2H), 2.57(m, 1H)，2.28(q，1H)，1.92-0.83(m，23H)。化合物 170: MS: m/z 772.2(M++1);NMR(CDC13) δ 87 201109028 10.31(s, lH), 8.22(d, 1H), 8.00(m, 2H), 7.59(m, 2H), 7.41(m, 1H), 7.20-7.10(m, 4H), 6.12(d, 1H), 5.72(m, 2H), 4.96(dd, 1H), 4.64(m, 1H), 4.55(m, 1H), 4.40(d, IH), 4.01(m, 1H), 2.88(m, 1H), 2.66(m, 2H), 2.50(m, 1H), 2.26(q, 1H), 1.92-1.05(m，13H)，1.91(s，3H)，0.97-0.85(m，2H)。化合物 171: MS: m/z 768·2(Μ++1) ; 4 NMR(CDC13) δ 10.29(s, 1H), 8.26(d, 1H), 7.93(d, 2H), 7.57(m, 2H), 7.42(m, 1H), 7.27(m, 4H), 6.16(d, 1H), 5.69(m, 2H), 4.94(dd, 1H), 4.67(m, 1H), 4.57(m, 1H), 4.40(d, 1H), 4.05(m, 1H), 2.89(m, 1H), 2.68(m, 2H), 2.51(m, 1H), 2.39(s, 3H),2.30(q, 1H), 1.94-1.05(m5 13H)，1.92(s, 3:H), 0.97-0.84(m，2H)。化合物 172: MS: m/z 788.2(M++1) ; b NMR(CDC13) δ 10.32(s, 1H), 8.22(d, 1H), 8.01(m, 2H), 7.57(m, 2H), 7.42(m, 1H), 7.22-7.11(m, 4H), 5.72(m, 2H), 5.39(d, 1H), 4.96(dd, 1H), 4.71(m, 1H), 4.39(m, 2H), 4.04(m, 1H), 3.54(s, 3H), 2.89(m,lH),2.71(m,2H)，2.54(m，lH)，2.25(q，lH)，1.91-1.06(m，13H)，0.93-0.83(m，2H)。化合物 173: MS: m/z 822.2(M++1) ; 4 NMR(CDC13) δ 10.15(s, 1H), 8.27(d, 1H), 7.91(d, 2H), 7.59(m, 2H), 7.44(m, 1H), 7.27(m, 3H), 7.15(d, 1H), 7.07(s, 1H), 5.75(s, 1H), 5.69(q, 1H), 4.91(dd, 1H), 4.68(m, 2H), 4.32(d, 1H), 4.06(m, 1H), 2.89(m, 1H), 2.68(m, 2H), 2.41(m, 1H), 2.39(s, 3H), 2.21(q，1H), 1.96-1.08(m，13H), 0.96-0.83(m，2H)。化合物 174: MS: m/z 826_2(M++1) ; 4 NMR(CDC13) δ 88 201109028 10.21(s, 1H), 8.22(d, 1H), 8.02(m, 2H), 7.59(m, 2H), 7.41(m, 1H), 7.24-7.13(m, 5H), 5.73(s, 1H), 5.67(q, 1H), 4.89(dd, 1H), 4.72(m, 2H), 4.31(d, 1H), 4.05(m, 1H), 2.87(m, 1H), 2.69(m, 2H), 2.47(m, 1H), 2.24(q, 1H), 1.93-1.04(m, 13H), 0.93-0.82(m，2H)。化合物 175: MS: m/z 842.3(M++1) ; 4 NMR(CDC13) δ 10.30(s，lH)，8.58(s,lH)，8.26(d，lH)，8.10(dd，lH)，7.61-7.14(m, 7H), 6.91(s, 1H), 5.67(m, 2H), 5.38(d, 1H), 4.96(dd, 1H), 4.70(m, 1H), 4.56(d, 1H), 4.36(m, 1H), 4.06(m, 1H), 2.88(m, 1H), 2.69(m, 2H), 2.51(m, 1H), 2.28(q, 1H), 1.87- 0.88(m，23H)。化合物 176: MS: m/z 844.3(M++1) ; ’H NMR(CDC13) δ 10.28(s, 1H), 8.00(m, 3H), 7.42(d, 1H), 7.37(d, 1H), 7.19(m, 3H), 6.98(s, 1H), 5.68(m, 2H), 5.19(d, 1H), 4.96(dd, 1H), 4.66(m, 2H), 4.30(m, 1H), 4.04(m, 1H), 2.89(m, 1H), 2.67(m, 2H), 2.52(s, 3H), 2.51(m, 1H), 2.26(q, 1H), 1.94-1.05(m, 13H)，1.20(s, 9H), 0.98-0.83(m, 2H)。化合物 177: MS: m/z 840.2(M++1) ; !H NMR(CDC13) δ 10.25(s, 1H), 8.00(m, 3H), 7.42(d, 1H), 7.35-7.11(m, 6H), 5.73(s, 1H), 5.69(q, 1H), 4.93(dd, 1H), 4.66(m, 2H), 4.32(d, 1H), 4.04(m, 1H), 2.89(m, 1H), 2.70(m, 2H), 2.51(s, 3H), 2.48(m, 1H), 2.23(q, 1H), 1.95-1.04(m, 13H), 0.96-0.82(m, 2H)。化合物 178: MS: m/z 784.2(M++1) ; 4 NMR(CDC13) δ 89 201109028 10.33(s, 1H)S 8.27(d, 1H), 7.92(d, 2H), 7.55(m, 2H), 7.41(m, 1H), 7.27(m, 4H), 5.70(m, 2H), 5.45(d, 1H), 4.95(dd, 1H), 4.67(m, 1H), 4.36(m, 2H)S 4.06(m, 1H), 3.49(s, 3H), 2.89(m, 1H), 2.69(m, 2H), 2.51(m, 1H), 2.39(s, 3H),2.26(q, 1H), 1.96-1.06(m，]3H), 0.97-0.83(m，2H)。化合物 179: MS: m/z 856_3(M++1) ; iH NMR(CDC13) δ 10.28(s, 1H), 7.92(d, 2H), 7.69(d, 1H), 7.44(d, 1H), 7.29(d, 2H), 7.15(s, 1H), 7.05(dd, 1H), 6.97(s, 1H), 5.68(m, 2H), 5.22(d, 1H), 4.95(dd, 1H), 4.62(m, 2H), 4.30(m, 1H), 4.03(m, 1H), 3.93(s, 3H), 2.87(m, 1H), 2.66(m, 2H), 2.54(m, 1H), 2.41(s, 3H), , 2.29(q, 1H), 1.94-0.82(m, 15H), 1.21(s, 9H) ^ 化合物 180: MS: m/z 814·3(Μ++1) ; 'H NMR(CDC13) δ 10.35(s, 1H), 7.92(d, 2H), 7.63(d, 1H), 7.42(d, 1H), 7.33-7.21(m, 4H)S 7.10(dd, 1H), 5.66(m, 2H), 5.41(d, 1H), 4.94(dd, 1H), 4.65(m, 1H), 4.37(m, 2H), 4.03(m, 1H), 3.91(s, 3H), 3.50(s, 3H), 2.87(m, 1H), 2.66(m, 2H), 2.51(m, 1H), 2.41(s, 3H)，2.25(q, 1H), 1.94-1.07(m，13H)，0.93-0.83(m，2H)。化合物 181: MS: m/z 852.2(M++1);丨H NMR(CDCl〇 δ 10.19(s，lH)，7.91(d，2H)，7.71(d,lH)，7.48(d，lH)，7.30-7.15(m, 5H), 7.13(dd, 1H), 5.66(s, 1H), 5.64(q, 1H), 4.94(dd, 1H), 4.65(m, 2H), 4.30(d, 1H), 4.03(m, 1H), 3.93(s, 3H), 2.84(m, 1H), 2.67(m, 2H), 2.46(m, 1H), 2.40(s, 3H), 2.22.(q, 1H)，1.95-0.84(m，15H)。化合物 182: MS: m/z 798.3(M++1);】H NMR(CDC13) δ 90 201109028 10.33(s, 1H), 7.92(d, 2H), 7.72(d, 1H), 7.43(d, 1H), 7.39(s, 1H), 7.21(m, 3H), 7.11(dd, 1H), 6.18(d, 1H), 5.70(q, 1H), 5.64(s, 1H), 4.94(dd, 1H), 4.66(dd, 1H), 4.56(m, 1H), 4.39(d, 1H), 4.02(m, 1H), 3.93(s, 3H), 2.84(m, 1H), 2.68(m, 2H), 2.47(m, 1H), 2.39(s, 3H), 2.25(q, 1H), 1.95-0.83(m, 15H), 1.91(s, 3H)。化合物 183: MS: m/z 802.2(M++1) ; iH NMR(CDC13) δ 10.39(s, 1H), 7.96(m, 3H), 7.44(m, 2H), 7.35(m, 1H), 7.14(m, 3H), 5.66(m, 2H), 5.41(d, 1H), 4.92(dd, 1H), 4.61(m, 1H), 4.30(m, 2H), 4.00(m, 1H), 3.50(s, 3H), 2.89(m, 1H), 2.72(m, 2H), 2.51(s, 3H), 2.50(m, 1H), 2.26(q, 1H), 1.93-1.06(m, 13H), 0.97-0_83(m, 2H)。化合物 184: MS: m/z 786.2(M++1) ; 4 NMR(CDC13) δ 10.36(s, 1H), 7.96(m, 3H), 7.42(m, 2H), 7.32(m, 1H), 7.15(m, 3H), 6.12(d, 1H), 5.69(q, 1H), 5.65(s, 1H), 4.94(dd, 1H), 4.64(m, 1H), 4.54(m, 1H), 4.38(d, 1H), 3.98(m, 1H), 2.88(m, 1H), 2.71(m, 2H), 2.50(m, 1H), 2.49(s, 3H), 2.27(q, 1H), 1.92-0.82(m，15H)，1.91(s, 3H)。化合物 185: MS: m/z 812·3(Μ++1) ; b NMR(CDC13) δ 10.37(s, 1H), 7.96(m, 3H), 7.41(d, 1H), 7.36(d, 1H), 7.25(m, 1H), 7.10(m, 3H), 6.19(d, 1H), 5.71(q, 1H), 5.64(s, 1H), 4.95(dd, 1H), 4.66(m, 1H), 4.48(m, 2H), 3.99(m, 1H), 2.89(m, 1H), 2.70(m, 2H), 2.51(m, 1H), 2.50(s, 3H), 2.27(q, 1H), 1.91-1.10(m，14H)，0.97-0.80(m，2H)，0.80-0.68(m, 4H)。 91 201109028 化合物 186: MS: m/z 856.3(M++1) ; ’H NMR(CDC13) δ 10.28(s, 1H), 8.00(m, 3H), 7.42(d, 1H), 7.37(d, 1H), 7.25-7.13(m, 3H), 7.04(s, 1H), 5.72(s, 1H), 5.69(q, 1H), 5.23(d, 1H), 4.97(dd, 1H), 4.77(s, 1H), 4.67(m, 1H), 4.55(d, 1H), 4.35(m, 1H), 4.04(m, 1H), 2.89(m, 1H), 2.68(m, 2H), 2.52(s, 3H), 2.51(m, 1H), 2.25(q, 1H), 1.93-1.06(m, 21H), 0.97-0.83(m，2H)。化合物 187: MS: m/z 830.2(M++1) ; 4 NMR(CDC13) δ 10.29(s，】H)，8.01(d，2H)，7.93(d, 1H)，7.50(m, 4H)，7.29(m， 2H), 7.07(s, 1H), 5.67(m, 2H), 5.19(d, 1H), 4.94(dd, 1H), 4.67(m, 2H)3 4.30(m, 1H), 4.04(m, 1H), 2.89(m, 1H), 2.69(m, 2H), 2.52(m, 1H), 2.28(q, IH), 1.94-1.05(m, 13H), 1.19(s, 9H)，0.97-0.84(m，2H)。化合物 188: MS: m/z 842.2(M++1);【H NMR(CDC13) δ 10.27(s, 1H), 8.02(d, 2H), 7.93(d, 1H), 7.52(m, 4H), 7.32.(s, 1H), 7.26(m, 1H), 7.08(s, 1H), 5.68(s, 1H), 5.66(q, 1H), 5.22(d, 1H), 4.92(dd, 1H), 4.71(m, 2H), 4.57(d, 1H), 4.33(m, 1H), 4.05(m, 1H), 2.89(m, 1H), 2.68(m, 2H), 2.53(m, 1H), 2.28(q，1H)，1.95-0.83(m，23H)。化合物 189: MS: m/z 882.4(M++1)。化合物 190: MS: m/z 884.2(M++1) ; ’H NMR(CDC13) δ 10.29(s, 1H), 7.96(m, 3H), 7.54(m, 1H), 7.36-7.26(m, 5H), 5.70(m, 2H), 5.27(d, 1H), 4.95(dd, 1H), 4.74(m, 1H), 4.53(d, 1H), 4.32(m, 1H), 4.05(m, 2H), 2.95(m, 2H), 2.69(m, 2H), 92 201109028 2.52(m，1H)，2.28(q，1H)，1.94-0.83(m, 23H), 1.29(d，6H)。化合物 191: MS: m/z 898·2(Μ++1)。化合物 192: MS: m/z 880·2(Μ++1) ; ’H NMR(CDC13) δ 10.31(s, 1H), 8.28(d, 1H), 7.95(d, 2H), 7.50(m, 4H), 7.42(dd, 1H), 7.27(s, 1H), 7.21(s, 1H), 5.68(s, 1H), 5.65(q, 1H), 5.35(d, 1H), 4.94(dd, 1H), 4.72(m, 2H), 4.57(d, 1H), 4.35(m, 1H), 4.04(m, 1H), 2.88(m, 1H), 2.68(m, 2H), 2.53(m, 1H), 2.28(q, 1H), 1.93-1.05(m, 21H), 1.36(s, 9H), 0.97-0.82(m, 2H)。化合物 193: MS: m/z 894.2(M++1) ; NMR(CDC13) δ 10.21(s, 1H), 8.28(d, 1H), 7.95(d, 2H), 7.52(m, 4H), 7.41(dd, 1H), 7.34(s, 1H), 7.26(s, 1H), 5.70(s, 1H), 5.65(q, 1H), 5.41(d, 1H), 4.95(dd, 1H), 4.75(m, 2H), 4.57(d, 1H), 4.36(m, 1H), 4.05(m, 1H), 2.70(m, 2H), 2.50(m, 1H), 2.29(q, 1H), 1.93-0.82(m, 23H), 1.46(s, 3H), 1.36(s, 9H)。化合物 194: MS: m/z 857.3(M++1)。化合物 195: MS: m/z 857·3(Μ++1)。化合物 196: MS: m/z 784·3(Μ++1) ; 4 NMR(CDC13) δ 10.20(s, 1H), 8.27(d,lH), 7.88(d, 1H), 7.57(m, 2H), 7.39(m, 3H), 7.13(dd, 1H), 7.01(d, 2H), 6.14(d, 1H), 5.68(q, 1H), 5.62(s, 1H), 4.97(dd, 1H), 4.64(m, 2H), 4.41(d, 1H), 4.07(m, 1H), 3.87(s, 3H), 2.87(m,lH), 2.67(m, 2H), 2.45(m, 1H), 2.25(q, 1H), 1.93-0.85(m, 15H)，1.92(s, 3H)。化合物 197: MS: m/z 856.3(M++1) ; 4 NMR(CDC13) δ s; 93 201109028 10.34(s, 1H), 8.03(s, 1H), 8.00(d, 2H), 7.45(d, 1H), 7.35{d, 1H), 7.16(m, 2H), 7.00(d, 2H), 5.71(s, 1H), 5.69(q, 1H), 5.23(d, 1H), 4.95(dd, 1H), 4.62(m, 2H), 4.30(m, 1H), 4.03(m, 1H), 3.86(s, 3H), 2.88(m, 1H), 2.66(ra, 2H), 2.5l(s, 3H), 2.50(m, 1H)，2.31(q，1H)，1.91-0.82(m，15H)，1.22(s, 9H)。化合物 198: MS: m/z 784.2(M++1)。化合物 199: MS: m/z 798.3(M++1) ; i.H NMR(CDC13) δ 10.37(s, 1H), 7.96(m, 3H), 7.58(s, 1H), 7.43(d, 1H), 7.32(d, 1H), 7.16(s, 1H), 6.97(d, 2H), 6.24(d, 1H), 5.69(q, 1H), 5.64(s, 1H), 4.96(dd, 1H)S 4.66(m, 1H), 4.55(m, 1H), 4.40(d, 1H), 4.02(m, 1H), 3.84(s, 3H), 2.87(m, 1H), 2.68(m, 2H), 2.49(s, 3H), 2.50(m, 1H), 2.28(q, 1H), 1.91-0.83(m, 15H), 1.91(s，3H)。化合物200: MS: m/z 852.2(M++1) ; iH NMR(CDC13) δ 10.26(s, 1H), 8.03(s, 1H), 7.96(d, 2H), 7.52(s, 1H), 7.45(d, 1H), 7.34(d, 1H), 7.23(s, 1H), 6.98(d, 2H), 5.67(s, 1H), 5.64(q, 1H), 5.21(m, 1H), 4.93(dd, 1H), 4.67(m, 2H), 4.30(d, 1H), 4.04(m, 1H), 3.85(s, 3H), 2.87(m, 1H), 2.66-2.40(m, 3H), 2.51(s，3H)，2.22(q，1H)，1.95-0.82(m, 】 5H)。化合物201: MS: m/z 814·3(Μ++1) ; NMR(CDC13) δ 10.41(s, 1H), 7.98(m, 3H), 7.60(s, 1H), 7.43(d, 1H), 7.33(d, 1H), 7.16(s, 1H), 6.98(d, 2H), 5.64(m, 2H), 5.29(m, 2H), 4.93(dd, 1H), 4.69(m, 1H), 4.36(m, 1H), 4.01(m, lH), 3.84(s, 3H), 3.42(s, 3H), 2.87(m, IH), 2.66(m, 2H), 2.50(m, 1H), 94 201109028 2.49(s，3H)，2.25(q，1H)，1.94-0.82(m，15H)。化合物202: MS: m/z 838.2(M++1) ; 4 NMR(CDC13) δ 10.23(s, 1H), 8.26(d, 1H), 8.00(d, 2H), 7.60(m, 2H), 7.44(m, 2H), 7.23(m, 2H), 7.01(d, 2H), 5.73(s, 1H), 5.67(q, 1H), 4.94(dd, 1H), 4.68(m, 2H), 4.32(d, 1H), 4.07(m, 1H), 3.86(s, 3H), 2.86(m, 1H), 2.67(m, 2H), 2.41(m, 1H), 2.23(q, 1H), 1.94-1.08(m, 13H), 0.94-0.87(m,2H)。化合物203: MS: m/z 842·3(Μ++1) ; ’H NMR(CDC13) δ 10.30(s, 1H), 8.28(d, 1H), 7.63(s, 1H), 7.57(m, 3H), 7.42(m, 2H), 7.25(m, 1H), 7.08(s, 1H), 6.97(dd,lH), 5.71(m, 2H), 5.22(d, 1H), 4.92(dd, 1H), 4.64(m, 2H), 4.3l(m, 1H), 4.00(m, 1H), 3.91(s, 3H), 2.89(m, 1H), 2.69(m,2H), 2.55(m, 1H), 2.29(q, 1H)，1.85-0.83(m, 15H), l-19(s, 9H)。化合物204: MS: m/z 784·2(Μ++1) ; 4 NMR(CDC13) δ 10.28(s, 1H), 8.26(d, 1H), 7.62(s, 1H), 7.58(m, 3H), 7.41(m, 2H), 7.25(m, 2H), 6.96(dd,lH), 6.13(d, 1H), 5.71(q, 1H), 5.68(s, 1H), 4.95(dd, 1H), 4.63(t, 1H), 4.59(m, 1H), 4.41(d, 1H), 4.04(m, 1H), 3.90(s, 3H), 2.88(m, 1H), 2.71(m,2H), 2.52(m, 1H), 2.29(q, 1H), 1.92-1.1.05(m, 13H), 1.91(s, 3H), 0.97-0.84(m，2H)。化合物205: MS: m/z 801.3(M++1);NMR(CDC13) δ 10.34(s, 1H), 8.25(d, 1H), 7.61(s, 1H), 7.57(m, 3H), 7.39-7.25(m, 4H), 6.93(dd,lH), 5.70(m, 2H), 5.44(d, 1H), 4.94(dd, 1H), 4.70(m, 1H), 4.39(d, 1H), 4.32(m, 1H), 4.03(m, 1H), 95 201109028 3.90(s, 3H), 3.48(s, 3H), 2.88(m, 1H), 2.70(m,2H), 2.52(m, 1H)，2.26(q，1H), 1.89-0.82(m，15H)。化合物206: MS: m/z 838_2(M++1);丨《[ NMR(CDC13) δ 10.19(s, 1H), 8.27(d, 1H), 7.62(s, 1H), 7.58(m, 3H), 7.41(m, 2H), 7.25(m, 3H), 6.97(dd,lH), 5.71(s, 1H), 5.63(q,lH), 4.92(dd, 1H), 4.64(m, 2H), 4.33(d, 1H), 4.05(m, 1H), 3.90(s, 3H), 2.88(m, 1H), 2.69(m,2H), 2.46(m, 1H), 2.23(q, 1H), 1.94- 1.1.03(m，13H), 0.95-0.84(m, 2H)。化合物207: MS: m/z 8(〕0.2(M++1) ; b NMR(CDC13) δ 10.24(s, 1H), 8.27(d,lH), 7.86(d, 1H), 7.55(m, 2H), 7.42(m, 3H), 7.12(m, 2H), 7.00(d, 1H), 5.68(q, 1H), 5.62(s, 1H), 5.47(d, 1H), 4.92(dd, 1H)S 4.68(m, 1H), 4.40(m, 2H), 4.04(m, 1H), 3.87(s, 3H), 3.50(s, ：3H), 2.89(m,lH), 2.68(m, 2H), 2.50(m, 1H), 2.25(q, 1H), 1.91-1.03(m, 13H), 0.98-0.82(m, 2H)。化合物208: MS: m/z 838.2(M++1) : ’H NMR(CDC13) δ 10.19(s, 1H), 8.27(d,lH), 7.82(d, 1H), 7.57(m, 2H), 7.39(m, 5H), 7.12(dd, 1H), 7.02(d, 1H), 5.63(q, 1H), 5.60(s, 1H), 4.90(dd, 1H), 4.70(m, 2H), 4.32(d, 1H), 4.03(m, 1H), 3.85(s, 3H), 2.86(m,lH), 2.71-2.52(m, 2H), 2.39(m, 1H), 2.20(q, 1H), 1.94- 0.84(m，15H)。化合物209: MS: m/z 896.4(M++1) ; 4 NMR(CDC13) δ 10.20(s，1H)，8.31(d，1H), 7.99(d, 2H)，7.58(m，2H), 7.42(m， 1H), 7.30-7.22(m, 2H), 7.01(d, 2H), 5.68(s, 1H), 5.66(q, 1H), 96 201109028 5.37(d, 1H), 4.96(dd, 1H), 4.78-4.51(m, 4H), 4.37(m, 1H), 4.06(m, 1H), 2.69(m, 2H), 2.51(m, 1H), 2.28(q, 1H), 1.94-0.83(m, 23H), 1.46(s, 3H), 1.37(d，6H)。化合物210: MS: m/z 882.4(M++1);NMR(CDC13) δ 10.24(s, 1H), 8.27(d, 1H), 7.98(d, 2H), 7.58(m, 2H), 7.42(m, 1H), 7.24(m, 1H), 7.01(d, 2H), 6.89(s, 1H), 5.68(s, 1H), 5.66(q, 1H), 5.22(d, 1H), 4.97(dd, 1H), 4.78-4.52(m, 4H), 4.36(m, 1H), 4.04(m, 1H), 2.88(m, 1H), 2.68(m, 2H), 2.54(m, 1H), 2.29(q, 1H), 1.94-1.05(m, 21H), 1.37(d, 6H), 0.97-0.83(m，2H)。化合物211: MS: m/z 922·2(Μ++1) ; ’H NMR(CDC13) δ 10.13(s, 1H), 8.26(d, 1H), 8.10(d, 2H), 7.59(m, 2H), 7.42(m, 1H), 7.35-7.25(m, 3H), 7.03(s, 1H), 5.77(s, 1H), 5.66(q, 1H), 5.20(d, 1H), 4.99(dd, 1H), 4.71(m, 2H), 4.56(d, 1H), 4.35(m, 1H), 4.03(m, 1H), 2.70(m, 2H), 2.50(m, 1H), 2.29(q, 1H), 1.90-0.84(m，23H), 0.85(s, 3H)。化合物212: MS: m/z 892·4(Μ++1) ; ’H NMR(CDC13) δ 10.36(s, 1H), 8.59(s, 1H), 8.25(d, 1H), 8.18(d, 2H), 7.73(d, 2H), 7.58(m, 2H), 7.45(m, 1H), 7.34(s, 1H), 5.74(s, 1H), 5.68(q, 1H), 5.39(d, 1H), 4.94(dd, 1H), 4.72(m, 2H), 4.55(d, 1H), 4.31(m, 1H), 4.04(m, 1H), 2.86(m, 1H), 2.67(m, 2H), 2.49(m，1H)，2.26(q，1H), 1.91-1.05(m，23H)。化合物213: MS: m/z 880.4(M++1) ; ’H NMR(CDC13) δ 10.36(s, 1H), 8.26(d, 1H), 8.16(d, 2H), 7.74(d, 2H), 7.59(m, s 97 201109028 2H), 7.45(m, 1H), 7.30(m, 2H), 5.71(s, 1H), 5.66(q, 1H), 5.25(d, 1H), 4.95(dd, 1H), 4.71(m, 1H), 4.65(d, 1H), 4.28(m, 1H), 4.03(m, 1H), 2.87(m, 1H), 2.70(m, 2H), 2.5l(m, 1H), 2.27(q, 1H), 1.92-1.06(m, 13H), 1.19(s, 9H), 0.97-0.82(m, 2H)。化合物214: MS: m/z 780·2(Μ++1)。化合物215:]^8:111/2 822.2(1^++1)。化合物216: MS: m/z 910_3(M++1);NMR(CDC13) δ 10.30(s, 1H), 8.15(d, 2H), 7.75(d, 2H), 7.61(s, 1H), 7.47(d, 1H), 7.25-7.15(m, 3H), 5.72(s, 1H), 5.68(q, 1H), 5.18(d, 1H), 4.98(dd, 1H), 4.67(m, 2H), 4.28(m, 1H), 4.04(m, 1H), 3.93(s, 3H), 2.89(m, 1H), 2.69(m, 2H), 2.52(m, 1H), 2.28(q, 1H), 1.91-0.85(m5 】5H)，1.20(s，9H)。化合物217: MS: m/z 9:22.3(M++1) ; h NMR(CDC13) δ 10.28(s, 1H), 8.17(m, 3H), 7.74(d, 2H), 7.26(m, 1H), 7.17(s, 1H), 7.02(m, 2H), 5.77(s, 1H), 5.69(q, 1H), 5.20(d, 1H), 4.96(dd, 1H), 4.77(s, 1H), 4.69(m, 1H), 4.54(d, 1H), 4.33(m, 1H), 4.04(m, 1H), 3.92(s, 3H), 2.89(m, 1H), 2.71(m, 2H), 2.52(m, 1H), 2.28(q, 1H), 1.90-1.05(m, 21H), 0.97-0.83(m, 2H)。化合物218: MS: m/z 892·4(Μ++1) ; NMR(CDC13) δ 10.29(s, 1H), 8.35(s，1H), 8.28(d, 1H)，8.24(d，1H)，7.59(m， 4H), 7.44(m, 1H), 7.33(s, 1H), 7.15(s, 1H), 5.80(s, 1H), 5.67 (q, 1H), 5.27(d, 1H), 4.95(dd, 1H), 4.70(m, 2H), 4.58(d, 1 H), 98 201109028 4.30(m, 1H), 4.06(m, 1H), 2.88(m, 1H), 2.70(m, 2H), 2.54(m, 1H)，2.28(q, 1H)，1.92-0.83(m, 23H)。化合物219: MS: m/z 880_2(M++1) ; 4 NMR(CDC13) δ 10.3l(s, 1H), 8.34(s, 1H), 8.28(d, 1H), 8.20(d, 1H), 7.60(m, 4H), 7.45(m, 1H), 7.29(s, 1H), 7.13(s, 1H), 5.77(s, 1H), 5.67(q, 1H), 5.19(m, 1H), 4.94(dd, 1H), 4.67(m, 2H), 4.26(m, 1H), 4.05(m, 1H), 2.88(m, 1H), 2.71(m, 2H), 2.53(m, 1H), 2.29(q, 1H)，1.90-0.83(m，15H), 1.18(s, 9H)。化合物220: MS: m/z 892.2(M++1) ; 'H NMR(CDC13) δ 10.29(s, 1H), 8.39(d, 1H), 8.06(d, 2H), 7.88(s, 1H), 7.71(d, 1H), 7.45(m, 3H), 7.36(s, 1H), 7.18(s, 1H), 5.68(s, 1H), 5.65(q, 1H), 5.33(d, 1H), 4.93(dd, 1H), 4.72(m, 2H), 4.67(d, 1H), 4.36(m, 1H), 4.05(m, 1H), 2.88(m, 1H), 2.70(m, 2H), 2.53(m，1H)，2.28(q，1H), 1.92-0.84(m, 23H)。化合物221: MS: m/z 880·4(Μ++1) ; NMR(CDC13) δ 10.30(s, 1H), 8.39(d, 1H), 8.04(d, 2H), 7.87(s, 1H), 7.69(d, 1H), 7.48(m, 3H), 7.33(s, 1H), 7.25(s, 1H), 5.67(m, 2H), 5.21(d, 1H), 4.94(dd, 1H), 4.68(m, 2H), 4.30(m, 1H), 4.04(m, 1H), 2.88(m, 1H), 2.69(m, 2H), 2.52(m, 1H), 2.28(q, 1H), 1.93-0.84(m，15H)，1.17(s, 9H)。化合物222: MS: m/z 814·3(Μ++1) ; ’H NMR(CDC13) δ 10.29(s, 1H), 8.46(s, 1H), 8.27(d,lH), 7.47(m, 3H), 7.41(m, 1H), 7.33(s, 1H), 7.16(d, 1H), 7.05(s, 1H), 6.56(d, 1H), 5.69 (m, 2H), 5.24(d, 1H), 4.95(dd, 1H), 4.66(m, 1H), 4.58(d, 1H), 99 201109028 4.38(m, 1H), 4.05(m, 1H), 2.89(m, 1H), 2.70(m, 2H), 2.34(m, 1H)，2.29(q, 1H)，1.90-1.06(m, 21H)，0.96-0.83(m, 2H)。化合物223: MS: m/z 802.2(M++1) ; ’H NMR(CDC13) δ 10.30(s, 1H), 8.28(d,lH), 7.54(m, 3H), 7.42(m, 1H), 7.29(s, 1H), 7.20(d, IH), 7.08(s, 1H), 6.56(d, 1H), 5.66(m, 2H), 5.15(d, 1H), 4.95(dd, 1H), 4.69(m, 2H), 4.30(m, 1H), 4.05(m, 1H), 2.89(m, 1H), 2.68(m, 2H), 2.35(m, 1H), 2.29(q, 1H), ].89-l_04(m，13H)，1.19(s，9H)，0.97-0.83(m, 2H)。化合物224: MS: m/z 848·2(Μ++1) ; 'H NMR(CDC13) δ 10.30(s, 1H), 8.08(d,lH), 7.58(d, 1H), 7.39(d, 1H), 7.14(s, 1H), 7.12-6.95(m, 4H), 5.70(m, 2H), 5.20(d, 1H), 4.95(dd, 1H), 4.66(m, 1H), 4.59(d, IH), 4.33(m, 1H), 4.03(m, 1H), 3.91(s, 3H), 2.90(m, 1H), 2.66(m, 2H), 2.52(m, 1H), 2.28(q, 1H)，1.89-1.06(m，13H)，].24(s, 9H)，0.94-0.83(m，2H)。化合物225: MS: m/z 760.2(M++1) ; 4 NMR(CDC13> δ 10.35(s，1H)，8.25(d，lH)，7.55(m，3H), 7.40(m，1H)，7_27(m， 2H), 7.16(d, 1H), 6.54(d, 1H), 5.66(m, 2H), 5.42(d, 1H), 4.94(dd, 1H), 4.67(m, 1H), 4.46(d, 1H), 4.35(m, 1H), 4.04(m, 1H), 3.50(s, 3H), 2.89(m, 1H), 2.66(m, 2H), 2.33(m, 1H), 2.26(q，1H)，1.92-0.83(m，15H)。化合物226: MS: m/z 798.2(M++1) ; 'H NMR(CDC13) δ 10.20(s, 1H), 8.25(d, 1H), 7.55(m, 3H), 7.4l(m, 1H), 7.27(m, 3H), 7.16(d, IH), 6.56(d, 1H), 5.66(m, 2H), 4.94(dd, 1H), 4.67(m, 2H), 4.35(d, 1H), 4.05(m, 1H), 2.88(m, 1H), 2.66(m, 100 201109028 2H)，2.43(m，1H)，2.26(q，1H)，1.96-0.83(m, 15H)。化合物227: MS: m/z 744.2(M++1) ; iH NMR(CDC13) δ 10.31(s, 1H), 8.21(d,lH), 7.55(m, 3H), 7.39(m, 1H), 7.33-7.25(m, 2H), 7.12(d, 1H), 6.56(d, 1H), 6.16(d, 1H), 5.66(q, 1H), 5.62(s, 1H), 4.94(dd, 1H), 4.62(m, 1H), 4.59(m, 1H), 4.41(d, 1H), 4.06(m, 1H), 2.87(m, 1H), 2.68(m, 2H), 2.50(m, 1H)，2.26(q，1H)，1.95-0.83(m，15H)，1.90(s，3H)。化合物228: MS: m/z 857_3(M++1)。化合物229: MS: m/z 830.3(M++1) ; h NMR(CDC13) δ 10.25(s, 1H), 8.26(d,lH), 7.59(m, 2H), 7.43(m, 2H), 7.25(m, 2H), 7.19(m, 1H), 7.06(m, 1H), 5.76(s, 1H), 5.72(q, 1H), 5.18(m, 1H), 4.97(dd, 1H), 4.68(m, 2H), 4.56(d, 1H), 4.30(m, 1H), 4.04(m, 1H), 2.90(m, 1H), 2.70(m, 2H), 2.39(m, 1H), 2.27(q, 1H), 1.90-0.80(m, 23H)。化合物230·· MS: m/z 860_3(M++1) ; 4 NMR(CDC13) δ 10.28(s, 1H), 8.10(d,lH), 7.58(d, 1H), 7.39(d, 1H), 7.18(s, 1H), 7.09-6.97(m, 4H), 5.72(s, 1H), 5.68(q, 1H), 5.24(d, 1H), 4.95(dd, 1H), 4.80(s, 1H), 4.65(m, 1H), 4.54(d, 1H), 4.32(m, 1H), 4.03(m, 1H), 3.91(s, 3H), 2.94(m, 1H), 2.68(m, 2H), 2.54(m, 1H), 2.28(q, 1H), 1.90-1.05(m, 21H), 0.95-0.84(m, 2H)。化合物231: MS: m/z 848.2(M++1) ; ’H NMR(CDC13) δ 10.26(s, 1H), 7.64(d,lH), 7.60(d, 1H), 7.48(d, 1H), 7.40(d, 1H), 7.20(s, 1H), 7.15(m, 2H), 6.88(s, 1H), 5.65(m, 2H), 101 201109028 5.10(d, 1H), 4.96(dd, 1H), 4.63(m, 2H), 4.31(m, 1H), 4.04(m, 1H), 3.94(s, 3H), 2.86(m, 1H), 2.68(m, 2H), 2.56(m, 1H), 2.29(q，1H)，1.94-0.83(m，15H)，1.22(s，9H)。化合物232: MS: m/z 836.2(M++1) ; 4 NMR(CDC13) δ 10.29(s, 1H), 7.89(dd,lH), 7.60(d, 1H), 7.50(dd, 1H), 7.40(d, 1H), 7.22(m, 2H), 7.10(m, 1H), 7.00(s, 1H), 5.68(m, 2H), 5.18(d, 1H), 4.95(dd, 1H), 4.66(m, 2H), 4.29(m, 1H), 4.04(m, 1H), 2.88(m, 1H), 2.67(m, 2H), 2.53(m, 1H), 2.26(q, 1H), 1.92-0.83(m，15H), 1.20(s, 9H)。化合物233: MS: m/z 806·2(Μ++1) ; NMR(CDC13) δ 10.36(s，]H)，8.05(d，lH)，7.59(d，lH)，7.38(m,2H)，7.14-6.97(m，4H)，5.70(m，2H)，5.64(d, 1H)，4.96(dd，1H)，4.65(m， 1H), 4.58(m, 2H), 4.04(m, 1H), 3.90(s, 3H), 3.58(s, 3H), 2.89(m, 1H), 2.68(m, 2H), 2.53(m, LH), 2.25(q, 1H), 1.88-0.82(m，15H)。化合物234: MS: m/z 860.2(M++1) ; A NMR(CDC13) δ 10.31(s, 1H), 7.63(d,lH), 7.60(d, 1H), 7.45(d, 1H), 7.40(d, 1H), 7.20(m, 2H), 7.10(m, 2H), 5.69(s, 1H), 5.67(q, 1H), 5.30(d, 1H), 4.94(dd, 1H), 4.78(s, 1H), 4.64(m, 1H), 4.55(d, 1H), 4.36(m, 1H), 4.04(m, 1H), 3.94(s, 3H), 2.89(m, 1H), 2.68(m, 2H), 2.53(m, 1H), 2.26(q, 1H), 1.93-1.04(m, 21H), 0.97-0.82(m, 2H)。化合物235: MS: m/z 844·2(Μ++1) ; ’H NMR(CDC13) δ 10.24(s, 1H), 8.04(d,lH), 7.58(d, 1H), 7.39(d, lH),7.31(m, 102 201109028 2H), 7.18(s, 1H), 7.08(m, 3H), 5.70(s, 1H), 5.67(q, 1H), 4.86(dd, 1H), 4.64(m, 2H), 4.26(d, 1H), 4.02(m, 1H), 3.90(s, 3H), 2.84(m, 1H), 2.65(m, 2H), 2.44(m, 1H), 2.20(q, 1H), 1.91-0_83(m，15H)。化合物236: MS: m/z 832·2(Μ++1) ; 'H NMR(CDC13) δ 10.27(s, 1H), 8.22(d,lH), 7.58(m, 2H), 7.44(m, 1H), 7.29(m, 1H), 7.10(s, 1H), 6.94(d, 1H), 6.90(s, 1H), 5.69(m, 2H), 5.18(d, 1H), 4.93(dd, 1H), 4.67(m, 2H), 4.28(m, 1H), 4.05(m, 1H), 2.85(m, 1H), 2.68(m, 2H), 2.55(s, 3H), 2.54(m, 1H), 2.28(q，1H), 1.91-0_83(m，15H), 1.19(s，9H)。化合物237: MS: m/z 844_3(M++1) ; NMR(CDC13) δ 10.23(s, 1H), 8.22(d,lH), 7.58(m, 2H), 7.40(m, 1H), 7.29(m, 2H), 6.96(d, 1H), 6.84(s, 1H), 5.69(s, 1H), 5.66(q, 1H), 5.20(d, 1H), 4.94(dd, 1H), 4.73(s, 1H), 4.67(m, 1H), 4.58(d, 1H), 4.35(m, 1H), 4.05(m, 1H), 2.89(m, 1H), 2.68(m, 2H), 2.56(s，3H)，2.54(m, 1H)，2.26(q，1H), 1.91-0.83(m，23H)。化合物238: MS: m/z 844.3(M++1) ; NMR(CDC13) δ 10.26(s，1H)，8.22(d，lH)，7.55(m，2H), 7.43(m，2H)，7.18(m， 1H), 6.93(s, 1H), 6.75(s, 1H), 5.70(m, 2H), 5.21(d, 1H), 4.94(dd, 1H), 4.78(s, 1H), 4.63(m, 1H), 4.53(d, 1H), 4.35(m, 1H), 4.05(m, 1H), 2.89(m, 1H), 2.67(m, 2H), 2.53(s, 3H), 2.52(m, 1H), 2.26(q, 1H), 1.92-1.04(m, 21H), 0.95-0.83(m, 2H)。化合物239: MS: m/z 790.2(M++1) ; 4 NMR(CDC13) δ s 103 201109028 10.34(s, 1H), 8.20(d,lH), 7.54(m, 2H), 7.38(m, 2H), 7.28(s, 1H), 7.14(s, 1H), 6.73(s, 1H), 5.68(m, 2H), 5.43(d, 1H), 4.94(dd, 1H), 4.65(m, 1H), 4.39(m, 2H), 4.04(m, 1H), 3.58(s, 3H), 2.89(m, 1H), 2.68(m, 2H), 2.5 l(s, 3H), 2.50(m, 1H), 2.28(q，1H)，1.93-1.06(m，13H)，0.94-0.82(m，2H)。化合物240: MS: m/z 828.2(M++1) ; 4 NMR(CDC13) δ 10.18(s, 1H), 8.22(d,lH), 7.56(m, 2H), 7.40(m, 2H), 7.20(s, 2H), 7.08(s, 1H), 6.76(d, IH), 5.71(s, 1H), 5.66(q, 1H), 4.94(dd, 1H), 4.66(m, 2H), 4.29(d, 1H), 4.04(m, 1H), 2.88(m, 1H), 2.65(m, 2H), 2.53(s, 3H), 2.45(m, 1H), 2.23(q, 1H), 1.96-1.05(m，13H)，0.95-0.83(m，2H)。化合物241: MS: m/z 778_1(M++1) ; 4 NMR(CDC13) δ 10.38(s, 1H), 7.89(dd,lH), 7.58(d, 2H), 7.44(dd, 1H), 7.35(d, 1H), 7.24(m, 2H), 7.05(m, 1H), 6.18(d, 1H), 5.7l(q, 1H), 5.62(s, 1H), 4.95(dd, 1H), 4.63(m, 1H), 4.50(m, 1H), 4.40(d, 1H), 4.00(m, 1H), 2.88(m, 1H), 2.66(m, 2H), 2.53(m, 1H), 2.22(q，lil)，1.96-0.82(m, 15H), 1.91(s, 3H)。化合物242: MS: m/z 846.4(M++1)。化合物243: MS: m/z 858.3(M++1) ; i NMR(CDC13) δ 10.28(s, 1H), 8.24(d, 1H), 7.57(m, 2H), 7.42.(m, 2H), 7.19(s, 1H), 7.08(ss 1H), 6.79(d, IH), 5.66(m, 2H), 5.24(d, 1H), 4.96(m, 1H), 4.78(s, 1H), 4.67(m, 1H), 4.55(d, 1H), 4.35(m, 1H), 4.03(m, 1H), 2.85(ra, 3H), 2.67(m, 2H), 2.53(m, 1H), 2.28(q, 1H), ：1.94-0.84(m，26H)。 104 201109028 化合物244: MS: m/z 872.3(M++1) ; 'H NMR(CDC13) δ 10.13(s, 1H), 8.24(d, 1H), 7.53(m, 2H), 7.41(m, 2H), 7.19(s, 1H), 6.99(s, 1H), 6.79(d, 1H), 5.69(m, 2H), 5.23(d, 1H), 4.98(dd, 1H), 4.77(s, 1H), 4.65(m, 1H), 4.55(d, 1H), 4.35(m, 1H), 4.04(m, 1H), 2.87(q, 2H), 2.68(m, 2H), 2.53(m, 1H), 2.29(q, 1H), 1.94-0.84(m，26H)，0.83(s, 3H)。化合物245: MS: m/z 831.2(M++1) ; iH NMR(CDC13) δ 10.21(s, 1H), 8.26(d,lH), 7.90(d, 2H), 7.58(m, 2H), 7.46(d, 2H), 7.00(s, 1H), 5.69(m, 2H), 5.09(d, 1H), 4.99(dd, 1H), 4.62(m, 3H), 4.27(m, 1H), 4.05(m, 1H), 2.89(m, 1H), 2.70(m, 2H)，2_56(m，1H)，2.29(q，1H)，1.94-0.84(m，23H)。化合物246: MS: m/z 761.4(M++1) ; 4 NMR(CDC13) δ 10.21(s, 1H), 8.17(d,lH), 7.80(d, 3H), 7.56(m, 2H), 7.41(d, 2H), 6.58(s, 1H), 5.61(m, 2H), 5.21(d, 1H), 4.65(m, 2H), 4.24(m, 1H), 4.05(m, 1H), 2.89(m, 1H), 2.70(m, 2H), 2.56-2.21(m, 2H), 1.94-0.84(m, 15H), 1.87(s，3H) 〇化合物247: MS: m/z 803.4(M++1)。化合物248: MS: m/z 845.3(M++1)。化合物249: MS: m/z 917.2(M++1) ; 4 NMR(CDC13) δ 10.22(s, 1H)，8.08(d，lH)，7.78(s，1H)，7.40(s，1H)，7.06(s， 1H), 6.97(m, 2H), 5.64(m, 2H), 5.32(d, 1H), 4.94(dd, 1H), 4.70(m, 2H), 4.54(d, 1H), 4.34(dd, 1H), 4.08(m, 1H), 3.83(s, 3H), 3.18(m, 1H), 2.73-2.43(m, 2H), 2.33(q, 1H), 2.15-1.20 (m，30H), 0.83(s，3H)。 105 201109028 化合物250: MS: m/z 905·4(Μ++1)。化合物251: MS: m/z 901.3(Μ++1)。化合物252: MS: m/z 917.4(Μ++1)。化合物253: MS: m/z 903.3(Μ++1)。實施例254:合成[4-環丙磺醯基氨基羰基-18-(2-氟-苯並[4,5] 呋喃並[3,2-b]喹啉-11-基氧基)-2,15-二氧代-3，16-二氮雜三環[14.3.0.04,6]十九烷-14-基]-氨基甲酸環戊酯（化合物254) 化合物254通過以下合成路線製備。 106 2011090281_13 (31 g' yield: 70.3%). MS: m/z 176.0 (M++1); 4 NMR (CDCI3) δ 7.59 (d, 1H), 7.46 (dd, 1H), 7.41 (d, 1H), 7.24 (dd, out), 2.50 (s) , 3H). To 2-ethylhydrazino-3-aminobenzofuran 1-13 (2.17 g, 12.38 mmol) and claudaldehyde (1.31 g, 12.38 mmol) at 5-10 ° C with constant stirring Aqueous sodium hydroxide (7 〇0/〇, 5 mL) was added dropwise to a solution of ethanol (30 mL). After stirring overnight, the crude product of the bright yellow solid was suspended in the reaction mixture. The solid was filtered, collected, and recrystallized from ethanol to give a filamentous needle 1-14 (2.7 g, 90%). MS: m/z 264.0 (M++1); 'H NMR (CDC13) δ 7.83 (d, 1H), 7.71 (dd, 2H), 7.64 (d, 1H), 7.62 (d, 1H)» 7.58- 7.39(m, 5H), 7.29-7.24 (m, 1H), 5.83 (ms 2H) ° Intermediate IM (1.32 g, 5.0 mmol) was suspended in acetic anhydride (10 mL) and in a hot water bath Stir. After stirring overnight, the reaction mixture was poured into ice and water. The suspended crude product was separated and collected, and then reconstituted with ethanol to obtain I-15 (1.52 g, 90 〇/〇). MS: m/z 306·0 (Μ++1); 丨H NMR (CDc!3) δ 8.58 (d, 1 Η), 7.91 (d, 1 Η), 7.72 (m, 3 Η), 7.54-7.44 , 5H), 7.34.7.7 28 (m, 1H), 2.35 (s, 3H). Intermediate 1-15 (1.22 g of '4.0 mmol) in celite of CHC13 (20 mL) was slowly added dropwise to bromo (〇72 g 4 5 mmol) in CHCb (15 mL) in sol. 77 201109028 . After stirring overnight, the reaction mixture was quenched with ice water. The suspended solids were separated, collected and recrystallized from ethanol/h2o to give 1-16 (1·12 g ' 60%). MS: m/z 465.9 (M++1); 'HNMR (CDC13) δ l 〇.22 (brs, 1 Η), 8.63 (d, 1H), 7.61-7.25 (m, 8H), 5.92 (d, 1H) ), 5.62(d, 1H), 2.37(s, 3H). Anhydrous potassium acetate (0.2 g, 2.0 mmol) was added to a solution of 1-16 (0.93 g, 2.0 mmol). After stirring overnight, the reaction mixture was poured into cold water. The suspended solid was separated, collected and recrystallized from ethanol to give monobromide-compound 1-17 (0.46 g, 60%). MS: m/z 385.9 (M++1); 'HNMR (CDC13) δ 10.50 (brs, 1H), 8.54 (d, 1H), 8.48 (s, 1H)} 7.93 (m, 2H), 7.56-7.46 (m, 5H), 7.36-7.3l (m, lH), 2.35 (s, 3H). The compound Μ7 (0. 35 g, 1.0 mmol) was refluxed in acetic acid (5 ml) and then. The reaction mixture was cooled to room temperature, poured into ice water and stirred for 30 min. The suspended solids were separated 'collected and recrystallized from DMF to give 1-18 (0.2 g, 80%). 1^: 111^ 262.0(]^++1). A solution of 1-18 (1.0 g, 3.8 mmol) and phosphonium chloride (?? (: 13) (10 ml) was refluxed for 2 hours. After the solution was cooled and completely concentrated, the resulting residue was treated with 10% hydr. The sodium was quenched and extracted with di-methane (20 mL EtOAc). The organic layer was collected and dried with sodium sulfate and concentrated. The crude product was recrystallized from CH2C12 and hexanes to obtain Ι-19 (〇.7 g, 75%) °MS: m/z 279·9(Μ++1); ,H NMR(CDC13) δ 8.45(d, 1Η), 8.09(d, 2H), 7.84(s, 1H), 7.71-7.64(m , 2H), 7.56-7.47(m, 4H) «= to °C to Boc-trans- 4-hydroxy-L-proline (0.53 g, 2.3 mmol) 78 201109028 Suspension in DMSO (10 ml) i_BuONa (0.49 g, 5-10 mmol) was added to the solution. After heating to room temperature and mixing for 1 hour, intermediate 1-19 (0.64 g '2.3 mmol) was slowly added at 1 ° C. The reaction mixture was stirred 4 </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; ; 'H NMR(CDC13) δ 8.27(d5 1Η), 7.97(m, 2H), 7.86-7.76(m,3H), 7.66-7.44(ms 4H), 5.81(s, 1H), 4 .47 (m, 1H), 4.03-3.89 (m, 2H), 2-81 (m, lH), 2.50 (q, 1H). Room temperature, 1-20 (1.1 g '2.3 mmol) of MeOH 8 〇 0:12 (1.17 g, 9.9 mmol) was added to a solution (20 mL). MS: m/z 389.1 (M++1), mp (1 - (1 - s), </ RTI> </ RTI> <RTIgt; , 3,3-tetramethylurea cation hexafluoro-salt sulphate (HATU, 1.12 g, 3.0 mmol), N-hydroxybenzotriazole (HOBT, 0.4 g, 3.0 mmol) and 2-un To a solution of butoxycarbonylamino-indol-8-enoic acid (1.19 g, 5.2 mmol) in CH2C12 (20 mL) Purification by gel column chromatography gave compound 1-22 (1.02 g, 80.7%). MS: m/z 642.3 (M++1);]H NMR (CDC13) δ 8.24 (d, 1H), 8.05 (d, 2H), 7.58 (m, 2H), 7.56-7.41 (m, 4H), 7.28(d, 1H), 5.83-5.76(q, 1H), 5.71(s, 1H), 5.24(d, 1H), 5.01-4.82(m, 2H), 4.76(dd, 1H), 4.75-4.34( m, 2H), 4.03(m, 1H), 3.77(s, 3H), 2.78(m, 1H), 2.36(q, 1H), 2.01(m, 2H), 1.75(m, 1H), 1.54(m , 1H), 1.42 (m, 6H), 79 5 201109028 1.31 (s, 9H). To a solution of 1-22 (1.0 g, 1.6 mmol) in THF (20 mL). The reaction mixture was stirred overnight before being acidified to pH. <7' and concentrated in vacuo to give a solid product which was filtered and washed with water to afford 1-23. MS: m/z 628. 1(M++1) * 'HNMRCCDCb) δ 8. 34(brs, 1H), 8. 04(d, 2H), 7. 62(m, 2H), 7. 60-7. 41(m, 4H), 7. 28(m, 2H), 5. 81-5. 72(q, 1H), 5. 70(s, 1H), 5. 29(d, 1H), 5. 00-4. 87(m, 3H), 4. 48 (m, 2H), 4. 01(m, 1H), 2. 77(m, 2H), 1. 98(m, 2H), 1. 72(m, 1H), 1. 61(m, 1H), 1. 44 (m, 6H), 1. 33(s, 9H). At room temperature, the NMM (0. 12 grams, 1. 2 mmol) was added to compound 1-23 (0-26 g, 〇·41 mmol), HATU (0. 31 grams ‘ 0_81 millimoles), HOBT (0. 084 grams, 0. 61 mmol) and cyclopropanesulfonic acid (1-amino-2-vinyl-cyclopropanecarbonyl)-decylamine (0. 094 grams, 0. 41 mmol) in a solution of CH2C12 (10 mL). After the reaction mixture was stirred overnight, concentrated in vacuo. The residue was purified by silica gel column chromatography to give compound 1-24 (0. 15g, 45%). MS: m/z 804. 3(M++1) ; 'H NMR(CDC13) δ 10. 22(s, 1H), 8. 35(d, 1H), 8. 01(d, 2H), 7. 59(d, 2H), 7. 48-7. 30 (m, 5H), 7. 04(s, 1H), 5. 78(m, 3H), 5. 35(d, 1H), 5. 23(d, 1H), 5. 15(d, 1H), 4. 93(m, 2H), 4. 53(dd, 1H), 4. 41-4. 30 (m, 2H), 4. 05(m, 1H), 2. 91 (m, 1H), 2. 61(m, 2H), 2. 14 (dd, 1H), 2. 04(m, 3H), 1. 91-L52 (m, 3H), 1. 45-1. 22 (18H), 1. 21 (m, 2H). At room temperature, under N2 to compound 1-24 (100 mg, 0. 12 mmol) Add Hovida-Grubb second generation catalyst in a solution of CH2C12 (35 mil 80 201109028 g, 0. 056 mmol), then the reaction mixture was heated to 40 ° C and allowed to mix for 24 hours. The reaction mixture was concentrated and purified by column to afford compound 142 (30 mg, 31%). MS: m/z 812. 3(M++1); 'HNMR^CDCh) δ 10. 29 (s, 1H), 8. 28(d,lH), 8. 04(d, 2H), 7. 61-7. 41 (m, 7H), 7. 00(s, 1H), 5. 69 (m, 2H), 5. 19(d, 1H), 4. 97 (dd, 1H), 4. 67(m, 2H), 4. 31 (m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2. 55 (m, 1H), 2. 29(q, 1H), 1. 89-l. Ll(m, 13H), 1. 19(s, 9H), 0. 97-0. 86 (m, 2H) 0 room temperature ' to compound 142 (0. 1 gram' 0. A solution of excess 4 N HCl in dioxane (2 ml) was added to a solution of CH2Cl2 (5 mL). After stirring for 4 hours, HCl, dioxane and CH2C12 were evaporated to give crude compound 1-25. MS: m/z 712·3 (Μ++1). 1-25 was dissolved in acetonitrile (2 mL) then saturated NaHC03 (1 mL). The reaction mixture was stirred for 10 minutes. Add cyclopentyl chloroformate to the reaction mixture at room temperature (0. 02 g, 0_15 mmol). After stirring for an additional 2 hours, the reaction mixture was quenched with saturated NaHC. The residue was purified by silica gel column chromatography to afford compound 143 (0. 1 gram, 87%). MS: m/z 824. 3(M++1) ; 'H NMR(CDC13) δ 10. 26(s, 1Η), 8. 29(d,lH), 8. 07(d, 2H), 7. 62-7. 32(m, 7H), 7. 00(s, 1H), 5. 75(s, 1H), 5. 70(q, 1H), 5. 22(d, 1H), 4. 99(dd, 1H), 4. 75(m, 2H), 4. 56(d, 1H), 4. 32(m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2. 52(m, 1H), 2. 29(q, 1H), 1. 91-0. 85 (m, 23H). 81 201109028 Examples 144-253: Synthesis of Compound M4-253 Compounds 144-253 were each prepared in a similar manner as described in Examples 142 and 143. Compound 144: MS: m/z 7887. 3(M++1) ; ^HNNlI^CDCb) δ 10. 36(s, 1H), 8. 40(s, 1H), 8. 21(d,lH), 8. 08(dd, 1H), 7. 56-7. 11 (m, 7H), 6. 80(s, 1H), 5. 63(m, 2H), 4. 93(m, 1H), 4. 79(m, 1H), 4. 31(m, 2H), 4. 05(m, 1H), 3. 45(s, 3H), 2. 87 (m, 1H), 2. 70 (m, 2H), 2. 52(m, 1H), 2. 25(q,1H), 1. 91-0. 84 (m, 15H). Compound 145: MS: m/z 872. 3 (M++1). Compound 146: MS: m/z 770. 3(M++1) ; 4 NMR(CDC13) δ 10. 35(s, 1H), 8. 25(d,lH), 8. 00(d, 2H), 7. 56-7. 25 (m, 7H), 6. 66(s, 1H), 5. 69 (m, 2H), 5. 45(d, 1H), 4. 95 (dd, 1H), 4. 70 (m, 1H), 4. 40-4. 28(m, 2H), 4. 05(m, 1H), 3. 52(s, 3H), 2. 88(m, 1H), 2. 70 (m, 2H), 2. 51(m, 1H), 2. 30(q, 1H), 1. 87-1. 09(m, 13H), 0. 97-0. 84 (m, 2H). Compound 147: MS: m/z 697·2 (Μ++1); 4 NMR (CDC13) δ 10. 37(s, 1H), 8. 24(d, 1H), 8. 04(d, 2H), 7. 56-7. 31 (m, 8H), 5. 63(m, 2H), 4. 97 (dd, 1H), 4. 63(m, 1H), 4. 09(m, 1H), 3. 96(m, 1H), 2. 84 (m, lH), 2. 62 (m, 2H), 2. 6-2. 03(m, 4H), 1. 95-0. 84(m, 15H) » Compound 148: MS: m/z 872·3 (Μ++1); 'H NMR (CDC13) δ 10. 29(s, 1H), 8. 09(dd, 1H), 7. 69(d, 1H), 7. 48-7. 14(m, 7H), 5. 71(m, 2H), 5. 31(d,lH), 4. 98 (dd, 1H), 4. 74 (m, 1H), 4. 55(d, 1H), 4. 36(m, 1H), 4. 05(m, 2H), 3. 96(s, 3H), 2. 89(m, 1H), 82 201109028 2. 68 (m, 2H), 2. 52(m, 1H), 2. 28(q,1H), 2. 00-0. 88 (m, 23H). Compound 149: MS: m/z 381. Compound 150: MS: m/z 802·2 (Μ++1); 'H NMR (CDC13) δ 10. 23(s, 1H), 8. 08(dd, 1H), 7. 68(d, 1H), 7. 49(d, 1H), 7. 39-7. 13(m, 6H), 6. 10(d, 1H), 5. 72(m, 2H), 4. 95 (dd, 1H), 4. 63(m, 2H), 4. 17(d, 1H), 4. 06(m, 1H), 3. 92(s, 3H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 46(m, 1H), 2. 26(q, 1H), 1. 94-0. 86(m, 15H), 1. 91(s, 3H). Compound 151: MS: m/z 854·3 (Μ++1); 'H NMR (CDC13) δ 10. 26(s, 1H), 8. 27(d, 1H), 8. 03(d, 2H), 7. 59(m, 3H), 7. 45 (dd, 1H), 7. 01(d, 2H), 6. 88(m, 1H), 5. 74(m, 2H), 5. 19(d, 1H), 4. 96(m, 2H), 4. 75(s, 1H), 4. 53(d, 1H), 4. 32(m, 1H), 4. 04(m, 1H), 3. 87(s, 3H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 46(m, 1H), 2_27(q, 1H), 1. 90-1. 12(m, 21H), 0. 92-0. 87 (m, 2H). Compound 152: MS: m/z 842. 3 (M++1). Compound 153: MS: m/z 854. 3(M++1) ; h NMR(CDC13) δ 10. 31(s, 1H), 8. 58(s, 1H), 8. 43(m,lH), 7. 85(d, 1H), 7. 59(m, 2H), 7. 37(m, 3H), 7. 12(dd, 1H), 7. 01(d, 1H), 5. 65 (m, 2H), 5. 31(d, 1H), 4. 94 (dd, 1H), 4. 72(m, 2H), 4. 53(d, 1H), 4. 37(m, 1H), 4. 07(m, 1H), 3. 87(s, 3H), 2. 88(m,lH), 2. 66(m, 2H), 2_50(m, 1H), 2. 28(q, 1H), l_88-0_82 (m, 23H). Compound 154: MS: m/z 854. 3(M++1) ; 'H NMR(CDC13) δ 10. 29(s, 1H), 8. 50(s, 1H), 8. 29(d, 1H), 7. 63(s, 1H), 7. 56(m, 3H), 7. 43(m, 2H), 7. 28(m, 1H), 7. 11(s, 1H), 6. 98(dd,lH), 83 201109028 5. 74(s, 1H), 5. 69(q, 1H), 5. 29(d, 1H), 4. 94 (dd, 1H), 4. 73 (m, 1H), 4. 57(d,1H), 4. 34(m, 1H), 4. 04(m, 1H), 3. 92(s,3H), 2. 88(m, 1H), 2. 68 (m, 2H), 2. 51(m, 1H), 2. 29(q, 1H), 1. 87-0. 84 (m, 23H). Compound 155: MS: m/z 842. 3 (M++1); 丨 only NMR (CDC13) δ 10. 28(s, 1H), 8. 28(d,lH), 7. 85(d, 1H), 7. 57(m, 2H), 7. 40(tn, 3H), 7. 14(dd, 1H), 7. 01(d, 2H), 5. 68(q, 1H), 5. 58(s, 1H), 5. 19(d, 1H), 4. 92(dd, 1H), 4. 67(m, 2H), 4. 33(m, 1H), 4. 03(m, 1H), 3. 87(s, 3H), 2. 89(m,lH), 2. 68(m, 2H), 2. 54 (m, 1H), 2. 28(q, 1H), 1. 90-l. Ll(m, 13H), 1. 21(s, 9H), 0. 97-0. 87 (m, 2H). Compound 156: MS: m/z 854·3 (Μ++1); 'H NMR (CDC13) δ 10. 24(s, 1H), 8. 59(s, 1H), 8. 04(m, 2H), 7. 84(d, 1H), 7. 49-7. 28(m, 4H), 7. 08(d, 1H), 6. 91(s, 1H), 5. 72(s, 1H), 5. 68(q, 1H), 5. 21(d, 1H), 4. 97 (dd, 1H), 4. 71-4. 67(m, 2H), 4. 56(d, 1H), 4. 36(m, 1H), 4. 05(s, 3H), 4. 04(m, 1H), 2. 90 (m, 1H), 2. 69 (m, 2H), 2. 54 (m, 1H), 2. 31(q, 1H), 1. 96-1. 06(m, 21H), 0. 95-0. 83 (m, 2H). Compound 157: MS: m/z 838·3 (Μ++1); NMR (CDC13) δ 10. 30(s, 1H), 8. 59(s, 1H), 8. 27(d, 1H), 7. 92(d, 2H), 7. 57(m, 2H), 7. 44(m, 1 H), 7. 26-7. 17(m, 3H), 5. 68(s, 1H), 5. 64(q, 1H), 5. 37(d, 1H), 4. 96(m, 1H), 4. 76(m, 1H), 4. 67(m, 1H), 4. 56(d, 1H), 4. 36(m, 1H), 4. 04(m, 1H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 53 (m, 1H), 2. 40(s, 3H), 2. 31(q, 1H), 1. 94-1. 07(m, 21H), 84 201109028 0_95-0. 83 (m, 2H). Compound 158: MS: m/z 842·3 (Μ++1); 4 NMR (CDC13) δ 10. 31(s, 1H), 8. 26(d, 1H), 8. 05(m, 2H), 7. 58(m, 2H), 7. 43(m, 1H), 7. 25-7. 19(m, 4H), 5. 72(s, 1H), 5. 68(q, 1H), 5. 35(d, 1H), 4. 96 (dd, 1H), 4. 75-4. 69 (m, 2H), 4. 56(d, 1H), 4. 36(m, 1H), 4. 04(m, 1H), 2. 87 (m, 1H), 2. 67(m, 2H), 2. 50 (m, 1H), 2. 28(q, 1H), 1. 91-1. 07(m, 21H), 0. 97-0. 84 (m, 2H). Compound 159: MS: m/z 872. 3 (M++1). Compound 160: MS: m/z 872. 1 (M++1) ; NMR (CDC13) δ 10. 48(s, 1H), 8. 02(m, 2H), 7. 68(d, 1H), 7. 47(d, 1H), 7. 23-7. 17(m, 4H), 5. 74(m, 2H), 5. 68(q, 1H), 5. 23(d, 1H), 4. 97 (dd, 1H), 4. 76(s, 1H), 4. 67(m, 1H), 4. 54(d, 1H), 4. 33(m, 1H), 4. 04(m, 1H), 3. 93(s, 3H), 2. 89 (m, 1H), 2. 67(m, 2H), 2. 52(m, 1H), 2. 27(q, 1H), 1. 92-1. 06(m, 21H), 0. 97-0. 84 (m, 2H). Compound 161: MS: m/z 860·2 (Μ++1); NMR (CDC13) δ 10. 34(s, 1H), 8. 01(m, 2H), 7. 67(d, 1H), 7. 47(d, 1H), 7. 29-7. 16(m, 5H), 5. 68(m, 2H), 5. 23(d, 1H), 4. 95 (dd, 1H), 4. 69-4. 63(m, 2H), 4. 31 (m, 1H), 4. 04(m, 1H), 3. 92(s, 3H), 2. 88(m, 1H), 2. 67(m, 2H), 2. 54 (m, 1H), 2. 27(q, 1H), 1. 92-0. 83(m, 15H), 1. 20(s, 9H). Compound 162: MS: m/z 856·1 (Μ++1); 4 NMR (CDC13) δ 10. 23(s, 1H), 8. 03(m, 2H), 7. 66(d, 1H), 7. 48(d, 1H), 7. 32(s, 1H), 7. 29-7. 15(m, 5H), 5. 73(m, 2H), 4. 92(dd, 1H), 4. 69 (m, 2H), 4. 31(d, 1H), 4. 06(m, 1H), 3. 91(s, 3H), 2. 85(m, 1H), 85 201109028 2. 68(m, 2H), 2. 44 (m, 1H), 2. 20(q, 1H), 1. 93-0. 83(m, 15H) ·> Compound 163: MS: m/z 854·2 (Μ++1); NMR (CDC13) δ 10. 30(s, 1H), 8. 60(s, 1H), 8. 01(m, 2H), 7. 68(d, 1H), 7. 46(m, 4H), 7. 15(m, 2H), 5. 71(s, 1H), 5. 68(q, 1H), 5. 37(d, 1H), 4. 96 (dd, 1H), 4. 67(s, 1H), 4. 64 (m, 1H), 4. 55(d, 1H), 4. 36(tn, 1H), 4. 03(m, 1H), 3. 93(s, 3H), 2. 88(m, 1H), 2. 68(m, 2H), 2. 52(m, 1H), 2. 28(q, 1H), 1. 94-1. 07(m, 21H), 0. 97-0. 84 (m, 2H). Compound 164: MS: m/z 830. 4(M++1) ; 'H NMR(CDC13) δ 10. 33(s, 1H), 8. 25(d, 1H), 8. 04(m, 2H), 7. 57(m, 2H), 7. 42(m, 1H), 7. 25-7. 14(m, 4H), 5. 68(m, 2H), 5. 25(d, 1H), 4. 92(dd, 1H), 4. 66(m, 2H), 4. 32(m, 1H), 4. 05(m, 1H), 2. 87 (m, 1H), 2. 68(m, 2H), 2. 55 (m, 1H), 2. 28(q, 1H), 1. 91-1. 06(m, 13H), 1. 20(s,9H),0. 97-0. 84 (m, 2H). Compound 165: MS: m/z 868. 2(M++1) ; NMR(CDC13) δ 10. 29(s, 1H), 8. 53(s, 1H), 8. 13(d, LH), 7. 91(m, 2H), 7. 58(m, 1H), 7. 19(m, 1H), 7. 00 (m, 3H), 5. 72(s, 1H), 5. 68(q, 1H), 5. 28(d, 1H), 4. 95 (dd, 1H), 4. 79(s, 1H), 4. 68(m, 1H), 4. 53(d, 1H), 4. 37(m, 1H), 4. 05(m, 1H), 3. 91(s, 3H), 2. 88(m, 1H), 2. 66(m, 2H), 2. 50 (m, 1H), 2. 40(s, 3H), 2. 25(q, 1H), 1. 90-1. 06(m, 21H), 0. 97-0. 83 (m, 2H). Compound 166: MS: m/z 868·3 (Μ++1); NMR (CDC13) δ 10. 30(s, 1H), 8. 59(s, 1H), 7. 98(m, 2H), 7. 71(s, 1H), 7. 46(d, 1H), 7. 27(m, 2H), 7. 15(m, 2H), 5. 71(s, 1H), 5. 68(q, 1H), 86 201109028 5. 29(d, 1H), 4. 94 (dd, 1H), 4. 78(s, 1H), 4. 67(m, 1H), 4. 54(d, 1H), 4. 36(m, 1H), 4. 04(m, 1H), 3. 93(s, 3H), 2. 88(m, 1H), 2. 68(m, 2H), 2. 53 (m, 1H), 2. 40(s, 3H), 2. 28(q, 1H), 1. 92-1. 08(m, 21H), 0. 97-0. 83 (m, 2H). Compound 167: MS: m/z 872·4 (Μ++1); NMR (CDC13) δ 10. 29(s, 1H), 8. 51(s, 1H), 8. 08(d, 1H), 8. 01(m, 2H), 7. 15(d, 2H), 7. 04(m, 3H), 5. 73(s, 1H), 5. 69(q, 1H), 5. 30(d, 1H), 4. 95 (dd, 1H), 4. 79(s, 1H), 4. 65 (m, 1H), 4. 53(d, 1H), 4. 37(m, 1H), 4. 04(m, 1H), 3. 91(s, 3H), 2. 88(m, 1H), 2. 66(m, 2H), 2. 50 (m, 1H), 2. 28(q, 1H), 1. 90-1. 05(m, 21H), 0. 97-0. 83 (m, 2H). Compound 168: MS: m/z 826. 4(M++1) ; NMR(CDC13) δ 10. 23(s, 1H), 8. 28(d, 1H), 7. 94(d, 2H), 7. 56(m, 2H), 7. 42(m, 1H), 7. 28(m, 3H), 7. 03(s, 1H), 5. 68(m, 2H), 5. 21(d, 1H), 4. 94 (dd, 1H), 4. 67(m, 2H), 4. 32(m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 55 (m, 1H), 2. 55(s, 3H), 2. 35(q, 1H), 1. 94-1. 07(m, 13H), 1. 20(s, 9H), 0. 97-0. 84 (m, 2H). Compound 169: MS: m/z 858. 3,859·3(Μ++1) ; NMR (CDC13) δ 10. 35(s, 1H), 8. 58(s, 1H), 8. 24(d, 1H), 8. 00(d, 2H), 7. 57(m, 2H), 7. 45 (m, 3H), 7. 25(s, 1H), 5. 71(s, 1H), 5. 66(q, 1H), 5. 41(d, 1H), 4. 96 (dd, 1H), 4. 75(m, 2H), 4. 55(d, 1H), 4. 35 (m, 1H), 4. 04(m, 1H), 2. 87 (m, 1H), 2. 69 (m, 2H), 2. 57 (m, 1H), 2. 28(q,1H), 1. 92-0. 83 (m, 23H). Compound 170: MS: m/z 772. 2(M++1); NMR(CDC13) δ 87 201109028 10. 31(s, lH), 8. 22(d, 1H), 8. 00(m, 2H), 7. 59(m, 2H), 7. 41 (m, 1H), 7. 20-7. 10(m, 4H), 6. 12(d, 1H), 5. 72(m, 2H), 4. 96 (dd, 1H), 4. 64 (m, 1H), 4. 55 (m, 1H), 4. 40(d, IH), 4. 01(m, 1H), 2. 88(m, 1H), 2. 66(m, 2H), 2. 50 (m, 1H), 2. 26(q, 1H), 1. 92-1. 05 (m, 13H), 1. 91(s,3H),0. 97-0. 85 (m, 2H). Compound 171: MS: m/z 768·2 (Μ++1); 4 NMR (CDC13) δ 10. 29(s, 1H), 8. 26(d, 1H), 7. 93(d, 2H), 7. 57(m, 2H), 7. 42(m, 1H), 7. 27(m, 4H), 6. 16(d, 1H), 5. 69 (m, 2H), 4. 94 (dd, 1H), 4. 67(m, 1H), 4. 57(m, 1H), 4. 40(d, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 51(m, 1H), 2. 39(s, 3H), 2. 30(q, 1H), 1. 94-1. 05(m5 13H), 1. 92(s, 3:H), 0. 97-0. 84 (m, 2H). Compound 172: MS: m/z 788. 2(M++1) ; b NMR(CDC13) δ 10. 32(s, 1H), 8. 22(d, 1H), 8. 01(m, 2H), 7. 57(m, 2H), 7. 42(m, 1H), 7. 22-7. 11 (m, 4H), 5. 72(m, 2H), 5. 39(d, 1H), 4. 96 (dd, 1H), 4. 71 (m, 1H), 4. 39(m, 2H), 4. 04(m, 1H), 3. 54(s, 3H), 2. 89 (m, lH), 2. 71 (m, 2H), 2. 54 (m, lH), 2. 25(q,lH), 1. 91-1. 06(m, 13H), 0. 93-0. 83 (m, 2H). Compound 173: MS: m/z 822. 2(M++1) ; 4 NMR(CDC13) δ 10. 15(s, 1H), 8. 27(d, 1H), 7. 91(d, 2H), 7. 59(m, 2H), 7. 44(m, 1H), 7. 27(m, 3H), 7. 15(d, 1H), 7. 07(s, 1H), 5. 75(s, 1H), 5. 69(q, 1H), 4. 91 (dd, 1H), 4. 68(m, 2H), 4. 32(d, 1H), 4. 06(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 41 (m, 1H), 2. 39(s, 3H), 2. 21(q,1H), 1. 96-1. 08(m,13H), 0. 96-0. 83 (m, 2H). Compound 174: MS: m/z 826_2 (M++1); 4 NMR (CDC13) δ 88 201109028 10. 21(s, 1H), 8. 22(d, 1H), 8. 02(m, 2H), 7. 59(m, 2H), 7. 41 (m, 1H), 7. 24-7. 13(m, 5H), 5. 73(s, 1H), 5. 67(q, 1H), 4. 89 (dd, 1H), 4. 72(m, 2H), 4. 31(d, 1H), 4. 05(m, 1H), 2. 87 (m, 1H), 2. 69 (m, 2H), 2. 47(m, 1H), 2. 24(q, 1H), 1. 93-1. 04(m, 13H), 0. 93-0. 82 (m, 2H). Compound 175: MS: m/z 842. 3(M++1) ; 4 NMR(CDC13) δ 10. 30(s,lH), 8. 58(s,lH), 8. 26(d,lH), 8. 10 (dd, lH), 7. 61-7. 14(m, 7H), 6. 91(s, 1H), 5. 67(m, 2H), 5. 38(d, 1H), 4. 96 (dd, 1H), 4. 70 (m, 1H), 4. 56(d, 1H), 4. 36(m, 1H), 4. 06(m, 1H), 2. 88(m, 1H), 2. 69 (m, 2H), 2. 51(m, 1H), 2. 28(q, 1H), 1. 87- 0. 88 (m, 23H). Compound 176: MS: m/z 844. 3(M++1) ; 'H NMR(CDC13) δ 10. 28(s, 1H), 8. 00(m, 3H), 7. 42(d, 1H), 7. 37(d, 1H), 7. 19(m, 3H), 6. 98(s, 1H), 5. 68(m, 2H), 5. 19(d, 1H), 4. 96 (dd, 1H), 4. 66(m, 2H), 4. 30 (m, 1H), 4. 04(m, 1H), 2. 89 (m, 1H), 2. 67(m, 2H), 2. 52(s, 3H), 2. 51(m, 1H), 2. 26(q, 1H), 1. 94-1. 05(m, 13H), 1. 20(s, 9H), 0. 98-0. 83 (m, 2H). Compound 177: MS: m/z 840. 2(M++1) ; !H NMR(CDC13) δ 10. 25(s, 1H), 8. 00(m, 3H), 7. 42(d, 1H), 7. 35-7. 11 (m, 6H), 5. 73(s, 1H), 5. 69(q, 1H), 4. 93(dd, 1H), 4. 66(m, 2H), 4. 32(d, 1H), 4. 04(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2. 51(s, 3H), 2. 48 (m, 1H), 2. 23(q, 1H), 1. 95-1. 04(m, 13H), 0. 96-0. 82 (m, 2H). Compound 178: MS: m/z 784. 2(M++1) ; 4 NMR(CDC13) δ 89 201109028 10. 33(s, 1H)S 8. 27(d, 1H), 7. 92(d, 2H), 7. 55(m, 2H), 7. 41 (m, 1H), 7. 27(m, 4H), 5. 70 (m, 2H), 5. 45(d, 1H), 4. 95 (dd, 1H), 4. 67(m, 1H), 4. 36(m, 2H)S 4. 06(m, 1H), 3. 49(s, 3H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 51(m, 1H), 2. 39(s, 3H), 2. 26(q, 1H), 1. 96-1. 06(m,]3H), 0. 97-0. 83 (m, 2H). Compound 179: MS: m/z 856_3 (M++1); iH NMR (CDC13) δ 10. 28(s, 1H), 7. 92(d, 2H), 7. 69(d, 1H), 7. 44(d, 1H), 7. 29(d, 2H), 7. 15(s, 1H), 7. 05(dd, 1H), 6. 97(s, 1H), 5. 68(m, 2H), 5. 22(d, 1H), 4. 95 (dd, 1H), 4. 62(m, 2H), 4. 30 (m, 1H), 4. 03(m, 1H), 3. 93(s, 3H), 2. 87 (m, 1H), 2. 66(m, 2H), 2. 54 (m, 1H), 2. 41(s, 3H), , 2. 29(q, 1H), 1. 94-0. 82(m, 15H), 1. 21(s, 9H) ^ Compound 180: MS: m/z 814·3 (Μ++1); 'H NMR (CDC13) δ 10. 35(s, 1H), 7. 92(d, 2H), 7. 63(d, 1H), 7. 42(d, 1H), 7. 33-7. 21(m, 4H)S 7. 10(dd, 1H), 5. 66(m, 2H), 5. 41(d, 1H), 4. 94 (dd, 1H), 4. 65 (m, 1H), 4. 37(m, 2H), 4. 03(m, 1H), 3. 91(s, 3H), 3. 50(s, 3H), 2. 87 (m, 1H), 2. 66(m, 2H), 2. 51(m, 1H), 2. 41(s, 3H), 2. 25(q, 1H), 1. 94-1. 07(m,13H),0. 93-0. 83 (m, 2H). Compound 181: MS: m/z 852. 2(M++1); 丨H NMR (CDCl〇 δ 10. 19(s,lH), 7. 91(d, 2H), 7. 71 (d, lH), 7. 48(d,lH), 7. 30-7. 15(m, 5H), 7. 13(dd, 1H), 5. 66(s, 1H), 5. 64(q, 1H), 4. 94 (dd, 1H), 4. 65 (m, 2H), 4. 30(d, 1H), 4. 03(m, 1H), 3. 93(s, 3H), 2. 84 (m, 1H), 2. 67(m, 2H), 2. 46(m, 1H), 2. 40(s, 3H), 2. twenty two. (q, 1H), 1. 95-0. 84 (m, 15H). Compound 182: MS: m/z 798. 3(M++1);]H NMR(CDC13) δ 90 201109028 10. 33(s, 1H), 7. 92(d, 2H), 7. 72(d, 1H), 7. 43(d, 1H), 7. 39(s, 1H), 7. 21(m, 3H), 7. 11 (dd, 1H), 6. 18(d, 1H), 5. 70(q, 1H), 5. 64(s, 1H), 4. 94 (dd, 1H), 4. 66(dd, 1H), 4. 56(m, 1H), 4. 39(d, 1H), 4. 02(m, 1H), 3. 93(s, 3H), 2. 84 (m, 1H), 2. 68(m, 2H), 2. 47(m, 1H), 2. 39(s, 3H), 2. 25(q, 1H), 1. 95-0. 83(m, 15H), 1. 91(s, 3H). Compound 183: MS: m/z 802. 2(M++1) ; iH NMR(CDC13) δ 10. 39(s, 1H), 7. 96(m, 3H), 7. 44(m, 2H), 7. 35 (m, 1H), 7. 14(m, 3H), 5. 66(m, 2H), 5. 41(d, 1H), 4. 92(dd, 1H), 4. 61 (m, 1H), 4. 30 (m, 2H), 4. 00 (m, 1H), 3. 50(s, 3H), 2. 89 (m, 1H), 2. 72(m, 2H), 2. 51(s, 3H), 2. 50 (m, 1H), 2. 26(q, 1H), 1. 93-1. 06(m, 13H), 0. 97-0_83 (m, 2H). Compound 184: MS: m/z 786. 2(M++1) ; 4 NMR(CDC13) δ 10. 36(s, 1H), 7. 96(m, 3H), 7. 42(m, 2H), 7. 32(m, 1H), 7. 15(m, 3H), 6. 12(d, 1H), 5. 69(q, 1H), 5. 65(s, 1H), 4. 94 (dd, 1H), 4. 64 (m, 1H), 4. 54(m, 1H), 4. 38(d, 1H), 3. 98(m, 1H), 2. 88(m, 1H), 2. 71(m, 2H), 2. 50 (m, 1H), 2. 49(s, 3H), 2. 27(q, 1H), 1. 92-0. 82 (m, 15H), 1. 91(s, 3H). Compound 185: MS: m/z 812·3 (Μ++1); b NMR (CDC13) δ 10. 37(s, 1H), 7. 96(m, 3H), 7. 41(d, 1H), 7. 36(d, 1H), 7. 25(m, 1H), 7. 10(m, 3H), 6. 19(d, 1H), 5. 71(q, 1H), 5. 64(s, 1H), 4. 95 (dd, 1H), 4. 66(m, 1H), 4. 48 (m, 2H), 3. 99(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2. 51(m, 1H), 2. 50(s, 3H), 2. 27(q, 1H), 1. 91-1. 10 (m, 14H), 0. 97-0. 80 (m, 2H), 0. 80-0. 68 (m, 4H). 91 201109028 Compound 186: MS: m/z 856. 3(M++1) ; 'H NMR(CDC13) δ 10. 28(s, 1H), 8. 00(m, 3H), 7. 42(d, 1H), 7. 37(d, 1H), 7. 25-7. 13(m, 3H), 7. 04(s, 1H), 5. 72(s, 1H), 5. 69(q, 1H), 5. 23(d, 1H), 4. 97 (dd, 1H), 4. 77(s, 1H), 4. 67(m, 1H), 4. 55(d, 1H), 4. 35 (m, 1H), 4. 04(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 52(s, 3H), 2. 51(m, 1H), 2. 25(q, 1H), 1. 93-1. 06(m, 21H), 0. 97-0. 83 (m, 2H). Compound 187: MS: m/z 830. 2(M++1) ; 4 NMR(CDC13) δ 10. 29(s,]H), 8. 01(d, 2H), 7. 93(d, 1H), 7. 50 (m, 4H), 7. 29(m, 2H), 7. 07(s, 1H), 5. 67(m, 2H), 5. 19(d, 1H), 4. 94 (dd, 1H), 4. 67(m, 2H)3 4. 30 (m, 1H), 4. 04(m, 1H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 52(m, 1H), 2. 28(q, IH), 1. 94-1. 05(m, 13H), 1. 19(s, 9H), 0. 97-0. 84 (m, 2H). Compound 188: MS: m/z 842. 2 (M++1); [H NMR (CDC13) δ 10. 27(s, 1H), 8. 02(d, 2H), 7. 93(d, 1H), 7. 52(m, 4H), 7. 32. (s, 1H), 7. 26(m, 1H), 7. 08(s, 1H), 5. 68(s, 1H), 5. 66(q, 1H), 5. 22(d, 1H), 4. 92(dd, 1H), 4. 71(m, 2H), 4. 57(d, 1H), 4. 33(m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 53 (m, 1H), 2. 28(q,1H), 1. 95-0. 83 (m, 23H). Compound 189: MS: m/z 882. 4 (M++1). Compound 190: MS: m/z 884. 2(M++1) ; 'H NMR(CDC13) δ 10. 29(s, 1H), 7. 96(m, 3H), 7. 54(m, 1H), 7. 36-7. 26(m, 5H), 5. 70 (m, 2H), 5. 27(d, 1H), 4. 95 (dd, 1H), 4. 74 (m, 1H), 4. 53(d, 1H), 4. 32(m, 1H), 4. 05(m, 2H), 2. 95 (m, 2H), 2. 69(m, 2H), 92 201109028 2. 52 (m, 1H), 2. 28(q,1H), 1. 94-0. 83(m, 23H), 1. 29 (d, 6H). Compound 191: MS: m/z 8 98·2 ( Μ ++1). Compound 192: MS: m/z 880·2 (Μ++1); 'H NMR (CDC13) δ 10. 31(s, 1H), 8. 28(d, 1H), 7. 95(d, 2H), 7. 50 (m, 4H), 7. 42 (dd, 1H), 7. 27(s, 1H), 7. 21(s, 1H), 5. 68(s, 1H), 5. 65(q, 1H), 5. 35(d, 1H), 4. 94 (dd, 1H), 4. 72(m, 2H), 4. 57(d, 1H), 4. 35 (m, 1H), 4. 04(m, 1H), 2. 88(m, 1H), 2. 68(m, 2H), 2. 53 (m, 1H), 2. 28(q, 1H), 1. 93-1. 05(m, 21H), 1. 36(s, 9H), 0. 97-0. 82 (m, 2H). Compound 193: MS: m/z 894. 2(M++1) ; NMR(CDC13) δ 10. 21(s, 1H), 8. 28(d, 1H), 7. 95(d, 2H), 7. 52(m, 4H), 7. 41 (dd, 1H), 7. 34(s, 1H), 7. 26(s, 1H), 5. 70(s, 1H), 5. 65(q, 1H), 5. 41(d, 1H), 4. 95 (dd, 1H), 4. 75(m, 2H), 4. 57(d, 1H), 4. 36(m, 1H), 4. 05(m, 1H), 2. 70 (m, 2H), 2. 50 (m, 1H), 2. 29(q, 1H), 1. 93-0. 82(m, 23H), 1. 46(s, 3H), 1. 36(s, 9H). Compound 194: MS: m/z 857. 3 (M++1). Compound 195: MS: m/z 857·3 (Μ++1). Compound 196: MS: m/z 784·3 (Μ++1); 4 NMR (CDC13) δ 10. 20(s, 1H), 8. 27(d,lH), 7. 88(d, 1H), 7. 57(m, 2H), 7. 39(m, 3H), 7. 13(dd, 1H), 7. 01(d, 2H), 6. 14(d, 1H), 5. 68(q, 1H), 5. 62(s, 1H), 4. 97 (dd, 1H), 4. 64 (m, 2H), 4. 41(d, 1H), 4. 07(m, 1H), 3. 87(s, 3H), 2. 87 (m, lH), 2. 67(m, 2H), 2. 45 (m, 1H), 2. 25(q, 1H), 1. 93-0. 85 (m, 15H), 1. 92(s, 3H). Compound 197: MS: m/z 856. 3(M++1) ; 4 NMR(CDC13) δ s; 93 201109028 10. 34(s, 1H), 8. 03(s, 1H), 8. 00(d, 2H), 7. 45(d, 1H), 7. 35{d, 1H), 7. 16(m, 2H), 7. 00(d, 2H), 5. 71(s, 1H), 5. 69(q, 1H), 5. 23(d, 1H), 4. 95 (dd, 1H), 4. 62(m, 2H), 4. 30 (m, 1H), 4. 03(m, 1H), 3. 86(s, 3H), 2. 88(m, 1H), 2. 66(ra, 2H), 2. 5l(s, 3H), 2. 50 (m, 1H), 2. 31(q,1H), 1. 91-0. 82 (m, 15H), 1. 22(s, 9H). Compound 198: MS: m/z 784. 2 (M++1). Compound 199: MS: m/z 798. 3 (M++1); i. H NMR (CDC13) δ 10. 37(s, 1H), 7. 96(m, 3H), 7. 58(s, 1H), 7. 43(d, 1H), 7. 32(d, 1H), 7. 16(s, 1H), 6. 97(d, 2H), 6. 24(d, 1H), 5. 69(q, 1H), 5. 64(s, 1H), 4. 96(dd, 1H)S 4. 66(m, 1H), 4. 55 (m, 1H), 4. 40(d, 1H), 4. 02(m, 1H), 3. 84(s, 3H), 2. 87 (m, 1H), 2. 68(m, 2H), 2. 49(s, 3H), 2. 50 (m, 1H), 2. 28(q, 1H), 1. 91-0. 83(m, 15H), 1. 91 (s, 3H). Compound 200: MS: m/z 852. 2(M++1) ; iH NMR(CDC13) δ 10. 26(s, 1H), 8. 03(s, 1H), 7. 96(d, 2H), 7. 52(s, 1H), 7. 45(d, 1H), 7. 34(d, 1H), 7. 23(s, 1H), 6. 98(d, 2H), 5. 67(s, 1H), 5. 64(q, 1H), 5. 21 (m, 1H), 4. 93(dd, 1H), 4. 67(m, 2H), 4. 30(d, 1H), 4. 04(m, 1H), 3. 85(s, 3H), 2. 87 (m, 1H), 2. 66-2. 40 (m, 3H), 2. 51(s,3H), 2. 22(q,1H), 1. 95-0. 82 (m, 】 5H). Compound 201: MS: m/z 814·3 (Μ++1); NMR (CDC13) δ 10. 41(s, 1H), 7. 98(m, 3H), 7. 60(s, 1H), 7. 43(d, 1H), 7. 33(d, 1H), 7. 16(s, 1H), 6. 98(d, 2H), 5. 64 (m, 2H), 5. 29(m, 2H), 4. 93(dd, 1H), 4. 69 (m, 1H), 4. 36(m, 1H), 4. 01(m, lH), 3. 84(s, 3H), 3. 42(s, 3H), 2. 87(m, IH), 2. 66(m, 2H), 2. 50(m, 1H), 94 201109028 2. 49(s,3H), 2. 25(q,1H), 1. 94-0. 82 (m, 15H). Compound 202: MS: m/z 838. 2(M++1) ; 4 NMR(CDC13) δ 10. 23(s, 1H), 8. 26(d, 1H), 8. 00(d, 2H), 7. 60 (m, 2H), 7. 44(m, 2H), 7. 23(m, 2H), 7. 01(d, 2H), 5. 73(s, 1H), 5. 67(q, 1H), 4. 94 (dd, 1H), 4. 68(m, 2H), 4. 32(d, 1H), 4. 07(m, 1H), 3. 86(s, 3H), 2. 86(m, 1H), 2. 67(m, 2H), 2. 41 (m, 1H), 2. 23(q, 1H), 1. 94-1. 08(m, 13H), 0. 94-0. 87 (m, 2H). Compound 203: MS: m/z 842·3 (Μ++1); 'H NMR (CDC13) δ 10. 30(s, 1H), 8. 28(d, 1H), 7. 63(s, 1H), 7. 57(m, 3H), 7. 42(m, 2H), 7. 25(m, 1H), 7. 08(s, 1H), 6. 97(dd,lH), 5. 71(m, 2H), 5. 22(d, 1H), 4. 92(dd, 1H), 4. 64 (m, 2H), 4. 3l (m, 1H), 4. 00 (m, 1H), 3. 91(s, 3H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 55 (m, 1H), 2. 29(q, 1H), 1. 85-0. 83 (m, 15H), l-19 (s, 9H). Compound 204: MS: m/z 784·2 (Μ++1); 4 NMR (CDC13) δ 10. 28(s, 1H), 8. 26(d, 1H), 7. 62(s, 1H), 7. 58(m, 3H), 7. 41(m, 2H), 7. 25(m, 2H), 6. 96 (dd, lH), 6. 13(d, 1H), 5. 71(q, 1H), 5. 68(s, 1H), 4. 95 (dd, 1H), 4. 63(t, 1H), 4. 59(m, 1H), 4. 41(d, 1H), 4. 04(m, 1H), 3. 90(s, 3H), 2. 88(m, 1H), 2. 71 (m, 2H), 2. 52(m, 1H), 2. 29(q, 1H), 1. 92-1. 1. 05(m, 13H), 1. 91(s, 3H), 0. 97-0. 84 (m, 2H). Compound 205: MS: m/z 801. 3 (M++1); NMR (CDC13) δ 10. 34(s, 1H), 8. 25(d, 1H), 7. 61(s, 1H), 7. 57(m, 3H), 7. 39-7. 25(m, 4H), 6. 93(dd,lH), 5. 70 (m, 2H), 5. 44(d, 1H), 4. 94 (dd, 1H), 4. 70 (m, 1H), 4. 39(d, 1H), 4. 32(m, 1H), 4. 03(m, 1H), 95 201109028 3. 90(s, 3H), 3. 48(s, 3H), 2. 88(m, 1H), 2. 70 (m, 2H), 2. 52(m, 1H), 2. 26(q,1H), 1. 89-0. 82 (m, 15H). Compound 206: MS: m/z 838_2 (M++1); 丨 "[ NMR(CDC13) δ 10. 19(s, 1H), 8. 27(d, 1H), 7. 62(s, 1H), 7. 58(m, 3H), 7. 41(m, 2H), 7. 25(m, 3H), 6. 97(dd,lH), 5. 71(s, 1H), 5. 63(q,lH), 4. 92(dd, 1H), 4. 64 (m, 2H), 4. 33(d, 1H), 4. 05(m, 1H), 3. 90(s, 3H), 2. 88(m, 1H), 2. 69 (m, 2H), 2. 46(m, 1H), 2. 23(q, 1H), 1. 94- 1. 1. 03(m,13H), 0. 95-0. 84 (m, 2H). Compound 207: MS: m/z 8 (1). 2(M++1) ; b NMR(CDC13) δ 10. 24(s, 1H), 8. 27(d,lH), 7. 86(d, 1H), 7. 55(m, 2H), 7. 42(m, 3H), 7. 12(m, 2H), 7. 00(d, 1H), 5. 68(q, 1H), 5. 62(s, 1H), 5. 47(d, 1H), 4. 92(dd, 1H)S 4. 68(m, 1H), 4. 40 (m, 2H), 4. 04(m, 1H), 3. 87(s, 3H), 3. 50(s, :3H), 2. 89(m,lH), 2. 68(m, 2H), 2. 50 (m, 1H), 2. 25(q, 1H), 1. 91-1. 03(m, 13H), 0. 98-0. 82 (m, 2H). Compound 208: MS: m/z 838. 2(M++1) : 'H NMR(CDC13) δ 10. 19(s, 1H), 8. 27(d,lH), 7. 82(d, 1H), 7. 57(m, 2H), 7. 39(m, 5H), 7. 12(dd, 1H), 7. 02(d, 1H), 5. 63(q, 1H), 5. 60(s, 1H), 4. 90 (dd, 1H), 4. 70 (m, 2H), 4. 32(d, 1H), 4. 03(m, 1H), 3. 85(s, 3H), 2. 86(m,lH), 2. 71-2. 52(m, 2H), 2. 39(m, 1H), 2. 20(q, 1H), 1. 94- 0. 84 (m, 15H). Compound 209: MS: m/z 896. 4(M++1) ; 4 NMR(CDC13) δ 10. 20(s,1H), 8. 31(d,1H), 7. 99(d, 2H), 7. 58(m, 2H), 7. 42(m, 1H), 7. 30-7. 22(m, 2H), 7. 01(d, 2H), 5. 68(s, 1H), 5. 66(q, 1H), 96 201109028 5. 37(d, 1H), 4. 96 (dd, 1H), 4. 78-4. 51(m, 4H), 4. 37(m, 1H), 4. 06(m, 1H), 2. 69 (m, 2H), 2. 51(m, 1H), 2. 28(q, 1H), 1. 94-0. 83(m, 23H), 1. 46(s, 3H), 1. 37 (d, 6H). Compound 210: MS: m/z 882. 4 (M++1); NMR (CDC13) δ 10. 24(s, 1H), 8. 27(d, 1H), 7. 98(d, 2H), 7. 58(m, 2H), 7. 42(m, 1H), 7. 24(m, 1H), 7. 01(d, 2H), 6. 89(s, 1H), 5. 68(s, 1H), 5. 66(q, 1H), 5. 22(d, 1H), 4. 97 (dd, 1H), 4. 78-4. 52(m, 4H), 4. 36(m, 1H), 4. 04(m, 1H), 2. 88(m, 1H), 2. 68(m, 2H), 2. 54 (m, 1H), 2. 29(q, 1H), 1. 94-1. 05(m, 21H), 1. 37(d, 6H), 0. 97-0. 83 (m, 2H). Compound 211: MS: m/z 922·2 (Μ++1); 'H NMR (CDC13) δ 10. 13(s, 1H), 8. 26(d, 1H), 8. 10(d, 2H), 7. 59(m, 2H), 7. 42(m, 1H), 7. 35-7. 25(m, 3H), 7. 03(s, 1H), 5. 77(s, 1H), 5. 66(q, 1H), 5. 20(d, 1H), 4. 99(dd, 1H), 4. 71(m, 2H), 4. 56(d, 1H), 4. 35 (m, 1H), 4. 03(m, 1H), 2. 70 (m, 2H), 2. 50 (m, 1H), 2. 29(q, 1H), 1. 90-0. 84(m, 23H), 0. 85(s, 3H). Compound 212: MS: m/z 892·4 (Μ++1); 'H NMR (CDC13) δ 10. 36(s, 1H), 8. 59(s, 1H), 8. 25(d, 1H), 8. 18(d, 2H), 7. 73(d, 2H), 7. 58(m, 2H), 7. 45 (m, 1H), 7. 34(s, 1H), 5. 74(s, 1H), 5. 68(q, 1H), 5. 39(d, 1H), 4. 94 (dd, 1H), 4. 72(m, 2H), 4. 55(d, 1H), 4. 31 (m, 1H), 4. 04(m, 1H), 2. 86(m, 1H), 2. 67(m, 2H), 2. 49 (m, 1H), 2. 26(q,1H), 1. 91-1. 05 (m, 23H). Compound 213: MS: m/z 880. 4(M++1) ; 'H NMR(CDC13) δ 10. 36(s, 1H), 8. 26(d, 1H), 8. 16(d, 2H), 7. 74(d, 2H), 7. 59(m, s 97 201109028 2H), 7. 45 (m, 1H), 7. 30 (m, 2H), 5. 71(s, 1H), 5. 66(q, 1H), 5. 25(d, 1H), 4. 95 (dd, 1H), 4. 71 (m, 1H), 4. 65(d, 1H), 4. 28(m, 1H), 4. 03(m, 1H), 2. 87 (m, 1H), 2. 70 (m, 2H), 2. 5l (m, 1H), 2. 27(q, 1H), 1. 92-1. 06(m, 13H), 1. 19(s, 9H), 0. 97-0. 82 (m, 2H). Compound 214: MS: m/z 780. Compound 215:]^8:111/2 822. 2 (1^++1). Compound 216: MS: m/z 910_3 (M++1); NMR (CDC13) δ 10. 30(s, 1H), 8. 15(d, 2H), 7. 75(d, 2H), 7. 61(s, 1H), 7. 47(d, 1H), 7. 25-7. 15(m, 3H), 5. 72(s, 1H), 5. 68(q, 1H), 5. 18(d, 1H), 4. 98 (dd, 1H), 4. 67(m, 2H), 4. 28(m, 1H), 4. 04(m, 1H), 3. 93(s, 3H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 52(m, 1H), 2. 28(q, 1H), 1. 91-0. 85(m5 】5H), 1. 20 (s, 9H). Compound 217: MS: m/z 9:22. 3(M++1) ; h NMR(CDC13) δ 10. 28(s, 1H), 8. 17(m, 3H), 7. 74(d, 2H), 7. 26(m, 1H), 7. 17(s, 1H), 7. 02(m, 2H), 5. 77(s, 1H), 5. 69(q, 1H), 5. 20(d, 1H), 4. 96 (dd, 1H), 4. 77(s, 1H), 4. 69 (m, 1H), 4. 54(d, 1H), 4. 33(m, 1H), 4. 04(m, 1H), 3. 92(s, 3H), 2. 89 (m, 1H), 2. 71(m, 2H), 2. 52(m, 1H), 2. 28(q, 1H), 1. 90-1. 05(m, 21H), 0. 97-0. 83 (m, 2H). Compound 218: MS: m/z 892·4 (Μ++1); NMR (CDC13) δ 10. 29(s, 1H), 8. 35(s,1H), 8. 28(d, 1H), 8. 24(d,1H), 7. 59(m, 4H), 7. 44(m, 1H), 7. 33(s, 1H), 7. 15(s, 1H), 5. 80(s, 1H), 5. 67 (q, 1H), 5. 27(d, 1H), 4. 95 (dd, 1H), 4. 70 (m, 2H), 4. 58(d, 1 H), 98 201109028 4. 30 (m, 1H), 4. 06(m, 1H), 2. 88(m, 1H), 2. 70 (m, 2H), 2. 54 (m, 1H), 2. 28(q, 1H), 1. 92-0. 83 (m, 23H). Compound 219: MS: m/z 880 (M++1); 4 NMR (CDC13) δ 10. 3l(s, 1H), 8. 34(s, 1H), 8. 28(d, 1H), 8. 20(d, 1H), 7. 60 (m, 4H), 7. 45 (m, 1H), 7. 29(s, 1H), 7. 13(s, 1H), 5. 77(s, 1H), 5. 67(q, 1H), 5. 19(m, 1H), 4. 94 (dd, 1H), 4. 67(m, 2H), 4. 26(m, 1H), 4. 05(m, 1H), 2. 88(m, 1H), 2. 71(m, 2H), 2. 53 (m, 1H), 2. 29(q, 1H), 1. 90-0. 83 (m, 15H), 1. 18(s, 9H). Compound 220: MS: m/z 892. 2(M++1) ; 'H NMR(CDC13) δ 10. 29(s, 1H), 8. 39(d, 1H), 8. 06(d, 2H), 7. 88(s, 1H), 7. 71(d, 1H), 7. 45 (m, 3H), 7. 36(s, 1H), 7. 18(s, 1H), 5. 68(s, 1H), 5. 65(q, 1H), 5. 33(d, 1H), 4. 93(dd, 1H), 4. 72(m, 2H), 4. 67(d, 1H), 4. 36(m, 1H), 4. 05(m, 1H), 2. 88(m, 1H), 2. 70 (m, 2H), 2. 53 (m, 1H), 2. 28(q,1H), 1. 92-0. 84 (m, 23H). Compound 221: MS: m/z 880·4 (Μ++1); NMR (CDC13) δ 10. 30(s, 1H), 8. 39(d, 1H), 8. 04(d, 2H), 7. 87(s, 1H), 7. 69(d, 1H), 7. 48(m, 3H), 7. 33(s, 1H), 7. 25(s, 1H), 5. 67(m, 2H), 5. 21(d, 1H), 4. 94 (dd, 1H), 4. 68(m, 2H), 4. 30 (m, 1H), 4. 04(m, 1H), 2. 88(m, 1H), 2. 69 (m, 2H), 2. 52(m, 1H), 2. 28(q, 1H), 1. 93-0. 84 (m, 15H), 1. 17(s, 9H). Compound 222: MS: m/z 814·3 (Μ++1); 'H NMR (CDC13) δ 10. 29(s, 1H), 8. 46(s, 1H), 8. 27(d,lH), 7. 47(m, 3H), 7. 41 (m, 1H), 7. 33(s, 1H), 7. 16(d, 1H), 7. 05(s, 1H), 6. 56(d, 1H), 5. 69 (m, 2H), 5. 24(d, 1H), 4. 95 (dd, 1H), 4. 66(m, 1H), 4. 58(d, 1H), 99 201109028 4. 38(m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2. 34(m, 1H), 2. 29(q, 1H), 1. 90-1. 06(m, 21H), 0. 96-0. 83 (m, 2H). Compound 223: MS: m/z 802. 2(M++1) ; 'H NMR(CDC13) δ 10. 30(s, 1H), 8. 28(d,lH), 7. 54(m, 3H), 7. 42(m, 1H), 7. 29(s, 1H), 7. 20(d, IH), 7. 08(s, 1H), 6. 56(d, 1H), 5. 66(m, 2H), 5. 15(d, 1H), 4. 95 (dd, 1H), 4. 69 (m, 2H), 4. 30 (m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 35 (m, 1H), 2. 29(q, 1H), ]. 89-l_04 (m, 13H), 1. 19(s,9H),0. 97-0. 83 (m, 2H). Compound 224: MS: m/z 848·2 (Μ++1); 'H NMR (CDC13) δ 10. 30(s, 1H), 8. 08(d,lH), 7. 58(d, 1H), 7. 39(d, 1H), 7. 14(s, 1H), 7. 12-6. 95(m, 4H), 5. 70 (m, 2H), 5. 20(d, 1H), 4. 95 (dd, 1H), 4. 66(m, 1H), 4. 59(d, IH), 4. 33(m, 1H), 4. 03(m, 1H), 3. 91(s, 3H), 2. 90 (m, 1H), 2. 66(m, 2H), 2. 52(m, 1H), 2. 28(q, 1H), 1. 89-1. 06(m,13H),]. 24(s, 9H), 0. 94-0. 83 (m, 2H). Compound 225: MS: m/z 760. 2 (M++1); 4 NMR (CDC13> δ 10. 35(s,1H), 8. 25(d,lH), 7. 55 (m, 3H), 7. 40 (m, 1H), 7_27 (m, 2H), 7. 16(d, 1H), 6. 54(d, 1H), 5. 66(m, 2H), 5. 42(d, 1H), 4. 94 (dd, 1H), 4. 67(m, 1H), 4. 46(d, 1H), 4. 35 (m, 1H), 4. 04(m, 1H), 3. 50(s, 3H), 2. 89 (m, 1H), 2. 66(m, 2H), 2. 33(m, 1H), 2. 26(q,1H), 1. 92-0. 83 (m, 15H). Compound 226: MS: m/z 798. 2(M++1) ; 'H NMR(CDC13) δ 10. 20(s, 1H), 8. 25(d, 1H), 7. 55(m, 3H), 7. 4l (m, 1H), 7. 27(m, 3H), 7. 16(d, IH), 6. 56(d, 1H), 5. 66(m, 2H), 4. 94 (dd, 1H), 4. 67(m, 2H), 4. 35(d, 1H), 4. 05(m, 1H), 2. 88(m, 1H), 2. 66(m, 100 201109028 2H), 2. 43 (m, 1H), 2. 26(q,1H), 1. 96-0. 83 (m, 15H). Compound 227: MS: m/z 744. 2(M++1) ; iH NMR(CDC13) δ 10. 31(s, 1H), 8. 21(d,lH), 7. 55(m, 3H), 7. 39(m, 1H), 7. 33-7. 25(m, 2H), 7. 12(d, 1H), 6. 56(d, 1H), 6. 16(d, 1H), 5. 66(q, 1H), 5. 62(s, 1H), 4. 94 (dd, 1H), 4. 62 (m, 1H), 4. 59(m, 1H), 4. 41(d, 1H), 4. 06(m, 1H), 2. 87 (m, 1H), 2. 68(m, 2H), 2. 50 (m, 1H), 2. 26(q,1H), 1. 95-0. 83 (m, 15H), 1. 90 (s, 3H). Compound 228: MS: m/z 857. Compound 229: MS: m/z 830. 3(M++1) ; h NMR(CDC13) δ 10. 25(s, 1H), 8. 26(d,lH), 7. 59(m, 2H), 7. 43(m, 2H), 7. 25(m, 2H), 7. 19(m, 1H), 7. 06(m, 1H), 5. 76(s, 1H), 5. 72(q, 1H), 5. 18(m, 1H), 4. 97 (dd, 1H), 4. 68(m, 2H), 4. 56(d, 1H), 4. 30 (m, 1H), 4. 04(m, 1H), 2. 90 (m, 1H), 2. 70 (m, 2H), 2. 39(m, 1H), 2. 27(q, 1H), 1. 90-0. 80 (m, 23H). Compound 230·· MS: m/z 860_3 (M++1); 4 NMR (CDC13) δ 10. 28(s, 1H), 8. 10(d,lH), 7. 58(d, 1H), 7. 39(d, 1H), 7. 18(s, 1H), 7. 09-6. 97(m, 4H), 5. 72(s, 1H), 5. 68(q, 1H), 5. 24(d, 1H), 4. 95 (dd, 1H), 4. 80(s, 1H), 4. 65 (m, 1H), 4. 54(d, 1H), 4. 32(m, 1H), 4. 03(m, 1H), 3. 91(s, 3H), 2. 94 (m, 1H), 2. 68(m, 2H), 2. 54 (m, 1H), 2. 28(q, 1H), 1. 90-1. 05(m, 21H), 0. 95-0. 84 (m, 2H). Compound 231: MS: m/z 848. 2(M++1) ; 'H NMR(CDC13) δ 10. 26(s, 1H), 7. 64(d,lH), 7. 60(d, 1H), 7. 48(d, 1H), 7. 40(d, 1H), 7. 20(s, 1H), 7. 15(m, 2H), 6. 88(s, 1H), 5. 65(m, 2H), 101 201109028 5. 10(d, 1H), 4. 96 (dd, 1H), 4. 63(m, 2H), 4. 31 (m, 1H), 4. 04(m, 1H), 3. 94(s, 3H), 2. 86(m, 1H), 2. 68(m, 2H), 2. 56(m, 1H), 2. 29(q,1H), 1. 94-0. 83 (m, 15H), 1. 22 (s, 9H). Compound 232: MS: m/z 836. 2(M++1) ; 4 NMR(CDC13) δ 10. 29(s, 1H), 7. 89 (dd, lH), 7. 60(d, 1H), 7. 50 (dd, 1H), 7. 40(d, 1H), 7. 22(m, 2H), 7. 10(m, 1H), 7. 00(s, 1H), 5. 68(m, 2H), 5. 18(d, 1H), 4. 95 (dd, 1H), 4. 66(m, 2H), 4. 29(m, 1H), 4. 04(m, 1H), 2. 88(m, 1H), 2. 67(m, 2H), 2. 53 (m, 1H), 2. 26(q, 1H), 1. 92-0. 83 (m, 15H), 1. 20(s, 9H). Compound 233: MS: m/z 806·2 (Μ++1); NMR (CDC13) δ 10. 36(s,]H), 8. 05(d,lH), 7. 59(d,lH), 7. 38 (m, 2H), 7. 14-6. 97 (m, 4H), 5. 70 (m, 2H), 5. 64(d, 1H), 4. 96 (dd, 1H), 4. 65 (m, 1H), 4. 58(m, 2H), 4. 04(m, 1H), 3. 90(s, 3H), 3. 58(s, 3H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 53(m, LH), 2. 25(q, 1H), 1. 88-0. 82 (m, 15H). Compound 234: MS: m/z 860. 2(M++1) ; A NMR(CDC13) δ 10. 31(s, 1H), 7. 63(d,lH), 7. 60(d, 1H), 7. 45(d, 1H), 7. 40(d, 1H), 7. 20(m, 2H), 7. 10(m, 2H), 5. 69(s, 1H), 5. 67(q, 1H), 5. 30(d, 1H), 4. 94 (dd, 1H), 4. 78(s, 1H), 4. 64 (m, 1H), 4. 55(d, 1H), 4. 36(m, 1H), 4. 04(m, 1H), 3. 94(s, 3H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 53 (m, 1H), 2. 26(q, 1H), 1. 93-1. 04(m, 21H), 0. 97-0. 82 (m, 2H). Compound 235: MS: m/z 844·2 (Μ++1); 'H NMR (CDC13) δ 10. 24(s, 1H), 8. 04(d,lH), 7. 58(d, 1H), 7. 39(d, lH), 7. 31 (m, 102 201109028 2H), 7. 18(s, 1H), 7. 08(m, 3H), 5. 70(s, 1H), 5. 67(q, 1H), 4. 86 (dd, 1H), 4. 64 (m, 2H), 4. 26(d, 1H), 4. 02(m, 1H), 3. 90(s, 3H), 2. 84 (m, 1H), 2. 65 (m, 2H), 2. 44 (m, 1H), 2. 20(q, 1H), 1. 91-0_83 (m, 15H). Compound 236: MS: m/z 832·2 (Μ++1); 'H NMR (CDC13) δ 10. 27(s, 1H), 8. 22(d,lH), 7. 58(m, 2H), 7. 44(m, 1H), 7. 29(m, 1H), 7. 10(s, 1H), 6. 94(d, 1H), 6. 90(s, 1H), 5. 69 (m, 2H), 5. 18(d, 1H), 4. 93(dd, 1H), 4. 67(m, 2H), 4. 28(m, 1H), 4. 05(m, 1H), 2. 85 (m, 1H), 2. 68(m, 2H), 2. 55(s, 3H), 2. 54 (m, 1H), 2. 28(q,1H), 1. 91-0_83 (m, 15H), 1. 19 (s, 9H). Compound 237: MS: m/z 844_3 (M++1); NMR (CDC13) δ 10. 23(s, 1H), 8. 22(d,lH), 7. 58(m, 2H), 7. 40 (m, 1H), 7. 29(m, 2H), 6. 96(d, 1H), 6. 84(s, 1H), 5. 69(s, 1H), 5. 66(q, 1H), 5. 20(d, 1H), 4. 94 (dd, 1H), 4. 73(s, 1H), 4. 67(m, 1H), 4. 58(d, 1H), 4. 35 (m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 56(s,3H), 2. 54 (m, 1H), 2. 26(q,1H), 1. 91-0. 83 (m, 23H). Compound 238: MS: m/z 844. 3(M++1) ; NMR(CDC13) δ 10. 26(s,1H), 8. 22(d,lH), 7. 55 (m, 2H), 7. 43 (m, 2H), 7. 18(m, 1H), 6. 93(s, 1H), 6. 75(s, 1H), 5. 70 (m, 2H), 5. 21(d, 1H), 4. 94 (dd, 1H), 4. 78(s, 1H), 4. 63(m, 1H), 4. 53(d, 1H), 4. 35 (m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 67(m, 2H), 2. 53(s, 3H), 2. 52(m, 1H), 2. 26(q, 1H), 1. 92-1. 04(m, 21H), 0. 95-0. 83 (m, 2H). Compound 239: MS: m/z 790. 2(M++1) ; 4 NMR(CDC13) δ s 103 201109028 10. 34(s, 1H), 8. 20(d,lH), 7. 54(m, 2H), 7. 38(m, 2H), 7. 28(s, 1H), 7. 14(s, 1H), 6. 73(s, 1H), 5. 68(m, 2H), 5. 43(d, 1H), 4. 94 (dd, 1H), 4. 65 (m, 1H), 4. 39(m, 2H), 4. 04(m, 1H), 3. 58(s, 3H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 5 l(s, 3H), 2. 50 (m, 1H), 2. 28(q,1H), 1. 93-1. 06(m, 13H), 0. 94-0. 82 (m, 2H). Compound 240: MS: m/z 828. 2(M++1) ; 4 NMR(CDC13) δ 10. 18(s, 1H), 8. 22(d,lH), 7. 56(m, 2H), 7. 40 (m, 2H), 7. 20(s, 2H), 7. 08(s, 1H), 6. 76(d, IH), 5. 71(s, 1H), 5. 66(q, 1H), 4. 94 (dd, 1H), 4. 66(m, 2H), 4. 29(d, 1H), 4. 04(m, 1H), 2. 88(m, 1H), 2. 65 (m, 2H), 2. 53(s, 3H), 2. 45 (m, 1H), 2. 23(q, 1H), 1. 96-1. 05(m, 13H), 0. 95-0. 83 (m, 2H). Compound 241: MS: m/z </RTI> </RTI> <RTI ID=0.0></RTI> <RTI ID=0.0> 38(s, 1H), 7. 89 (dd, lH), 7. 58(d, 2H), 7. 44 (dd, 1H), 7. 35(d, 1H), 7. 24(m, 2H), 7. 05(m, 1H), 6. 18(d, 1H), 5. 7l (q, 1H), 5. 62(s, 1H), 4. 95 (dd, 1H), 4. 63(m, 1H), 4. 50 (m, 1H), 4. 40(d, 1H), 4. 00 (m, 1H), 2. 88(m, 1H), 2. 66(m, 2H), 2. 53 (m, 1H), 2. 22 (q, lil), 1. 96-0. 82(m, 15H), 1. 91(s, 3H). Compound 242: MS: m/z 846. 4 (M++1). Compound 243: MS: m/z 858. 3(M++1) ; i NMR(CDC13) δ 10. 28(s, 1H), 8. 24(d, 1H), 7. 57(m, 2H), 7. 42. (m, 2H), 7. 19(s, 1H), 7. 08(ss 1H), 6. 79(d, IH), 5. 66(m, 2H), 5. 24(d, 1H), 4. 96(m, 1H), 4. 78(s, 1H), 4. 67(m, 1H), 4. 55(d, 1H), 4. 35 (m, 1H), 4. 03(m, 1H), 2. 85 (ra, 3H), 2. 67(m, 2H), 2. 53 (m, 1H), 2. 28(q, 1H), :1. 94-0. 84 (m, 26H). 104 201109028 Compound 244: MS: m/z 872. 3(M++1) ; 'H NMR(CDC13) δ 10. 13(s, 1H), 8. 24(d, 1H), 7. 53(m, 2H), 7. 41(m, 2H), 7. 19(s, 1H), 6. 99(s, 1H), 6. 79(d, 1H), 5. 69 (m, 2H), 5. 23(d, 1H), 4. 98 (dd, 1H), 4. 77(s, 1H), 4. 65 (m, 1H), 4. 55(d, 1H), 4. 35 (m, 1H), 4. 04(m, 1H), 2. 87(q, 2H), 2. 68(m, 2H), 2. 53 (m, 1H), 2. 29(q, 1H), 1. 94-0. 84 (m, 26H), 0. 83(s, 3H). Compound 245: MS: m/z 831. 2(M++1) ; iH NMR(CDC13) δ 10. 21(s, 1H), 8. 26(d,lH), 7. 90(d, 2H), 7. 58(m, 2H), 7. 46(d, 2H), 7. 00(s, 1H), 5. 69 (m, 2H), 5. 09(d, 1H), 4. 99(dd, 1H), 4. 62(m, 3H), 4. 27(m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2_56 (m, 1H), 2. 29(q,1H), 1. 94-0. 84 (m, 23H). Compound 246: MS: m/z 761. 4(M++1) ; 4 NMR(CDC13) δ 10. 21(s, 1H), 8. 17(d,lH), 7. 80(d, 3H), 7. 56(m, 2H), 7. 41(d, 2H), 6. 58(s, 1H), 5. 61(m, 2H), 5. 21(d, 1H), 4. 65 (m, 2H), 4. 24(m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2. 56-2. 21(m, 2H), 1. 94-0. 84(m, 15H), 1. 87(s,3H) 化合物 Compound 247: MS: m/z 803. 4 (M++1). Compound 248: MS: m/z 845. 3 (M++1). Compound 249: MS: m/z 917. 2(M++1) ; 4 NMR(CDC13) δ 10. 22(s, 1H), 8. 08(d,lH), 7. 78(s,1H), 7. 40 (s, 1H), 7. 06(s, 1H), 6. 97(m, 2H), 5. 64 (m, 2H), 5. 32(d, 1H), 4. 94 (dd, 1H), 4. 70 (m, 2H), 4. 54(d, 1H), 4. 34 (dd, 1H), 4. 08(m, 1H), 3. 83(s, 3H), 3. 18(m, 1H), 2. 73-2. 43(m, 2H), 2. 33(q, 1H), 2. 15-1. 20 (m, 30H), 0. 83 (s, 3H). 105 201109028 Compound 250: MS: m/z 905·4 (Μ++1). Compound 251: MS: m/z 901. 3 (Μ++1). Compound 252: MS: m/z 917. 4 (Μ++1). Compound 253: MS: m/z 903. 3 (Μ++1). Example 254: Synthesis of [4-cyclopropanesulfonylaminocarbonyl-18-(2-fluoro-benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-2 , 15-dioxo-3,16-diazatricyclo[14. 3. 0. 04,6]nonadecane-14-yl]-carbamic acid cyclopentyl ester (Compound 254) Compound 254 was prepared by the following synthetic route. 106 201109028

Cl 1-26 P〇Cl3 回流，3小時Cl 1-26 P〇Cl3 reflux, 3 hours

]-27]-27

ΙΜΐυ,ΗΟΒ^ΜΙΜΐυ,ΗΟΒ^Μ

1·291·29

lb/Pd-C MeOIiLb/Pd-C MeOIi

α°ί°°°

Ct 1-31 。柳 %〇 254 〇°C，向Boc-反-4-羥基-L-脯氨酸(0.53克，2.30毫摩爾）在DMSO(10毫升）的溶液中加入i-BuONa(0.49克，5.08亳摩爾）。溫熱至室溫並再攪拌丨小時後，於1〇。〇緩慢加入中間體I-26(G.62克’ 2.31毫摩_)。搜拌該反應混合物4小時，缺 107 201109028 後用10% HC1水溶液猝滅至PH為6-7。過濾粗懸浮固體，用水洗滌，姦空乾燥，得到1-27(0.92克，86%)。MS: m/z 467.1(M++1)。 5°C，向 1-27(0.90克，1.93毫摩爾）、HATU(58.9克，1.55 毫摩爾）、HOBt(7.0克，0.52毫摩爾）和NMM(38.3 克，3.86 毫摩爾）在CH2C12(10毫升）的溶液中滴加環丙烷磺酸（丨-氨基 -2-乙烯基-環丙烷羰基）-醯胺（54.0克，2.03毫摩爾）和 NMM(0.19克，1.93毫摩爾）溶解於CH2C12的混合物。溫熱至室溫並再攪拌16小時後，將反應混合物過濾，濃縮和通過矽膠柱層析純化，獲得粗產物1-28(0.89克，產率80% )。MS: m/z 679·1(Μ++1)。室溫，将化合物1-28(1.20克，1.77毫摩爾）溶解於MeOH (18毫升），然後利用冰浴冷卻該溶液。在反應混合物中逐滴加入亞硫醯氣(0.39毫升，5,30毫摩爾）。移去冰浴之後，反應混合物在65°C加熱1小時。將形成的溶液冷卻至4〇°C，過濾，用冷MeOH和醚洗滌，獲得淺黃色粉末，以得到白色粉末的1-29，該化合物無需進一步純化即可用於下一反應步驟。MS: m/z 579·1(Μ++1)。 5°C，向2-環戊氧基羰基氨基-壬-8-烯酸(0.87克，2,34 毫摩爾）、HATU(1.16克，3_05毫摩爾）和 H〇Bt(0.14克，1.02 毫摩爾）在CH2C12(10毫升）的溶液中滴加溶解於DMF(1()毫升）的1-29(1.18克，2.03毫摩爾；^，]^11^(0.49克，4.87毫摩爾）的混合物。溫熱至室溫並再搜拌16小時之後’加入1.0% HC1(1毫升），將反應混合物濃縮。將殘餘物冷卻至5°C，用 108 201109028 5% HC1(水溶液)(10毫升χ 2)和NaHC03(水溶液)(10毫升x 2) 順序洗滌，得到淺黃色固體。將該固體溶解於MeOH(10毫升），並通過緩慢加入少量醚進一步沉澱，獲得1-30(1.51克，產率 88%)。MS: m/z 844.3(M++1)。通過氮氣鼓泡將化合物1-30(0.50克，0·59毫摩爾）在 CH2C12(120毫升）中的溶液脫氣1小時。加入第二代霍維達-格拉布催化劑（48毫克，0.076毫摩爾），然後反應混合物於 40°C加熱16小時。由HPLC指示反應完成後，將反應混合物冷卻至30°C，濃縮並通過矽膠柱層析純化，得到產物 I-31(0.30克，產率62°/c))。MS:m/z816·3(M++l);1HNMR (CDC13) δ 10.33(s, 1H), 8.30(d, 1H), 8.11(dd, 1H), 7.88 (dd, 1H), 7.67-7.56(m, 2H), 7.46(dd, 1H), 7.43-7.30(m, 2H), 6.12(s, 1H), 5.64(q, 1H), 5.22(d, 1H), 4.92(dd, 1H), 4.77(d, 1H), 4.66(dd, 1H), 4.32-4.22(m, 1H), 4.04(dd, 1H), 2.93-2.46(m，3H)，2_31(q, 1H)，1.92-0.80(m，25H)。室溫A氣氛下，向化合物i_3i(5〇毫克，〇〇61毫摩爾）在MeOH(10毫升）的溶液中加入5〇/〇Pd_c(5毫克）。然後，在氫氣氣氛，60 psi壓力和室溫條件下攪拌反應混合物4小時。將反應混合物過濾並通過杈層析純化，得到化合物 254(27.6毫克’55%)°MS: m/z 818.3(m++i); hlSiMRXCDCb) δ 10.50(s, 1H), 8.28(d，1H)，8.l3(dd，1H)，7 8〇(dd，m), 7.65-7.57(m5 2H), 7.45(dd, 1H), 7.39-7.30(m, 2H), 6.1 l(s, 1H), 5.25(d, 1H), 4.96(brs, 1H), 4.68(dd, 1H), 4.60(d, 1H), 4.37(dd, 1H), 4.14(dd, 1H), 3.02.2.57(m, 3H), 1.92-0.80(m, 109 201109028 29H)。實施例255-281 :化合物255-281的合成化合物255-281各自按照與實施例254中所述類似的方式製備。化合物255: MS: m/z 764.2(M++1) ; 4 NMR(CDC13) δ 10.47(s, 1H), 7.88-7.84(m, 3H), 7.70(s, 1H), 7.56(dd, 1H), 7.37(m, 1H), 7.18(m, 1H), 6.20(d, 1H), 5.97(s, 1H), 5.64(q, 1H), 4.94(dd, 1H), 4.68(m, 1H), 4.61(d, 1H), 4.44(m, 1H), 4.02(m, 1H), 2.85(m, 2H), 2.70(m, 1H), 2.58(m, 1H), 2..25(q, 1H)，1.92(s，3H)，1.90-1.03(m，15H)。化合物256: MS: m/z 815.6(M++1) ; 'H NMR(CDC13) δ 10.31(s，】H)，8.32(d，1H), 8.25(m，1H)，7.81(dd, 1H)，7.64(m， 2H), 7.46(dd, 1H), 7.23-7.12(m, 2H), 6.20(s, 1H), 5.66(q, 1H), 5.16(d, 1H), 4.98(dd, 1H), 4.75-4.64(m, 3H), 4.31(m, 1H), 4.08(m, 1H), 2.88(m, 1H), 2.78(m, 2H), 2.55(m, 1H), 2.29(q, 1H), 1.92-0.84(m，23H)。化合物257: MS: m/z 804.1(M++1);NMR(CDC13> δ 10.52(s, 1H), 8.29(d, 1H), 8.03-7.97(m, 2H), 7.82(dd, 1H), 7.63-7.42(m, 3H), 7.21(m, 1H), 5.97(s, 1H), 5.60(q, 1H), 5.44(d, 1H), 4.85(dd, 1H), 4.66(m, 2H), 4.29(m, 1H), 4.02(m, 1H), 3.88-3.62(m, 2H), 2.87-2.58(m, 5H), 2.33(q, 1H), 1.90-0.78(m, 15H)，0.97(s，6H)。化合物258: MS: m/z 806_1(M++1) ; ’H NMR(CDC13) δ 10.36(s, 1H), 8.28(d, 1H), 8.07(m, 1H), 7.84(s, 1H), 7.62(m, 110 201109028 3H), 7.44(m, 2H), 7.18(m, 1H), 6.06(s, 1H), 5.67(q, 1H), 4.96(dd, 1H), 4.80(d, 1H), 4.60(m, 1H), 4.41(m, 1H), 4.10(m, 2H), 3.66(m, 1H), 3.39(m, 2H), 3.22(s, 3H), 2.91-2.58(m, 4H)，2.20(q, 1H), 1.90-0.86(m，15H)。化合物259: MS: m/z 788.1(M++1) ; ’H NMR(CDC13) δ 10.51(s, 1H), 8.28(d, 1H), 7.94(m, 1H), 7.86(s, 1H), 7.64(d, 1H), 7.60-7.43(m, 4H), 7.16(m, 1H), 6.00(s, 1H), 5.85(m, 1H), 5.62(m, 2H), 5.30-5.19(m, 2H), 4.93(dd, 1H), 4.66(m, 1H), 4.58-4.36(m, 3H), 4.02(m, 1H), 2.87-2.56(m, 4H), 2.26(q, 1H)，1-86-0.86(m, 15H)。化合物260: MS: m/z 762.2(M++1) ; 4 NMR(CDC13) δ 10.63(s, 1H), 8.26(d, 1H), 8.10(s, 1H), 7.88(d, 1H), 7.67-7.44(m, 4H), 6.84(s, 1H), 5.89(s, 1H), 5.68(q, 1H), 5.38(d, 1H), 4.97(dd, 1H), 4.76(m, 1H), 4.58(d, 1H), 4.21(m, 1H), 3.96(m, 1H), 3.66(s, 3H), 2.91-2.60(m, 4H), 2.25(q, 1H), 1.89-0.89(m, 15H)。化合物261: MS: m/z 704.2(M++1) ; iH NMR(CD3OD) δ 9.26(s, 1H), 8.47(d, 1H), 8.26(m, 1H), 8.15(dd, 1H), 7.97-7.82(m, 3H), 7.66(m, 1H), 6.54(s, 1H), 5.74(q, 1H), 5.13(dd, 1H), 4.60(d, 1H), 4.35(m, 2H), 3.72-3.58(m, 2H), 2.97-2.81 (m, 3H)，2.51(m，1H)，2.33(q，1H)，1.99-1.06(m, 15H)。化合物262: MS: m/z 818.3(M++1) ; iH NMR(CDC13) δ 10.42(s, 1H), 8.30(d, 1H), 8.12(m, 1H), 7.86(m, 1H), 7.49- 7.33(m, 5H), 6.10(s, 1H), 5.66(m, 2H), 5.08-4.66(m, 4H), 111 201109028 4.28(m, 1H), 4.03(m, 1H), 3.86-3.58(m, 4H), 2.86-2.57(m, 4H)，2.34(q，1H)，2.03-0.87(m，17H)。化合物263: MS: m/z 780·2(Μ++1) ; 4 NMR(CDC13) δ 10.60(s, 1H)，8.04-7.92(m, 3H)，7.78(m, 1H)，7.56(dd，1H)， 7.38(m, 1H), 6.94(m, 1H), 5.89(s, 1H), 5.67(q, 1H), 5.40(d, 1H), 4.95(dd, 1H), 4.76(ra, 1H), 4.57(d, 1H), 4.20(m, 1H), 3.97(m, 1H), 3.64(s, 3H), ：2.94-2.63(m, 4H), 2.23(q, 1H), 1.88-1.09(m, 15H)。化合物264: MS: m/z 9:Π.3(Μ++1);NMR(CDC13) δ 10.43(s, 1H), 8.30(d, 1H), 8.10(m, 1H), 7.86(d, 1H), 7.62- 7.34(m, 5H), 6.08(s, 1H), 5.60(q, 1H), 5.38(s, 1H), 4.90- 4.62(m, 4H), 4.26(m, 1H), 4.03(m, 1H), 3.64(m, 2H), 3.15(m, 2H), 2.85-2.55(m, 4H), 2.：33(q, 1H), 1.83-0.86(m, 19H), 1.44(s, 9H)。化合物265: MS: m/z 780.2(M++1) ; 4 NMR(CDC13) δ 10.45(s, 1H), 8.29(d, 1H), 8.05(m, 1H), 7.78(d, 1H), 7.63-7.25(m, 4H), 6.04(m, 2H), 5.63(q, 1H), 4.91(dd, 1H), 4.72-4.63(m, 3H), 4.43-4.32(m, 2H), 4.02(m, 1H), 3.78-3.58 (m, 1H)，2.85-2.35(m，6H)，2.03-0.86(m，15H)。化合物266: MS: m/z 776.3(M++1) ; 'H NMR(CDC13) δ 10.56(s, 1H), 8.24(d, 1H), 8.00(s, 1H), 7.87-7.79(m, 2H), 7.61-7.42(m, 4H), 7.06(m, 1H), 5.93(s, 1H), 5.61(q, 1H), 5.44(m, 1H), 4.91(dd, 1H), 4.68(m, 1H), 4.25-3.96(m, 4H), 2.86-2.57(m, 4H), 2.29(q，1H)，1.8 卜0.88(m, 18H)。 112 201109028 化合物267: MS: m/z 812·2(Μ++1) ; NMR(CDC13) δ 10.47(s, 1Η), 8.27(d, 1H), 7.90(m, 1H), 7.81(m, 2H), 7.76-7.43(m, 4H), 7.17(m, 1H), 6.03-5.85(m, 2H), 5.61(q, 1H), 4.88(dd, 1H), 4.72-4.61(m, 2H), 4.25-3.98(m, 4H), 2.86-2.58 (m，4H)，2.30(q, 1H)，1.84-0_88(m, 15H)。化合物268: MS: m/z 832·2(Μ++1) ; ’H NMR(CDC13) δ 10.50(s, 1H), 8.35-8.29(m, 1H), 8.15-8.01(m, 1H), 7.84-7.32 (m, 5H), 7.13-7.03(m, 1H), 6.10(s, 1H), 5.54(m, 1H), 5.36(d, 1H), 5.05-4.83(m, 2H), 4.74-4.65(m, 1H), 4.36(m, 1H), 4.14-4.05(m, 1H)，2.88-2.51(m，4H), 2.12-0.88(m, 24H)。化合物269: MS: m/z 834.3(M++1)。化合物270: MS: m/z 792.2(M++1)。化合物271: MS: m/z 822.2(M++1) ; NMR(CDC13) δ 10.38(s, 1H), 8.09(m, 1H), 7.99(dd, 1H), 7.83(dd, 1H), 7.58(dd, 1H), 7.41-7.25(m, 3H), 6.15(s, 1H), 5.59(q, 1H), 5.16(d, 1H), 4.89(dd, 1H), 4.78-4.67(m, 2H), 4.25(m, 1H), 4.07(m, 1H), 2.77-2.70(m, 3H), 2.57(m, 1H), 2.30(q, 1H), 1.90-0.82(m, 15H), 1.23(s，9H)。化合物272: MS: m/z 822·2(Μ++1) ; ’H NMR(CDC13) δ 10.37(s, 1H), 8.10(m, 1H), 7.98(dd, 1H), 7.83(dd, 1H), 7.58(dd, 1H), 7.42-7.27(m, 2H), 7.19(s, 1H), 6.16(s, 1H), 5.62(q, 1H), 5.11(d, 1H), 4.92(dd, 1H), 4.78-4.67(m, 2H), 4.24(m, 1H), 4.07(m, 1H), 2.86-2.77(m, 3H), 2.56(m, 1H), 2.32(q, 1H)，1.90-0.82(m，15H)，1.23(s，9H)。 113 201109028 化合物273: MS: m/z 850.3, 852.3(M++1)。化合物274: MS: m/z 8:34.2(M++1) ; 4 NMR(CDC13) δ 10.43(s, 1H), 8.08(m, 1H), 7.95(dd, 1H), 7.91(dd, 1H), 7.56(dd, 1H), 7.50(s, 1H), 7.37-7.31(m, 2H), 6.05(s, 1H), 5.58(q, 1H), 5.39(d, 1H), 4.72-4.67(m, 4H), 4.27(m, 1H), 4.03(m, 1H), 2.89-2.67(m, 3H), 2.55(m, 1H), 2.29(q, 1H), 1.90-0.87(m，23H)。化合物275: MS: m/z 780_2(M++1) ; 4 NMR(CDC13) δ 10.61(s, 1H), 8.06-7.92(m, 3H), 7.75(m, 1H), 7.55(dd, 1H), 7.39(m, 1H), 6.90(m, 1H), 5.89(s, 1H), 5.66(q, 1H), 5.44(d, 1H), 4.94(dd, 1H), 4.77(m, 1H), 4.58(d, 1H), 4.20(m, 1H), 3.96(m, 1H), 3.65(s, 3H), 2.93-2.67(m, 4H), 2.24(q, 1H), 1.87-1.09(m5 15H)。化合物276: MS: m/z 818.1(M++1) ; NMR(CDC13) δ 10.35(s, 1H), 8.05(m, 1H), 7.96(dd, 1H), 7.75(dd, 1H), 7.57-7.52(m, 2H), 7.39-7.32(m, 3H), 6.06(s, 1H), 5.60(q, 1H), 4.85-4.73(m, 2H), 4.55-4.48(m, 2H), 4.06(m, 1H), 2.83(m, 2H), 2.69(m, 1H), 2.50(m, 1H), 2.23(q, 1H), 1.85-1.05(m, 15H)。化合物277: MS: m/z 856.3(M++1)。化合物278: MS: m/z 764·2(Μ++1) ; 4 NMR(CDC13) δ 10.49(s, 1H), 7.94-7.82(m, 3H), 7.72(s, 1H), 7.55(dd, 1H), 7.38(m, 1H), 7.17(m, 1H), 6.21(d, 1H), 5.99(s, 1H), 5.62.(q, 1H), 4.94(dd, 1H), 4.68(m, 1H), 4.61(d, 1H), 4.45(m, 1H), 114 201109028 4.02(m, 1H), 2.85(m, 2H), 2.71(m, 1H), 2.56(m, 1H), 2.27(q, 1H)，1.92(s, 3H), 1.90-1.03(m, 15H)。化合物279: MS: m/z 834.3(M++1) ; ’H NMR(CDC13) δ 10.43(s, 1H), 8.05(m, 1H), 7.96(dd, 1H), 7.91(dd, 1H), 7.55(dd, 1H), 7.48(s, 1H), 7.37-7.32(m, 2H), 6.05(s, 1H), 5.57(q, 1H), 5.39(d, 1H), 4.79-4.67(m, 4H), 4.28(m, 1H), 4.03(m, 1H), 2.87-2.67(m, 3H), 2.54(m, 1H), 2.29(q, 1H), 1.90-0.87(m，23H)。化合物280: MS: m/z 818.2(M++1) ; 4 NMR(CDC13) δ 10.36(s, 1H), 8.02(m, 1H), 7.94(dd, 1H), 7.71(dd, 1H), 7.60(s, 1H), 7.54-7.51(dd, 1H), 7.42(d, 1H), 7.36-7.30(m, 2H), 6.03(s, 1H), 5.60(q, 1H), 4.86-4.72(m, 2H), 4.56-4.48(m, 2H), 4.05(m, 1H), 2.84(m, 2H), 2.68(m, 1H), 2.48(m, 1H), 2.23(q, 1H)，1.88-1.05(m，15H)。化合物2 81按照與實施例1中所述類似的方式製備：化合物281: MS: m/z 901.2(M++1) ; NMR(CDC13) δ 10.25(s, 1H), 8.48(d, 1H), 7.59(dd, 1H), 7.39(d, 1H), 7.32(dd, 1H), 7.15(s, 1H), 7.04(s, 1H), 6.14(s, 1H), 5.69(ddd, 1H), 5.04(m, 2H), 4.72(m, 1H), 4.56(m, 2H), 4.24-4.15(m, 2H), 3.97(s, 3H), 3.34(tt, 1H), 2.55(m, 1H), 2.24-2.26(m, 1H), 2.01-0.69(m, 34H)。實施例282 : NS3/4A蛋白酶的抑制蛋白質的表達和純化將含有編碼N-末端His6-標簽的NS4A(21_32)-GSGS- 115 201109028 1^3(3-181)基因的質粒轉化入諾瓦金公司（]^0¥3§611)的大腸桿菌(五· co//)菌株BL21(DE3) pLysS中來過度表達蛋白質。37 °C ’在200毫升含有卡那徽素和氣黴素的Lauria-Bertani (LB) 培養基中過夜培養轉化的BL21 (DE3) pLysS單菌落。將細菌培養液轉移至迪菲科公司（D i fc 〇)的6升含抗生素的L B培養基中，22t振盪培育。600 nm吸光度達到0.6後，在22°C 用1 mM異丙基-1-硫代-β-D-吡喃半乳糖苷(IPTG)誘導培養物5小時。然後離心(4°C，6,000 X g，15分鐘）收集培養物。將細胞糰粒重懸在150毫升緩衝液A (50 rnM HEPES，pH 7·4,0.3 M NaCl，0.1% (w/v) CHAPS，10 mM咪唑，10% (v/v) 甘油）中。使混合物流過在30 psi操作的微流化儀 (Microfluidizer)四次使之分散，然後離心（4。〇，58,250 X g， 3〇分鐘）除去細胞碎片。在有10 mMu米。坐存在下，用法瑪西亞公司（Pharmacia)的GradiFrac系統將含His6-標簽蛋白的細胞裂解液以3毫升/分鐘加載到25毫升恰根公司（()比§611)的 Νι-ΝΤΑ柱上。用1 〇個柱體積的裂解緩衝液洗滌柱。用8個柱體積的補加了 300 mM σ米唾的緩衝液a洗脫結合的 NS4A(2丨·32Γ<3808-Ν83(3-ι8ι)。通過用緩衝液 β(5〇 ηιΜCt 1-31. To a solution of Boc-trans-4-hydroxy-L-proline (0.53 g, 2.30 mmol) in DMSO (10 mL) was added i-BuONa (0.49 g, 5.08 mmol). ). Warm to room temperature and stir for an additional hour, then at 1 Torr. 〇 Slowly add intermediate I-26 (G.62 g ' 2.31 mmol _). The reaction mixture was mixed for 4 hours, devoid of 107 201109028 and then quenched with a 10% aqueous HCl solution to a pH of 6-7. The crude suspended solid was filtered, washed with water and dried to give 1-27 (0.92 g, 86%). MS: m/z 467.1 (M++1). 5 ° C, to 1-27 (0.90 g, 1.93 mmol), HATU (58.9 g, 1.55 mmol), HOBt (7.0 g, 0.52 mmol) and NMM (38.3 g, 3.86 mmol) in CH2C12 (10 Cyclohexane propanesulfonic acid (丨-amino-2-vinyl-cyclopropanecarbonyl)-decylamine (54.0 g, 2.03 mmol) and NMM (0.19 g, 1.93 mmol) were dissolved in CH2C12 dropwise. mixture. The mixture was warmed to rt. MS: m/z 679·1 (Μ++1). Compound 1-28 (1.20 g, 1.77 mmol) was dissolved in MeOH (18 mL). Thionium gas (0.39 ml, 5, 30 mmol) was added dropwise to the reaction mixture. After removing the ice bath, the reaction mixture was heated at 65 ° C for 1 hour. The resulting solution was cooled to 4 ° C, filtered, washed with cold MeOH and ether to afford pale yellow powder to afford white powders 1-29, which was used in the next reaction step without further purification. MS: m/z 579·1 (Μ++1). 5 ° C to 2-cyclopentyloxycarbonylamino-indole-8-enoic acid (0.87 g, 2,34 mmol), HATU (1.16 g, 3_05 mmol) and H〇Bt (0.14 g, 1.02 m a mixture of 1-29 (1.18 g, 2.03 mmol; ^,]^11^ (0.49 g, 4.87 mmol) dissolved in DMF (1 () mL) was added dropwise to a solution of CH2C12 (10 mL) After warming to room temperature and re-mixing for 16 hours, '1.0% HCl (1 mL) was added and the reaction mixture was concentrated. The residue was cooled to 5 ° C, using 108 201109028 5% HCl (aq) (10 ml χ) 2) Washed sequentially with NaHC03 (aq.) (10 mL EtOAc) (EtOAc) (EtOAc) The solution was degassed for 1 hour by a bubbling of a solution of compound 1-30 (0.50 g, 0·59 mmol) in CH2C12 (120 ml). A second generation Hovda-Grubb catalyst (48 mg, 0.076 mmol) was added and the reaction mixture was heated at 40 ° C for 16 hours. After the reaction was indicated by HPLC, the reaction mixture was cooled to 30 ° C. Concentrated and purified by silica gel column chromatography to obtain product I-31 (0.30 g, yield 62 ° / c)). MS: m/z 816·3 (M++1); 1HNMR (CDC13) δ 10.33 (s, 1H), 8.30 (d, 1H), 8.11 (dd, 1H), 7.88 (dd, 1H), 7.67-7.56 (m, 2H), 7.46(dd, 1H), 7.43-7.30(m, 2H), 6.12(s, 1H), 5.64(q, 1H), 5.22(d, 1H), 4.92(dd, 1H), 4.77(d, 1H), 4.66(dd, 1H), 4.32-4.22(m, 1H), 4.04(dd, 1H), 2.93-2.46(m,3H), 2_31(q, 1H), 1.92-0.80 ( m, 25H). To a solution of the compound i_3i (5 mg, 〇〇61 mmol) in MeOH (10 ml) was added 5 〇/〇Pd_c (5 mg). Then, the reaction mixture was stirred under a hydrogen atmosphere at a pressure of 60 psi and room temperature for 4 hours. The reaction mixture was filtered and purified by EtOAc EtOAc (EtOAc: EtOAc: EtOAc: ssssssssssssssssssssssssssss ), 8.l3 (dd, 1H), 7 8 〇 (dd, m), 7.65-7.57 (m5 2H), 7.45 (dd, 1H), 7.39-7.30 (m, 2H), 6.1 l(s, 1H ), 5.25(d, 1H), 4.96(brs, 1H), 4.68(dd, 1H), 4.60(d, 1H), 4.37(dd, 1H), 4.14(dd, 1H), 3.02.2.57(m, 3H), 1.92-0.80 (m, 109 201109028 29H). Examples 255-281: Synthesis of Compound 255-281 Compounds 255-281 were each prepared in a similar manner as described in Example 254. </ RTI> <RTI ), 7.37(m, 1H), 7.18(m, 1H), 6.20(d, 1H), 5.97(s, 1H), 5.64(q, 1H), 4.94(dd, 1H), 4.68(m, 1H) , 4.61(d, 1H), 4.44(m, 1H), 4.02(m, 1H), 2.85(m, 2H), 2.70(m, 1H), 2.58(m, 1H), 2..25(q, 1H), 1.92 (s, 3H), 1.90 - 1.03 (m, 15H). Compound 256: MS: m/z 815.6 (M++1); 'H NMR (CDC13) δ 10.31 (s, H), 8.32 (d, 1H), 8.25 (m, 1H), 7.81 (dd, 1H) ), 7.64(m, 2H), 7.46(dd, 1H), 7.23-7.12(m, 2H), 6.20(s, 1H), 5.66(q, 1H), 5.16(d, 1H), 4.98(dd, 1H), 4.75-4.64(m, 3H), 4.31(m, 1H), 4.08(m, 1H), 2.88(m, 1H), 2.78(m, 2H), 2.55(m, 1H), 2.29(q , 1H), 1.92-0.84 (m, 23H). Compound 257: MS: m/z (m/z) (m/m), NMR (CD, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, , 7.63-7.42(m, 3H), 7.21(m, 1H), 5.97(s, 1H), 5.60(q, 1H), 5.44(d, 1H), 4.85(dd, 1H), 4.66(m, 2H) ), 4.29 (m, 1H), 4.02 (m, 1H), 3.88-3.62 (m, 2H), 2.87-2.58 (m, 5H), 2.33 (q, 1H), 1.90-0.78 (m, 15H), 0.97 (s, 6H). Compound 258: MS: m/z </ </ </RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; , 7.84(s, 1H), 7.62(m, 110 201109028 3H), 7.44(m, 2H), 7.18(m, 1H), 6.06(s, 1H), 5.67(q, 1H), 4.96(dd, 1H ), 4.80(d, 1H), 4.60(m, 1H), 4.41(m, 1H), 4.10(m, 2H), 3.66(m, 1H), 3.39(m, 2H), 3.22(s, 3H) , 2.91-2.58 (m, 4H), 2.20 (q, 1H), 1.90-0.86 (m, 15H). Compound 259: MS: m/z 788.1 (M++1); 'H NMR (CDC13) δ 10.51 (s, 1H), 8.28(d, 1H), 7.94(m, 1H), 7.86(s, 1H), 7.64(d, 1H), 7.60-7.43(m, 4H), 7.16(m, 1H), 6.00(s, 1H), 5.85(m, 1H), 5.62(m, 2H), 5.30-5.19(m, 2H), 4.93(dd, 1H), 4.66(m, 1H), 4.58-4.36(m, 3H), 4.02 (m, 1H), 2.87-2.56 (m, 4H), 2.26 (q, 1H), 1-86-0.86 (m, 15H). Compound 260: MS m/z 762.2(M++1); 4 NMR(CDC13) δ 10.63(s, 1H), 8.26(d, 1H), 8.10(s, 1H), 7.88(d, 1H), 7.67-7.44 ( m, 4H), 6.84(s, 1H), 5.89(s, 1H), 5.68(q, 1H), 5.38(d, 1H), 4.97(dd, 1H), 4.76(m, 1H), 4.58(d , 1H), 4.21 (m, 1H), 3.96 (m, 1H), 3.66 (s, 3H), 2.91-2.60 (m, 4H), 2.25 (q, 1H), 1.89-0.89 (m, 15H). Compound 261: MS: m/z: 704.2 (M++1); iH NMR (CD3OD) δ 9.26 (s, 1H), 8.47 (d, 1H), 8.26 (m, 1H), 8.15 (dd, 1H), 7.97-7.82(m, 3H), 7.66(m, 1H), 6.54(s, 1H), 5.74(q, 1H), 5.13(dd, 1H), 4.60(d, 1H), 4.35(m, 2H) , 3.72-3.58 (m, 2H), 2.97-2.81 (m, 3H), 2.51 (m, 1H), 2.33 (q, 1H), 1.99-1.06 (m, 15H). Compound 262: MS: m/z 818.3 (M++1); iH NMR (CDC13) δ 10.42 (s, 1H), 8.30 (d, 1H), 8.12 (m, 1H), 7.86 (m, 1H), 7.49- 7.33(m, 5H), 6.10(s, 1H), 5.66(m, 2H), 5.08-4.66(m, 4H), 111 201109028 4.28(m, 1H), 4.03(m, 1H), 3.86- 3.58 (m, 4H), 2.86-2.57 (m, 4H), 2.34 (q, 1H), 2.03-0.87 (m, 17H). Compound 263: MS: m/z 780·2 ( Μ +1); 4 NMR (CDC13) δ 10.60 (s, 1H), 8.04-7.92 (m, 3H), 7.78 (m, 1H), 7. , 1H), 7.38 (m, 1H), 6.94 (m, 1H), 5.89 (s, 1H), 5.67 (q, 1H), 5.40 (d, 1H), 4.95 (dd, 1H), 4.76 (ra, 1H), 4.57(d, 1H), 4.20(m, 1H), 3.97(m, 1H), 3.64(s, 3H), :2.94-2.63(m, 4H), 2.23(q, 1H), 1.88- 1.09 (m, 15H). Compound 264: MS: m/z 9: Π.3 (Μ+1); NMR (CDC13) δ 10.43 (s, 1H), 8.30 (d, 1H), 8.10 (m, 1H), 7.86 (d, 1H), 7.62- 7.34(m, 5H), 6.08(s, 1H), 5.60(q, 1H), 5.38(s, 1H), 4.90- 4.62(m, 4H), 4.26(m, 1H), 4.03 (m, 1H), 3.64(m, 2H), 3.15(m, 2H), 2.85-2.55(m, 4H), 2.:33(q, 1H), 1.83-0.86(m, 19H), 1.44( s, 9H). Compound 265: MS: m/z 780.2 (M++1); 4 NMR (CDC13) δ 10.45 (s, 1H), 8.29 (d, 1H), 8.05 (m, 1H), 7.78 (d, 1H), 7.63-7.25(m, 4H), 6.04(m, 2H), 5.63(q, 1H), 4.91(dd, 1H), 4.72-4.63(m, 3H), 4.43-4.32(m, 2H), 4.02( m, 1H), 3.78-3.58 (m, 1H), 2.85-2.35 (m, 6H), 2.03-0.86 (m, 15H). Compound 266: MS: m/z 776.3 (M++1); 'H NMR (CDC13) δ 10.56 (s, 1H), 8.24 (d, 1H), 8.00 (s, 1H), 7.87-7.79 (m, 2H), 7.61-7.42(m, 4H), 7.06(m, 1H), 5.93(s, 1H), 5.61(q, 1H), 5.44(m, 1H), 4.91(dd, 1H), 4.68(m , 1H), 4.25-3.96 (m, 4H), 2.86-2.57 (m, 4H), 2.29 (q, 1H), 1.8, 0.88 (m, 18H). 112 201109028 Compound 267: MS: m/z 812·2 (Μ++1); NMR (CDC13) δ 10.47 (s, 1 Η), 8.27 (d, 1H), 7.90 (m, 1H), 7.81 (m, 2H), 7.76-7.43(m, 4H), 7.17(m, 1H), 6.03-5.85(m, 2H), 5.61(q, 1H), 4.88(dd, 1H), 4.72-4.61(m, 2H) , 4.25-3.98 (m, 4H), 2.86-2.58 (m, 4H), 2.30 (q, 1H), 1.84-0_88 (m, 15H). Compound 268: MS: m/z 832·2 (Μ+1); 'H NMR (CDC13) δ 10.50 (s, 1H), 8.35-8.29 (m, 1H), 8.15-8.01 (m, 1H), 7.84-7.32 (m, 5H), 7.13-7.03(m, 1H), 6.10(s, 1H), 5.54(m, 1H), 5.36(d, 1H), 5.05-4.83(m, 2H), 4.74- 4.65 (m, 1H), 4.36 (m, 1H), 4.14-4.05 (m, 1H), 2.88-2.51 (m, 4H), 2.12-0.88 (m, 24H). Compound 269: MS: m/z 834.3 (M++1). Compound 270: MS: m/z 792.2 (M++1). Compound 271: MS: m/z 822.2 (M++1); NMR (CDC13) δ 10.38 (s, 1H), 8.09 (m, 1H), 7.99 (dd, 1H), 7.83 (dd, 1H), 7.58 (dd, 1H), 7.41-7.25(m, 3H), 6.15(s, 1H), 5.59(q, 1H), 5.16(d, 1H), 4.89(dd, 1H), 4.78-4.67(m, 2H ), 4.25(m, 1H), 4.07(m, 1H), 2.77-2.70(m, 3H), 2.57(m, 1H), 2.30(q, 1H), 1.90-0.82(m, 15H), 1.23( s, 9H). Compound 272: MS: m/z 822·2 ( Μ +1); 'H NMR (CDC13) δ 10.37 (s, 1H), 8.10 (m, 1H), 7.98 (dd, 1H), 7.83 (dd, 1H), 7.58(dd, 1H), 7.42-7.27(m, 2H), 7.19(s, 1H), 6.16(s, 1H), 5.62(q, 1H), 5.11(d, 1H), 4.92(dd , 1H), 4.78-4.67 (m, 2H), 4.24 (m, 1H), 4.07 (m, 1H), 2.86-2.77 (m, 3H), 2.56 (m, 1H), 2.32 (q, 1H), 1.90-0.82 (m, 15H), 1.23 (s, 9H). 113 201109028 Compound 273: MS: m/z 850.3, 852.3 (M++1). Compound 274: MS: m/z 8:34.2 (M++1); 4 NMR (CDC13) δ 10.43 (s, 1H), 8.08 (m, 1H), 7.95 (dd, 1H), 7.91 (dd, 1H) ), 7.56 (dd, 1H), 7.50 (s, 1H), 7.37-7.31 (m, 2H), 6.05 (s, 1H), 5.58 (q, 1H), 5.39 (d, 1H), 4.72-4.67 ( m, 4H), 4.27(m, 1H), 4.03(m, 1H), 2.89-2.67(m, 3H), 2.55(m, 1H), 2.29(q, 1H), 1.90-0.87(m,23H) . Compound 275: MS: m/z 780 </RTI> (M++1); 4 NMR (CDC13) δ 10.61 (s, 1H), 8.06-7.92 (m, 3H), 7.75 (m, 1H), 7.55 (dd, 1H) ), 7.39(m, 1H), 6.90(m, 1H), 5.89(s, 1H), 5.66(q, 1H), 5.44(d, 1H), 4.94(dd, 1H), 4.77(m, 1H) , 4.58(d, 1H), 4.20(m, 1H), 3.96(m, 1H), 3.65(s, 3H), 2.93-2.67(m, 4H), 2.24(q, 1H), 1.87-1.09(m5 15H). Compound 276: MS: m/z 818.1 (M++1); NMR (CDC13) δ 10.35 (s, 1H), 8.05 (m, 1H), 7.96 (dd, 1H), 7.75 (dd, 1H), 7.57 -7.52(m, 2H), 7.39-7.32(m, 3H), 6.06(s, 1H), 5.60(q, 1H), 4.85-4.73(m, 2H), 4.55-4.48(m, 2H), 4.06 (m, 1H), 2.83 (m, 2H), 2.69 (m, 1H), 2.50 (m, 1H), 2.23 (q, 1H), 1.85-1.05 (m, 15H). Compound 277: MS: m/z 856.3 (M++1). Compound 278: MS: m/z 764·2 ( Μ +1); 4 NMR (CDC13) δ 10.49 (s, 1H), 7.94-7.82 (m, 3H), 7.72 (s, 1H), 7.55 (dd , 1H), 7.38(m, 1H), 7.17(m, 1H), 6.21(d, 1H), 5.99(s, 1H), 5.62.(q, 1H), 4.94(dd, 1H), 4.68(m , 1H), 4.61(d, 1H), 4.45(m, 1H), 114 201109028 4.02(m, 1H), 2.85(m, 2H), 2.71(m, 1H), 2.56(m, 1H), 2.27( q, 1H), 1.92 (s, 3H), 1.90-1.03 (m, 15H). Compound 279: MS: m/z 834.3 (M++1); 'H NMR (CDC13) δ 10.43 (s, 1H), 8.05 (m, 1H), 7.96 (dd, 1H), 7.91 (dd, 1H) , 7.55(dd, 1H), 7.48(s, 1H), 7.37-7.32(m, 2H), 6.05(s, 1H), 5.57(q, 1H), 5.39(d, 1H), 4.79-4.67(m , 4H), 4.28 (m, 1H), 4.03 (m, 1H), 2.87-2.67 (m, 3H), 2.54 (m, 1H), 2.29 (q, 1H), 1.90-0.87 (m, 23H). Compound 280: MS: m/z 818.2 (M++1); 4 NMR (CDC13) δ 10.36 (s, 1H), 8.02 (m, 1H), 7.94 (dd, 1H), 7.71 (dd, 1H), 7.60(s, 1H), 7.54-7.51(dd, 1H), 7.42(d, 1H), 7.36-7.30(m, 2H), 6.03(s, 1H), 5.60(q, 1H), 4.86-4.72( m, 2H), 4.56-4.48 (m, 2H), 4.05 (m, 1H), 2.84 (m, 2H), 2.68 (m, 1H), 2.48 (m, 1H), 2.23 (q, 1H), 1.88 -1.05 (m, 15H). Compound 2 81 was prepared in a similar manner as described in Example 1: Compound 281: MS: m/z: s.ss.ssssssssssssssssssssssssssssssssssssss , 7.59(dd, 1H), 7.39(d, 1H), 7.32(dd, 1H), 7.15(s, 1H), 7.04(s, 1H), 6.14(s, 1H), 5.69(ddd, 1H), 5.04(m, 2H), 4.72(m, 1H), 4.56(m, 2H), 4.24-4.15(m, 2H), 3.97(s, 3H), 3.34(tt, 1H), 2.55(m, 1H) , 2.24-2.26 (m, 1H), 2.01-0.69 (m, 34H). Example 282: Inhibition of NS3/4A protease Protein expression and purification A plasmid containing the N-terminal His6-tagged NS4A(21_32)-GSGS-115 201109028 1^3 (3-181) gene was transformed into Novakine. The company (]^0¥3§611) was overexpressed in the E. coli (five co//) strain BL21(DE3) pLysS. Transformed BL21 (DE3) pLysS single colonies were grown overnight in 200 ml of Lauria-Bertani (LB) medium containing cadinacin and oxytetracycline at 37 °C. The bacterial culture was transferred to 6 liters of antibiotic-containing L B medium of Difico (D i fc 〇) and incubated at 22t with shaking. After the absorbance at 600 nm reached 0.6, the culture was induced with 1 mM isopropyl-1-thio-β-D-galactopyranoside (IPTG) at 22 °C for 5 hours. The culture was then collected by centrifugation (4 ° C, 6,000 X g, 15 minutes). The cell pellet was resuspended in 150 ml of buffer A (50 rnM HEPES, pH 7.4, 0.3 M NaCl, 0.1% (w/v) CHAPS, 10 mM imidazole, 10% (v/v) glycerol). The mixture was allowed to flow through a Microfluidizer operated at 30 psi four times to disperse, and then centrifuged (4. 〇, 58, 250 X g, 3 Torr) to remove cell debris. There are 10 mMu meters. In the presence of Pharmacia's GradiFrac system, a His6-tagged protein-containing lysate was loaded at 3 ml/min onto a 25 ml 恰ι-ΝΤΑ column of Chagan (() § 611). The column was washed with 1 column volume of lysis buffer. The bound NS4A (2丨·32Γ<3808-Ν83(3-ι8ι) was eluted with 8 column volumes of buffer a supplemented with 300 mM sigma saliva. By using buffer β (5〇 ηιΜ)

HEPES ’ pH 7.4，0_1% (w/v) CHAPS，10% (v/v)甘油，5 mM 二硫蘇糖醇(DTT)和1 M NaCl)平衡的Q·瓊脂糖柱進一步純化合並的諸組分。收集含的洗脫液，利用用緩衝液C(50 mM HEPES，pH 7.4，〇.1〇/0 (w/v) CHAPS，5 mM DTT，10% (v/v)甘油）預平衡的聚丙烯醯胺葡聚糖(sephacryl)-75柱（16 x 100 cm，法瑪西亞公司）以流速 116 201109028 5毫升/分鐘通過尺寸排阻層析進一步純化。冷凍純化的蛋白質，保存於-80°C備用。 HPLC微孔測試製備含50 mM Tris，pH 7.4, 100 mM NaCl，20%甘油， 0.012% CHAPS，10 mM DTT，5 μΜ 底物 Ac-Asp-Glu-Asp(EDANS)-Glu-Glu-Abu-y-[COOAla]-Ser-Lys(DABCYL) -NH2(RET S1，ANASPEC)和10 μΜ測試化合物的溶液。在96 孔板的各孔中加入80微升的所述溶液。加入20 pL用含有50 mMTris緩衝液，pH7·4，100mMNaα，20°/。甘油和0.012o/o CHAPS的緩衝液配製的10 nM NS3/4A蛋白酶開始反應。 NS3/4A蛋白酶的終濃度是2 ηΜ，低於底物RET S1的Km。 30°C培育試驗溶液30分鐘。然後加入1〇〇 pL 1%TFA終止反應。將200 pL等份試樣轉移至安捷侖公司（Agiient)的 96-孔板的各孔中。採用下述的反相HPLC分析反應產物。HPLC系統包括：Agilent 1100 ’ 脫氣柱G1379A，二元泵G1312A，自動進樣器G1I367A，柱恒溫室G1316A，二極管陣列檢測器 G1315B，柱：Agilent，ZORBAX Eclipse XDB-C18，4.6 mm， 5 μιη，P/N 993967-902，柱恒溫器：室溫，注射體積：1〇〇 pL ;溶劑A = HPLC級水 + 0.09% TFA，溶劑B = HPLC級乙腈+ 0.09% TFA。HPLC總的運行時間為7 6分鐘，包括4分鐘線性梯度從25到50°/〇溶劑B ’ 50%溶劑B保持30秒，梯度從 50到25%溶劑B再保持30秒。用25%溶劑B再次平衡柱2·6分鐘，然後注射下一樣品。根據HPLC結果計算各測試化合物 117 201109028 的1Cso值(觀察到50% NS3/4A活性受抑制時的濃度）β 在上述抑制試驗中測試了化合物丨_28卜結果顯示，274 個化合物的ICw低於20 ηΜ，7個化合物的1(：5()在2〇_1〇〇 ηΜ 範圍。此外，發現某些本發明的化合物出乎意料地能以有效方式抑制耐受一種或多種其他HCV藥物的HcV蛋白酶突變體。實施例283 : HCV複製子細胞試驗方案在含10%胎牛血清(FBS)、1.0毫克/毫升G4〗8和適當補充劑的DMEM(培養基A)中培養含HCV複製子的細胞。在第丨天，用胰蛋白酶/EDTA混合物處理複製子細胞單層，移取該細胞單層，用培養基A稀釋至終濃度48,000細胞 /毫升。將該溶液（1毫升)接種于24-孔組織培養平板的各孔中，37°C ’ 5°/。C〇2氣氛下，在組織培育箱中培養過夜。在第2天’用含1 〇%FBS和適當補充劑的DMEM(培養基 B)順序稀釋測試化合物（用100%DMSO配製）。在所有系列豨釋中，DMSO的終濃度維持在〇.20/〇。除去複製子細胞單層上的培養基，然後加入將含各種濃度化合物的培養基B。將不含化合物的培養基B加入其它孔作為無化合物的對照。 37°C，5% C02氣氛下，在組織培育箱中將細胞與化合物或0.2% DMSO在培養基B中培育72小時。然後，除去培養基，用PBS洗滌複製子細胞單層一次。將RNA提取試劑（例如，Rneasy試劑盒的試劑或TRIZOL試劑）立即加入細胞以 118 201109028 避免RNA降解。按照生產商的使用說明書的改進方法提取總RNA以改善提取效率和一致性。最後，洗脫包含hcv複製子RNA的細胞總RNA，保存在-80°C以待進一步加工。用兩套特異性引物實施TaqMan®實時RT-PCR定量測定試驗：一套用於HCV，另一套Α(：ΤΒ(β-肌動蛋白）。將總 RNA加入PCR反應，從而在同一 pcr孔中定量測定HCV和 ACTB RNA。根據各孔中ACTB RNA的水準對實驗失敗作標記並捨棄。根據同一PCR板中獲得的標準曲線計算各孔中的HCV RNA水準。利用DMSO或無化合物對照作為〇%抑制來計算化合物處理所致的HCV RNA水準的抑制百分比。根據任何給定化合物的滴定曲線計算EC5()(HCV RNA 水準達到50%抑制時的濃度）。在HCV複製子細胞試驗中測試了化合物丨_281。結果顯示，274個化合物的ECso值低於20 nM，7個化合物的EC50 值在20-100 nM之間。實施例284:藥物代謝動力學研究試驗前一天，雄性Sprague-Dawley大鼠（300-400克）在戊巴比妥麻醉下頸靜脈外科移植聚乙烯插管用於血液採樣。任意飲水禁食過夜，然後在第二天通過口服強飼（p〇) 給予測試化合物。給藥後48小時收集一系列的大鼠血液樣品，並在離心後回收肝素化血漿。提取血漿中的測試化合物，並通過液相色譜-質譜(LC_MS/MS)分析進行測定。標準藥物代謝動力學參數採用WinN〇nlin(版本4 〇, Pharsight, CA，USA)通過非房室分析進行評價。血漿中測試 119 201109028 化合物的濃度相對於時間的曲線中最大的點標注為c a。表觀最終相消除(?1/2)按1η(2)/λζ計算，其中λζ是消除速率常數。自給藥時間點至無窮的（AUC^im)濃度-時間曲線下面積按照線性梯形規則計算。HEPES 'pH 7.4, 0_1% (w/v) CHAPS, 10% (v/v) glycerol, 5 mM dithiothreitol (DTT) and 1 M NaCl) equilibrated Q·Sepharose column for further purification of the combined Component. The contained eluate was collected and pre-equilibrated with buffer C (50 mM HEPES, pH 7.4, 〇.1〇/0 (w/v) CHAPS, 5 mM DTT, 10% (v/v) glycerol) Sephacryl-75 column (16 x 100 cm, Pharmacia) was further purified by size exclusion chromatography at a flow rate of 116 201109028 5 ml/min. The purified protein was frozen and stored at -80 °C until use. HPLC micropore test preparation containing 50 mM Tris, pH 7.4, 100 mM NaCl, 20% glycerol, 0.012% CHAPS, 10 mM DTT, 5 μΜ Substrate Ac-Asp-Glu-Asp (EDANS)-Glu-Glu-Abu- A solution of y-[COOAla]-Ser-Lys(DABCYL)-NH2(RET S1,ANASPEC) and 10 μΜ test compound. 80 microliters of the solution was added to each well of a 96-well plate. Add 20 pL with 50 mMTris buffer, pH 7.4, 100 mM Naα, 20°/. The 10 nM NS3/4A protease formulated with glycerol and 0.012o/o CHAPS buffer began to react. The final concentration of the NS3/4A protease is 2 η Μ, which is lower than the Km of the substrate RET S1. The test solution was incubated at 30 ° C for 30 minutes. The reaction was then terminated by the addition of 1 〇〇 pL 1% TFA. Aliquots of 200 pL were transferred to each well of a 96-well plate from Agilent. The reaction product was analyzed by reverse phase HPLC as described below. The HPLC system consisted of: Agilent 1100' degassing column G1379A, binary pump G1312A, autosampler G1I367A, column thermostat G1316A, diode array detector G1315B, column: Agilent, ZORBAX Eclipse XDB-C18, 4.6 mm, 5 μιη, P/N 993967-902, column thermostat: room temperature, injection volume: 1 〇〇 pL; solvent A = HPLC grade water + 0.09% TFA, solvent B = HPLC grade acetonitrile + 0.09% TFA. The total run time of the HPLC was 7 6 minutes, including a 4 minute linear gradient from 25 to 50 ° / 〇 solvent B ' 50% solvent B for 30 seconds, and a gradient from 50 to 25% solvent B for another 30 seconds. The column was again equilibrated with 25% solvent B for 2-6 minutes and then the next sample was injected. The 1 Cso value of each test compound 117 201109028 was calculated according to the HPLC result (concentration at which 50% of NS3/4A activity was inhibited was observed). β The compound 丨 _28 was tested in the above inhibition test, and the ICw of 274 compounds was lower than that. 20 ηΜ, 7 compounds of 1 (:5() in the range of 2〇_1〇〇ηΜ. Furthermore, it has been found that certain compounds of the invention unexpectedly inhibit the tolerance to one or more other HCV drugs in an effective manner. HcV protease mutant. Example 283: HCV replicon cell assay protocol Culture of HCV-containing replicons in DMEM (medium A) containing 10% fetal calf serum (FBS), 1.0 mg/ml G4 8 and appropriate supplements On day 1-3, the replicon cell monolayer was treated with trypsin/EDTA mixture, the cell monolayer was removed, and diluted to a final concentration of 48,000 cells/ml with medium A. This solution (1 ml) was inoculated into 24- The wells of the well tissue culture plate were cultured overnight in a tissue incubator at 37 ° C ' 5 ° / C C 2 atmosphere. On day 2 'DMEM containing 1% FBS and appropriate supplements (medium) B) Serial dilution of test compound (with 100% DMSO) In all series of releases, the final concentration of DMSO was maintained at 〇20/〇. The medium on the replicon cell monolayer was removed, and then the medium B containing various concentrations of the compound was added. Additional wells were added as controls without compound. Cells were incubated with compound or 0.2% DMSO in medium B for 72 hours at 37 ° C, 5% CO 2 atmosphere. Then, the medium was removed and the replicon was washed with PBS. The cell monolayer is once. RNA extraction reagents (eg, reagents from the Rneasy kit or TRIZOL reagent) are immediately added to the cells to avoid RNA degradation at 118 201109028. Total RNA is extracted according to the manufacturer's instructions for improved extraction efficiency and consistency. Finally, the total RNA of the cells containing the hcv replicon RNA was eluted and stored at -80 ° C for further processing. TaqMan® real-time RT-PCR quantitative assay was performed with two sets of specific primers: one for HCV and one for HCV. Α (: ΤΒ (β-actin). Total RNA was added to the PCR reaction to quantify HCV and ACTB RNA in the same PCR hole. According to ACTB RNA in each well The experimental failure was marked and discarded. The HCV RNA level in each well was calculated from the standard curve obtained in the same PCR plate. The percent inhibition of HCV RNA level by compound treatment was calculated using DMSO or no compound control as 〇% inhibition. Calculate EC5() based on the titration curve of any given compound (concentration at which HCV RNA levels reach 50% inhibition). The compound 丨_281 was tested in the HCV replicon cell assay. The results showed that 274 compounds had ECso values below 20 nM and 7 compounds had EC50 values between 20 and 100 nM. Example 284: Pharmacokinetic Study One day prior to the experiment, male Sprague-Dawley rats (300-400 g) underwent a jugular vein grafted polyethylene cannula under pentobarbital anesthesia for blood sampling. The rats were fasted overnight with any drinking water, and then the test compound was administered by oral gavage (p〇) the next day. A series of rat blood samples were collected 48 hours after administration, and heparinized plasma was recovered after centrifugation. The test compound in plasma was extracted and assayed by liquid chromatography-mass spectrometry (LC_MS/MS) analysis. Standard pharmacokinetic parameters were evaluated by non-compartmental analysis using WinN〇nlin (version 4 〇, Pharsight, CA, USA). Plasma test 119 201109028 The largest point in the curve of the concentration of the compound versus time is denoted as c a. The apparent final phase elimination (?1/2) is calculated as 1η(2)/λζ, where λζ is the elimination rate constant. The area under the concentration-time curve from the time point of administration to the infinity (AUC^im) was calculated according to the linear trapezoidal rule.

某些本發明的化合物顯示延長的半衰期和大的AIJC 值。其他實施方式說明書中所揭示的所有特徵可以以任意的組合方式結合。說明書中所揭示的各種特徵可以被起到相同、等價或類似目的的特徵代替。因此，除非另外說明，所揭示的各種特徵僅僅是一系列等價或類似特徵的一個例子。通過以上說明，本領域技術人員可以很容易地確定本發明的主要特徵，同時可以在不背離本發明的精神和範圍的前提下，對本發明進行各種改變和改良，以使其適用於各種應用和條件。因此，其他的實施方式也在所附申請專利範圍之内。 I：圖式簡單說明3 (無）【主要元件符號說明】 (無） 120Certain compounds of the invention exhibit extended half-lives and large AIJC values. Other Embodiments All of the features disclosed in the specification can be combined in any combination. The various features disclosed in the specification can be replaced by features that serve the same, equivalent or similar purpose. Accordingly, the various features disclosed are only one example of a series of equivalent or similar features, unless otherwise indicated. From the above description, those skilled in the art can easily determine the main features of the present invention, and various modifications and improvements can be made to the various applications and without departing from the spirit and scope of the invention. condition. Accordingly, other embodiments are also within the scope of the appended claims. I: Simple description of the diagram 3 (none) [Description of main component symbols] (none) 120

Claims

201109028 七、申請專利範圍： 1. 一種以下結構式的化合物：201109028 VII. Patent application scope: 1. A compound of the following structural formula:

其中，心是七、-OH、Cm烷基、Cw烷氧基、C3.1G環烷基、 CM〇雜環烷基、芳基、雜芳基或-Z-R，或-NH-Z-R ;其中R是Η，或者是選自以下的部分：Cm烷基、C3_1G環烷基、CMG雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：il素、硝基、氰基、氨基、C,_6烷基、(^_6烷氧基、C2_6烯基、C2_6炔基、芳基或雜芳基；Z 是-c(o)-、-c(o)o-、-c(o)c(o)o-、 -C(0)C(0)NH-、-C(0)NR，-、-OC(S)-、-C(S)NR’-或 -C(NH)0-，R’是H、Cw烷基、C3.1()環烷基、CM。雜環烷基、芳基或雜芳基； R2是Η，或者是選自以下的部分：Ci_6烷基、C3.10 環烷基、雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：鹵素、硝基、氰基、氨基、CN6烷基、CN6烷氧基、C2.6烯基、C2_6炔基、芳基或雜芳基； A是CH或N ; 121 201109028 U是-Ο-、-NH-、-NH(CO)-、-NHSO-或-NHS02-; W是-(CH2)m-、-NH(CH2)n-、-(CH2)nNH-、-0(CH2)n-、 -(CH2)nO-、-S(CH2)n-、-(CH2)nS-、-SO-、-SO(C:H2)n-、 -(CH2)nSO-、-S02(CH2)n-或-(CH2)nS02-，m是 1, 2 或3，n 是0,]或2 ; X是-Ο-、-S-、-NH-或-OCH2-;Wherein, the heart is seven, -OH, Cm alkyl, Cw alkoxy, C3.1G cycloalkyl, CM〇 heterocycloalkyl, aryl, heteroaryl or -ZR, or -NH-ZR; wherein R Is a hydrazine, or a moiety selected from the group consisting of Cm alkyl, C3_1G cycloalkyl, CMG heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: Il, nitro, cyano, amino, C, _6 alkyl, (^_6 alkoxy, C2_6 alkenyl, C2_6 alkynyl, aryl or heteroaryl; Z is -c(o)-, -c (o)o-, -c(o)c(o)o-, -C(0)C(0)NH-, -C(0)NR,-, -OC(S)-, -C(S )NR'- or -C(NH)0-, R' is H, Cw alkyl, C3.1()cycloalkyl, CM. Heterocycloalkyl, aryl or heteroaryl; R2 is hydrazine, or Is a moiety selected from the group consisting of Ci-6 alkyl, C3.10 cycloalkyl, heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or trisubstituted by halogen: , cyano, amino, CN6 alkyl, CN6 alkoxy, C2.6 alkenyl, C2_6 alkynyl, aryl or heteroaryl; A is CH or N; 121 201109028 U is -Ο-, -NH- , -NH(CO)-, -NHSO- or -NHS02-; W -(CH2)m-, -NH(CH2)n-, -(CH2)nNH-, -0(CH2)n-, -(CH2)nO-, -S(CH2)n-, -(CH2)nS -, -SO-, -SO(C:H2)n-, -(CH2)nSO-, -S02(CH2)n- or -(CH2)nS02-, m is 1, 2 or 3, n is 0, ] or 2 ; X is -Ο-, -S-, -NH- or -OCH2-;

Y是 ^ 或 T ，其中，V和T 各自獨立地是-CH-或-N-;八丨和八2各自獨立地是選自以下的部分：C4.1Q環烷基、Cm〇雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：鹵素、石肖基、氰基、說基、C|.6烧基、Ci-6炫·氧基、C2-6 烯基、C2-6炔基、芳基或雜芳基，或任選與c3_1()環烷基、 CM〇雜‘環烷基、芳基或雜芳基稠合；Ri是Η、鹵素、硝基、氰基或氨基，或者是選自以下的部分：Cw烷基、 C|-6烧氧基、C2-6稀基、（〕2.6快基、C3-H)環烧基、C|.|〇雜環烷基、芳基和雜芳基，CN6烷基、Ck烷氧基、C2.6烯基和C2_6炔基各自任選被以下取代基單取代、二取代或三取代：鹵素、蛾基、氰基、氨基、C|_6院基、Ci_6烧軋基、C2-6稀基、C2-6快基、C3-1G環院基、Ci-io雜環烧基、芳基或雜芳基，c3.1()環烷基、CMG雜環烷基、芳基和雜芳基各自任選被以下取代基單取代、二取代或三取代：鹵素、硝基、氰基、氨基、CN6烷基、c,_6烷氧基、c2.6 122 201109028 烯基、c2_6炔基、c3_1G環烷基、cMG雜環烷基、芳基或雜芳基，或任選與c3_1()環烷基、CMG雜環烷基、芳基或雜芳基稠合；和二^是單鍵或雙鍵。 2. 如申請專利範圍第1項所述的化合物，其特徵在於，X 是0。 3. 如申請專利範圍第1項所述的化合物，其特徵在於，A 是CH，W是-CH2CH2-、-OCH2-、-SCH2-或-SOCH2-。 4. 如申請專利範圍第1項所述的化合物，其特徵在於，A 是N，W是-CH2CH2-、-OCH2-、-SCH2-或-SOCH2-。 5. 如申請專利範圍第1項所述的化合物，其特徵在於，U 是-nhso2-。 6. 如申請專利範圍第1項所述的化合物，其特徵在於，=是雙鍵。 7. 如申請專利範圍第1項所述的化合物，其特徵在於，YY is ^ or T, wherein V and T are each independently -CH- or -N-; and octagonal and octa 2 are each independently selected from the group consisting of C4.1Q cycloalkyl, Cm nonheterocycloalkane a aryl group, an aryl group and a heteroaryl group, each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: halogen, schlossyl, cyano, thiol, C|.6 alkyl, Ci-6 oxi , C2-6 alkenyl, C2-6 alkynyl, aryl or heteroaryl, or optionally fused to c3_1()cycloalkyl, CM〇'cycloalkyl, aryl or heteroaryl; Ri is Anthracene, halogen, nitro, cyano or amino, or a moiety selected from the group consisting of Cw alkyl, C|-6 alkoxy, C2-6 dilute, ()2.6 fast radical, C3-H) a group, a C=. Trisubstituted: halogen, moth, cyano, amino, C|_6, Cu_6 calcined, C2-6, C2-6, C3-1G ring, Ci-io heterocyclic , aryl or heteroaryl, c3.1()cycloalkyl, CMG heterocycloalkyl, aryl and heteroaryl are each optionally substituted by Monosubstituted, disubstituted or trisubstituted: halogen, nitro, cyano, amino, CN6 alkyl, c, -6 alkoxy, c2.6 122 201109028 alkenyl, c2_6 alkynyl, c3_1G cycloalkyl, cMG heterocycle An alkyl group, an aryl group or a heteroaryl group, or optionally fused to a c3_1()cycloalkyl group, a CMG heterocycloalkyl group, an aryl group or a heteroaryl group; and a di- or a single bond or a double bond. 2. The compound according to claim 1, wherein X is 0. 3. The compound according to claim 1, wherein A is CH and W is -CH2CH2-, -OCH2-, -SCH2- or -SOCH2-. 4. The compound according to claim 1, wherein A is N and W is -CH2CH2-, -OCH2-, -SCH2- or -SOCH2-. 5. The compound of claim 1, wherein U is -nhso2-. 6. The compound according to claim 1, wherein = is a double bond. 7. The compound according to claim 1, wherein Y

Riv ，其中，T是 CH或N，且Ri, Rib Rm，Riv 和Rv各自獨立地是Η、鹵素、硝基、氰基、氨基、Q.6 烷基、CV6烷氧基、C2.6烯基或C2.6炔基，或者是選自以下的部分：C3.1()環烷基、CM〇雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：鹵素、破基、氰基、氨基、Ck烧基、CN6烧氧基、C2_6 123 201109028 烯基、c2.6炔基、芳基或雜芳基，或與c3_l()環烷基、CM0 雜環烷基、芳基或雜芳基稠合。 8. 如申請專利範圍第7項所述的化合物，其特徵在於，Ri 是任選被鹵素、氨基、Cm烷基或Cm烷氧基取代的苯基或嘆。坐基。 9. 如申請專利範圍第1項所述的化合物，其特徵在於，R2 是△或△。 10. 如申請專利範圍第9項所述的化合物，其特徵在於，YRiv , wherein T is CH or N, and Ri, Rib Rm, Riv and Rv are each independently oxime, halogen, nitro, cyano, amino, Q.6 alkyl, CV6 alkoxy, C2.6 olefin Or a C2.6 alkynyl group, or a moiety selected from the group consisting of C3.1()cycloalkyl, CM〇heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted by the following substituents, Disubstituted or trisubstituted: halogen, cyclyl, cyano, amino, Ck alkyl, CN6 alkoxy, C2_6 123 201109028 alkenyl, c2.6 alkynyl, aryl or heteroaryl, or with c3_l() ring Alkyl, CM0 heterocycloalkyl, aryl or heteroaryl is fused. 8. The compound according to claim 7, wherein Ri is a phenyl group or a singyl optionally substituted by halogen, amino, Cm alkyl or Cm alkoxy. Sitting on the base. 9. The compound of claim 1, wherein R2 is Δ or Δ. 10. The compound according to claim 9 which is characterized in that Y

是 T ，其中T是CH或N : &是任選被鹵素、氨基、CU6烷基或Cu6烷氧基取代的苯基或噻唑基； Rn, Rm, Riv*Rv各自獨立地是：Η、鹵素、硝基、氰基、氨基、Ci_6烷基、C,_6烷氧基、C2.6烯基或C2_6炔基，或者是選自以下的部分：C3.1()環烷基、C1-10雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：鹵素、墻基、氰基、氨基、C1-6烧基、C:.6 烷氧基、c2_6烯基、c2.6炔基、芳基或雜芳基，或與c3..10 環烷基、CM〇雜環烷基、芳基或雜芳基稠合。 η.如申請專利範圍第1項所述的化合物，其特徵在於，R, 是-NH-Z-R，其中的Ζ是-C(O)-、-C(0)0-、-C(0)C(0)0-或-C(0)C(0)NH-。 12.如申請專利範圍第11項所述的化合物，其特徵在於，:R, 124 201109028 是-NH-C(0)0-t-Bu 或-NH-C(0)0-環戊基。 13.如申請專利範圍第12項所述的化合物，其特徵在於，R2 .CH, 是△或 14.如申請專利範圍第13項所述的化合物，其特徵在於，YIs T, wherein T is CH or N: & is phenyl or thiazolyl optionally substituted by halogen, amino, CU6 alkyl or Cu6 alkoxy; Rn, Rm, Riv*Rv are each independently: Η, Halogen, nitro, cyano, amino, Ci-6 alkyl, C,-6 alkoxy, C2.6 alkenyl or C2-6 alkynyl, or a moiety selected from the group consisting of C3.1()cycloalkyl, C1- 10 heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or trisubstituted by halogen, wall group, cyano group, amino group, C1-6 alkyl group, C:.6 Alkoxy, c2_6 alkenyl, c2.6 alkynyl, aryl or heteroaryl, or fused to c3..10 cycloalkyl, CM〇 heterocycloalkyl, aryl or heteroaryl. The compound according to claim 1, wherein R is -NH-ZR, wherein hydrazine is -C(O)-, -C(0)0-, -C(0) C(0)0- or -C(0)C(0)NH-. 12. The compound according to claim 11, wherein: R, 124 201109028 is -NH-C(0)0-t-Bu or -NH-C(0)0-cyclopentyl. The compound according to claim 12, wherein R 2 .CH is Δ or 14. The compound according to claim 13 is characterized in that Y

是个，其中T是CH或N ; Ri是任選被鹵素、氨基、CN6烷基或Cw烷氧基取代的苯基或噻唑基； RhRiii, Riv*Rv各自獨立地是：H、鹵素、硝基、氰基、氨基、CN6烷基、Cm烷氧基、C2_6烯基或C2.6炔基，或者是選自以下的部分：C3.1G環烷基、C1-10雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：鹵素、瑞基、氰基、氨基、C1.6烧基、C 1 -6 烷氧基、c2_6烯基、c2.6炔基、芳基或雜芳基，或與c3.l0 環烷基、CM〇雜環烷基、芳基或雜芳基稠合。 15. 如申請專利範圍第14項所述的化合物，其特徵在於，X 是 Ο，A 是 CH，W 是-CH2CH2-、-OCH2-、-SCH2-或 -SOCH2- ; U是-nhso2-;二是雙鍵。 16. 如申請專利範圍第11項所述的化合物，其特徵在於，Ri 是-NH-C(O)-呋喃基。 17. 如申請專利範圍第16項所述的化合物，其特徵在於，R2 .CH, 125 201109028 如申請專利範圍第17項所述的化合物，其特徵在於，γIs a wherein T is CH or N; Ri is phenyl or thiazolyl optionally substituted by halogen, amino, CN6 alkyl or Cw alkoxy; RhRiii, Riv*Rv are each independently: H, halogen, nitro , cyano, amino, CN6 alkyl, Cm alkoxy, C2_6 alkenyl or C2.6 alkynyl, or a moiety selected from the group consisting of C3.1G cycloalkyl, C1-10 heterocycloalkyl, aryl And a heteroaryl group, each of which is optionally mono-, di- or tri-substituted with a halogen, ruthenyl, cyano, amino, C1.6 alkyl, C 1 -6 alkoxy, c 2-6 alkenyl, C2.6 alkynyl, aryl or heteroaryl, or fused to c3.10 cycloalkyl, CM〇 heterocycloalkyl, aryl or heteroaryl. 15. The compound of claim 14, wherein X is Ο, A is CH, W is -CH2CH2-, -OCH2-, -SCH2- or -SOCH2-; U is -nhso2-; The second is a double bond. 16. The compound of claim 11, wherein Ri is -NH-C(O)-furanyl. 17. The compound of claim 16, wherein R2.CH, 125 201109028 is a compound according to claim 17, characterized in that γ

素、氨基、C!·6烷基或CM,烧氧基取代的苯基或噻唑基； Rii, Rm，RiV和Rv各自獨立地是：Η、鹵素、石肖基、氰基、氨基、Ci·6炫基、C,_6烷氧基、c2-6稀基或C2-6炔基，或者是選自以下的部分：C3-IG環烷基、C1-10雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：齒素、硝基 '氰基、氨基、Ci 6烷基、C| 6 烧氧基、C2·6烯基、C2·6炔基、芳基或雜芳基，或與c3l〇 %·院基、C|.1Q雜環烧基、芳基或雜芳基稍合。 19.如申請專利範圍第18項所述的化合物，其特徵在於，X 是〇，A 是 CH，W 是 _CH2CH2-、_OCH2-、-SCH2-或 -soch2- ; U是-nhso2-;=是雙鍵。 2〇.如申請專利範圍第1項所述的化合物，其特徵在於，γ 是以下化合物：Amino, C, 6 alkyl or CM, alkoxy substituted phenyl or thiazolyl; Rii, Rm, RiV and Rv are each independently: fluorene, halogen, schlossyl, cyano, amino, Ci·6 Hyun, C, -6 alkoxy, c2-6 or C2-6 alkynyl, or a moiety selected from the group consisting of C3-IG cycloalkyl, C1-10 heterocycloalkyl, aryl and heteroaryl And each of them is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: dentate, nitro 'cyano, amino, Ci 6 alkyl, C| 6 alkoxy, C 2 · alkenyl, C 2 · 6 alkynyl, aryl or heteroaryl, or slightly coincident with c3l%, a C|.1Q heterocycloalkyl, aryl or heteroaryl. 19. The compound according to claim 18, wherein X is 〇, A is CH, W is _CH2CH2-, _OCH2-, -SCH2- or -soch2-; U is -nhso2-; It is a double bond. The compound according to claim 1, wherein γ is the following compound:

126 201109028126 201109028

RiiRii

Rvi Rv 其中，Ri ’ Rii，Riii，Riv，Hv和Rvi各自獨立地是：H、 _素、确基、氰基、氨基、Ci6院基、Ci 6烧氧基、C26 烯基、C：2·6炔基、（：3_10環烷基、Ci i〇雜環烷基、芳基或雜芳基，環烷基、雜環烷基、芳基或雜芳基各自任選被以下取代基單取代、二取代或三取代：_素、硝基、氰基、氨基、Cw炫基、c,.6院氧基、c2 6稀基、c2 6炔基、方基或雜芳基，或與C3-10環烷基、CMG雜環烷基、芳基或雜芳基祠合。 21·如申請專利範圍第20項所述的化合物，其特徵在於，Ri 是以下化合物 127 201109028Rvi Rv wherein Ri' Rii, Riii, Riv, Hv and Rvi are each independently: H, _, cis, cyano, amino, Ci6, Ci 6 alkoxy, C26 alkenyl, C: 2 • 6 alkynyl, (: 3-10 cycloalkyl, Ci i 〇 heterocycloalkyl, aryl or heteroaryl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl each optionally substituted by the following substituents Substituted, disubstituted or trisubstituted: _, nitro, cyano, amino, Cw decyl, c, .6 oxime, c 2 6 dilute, c 2 6 alkynyl, aryl or heteroaryl, or A C3-10 cycloalkyl group, a CMG heterocycloalkyl group, an aryl group or a heteroaryl group. 21. The compound according to claim 20, wherein Ri is the following compound 127 201109028

其中，η為1或2。 22. 如申請專利範圍第1項所述的化合物，其特徵在於，所述化合物是化合物1-281中的一種化合物。 23. —種藥物組合物，其包含申請專利範圍第1項所述的化合物以及藥學上可接受的載體。 24. —種治療丙型肝炎病毒感染的方法，該方法包括給予需要的對象一種包含有效量的如申請專利範圍第1項所述的化合物的藥物組合物。 25. 如申請專利範圍第24項所述的方法，其特徵在於，所述組合物一天給予對象一次。 26. 如申請專利範圍第25項所述的方法，其特徵在於，所述組合物通過口服給予。 27. 如申請專利範圍第24項所述的方法，其特徵在於，所述化合物是化合物1 -281中的一種化合物。 128 201109028 四、指定代表圖： (一) 本案指定代表圖為：第（）圖。（無) (二) 本代表圆之元件符號簡單說明：五、本案若有化學式時，請揭示最能顯示發明特徵的化學式：Where η is 1 or 2. 22. The compound of claim 1, wherein the compound is a compound of the compound 1-281. 23. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier. 24. A method of treating a hepatitis C virus infection, the method comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition according to the compound of claim 1 of the patent application. 25. The method of claim 24, wherein the composition is administered to the subject once a day. 26. The method of claim 25, wherein the composition is administered orally. 27. The method of claim 24, wherein the compound is a compound of compound 1-281. 128 201109028 IV. Designated representative map: (1) The representative representative of the case is: ( ). (None) (2) A brief description of the symbol of the representative circle: 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention:

201109028 第98131053號申請案申請專利範圍修正本修正日：99卑3月七、申請專利範圍： 1· 一種以下結構式的化合物：201109028 Application No. 98131053 Application for Patent Scope Amendment Revision Date: 99 Hidden March VII. Patent Application Range: 1. A compound of the following structural formula:

其中， Ri是-H、-OH、Cy烷基、(^_6烷氧基、c3_1G環烷基、CU1() 雜環烷基、芳基、雜芳基或—NH-Z-R ;其中R是H，或者是選自以下的部分：Q·6烷基、(：3_1()環烷基、Cmq雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：鹵素、硝基、氰基、氨基、cU6烷基、α6烷氧基、c2-6 烯基、C2.6炔基、芳基或雜芳基；Z是-C(o)-、-C(0)0-、 -C(0)c(0)0-、-C(0)C(0)NH-、-C(0)NR，-、-〇C(S)-、-C(S)NR，-或-C(NH)〇- ’ R’是H、Cw烷基、C3_1()環烷基、Cw。雜環烷基、芳基或雜芳基； &是H，或者是選自以下的部分：CU6烧基、C3_1()環烧基、 Cho雜環烧基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：鹵素、硝基、氰基、氨基、Cl_6 烷基、Cm烷氧基、C2_6烯基、C2-6炔基、芳基或雜芳基； A是N或CH ; U是-〇-、-NH-、-NH(CO)-、-NHSO-或_NHS02-; W 是-(CH2)m-、-NH(CH2)n-、-(CH2)nNH-、-〇(CH2)n-、 121 201109028 -(CH2)n〇. , -S(CH2)n- ^ >(CH2)nS- ^ -SO- ^ -SO(CH2)n- > -(cH2)nS〇-. -S02(CH2)n^_(CH2)nS〇2., m^1? 2^3 , n^〇5 { 或2 ; X為-〇·、_s---NH-或_〇ch2-;和Wherein Ri is -H, -OH, Cy alkyl, (^_6 alkoxy, c3_1G cycloalkyl, CU1()heterocycloalkyl, aryl, heteroaryl or -NH-ZR; wherein R is H Or a moiety selected from the group consisting of Q.6 alkyl, (:3_1()cycloalkyl, Cmq heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted by the following substituents Or trisubstituted: halogen, nitro, cyano, amino, cU6 alkyl, a6 alkoxy, c2-6 alkenyl, C2.6 alkynyl, aryl or heteroaryl; Z is -C(o)- , -C(0)0-, -C(0)c(0)0-, -C(0)C(0)NH-, -C(0)NR,-, -〇C(S)-, -C(S)NR,- or -C(NH)〇- 'R' is H, Cw alkyl, C3_1()cycloalkyl, Cw.heterocycloalkyl, aryl or heteroaryl; & H, or a moiety selected from the group consisting of CU6 alkyl, C3_1 () cycloalkyl, Cho heterocycloalkyl, aryl and heteroaryl, each of which is optionally mono-, di- or tri-substituted by the following substituents : halogen, nitro, cyano, amino, Cl_6 alkyl, Cm alkoxy, C2_6 alkenyl, C2-6 alkynyl, aryl or heteroaryl; A is N or CH; U is -〇-, - NH-, -NH(CO)-, -NHSO- or _NHS02-; W is -(CH2)m- -NH(CH2)n-, -(CH2)nNH-, -〇(CH2)n-, 121 201109028 -(CH2)n〇. , -S(CH2)n- ^ >(CH2)nS- ^ - SO-^-SO(CH2)n- > -(cH2)nS〇-. -S02(CH2)n^_(CH2)nS〇2., m^1? 2^3 , n^〇5 { or 2 ; X is -〇·, _s---NH- or _〇ch2-; and

，其中，V和T各自獨立地是_CH_或_N_ ; Αι和A2各自獨立地是選自以下的部分：C4-1G環烷基、(:㈣雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：_素、硝基、氛基、氨基、Q-6烷基、Cl_6烷氧基、（:2_6烯基、c2 6炔基、芳基或雜芳基，或任選與C3_1G環烷基、(^七雜環烷基、芳基或雜芳基稠合；Ri是Η、_素、硝基、氰基或氨基，或者是選自以下的部分：Cw烷基' Cl_6烷氧基、C26烯基、C26炔基、 Cwo環烧基、（:]_10雜環烷基、芳基和雜芳基’ Ci 6烷基、Ci 6 烷氧基、CM烯基和CM炔基各自任選被以下取代基單取代、二取代或三取代：i素、石肖基、氰基、氨基、Ci 6院基、Q 6 院氧基、c2_6稀基、c2_6块基、C31G環院基' Ci iD雜環烷基、芳基或雜芳基，Q.丨Q環烷基、CMG雜環烷基、芳基和雜芳基各自任選被以下取代基單取代、二取代或三取代：齒素、硝基、氰基、氨基、C】-6烧基、CV6烧氧基、c2.6稀基、c2 6块基、 C^o環烷基、CMG雜環烷基、芳基或雜芳基，或任選與環烷基、(^-⑴雜環烷基、芳基或雜芳基稠合。 2.如申請專利範圍第！項所述的化合物，其特徵在於，X是〇。 122 201109028 3. 如申請專利範圍第1或2項所述的化合物，其特徵在於，Α是 CH，W是-CH2CH2-、-OCHr、-SCH2-或-SOCH2-。 4. 如申請專利範圍第1-3項中任一項所述的化合物，其特徵在於，U是-NHSOr。 5.如申請專利範圍第1-4項中任一項所述的化合物，其特徵在Wherein V and T are each independently _CH_ or _N_; Αι and A2 are each independently selected from the group consisting of C4-1G cycloalkyl, (:(tetra)heterocycloalkyl, aryl and heteroaryl) Each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: _, nitro, aryl, amino, Q-6 alkyl, Cl-6 alkoxy, (: 2-6 alkenyl, c2 6 alkyne a aryl group, an aryl group or a heteroaryl group, or optionally fused to a C3_1G cycloalkyl group, a (hetero-7 heterocycloalkyl group, an aryl group or a heteroaryl group; Ri is a hydrazine, a hydrazine, a nitro group, a cyano group or an amino group, Or a moiety selected from the group consisting of Cw alkyl 'Cl_6 alkoxy, C26 alkenyl, C26 alkynyl, Cwo cycloalkyl, (:]-10 heterocycloalkyl, aryl and heteroaryl 'Ci6 alkyl Each of Ci 6 alkoxy, CM alkenyl and CM alkynyl is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: i, schwitz, cyano, amino, Ci 6, Q 6 , c2_6 dilute group, c2_6 block group, C31G ring-based group 'Ci iD heterocycloalkyl group, aryl or heteroaryl group, Q.丨Q cycloalkyl group, CMG heterocycloalkyl group, aryl group and heteroaryl group Monosubstituted, disubstituted or trisubstituted by the following substituents: , nitro, cyano, amino, C]-6 alkyl, CV6 alkoxy, c2.6 dilute, c2 6 block, C^o cycloalkyl, CMG heterocycloalkyl, aryl or hetero An aryl group, or optionally fused to a cycloalkyl group, a (^-(1)heterocycloalkyl group, an aryl group or a heteroaryl group. 2. A compound according to claim </RTI> wherein X is hydrazine. The compound according to claim 1 or 2, wherein Α is CH, W is -CH2CH2-, -OCHr, -SCH2- or -SOCH2-. 4. Patent application scope The compound of any one of the preceding claims, wherein U is -NHSOr.

R匕R匕

Ο ，其中，T是CH或N，且Rb Rib Riii，和Rv各自獨立地是η、鹵素、確基、氣基、氨基、（^_6烧基、C!_6烧氧基、C2-6晞基或C2-6炔基，或者是選自以下的部分.匸3_1()環烧基、雜環烧基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：_素、硝基、氰基、氣基、Ci_6烧基、〇μ6烧氧基、C2-6烯基、C2-6快基、芳基或雜芳基，或者任選與C3_1()環烷基、Ckk)雜環烷基、芳基或雜方基稠合。 6. —種以下結構式的化合物：Ο , wherein T is CH or N, and Rb Rib Riii, and Rv are each independently η, halogen, exact, gas, amino, (^_6 alkyl, C!-6 alkoxy, C2-6晞Or a C2-6 alkynyl group, or a moiety selected from the group consisting of 匸3_1()cycloalkyl, heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or Trisubstituted: _, nitro, cyano, carbyl, Ci_6 alkyl, 〇μ6 alkoxy, C2-6 alkenyl, C2-6 fast radical, aryl or heteroaryl, or optionally with C3_1 ( A cycloalkyl, Ckk) heterocycloalkyl, aryl or heteroaryl group is fused. 6. - Compounds of the following structural formula:

Rl是-H、-OH、Q_6烷基、Cn6烷氧基、Cy。環烷基、Cw 雜環烧基、芳基、雜芳基或-Z-R;其中R是Η，或者是選自以 123 201109028 下的部分：Q.成基、w魏基、Q•邊環院基、芳基和雜芳基’它們各自任選独下取絲單取代、二取代或三取代肖基、氛基、氨基、Ci•濃基、&烧氧基、CM 烯基、‘块基、芳基或雜芳基；2是（⑼_、_c(〇)〇_、 -C(0)C(0)0-、-C(0)C(0)NH-、-C(〇)NR，_、_0C⑻_、_ C(S)NR’-或-C_〇-，R，是Η、Ci 6院基、Q i〇我基、C, a 雜環烷基、芳基或雜芳基；R1 is -H, -OH, Q_6 alkyl, Cn6 alkoxy, Cy. Cycloalkyl, Cw heterocycloalkyl, aryl, heteroaryl or -ZR; wherein R is deuterium or is selected from the group under 123 201109028: Q. Alkyl, aryl and heteroaryl' each of which is optionally taken to monosubstituted, disubstituted or trisubstituted Schottyl, aryl, amino, Ci•concentrator, &oxyalkyl, CM alkenyl, 'block Base, aryl or heteroaryl; 2 is ((9)_, _c(〇)〇_, -C(0)C(0)0-, -C(0)C(0)NH-, -C(〇) NR, _, _0C(8)_, _ C(S)NR'- or -C_〇-, R, is Η, Ci 6 院, Q i〇, C, a heterocycloalkyl, aryl or heteroaryl base;

R2是Η ’或者是選自以下的部分：& *絲、C3i。環烧基、 C丨-丨。雜ί衷烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：録、赫、氰基、氨基、C“6 烧基、Ci.6烧氧基、（：2.6稀基、C26炔基、芳基或雜芳基； A是CH或N ; U是-Ο-、-NH-、-NH(CO)-、-NHSO-或-NHS02-; W 是-(CH2)m-、-NH(CH2)n-、-(CH2)nNH-、-〇(CH2)n-、R2 is Η ' or a portion selected from the following: & * silk, C3i. Ring-burning, C丨-丨. An alkyl group, an aryl group, and a heteroaryl group, each of which is optionally monosubstituted, disubstituted or trisubstituted by a substituent: hexa, cyano, amino, C"6 alkyl, Ci.6. a group, (: 2.6 dilute, C26 alkynyl, aryl or heteroaryl; A is CH or N; U is -Ο-, -NH-, -NH(CO)-, -NHSO- or -NHS02-; W is -(CH2)m-, -NH(CH2)n-, -(CH2)nNH-, -〇(CH2)n-,

-(CH2)nO- > -S(CH2)n- > -(CH2)nS- ' -SO- ' -SO(CH2)n- > -(CH2)nSO-、-S02(CH2)n-或_(CH2)nS〇2_，m是 i，2 或3，^〇, ！或2 ; X是-O-、-S-、-NH-或-〇CHr ;-(CH2)nO- > -S(CH2)n- > -(CH2)nS- ' -SO- ' -SO(CH2)n- > -(CH2)nSO-, -S02(CH2)n -or _(CH2)nS〇2_,m is i,2 or 3,^〇, ! Or 2; X is -O-, -S-, -NH- or -〇CHr;

其中，V和T各自獨立地是-CH-或-N- ; Aj〇A2各自獨立地是選自以下的部分：Q-m環烷基、CMQ雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：_素、硝基、 124 201109028 氰基、氣基、Cl·6院基、C!_6烧氧基、C2·6浠基、C2-6块基、芳基或雜芳基，或任選與C3_1G環烷基、Cmo雜環烷基、芳基或雜^•基稠合，Ri是Η、_素、硝基、氰基或氨基，或者是選自以下的部分：（：“烷基、C〗_6烷氧基、CM烯基、C2_6快基、 C3-l〇環烧基、Cl-IQ雜環烧基、芳基和雜芳基，CN6燒基、C16 烷氧基、C2·6烯基和C2·6炔基各自任選被以下取代基單取代、二取代或三取代：i素、硝基、氰基、氨基、Cl_6烷基、Cm 〇院氧基、C2·6烯基、Gw炔基、Cwq環烧基、cM()雜環院基、芳基或雜芳基，Cwg環烷基、CM〇雜環烷基、芳基和雜芳基各自任選被以下取代基單取代、二取代或三取代：南素、硝基、氰基、氨基、Cw焼基、C,_6烧氧基、c^6烯基、c2 6块基、 C3-i〇環烧基、CuH)雜環烧基、芳基或雜芳基，或任選與q %院基、Cuo雜環炫《基、芳基或雜芳基稍合；和 =是單鍵或雙鍵。Wherein V and T are each independently -CH- or -N-; Aj〇A2 are each independently selected from the group consisting of Qm cycloalkyl, CMQ heterocycloalkyl, aryl and heteroaryl, each of which Optionally, monosubstituted, disubstituted or trisubstituted by the following substituents: _, nitro, 124 201109028 cyano, gas, Cl.6, C!-6 alkoxy, C2·6 fluorenyl, C2- a 6-based, aryl or heteroaryl group, or optionally fused to a C3_1G cycloalkyl, Cmo heterocycloalkyl, aryl or hetero group, Ri is a hydrazine, a hydrazine, a nitro group, a cyano group or an amino group Or a moiety selected from the group consisting of: (""alkyl, C"-6 alkoxy, CM alkenyl, C2_6 fast radical, C3-l〇cycloalkyl, Cl-IQ heterocycloalkyl, aryl and hetero The aryl group, the CN6 alkyl group, the C16 alkoxy group, the C2·6 alkenyl group and the C2·6 alkynyl group are each optionally monosubstituted, disubstituted or trisubstituted by the following substituents: i, nitro, cyano, amino, Cl_6 alkyl, Cm oxime oxime, C2·6 alkenyl, Gw alkynyl, Cwq cycloalkyl, cM()heterocyclic, aryl or heteroaryl, Cwg cycloalkyl, CM 〇 heterocycloalkane The aryl group, the aryl group and the heteroaryl group are each optionally substituted by the following substituents, Substituted or trisubstituted: south, nitro, cyano, amino, Cw fluorenyl, C, -6 alkyloxy, c^6 alkenyl, c2 6 block, C3-i fluorene, CuH) heterocycle An alkyl, aryl or heteroaryl group, or optionally a slight combination with a q% phenyl group, a Cuo heterocyclic group, a aryl group or a heteroaryl group; and = is a single bond or a double bond.

9. 如申请專利範圍第6項所述的化合物，其特徵在於，X是〇。如申請專利範圍第6或7項所述的化合物，其特徵在於，〜是 -CH2CHr、-〇CH2-、-SCH2-或-S〇CHr ;二是雙鍵。如申請專利範圍第6-8項中任一項所述的化合物，其特徵在於，U是-NHSOr。如申請專魏圍第6·9項中任-項所_化合物，其特徵在9. The compound of claim 6, wherein X is hydrazine. The compound according to claim 6 or 7, wherein - is -CH2CHr, -〇CH2-, -SCH2- or -S〇CHr; and the second is a double bond. The compound according to any one of claims 6-8, wherein U is -NHSOr. For example, if you apply for a special compound in Weiwei, No. 6/9, the compound is characterized by

125 10. 201109028 Riv和Rv各自獨立地是H、_素、硝基、氰基、氨基、C, 6貌土 1 6’元氣基C：2·6稀基或C2_6块基，或者是選自以下的部刀310衣燒基、CM0雜環烧基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：齒素硝基、氰基、氨基' cN6絲、氧基、C2 6烯基、C26块基、芳基或雜芳基’或與C31G魏基、Q讀觀基、絲或雜芳基稠合。 11. 一種以下結構式的化合物：125 10. 201109028 Riv and Rv are each independently H, _, nitro, cyano, amino, C, 6, 1 6', gas, C: 2·6 or C 2-6, or selected from The following knife 310 is a decyl group, a CM0 heterocycloalkyl group, an aryl group and a heteroaryl group, each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: dentate nitro, cyano, amino 'cN6 A silk, an oxy group, a C2 6 alkenyl group, a C26 block group, an aryl group or a heteroaryl group' is fused to a C31G-Weiyl group, a Q-reading group, a silk or a heteroaryl group. 11. A compound of the formula:

其中， Ritc H -oh、c〗_6烧基、c丨·6炫氧基、C3_丨〇環:)¾基、Cmo 雜王哀烷基、芳基、雜芳基、-Z-R或-NH-Z-R ;其中R是η，或者是選自以下的部分：Ci6烧基、c㈣環烷基、Cii。雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：_素、石肖基、氰基、氨基、Q.6烧基、CV6炫氧基、 C2-6烯基、C2_6炔基、芳基或雜芳基；z是_c(0)_、_c(〇)〇_、 -C(0)C(0)0- ^ -C(0)C(0)NH- ' -C(0)NR,- ' -OC(S)- ' -C(S)NR’-或_c(NH)〇-，r，是h、Cm烧基、〔3_ι〇5果烧基、Ci-io 雜環烷基、芳基或雜芳基； A是N或CH ; 201109028 υ是-Ο-、-ΝΗ·、-NH(CO)-、-NHSO-或-NHS〇2-; W 是-(CH2)m-、-NH(CH2)n-、-(CH2)nNH-、-〇(CH2)n-、 _(CH2)nO-、-S(CH2)n-、-(CH2)nS-、-SO-、，SO(CH2)n-、 -(CH2)nSO-、-S02(CH2)n-或-(CH2)nS02-，m是 1，2 或3，n是〇, 1或2 ; X是-Ο-、-S-、-NH-或-0CHr ; ΟWherein, Ritc H -oh, c _6 alkyl, c丨·6 methoxy, C3_丨〇:) 3⁄4, Cmo, alkyl, aryl, heteroaryl, -ZR or -NH -ZR; wherein R is η or a moiety selected from the group consisting of Ci6 alkyl, c(tetra)cycloalkyl, Cii. Heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: _, succinyl, cyano, amino, Q.6 alkyl, CV6 methoxy, C2-6 alkenyl, C2_6 alkynyl, aryl or heteroaryl; z is _c(0)_, _c(〇)〇_, -C(0)C(0)0-^-C(0) C(0)NH- '-C(0)NR,- '-OC(S)- '-C(S)NR'- or _c(NH)〇-,r, is h, Cm alkyl, 3_ι〇5 fruit alkyl, Ci-io heterocycloalkyl, aryl or heteroaryl; A is N or CH; 201109028 υ is -Ο-, -ΝΗ·, -NH(CO)-, -NHSO- or -NHS〇2-; W is -(CH2)m-, -NH(CH2)n-, -(CH2)nNH-, -〇(CH2)n-, _(CH2)nO-, -S(CH2) N-, -(CH2)nS-, -SO-,,SO(CH2)n-, -(CH2)nSO-, -S02(CH2)n- or -(CH2)nS02-,m is 1,2 or 3, n is 〇, 1 or 2; X is -Ο-, -S-, -NH- or -CHr; Ο

，其中，V和T各, where V and T are each

自獨立地是-CH-或-N-;八丨和八2各自獨立地是選自以下的部分.C4-IO環烧基、Cw雜環烧基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：函素、硝基、氰基、氨基、Q_6烷基、Q-6烷氧基、C2-6烯基、C2_6炔基、芳基或雜芳基，或任選與C3.1()環烷基、雜環烷基、芳基或雜芳基稠合；Ri是Η、鹵素、硝基、氰基或氨基，或者是選自以下的部分：CN6烷基、Cw烷氧基、C2-6烯基、C2_6炔基、匸3-10續烧基、Ci-i〇雜環烧基、芳基和雜芳基，Ci-6燒基、Ci_6 烷氧基、C2_6烯基和(：2_6炔基各自任選被以下取代基單取代、二取代或三取代：齒素、硝基、氰基、氨基、(:!_6烷基、Cl 6 貌氧基、C2-6烯基、C2·6快基、C3-10環烧基、Ci_1G雜環烧基、芳基或雜芳基，C3.1Q環院基、Q.w雜環烧基、芳基和雜芳基各自任選被以下取代基單取代、二取代或三取代：_素、硝基、氰基、I基、Ci.6烧基、Ci.6烧氧基、C2-6稀基、C2-6炔基、 C3-U)環烷基、Q-U)雜環烷基、芳基或雜芳基，或任選與C31() 127 201109028 環烷基、(:MG雜環烷基、芳基或雜芳基稠合；和二^是單鍵或雙鍵。 12_如申請專利範圍第丨丨項所述的化合物，其特徵在於，X是〇。 13. 如申請專利範圍第丨丨或^項所述的化合物，其特徵在於，a 是CH ; W是-CH2CH2-、-〇CHr、-SCHr或-SOCH2-;心是雙鍵。 14. 如申請專利範圍第1 M3項中任一項所述的化合物，其特徵在於，U是-nhso2-。 15. 如申請專利範圍第ιι_14項中任一項所述的化合物，其特徵在於，Υ是个From independently -CH- or -N-; octagonal and octa 2 are each independently selected from the group consisting of C4-IO cycloalkyl, Cw heterocycloalkyl, aryl and heteroaryl, each of which Monosubstituted, disubstituted or trisubstituted by the following substituents: a cyclin, a nitro group, a cyano group, an amino group, a Q-6 alkyl group, a Q-6 alkoxy group, a C2-6 alkenyl group, a C2-6 alkynyl group, an aryl group or a hetero group. An aryl group, or optionally fused to a C3.1()cycloalkyl, heterocycloalkyl, aryl or heteroaryl group; Ri is an anthracene, a halogen, a nitro group, a cyano group or an amino group, or is selected from the group consisting of Part: CN6 alkyl, Cw alkoxy, C2-6 alkenyl, C2_6 alkynyl, 匸3-10 decyl, Ci-i 〇 heterocycloalkyl, aryl and heteroaryl, Ci-6 alkyl Each of Ci_6 alkoxy, C2_6 alkenyl and (:2_6 alkynyl) is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: dentate, nitro, cyano, amino, (:!_6 alkyl, Cl 6 morphineoxy, C2-6 alkenyl, C2·6 fast radical, C3-10 cycloalkyl, Ci_1G heterocycloalkyl, aryl or heteroaryl, C3.1Q ring, Qw heterocycloalkyl, Each of the aryl and heteroaryl groups is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: _, nitro Cyano, I-based, Ci.6 alkyl, Ci.6 alkoxy, C2-6, C2-6 alkynyl, C3-U)cycloalkyl, QU)heterocycloalkyl, aryl or hetero An aryl group, or optionally fused to a C31() 127 201109028 cycloalkyl group, (: MG heterocycloalkyl, aryl or heteroaryl group; and bis is a single bond or a double bond. The compound according to the above item, wherein X is hydrazine. 13. The compound according to claim </RTI> or wherein the a is CH; W is -CH2CH2-, -〇CHr And -SCHr or -SOCH2-; the heart is a double bond. 14. The compound according to any one of claims 1 to 3, wherein U is -nhso2-. 15. Patent Application No. ιι_14 The compound according to any one of the preceding claims, wherein

，其中，Τ是CH或Ν，且Rb Rib R Riv和Rv各自獨立地是Η、鹵素、硝基、氰基、氨基、ci6燒基、烧氧基、C2·6烯基或c：2·6炔基，或者是選自以下的部分：C3.1()環烷基、Cwo雜環烷基、芳基和雜芳基，它們各自任選被以下取代基單取代、二取代或三取代：函素、硝基、氰基、氨基、Q_6烷基、Cw烷氧基、c2-6烯基、c2_6炔基、芳基或雜芳基，或任選與<:3_1()環烷基、C1_1()雜環烷基、芳基或雜芳基稠合。 16. —種化合物，所述化合物丨_281中的一種化合物。 Π_ —種藥物組合物，其包含申請專利範圍第卜^項中任—項所述的化合物以及藥學上可接受的载體。 18.如申請專利範圍第1-16項中任—項所述的化合物用於治療丙 128 201109028 型肝炎病毒感染的用途。 19. 如申請專利範圍第18項所述的用途，其特徵在於，所述化合物通過口服給予需要治療的對象。 20. 如申請專利範圍第卿9項所述的用途，其特徵在於，所述化合物一天給予一次。 21. 如申請專利範圍第1-16項中任一項所述的化合物在製備用於治療丙型肝炎病毒感染的藥物中的應用。〇Wherein, Τ is CH or Ν, and Rb Rib R Riv and Rv are each independently oxime, halogen, nitro, cyano, amino, ci6 alkyl, alkoxy, C2·6 alkenyl or c:2. Alkynyl, or a moiety selected from the group consisting of C3.1()cycloalkyl, Cwoheterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents : a lignin, a nitro group, a cyano group, an amino group, a Q_6 alkyl group, a Cw alkoxy group, a c2-6 alkenyl group, a c2_6 alkynyl group, an aryl group or a heteroaryl group, or optionally with a <:3_1() naphthenic group The group, C1_1() heterocycloalkyl, aryl or heteroaryl is fused. 16. A compound, a compound of the compound 丨 281. A pharmaceutical composition comprising a compound according to any one of the claims and a pharmaceutically acceptable carrier. 18. The use of a compound according to any one of claims 1 to 16 for the treatment of a hepatitis C virus infection of hepatitis C 201109028. 19. The use according to claim 18, wherein the compound is administered orally to a subject in need of treatment. 20. The use of claim 9, wherein the compound is administered once a day. The use of a compound according to any one of claims 1 to 16 for the preparation of a medicament for the treatment of hepatitis C virus infection. 〇

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