TW520362B - Substituted pyrimidine compounds and pharmaceutical composition comprising same - Google Patents

Substituted pyrimidine compounds and pharmaceutical composition comprising same Download PDF

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TW520362B
TW520362B TW086118244A TW86118244A TW520362B TW 520362 B TW520362 B TW 520362B TW 086118244 A TW086118244 A TW 086118244A TW 86118244 A TW86118244 A TW 86118244A TW 520362 B TW520362 B TW 520362B
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amino
fluorophenyl
pyridyl
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phenyl
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TW086118244A
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Chinese (zh)
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Ulrike D Spohr
Michael J Malone
Nathan B Mantlo
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Amgen Inc
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    • C07D487/04—Ortho-condensed systems

Abstract

Selected novel substituted pyridine compounds are effective for prophylaxis and treatment of diseases, such as TNF-Α IL-β IL-6 and/or IL-8 mediated diseases, and other maladies, such as pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, pain, diabetes and the like. The subject invention also relates, to processes for making such compounds as well as to intermediates useful in such processes.

Description

DZUJOZ 五、發明説明（1 ) 本發明包括-類新穎化合物可用於 …W…及/或工"媒介之疾病， 丄如T: 疼痛及糖尿病。特別，本發明化合物可用= 涉發炎之疾病或病情。本發明 、"万及>0潦牵 合物之中間物及方法。耗關於可用於製備此等化 人^白素-叫-D及腫瘤壞死因子α(脈α)爲多種細胞包 3早核細胞及巨噬細胞，回應於多種發炎刺激(例如脂多醣 -LPS)或胞外應力（例如滲透壓衝擊及過氧化物）分泌的發炎 前期細胞激素。 TNF-α及/或IL-1比較基礎濃度升高涉及媒介或惡化多種 疾病狀態包含類風濕性關節炎；巴吉特氏（pagets)病；鬆骨 病；多發性骨髓瘤；葡萄膜炎；急性及慢性骨髓原性白血 病；胰臟β細胞破壞；骨關節炎；類風濕性脊椎炎；痛風性 關節炎；發炎性腸病；成人呼吸窘迫症候群（ARDS);乾癬 ’柯恩氏（Crohn’s)病；過敏性鼻炎；潰瘍性結腸炎；無防 衛性過敏（anaphylaxis) ·，接觸性皮炎；氣喘；肌肉退化； 經濟部中央標準局員工消費合作社印製 惡病質；莱特氏（Reiter’s)症候群；第I型及第η型糖尿病 •’骨質吸收病；移植物對寄主反應；缺血再灌流傷害；動 脈粥瘤硬化；腦創傷；多發性硬化；腦癔；敗血病；敗血 性休克；中毒性休克症候群；發燒，及感染引起肌痛。HIV-1 ，HIV_2，HIV_3，細胞巨病毒（CMV)”流行性感冒病毒 ，腺病毒，疱疹病毒（包含HSV-1，HSV-2)，及帶狀苑療 也因TNF-α而惡化。 520362 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（2 ) 據報告，TNF-α於頭部創傷，中風及缺血扮演某種角色 。例如，於頭部創傷之動物模式（大鼠）中，TNF-a濃度於挫 傷的腦半球升高（Shohami et al.，J. Ceieb. Blood Flow Metab. 14，615(1994))。於大鼠缺血模式中，中腦動脈阻 塞，TNF-α之 TNF-α mRNA 濃度升高（Feursteill et al.， Neurosci. Lett. 164，125 (1993))。TNF_a投予大鼠腦皮質 具報告可導致微血管顯著嗜中性細胞堆積並黏著於小血管 。TNF-a可促進其它細胞激素（IL-Ιβ，IL-6)浸潤，也促進 化學激素浸潤，化學激素可促進嗜中性細胞浸潤於梗塞區 (Feurstein，Stroke 25，1481 (1994))。TNF-a也於第 II 型 糖尿病扮演某種角色（Endocrinol. 130，43-52，1994 ;及 Endocrinol. 136，1474-1481，1995) 〇 TNF-a顯然對促進某些病毒生命周期及其相關疾病狀態 扮演某種角色。例如，單核細胞分泌的TNF-a於慢性感染T 細胞種系謗使HIV表現程度升高（Clouse et al.， J. Immunol. 142 ’ 43 1 (1989))。Lahdevirta 等（Am· J· Med. 85 ，289 (1988))討論TNF-α於HIV引起惡病質及肌肉退化狀 態之角色。 TNF-a位於發炎之細胞激素串級上游。結果，TNF-a濃度 升高可能導致其它發炎及發炎前期細胞激素濃度升高，例 如 IL-1，IL-6 及 IL-8。 IL-1濃度比較基礎濃度升高涉及媒介或惡化多種疾病狀 悲包含類風濕性關節炎；骨關節炎；類風濕性脊椎炎；痛 風性關節炎；發炎性腸病；成人呼吸窘迫症候群（ARDS); (請先閱讀背面之注意事項再填寫本頁) 訂 -ml I I— ·i ·DZUJOZ V. Description of the invention (1) The present invention includes novel compounds which can be used in ...... and / or industrial diseases, such as T: pain and diabetes. In particular, the compounds of the invention are useful = diseases or conditions involving inflammation. The present invention, " Wan > 0 " intermediates and methods. It can be used to prepare such humanized human leukin-d-D and tumor necrosis factor α (vein α) into a variety of cells including 3 early nuclear cells and macrophages in response to various inflammatory stimuli (such as lipopolysaccharide-LPS) Or extracellular stress (such as osmotic shock and peroxide) secreted pre-inflammatory cytokines. Increased basal concentrations of TNF-α and / or IL-1 involve mediators or worsen a variety of disease states including rheumatoid arthritis; Pagets' disease; osteoporosis; multiple myeloma; uveitis; Acute and chronic myelogenous leukemia; destruction of pancreatic beta cells; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; adult respiratory distress syndrome (ARDS); psoriasis' Crohn's Disease; allergic rhinitis; ulcerative colitis; non-defensive allergy (anaphylaxis); contact dermatitis; asthma; muscle degeneration; cachexia printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs; Reiter's syndrome; And type η diabetes mellitus • 'bone resorption disease; graft response to host; ischemia-reperfusion injury; atherosclerosis; brain trauma; multiple sclerosis; cerebral palsy; sepsis; septic shock; toxic shock Symptoms; fever, and myalgia caused by infection. HIV-1, HIV_2, HIV_3, Cytomegalovirus (CMV) "influenza virus, adenovirus, herpes virus (including HSV-1, HSV-2), and band therapy have also deteriorated due to TNF-α. 520362 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (2) It is reported that TNF-α plays a role in head trauma, stroke and ischemia. For example, in the animal model of head trauma (large In mice), the concentration of TNF-a is increased in the contused cerebral hemisphere (Shohami et al., J. Ceieb. Blood Flow Metab. 14, 615 (1994)). In the ischemic model of the rat, the middle cerebral artery is blocked, Increased TNF-α mRNA concentration of TNF-α (Feursteill et al., Neurosci. Lett. 164, 125 (1993)). Administration of TNF_a to rat cerebral cortex has been reported to cause significant accumulation of microvascular neutrophils and adhesion to Small blood vessels. TNF-a can promote the infiltration of other cytokines (IL-1β, IL-6), as well as the infiltration of chemical hormones, which can promote the infiltration of neutrophils into the infarcted area (Feurstein, Stroke 25, 1481 (1994) ) .TNF-a also plays a role in type II diabetes (Endocrinol. 130, 43-52 , 1994; and Endocrinol. 136, 1474-1481, 1995) TNF-a obviously plays a role in promoting the life cycle of certain viruses and their associated disease states. For example, TNF-a secreted by monocytes is a chronic infection of T Cell lineage defamation increases the extent of HIV expression (Clouse et al., J. Immunol. 142 '43 1 (1989)). Lahdevirta et al. (Am. J. Med. 85, 289 (1988)) discuss TNF-α in The role of HIV in cachexia and muscle degeneration. TNF-a is located upstream of the inflammatory cytokine cascade. As a result, increased TNF-a concentrations may lead to increased cytokine concentrations in other inflammatory and pre-inflammatory phases, such as IL-1, IL- 6 and IL-8. Increased IL-1 concentration compared with the basal concentration involves mediators or worsens a variety of diseases including rheumatoid arthritis; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; Adult Respiratory Distress Syndrome (ARDS); (Please read the precautions on the back before filling out this page) Order-ml II— · i ·

520362 Γ A7 B7 五、發明説明（3 經濟部中央標準局員工消費合作社印製 乾癖；柯恩氏病；潰瘍性結腸炎；無防衛性過敏反應；肌 肉退化；惡病質；莱特氏症候群；第1型及第π型糖尿病 •，骨質吸收病；缺血後再灌流傷害；動脈粥瘤硬化；腦創 傷；多發性硬化；敗血病；敗血性休克及中毒性休克症候 群。對TNF-α抑制作用敏感的病毒例如，hiv_2， HIV-3也受IL_1影響。 TNF_a及IL· 1顯然於胰臟β細胞破壞及糖尿病扮演某種角 色。胰臟β細胞產生胰島素輔助媒介血糖的恆定。胰臟^細 胞劣化常扮隨弟I型糖尿病。胰臟β細胞功能異常出現於第 II型糖尿病病人。第II型糖尿病之特徵爲對胰島素具有功 能耐性。又，第II型糖尿病常伴隨有血漿升糖素濃度升高 及肝臟葡萄糖生產速率加快。升糖素是一種調節激素可減 輕肝臟葡萄糖新生作用受胰島素抑制。升糖素受體出現於 肝臟，腎臟及脂肪組織。因此，升糖素拮抗劑可用於降低 血漿葡萄糖濃度（W0 97/10442，併述於此以供參考）。藉著 拮抗升糖素受體，相信可改良肝臟之胰島素反應，因而減 少葡萄糖新生及降低肝臟之葡萄糖生產速率。 類風/然性關卽炎動物模式中，多次關節内注射IL__ 1導致 急性破壞型關節炎（Chandrasekhar et al.，Clinical Imnumol Immunopatliol· 55，382 (1990))。使用類風濕性滑膜細胞 培養研究中，IL-1爲比較TNF_a更強力的str〇melysin謗生 齊1J (Firestein, Am· J· Pathol. 140，1309 (1992))。於局部注 射部位觀察到嗜中性細胞、淋巴細胞及單核細胞向外遷移 。向外遷移係來自於謗生化學激素（例如IL·8)，及黏著分520362 Γ A7 B7 V. Description of the invention (3 printed dry addiction by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs; Cohen's disease; ulcerative colitis; non-defensive allergic reaction; muscle degeneration; cachexia; Wright's syndrome; section 1 And type π diabetes, bone resorption disease; reperfusion injury after ischemia; atherosclerosis; brain trauma; multiple sclerosis; septicemia; septic shock and toxic shock syndrome. Inhibitory effect on TNF-α Sensitive viruses such as HIV_2 and HIV-3 are also affected by IL_1. TNF_a and IL · 1 obviously play a role in pancreatic β-cell destruction and diabetes. Pancreatic β-cells produce constant insulin-assisted blood glucose. Pancreatic ^ cells Deterioration often affects type I diabetes. Pancreatic β-cell dysfunction occurs in patients with type II diabetes. Type II diabetes is characterized by functional tolerance to insulin. In addition, type II diabetes is often accompanied by plasma glucagon concentrations Elevated and accelerated glucose production in the liver. Glucagon is a hormone that can reduce liver glucose regeneration by insulin inhibition. Glucagon receptors appear It is used in liver, kidney and adipose tissue. Therefore, glucagon antagonists can be used to reduce plasma glucose concentration (W0 97/10442, which is described here for reference). By antagonizing the glucagon receptor, it is believed that it can improve the liver Insulin response, thus reducing glucose renewal and reducing the rate of glucose production in the liver. In the animal model of wind / random inflammatory disease, multiple intra-articular injections of IL__ 1 lead to acute destructive arthritis (Chandrasekhar et al., Clinical Imnumol Immunopatliol 55, 382 (1990)). In studies using rheumatoid synovial cell culture, IL-1 is stromolysin, which is more potent than TNF_a, 1J (Firestein, Am. J. Pathol. 140, 1309 (1992)). Outward migration of neutrophils, lymphocytes, and monocytes was observed at the local injection site. Outward migration was due to phytochemical hormones (such as IL · 8), and adhesion components

(請先閱讀背面之注意事項再填寫本頁) 象(Please read the notes on the back before filling this page)

、1T 1Γ_ 520362 Α7 Β7 五、發明説明（4 ) 子向上調節（Dinarello，Eur· Cytokine Netw. 5 ， 517-53 1 (1994)) 〇 (請先閱讀背面之注意事項再填寫本頁) iL-1顯然對促進某些病毒生命周期扮演某種角色。例如 ’細胞激素謗生慢性感染巨噬細胞種系之HIV表現增高伴 1¼•及 ％擇性引起 IL-1 產量增南（Folks etal.，J. Immunol. 1 36 ’ 40 (1986))。Beutler 等（J· Immunol· 135，3969 (1985)) 4論IL· 1於惡病質扮演的角色。Baracos等（New Eng. J. Med· 3 08，553 (1983))討論IL_1於肌肉退化扮演的角色。 於類風濕性關節炎，IL· 1及TNF-α皆可謗生滑膜細胞及 軟骨細胞產生膠原酶及中性蛋白解酶，結果導致關節炎關 節内部的組織破壞。關節炎模式中（大鼠及小鼠之膠原謗生 關節炎（CIA))，於謗生CIA前或後關節内投予TNF-a導致關 郎炎發病加速及病程更嚴重（Brahn et al.5 Lymphokine Cytokine Res· 11 ，253 (1992);及 Cooper，Clin· Exp.、 1T 1Γ_ 520362 Α7 Β7 V. Description of the invention (4) Up-regulation of the subunit (Dinarello, Eur · Cytokine Netw. 5, 517-53 1 (1994)) 〇 (Please read the precautions on the back before filling this page) iL- 1 Apparently plays a role in promoting the life cycle of certain viruses. For example, the cytokine phenotype of chronically infected macrophages has an increased HIV performance accompanied by 1¼ •% selective growth in IL-1 production (Folks etal., J. Immunol. 1 36 ′ 40 (1986)). Beutler et al. (J. Immunol. 135, 3969 (1985)) 4 On the role of IL · 1 in cachexia. Baracos et al. (New Eng. J. Med. 3 08,553 (1983)) discuss the role of IL_1 in muscle degeneration. In rheumatoid arthritis, both IL · 1 and TNF-α can produce collagenases and neutral proteolytic enzymes in synovial cells and chondrocytes, resulting in tissue destruction inside the arthritis joint. In the arthritic model (collagenous arthritis (CIA) in rats and mice), administration of TNF-a in the joints before or after the CIA leads to an accelerated onset of the disease and a more severe course (Brahn et al. 5 Lymphokine Cytokine Res. 11, 253 (1992); and Cooper, Clin. Exp.

Immunol. 898，244 (1992)) o 經濟部中央標準局員工消費合作社印裝 IL-8惡化及/或引發多種疾病狀態，其中大量嗜中性細胞 浸潤於發炎或受傷部位（例如缺血）係由IL-8之趨化特性媒 介，此等疾病狀態包含但非僅限於下列：氣喘，發炎性腸 病，乾癖，成人呼吸窘迫症候群，心臟及腎臟再灌流傷害 ，血栓及腎小球腎炎。：[L-8除對嗜中性細胞之趨化作用外 ’ IL-8也可活化嗜中性細胞。如此，降低IL-8濃度可導致 嗜中性細胞浸潤減少。 、 冒經採行若干辦法來阻斷TNF-α的影響。一種辦法包栝 使用TNF-a之可溶性受體（例如tnFR-55或TNFR-75)，其 ^度適—用中 格(210:^-- --一 520362 A7 B7 五、發明説明（5 用於TNF-α媒介疾病狀態之動物模式證實有效。第二種辨 法係使用TNF-a特異性單株抗體，cA2，中和TNF-a驗證可 改良類風濕性關節炎第II期人類試驗之腫脹關節數目 (Feldmann et al·，Immunological Reviews, ρρ· 195-223 (1995))。此等辦法經由蛋白質隔離或受體拮抗作用阻斷 TNF-α及IL_1之影響。Immunol. 898, 244 (1992)) o Consumers' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs prints that IL-8 deteriorates and / or causes a variety of disease states, in which a large number of neutrophils infiltrate the inflamed or injured area (such as ischemia) By the chemotaxis properties of IL-8, these disease states include but are not limited to the following: asthma, inflammatory bowel disease, dry addiction, adult respiratory distress syndrome, heart and kidney reperfusion injury, thrombosis and glomerulonephritis. : [L-8 In addition to its chemotactic effect on neutrophils ’IL-8 can also activate neutrophils. As such, reducing IL-8 concentration can result in reduced neutrophil infiltration. Several measures have been taken to block the effects of TNF-α. One method involves the use of soluble receptors for TNF-a (such as tnFR-55 or TNFR-75), the appropriate degree of which is moderate-use the middle case (210: ^--520362 A7 B7 V. Description of the invention (5 uses The animal model of TNF-α-mediated disease status has proven effective. The second method is to use TNF-a-specific monoclonal antibodies, cA2, and neutralize TNF-a to verify the improvement of rheumatoid arthritis Phase II human trials. Number of swollen joints (Feldmann et al., Immunological Reviews, ρρ 195-223 (1995)). These methods block the effects of TNF-α and IL_1 through protein isolation or receptor antagonism.

Bennett 等（J. Med. Chem. 21，623 (1978))合成多種下述 形式喃淀： (請先閱讀背面之注意事項再填寫本頁)Bennett et al. (J. Med. Chem. 21, 623 (1978)) synthesize several kinds of monolayers as follows: (Please read the precautions on the back before filling this page)

Ν 訂 其中，Ra1爲2-，3-或4-吡啶基，Ra2爲Η，甲基或苯基， 及Ra3爲Η，胺基。報告此等化合物對大鼠佐藥謗發水腫 進行试驗’皆未顯示足夠保證進一步研究的活性程度，額 外試驗確證此等化合物於鹿角菜膠謗發水腫模式產生一系 列僞陽性反應。Where R1 is 2-, 3- or 4-pyridyl, Ra2 is fluorene, methyl or phenyl, and Ra3 is fluorene, amine. These compounds were reported to have been tested in rats with adjuvant edema edema, but none showed sufficient levels of activity to warrant further research. Additional tests confirmed that these compounds produced a series of false positive reactions in the carrageenan edema mode.

Ife 等（Bio org. Med· Chem· Lett .5，543(1995))報告另一 種喃呢（Κ^=2-甲基苯基，Ra2 = 2-毗啶基，及心‘正丙基， 其中Ra ，Ra2及Ra皆同上結構式i)具有比較相關4_(2-吡 啶基）-5-苯基嘧唑化合物低數倍的Η+/κ+_ΑΤρ^^ψ制活性。 WO 97/3 3 8 83敘述可用於治療細胞激素媒介疾病之取代 ρ密淀化合物。 - 經濟部中央標準局員工消費合作社印製Ife et al. (Bio org. Med. Chem. Lett. 5, 543 (1995)) report another ranane (K ^ = 2-methylphenyl, Ra2 = 2-pyridinyl, and ox'n-propyl, Among them, Ra, Ra2 and Ra all have the same structural formula i) as above, and have a 制 + / κ + _ΑΤρ ^^ ψ activity that is several times lower than that of related 4- (2-pyridyl) -5-phenylpyrazole compounds. WO 97/3 3 8 83 describes alternative pmid compounds that can be used to treat cytokine-mediated diseases. -Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs

520362 A7 B7 五、發明説明（ 6 發明之簡單説明 本發明包括一類新穎化合物可用於預防及治療疾病，如 TNF_a，lL_ip，仏^及/或比^媒介之疾病及其它病症 幻如疼痛及糖尿病。特別，本發明化合物可用於預防及 2療發炎相關疾病或病情。如此，本發明亦包括含該等化 合物之醫藥組成物，使用本發明之化合物及組成物預防及 治療TNF-a，Π^β，仏^及/或比_8媒介疾病，如發炎、 疼痛及糖尿病之方法，其可用於製備本發明化合物中間物 之方法。 本發明化合物可以如下結構通式表示：520362 A7 B7 5. Description of the invention (6 Brief description of the invention The invention includes a novel class of compounds that can be used to prevent and treat diseases, such as TNF_a, lL_ip, 仏 ^ and / or other diseases and other conditions such as pain and diabetes. In particular, the compounds of the present invention can be used for the prevention and treatment of inflammation-related diseases or conditions. Thus, the present invention also includes pharmaceutical compositions containing these compounds, and the use of the compounds and compositions of the present invention for the prevention and treatment of TNF-a, β ^ β The method of vector disease, such as inflammation, pain and diabetes, can be used for the method of preparing the intermediate of the compound of the present invention. The compound of the present invention can be represented by the following general formula:

RR

Ri R2'τ入。 N R1Ri R2'τ in. N R1

經濟部中央標隼局員工消費合作社印製 其中R1，R2，R11及R12定義如後。 前文僅摘述本發明之某些態樣而決非預期或被視爲限制 本發明。此處引述 < 全邵專利案及其它公開文獻皆併述於 此以供參考。 、 發明之詳細説I 根據本發明提供下式化合物： 本紙張尺度適用中國國家標準（CNS ) A4規格（210X公釐） (請先閱讀背面之注意事項再填寫本頁)Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs, where R1, R2, R11 and R12 are defined as follows. The foregoing merely summarizes certain aspects of the invention and is by no means intended or considered as limiting the invention. References to the < Quan Shao patent case and other publications are incorporated herein by reference. I. Detailed description of the invention I According to the present invention, compounds of the following formula are provided: The paper size applies to the Chinese National Standard (CNS) A4 specification (210X mm) (Please read the precautions on the back before filling this page)

520362 A7 B7 五、發明説明（7520362 A7 B7 V. Description of the invention (7

RR

R Λ 12 N R, (I) 經濟部中央標準局員工消費合作社印製 或其醫藥可接受性鹽，其中 Ri及R2各自分別爲-Z-Y，但（1)各_2-丫中芳基，雜芳基， 環烷基及雜環基基團總數爲〇·3 ;較佳〇-2 ;更佳〇_1 ;及 (2)Ri及R2中芳基，雜芳基，環烷基及雜環基基團合併總 數爲0·4 ;較佳〇_3 ;更佳0-2 ;最佳〇-1 ; 較佳，R2爲氳，CVC4烷基，鹵原子，羥基，CVC4烷氧 基，含1-3個鹵原子之CVC2鹵烷氧基，銃基，（VC4烷硫 基，胺基磺醯基，烷基胺基磺醯基，二-(Ci-C#烷基） 胺基磺醯基，胺基，Ci-C^烷基胺基，二-((^-山烷基）胺基 ，CVC5烷醯胺基，（(VC4烷氧）羰基胺基，Ci-C4烷基磺醯 胺基，或含1_3個鹵原子之Ci-C2鹵燒基； 更佳，R2爲氫，Ci-C4燒基，鹵原子，巍基，CVC4嫁氧 基，三氟甲氧基，銃基，CVC4烷硫基，胺基，CVC4烷基 胺基，二·（(:广山烷基）胺基，CVC5烷醯胺基，（CVC4烷氧 )羰基胺基，烷基磺醯胺基，或三氟甲基； 更佳，R2爲氫，甲基，乙基，氟，氯，羥基，甲氧基，三 氟甲基，胺基，甲基胺基，二甲基胺基”乙醯胺基或三氟 甲基；及最佳r2爲氫或經基； 其中各個Z分別爲 -10- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） (請先閱讀背面之注意事項再填寫本頁) 520362 A7 B7 五、發明説明（8 ) (1) 键結！ (2) 烷基，晞基或块基選擇性由下列取代：（a)i_3個胺基， 烷基胺基，二烷基胺基，烷醯胺基，燒氧羰基胺基，貌基 磺醯胺基，羥基，烷氧基，烷硫基或函原子’及（b)1或2 個雜環基，芳基或雜芳基選擇性由1 個選自下列之基團 取代：胺基，烷基胺基，二烷基胺基，烷醯胺基，烷氧羰 基胺基，烷基磺醯胺基，羥基，烷氧基’烷硫基，自原子 ，燒基或自燒基，· (3) 選擇性由1至3個選自下列之取代基取代之雜環基··胺 基，燒基胺基，二虎基胺基，燒縫胺基’坑氧羧基胺基， 燒基續醯胺基，#1基，貌氧基，燒硫基’燒基或自燒基； 或 (4) 選擇性由1至3個選自下列之取代基取代之芳基或雜芳 基：胺基，烷基胺基，二烷基胺基，烷醯胺基，烷氧羰基 胺基，烷基磺醯胺基，羥基，烷氧基，烷硫基，氰基，鹵 原子，燒基或_燒基； 較佳，其中各個Z分別爲 (1) 鍵結： 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁} (2) 選擇性由下列各者取代之C^-Cs烷基，C2_C8烯基或 C 2 - C 8 決基：（a) 1 - 3 個胺基 ’ C1 - C 4 基胺基’ —-(C1 - C 4 fe 基）胺基’ C1-C5燒S备胺基，（Ci-Cefe乳）叙基胺基’ C1-C4 虎基續醯胺基，謹基，CVC4跪氧基，CpC4燒硫基或鹵原 子，及（b) 1或2個選擇性由1至3個選自下列之取代基取代 之雜環基，芳基或雜芳基··胺基，烷基胺基，二-((^-匕 -11 - H張尺度適用中國國家標準（CNS ) A4規格（2丨0'〆297公釐） 520362 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（9 ) fe基）胺基’（^-(^燒醯胺基，（C1-C4坑氧）幾基胺基， C4坑基績gi胺基，幾基，匚：_ c 4嫁氧基’ c 1 - C4燒硫基，鹵 原子’ Ci_C4fe基或1_3個_原子之C1-C4鹵燒基； (3) 選擇性由1至3個選自下列之取代基取代之雜環基：胺 基，CVC4烷基胺基，二_(Ci_c4烷基）胺基，（VC;烷醯胺 基，（CrC4烷氧）羰基胺基，Cl-C4烷基磺醯胺基，羥基， CVC4烷氧基，Κ4烷硫基，CVC4烷基或含1-3個鹵原子 之鹵燒基；或 (4) 選擇性由1至3個選自下列之取代基取代之芳基或雜芳 基：胺基，CVC4烷基胺基，二-(CrG烷基）胺基，cvc5 燒醯胺基，（CrC4烷氧）羰基胺基，CrC#烷基磺醯胺基， 羥基，CVC4烷氧基，Cl_C4烷硫基，氰基，鹵原子，CV C4烷基或含1-3個鹵原子之Cl-C4鹵烷基； 更佳，其中各個Z分別爲 (1) 键結： (2) 選擇性由下列各者取代之Cl_Cs烷基，c2_c8晞基或 匸2-(1；8块基··（a)l_3個胺基，Ci-C4燒基胺基，二燒 基）胺基’ Ci-Csfe酸胺基，（Ci-C4坑氧）幾基胺基， 烷基磺醯胺基，羥基，Ci-C：4烷氧基，Cl-c4烷硫基或鹵原 子’及（b) 1或2個選擇性由1至3個選自下列之取代基取代 之雜環基’方基或雜芳基：胺基，Ci-C4燒基胺基，二 基）胺基，醯胺基，（CVC4燒氧）襞基胺基，Cl-C4烷基磺St胺基，羥基，CVC4烷氧基，Cl-c4烷硫基，鹵 原子，C!-C4虎基或1-3個鹵原子之燒基； -12- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） (請先閲讀背面之注意事項再填寫本頁)R Λ 12 NR, (I) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs or a pharmaceutically acceptable salt thereof, where Ri and R2 are -ZY, respectively, but (1) each _2-γ aryl, miscellaneous The total number of aryl, cycloalkyl and heterocyclyl groups is 0.3; preferably 0-2; more preferably 0_1; and (2) aryl, heteroaryl, cycloalkyl and heteroaryl in Ri and R2 The combined total of cyclic group is 0.4; preferably 0-3; more preferably 0-2; best 0-1; better, R2 is fluorene, CVC4 alkyl, halogen atom, hydroxyl, CVC4 alkoxy, CVC2 haloalkoxy, fluorenyl, (VC4 alkylthio, aminosulfonyl, alkylaminosulfonyl, di- (Ci-C # alkyl) aminosulfonyl) containing 1-3 halogen atoms Group, amine group, Ci-C ^ alkylamino group, di-((^-alkyl) amino group, CVC5 alkylamino group, ((VC4alkoxy) carbonylamino group, Ci-C4 alkylsulfonyl group An amine group, or a Ci-C2 haloalkyl group containing 1 to 3 halogen atoms; more preferably, R2 is hydrogen, a Ci-C4 halo group, a halogen atom, an alkyl group, a CVC4 alkyloxy group, a trifluoromethoxy group, a fluorenyl group, CVC4 alkylthio, amine, CVC4 alkylamino, di · ((: Huangshan alkyl) amino, CVC5 alkylamino, (CVC4 alkoxy) carbonylamino, alkyl Sulfonamido, or trifluoromethyl; more preferably, R2 is hydrogen, methyl, ethyl, fluorine, chlorine, hydroxyl, methoxy, trifluoromethyl, amine, methylamino, dimethyl "Amino" acetamido or trifluoromethyl; and the best r2 is hydrogen or warp; each Z is -10- This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) ( Please read the precautions on the back before filling this page) 520362 A7 B7 V. Description of the invention (8) (1) Bonding! (2) Alkyl, fluorenyl or block groups are optionally substituted by: (a) i_3 Amine, Alkylamino, Dialkylamino, Alkylamino, Alkoxycarbonylamino, Mesosulfonamido, Hydroxyl, Alkoxy, Alkylthio or Functional Atoms' and (b) 1 Or 2 heterocyclic groups, aryl or heteroaryl are optionally substituted by 1 group selected from the group consisting of: amino, alkylamino, dialkylamino, alkylamino, alkoxycarbonylamino , Alkylsulfonamido, hydroxy, alkoxy 'alkylthio, self-atom, alkyl or self-alkyl, (3) Heterocyclic group optionally substituted by 1 to 3 substituents selected from ·· Amine Group, dihexylamino group, burned-out amino group, pitoxy carboxylamino group, burntyl group, fluorenylamino group, # 1 group, alkoxy group, burntyl group, or self-burned group; or (4) select An aryl or heteroaryl group substituted by 1 to 3 substituents selected from the group consisting of amine, alkylamino, dialkylamino, alkylamino, alkoxycarbonylamino, alkylsulfonyl Amine group, hydroxyl group, alkoxy group, alkylthio group, cyano group, halogen atom, alkynyl group or alkynyl group; Preferably, each Z is (1) Bonding: Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the notes on the back before filling out this page} (2) C ^ -Cs alkyl, C2_C8 alkenyl or C 2-C 8 alkenyl optionally substituted by: (a) 1-3 Amino group 'C1-C 4 based amino group' —- (C1-C 4 fe based) amino group ' Sulfonylamino, amido, CVC4oxy, CpC4sulfanyl or halogen atom, and (b) 1 or 2 heterocyclic groups optionally substituted by 1 to 3 substituents selected from the group consisting of aryl or Heteroaryl · Amino, Alkylamino, Di-((^-d-11-11-H Zhang scale Applicable to China National Standard (CNS) A4 specification (2 丨 0'〆297 mm) 520362 Printed by A7 B7, Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (9) Fe-based) Amine-based ”(^-(^ Burning amine group, (C1-C4 pit oxygen) chlorinyl amine group, C4 pit group gi amine group, quinyl group, fluorene: _c 4 alkyloxy group 'c 1-C4 thiol group, halogen atom' Ci_C4fe group Or a C1-C4 haloalkyl group of 1 to 3 atoms; (3) a heterocyclic group optionally substituted by 1 to 3 substituents selected from the group consisting of: amino, CVC4 alkylamino, di_ (Ci_c4 alkyl ) Amine, (VC; Alkylamino, (CrC4 Alkoxy) carbonylamino, Cl-C4 Alkylsulfonamido, Hydroxyl, CVC4 Alkoxy, K4 Alkylthio, CVC4 Alkyl or containing 1- A halogenated group of 3 halogen atoms; or (4) an aryl or heteroaryl group optionally substituted by 1 to 3 substituents selected from: amine, CVC4 alkylamino, di- (CrG alkyl ) Amine, cvc5 sulfonylamino, (CrC4 alkoxy) carbonylamino, CrC # alkylsulfonamido, hydroxyl, CVC4 alkoxy, Cl_C4 alkylthio, cyano, halogen atom, CV C4 alkyl Or Cl-C4 haloalkyl containing 1-3 halogen atoms; more preferably, Each Z is (1) bonded: (2) Cl_Cs alkyl, c2_c8 fluorenyl, or fluorene 2- (1; 8 block ·· (a) 1-3 amine groups, Ci- C4 alkylamino, dialkyl) amine 'Ci-Csfe acid amine, (Ci-C4 pit oxygen) several amines, alkylsulfonamido, hydroxyl, Ci-C: 4 alkoxy, Cl-c4 alkylthio or halogen atom 'and (b) 1 or 2 heterocyclyl' square or heteroaryl groups optionally substituted with 1 to 3 substituents selected from: amino, Ci-C4 Alkylamino, diyl) amino, fluorenylamino, (CVC4oxy) fluorenylamino, Cl-C4alkylsulfonylStamino, hydroxyl, CVC4alkoxy, Cl-c4alkylthio, halogen Atoms, C! -C4 tiger radicals or 1-3 halogen atom burned radicals; -12- This paper size applies to China National Standard (CNS) A4 specifications (210X 297 mm) (Please read the notes on the back before filling (This page)

、1T WI. 經濟部中央標準局員工消費合作社印製 520362 A7 _-___ 五、發明説明（10) (3) 選擇性由1至2個選自下列之取代基取代之雜環基：胺 基，Ci-C#烷基胺基，二_(Ci-C4烷基）胺基，ci-c5坑酸胺 基，（CrQ烷氧）羰基胺基，Ci-C4烷基磺醯胺基，羥基， 烷氧基，CVCj硫基，CVC4院基或含1-3個i原子 之Ci-C^鹵烷基；或 (4) 選擇性由1至3個選自下列之取代基取代之芳基或雜芳 基··胺基，CVC4烷基胺基，二_(Ci-C4烷基）胺基，Ci_C5 烷醯胺基，（CrC^烷氧）羰基胺基，CrC4烷基磺醯胺基， 羥基，CVC4烷氧基，CVC4烷硫基，氰基，鹵原子，C” 匸4燒基或含1-3個自原子之Ci-C4_坑基’ 更佳，其中各個Z分別爲 (1) 鍵結： (2) 選擇性由下列各者取代之C「C8烷基或C2_C8烯基： (a)l_3個胺基，CVC4烷基胺基，二-(Ci-C^烷基）胺基， C!-C5烷醯胺基，（CVC4烷氧）羰基胺基，羥基，烷氧 基，Ci-C^烷硫基或鹵原子，及（b)l或2個選擇性由1至3 個選自下列之取代基取代之雜環基，芳基或雜芳基：胺基 ’ C 1 - C 4纟充基胺基，二-(C 1 " C 4挺*基）私^基’ C 1 - C 5驗胺基 ’（Ci-Cj娱*氧）談基胺基，羥基’ Ci-C4坑氧基’ 燒硫 基，鹵原子，CVC4烷基或1-3個鹵原子之Ci-C：2鹵乾基； (3) 選擇性由1至2個選自下列之取代基取代之雜環基：胺 基，二燒基）胺基，（cvcu燒氧）幾基胺基，趣基， 氧基，Ci-C/^fe 硫基或 Ci_C4fe基；或 (4) 選擇性由1至3個選自下列之取代基取代之方基或雜芳 -13- 本紙張尺度適用中國國家標準CNS ) A4規格（210X 297公釐)—^ - (請先閱讀背面之注意事項再填寫本頁j 訂 HI— 520362 A7 ___— _______ __ 五、發明説明（Μ) ~~ 基：胺基，（VC4烷基胺基，二-(CrG烷基）胺基，CVC5 烷醯胺基，（CrC^烷氧）羰基胺基，CrQ烷基磺醯胺基， 羥基，CVC4烷氧基，烷硫基，氰基，鹵原子，c” C4烷基或含1_3個鹵原子之Ci-C2鹵烷基； 更佳，其中各個z分別爲 (1) 鍵結： (2) 選擇性由下列各者取代之CrC#烷基或C2_C5烯基·· (a) 1-3個胺基，二-(CVC2烷基）胺基，Ci-C5燒醯胺基， (Ci-C*烷氧）羰基胺基，羥基，CVC2烷氧基，CVC2烷硫基 或_原子，及（b) 1或2個選擇性由1至3個選自下列之取代 基取代之雜環基，芳基或雜芳基：胺基，c 1-C4坑基胺基 ，二- (Ci-C2燒基）胺基，C1-C5燒酿胺基’（C1-C4燒氧）羰基 胺基，羥基，Ci-CU烷氧基，CrC4烷硫基，鹵原子，CV C4fe基或三氟甲基； (3) 選擇性由1至2個選自下列之取代基取代之雜環基：胺 基，二-(Cl-C2烷基）胺基，（CVC4烷氧）羰基胺基，羥基， Ci-c2燒氧基，Ci-c2^硫基或基；或 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) (4) 選擇性由1至3個選自下列之取代基取代之芳基或雜芳 基：胺基，二-(C1-C2纟完基）胺基，Ci-C5坑醯^胺基，（Ci_C4 烷氧）羰基胺基，羥基，CVC2烷氧基，CrC2燒硫基’氰 基，鹵原子，Ci-Cq烷基或三氟甲基； 更佳，其中各個Z分別爲 ' (1) 鍵結： (2) 選擇性由下列各者取代之CrC4烷基或CrC5晞基： -14- ________ 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 經濟部中央標準局員工消費合作社印製 520362 A7 —_______ ___-___ 五、發明説明（12) (a) 1-3個胺基，二4C1-C2燒基）胺基，（Cl-C4抗氧）羰基胺基 ，羥基，Ci-C2烷氧基，Ci-C2烷硫基或鹵原子’及（b)l或 2個選擇性由1至2個選自下列之取代基取代之雜環基，芳 基或雜芳基：胺基，二- (Ci-C2嫁基）胺基，乙醒胺基，（cvcu 烷氧）羰基胺基，羥基，C!-C2烷氧基，CrC2烷硫基，鹵 原子，Ci-Czj烷基或三氟甲基；或 (3)選擇性由1至3個選自下列之取代基取代之芳基或雜芳 基：胺基，二_(Cl-C2烷基）胺基，乙酸胺基，（Ci-C4烷氧） 羰基胺基，羥基，Cl-C2烷氧基，烷硫基，氰基，鹵 原子，Ci-q烷基或三氟甲基； 更佳，各個Z分別爲 (1) 鍵結；或 (2) C「C4燒基選擇性由1或2個選自下列之取代基取代：胺 基’--（Ci-C2燒基）胺基，（Ci-C4：fe氧）窥基胺基，幾基， C「C2烷氧基，Cl-C2烷硫基或鹵原子；或芳基或雜芳基選 擇性由1至2個選自下列之取代基取代：羥基，（^-(：2烷氧 基’ Ci-C〕燒硫基，鹵原子，Ci-CU虎基或三氟甲基；及 最佳，各個Z分別爲 (1) 鍵結；或 (2) C i -C4燒基選擇性由1或2個選自下列之取代基取代：胺 基，第三丁氧羰基胺基，二甲基胺基，羥基，甲氧基，甲 石見基或卣原子； 、 較佳各個γ分別爲 ⑴氫； __ —__- 15- 本紙張尺度適用中國國家標準（CNs ) A4規格（210X297公釐） (請先閲讀背面之注意事項再填寫本頁) 訂 - 520362 A7 ____ B7 五、發明説明（13) (2) ¾原子或硝基； (3) _C(O)-R20 或-C(NR5)-NR5R21 ; (4) -〇R21 ，-0-C(0)-R21 ，-o-c(o)-nr5r21 或-o-c(o)- NR22-S(O)2_R20 ; (5) _SR2l ’ -S(0)_R2〇 ’ -S(O)2_R20 ’ _S(0)2_NR5R2i ，_ s(o)2_nr22_c(o)_r21 ，-s(o)2_nr22-c(o)_or20 或-s(o)2-nr22-c(o)-nr5r21 ;或 (6) -NR5R21 ? -NR22"C(O)-R21 ? -NR22 C(O)-OR20 ? -NR22· C(0)-NR5R21 ’ _NR22_C(NR5)_NR5R21 ’ -NR22_S(O)2_R20 或 -N R.2 2 - S ( O ) 2 R5 R.2 1 ^ 較佳，各個Y分別爲 ⑴氫； (2) 鹵原子； (3) -C(O)-R204-C(NR5)_NR5R21 ; (4) _OR2】，-0-C(0)_R21 或-0-C(0)-NR5R2i ; (5) -SR21，-S(0)-R2。，-s(o)2-r2〇 或-S(0)2-NR5R21 ;或 (6) -NR5R21 ’ -NR22-C(O)_R21 ’ -NR22-C(O)-OR2〇 ’ -NR22 C(0)-NR5R2i y -NR22-C(NR5)-NR5R21 ? -NR22 S(O)2 R20 -¾ 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) -nr22-s(o)2_nr5r21 ; 更佳，各個Y分別爲 ⑴氫； (2) -C(O).R20 ; (3) -OR2i ’ -SR21，$(0)-R20 ’ -S(0)2-R2〇 或-S(0)2_NR5R2i ;或 ___ 16_ 本紙張尺度適用中國國家標準（CNS ) A4規格（2丨OX 297公釐） 520362 A7 B7 五、發明説明（14) (4)_NR5R21，_NR22_C(0)-R21，-NR22-C(O)-OR20，-NR22-C(0)-NR5R21，-NR22-S(0)2-R2〇 或-nr22-s(o)2-nr5r21 ; 更佳，各個Y分別爲 ⑴氫； (2) -C(O)_R20 ; (3) -〇R21，-SR21，-S(0)-R2〇，-S(O)2-R20 或-S(〇)2-NR5R21 ;或 (4) _NR5R21，-NR22_c(〇)-R24-NR22-S(O)2_R20; 更佳，各個γ分別爲 (1) -C(O).R20 ； (2) -〇R21，-SR21，-S(O)-R20，·8(Ο)2·Γ120 或-S(〇)2-NR5R21 ;或 (3) -NR5R21，-NR22_c(〇)-R21 或-NR22-S(O)2，R20 ; 更佳，各個 Y 分別爲-〇r21，-SR21 4-NR5R21 ; 其中各個R5分別爲 ⑴氳； (2) 烷基，晞基或炔基選擇性由i至3個選自下列之取代基 取代：胺基，烷基胺基，二烷基胺基，羥基，嫁氧基’ ^ 硫基，_ S 0 3 Η或鹵原子；或 (3) 芳基，雜芳基，芳烷基，雜芳烷基，雜環基’雜5尽基^ 基，環燒基，或環燒基燒基選擇性由1 - 3個遂自下歹】之取 代基取代：胺基，烷基胺基，二烷基胺基，寒基’坑氧基 ’ fe硫基’燒基或自燒基； 較佳，各個R5分別爲 -17- __ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） (請先閱讀背面之注意事項再填寫本頁) 訂 經濟部中央標準局員工消費合作社印製 520362 A7 B7 五、發明説明（15) (1) 氫； (2) Ci-C8烷基，C2-C8晞基或C2-C8块基選擇性由1至3個 選自下列之取代基取代：胺基，CM4烷基胺基，：-(〇-C 4 -嫁基）胺基’赛基’ C 1 - C 4燒氧基，C 1 · C 4燒硫基’ -S 0 3 Η 或鹵原子；或 (3) 芳基，雜芳基，芳基烷基，雜芳基-CVC4·烷基， 雜環基，雜環基-CVC4-烷基，C3-C8環烷基，或C3-C8-環 烷基烷基選擇性由1-3個選自下列之取代基取代： 胺基’ C1-C4坑基胺基’二-(C1-C4-燒基）胺基’無基’ Ci- C4烷氧基，Ci-C^烷硫基，CrQ烷基或含1-3個鹵原子之 Ci-C#鹵烷基； 更佳，各個R5分別爲 (1)氫； • (2)cvc4烷基，C2-C5烯基或C2-C5块基選擇性由1至3個 選自下列之取代基取代：胺基，Ci-C4虎基胺基’二-(Cl-C4-烷基）胺基，羥基，CVC4烷氧基，CrC4燒硫基，-so3H 或鹵原子；或 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) (3)芳基，雜芳基，芳基-Ci-CV烷基，雜芳基-Ci_c4-燒基’ 雜環基，雜環基-CVC4-烷基，C3-C8環烷基，或C3-C8-環 烷基-Ci-Cc烷基選擇性由1_3個選自下列之取代基取代： 胺基，CrQ烷基胺基，二-(CVC4-烷基）胺基’經基’ Cl-C4烷氧基，CVC4烷硫基，CVC4烷基或含卜3個自原子之 C 1 C 4 自 基； 更佳，各個R5分別爲 -18-__ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（16) (1) 氳； (2) Ci-C4fe基或C2-C5烯基選擇性由1至3個選自下列之取 代基取代：胺基，二-(Ci-C4-烷基）胺基，羥基，CrQ烷氧 基’ C1-C4燒硫基，-SO3H或鹵原子；或 (3) 冬基- Ci-C2_：l充基，雜芳基- Ci-C〗 -恍基’雜$尽基·Ci-Cy 烷基或C3_C6_環烷基-Ci-Cr烷基選擇性由1-3個選自下列 之取代基取代：胺基，二-(Ci-Cr烷基）胺基，羥基， 氧基，CpCzt燒硫基，Ci-C4燒基或含1-3個鹵原子之 CrQ鹵烷基； 更佳，各個分別爲 ⑴氫； (2) C 1-C4坑基選擇性由1至3個選自下列之取代基取代：胺 基，二-(CVCV烷基）胺基，羥基，CVG烷氧基，（^-(^烷 硫基或卣原子；或 (3) 苯基-CVC2-烷基，雜芳基-CVC2-烷基，雜環基-CVc2-烷基或C3_C6-環烷基-Ci-Cr烷基選擇性由1-3個選自下列 之取代基取代：胺基，二-(C^-Cr燒基）胺基，巍·基， 烷氧基，烷硫基，甲氧基，甲硫基，Ci-Cj烷基或三 氟甲基； 更佳，各個R5分別爲 (1) 氫； (2) 選擇性由1至3個鹵原子取代之Ci-C#烷基；或 (3) 苯基-Ci-Cy烷基或雜芳基_Cl_c2-烷基選擇性由1_3個選 自下列之取代基取代：胺基，二甲基胺基，羥基，甲氧基 _____-19- 本紙張尺度適用中_家標準（CNS ) Μ規袼（21GX297公釐） (請先閲讀背面之注意事項再填寫本頁} 、-=口 520362 A7 ______ __ B7 五、發明説明（17 ) ’甲硫基’甲基或三氣甲基； (請先閱讀背面之注意事項再填寫本頁) 更佳，各個R5分別爲氬或Cl-c4烷基；及最佳各個r5爲氫； 其中各個R20分別爲 (1) 烷基，烯基或炔基選擇性由1至3個選自下列之取代基 取代：胺基，烷基胺基，二烷基胺基，烷醯胺基，烷氧羰 基胺基，N-(烷氧羰基）-N_(烷基）胺基，胺基羰基胺基，烷 基磺醯胺基，羥基，烷氧基，烷硫基，烷基亞磺醯基，烷 基磺醯基，自原子或芳基烷氧基，芳基烷硫基，芳基烷基 磺醯基，環烷基，雜環基，芳基或雜芳基選擇性由1至3 個選自下列之取代基取代：胺基，烷基胺基，二烷基胺基 ，烷醯胺基，烷氧羰基胺基，烷基磺醯胺基，烷醯基，羥 基，燒氧基，燒硫基，燒基亞橫基，燒基橫醯基，鹵原 子，烷基或自烷基； (2) 雜環基選擇性由1至3個選自下列之取代基取代：胺基 ，烷基胺基，二烷基胺基，烷醯胺基，烷氧羰基胺基，烷 基磺醯胺基，羥基，烷氧基，烷硫基，烷基或自烷基；或 (3) 芳基或雜芳基選擇性由1至3個選自下列之取代基取代 :胺基，烷基胺基，二烷基胺基，烷醯胺基，烷氧羰基胺 經濟部中央標準局員工消費合作社印製 基，烷基磺醯胺基，烷氧羰基，羥基，烷氧基，烷硫基， 氰基，鹵原子，疊氮基，燒基或齒燒基； 較佳，各個R2〇分別爲 (UCi-Cs烷基，C2-C8烯基或C2-C8炔基選擇性由1至3個 選自下列之取代基取代：胺基，CrC4烷基胺基，二 C4燒基）胺基’ C1-C5燒酿胺基’（C1-C4坑氧）談基胺基’ -20-__ 本紙張尺度適^1^國家標準（(：1^)八4規格（21〇>< 297公釐） * 520362 A7 B7 五、發明説明（18 ) (請先閱讀背面之注意事項再填寫本頁} N-GCVC4抗氧）後基燒基）胺基，胺基黢基胺基 ，eve)烷基磺醯胺基，羥基，C!-C4烷氧基，CVC4烷硫 基，Ci-C4燒基亞橫醯基，CVC4燒基績醯基，鹵原子或芳 基-CVC4·烷氧基，芳基-CVCV烷硫基，芳基烷基磺 Si：基’ C 3 - C 8壤坑基’雜環基，芳基或雜芳基選擇性由1 至3個選自下列之取代基取代：胺基，CrG烷基胺基，二 -(CVC4烷基）胺基，CrC5烷醯胺基，（CVC4烷氧）羰基胺基 ’ Ci-C^燒基續酿胺基，Ci-C〗燒驢基，藉基，Ci-C^貌氧 基，（VC4烷硫基，CVC4烷基亞磺醯基，CVC4烷基磺醯 基，自原子，（^-€4虎基或含1-3個鹵原子之（1^-04鹵燒基； (2) 雜環基選擇性由1至3個選自下列之取代基取代：胺基 ，CVC4烷基胺基，二-(CVC4烷基）胺基，CrCs烷醯胺基 ’（CrQ烷氧）羰基胺基，Ci-C#烷基磺醯胺基，羥基，、 1T WI. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 520362 A7 _-___ V. Description of the Invention (10) (3) Heterocyclic group optionally substituted by 1 to 2 substituents selected from the group: amine , Ci-C # alkylamino, di- (Ci-C4 alkyl) amino, ci-c5 pit acid amine, (CrQ alkoxy) carbonylamino, Ci-C4 alkylsulfonamido, hydroxyl, Alkoxy, CVCj thio, CVC4 alkyl or Ci-C ^ haloalkyl containing 1-3 i atoms; or (4) an aryl group optionally substituted by 1 to 3 substituents selected from Heteroaryl · amino, CVC4 alkylamino, di_ (Ci-C4 alkyl) amino, Ci_C5 alkylamino, (CrC ^ alkoxy) carbonylamino, CrC4 alkylsulfonamido, Hydroxyl, CVC4 alkoxy, CVC4 alkylthio, cyano, halogen atom, C "hydrazone or Ci-C4_ pit group containing 1-3 self atoms is more preferred, wherein each Z is (1 ) Bonding: (2) C "C8 alkyl or C2_C8 alkenyl, optionally substituted by: (a) 1-3 amines, CVC4 alkylamino, bis- (Ci-C ^ alkyl) amine , C! -C5 alkylamino, (CVC4 alkoxy) carbonylamino, hydroxyl, alkoxy, Ci-C ^ alkylthio or halogen And (b) 1 or 2 heterocyclic groups, aryl or heteroaryl groups optionally substituted by 1 to 3 substituents selected from the group consisting of: amine 'C 1 -C 4 fluorenylamino, Bis- (C 1 " C 4 radicals) private radicals C 1-C 5 amino-amine radicals (Ci-Cj entertainment * oxygen) sulfanylamino radicals, hydroxyl 'Ci-C4 pitoxy' sulfur burning Group, halogen atom, CVC4 alkyl group or Ci-C of 1-3 halogen atom: 2 halogen dry group; (3) heterocyclic group optionally substituted by 1 to 2 substituents selected from: amino group, Dialkyl) amine, (cvcuoxy) amine, aryl, oxy, Ci-C / ^ fethio or Ci_C4fe; or (4) selectivity from 1 to 3 selected from Substituted square or heteroaryl-13- This paper size applies to Chinese National Standard CNS) A4 size (210X 297 mm) — ^-(Please read the precautions on the back before filling in this page. Order HI— 520362 A7 ___— _______ __ 5. Description of the Invention (Μ) ~~ Groups: Amino groups, (VC4 alkylamino groups, di- (CrG alkyl) amino groups, CVC5 alkylamino groups, (CrC ^ alkoxy) carbonylamino groups , CrQ alkylsulfonamido, hydroxyl, CVC4 alkoxy, alkylthio, cyano, halo , C ”C4 alkyl or Ci-C2 haloalkyl containing 1 to 3 halogen atoms; more preferably, each z is (1) bonded respectively: (2) CrC # alkyl optionally substituted by C2_C5 alkenyl ... (a) 1-3 amine groups, di- (CVC2 alkyl) amino group, Ci-C5 alkylamino group, (Ci-C * alkoxy) carbonylamino group, hydroxyl group, CVC2 alkoxy group Group, CVC2 alkylthio or _ atom, and (b) 1 or 2 heterocyclic groups, aryl or heteroaryl groups optionally substituted with 1 to 3 substituents selected from: amine group, c 1- C4 pit amino, di- (Ci-C2 alkyl) amino, C1-C5 alkylamino (C1-C4oxy) carbonylamino, hydroxyl, Ci-CU alkoxy, CrC4 alkylthio , A halogen atom, a CV C4fe group or a trifluoromethyl group; (3) a heterocyclic group optionally substituted by 1 to 2 substituents selected from the group consisting of: amino, di- (Cl-C2 alkyl) amino, (CVC4 alkoxy) carbonylamino, hydroxyl, Ci-c2 alkyloxy, Ci-c2 ^ thio or radical; or printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) ) (4) an aryl or heteroaryl group optionally substituted by 1 to 3 substituents selected from the group consisting of: amino Di- (C1-C2 fluorenyl) amino, Ci-C5 carbamine, (Ci_C4 alkoxy) carbonylamino, hydroxyl, CVC2 alkoxy, CrC2thiothio'cyano, halogen atom, Ci -Cq alkyl or trifluoromethyl; more preferably, each Z is' (1) bonded: (2) CrC4 alkyl or CrC5 fluorenyl optionally substituted by: -14- ________ This paper Standards are applicable to China National Standard (CNS) A4 specifications (210 X 297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 520362 A7 —_______ ___-___ 5. Description of the invention (12) (a) 1-3 amine groups , Di 4C1-C2 alkyl) amine, (Cl-C4 antioxidant) carbonylamino, hydroxyl, Ci-C2 alkoxy, Ci-C2 alkylthio or halogen atom 'and (b) 1 or 2 options Heterocyclic, aryl or heteroaryl substituted with 1 to 2 substituents selected from the group consisting of: amino, di- (Ci-C2 alkyl) amino, ethylamino, (cvcu alkoxy) Carbonylamino, hydroxyl, C! -C2 alkoxy, CrC2 alkylthio, halogen atom, Ci-Czj alkyl or trifluoromethyl; or (3) selectivity from 1 to 3 substituents selected from Substituted aryl or heteroaryl: amine, di_ (Cl-C2 Group) amine, acetate amine, (Ci-C4 alkoxy) carbonylamino, hydroxyl, Cl-C2 alkoxy, alkylthio, cyano, halogen, Ci-q alkyl or trifluoromethyl; More preferably, each Z is (1) bonded; or (2) C "C4 alkyl is optionally substituted with 1 or 2 substituents selected from the group consisting of: amine '-(Ci-C2 alkyl) amine Group, (Ci-C4: fe oxygen) peptylamino group, several groups, C "C2 alkoxy group, Cl-C2 alkylthio group or halogen atom; or aryl or heteroaryl group selectable from 1 to 2 Substituted from the following substituents: hydroxy, (^-(: 2alkoxy 'Ci-C] thio), halogen atom, Ci-CU oxo or trifluoromethyl; and most preferably, each Z is ( 1) Bonding; or (2) C i -C4 alkyl is optionally substituted by 1 or 2 substituents selected from the group consisting of amine, tertiary butoxycarbonylamino, dimethylamino, hydroxy, methyl Oxygen, methenyl or osmium atom;, preferably each γ is osmium hydrogen; __ —__- 15- This paper size applies to Chinese National Standards (CNs) A4 (210X297 mm) (Please read the note on the back first) Please fill in this page again) Order-520362 A7 ____ B7 V. Invention (13) (2) ¾ atom or nitro; (3) _C (O) -R20 or -C (NR5) -NR5R21; (4) -〇R21, -0-C (0) -R21, -oc (o) -nr5r21 or -oc (o)-NR22-S (O) 2_R20; (5) _SR2l '-S (0) _R2〇' -S (O) 2_R20 '_S (0) 2_NR5R2i, _s (o ) 2_nr22_c (o) _r21, -s (o) 2_nr22-c (o) _or20 or -s (o) 2-nr22-c (o) -nr5r21; or (6) -NR5R21? -NR22 " C (O) -R21? -NR22 C (O) -OR20? -NR22 2 1 ^ is preferred, each Y is fluorene hydrogen; (2) halogen atom; (3) -C (O) -R204-C (NR5) _NR5R21; (4) _OR2], -0-C (0) _R21 Or -0-C (0) -NR5R2i; (5) -SR21, -S (0) -R2. , -S (o) 2-r2〇 or -S (0) 2-NR5R21; or (6) -NR5R21 '-NR22-C (O) _R21' -NR22-C (O) -OR2〇 '-NR22 C (0) -NR5R2i y -NR22-C (NR5) -NR5R21? -NR22 S (O) 2 R20 -¾ Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling out this page)- nr22-s (o) 2_nr5r21; more preferably, each Y is tritium hydrogen; (2) -C (O) .R20; (3) -OR2i '-SR21, $ (0) -R20' -S (0) 2-R2〇 or -S (0) 2_NR5R2i; or _ 16_ This paper size applies to Chinese National Standard (CNS) A4 specifications (2 丨 OX 297 mm) 520362 A7 B7 V. Description of the invention (14) (4) _NR5R21 _NR22_C (0) -R21, -NR22-C (O) -OR20, -NR22-C (0) -NR5R21, -NR22-S (0) 2-R2〇 or -nr22-s (o) 2-nr5r21 Preferably, each Y is fluorene hydrogen; (2) -C (O) _R20; (3) -〇R21, -SR21, -S (0) -R2〇, -S (O) 2-R20 or- S (〇) 2-NR5R21; or (4) _NR5R21, -NR22_c (〇) -R24-NR22-S (O) 2_R20; more preferably, each γ is (1) -C (O) .R20; (2) ) -〇R21, -SR21, -S (O) -R20, · 8 (Ο) 2 · Γ120 or -S (〇) 2-NR5R21; or (3) -NR5R21, -NR22_c (〇) -R21 or- NR22-S (O) 2, R20; better, each Y -0r21, -SR21 4-NR5R21; each R5 is fluorene; (2) alkyl, fluorenyl or alkynyl are optionally substituted by i to 3 substituents selected from: amine, alkane Amino, dialkylamino, hydroxy, aryloxy '^ thio, —S 0 3 hydrazone or halogen atom; or (3) aryl, heteroaryl, aralkyl, heteroaralkyl, hetero Cyclic 'hetero-5-alkyl, cycloalkynyl, or cycloalkynyl is optionally substituted with 1 to 3 substituents: amine, alkylamino, dialkylamino , Cold-based 'pit-oxyl', Fe-thio-based or self-fired; better, each R5 is -17- __ This paper size applies to China National Standard (CNS) A4 (210X 297 mm) (please Read the notes on the back before filling this page) Order printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 520362 A7 B7 V. Description of the invention (15) (1) Hydrogen; (2) Ci-C8 alkyl, C2-C8 晞Group or C2-C8 block group is optionally substituted by 1 to 3 substituents selected from the group consisting of: amino group, CM4 alkylamino group:-(0-C 4 -graft group) amino group "Sycyl" C 1 -C 4 alkoxy, C 1 · C 4 thio -S 0 3 Η or a halogen atom; or (3) aryl, heteroaryl, arylalkyl, heteroaryl-CVC4 · alkyl, heterocyclyl, heterocyclyl-CVC4-alkyl, C3-C8 A cycloalkyl, or C3-C8-cycloalkylalkyl, is optionally substituted with 1-3 substituents selected from the group: Amine 'C1-C4 Phenylamino'di- (C1-C4-alkyl) Amine 'Cyl-C4 alkoxy, Ci-C ^ alkylthio, CrQ alkyl or Ci-C # haloalkyl containing 1-3 halogen atoms; more preferably, each R5 is (1) Hydrogen; (2) cvc4 alkyl, C2-C5 alkenyl or C2-C5 block optionally substituted with 1 to 3 substituents selected from: amine, Ci-C4 tigerylamino 'di- ( Cl-C4-alkyl) amine, hydroxyl, CVC4 alkoxy, CrC4 sulfur, -so3H or halogen atom; or printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling in this (3) aryl, heteroaryl, aryl-Ci-CV alkyl, heteroaryl-Ci_c4-alkyl, heterocyclyl, heterocyclyl-CVC4-alkyl, C3-C8 cycloalkyl, Or C3-C8-cycloalkyl-Ci-Cc alkyl is optionally substituted with 1-3 substituents selected from the group consisting of: amine, CrQ alkylamine, bis- (CVC4-alkyl) amine Radical 'Cycloyl' Cl-C4 alkoxy, CVC4 alkylthio, CVC4 alkyl or C 1 C 4 self radical containing 3 self atoms; more preferably, each R5 is -18 -__ This paper size applies China National Standard (CNS) A4 specification (210X297 mm) 520362 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (16) (1) 氲; (2) Ci-C4fe-based or C2-C5 ene The group selectivity is substituted by 1 to 3 substituents selected from the group consisting of amine, di- (Ci-C4-alkyl) amino, hydroxyl, CrQ alkoxy 'C1-C4sulfanyl, -SO3H or halogen Atom; or (3) Winteryl-Ci-C2_: l-filler, heteroaryl-Ci-C〗 -fluorenyl'heterosyl · Ci-Cy alkyl or C3_C6_cycloalkyl-Ci-Cr alkane The group selectivity is substituted by 1-3 substituents selected from the group consisting of amine, di- (Ci-Cr alkyl) amino, hydroxyl, oxy, CpCztthio, Ci-C4thio or containing 1- CrQ haloalkyl with 3 halogen atoms; more preferably, each is fluorene hydrogen; (2) C 1-C4 pit groups are optionally substituted with 1 to 3 substituents selected from: amine, di- (CVCV Alkyl) amino, hydroxyl, CVGalkoxy, (^-(^ alkylthio or fluorene atom; or (3) -CVC2-alkyl, heteroaryl-CVC2-alkyl, heterocyclyl-CVc2-alkyl or C3-C6-cycloalkyl-Ci-Cr alkyl are optionally substituted with 1-3 substituents selected from : Amine group, di- (C ^ -Cr alkyl) amino group, alkoxy group, alkoxy group, alkylthio group, methoxy group, methylthio group, Ci-Cj alkyl group or trifluoromethyl group; more preferred Each R5 is (1) hydrogen; (2) Ci-C # alkyl optionally substituted by 1 to 3 halogen atoms; or (3) phenyl-Ci-Cy alkyl or heteroaryl_Cl_c2-alkane The group selectivity is substituted by 1 to 3 substituents selected from the group consisting of amine, dimethylamino, hydroxyl, and methoxy. ______ 19- This paper is applicable to China Standards (CNS) M Regulation (21GX297) (%) (Please read the precautions on the back before filling out this page} 、-= 口 520362 A7 ______ __ B7 V. Description of the invention (17) 'Methylthio' methyl or trimethyl group; (Please read the first Note that please fill in this page) More preferably, each R5 is argon or Cl-c4 alkyl; and most preferably each r5 is hydrogen; where each R20 is (1) alkyl, the alkenyl or alkynyl selectivity is 1 Substituted by 3 substituents selected from: amino, alkylamino , Dialkylamino, alkylamino, alkoxycarbonylamino, N- (alkoxycarbonyl) -N_ (alkyl) amino, aminocarbonylamino, alkylsulfoamido, hydroxyl, alkyl Oxy, alkylthio, alkylsulfinyl, alkylsulfonyl, self-atomic or arylalkoxy, arylalkylthio, arylalkylsulfonyl, cycloalkyl, heterocyclyl , Aryl or heteroaryl is optionally substituted by 1 to 3 substituents selected from the group consisting of amine, alkylamino, dialkylamino, alkylamino, alkoxycarbonylamino, alkylsulfonate Fluorenylamino, alkylfluorenyl, hydroxy, alkoxy, thiosulfanyl, alkynylsulfenyl, alkynylsulfenyl, halogen atom, alkyl, or alkyl; (2) heterocyclic group is optionally Substituted by 3 substituents selected from the group consisting of: amino, alkylamino, dialkylamino, alkylamino, alkoxycarbonylamino, alkylsulfonamido, hydroxyl, alkoxy, alkyl Thio, alkyl or self-alkyl; or (3) aryl or heteroaryl is optionally substituted with 1 to 3 substituents selected from: amino, alkylamino, dialkylamino, alkyl Amido, alkoxycarbonylamine Member of the Central Standards Bureau of the Ministry of Economic Affairs Consumer cooperative printing group, alkylsulfonylamino, alkoxycarbonyl, hydroxyl, alkoxy, alkylthio, cyano, halogen atom, azide, alkyl or oxyalkyl; preferably, each R2. Respectively (UCi-Cs alkyl, C2-C8 alkenyl or C2-C8 alkynyl are optionally substituted by 1 to 3 substituents selected from the group consisting of: amine, CrC4 alkylamino, di-C4 alkyl) amine Base 'C1-C5 Amine Group' (C1-C4 Pit Oxygen) Talking about Amine Group '-20 -__ This paper is suitable for ^ 1 ^ national standard ((: 1 ^) eight 4 specifications (21〇 > <; 297 mm) * 520362 A7 B7 V. Description of the invention (18) (Please read the notes on the back before filling out this page} N-GCVC4 Antioxidant) Amino, Amino, Amino, Amino, eve) alkylsulfonamido, hydroxyl, C! -C4 alkoxy, CVC4 alkylthio, Ci-C4 alkylsulfenyl, CVC4 alkylsulfenyl, halogen atom or aryl-CVC4 · alkane Oxy, aryl-CVCV alkylthio, arylalkylsulfone Si: group 'C 3-C 8 rimyl' heterocyclic, aryl or heteroaryl selectable from 1 to 3 selected from Substituent substitution: amine, CrG alkylamine, di- (CVC4 alkyl) amine, CrC5醯 amino group, (CVC4 alkoxy) carbonylamino group 'Ci-C ^ alkyl group continued amine group, Ci-C〗 donkey group, borrowing group, Ci-C ^ alkoxy group, (VC4 alkylthio group, CVC4 Alkylsulfinyl, CVC4 alkylsulfonyl, self atom, (^-€ 4 tigeryl or (1 ^ -04 haloalkyl) containing 1-3 halogen atoms; (2) heterocyclic group selectivity Substituted by 1 to 3 substituents selected from the group consisting of amine, CVC4 alkylamino, di- (CVC4 alkyl) amino, CrCs alkylamino '(CrQ alkoxy) carbonylamino, Ci-C # Alkylsulfonamido, hydroxyl,

CrQ烷氧基，CVC4烷硫基，CVC4烷基或含1-3個鹵原子 之CVC4鹵燒基；或 (3) 芳基或雜芳基選擇性由1至3個選自下列之取代基取代 :胺基，CVC4烷基胺基，二-(CVCU烷基）胺基，CVCs烷 經濟部中央標準局員、工消費合作社印製 酉從版基’（C 1 _ C 4坑氧》)基胺基’ C 1 - C 4坑基續酿胺基’ (Ci-C4：fe氧）援基，藉基，Ci_C4燒氧基，C1-C4坑硫基’氰 基，鹵原子，疊氮基，烷基或含1-3個鹵原子之C^ c4鹵貌基； 更佳’各個R20分別爲 (UCrCs烷基，C2-C5烯基或C2-C5炔基選擇性由1至3個 選自下列之取代基取代：胺基，Ci-Q烷基胺基，二-(q- -21 - 晒 " - 本紙張尺度適用中國國家標準（CNS ) A4規格（21〇><297公釐） 經濟部中央標準局員工消費合作社印製 520362 A7 __E___ 五、發明説明（19 ) C4烷基）胺基，Ci-Cs烷醯胺基，（CVC4烷氧）羰基胺基， 烷氧）羰基）_N-(CVC4烷基）胺基，胺基羰基胺基 ，CVC4烷基磺醯胺基，羥基，CrC4烷氧基，CVC4烷硫 基，烷基亞磺醯基，烷基磺醯基，鹵原子或芳 基-CVC4-烷氧基，芳基-CVC4-烷硫基，芳基烷基磺 醯基，c3-c8環烷基，雜環基，芳基或雜芳基選擇性由1 至3個選自下列之取代基取代：胺基，Ci -C4烷基胺基，二 -(CVC4烷基）胺基，cvc5烷醯胺基，（CrC4烷氧）羰基胺基 ’ Ci-Ce燒基橫醯胺基，C1-C5燒酸基，基’ C1-C4坑氧 基，Ci-C^烷硫基，CVC4烷基亞磺醯基，CVC4烷基磺醯 基’鹵原子，C1-C4燒基或含1-3個鹵原子之C1-C4鹵燒基； (2) 雜環基選擇性由1至3個選自下列之取代基取代：胺基 ，（VC4烷基胺基，二-(CVC4烷基）胺基，CrCs烷醯胺基 ，（CrQ烷氧）羰基胺基，CrC#烷基磺醯胺基，羥基， cvc4烷氧基，CVC4烷硫基，CVC4烷基或含1-3個鹵原子 之c^cu鹵院基；或 (3) 芳基或雜芳基選擇性由1至3個選自下列之取代基取代 :胺基，Κ4烷基胺基，二-(CVC4烷基）胺基，Ci-C5烷 醯胺基，（Cl_C4烷氧）羰基胺基，Cl-C4烷基磺醯胺基， (Ci-C4垸氧）羧基，幾基，d-C#院氧基，Cl-C4统硫基’氰 基，鹵原子，疊氮基，烷基或含I-3個鹵原子之Cl· C4鹵烷基·， 、 更佳，各個R2G分別爲 (UCrC8烷基或c2-C5烯基選擇性由1至3個選自下列之取 _____ -22- ___ 本紙張尺度適用中國國家標準（CNS ) M規袼（2獻297公董） (請先閱讀背面之注意事項再填寫本頁)CrQ alkoxy, CVC4 alkylthio, CVC4 alkyl or CVC4 haloalkyl containing 1-3 halogen atoms; or (3) aryl or heteroaryl optionally selected from 1 to 3 substituents selected from Substitution: Amine, CVC4 alkylamino, di- (CVCU alkyl) amino, printed by CVCs alkane Central Standards Bureau of the Ministry of Economic Affairs, Industrial and Consumer Cooperatives, "C1_C4 pit oxygen" group Amine group 'C 1-C 4 pit group continued amine group' (Ci-C4: fe oxygen) alkoxy group, borrowing group, Ci_C4 alkoxy group, C1-C4 pit thio group 'cyano group, halogen atom, azide group , Alkyl or C ^ c4 haloalkyl groups containing 1-3 halogen atoms; more preferably, each R20 is (UCrCs alkyl, C2-C5 alkenyl or C2-C5 alkynyl, selectable from 1 to 3 Substituted from the following substituents: amine group, Ci-Q alkylamine group, di- (q- -21-tan "-This paper size applies to China National Standard (CNS) A4 specification (21〇 > < 297 (Mm) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 520362 A7 __E___ V. Description of the invention (19) C4 alkyl) amine, Ci-Cs alkylamino, (CVC4 alkoxy) carbonylamino, alkoxy) Carbonyl) _N- (CVC4 alkyl) amino, aminocarbonylamine , CVC4 alkylsulfonamido, hydroxyl, CrC4 alkoxy, CVC4 alkylthio, alkylsulfinyl, alkylsulfonyl, halogen or aryl-CVC4-alkoxy, aryl-CVC4 -Alkylthio, arylalkylsulfonyl, c3-c8 cycloalkyl, heterocyclyl, aryl or heteroaryl are optionally substituted with 1 to 3 substituents selected from: amine, Ci- C4 alkylamino group, di- (CVC4 alkyl) amino group, cvc5 alkylamino group, (CrC4 alkoxy) carbonylamino group 'Ci-Ce alkylamino group, C1-C5 alkylamino group, group' C1-C4 pitoxy, Ci-C ^ alkylthio, CVC4 alkylsulfinyl, CVC4 alkylsulfinyl 'halogen atom, C1-C4 alkyl or C1-C4 containing 1-3 halogen atoms Haloalkyl; (2) Heterocyclic groups are optionally substituted with 1 to 3 substituents selected from: amine, (VC4 alkylamino, di- (CVC4 alkyl) amino, CrCs alkylamino , (CrQ alkoxy) carbonylamino, CrC # alkylsulfonamido, hydroxyl, cvc4 alkoxy, CVC4 alkylthio, CVC4 alkyl or c ^ cu halide group containing 1-3 halogen atoms; Or (3) an aryl or heteroaryl group is optionally substituted by 1 to 3 substituents selected from the group consisting of: amino, K4 alkylamino , Di- (CVC4 alkyl) amino group, Ci-C5 alkylamino group, (Cl_C4 alkyloxy) carbonylamino group, Cl-C4 alkylsulfonamido group, (Ci-C4 alkyloxy) carboxyl group, several groups, dC # Hydroxy, Cl-C4 thio'cyano, halogen atom, azide, alkyl or Cl · C4 haloalkyl group containing 1 to 3 halogen atoms, and more preferably, each R2G is (UCrC8 alkyl or c2-C5 alkenyl selectivity is from 1 to 3 selected from the following _____ -22- ___ This paper size applies to Chinese National Standard (CNS) M Regulations (2 Xian297)) (Please (Read the notes on the back before filling out this page)

、1T 520362 A7 B7 五、發明説明（2〇 ) (請先閲讀背面之注意事項再填寫本頁) 代基取代：胺基，CrQ烷基胺基，二-(Crq烷基）胺基， (^-(：5燒醯胺基，（CVC4烷氧）羰基胺基，N-GCVC#烷氧） 羰基hN-CCrC^烷基）胺基，胺基羰基胺基，羥基，CVC4 烷氧基，CVC4烷硫基，CVC4烷基亞磺醯基，CVC4烷基 磺醯基，鹵原子或芳基-Ci-CU-烷氧基，芳基-Ci-C^烷硫基 ，芳基烷基磺醯基，c3-c6環烷基，雜環基，芳基 或雜芳基選擇性由1至3個選自下列之取代基取代：胺基 ，CVC4烷基胺基，二烷基）胺基，CVC5烷醯胺基 ，（CVC4烷氧）羧基胺基，CVC4烷基磺醯胺基，cvc5烷 醯基，羥基，CVC4烷氧基，CVC4烷硫基，鹵原子，Cr c4烷基或含1-3個鹵原子之鹵烷基； (2) 雜環基選擇性由1至2個選自下列之取代基取代：胺基 ，CVC4烷基胺基，二-(CVC4烷基）胺基，CrC5烷醯胺基 ，（(ν(：4烷氧）羰基胺基，羥基，CVC4烷氧基，CVC4烷硫 基或C1-C4坑基；或 (3) 芳基或雜芳基選擇性由1至3個選自下列之取代基取代 :胺基，CVC4烷基胺基，二-(CVC4烷基）胺基，CVC5烷 經濟部中央標準局員工消費合作社印製 醯胺基，（CrQ烷氧）羰基胺基，CrQ烷基磺醯胺基， (Ci-C#燒氧）羧基，義基，氧基，Ci-C4燒硫基，氰 基，鹵原子，疊氮基，Ci-C#烷基或含I-3個鹵原子之Cl-C2卣坑基； 更佳，各個R2G分別爲 < (l)Ci_C8坑基或C2-C5晞基選擇性由1至3個選自下列之取 代基取代：胺基，Ci-C#烷基胺基，二-(Ci-C4烷基）胺基， ___ -23- _ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐）—一 520362 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（21 ) CVC5烷醯胺基，（CVC4烷氧）羰基胺基，烷氧） 羰基）-N-(CVC4烷基）胺基，胺基羰基胺基，羥基，Ci_C4 烷氧基，（VC4烷硫基，CrC4烷基亞磺醯基，Ci-C4烷基 磺醯基，鹵原子或芳基-Ci-Cr烷氧基，芳基-CrC4-烷硫基 ，芳基烷基磺醯基，c3-c6環烷基，雜環基，芳基 或雜芳基選擇性由1至3個選自下列之取代基取代：胺基 ，CVC4燒基胺基，二-(Ci-C4燒基）胺基，Ci-C5fest胺基 ，（CVC4烷氧）羰基胺基，CVC4烷基磺醯胺基，CrCs烷 醯基，羥基，（VC4烷氧基，（^_<：4烷硫基，_原子，Cr C4烷基或含1-3個鹵原子之鹵烷基； (2) 雜環基選擇性由1至2個選自下列之取代基取代：胺基 ，二-(CVC4烷基）胺基，（Ci-C4烷氧）羰基胺基，羥基，CVC4 烷氧基，（^-(：4烷硫基或c「c4烷基；或 (3) 芳基或雜芳基選擇性由1至2個選自下列之取代基取代 :胺基，0^-(：4烷基胺基，二-(CrC^烷基）胺基，乙醯胺基 ，（CrQ烷氧）羰基胺基，CrQ烷基磺醯胺基，（C「c4烷 氧）談基’藉基，C1-C4燒氧基，C1-C4燒硫基，氰基，鹵 原子，疊氮基，烷基或三氟甲基； 更佳，各個R2G分別爲 (1 烷基選擇性由1至3個選自下列之取代基取代：胺 基，CrC4烷基胺基，二-(CVC4烷基）胺基，CVC5烷醯胺 基，（cvc4烷氧）羰基胺基，N-CCCrC*燒氧）羰基hlsKCi-c4烷基）胺基，胺基羰基胺基，羥基，Ci-C^烷氧基，Ci-C4烷硫基，烷基亞磺醯基，烷基磺醯基，鹵原 -24- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） (請先閱讀背面之注意事項再填寫本頁) 、1· 520362 A7 __________B7 _______ 五、發明説明（22 ) 子或C3-C6環烷基，雜環基，芳基或雜芳基選擇性由1至2 個選自下列之取代基取代：胺基，二-(Cl_c4烷基）胺基， CrCs烷醯胺基，（Ci-C4烷氧）羰基胺基，CVC4燒基磺醯胺 基，羥基，Ci-C4烷氧基，CVC4烷硫基，鹵原子’ C1-C4 烷基或三氟甲基； (2) 雜環基選擇性由1至2個羥基，烷氧基，CrC4烷 硫基或C 1 - C 4坑基取代，或 (3) 芳基或雜芳基選擇性由1至2個選自下列之取代基取代 :(CVC4烷氧）羰基，胺基，CVC4烷基胺基，二烷 基）胺基，羥基，Ci-C4烷氧基，Ci-C4烷硫基’氰基’鹵 原子，疊氮基，Ci-C#烷基或三氟甲基； 更佳，各個R2G分別爲 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 烷基選擇性由1至3個選自下列之取代基取代：胺 基，甲基胺基，二甲基胺基，第三丁氧羰基胺基，N-((第 三丁氧）羰基）·Ν·(甲基）胺基，胺基羰基胺基’羥基，丁氧 基，甲氧基，丁硫基，甲硫基，甲基亞磺醯基，甲基磺醯 基，鹵原子或C5-C6環烷基，雜環基，苯基或雜芳基選擇 性由1至2個選自下列之取代基取代：胺基，二甲基胺基 ，乙醯胺基，羥基，甲氧基，甲硫基，卣原子，甲基或三 氟甲基； (2) 選擇性由1-2個經基或Ci-C4烷基取代之雜環基；或 (3) 芳基或雜芳基選擇性由1 -2個選自下列之取代基取代： 胺基，二甲基胺基，羥基，甲氧基，曱硫基，卣原子，甲 基或三氟甲基； -25- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（23) 更佳，各個R2。分別爲 (請先閱讀背面之注意事項再填寫本頁} (UCrQ烷基選擇性由1至3個選自下列之取代基取代：胺 基，曱基胺基，二甲基胺基，第三丁氧羰基胺基，N-((第 三丁氧）羰基）-N-(甲基）胺基，胺基羰基胺基，羥基，丁氧 基，甲氧基，丁硫基，甲硫基，甲基亞磺醯基，甲基磺醯 基，鹵原子或C5-C6環烷基，雜環基，苯基或雜芳基選擇 性由1至2個選自下列之取代基取代：胺基，二甲基胺基 ’乙酿胺基，藉基，甲氧基，甲硫基，函原子’甲基或三 氟甲基； (2) 雜環基·，或 (3) 芳基或雜芳基選擇性由1-2個選自下列之取代基取代： 胺基，二甲基胺基，羥基，甲氧基，甲硫基，自原子，甲 基或三氟甲基； 取佳’各個R 2 〇分別爲 (-C6烷基選擇性由1至3個選自下列之取代基取代：胺 基，甲基胺基，二甲基胺基，羥基或苯基或雜芳基選擇性 由1至2個選自下列之取代基取代··胺基，二甲基胺基， 羥基，曱氧基，甲硫基，卣原子，甲基或三氟甲基； 經濟部中央標準局員工消費合作社印製 (2) 雜環基；或 (3) 芳基或雜芳基選擇性由1-2個選自下列之取代基取代： 胺基，二甲基胺基，羥基，甲氧基，甲硫基，_原子’甲 基或三氟甲基； 各個r21分別爲氫或r20 ; 各個R22分別爲 -26- __ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（24 ) ⑴氫； (2) 烷基選擇性由雜環基，芳基或雜芳基基團取代，而又選 擇性由1至3個選自下列之取代基取代：胺基，烷基胺基 ，二娱*基胺基，燒醯胺基，燒氧羰基胺基，垸基績酿胺基 ，羥基，烷氧基，烷硫基，烷基亞磺醯基，烷基磺醯基， 氨基，_原子，虎基或_坑基；或 (3) 雜環基，芳基或雜芳基選擇性由1至3個選自下列之取 代基取代：胺基，烷基胺基，二烷基胺基，烷醯胺基，烷 氧羰基胺基，烷基磺醯胺基，羥基，烷氧基，烷硫基，烷 基亞續基，燒基續SS基，氰基，ή原子，燒基或_燒基 ;但當Ζ爲鍵結及Υ爲_NR22_C(0)-NH2時，R22非爲選擇 性取代芳基； 較佳，各個R22分別爲 •⑴氫； 經濟部中央標準局員工消費合作社印袋 (請先閱讀背面之注意事項再填寫本頁) 烷基選擇性由雜環基，芳基或雜芳基基團取代， 而又選擇性由1至3個選自下列之取代基取代：胺基， CVC4烷基胺基，二烷基）胺基，烷醯胺基， (CVC4烷氧）羰基胺基，CVC4烷基磺醯胺基，羥基，CVC4 坑氧基’ Ci-C4坑硫基’ C1-C4燒基亞績酿基’ Ci_C4：fe基 磺醯基，氰基，鹵原子，C/C4烷基或含1-3個鹵原子之 CVC4鹵烷基；或 (3)雜環基，芳基或雜芳基選擇性由i至3個選自下列之取 代基取代：胺基，烷基胺基，二-(Ci-C#烷基）胺基， Ci-C5fe&k胺基’（C1-C4燒氧）幾基胺基，C1-C4坑基崎酿胺 _______ -27- 本紙張尺度適用中國國家標準（CNS ) A4規格（27^97公釐） 520362 經濟部中央標準局員工消費合作社印裝 A7 B7 五、發明説明（25 ) " 基，基，Ci_C4燒乳基，（^-〔4燒硫基，垸基亞石簧 S&基，CVCUfe基續醯基，氰基，鹵原子，Ci_c4燒基或含 1_3個_原子之Cl_C4鹵烷基；但當z爲鍵結及γ爲_NR22_ C(〇)-NH2時，R22非爲選擇性取代芳基； 更佳，各個R22分別爲 (1) 氫；或 (2) Ci-C4坑基逼擇性由苯基或雜芳基4 —者取代，而又選 擇性由1至3個選自下列之取代基取代：胺基，二_(C1-C2 燒基）胺基，CVC5燒醯胺基，（CVC4燒氧）羧基胺基，經基 ’ CrC4燒氧基，Ci-Cd貌硫基，氰基，鹵原子，CpCU垸 基或含1_3個鹵原子之Ci-Ca鹵貌基； 更佳，各個R22分別爲氫或（^-山烷基；及最佳，各個r22 分別爲氫或甲基·，、 1T 520362 A7 B7 V. Description of the invention (20) (Please read the notes on the back before filling this page) Substituent substitution: amine, CrQ alkylamino, di- (Crq alkyl) amino, ( ^-(: 5 sulfonylamino, (CVC4 alkoxy) carbonylamino, N-GCVC # alkoxy) carbonyl hN-CCrC ^ alkyl) amino, aminocarbonylamino, hydroxyl, CVC4 alkoxy, CVC4 alkylthio, CVC4 alkylsulfinyl, CVC4 alkylsulfinyl, halogen or aryl-Ci-CU-alkoxy, aryl-Ci-C ^ alkylthio, arylalkylsulfonyl Fluorenyl, c3-c6 cycloalkyl, heterocyclyl, aryl or heteroaryl are optionally substituted with 1 to 3 substituents selected from the group consisting of: amino, CVC4 alkylamino, dialkyl) amino , CVC5 alkylamino, (CVC4 alkoxy) carboxyamino, CVC4 alkyl sulfonamido, cvc5 alkyl, hydroxy, CVC4 alkoxy, CVC4 alkylthio, halogen atom, Cr c4 alkyl or containing Haloalkyl groups of 1-3 halogen atoms; (2) Heterocyclic groups are optionally substituted by 1 to 2 substituents selected from the group consisting of: amino, CVC4 alkylamino, di- (CVC4 alkyl) amino , CrC5 alkylamino, ((ν (: 4alkoxy) carbonylamino, hydroxyl, CV C4 alkoxy, CVC4 alkylthio or C1-C4 pentyl; or (3) aryl or heteroaryl is optionally substituted with 1 to 3 substituents selected from: amino, CVC4 alkylamino, Di- (CVC4 alkyl) amino group, CVC5 alkane printed by the Consumer Standards Cooperative of the Central Standard Bureau of the Ministry of Economic Affairs, (CrQ alkoxy) carbonyl amine, CrQ alkyl sulfonyl amine, (Ci-C # burning oxygen) Carboxyl, sense, oxy, Ci-C4sulfanyl, cyano, halogen, azide, Ci-C # alkyl or Cl-C2 fluorenyl group containing 1 to 3 halogen atoms; more preferably, each R2G (1) Ci_C8 pit group or C2-C5 fluorenyl group are optionally substituted with 1 to 3 substituents selected from: amine group, Ci-C # alkylamino group, di- (Ci-C4 alkyl group ) Amine-based, ___ -23- _ This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm)-520362 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 5. Description of the invention (21) CVC5 Alkylamino, (CVC4alkoxy) carbonylamino, alkoxy) carbonyl) -N- (CVC4alkyl) amino, aminocarbonylamino, hydroxyl, Ci_C4 alkoxy, (VC4 alkylthio, CrC4 Alkylsulfinyl, Ci-C4 Alkylsulfonyl, halogen atom or aryl-Ci-Cralkoxy, aryl-CrC4-alkylthio, arylalkylsulfonyl, c3-c6 cycloalkyl, heterocyclyl, aryl or Heteroaryl is optionally substituted with 1 to 3 substituents selected from: amine, CVC4 alkylamino, di- (Ci-C4 alkyl) amino, Ci-C5fest amino, (CVC4 alkoxy) Carbonylamino, CVC4 alkylsulfonamido, CrCs alkylsulfonyl, hydroxyl, (VC4 alkoxy, (^ _ <: 4 alkylthio, _ atom, Cr C4 alkyl or 1-3 halogen atoms Haloalkyl; (2) the heterocyclic group is optionally substituted by 1 to 2 substituents selected from the group consisting of amine, di- (CVC4 alkyl) amino, (Ci-C4 alkoxy) carbonylamino, Hydroxyl, CVC4 alkoxy, (^-(: 4 alkylthio or c "c4 alkyl; or (3) aryl or heteroaryl is optionally substituted with 1 to 2 substituents selected from: amine , 0 ^-(: 4 alkylamino, di- (CrC ^ alkyl) amino, acetamido, (CrQ alkoxy) carbonylamino, CrQ alkylsulfonamido, (C "c4 alkyl Oxygen) alkynyl, boryl, C1-C4 thiol, C1-C4 thiol, cyano, halogen, azido, alkyl or trifluoromethyl; Preferably, each R2G is (1 alkyl optionally substituted by 1 to 3 substituents selected from: amine, CrC4 alkylamino, di- (CVC4 alkyl) amino, CVC5 alkylamino, (Cvc4 alkoxy) carbonylamino, N-CCCrC * oxy) carbonyl hlsKCi-c4alkyl) amino, aminecarbonylamino, hydroxyl, Ci-C ^ alkoxy, Ci-C4 alkylthio, alkane Sulfinyl sulfenyl, alkylsulfonyl sulfonyl, halogenogen-24- This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) (Please read the precautions on the back before filling this page) 、 1 · 520362 A7 __________B7 _______ V. Description of the invention (22) The proton or C3-C6 cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted by 1 to 2 substituents selected from the group consisting of: amino, di -(Cl_c4 alkyl) amino group, CrCs alkylamino group, (Ci-C4 alkoxy) carbonylamino group, CVC4 alkylsulfonamido group, hydroxyl group, Ci-C4 alkoxy group, CVC4 alkylthio group, halogen atom 'C1-C4 alkyl or trifluoromethyl; (2) Heterocyclic groups are optionally substituted with 1 to 2 hydroxyl, alkoxy, CrC4 alkylthio or C 1 -C 4 pit groups, or (3) aromatic Or heteroaryl selectivity from 1 to 2 A substituent selected from the group consisting of: (CVC4 alkoxy) carbonyl, amine, CVC4 alkylamino, dialkyl) amino, hydroxyl, Ci-C4 alkoxy, Ci-C4 alkylthio 'cyano' Halogen, azide, Ci-C # alkyl or trifluoromethyl; more preferably, each R2G is printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) Alkyl Selective substitution by 1 to 3 substituents selected from the group consisting of amino, methylamino, dimethylamino, third butoxycarbonylamino, N-((thirdbutoxy) carbonyl) · N · (Meth) amino, aminocarbonylamino'hydroxy, butoxy, methoxy, butylthio, methylthio, methylsulfinyl, methylsulfonyl, halogen atom or C5- C6 cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally substituted by 1 to 2 substituents selected from the group consisting of amine, dimethylamino, acetamido, hydroxy, methoxy, Methylthio, fluorene atom, methyl or trifluoromethyl; (2) optionally substituted by 1-2 heterocyclic groups substituted with a group or Ci-C4 alkyl; or (3) aryl or heteroaryl selection Sex is selected from 1-2 Substituent substitution: Amine, dimethylamino, hydroxy, methoxy, fluorenylthio, fluorene atom, methyl or trifluoromethyl; -25- This paper size applies to China National Standard (CNS) A4 specifications ( 210X297 mm) 520362 A7 B7 V. Invention description (23) is better, each R2. Respectively (Please read the notes on the back before filling out this page) (UCrQ alkyl is optionally substituted by 1 to 3 substituents selected from: amino, fluorenylamino, dimethylamino, third Butoxycarbonylamino, N-((third butoxy) carbonyl) -N- (methyl) amino, aminocarbonylamino, hydroxyl, butoxy, methoxy, butylthio, methylthio , Methylsulfinyl, methylsulfinyl, halogen, or C5-C6 cycloalkyl, heterocyclyl, phenyl, or heteroaryl are optionally substituted with 1 to 2 substituents selected from: amines Group, dimethylamino group, ethylamino group, boryl group, methoxy group, methylthio group, function atom group's methyl group or trifluoromethyl group; (2) heterocyclic group, or (3) aryl group or Heteroaryl is optionally substituted by 1-2 substituents selected from the group consisting of: amine, dimethylamino, hydroxyl, methoxy, methylthio, self-atom, methyl or trifluoromethyl; preferably 'Each R 2 0 is (-C6 alkyl optionally substituted by 1 to 3 substituents selected from: amino, methylamino, dimethylamino, hydroxy or phenyl or heteroaryl Select from 1 to 2 substituents · Amine, dimethylamino, hydroxy, methoxy, methylthio, fluorene, methyl or trifluoromethyl; (2) Heterocyclyl printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs; or (3) The aryl or heteroaryl group is optionally substituted by 1-2 substituents selected from the group consisting of: amine, dimethylamino, hydroxy, methoxy, methylthio, _ atom 'methyl or tris Fluoromethyl; each r21 is hydrogen or r20; each R22 is -26- (2) Alkyl is optionally substituted with heterocyclyl, aryl or heteroaryl group, and optionally substituted with 1 to 3 substituents selected from the group consisting of: amino, alkylamino, diammonium * Amino, sulfanylamino, oxocarbonylamino, sulfanylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, amino, _ atom , Tiger group or _ pit group; or (3) heterocyclic group, aryl or heteroaryl group is optionally substituted by 1 to 3 substituents selected from the group consisting of amino, alkylamino, dialkylamino , Alkylamino, alkoxycarbonylamino, alkylsulfonamido, hydroxy, alkoxy, alkylthio, alkylidene, alkyl, SS, cyano, alkyl, alkyl _ Burning group; but when Z is bonded and Υ is _NR22_C (0) -NH2, R22 is non-selectively substituted aryl group; better, each R22 is • Hydrogen; Employee Consumer Cooperative of Central Bureau of Standards Printed bags (please read the notes on the back before filling this page) Alkyl is optionally substituted by heterocyclyl, aryl or heteroaryl group, and optionally substituted by 1 to 3 substituents selected from : Amine, CVC4 alkylamino, dialkyl) amino, alkylamino, (CVC4alkoxy) carbonylamino, CVC4 alkylsulfonamido, hydroxyl, CVC4 pitoxy 'Ci-C4 pit Thio 'C1-C4 alkyl group Ci_C4: fe-sulfosulfanyl, cyano, halogen atom, C / C4 alkyl or CVC4 haloalkyl group containing 1-3 halogen atoms; or (3) Heterocyclyl, aryl or heteroaryl is optionally substituted by i to 3 substituents selected from the group consisting of amino, alkylamino, di- (Ci-C # alkyl) amino, Ci-C5fe & k Amine '(C1-C4 burned oxygen) , C1-C4 Hangjizhuang amine _______ -27- This paper size applies to Chinese National Standard (CNS) A4 (27 ^ 97 mm) 520362 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (25) " radical, radical, Ci_C4 alkyl group, (^-[4-sulfuryl group, fluorenyl sulfite group S & group, CVCUfe-based fluorenyl group, cyano group, halogen atom, Ci_c4 alkyl group or containing 1-3 Cl_C4 haloalkyl groups of _ atoms; but when z is bonded and γ is _NR22_C (〇) -NH2, R22 is not a selectively substituted aryl group; more preferably, each R22 is (1) hydrogen; or (2) Ci-C4 pit group is optionally substituted by phenyl or heteroaryl 4-, and optionally substituted by 1 to 3 substituents selected from the group: amine, di- (C1-C2 Group) amine group, CVC5 fluorenyl amine group, (CVC4 oxyl group) carboxyamine group, via the group 'CrC4 carboxy group, Ci-Cd thio group, cyano group, halogen atom, CpCU fluorenyl group or containing 1-3 halogen atoms Ci-Ca haloalkyl groups; more preferably, each R22 is hydrogen or (^ -shanyl); and most preferably, each r22 is hydrogen or methyl,

Ri 1及Ri2分別爲芳基或雜芳基選擇性由1至3個選自下列 之取代基取代： (1) R30 ; (2) 卣原子或氰基； (3) -C(O)_R30，-C(O)-OR29，-C(O)_NR31U-C(NR31)- N R 3 1 R 3 2 ; (4) _OR29 ，_0-C(0)-R29 ，-〇-c(o)，nr31r32 或-O-C(O)· NR33_S(O)2-R30 ; (5) -SR29，-S(O)-R30，-S(0)2-R3〇，-S(〇)2-NR31R32，-S(O)2-NR33-C(O)-R30，4(Ο)2-ΝΙ133·(：(Ο)-〇Κ30 或-s(0)2-NR33_C(0)-NR3iR32 ;或 -28 - 本紙張尺度適用中Ϊ國家標準(〇奶）八4規格（210乂297公釐） (請先閱讀背面之注意事項再填寫本頁) 訂 - 520362 A7 ____B7 _ 五、發明説明（26 ) (6)-NR3lR32 9 -NR33-C(0)-R29 9 -NR33-C(〇)-〇R30 9 -NR33-C(0)-NR3iR32 ? -NR33-C(NR3 1 )-NR3 1 R32 9 "N R3 3 - S ( 0) 2 - R3 0 或-NR33_S(0)2_NR3iR32 ; 但（1) R i i非爲4 _ p比淀基，4 -喃淀基，4 - 4 4基或6 -異p奎琳 基選擇性由1-2個取代基取代；及（2)取代於各個Rii及Ri2 上之芳基，雜芳基，環烷基及雜環基總數爲0-1 ; 較佳，Ri i及R12分別爲芳基或雜芳基選擇性由1至2個選 自下列之取代基取代： (1) R30 ; (2) 鹵原子或氰基； (3) -C(O)-R30 ’ -C(0)-0R29 ’ -C(0)-NR3lR32 4-C(NR31)_ NR31R32 ; (4) -〇R29 ’ -〇-C(0)-R29 ’ ·〇-〇(0)_ΝΙ^3ΐΙ^32 或-O-C(O)- NR33-S(O)2_R30 ; (5) -SR29 ? "S(0)-R3〇 ? ~S(0)2"R3〇 ? - S (0)2 "NR3 1R32 9 - S(O)2-NR33-C(O)_R30，-S(O)2-NR33_C(O)-OR30 或 4(0)2· nr33_c(o)-nr31r32 ;或 (6) -NR3】R32’-NR33-C(O)-R29’-NR33-C(O)-〇R30，-NR33· 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) c(o)_nr31r32，-nr33-c(nr31)_nr31r32，-nr33-s(o)2-r30 或-NR33-S(0)2-NR3iR32 ; 但（l)Rn非爲4-吡啶基，4-嘧啶基，4-喹啉基或6-異喹啉 基選擇性由1_2個取代基取代；及（2)取代淤各個Rn及R12 上之芳基，雜芳基，環烷基及雜環基總數爲0-1 ; 更佳’ R! i及R! 2各自分別爲芳基或雜芳基選擇性由1至2 -29- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 _B7 _ 五、發明説明（27 ) 個選自下列之取代基取代： (1) R30 ; (2) _原子或氰基； (3) -C(0)-R3〇，-C(〇)，〇R29，-C(〇)-NR31R32 或一C(NR31)_ nr31r32 ;或 (4) -〇R29，-SR29 ’ -S(〇)-R30 ’ -S(O)2_R30，_S(0)2_NR3iR32 ，-NR31R32，-NR33_C(0)_R29 或-NR33-C(O)_〇R30 ; 更佳，Rn爲芳基及R12爲雜芳基，其中芳基及雜芳基選擇 性由1至2個選自下列之取代基取代： (1) Rs〇 ; (2) 南原子或氰基； (3) -C(O)-R30，-C(O)-〇R29，-C(〇)，NR31U-C(NR31)- NR3 1R32 ;或 (4) -〇R29，-SR29，-S(〇)-R30 ’ -S(O)2_R30 ’ -S(0)2_NR3lR32 ’ -NR31R32 或-NR33_C(0)-R29， 更佳，Rn爲芳基及R12爲雜芳基’其中芳基及雜芳基選擇 性由1至2個選自下列之取代基取代·· (1) R30 ; 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) (2) iS原子或氰基； (3) -C(0)-NR31R32，-OR29，-SR29，_S(O)-R30，_S(O)2_R30 ，-S(0)2_NR31R32，-NR31R32 或-NR33_C(0)-R29 ; 更佳，Ri i爲芳基選擇性由1至2個選自下列之取代基取代 :(l)R3〇 ; (2)_ 原子或氰基；（3)-C(0)-NR3lR32 ’ -OR29 ’ -SR29，-S(O)-R30，-S(O)2-R30，-S(0)2-NR31R32，-NR31R32 -30- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（28 ) 或-NR33-C(0)-R29 ;更佳，Ru爲芳基選擇性由1_2個選自 下列之取代基取代：胺基，二甲基胺基，乙醯胺基，羥基 ，鹵原子，氰基，甲氧基，曱硫基，甲基亞磺醯基，甲基 磺醯基，胺基羰基，甲基或三氟甲基；更佳，爲無取 代苯基或莕基或苯基由1-2個選自下列之取代基取代：胺 基，二甲基胺基，乙醯胺基，羥基，齒原子，氰基，甲氧 基，甲硫基，甲基亞磺醯基，甲基磺醯基，胺基羰基，甲 基或三氟甲基；及最佳，Rii爲無取代苯基或苯基由1-2個 選自下列之取代基取代··胺基，二甲基胺基，乙醯胺基， 羥基，卣原子，氰基，甲氧基，甲硫基，甲基磺醯基，甲 基或三氟甲基； 經濟部中央標準局員工消費合作衽印製 更佳，R12爲芳基選擇性由1至2個選自下列之取代基取代 :(l)R3〇 ; (2)卣原子或氨基；或（3)-C(0)-NR3i R32 ’ -OR29 ’ _SR〗9 ’ -NR3iR>32 或，NR33-C(0)-R29 ;更佳 ’ R12 爲雜方 基選擇性由1 -2個選自下列之取代基取代：胺基，二曱基 胺基，乙醯胺基，羥基，||原子，氰基，甲氧基，甲基或 三氟甲基；更佳，R12爲4-吡啶基，4-喹4基，4·咪唑基 或4-嘧啶基選擇性由一個選自下列之基團取代：胺基，二 甲基胺基，乙酸胺基，經基，原子，氰基’甲氧基’甲 基或三氟曱基；及最佳，R12爲4-吡啶基選擇性由一個選 二甲基胺基’乙酸胺基’謹 甲基或三氟、甲基； (請先閱讀背面之注意事項再填寫本頁) - 自下列之取代基取代：胺基 基，_原子，氰基，甲氧基 其中，各個R3〇分別爲 (1)烷基，烯基或炔基選擇性由1-3個選自下列之取代基取 31 - 衣紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（29 ) 代：-NR31R31，-C02R23，羥基，烷氧基，烷硫基，烷基亞 磺醯基，烷基磺醯基，氰基，卣原子或芳基烷氧基，芳基 烷硫基，芳基烷基磺酸基，雜環基，芳基或雜環基選擇性 由1 -3個選自下列之取代基取代：胺基，烷基胺基，二燒 基胺基，烷醯胺基，烷氧羰基胺基，烷基磺醯胺基，羥基 ，燒氧基’燒硫基’ '坑基亞續酸基’坑基橫醯基’氧基’ 鹵原子，燒基或自坑基； (2) 雜環基選擇性由1-3個選自下列之取代基取代：胺基， 烷基胺基，二烷基胺基’烷醯胺基’烷氧羰基胺基，烷基 石黃醯胺基，謹基’院氧基’燒硫基’氰基’燒基或S燒基，· (3) 芳基或雜芳基選擇性由個選自下列之取代基取代： 胺基，烷基胺基，二烷基胺基，烷醯胺基，烷氧羰基胺基 ，烷基磺醯胺基，羥基’燒氧基，烷硫基，氰基，ί原子 ，貌基或自燒基； 較佳，各個R 3 G分別爲 (1)CVC4燒基，C2-C4烯基或C2-C4块基選擇性由1_3個選 自下列之取代基取代·…NRsiR31 ’ -C〇2R23，經基， 烷氧基，Ci-C4烷硫基，CrC4烷基亞磺醯基，CpC4烷基 磺醯基，氰基，鹵原子或芳基-Cl_C4·烷氧基，芳基-Ci-Czr 烷硫基，芳基-C^C4-烷基磺醯基，雜環基，芳基或雜環基 選擇性由1 -3個選自下列之取代基取代：胺基，crC4烷基 胺基，二-(C1-C4坑基）胺基，c 5纟元g蠢胺基’（c〗_ c 4燒氧 )羰基胺基，CrC4烷基磺醯胺基，羥基，CrC4烷氧基， (VC4烷硫基，CrC4烷基亞續驢基，CVC4烷基磺醯基， -32- 本紙張尺度適用中準（CNS)^g_「21GX 297公釐）〜 -- (請先閱讀背面之注意事項再填寫本頁) 訂 520362 A7 B7 五 經濟部中央標準局員工消費合作社印製 、發明説明（3〇 氰基，鹵原子，烷基或含1-3個鹵原子之Ci-C4鹵燒 (2 )雉環基選擇性由1 _ 3個選自下列之取代基取代：胺基’ Ci-C4fe基胺基，二-(CrQ貌基）胺基，Ci-Cs坑酸胺基， (CpC4烷氧）羧基胺基，Cl_c4燒基續醯胺基，禮基，Cl-C4 氣氧基，Κ4烷硫基，氰基，Ci-C#烷基或含I-3個鹵原 子之CrC4鹵烷基； (3)芳基或雜芳基選擇性由i_3個選自下列之取代基取代： 胺基，CrG烷基胺基，二_(Cl-C4烷基）胺基，CrC5烷醯 胺基，（(：广(：4烷氧）羰基胺基，Cl-C4烷基磺醯胺基，羥基 ，（VC4烷氧基，CVC4烷硫基，氰基，鹵原子，CVC4烷 基或含1-3個鹵原子之Ci-Cq鹵燒基； 更佳，各個R3G分別爲 (UCrq烷基選擇性由1-3個選自下列之取代基取代： (a) -NR31R31 ； (b) CrC4烷氧羰基或苯氧羰基或苯基甲氧羰基選擇性由1-3個選自下列之取代基取代：胺基，烷基胺基，二_(Ci_C4_ 燒基）胺基，CVCs烷醯胺基，（CVCU烷氧）羰基胺基，CV C4烷基磺醯胺基，羥基，Cl_C4烷氧基，CpCU烷硫基，氰 基，鹵原子，Ci-C4烷基或三氟甲基；或 (C)羥基，CVC4烷氧基，CVC4烷硫基，或苯基-CVC4-烷 氧基，苯基-Ci-Cf烷硫基，雜環基，苯基或雜芳基選擇性 由1-3個選自下列之取代基取代：胺基，烷基胺基， 二-(CVC4烷基）胺基，CVC5烷醯胺基，（CVC4烷氧）羰基胺 -33- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） (請先閲讀背面之注意事項再填寫本頁) 訂 520362 A7 -----_____B7_ —__ 五、發明説明（31 ) 基，羥基，烷氧基，CVC4烷硫基，氰基，鹵原子， C1-C4烷基或含1_3個鹵原子之Ci_c4鹵烷基； (2) 含1_3個鹵原子之（^-〔4鹵燒基；或 (3) 芳基或雜芳基選擇性由i至3個選自下列之取代基取代 :胺基，CVC4烷基胺基，二-(C^C]烷基）胺基，CrCs烷 t胺基’（C 1 - C 4纟见氧）談基胺基，每基’ C1-C4抗氧基’ C1-C4 垸硫基，氰基，鹵原子，Cl_c4烷基或三氟甲基； 更佳，各個R3G分別爲 (1 烷基選擇性由選自下列之取代基取代： (a) 胺基，烷基胺基或二-(Ci-Cc烷基）胺基；或 (b) 羥基，Cl-C4烷氧基，雜環基，苯基或雜芳基選擇性由 1-3個選自下列之取代基取代：胺基，Cl_C4烷基胺基，二 _(CVC4烷基）胺基，CVC5烷醯胺基，（CVC4烷氧）羰基胺基 ，羥基，CVC4烷氧基，CVC4烷硫基，氰基，鹵原子， Ci_C4烷基或三氟甲基； (2) 含1_3個鹵原子之CVC2鹵烷基；或 (3) 芳基或雜芳基選擇性由1至3個選自下列之取代基取代 :胺基，CVC4烷基胺基，二-(CVC4烷基）胺基，CVC5烷 醯胺基，（CVC4烷氧）羰基胺基，羥基，CVC4烷氧基，Ci-Ci 烷硫基，氰基，鹵原子，CrC#烷基或三氟甲基； 更佳，各個r3〇分別爲 烷基選擇性由苯基或雜芳基取代、而又選擇性由1-3個選自下列之取代基取代：胺基，二·（Cpq烷基）胺基， 乙酿胺基，#基，Ci_C2抗氧基’鹵原子，c^-CU燒基或三 -34- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） (請先閱讀背面之注意事項再填寫本頁)Ri 1 and Ri 2 are aryl or heteroaryl, respectively, and are optionally substituted with 1 to 3 substituents selected from: (1) R30; (2) fluorene atom or cyano; (3) -C (O) _R30 , -C (O) -OR29, -C (O) _NR31U-C (NR31)-NR 3 1 R 3 2; (4) _OR29, _0-C (0) -R29, -0-c (o), nr31r32 or -OC (O) · NR33_S (O) 2-R30; (5) -SR29, -S (O) -R30, -S (0) 2-R3〇, -S (〇) 2-NR31R32,- S (O) 2-NR33-C (O) -R30, 4 (Ο) 2-ΝΙ133 · (:( 〇) -〇Κ30 or -s (0) 2-NR33_C (0) -NR3iR32; or -28- This paper size applies to China National Standard (〇 奶) 8 4 specifications (210 乂 297 mm) (Please read the notes on the back before filling this page) Order-520362 A7 ____B7 _ V. Description of the invention (26) (6 ) -NR3lR32 9 -NR33-C (0) -R29 9 -NR33-C (〇) -〇R30 9 -NR33-C (0) -NR3iR32? -NR33-C (NR3 1) -NR3 1 R32 9 " N R3 3-S (0) 2-R3 0 or -NR33_S (0) 2_NR3iR32; but (1) R ii is not 4_p ratio, 4 -ranyl, 4-4 4 or 6 -iso p quelinyl is optionally substituted by 1-2 substituents; and (2) the total number of aryl, heteroaryl, cycloalkyl and heterocyclic groups substituted on each Rii and Ri2 is 0-1; preferably, Ri i and R12 Any other aryl or heteroaryl group is optionally substituted by 1 to 2 substituents selected from: (1) R30; (2) a halogen atom or a cyano group; (3) -C (O) -R30'-C (0) -0R29 '-C (0) -NR3lR32 4-C (NR31) _ NR31R32; (4) -〇R29' -〇-C (0) -R29 '· 〇-〇 (0) _ΝΙ ^ 3ΐΙ ^ 32 or -OC (O)-NR33-S (O) 2_R30; (5) -SR29? &Quot; S (0) -R3〇? ~ S (0) 2 " R3〇?-S (0) 2 " NR3 1R32 9-S (O) 2-NR33-C (O) _R30, -S (O) 2-NR33_C (O) -OR30 or 4 (0) 2 · nr33_c (o) -nr31r32; or (6)- NR3] R32'-NR33-C (O) -R29'-NR33-C (O) -〇R30, -NR33 · Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling out this page ) c (o) _nr31r32, -nr33-c (nr31) _nr31r32, -nr33-s (o) 2-r30 or -NR33-S (0) 2-NR3iR32; but (l) Rn is not 4-pyridyl, 4-pyrimidinyl, 4-quinolinyl or 6-isoquinolinyl are optionally substituted by 1_2 substituents; and (2) substituted aryl, heteroaryl, cycloalkyl and heteroaryl groups on each of Rn and R12 The total number of ring groups is 0-1; more preferably, R! I and R! 2 are aryl or heteroaryl, respectively. Selectivity ranges from 1 to 2 -29- This paper applies Chinese national standards ( CNS) A4 specification (210X297 mm) 520362 A7 _B7 _ 5. Description of the invention (27) Substituted by substituents selected from: (1) R30; (2) _ atom or cyano; (3) -C (0 ) -R3〇, -C (〇), 〇R29, -C (〇) -NR31R32 or -C (NR31) _ nr31r32; or (4) -〇R29, -SR29 '-S (〇) -R30'- S (O) 2_R30, _S (0) 2_NR3iR32, -NR31R32, -NR33_C (0) _R29 or -NR33-C (O) _〇R30; more preferably, Rn is aryl and R12 is heteroaryl, of which aryl And heteroaryl are optionally substituted with 1 to 2 substituents selected from: (1) Rs0; (2) south atom or cyano; (3) -C (O) -R30, -C (O) -〇R29, -C (〇), NR31U-C (NR31)-NR3 1R32; or (4) -〇R29, -SR29, -S (〇) -R30 '-S (O) 2_R30' -S (0 ) 2_NR3lR32 '-NR31R32 or -NR33_C (0) -R29, more preferably, Rn is aryl and R12 is heteroaryl' wherein aryl and heteroaryl are selectively substituted by 1 to 2 substituents selected from · (1) R30; Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) (2) iS atom or cyano; (3) -C (0) -NR31R32,- OR29, -SR29, _S (O) -R30, _S (O) 2_R30,- S (0) 2_NR31R32, -NR31R32 or -NR33_C (0) -R29; more preferably, Ri i is an aryl group selectively substituted by 1 to 2 substituents selected from: (1) R3〇; (2) _ Atom or cyano; (3) -C (0) -NR3lR32 '-OR29' -SR29, -S (O) -R30, -S (O) 2-R30, -S (0) 2-NR31R32, -NR31R32 -30- This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 520362 A7 B7 V. Description of the invention (28) or -NR33-C (0) -R29; better, Ru is aryl selective Substituted by 1_2 substituents selected from the group consisting of amine, dimethylamino, acetamido, hydroxyl, halogen atom, cyano, methoxy, sulfanyl, methylsulfinyl, methyl Sulfofluorenyl, aminocarbonyl, methyl or trifluoromethyl; more preferably, unsubstituted phenyl or fluorenyl or phenyl substituted with 1-2 substituents selected from: amine, dimethylamine Methyl, ethylamino, hydroxyl, tooth atom, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl; and most Preferably, Rii is an unsubstituted phenyl group or a phenyl group is substituted by 1-2 substituents selected from the following: amine group, dimethyl group Amine group, acetamido group, hydroxyl group, fluorene atom, cyano group, methoxy group, methylthio group, methylsulfonyl group, methyl group or trifluoromethyl group Preferably, R12 is an aryl group selectively substituted by 1 to 2 substituents selected from: (1) R3〇; (2) a fluorene atom or an amino group; or (3) -C (0) -NR3i R32'-OR29 '_SR〗 9' -NR3iR > 32 or, NR33-C (0) -R29; more preferably, R12 is a heterosquaryl group optionally substituted by 1-2 substituents selected from the group consisting of amine, diamidoamine Group, acetamido group, hydroxyl group, || atom, cyano group, methoxy group, methyl group or trifluoromethyl group; more preferably, R12 is 4-pyridyl group, 4-quinolyl group, 4 · imidazolyl group or 4 -The pyrimidinyl group is optionally substituted by a group selected from the group consisting of: amine, dimethylamino, acetamino, acetyl, atom, cyano'methoxy'methyl or trifluorofluorenyl; and most Good, R12 is 4-pyridyl. Selective by a dimethylamine 'acetamido' or methyl or trifluoro, methyl; (Please read the precautions on the back before filling this page)-From the following Substituent substitution: amino group, _ atom Among cyano and methoxy groups, each R30 is (1) alkyl group, alkenyl group or alkynyl group is selected from 1-3 substituents selected from the following 31-Applicable to Chinese National Standard (CNS) A4 specifications (210X297 mm) 520362 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (29) Generation: -NR31R31, -C02R23, hydroxyl, alkoxy, alkylthio, alkylsulfinium Group, alkylsulfonyl, cyano, fluorene atom or arylalkoxy, arylalkylthio, arylalkylsulfonyl, heterocyclyl, aryl or heterocyclyl Substituted by a substituent selected from the group consisting of: amino, alkylamino, dialkylamino, alkylamino, alkoxycarbonylamino, alkylsulfoamido, hydroxy, methyloxy '' 'Phenyl phosphinic acid group' Phenyl fluorenyl 'oxy' halogen atom, alkynyl or self-pitching group; (2) Heterocyclic group is optionally substituted with 1-3 substituents selected from: amine Group, alkylamino group, dialkylamino group 'alkylamino group' alkoxycarbonylamino group, alkyl stilbeneamine group, alkyl group 'cooxy group' thio group 'cyano group or S (3) Aryl or heteroaryl is optionally substituted by a substituent selected from the group consisting of: amino, alkylamino, dialkylamino, alkylamino, alkoxycarbonylamino, alkyl Sulfosulfenylamino, hydroxy'alkoxy, alkylthio, cyano, atom, aryl or self-alkyl; preferably, each R 3 G is (1) CVC4 alkyl, C2-C4 alkenyl Or the C2-C4 block is optionally substituted with 1-3 substituents selected from ... NRsiR31 '-C〇2R23, vial, alkoxy, Ci-C4 alkylthio, CrC4 alkylsulfinyl, CpC4 Alkylsulfonyl, cyano, halogen or aryl-Cl_C4 · alkoxy, aryl-Ci-Czr alkylthio, aryl-C ^ C4-alkylsulfonyl, heterocyclyl, aryl Or the heterocyclic group is optionally substituted by 1 to 3 substituents selected from the group consisting of: amine, crC4 alkylamino, di- (C1-C4 pentyl) amino, c 5 fluorenyl g ', c〗 _ c 4 Oxyoxy) carbonylamino, CrC4 alkylsulfonamido, hydroxyl, CrC4 alkoxy, (VC4 alkylthio, CrC4 alkylidene, CVC4 alkylsulfonyl, -32 -This paper size applies to CNS ^ g_ 「21GX 297mm」 ~-(Please read the Note: Please fill in this page again.) Order 520362 A7 B7 Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, and a description of the invention (30 cyano, halogen, alkyl, or Ci-C4 halogenated with 1-3 halogen atoms) (2) The fluorene ring group is optionally substituted by 1 to 3 substituents selected from the group consisting of: amine group 'Ci-C4fe amine group, di- (CrQ group) amine group, Ci-Cs pit acid amine group, ( CpC4 alkoxy) carboxyamino group, Cl_c4 alkyl group, fluorenylamino group, ceryl group, Cl-C4 aerooxy group, K4 alkylthio group, cyano group, Ci-C # alkyl group or CrC4 halide containing 1 to 3 halogen atoms Alkyl; (3) aryl or heteroaryl is optionally substituted by i_3 substituents selected from: amino, CrG alkylamino, di_ (Cl-C4 alkyl) amino, CrC5 alkylamine Group, ((: wide (: 4 alkoxy) carbonylamino, Cl-C4 alkylsulfonamido, hydroxyl, (VC4 alkoxy, CVC4 alkylthio, cyano, halogen atom, CVC4 alkyl or containing Ci-Cq haloalkyl groups of 1-3 halogen atoms; more preferably, each R3G is (UCrq alkyl optionally substituted by 1-3 substituents selected from: (a) -NR31R31; (b) CrC4 Alkoxycarbonyl or phenoxycarbonyl or phenylmethoxycarbonyl A substituent selected from the group consisting of: amino, alkylamino, di_ (Ci_C4_alkyl) amino, CVCs alkylamino, (CVCU alkoxy) carbonylamino, CV C4 alkylsulfonamido, Hydroxyl, Cl_C4 alkoxy, CpCU alkylthio, cyano, halogen, Ci-C4 alkyl or trifluoromethyl; or (C) hydroxyl, CVC4 alkoxy, CVC4 alkylthio, or phenyl-CVC4 -Alkoxy, phenyl-Ci-Cf alkylthio, heterocyclyl, phenyl or heteroaryl are optionally substituted with 1-3 substituents selected from the group consisting of: amino, alkylamino, di- (CVC4 alkyl) amine, CVC5 alkyl amine, (CVC4 alkoxy) carbonyl amine-33- This paper size applies to Chinese National Standard (CNS) A4 specification (210 × 297 mm) (Please read the precautions on the back before Fill in this page) Order 520362 A7 -----_____ B7_ —__ V. Description of the invention (31) Group, hydroxyl, alkoxy, CVC4 alkylthio, cyano, halogen atom, C1-C4 alkyl or containing 1-3 Ci_c4 haloalkyl of halogen atom; (2) (^-[4halohalo group containing 1 to 3 halogen atoms; or (3) aryl or heteroaryl group is optionally substituted by i to 3 substituents selected from the following : Amine, CVC4 alkylamino Di- (C ^ C) alkyl) amino group, CrCs alkyltamino group (C 1 -C 4 纟 See oxygen) thiolamino group, each group 'C1-C4 antioxidant' C1-C4 sulfanyl group , A cyano group, a halogen atom, a Cl_c4 alkyl group, or a trifluoromethyl group; more preferably, each R3G is (1 alkyl optionally substituted by a substituent selected from: (a) an amino group, an alkylamino group, or a difluoromethyl group; -(Ci-Cc alkyl) amine; or (b) hydroxy, Cl-C4 alkoxy, heterocyclyl, phenyl or heteroaryl are optionally substituted with 1-3 substituents selected from: amine Group, Cl_C4 alkylamino group, di_ (CVC4 alkyl) amino group, CVC5 alkylamino group, (CVC4 alkoxy) carbonylamino group, hydroxyl group, CVC4 alkoxy group, CVC4 alkylthio group, cyano group, halogen atom , Ci_C4 alkyl or trifluoromethyl; (2) CVC2 haloalkyl containing 1 to 3 halogen atoms; or (3) Aryl or heteroaryl optionally substituted by 1 to 3 substituents selected from: amine , CVC4 alkylamino, di- (CVC4 alkyl) amino, CVC5 alkylamino, (CVC4 alkoxy) carbonylamino, hydroxyl, CVC4 alkoxy, Ci-Ci alkylthio, cyano, Halogen atom, CrC # alkyl or trifluoromethyl; more preferably, each r30 is an alkyl choice Substituted by phenyl or heteroaryl, and optionally substituted by 1-3 substituents selected from the group consisting of amine, di · (Cpq alkyl) amino, ethylamine, # group, Ci_C2 antioxidant Radical 'halogen atom, c ^ -CU, or tri-34- This paper size applies to Chinese National Standard (CNS) A4 specification (210 × 297 mm) (Please read the precautions on the back before filling this page)

、1T 經濟部中央標準局員工消費合作社印袋 經濟部中央標準局員Μ消費合作社印裝 520362 A7 _________ B7___一 五、發明説明（32 ) 氟甲基； (2) 三氟甲基；或 (3) 芳基或雜芳基選擇性由1至3個選自下列之取代基取代 :胺基，二-(CrQ烷基）胺基，乙醯胺基，羥基，CVC2烷 氧基，鹵原子，Ci-C4烷基或三氟甲基； 更佳，各個R3G分別爲 (1) <^-(：4烷基選擇性由苯基或雜芳基取代而又選擇性由卜 3個選自下列之取代基取代：胺基，二甲基胺基，乙醯胺 基，羥基，iS原子，甲氧基，甲基或三氟甲基； (2) 三氟甲基；或 (3) 芳基或雜芳基選擇性由1至3個選自下列之取代基取代 :胺基，二甲基胺基’乙酿胺基，幾基，_原子，甲氧基 ，甲基或三氟甲基； 最佳，各個R3G分別爲 烷基選擇性由苯基或雜芳基取代而又選擇性由1-2個選自下列之取代基取代：胺基，二甲基胺基，乙醯胺 基，幾基，自原子，甲氧基，甲基或三氟甲基； (2) 三氟甲基·，或 (3) 芳基或雜芳基選擇性由1至3個選自下列之取代基取代 :胺基，二甲基胺基，乙醯胺基，羥基，卣原子，甲氧基 ，甲基或三氟甲基； 各個R29分別爲氫或R3G ;最佳R29爲芳基或雜芳基選擇性 由1-2個選自下列之取代基取代：胺基，二甲基胺基，乙 醯胺基，羥基，卣原子，甲氧基，甲基或三氟甲基； -35- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐j ' (請先閱讀背面之注意事項再填寫本頁) #· 訂 520362 A7 B7 五、發明説明（33 ) 各個R31分別爲 (1) 氫， (請先閲讀背面之注意事項再填寫本頁) (2) 烷基選擇性由環烷基，芳基，雜環基或雜芳基取代而又 選擇性由1 _3個選自下列之取代基取代：胺基，烷基胺基 ，二烷基胺基，烷醯胺基，烷氧羰基胺基，烷基磺醯胺基 ’幾基，燒*氧基，燒硫基’氰基’祝基或S抗基；或 (3) 芳基，雜芳基，雜環基或環烷基選擇性由1-3個選自下 列之取代基取代：胺基，烷基胺基，二烷基胺基，烷醯胺 基，烷氧羰基胺基，烷基磺醯胺基，羥基，烷氧基，貌硫 基，氰基，燒基或函娱》基； 較佳，各個R31分別爲 ⑴氫， 烷基選擇性由C3-C8環烷基，芳基，雜環基或雜芳 •基取代而又選擇性由1-3個選自下列之取代基取代：胺基 ，（VC4烷基胺基，二_(CVC4烷基）胺基，Ci-C5烷醯胺基 ，（CVC4烷氧）羰基胺基，CVC4烷基績酿胺基’髮基’ CVC4烷氧基，CVC4烷硫基，氰基’ CrC4悦基或含Μ 個鹵原子之鹵烷基；或 經濟部中央標準局員工消費合作社印製 (3)芳基，雜芳基，雜環基或C3-C8環烷基選擇性由I·3個 選自下列之取代基取代：胺基，Ci-C4烷基胺基，二-(C^ C4烷基）胺基，CVC5烷醯胺基，（CrC4奴氧）談基胺基’ CVC4烷基磺醯胺基，羥基，CVC4嫁氧基，ci_C4抗硫基 ，氰基，CVC4烷基或含1-3個鹵原子之_燒基； 更佳，各個R31分別爲 -36- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（34 ) (1) 氫；或 烷基選擇性苯基或雜芳基取代而又選擇性由1-3 個選自下列之取代基取代：胺基，Cl-c4烷基胺基，二-(CrC4烷基）胺基，CrC5烷醯胺基，（CVC4烷氧）羰基胺基 ，羥基，cvc4烷氧基，CrC#烷硫基，氰基，Ci-C^烷基 或三氟甲基； 更佳，各個R31分別爲氫或CrC4烷基；最佳，各個R31分 別爲氫，甲基或乙基； 各個R32分別爲 ⑴氫， (2) 烷基選擇性由環烷基，芳基，雜環基或雜芳基取代而又 選擇性由1 -3個選自下列之取代基取代：胺基，烷基胺基 ，二烷基胺基，烷醯胺基，烷氧羰基胺基，烷基磺醯胺基 ，謹基，燒氧基，燒硫基，氰基，燒基或自燒基；或 (3) 芳基，雜芳基，雜環基或環烷基選擇性由1-3個選自下 列之取代基取代：胺基，烷基胺基，二烷基胺基，烷醯胺 基，燒氧談基胺基，燒基續酿胺基’羥基’燒氧基’燒硫 基，氰基，烷基或自烷基； 較佳，各個R32分別爲 ⑴氫， (2)(^-(^4烷基選擇性由C3_C8環烷基，芳基，雜環基或雜芳 基取代而又選擇性由1 -3個選自下列之取代基取代：胺基 ，CVC4烷基胺基，二-(CVC4烷基）胺基，ci-c5淀醯胺基 ，（Ci-C4烷氧）羧基胺基，C「C4坑基磺醯胺基，超基， -37- 本紙張尺度適用中國國家榡準（CNS ) A4規格（210X 297公釐） (請先閲讀背面之注意事項再填寫本頁) 訂 520362 經濟部中央標準局員工消費合作社印f A7 B7 五、發明説明（35 )1, 1T Printed bags for employees of the Central Standards Bureau of the Ministry of Economic Affairs Consumer Cooperative Cooperatives Member of the Central Standards Bureau of the Ministry of Economic Affairs M Consumer Cooperatives printed 520362 A7 _________ B7___ 15. Description of the invention (32) fluoromethyl; (2) trifluoromethyl; or (3 ) Aryl or heteroaryl is optionally substituted by 1 to 3 substituents selected from the group consisting of amine, di- (CrQ alkyl) amino, acetamido, hydroxyl, CVC2 alkoxy, halogen atom, Ci-C4 alkyl or trifluoromethyl; more preferably, each R3G is (1) < ^-(: 4 alkyl is optionally substituted by phenyl or heteroaryl, and optionally selected by Bu 3 The following substituents are substituted: amine, dimethylamino, acetamido, hydroxyl, iS atom, methoxy, methyl or trifluoromethyl; (2) trifluoromethyl; or (3) aromatic Or heteroaryl is optionally substituted by 1 to 3 substituents selected from the group consisting of: amine, dimethylamino, ethylamine, aryl, aryl, methoxy, methyl, or trifluoromethyl Most preferably, each R3G is an alkyl group optionally substituted by a phenyl or heteroaryl group and optionally substituted by 1-2 substituents selected from the group consisting of amine, dimethylamino, and acetamido base Amino, self-atom, methoxy, methyl or trifluoromethyl; (2) trifluoromethyl, or (3) aryl or heteroaryl selectivity from 1 to 3 substituents selected from Substitution: amine, dimethylamino, acetamido, hydroxyl, fluorene, methoxy, methyl or trifluoromethyl; each R29 is hydrogen or R3G; preferably R29 is aryl or heteroaryl The group selectivity is substituted by 1-2 substituents selected from the group consisting of amine, dimethylamino, acetamido, hydroxyl, fluorene atom, methoxy, methyl or trifluoromethyl; This paper size applies to China National Standard (CNS) A4 specifications (210X 297mm j '(please read the precautions on the back before filling this page) # · 520362 A7 B7 V. Description of the invention (33) Each R31 is ( 1) Hydrogen, (Please read the notes on the back before filling this page) (2) Alkyl is optionally substituted by cycloalkyl, aryl, heterocyclyl or heteroaryl, and optionally by 1-3 selected from The following substituents are substituted: amine, alkylamino, dialkylamino, alkylamino, alkoxycarbonylamino, alkylsulfonamido ', aryl, thiol, thiol' Cyanide Or sulfonyl; or (3) aryl, heteroaryl, heterocyclyl or cycloalkyl are optionally substituted with 1-3 substituents selected from the group consisting of amine, alkylamine, Dialkylamino, alkylamino, alkoxycarbonylamino, alkylsulfonamido, hydroxyl, alkoxy, sulfanyl, cyano, alkyl or alkyl; preferably, each R31 Residual hydrogen, alkyl is optionally substituted by C3-C8 cycloalkyl, aryl, heterocyclyl or heteroaryl group, and optionally substituted by 1-3 substituents selected from the group: amine, ( VC4 alkyl amine, di- (CVC4 alkyl) amine, Ci-C5 alkyl amine, (CVC4 alkoxy) carbonyl amino, CVC 4 alkyl amine amine 'fat' CVC4 alkoxy, CVC4 Alkylthio, cyano 'CrC4 or haloalkyl containing M halogen atoms; or printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (3) aryl, heteroaryl, heterocyclic or C3-C8 rings Alkyl is optionally substituted with 1.3 substituents selected from the group consisting of: amine, Ci-C4 alkylamino, di- (C ^ C4 alkyl) amino, CVC5 alkylamino, (CrC4 slave oxygen ) Talking about aminoamino 'CVC4 alkylsulfonamido, hydroxyl, C VC4 is oxyoxy group, ci_C4 antisulfide group, cyano group, CVC4 alkyl group or _alkyl group containing 1-3 halogen atoms; more preferably, each R31 is -36- This paper size applies to Chinese National Standard (CNS) A4 Specifications (210X297 mm) 520362 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the Invention (34) (1) Hydrogen; or alkyl-selective phenyl or heteroaryl substituted by 1- 3 substituents selected from: amino, Cl-c4 alkylamino, di- (CrC4 alkyl) amino, CrC5 alkylamino, (CVC4 alkoxy) carbonylamino, hydroxyl, cvc4 alkyl Oxygen, CrC # alkylthio, cyano, Ci-C ^ alkyl or trifluoromethyl; more preferably, each R31 is hydrogen or CrC4 alkyl; most preferably, each R31 is hydrogen, methyl or ethyl Each R32 is a hydrogen atom, (2) an alkyl group is optionally substituted with a cycloalkyl group, an aryl group, a heterocyclic group or a heteroaryl group and is optionally substituted with 1 to 3 substituents selected from: amine Group, alkylamino group, dialkylamino group, alkylamino group, alkoxycarbonylamino group, alkylsulfonamido group, alkyl group, alkyl group, alkyl group, alkyl group, alkyl group Or (3) aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted with 1-3 substituents selected from the group consisting of amino, alkylamino, dialkylamino, alkyl Sulfonylamino, sulfonylamino, sulfanyl is continuously amine's hydroxy, alkynyl, sulfanyl, cyano, alkyl, or self-alkyl; preferably, each R32 is phosphonium hydrogen, (2 ) (^-(^ 4 alkyl is optionally substituted with C3_C8 cycloalkyl, aryl, heterocyclyl or heteroaryl and is optionally substituted with 1-3 substituents selected from: amine, CVC4 alkyl Amino group, di- (CVC4 alkyl) amino group, ci-c5 alkylamino group, (Ci-C4 alkoxy) carboxyamino group, C "C4 sulfonylamino group, super group, -37- Paper size applies to China National Standard (CNS) A4 (210X 297 mm) (Please read the notes on the back before filling out this page) Order 520362 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs f A7 B7 V. Description of the invention ( 35)

CrC4烷氧基，CVC4烷硫基，氰基，Cl-C4貌基或含卜3 個鹵原子之Ci-G鹵烷基；或 (3)芳基，雜芳基，雜環基或C3-C8環燒基選擇性由1-3個 選自下列之取代基取代：胺基，Cl-C4坑基胺基’二-(Cr c4烷基）胺基，Ci-Cs烷醯胺基，（CrC4燒氧）羰基胺基， cvc4烷基磺醯胺基，羥基，CVC4烷氧基’ C1-C4烷硫基 ，氰基，CVC4烷基或含1-3個鹵原子之C「C4 ί貌基； 更佳，各個R32分別爲 ⑴氫， (2) (^-(^4烷基選擇性由C3-C6環烷基，芳基’雜環基或雜芳 基取代而又選擇性由1 -3個選自下列之取代基取代：胺基 ，CVC4燒基胺基，二-(Ci-C4燒基）胺基’ C1_C5燒醯胺基 ，（Ci-C^烷氧）羰基胺基，Ci-C#烷基磺醯胺基，羥基， • CVC4烷氧基，CVC4烷硫基，氰基，CrQ烷基或含1-3 個卣原子之Ci-C4_坑基；或 (3) 芳基，雜芳基，雜環基或C3-C6環烷基選擇性由1-3個 選自下列之取代基取代··胺基，Ci-C#烷基胺基，二-(C」-C4烷基）胺基，C^-Cs烷醯胺基，（CVC4烷氧）羰基胺基， CVC4烷基磺醯胺基，羥基，CVCVM»氧基，（^-山烷硫基 ，氰基，C「C4烷基或含1-3個鹵原子之CVC4鹵烷基； 更佳，各個R32分別爲 ⑴氫·， 、 (2)Ci-C4虎基選擇性由苯基或雜芳基取代而又選擇性由1-3個選自下列之取代基取代：胺基，CVC4燒基胺基，二- -38 - ^紙張尺度適用中國國家標準（CNS ) A4規格（210X297^1 ------— (請先閲讀背面之注意事項再填寫本頁) 、tr 520362 A7 B7 五、發明説明（36) (請先閱讀背面之注意事項再填寫本頁) (Ci_C4丈元基）胺基，c1>Mc5垸g盔胺基，（€1-匚4$元氧）幾基胺基 ’每基’ Κ4烷氧基，Ci-Q烷基或三氟甲基；或 (3)苯基或雜芳基選擇性由1-3個選自下列之取代基取代： 胺基，Ci-C4烷基胺基，二_(Ci_c4烷基）胺基，Ci-C5烷醯 胺基，（C1-C4烷氧）羰基胺基，羥基，Ci-C4烷氧基，Ci-Czt 基或三氟甲基； 更佳，各個R32分別爲 ⑴氫； GA-C4烷基或Cl_C2烷基由苯基或雜芳基取代而又選擇 性由1 -3個選自下列之取代基取代：胺基，二甲基胺基， 乙醯胺基，羥基，甲氧基，甲基或三氟甲基；或 (3)苯基或雜芳基選擇性由1 _3個選自下列之取代基取代： 胺基，二甲基胺基，乙醯胺基，羥基，甲氧基，甲基或三 氟甲基； 最佳，R32分別爲 (1) 氳或CVC4燒基；或 經濟部中央標準局員工消費合作社印製 (2) 苯基或雜芳基選擇性由1-2個選自下列之取代基取代： 胺基，二甲基胺基，乙醯胺基，羥基，甲氧基，曱基或三 氣甲基；及 其中各個R33分別爲 (1) 氫；或 (2) 烷基選擇性由雜環基，芳基或雜芳基取代而又選擇性由 1 -3個選自下列之取代基取代：胺基，烷基胺基，二烷基胺 基，燒S盡胺基，燒氧窥基胺基’坑基續酸胺基’喪基’抗 -39- _ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 Β7 五、發明説明（37 ) 氧基’燒硫基，氰基，烷基或_烷基； 較佳，各個R33分別爲 (1) 氫；或 (2) (^-C4烷基選擇性由雜環基，芳基或雜芳基取代而又選 擇性由1-3個選自下列之取代基取代；胺基，Cl-C4烷基胺 基，二-(CVC4烷基）胺基，Cl_C5烷醯胺基，（Cl_C4烷氧） 羧基胺基，CrC4烷基磺醯胺基，羥基，Cl_c4烷氧基， CVC4垸硫基，氰基，Cl-C4烷基或含1-3個鹵原子之CVC4 鹵烷基； 更佳’各個R„分別爲氫，Cl-C4烷基；及最佳，各個R33 分別爲氫或甲基。 下文規定係有關本發明之化合物，而非有關醫藥組成物 用法’醫藥組成物或用法涵蓋前述全部化合物（除非另行陳 ‘明）： 1.當R1及R12爲相同且爲含個分別選自N，S及Ο 之雜原子之5-或6_員環，於該環選擇性稠合苯環，r1 1 爲苯基或莕基選擇性由鹵原子，Cl-C6烷基，C/C4 燒氧基，C^C：4烷硫基，羥基，胺基，Cl_C4烷基胺基 或一 fe基胺基取代，或R11爲含1_3個分別選自n，S 及0之雜原子之5-或6-員環，於該環選擇性稠合苯環 且選擇性由CVC6燒基取代時，R2非爲〇H或NH2 ; 2·當R2爲Η，R11爲苯基，R12爲苯基或4_峨淀基時， R1非爲Η，甲基或胺基； 3.當R2爲Η，R11爲2·甲基苯基及]^2爲2_吡啶基時， -40- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） (請先閱讀背面之注意事項再填寫本頁) -tv 經濟部中央標準局員工消費合作社印製 520362 A7CrC4 alkoxy, CVC4 alkylthio, cyano, Cl-C4 alkyl or Ci-G haloalkyl containing 3 halogen atoms; or (3) aryl, heteroaryl, heterocyclic or C3- The C8 ring alkyl group is optionally substituted with 1-3 substituents selected from the group consisting of: amine group, Cl-C4 pentylamino group 'di- (Cr c4 alkyl) amino group, Ci-Cs alkylamino group, ( CrC4 oxygen) carbonylamino, cvc4 alkylsulfonamido, hydroxyl, CVC4 alkoxy 'C1-C4 alkylthio, cyano, CVC4 alkyl, or C "C4 with 1 to 3 halogen atoms More preferably, each R32 is fluorene hydrogen, (2) (^-(^ 4 alkyl is optionally substituted by C3-C6 cycloalkyl, aryl 'heterocyclyl or heteroaryl, and optionally by 1 -3 substituents selected from the group consisting of: amino, CVC4-alkylamino, bis- (Ci-C4-alkyl) amino'C1-C5alkylamino, (Ci-C ^ alkoxy) carbonylamino, Ci-C # alkylsulfonamido, hydroxyl, • CVC4 alkoxy, CVC4 alkylthio, cyano, CrQ alkyl or Ci-C4_ pit containing 1-3 fluorene atoms; or (3) aromatic Group, heteroaryl group, heterocyclic group or C3-C6 cycloalkyl group are optionally substituted with 1-3 substituents selected from the group consisting of amine group, Ci-C # alkylamino group, di- (C "-C4 alkyl) amino, C ^ -Cs alkylamino, (CVC4 alkoxy) carbonylamino, CVC4 alkylsulfonamido, hydroxyl, CVCVM» oxy, (^ -shanethione) A cyano group, a cyano group, a C4 alkyl group or a CVC4 haloalkyl group having 1-3 halogen atoms; more preferably, each R32 is a hydrogen atom, respectively, (2) Ci-C4 is optionally selected from phenyl or Heteroaryl substitution and selective substitution by 1-3 substituents selected from the group consisting of: amine, CVC4 alkylamino, 2-38-^ Paper size applies Chinese National Standard (CNS) A4 specification (210X297 ^ 1 ------— (Please read the notes on the back before filling this page), tr 520362 A7 B7 V. Description of the invention (36) (Please read the notes on the back before filling this page) (Ci_C4C 元Group) amine group, c1> Mc5 垸 g helmet amine group, (€ 1- 匚 4 $ oxygen) several amine groups 'per group' K4 alkoxy group, Ci-Q alkyl group or trifluoromethyl group; or ( 3) The phenyl or heteroaryl group is optionally substituted by 1-3 substituents selected from the group consisting of: amine, Ci-C4 alkylamino, di_ (Ci_c4 alkyl) amino, Ci-C5 alkylamine (C1-C4 alkoxy) carbonylamino, hydroxyl, Ci-C4 alkoxy, Ci-Czt or trifluoro More preferably, each R32 is fluorene hydrogen; GA-C4 alkyl or Cl_C2 alkyl is substituted with phenyl or heteroaryl and optionally substituted with 1-3 substituents selected from the group: amine, di Methylamino, acetamido, hydroxy, methoxy, methyl, or trifluoromethyl; or (3) phenyl or heteroaryl is optionally substituted with 1 to 3 substituents selected from: amino , Dimethylamino, acetamido, hydroxy, methoxy, methyl, or trifluoromethyl; best, R32 is (1) fluorene or CVC4, respectively; or the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Print (2) Phenyl or heteroaryl is optionally substituted with 1-2 substituents selected from: amine, dimethylamino, acetamido, hydroxyl, methoxy, fluorenyl or tris Gas methyl; and each R33 is (1) hydrogen; or (2) alkyl is optionally substituted by heterocyclyl, aryl or heteroaryl and optionally by 1-3 substituents selected from Substitution: Amine, Alkylamine, Dialkylamino, Burning Amine, Burning Oxyamine, Phenylamino, Phenylamino, and Diamino. Anti-39- _ This paper is applicable to China Standard (C NS) A4 specification (210X 297 mm) 520362 A7 B7 V. Description of the invention (37) Oxythio, thio, cyano, alkyl or alkyl; preferably, each R33 is (1) hydrogen; or (2) (^ -C4 alkyl is optionally substituted with heterocyclyl, aryl or heteroaryl and optionally substituted with 1-3 substituents selected from: amine, Cl-C4 alkylamino , Di- (CVC4 alkyl) amino, Cl_C5 alkylamino, (Cl_C4 alkoxy) carboxyamino, CrC4 alkylsulfonamido, hydroxyl, Cl_c4 alkoxy, CVC4 thio, cyano, Cl -C4 alkyl or CVC4 haloalkyl containing 1-3 halogen atoms; more preferably, each R is hydrogen, Cl-C4 alkyl; and most preferably, each R33 is hydrogen or methyl. The following provisions are related to the compounds of the present invention, not related to the usage of the pharmaceutical composition. The pharmaceutical composition or usage covers all the aforementioned compounds (unless otherwise stated): 1. When R1 and R12 are the same and each contains one selected from N A 5- or 6-membered ring of a hetero atom of S and O, in which the benzene ring is selectively fused, and r1 1 is a phenyl or fluorenyl group, optionally from a halogen atom, Cl-C6 alkyl, or C / C4 Oxygen, C ^ C: 4 alkylthio, hydroxy, amine, Cl_C4 alkylamino or monofeaminyl substituted, or R11 is 5- containing 5 heteroatoms selected from n, S and 0, respectively Or 6-membered ring, when the ring is selectively fused to a benzene ring and optionally substituted by a CVC6 alkyl group, R2 is not 0H or NH2; 2. When R2 is fluorene, R11 is phenyl, and R12 is phenyl or 4_ Edian base, R1 is not fluorene, methyl or amine; 3. When R2 is fluorene, R11 is 2. methylphenyl and [2] is 2-pyridyl, -40- this paper size Applicable to China National Standard (CNS) Α4 specification (210X297 mm) (Please read the precautions on the back before filling out this page) -tv Printed by the Central Consumers Bureau of the Ministry of Economy Staff Consumer Cooperative 520362 A7

訂 520362Order 520362

AA

7 B 五、發明説明（39 ) 經濟部中央標準局員工消費合作社印製 R11 R12 R1 苯基 4-p比淀基 1-六氫吡畊基 4-氟苯基 4-p比淀基 1-六氫井基 3-鼠苯基 4-p比淀基 1-六氫吡畊基 2-氟苯基 4-p比淀基 1-六氫井基 4-氯苯基 4-p比淀基 1-六氫p比p井基 3-氯苯基 4-吡淀基 1-六氫吡畊基 2-氣苯基 4-ρ比淀基 1_六氫吡畊基 4-甲苯基 4-外b淀基 1-六氫吡畊基 3-甲苯基 4-p比淀基 1-六氫#bp井基 2-甲苯基 4-p比淀基 1-六氬吡畊基 4_三氟甲基苯基 4-峨淀基 1-六氫说"1 井基 3-三氟甲基苯基 4-p比淀基 1-六氫吡畊基 2,6·二鼠苯基 4-p比淀基 1-六氫p比1^井基 2,6-二甲基苯基 4-p比淀基 1-六氫井基 2,4--一氣苯基 4-峨淀基 1-六氫吹17井基 2,4-二甲基苯基 4-峨淀基 1-六氫吡畊基 苯基 2-胺基-4-p比淀基 1-六氫峨p井基 \ 4-氣苯基 2-胺基-4-ptt淀基 1-六氫晚"1井基 3-氟苯基 2-胺基-4-吡啶基 1-六氫咐^井基 (請先閱讀背面之注意事項再填寫本頁) 訂 -42- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 B7 五、發明説明（4〇 ) 經濟部中央標準局員工消費合作社印製 2-氟苯基 2-胺基-4-p比淀基 1-六氫吡畊基 4-氯苯基 2-胺基-4-p比淀基 1-六氫吡畊基 3-氯苯基 2-胺基-4-吡啶基 1-六氫外1^井基 2-鼠本基 2-胺基-4-p比淀基 1-六氫外1:_基 4-甲苯基 2-胺基-4-p比淀基 丨 1-六氫井基 3-甲苯基 2-胺基_4-p比淀基 1-六氫吡畊基 2-甲苯基 2-胺基-4-吡啶基 1-六氫吡畊基 4_三氟甲基苯基 2-胺基-4-^喊^基 1-六氫吡畊基 3-三氟甲基苯基 2-胺基基 1_六氫吡畊基 2,6-二氣苯基 2-胺基_4-p比淀基 1-六氫吡畊基 Z6-二甲基苯基 2-胺基-4-?比旋^基 1-六氫外bp井基 2,4-二鼠本基 2-胺基-4-吡啶基 1-六氫吡畊基 2,4-二甲基苯基 2-胺基-4-被淀基 1·六氫吡畊基 苯基 2-乙醯胺基-4-吡啶基 1-六氫吡畊基 4-氣苯基 2-乙醯胺基-4-吡啶基 1-六氫吡畊基 3-氟苯基 2-乙醯胺基-4-吡啶基 1-六氫吡畊基 2-鼠苯基 2·乙醯胺基-4_吡啶基 1-六氫吡畊基 4-氯苯基 2-乙醯胺基-4-吡啶基 1-六氫吡畊基 3-氯苯基 2_乙醯胺基-4-p比淀基 1-六氫井基 2-氣苯基 2_乙醯胺基-4-吡啶基 1-六氫咐/井基 (請先閱讀背面之注意事項再填寫本頁) 訂 ^wl. -43- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 5203627 B V. Description of the invention (39) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economy R11 R12 R1 Phenyl 4-p-pyridyl 1-hexahydropyridyl 4-fluorophenyl 4-p-pyridyl 1- Hexahydrophenyl 3-p-phenyl 4-p-pyridyl 1-hexahydropyridyl 2-fluorophenyl 4-p 1-hexahydro p-ratio p-based 3-chlorophenyl 4-pyridinyl 1-hexahydropyridinyl 2-phenyl 4-ρpyridyl 1-hexahydropyridinyl 4-tolyl 4- Outer b-yl 1-hexahydropyridyl 3-tolyl 4-p than ytyl 1-hexahydro Methylphenyl 4-Eodoyl 1-Hexyl Hydroxyl " 1 Jingji 3-trifluoromethylphenyl 4-p than Yodoyl 1-Hydroxypyryl 2,6 p ratio Yodo radical 1-hexahydro p ratio 1 ^ well base 2,6-dimethylphenyl 4-p ratio lake base 1-hexahydro well base 2,4--monophenylphenyl 4-ethanyl 1- Hexahydrogen 17 well-based 2,4-dimethylphenyl 4-amidoyl 1-hexahydropyridylphenyl 2-amino-4-p than yodoyl 1-hexahydroepyl \ 4 -Phenyl 2-amino-4-ptt-yttrium 1-hexahydro late " 1 well-based 3-fluorophenyl 2-amino 4-pyridyl 1-hexahydro late (Please read the precautions on the back before filling this page) Order-42- This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) 520362 B7 V. Description of Invention (4) Central Bureau of Standards, Ministry of Economic Affairs Employee Consumer Cooperative prints 2-fluorophenyl 2-amino-4-p than Yodo-l-hexahydropyracyl 4-chlorophenyl 2-amino 4-p 3-Chlorophenyl 2-amino-4-pyridyl 1-hexahydroexo 1 ^ yl 2-muryl 2-amino 4-p -Tolyl 2-amino-4-p ratio ytyl group 1-Hexylhydrocarbyl 3-tolyl 2-amino group 4-4-pyrrolyl 1-hexahydropyridyl 2-tolyl 2-amine 4-Pyridyl 1-Hydroxypyridyl 4-trifluoromethylphenyl 2-amino 4-Hydroyl 1-hexahydropyridyl 3-trifluoromethylphenyl 2-amine 1-Hydroxypyridyl 2,6-dioxophenyl 2-amino_4-p is more than 1-Hydroxypyridyl Z6-dimethylphenyl 2-amino-4-? Glucosyl 1-hexahydro exobp Isopropyl 2,4-dimuryl 2-amino-4-pyridyl 1-hexahydropyridyl 2,4-dimethylphenyl 2-amino- 4-Hydroyl hexahydropyridylphenyl 2-ethylamido-4-pyridyl 1-hexahydropyridine 4-Aminophenyl 2-ethylamido-4-pyridyl 1-hexahydropyracyl 3-fluorophenyl 2-ethylamido-4-pyridyl 1-hexahydropyracyl 2-rat Phenyl-2-acetamido-4_pyridyl1-hexahydropyridyl 4-chlorophenyl 2-acetamido-4-pyridyl1-hexahydropyridyl 3-chlorophenyl 2_ Acetylamino-4-p is better than Yodoyl 1-Hexahydrogenyl 2-Gaphenyl 2-Acetylamido-4-pyridyl 1-Hydroxy (Jingji) (Fill in this page) Order ^ wl. -43- This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) 520362

7 B 五、發明説明（41 ) 經濟部中央標準局員工消費合作社印製 4-甲苯基 2-乙醯胺基-4·吡啶基 1-六氫吡畊基 3-甲苯基 2-乙醯胺基-4-吡啶基 1-六氫?比^1井基 2-甲苯基 2-乙醯胺基-4-吡啶基 1·六氫被^7井基 4-三氟甲基苯基 2·乙醯胺基·4·ρ比啶基 1-六氫㈣："1井基 3-三氟甲基苯基 2-乙醯胺基-4-吡啶基 1-六氫井基 2,6-二氣豕基 2-乙醯胺基_4-ρ比咬基 1-六氫吡畊基 2,6-二甲基苯基 2-乙醯胺基_4-ρ比淀基 1-六氫p比p井基 2,4_二氯苯基 2-乙醯胺基-4-ρ比啶基 1-六氫吡畊基 2,4-二甲基苯基 2-乙醯胺基·4-吡啶基 1-六氫吡畊基 苯基 2-胺基-4-喃淀基 1-六氫峨_基 4-鼠苯基 2-胺基-4-喊淀基 1·六氫吡畊基 3_氣苯基 2-胺基-4-喊淀基 1-六氫p比17井基 2_氟苯基 2-胺基-4-喃淀基 1-六氫吡畊基 4-氯苯基 2-胺基-4-喊淀基 1-六氫吡畊基 3-氯苯基 2-胺基-4-喊淀基 1-六氫说11 井基 2-氯苯基 2-胺基-4-喊淀基 1-六氫吡畊基 4-甲苯基 2-胺基-4-喃淀基 1-六氫外1^井基 3_甲苯基 2-胺基-4-喊淀基 1-六氫井基 2-甲苯基 2-胺基-4-喃淀基 1-六氫井基 4-三氟甲基苯基 2-胺基-4-喃淀基 1-六氫吡畊基 (請先閱讀背面之注意事項再填寫本頁)7 B V. Description of the invention (41) 4-Tolyl 2-acetamido-4 · pyridyl 1-hexahydropyridyl 3-tolyl 2-acetamido printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Phenyl-4-pyridyl 1-hexahydro? Ratio ^ 1 yl 2- tolyl 2- acetamido-4-pyridyl 1 · hexahydro is ^ 7 yl 4- trifluoromethylphenyl 2 · Ethylamino · 4 · ρ than pyridyl 1-hexahydrofluorene: " 1 well-based 3-trifluoromethylphenyl 2-acetamido-4-pyridyl 1-hexahydro well 2,6 -Dioxoyl 2-ethenylamino 4-4-r.pyridyl 1-hexahydropyridyl 2,6-dimethylphenyl 2-ethenylamino 4-4-rpyridyl 1-hexa Hydrogen p ratio p wellyl 2,4-dichlorophenyl 2-acetamidinyl-4-ρ than pyridyl 1-hexahydropyridyl 2,4-dimethylphenyl 2-acetamido 4-pyridyl 1-hexahydropyridylphenyl 2-amino-4-anhydropyridyl 1-hexahydropyridyl 4-murylphenyl 2-amino 4-ylpyridyl 1.hexahydropyridine Phenyl 3-aminophenyl 2-amino-4-ylamino 1-hexahydro p ratio 17 wells 2-fluorophenyl 2-amino-4-aminodianyl 1-hexahydropyridyl 4- Chlorophenyl 2-amino-4-hexyl 1-hexahydropyridyl 3-chlorophenyl 2-amino 4-hexyl 1-hexahydrol 11 Isoyl 2-chlorophenyl 2-Amino-4-Hydroyl 1-Hydroxypyridyl 4-Tolyl 2-Amino-4-Hydroxy 1-Hexyl 1-Hexyl 3-Tolyl 2-Amino-4 -Hydrogenyl 1-hexahydrocarbyl 2-tolyl 2-amino-4-ranyl-1-yl hexahydrol 4-trifluoromethylphenyl 2-amino-4-ranyl 1- Hexahydropycnyl (Please read the notes on the back before filling out this page)

、1T -44- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（42 ) 經濟部中央標準局員工消費合作社印製 3-二氟甲基苯基 2-胺基-4-嘧啶基 1-六氫吡畊基 2,6--一氣冬基 2-胺基喊^基 1_六氫吡畊基 2,6-二甲基苯基 2-胺基-4-喊症基 1"Ά氯ρ比ρ井基 2,4-二氣私基 2-胺基_4·喃淀基 1-六氫井基 2,4-二甲基苯基 2-胺基-4-喃淀基 1-六氫p比p井基 苯基 4-ρ比淀基 2,6-二氯芊基 4-氟苯基 4-ρ比淀基 2,6-二氯苄基 3-氟苯基 4-ρ比淀基 2,6-二氯爷基 2-氟苯基 4-ρ比淀基 2,6-二氯爷基 4-氯苯基 4-0比淀基 2,6-二氯芊基 3-氯苯基 4_ρ比淀基 2,6-二氯芊基 2-氯苯基 4-口比淀基 2,6-二氯爷基 4_甲苯基 4-ρ比淀基 2,6_二氯爷基 3-甲苯基 4_ρ比淀基 2,6-二氯爷基 2-甲苯基 4-ρ比淀基 2,6-二氯爷基 4-二鼠甲基苯基 4-ρ比淀基 2,6-二氯爷基 3-三氟甲基苯基 4-口比淀基 2,6-二氯爷基 2,6-二氣本基 4-ρ比淀基 2,6-二氯爷基 2,6-二甲基苯基 4-ρ比淀基 2,6-二氯爷墓 2,4-二氣本基 4-ρ比淀基 2,6·二氯苄基 (請先閱讀背面之注意事項再填寫本頁) 訂 -45- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362、 1T -44- This paper size applies to Chinese National Standard (CNS) A4 (210X 297mm) 520362 A7 B7 V. Description of the invention (42) 3-Difluoromethylbenzene printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 2-Amino-4-pyrimidinyl 1-Hydroxypyridyl 2,6--aspartate 2-Aminopyridyl 1-hexahydropyridyl 2,6-dimethylphenyl 2- Amino-4-Hydroxyl 1 " Hydrogen chloride ρ ratio ρ Well group 2,4-Diamino group 2-amino group 4-Amino group 1-Hexahydro well group 2,4-Dimethylphenyl group 2-Amino-4-ranyl-l-hexahydro p-to-p-phenylphenyl 4-r-pyridyl 2,6-dichlorofluorenyl 4-fluorophenyl 4-r-pyridyl 2,6- Dichlorobenzyl 3-fluorophenyl 4-ρ than yodoyl 2,6-dichlorobenzyl 2-fluorophenyl 4-ρ pyridyl 2,6-dichlorobenzyl 4-chlorophenyl 4-0 Pyridyl 2,6-dichlorofluorenyl 3-chlorophenyl 4_ρ Pyridyl 2,6-dichlorofluorenyl 2-chlorophenyl 4-methylpyridyl 2,6-dichloromethyl 4-toluene 4-4-pyridyl 2,6-dichloromethyl 3-tolyl 4-pyridyl 2-, 6-dichloromethyl 2-tolyl 4-pyridyl 2-pyridyl 2,6-dichloromethyl 4 -Dirhamylmethylphenyl 4-p-pyridyl 2,6-dichloroethenyl 3-trifluoromethylphenyl 4-pyridyl 2,6-dichloroethenyl 2,6-difluorobenzyl 4-ρ than yodoyl 2,6-dichloroethenyl 2,6-dimethylphenyl 4-ρ ylidene 2,6-di Tomb of Chrysanthemum 2,4-Digas Benzoyl 4-ρ than Dianji 2,6 · Dichlorobenzyl (Please read the precautions on the back before filling this page) Revision-45- This paper size applies to Chinese national standards CNS) A4 size (210X 297 mm) 520362

B 五、發明説明（43 ) 經濟部中央標準局員工消費合作社印製 2,4-二甲基苯基 4-p比淀基 2,6-二氯卞基 苯基 2-胺基-4-?比淀基 2,6_二氯卞基 4-氟苯基 2-胺基基 2,6-二氯爷基 3-氟苯基 2-胺基-4-^比症^基 2,6-二氯苄基 2-氟苯基 2-胺基_4_吡啶基 2,6_二氯苄基 4-氯苯基 2·胺基-4·ρ比淀基 2,6·二氯苄基 3-氯苯基 2-胺基_4-p比淀基 2,6_二氯芊基 2-鼠本基 2-胺基_4·ρ比淀基 2,6-二氯芊基 4·甲苯基 2-胺基-4-#b淀基 2,6-二氯芊基 3-甲苯基 2_胺基-4-p比淀基 2,6_二氯苄基 2_甲苯基 2-胺基-4-吡啶基 2,6-二氣字基 4-三氟甲基苯基 2-胺基-4-p比啶基 2,6-二氯爷基 3-三氟甲基苯基 2-胺基-4-吡啶基 2,6-二氯苄基 2,6-二氣苯基 2_胺基-4-p比淀基 2,6-二氯爷基 2,6-二甲基苯基 2-胺基-4-说啶基 2,6-二氯爷基 2,4-—氣夺基 2-胺基-4-p比淀基 2,6-二氯爷基 2,4-二甲基苯基 2-胺基-4-p比基 2,6-二氯苄基 苯基 2-乙醯胺基-4-吡啶基 2,6-二氯爷基 4_氣苯基 2·乙廳:胺基 2,6-二氯爷基 3-氣苯基 2-乙醯胺基-4-p比啶基 2,6-二氯爷基 (請先閱讀背面之注意事項再填寫本頁) 訂 -46- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362B. Description of the invention (43) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs, 2,4-Dimethylphenyl 4-p-pyridyl 2,6-dichlorofluorenylphenyl 2-amino-4- Biyodo2,6-dichlorofluorenyl 4-fluorophenyl 2-amino group 2,6-dichloromethyl 3-fluorophenyl 2-amino group -Dichlorobenzyl 2-fluorophenyl 2-amino-4_pyridyl 2,6_dichlorobenzyl 4-chlorophenyl 2 · amino-4 · ρ than dianyl 2,6 · dichlorobenzyl 3-Chlorophenyl 2-amino group 4-p-pyridyl 2,6-dichlorofluorenyl 2-muryl 2-amino 4-p-pyridyl 2,6-dichlorofluorenyl 4 · Tolyl 2-amino-4- # b 淀 基 2,6-dichlorofluorenyl 3-tolyl 2-amino-4-p than yodo2,6_dichlorobenzyl 2_tolyl 2 -Amino-4-pyridyl 2,6-difluoromethyl 4-trifluoromethylphenyl 2-amino-4-p than pyridyl 2,6-dichloromethyl 3-trifluoromethylbenzene 2-amino-4-pyridyl 2,6-dichlorobenzyl 2,6-dichlorophenyl 2-amino-4-p than ydoyl 2,6-dichloromethyl 2,6-di Methylphenyl 2-amino-4-pyridinyl 2,6-dichloroethenyl 2,4--airpinyl 2-amino-4-p than pyridyl 2,6-dichloroethenyl 2 , 4-Dimethylphenyl 2-amino-4-p than 2,6-dichlorobenzylphenyl 2- Ethylamido-4-pyridyl 2,6-dichloroethenyl 4-fluorophenyl 2.ethene: amine 2,6-dichloroethenyl 3-aminophenyl 2-ethenylamino-4 -p than pyridyl 2,6-dichloroethene (please read the precautions on the back before filling in this page) Order -46- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) 520362

A B7 五、發明説明（44 ) 經濟部中央標準局員工消費合作社印製 2-氣苯基 2-乙醯胺基-4-吡啶基 2,6-二氯苄基 4-氯苯基 2-乙醯胺基-4-吡啶基 2,6-二氯苄基 3-氯苯基 2-乙醯胺基4-吡淀基 2,6-二氯苄基 2-氯苯基 2-乙醯胺基-4-吡啶基 2,6-二氯爷基 4-甲苯基 2·乙醯胺基·4-吡啶基 2,6-二氯苄基 3-甲苯基 2-乙醯胺基_4-ρ比淀基 2,6-二氯苄基 2·甲苯基 2-乙醯胺基-4-吡啶基 2,6·二氯爷基 4-三氟甲基苯基 2-乙醯胺基-4-吡啶基 2,6·二氯爷基 3·三氟甲基苯基 2-乙醯胺基-4·吡啶基 2,6-二氯爷基 2,6_二氣豕基 2-乙醯胺基-4-吡啶基 2,6·二氯芊基 2,6-二甲基苯基 2-乙醯胺基-4-外b淀基 2,6-二氯爷基 2,4-二氣豕基 2-乙醯胺基_4_吡啶基 2,6_二氯字基 2,4-二甲基苯基 2-乙醯胺基-4-吡啶基 2,6-二氯爷基 苯基 2-胺基-4-喊淀基 2,6-二氯字基 4-氟苯基 2-胺基-4-喊淀基 2,6-二氯爷基 3-氟苯基 2-胺基-4-嘧啶基 2,6-二氯爷基 2-氟苯基 2_胺基-4_喊淀基 2^6-二氯^基 4-氯苯基 2-胺基-4-喃淀基 2,6-二氯芊基 3-氯苯基 2-胺基-4-喃淀基 2,6-二氯苄基 2-氯苯基 2-胺基-4-癌淀基 2,6-二氯节基 (請先閱讀背面之注意事項再填寫本頁) 訂 .— -47- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362A B7 V. Description of the invention (44) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Ethylamido-4-pyridyl 2,6-dichlorobenzyl 3-chlorophenyl 2-acetamido 4-pyridyl 2,6-dichlorobenzyl 2-chlorophenyl 2-acetamidine Amino-4-pyridyl 2,6-dichloromethylene 4-tolyl 2 · acetamido · 4-pyridyl 2,6-dichlorobenzyl 3-tolyl 2-acetamido-4 -ρ ratio Yodoyl 2,6-dichlorobenzyl 2.tolyl 2-acetamido-4-pyridyl 2,6, dichloromethyl 4-trifluoromethylphenyl 2-acetamido -4-pyridyl 2,6 · dichloromethyl 3.trifluoromethylphenyl 2-acetamido-4 · pyridyl 2,6-dichloromethyl 2,6-difluoromethyl 2- Ethylamino-4-pyridyl 2,6 · dichlorofluorenyl 2,6-dimethylphenyl 2-ethenylamino-4-imidyl 2,6-dichloromethyl 2,4 -Diazinonyl 2-ethenylamino-4_pyridyl 2,6-dichlorobenzyl 2,4-dimethylphenyl 2-ethenylamino-4-pyridyl 2,6-dichloro Ethylphenyl 2-amino-4-ylamino 2,6-dichlorophenyl 4-fluorophenyl 2-amino-4-ylamino 2,6-dichloromethyl 3-fluorophenyl 2-amino-4- Pyridinyl 2,6-dichloroethenyl 2-fluorophenyl 2-amino-4_ylamine 2 ^ 6-dichloro ^ yl 4-chlorophenyl 2-amino-4-anylamino 2, 6-dichlorofluorenyl 3-chlorophenyl 2-amino-4-anhydrocarbyl 2,6-dichlorobenzyl 2-chlorophenyl 2-amino-4-carnanyl 2,6-dichloro Jieji (please read the notes on the back before filling this page) Order. — -47- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm)

AA

7 B 五、發明説明（45 ) 經濟部中央標準局員工消費合作社印製 4-甲苯基 2-胺基-4-喊淀基 2,6-二氯爷基 3-甲苯基 2-胺基-4-喊淀基 2,6·二氯爷基 2-甲苯基 2-胺基-4-續淀基 2,6-二氯爷基 4-三氟甲基苯基 2-胺基_4_哺淀基 2,6-二氯爷基 3-三氟甲基苯基 2-胺基-4-續淀基 2,6-二氯爷基 2,6-二氯苯基 2-胺基-4-喊淀基 2,6-二氯爷基 2,6-二甲基苯基 2-胺基-4-哺淀基 2,6_二氯爷基 2,4-二鼠本基 2_胺基-4-p密淀基 2,6-二氯爷基 2,4-二甲基苯基 2_胺基-4-癌淀基 2,6-二氯爷基 本基 4_p比淀基 2_(2_氯苯基)乙胺基 4-氟苯基 4_p比淀基 2-(2-氣木基)乙胺基 3-氣苯基 4-p比淀基 2-(2-氯苯基)乙胺基 2-氣豕基 4· 口比淀基 2-(2-氯苯基)乙胺基 4-氯苯基 4-p比基 2-(2·氯苯基)乙胺基 3-氯苯基 4-p比淀基 2-(2-氯苯基)乙胺基 2-氯苯基 4-口比淀基 2-(2-氯苯基)乙胺基 4-甲苯基 4-p比淀基 2-(2-氣本基)乙胺基 3-曱苯基 4-p比淀基 2-(2-氯苯基)乙胺基 2-甲苯基 4-叶1:淀基 2-(2·氯苯基)乙胺基 4-三氟曱基苯基 4-p比淀基 2-(2-氯苯基)乙胺基 (請先閱讀背面之注意事項再填寫本頁) 、-口 -48- 本紙張尺度適用中國國家標準（CNS ) A4規格（2IOX 297公釐） 520362 A7 B7 五、發明説明（46 ) 經濟部中央標準局員工消費合作社印製 3-三氟甲基苯基 4·ρ比淀基 2-(2·氯苯基)乙胺基 2,6-—鼠冬基 4·ρ比淀基 2-(2-氯苯基)乙胺基 2,6-二甲基苯基 4-口比淀基 2-(2-氯苯基)乙胺基 2,4-二氯苯基 4-峨淀基 2-(2-氯苯基)乙胺基 2,4-二甲基苯基 4-ρ比淀基 2-(2-氯苯基)乙胺基 4-氟苯基 4-ρ比淀基 3-(3-氟苯基)丙胺基 4-氟苯基 2-胺基-4-喊淀基 3 -(3 -氣本基)丙胺基 苄基 4-ρ比淀基 3-苯基丙胺基 苄基 4-ρ比淀基 2-(4·氟苯基)乙胺基 2-嘍吩基 比淀基 3-苯基丙胺基 2-遠吩基 4-口比淀基 2-(4-氣苯基)乙胺基 環己基 4-ρ比淀基 3-苯基丙胺基 環己基 4-ρ比淀基 2-(4-氣苯基)乙胺基 第三丁基 4-外b淀基 3-苯基丙胺基 第三丁基 4-ρ比淀基 2·(4-氟苯基)乙胺基 4-鼠苯基 4-六氫p比淀基 3_苯基丙胺基 4-氣苯基 4-六氫p比淀基 2-(4·氣本基)乙胺基 4-氟苯基 4_咬喃基 3-苯基丙胺基 4-氟苯基 4-咬喃基 2-(4-氟苯塞)乙胺基 苯基 2-胺基-4-p比淀基 2-(2-氯苯基)乙胺基 (請先閲讀背面之注意事項再填寫本頁) 訂 -^wi. -49- 本紙張尺度適用中國國家標準（CNS ) A4規格（21GX：297公釐） 520362 A7 B7 五、發明説明（47 ) 經濟部中央標準局員工消費合作社印製 4-氣苯基 2-胺基-4-p比淀基 2-(2-氣本基)乙胺基 3-氟苯基 2-胺基-4-?比淀基 2-(2-氯苯基)乙胺基 2-氟苯基 2-胺基-4-p比淀基 2-(2-氣豕基)乙胺基 4-氯苯基 2-胺基-4-吡啶基 2-(2-氣苯基)乙胺基 3-氯苯基 2-胺基-4-p比啶基 2-(2-氯苯基)乙胺基 2-氣苯基 2-胺基-4_p比淀基 2-(2-氯苯基)乙胺基 4-甲苯基 2-胺基-4-^7比淀基 2-(2-氣本基)乙胺基 3-甲苯基 2-胺基-4-p比淀基 2-(2-氯苯基)乙胺基 2-甲苯基 2-胺基淀基 2-(2-氣苯基)乙胺基 4-二氣甲基苯基 2-胺基-4-峨淀基 2-(2-氣本基)乙胺基 3_三氟甲基苯基 2-胺基基 2-(2-氯苯基)乙胺基 2,6-二氯苯基 2-胺基-4-吡啶基 2-(2-氣本基)乙胺基 2,6-二甲基苯基 2-胺基-4·吡啶基 2-(2-氣木基)乙胺基 2,4-—鼠苯基 2-胺基-4-p比淀基 2-(2-氯苯基)乙胺基 2,4-二甲基苯基 2-胺基-4-#b淀基 2-(2·氯苯基)乙胺基 苯基 2-乙醯胺基-4-p比淀基 2-(2-氯苯基)乙胺基 4-氟苯基 2-乙醯胺基-4_吡啶基 2-(2-氯苯基)乙胺基 3-氣苯基 2-乙醯胺基-4-吡啶基 2-(2-氯苯基)乙胺基 2-鼠苯基 2-乙醯胺基_4·吡啶基 2-(2-氯苯基)乙胺基 4-氯苯基 2-乙醯胺基-4-p比淀基 2-(2-氯苯基)乙胺基 (請先閲讀背面之注意事項再填寫本頁)7 B V. Description of the invention (45) 4-Tolyl 2-Amino-4-Houtyl 2,6-Dichloromethyl 3-Tolyl 2-Amino- 4-Hydroyl 2,6 · dichloromethyl 2-tolyl 2-amino-4-continyl 2,6-dichloromethyl 4-trifluoromethylphenyl 2-amino_4_ Mesityl 2,6-dichloroethenyl 3-trifluoromethylphenyl 2-amino 4-continyl 2,6-dichloroethenyl 2,6-dichlorophenyl 2-amino- 4-Hydroyl 2,6-dichloroethenyl 2,6-dimethylphenyl 2-amino-4-hexyl 2,6-dichloroethenyl 2,4-dimuryl 2_ Amino-4-p denselyl 2,6-dichloroethenyl 2,4-dimethylphenyl 2_amino-4-acidyl 2,6-dichloroethenyl radical 4_p (2-Chlorophenyl) ethylamino 4-fluorophenyl 4-p than Yodo 2- (2-Gaimyl) ethylamino 3-phenyl 4-p than Yodo 2- (2-chlorophenyl ) Ethylamino 2-Arylidene 4. Ethylamino 2- (2-chlorophenyl) ethylamino 4-chlorophenyl 4-p-pyridyl 2- (2 · chlorophenyl) ethylamino 3 -Chlorophenyl 4-p-pyridyl 2- (2-chlorophenyl) ethylamino 2-chlorophenyl 4-lipidyl 2- (2-chlorophenyl) ethylamino 4-tolyl 4 -p than Yodoyl 2- (2-aminobenzyl) ethylamino 3-fluorene 4-Phenyl 2- (2-chlorophenyl) ethylamino 2-tolyl 4-leaf 1: Yendyl 2- (2-chlorophenyl) ethylamino 4-trifluorofluorenylphenyl 4-p than Yodo-based 2- (2-chlorophenyl) ethylamino (Please read the precautions on the back before filling this page),-口 -48- This paper size is applicable to China National Standard (CNS) A4 specifications ( 2IOX 297 mm) 520362 A7 B7 V. Description of the invention (46) 3-trifluoromethylphenyl 4 · ρ compared with 2- (2 · chlorophenyl) ethylamine printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 2,6-Romydyl 4-p-pyridyl 2- (2-chlorophenyl) ethylamino 2,6-dimethylphenyl 4-lipidyl 2- (2-chlorophenyl ) Ethylamino 2,4-dichlorophenyl 4-etheryl 2- (2-chlorophenyl) ethylamino 2,4-dimethylphenyl 4-r Phenyl) ethylamino 4-fluorophenyl 4-ρ is more than 3- (3-fluorophenyl) propylamino 4-fluorophenyl 2-amino-4-amino Propyl) propylaminobenzyl 4-ρ than yodoyl 3-phenylpropylaminobenzyl 4-ρ yodoyl 2- (4-fluorophenyl) ethylamino 2-fluorenyl yodoyl 3-phenyl Ratio of propylamino 2-distenyl 4-methyl to 2-methyl 4- (phenylphenyl) ethylaminocyclohexyl 4-ρ 3-Phenylpropylaminocyclohexyl 4-ρ is better than 2- (4-aminophenyl) ethylamino, 3-butyl 4-exo, 3-phenylpropylamino, 3-butyl 4-ρ Pyridyl 2. · (4-fluorophenyl) ethylamino 4-murylphenyl 4-hexahydrop-pyridyl 3-phenylphenylamino 4-pyrophenyl 4-hexaphenyl p-pyridyl 2- ( 4 · benzyl) ethylamino 4-fluorophenyl 4-phenylanyl 3-phenylpropylamino 4-fluorophenyl 4-anthenyl 2- (4-fluorophenylene) ethylaminophenyl 2 -Amine-4-p than 2- (2-chlorophenyl) ethylamine (Please read the precautions on the back before filling this page) Order- ^ wi. -49- This paper size applies to Chinese national standards (CNS) A4 specification (21GX: 297 mm) 520362 A7 B7 V. Description of invention (47) 4-Gasphenyl 2-amino-4-p ratio lake base 2-printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (2-Gasyl) ethylamino 3-fluorophenyl 2-amino-4-? Pyridyl 2- (2-chlorophenyl) ethylamino 2-fluorophenyl 2-amino-4- p ratio 2- (2-Arylidene) ethylamino 4-chlorophenyl 2-amino-4-pyridyl 2- (2-aminophenyl) ethylamino 3-chlorophenyl 2-amine 4-Pyridinyl 2- (2-chlorophenyl) ethylamino 2-aminophenyl 2-amino-4_p 2-Chlorophenyl) ethylamino 4-tolyl 2-amino-4- ^ 7 ratio to 2- (2-aminobenzyl) ethylamino 3-tolyl 2-amino-4-p Yodo 2- (2-chlorophenyl) ethylamino 2-tolyl 2-amino Yodo 2- (2-fluorophenyl) ethylamino 4-difluoromethylphenyl 2-amino-4 -Edoyl 2- (2-aminobenzyl) ethylamino 3-trifluoromethylphenyl 2-amino- 2- (2-chlorophenyl) ethylamino 2,6-dichlorophenyl 2 -Amino-4-pyridyl 2- (2-aminobenzyl) ethylamino 2,6-dimethylphenyl 2-amino-4 · pyridyl 2- (2-aminobenzyl) ethylamino 2,4--Rhamnyl 2-amino-4-p than 2-Yenyl 2- (2-chlorophenyl) ethylamino 2,4-dimethylphenyl 2-amino-4- # b 2- (2-Chlorophenyl) ethylaminophenyl 2-acetamido-4-p than 2-methyl-2- (2-chlorophenyl) ethylamino 4-fluorophenyl 2-acetamido 4-pyridyl 2- (2-chlorophenyl) ethylamino 3-phenyl 2-acetamido-4-pyridyl 2- (2-chlorophenyl) ethylamino 2-Ethylamido-4pyridyl 2- (2-chlorophenyl) ethylamino 4-chlorophenyl 2-ethylamido-4-p ) Ethylamino (Please read the notes on the back before filling this page)

、1T -50- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 Β 五、發明説明（48 ) 經濟部中央標準局員工消費合作社印製 3-氯苯基 2·乙醯胺基-4-吡啶基 2-(2-氣本基)乙胺基 2-氯苯基 2·乙醯胺基-4-Ρ比啶基 2-(2-氣苯基)乙胺基 4-甲苯基 2-乙酿胺基-4-峨淀基 2-(2-氯苯基)乙胺基 3-甲苯基 2-乙醯胺基-4-吡啶基 2-(2-氣本基)乙胺基 2-甲苯基 2·乙醯胺基·4-吡啶基 2-(2-氯苯基)乙胺基 4-三氟甲基苯基 2-乙酿胺基-4-ρ比淀基 2-(2-氯苯基)乙胺基 3-三氟甲基苯基 2-乙醯胺基-4-吡啶基 2-(2-氯苯基)乙胺基 2,6-二氣本基 2-乙醯胺基-4-吡啶基 2-(2-氣本基)乙胺基 2,6-二甲基苯基 2-乙醯胺基-4-ρ比淀基 2-(2-氯苯基)乙胺基 2,4-二氯苯基 2-乙醯胺基-4·吡啶基 2-(2-氯苯基)乙胺基 2,4-二甲基苯基 2-乙酿胺基-4-ρ比淀基 2-(2-氯苯基)乙胺基 苯基 2-胺基_4_喊淀基 2-(2·氣本基)乙胺基 4_鼠苯基 2-胺基-4-喊淀基 2-(2-氯苯基)乙胺基 3-氟苯基 2-胺基-4-喊淀基 2-(2-氯苯基)乙胺基 2-氣本基 2-胺基-4·喊淀基 2-(2-氯苯基)乙胺基 4-氯苯基 2-胺基-4-喊淀基 2-(2-氯苯基)乙胺基 3-氯苯基 2-胺基-4-喃淀基 2-(2-氯苯基)乙胺基 2-氯苯基 2-胺基-4-喊淀基 2-(2·氯苯基)乙胺基 4-甲苯基 2-胺基-4-喃淀基 2-(2-氯苯基)乙胺基 3-甲苯基 2-胺基-4-喃淀基 2-(2-氯苯基)乙胺基 (請先閱讀背面之注意事項再填寫本頁)、 1T -50- This paper size is in accordance with Chinese National Standard (CNS) A4 (210X 297mm) 520362 Β 5. Description of the invention (48) 3-chlorophenyl 2 · B printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Ethylamino-4-pyridyl 2- (2-aminobenzyl) ethylamino 2-chlorophenyl 2.Ethylamino-4-Ppyridinyl 2- (2-aminophenyl) ethylamino 4-Tolyl 2-Ethylamino-4-eodoyl 2- (2-chlorophenyl) ethylamino 3-tolyl 2-ethylamido-4-pyridyl 2- (2-benzyl ) Ethylamino 2-tolyl 2. Ethylamino 4-pyridyl 2- (2-chlorophenyl) ethylamino 4-trifluoromethylphenyl 2-ethylamino-4-ρ Titanyl 2- (2-chlorophenyl) ethylamino 3-trifluoromethylphenyl 2-acetamido-4-pyridyl 2- (2-chlorophenyl) ethylamino 2,6- 2-Gasyl 2-Ethylamino-4-pyridyl 2- (2-Gasthymiyl) Ethylamino 2,6-Dimethylphenyl 2-Ethylamino-4-r -(2-chlorophenyl) ethylamino 2,4-dichlorophenyl 2-acetamido-4 · pyridyl 2- (2-chlorophenyl) ethylamino 2,4-dimethylbenzene 2-Ethylamino-4-p ratio than 2-Yodoyl 2- (2-chlorophenyl) ethylaminophenyl 2-amino-4_dimethylamino 2- (2.benzyl) ethylamine 4-Methenyl 2-amino-4-amino- (2-chlorophenyl) ethylamino 3-fluorophenyl 2-amino-4-amino- (2-chlorophenyl) ) Ethylamino 2-aminobenzyl-2-amino-4 · dimethylamino 2- (2-chlorophenyl) ethylamino 4-chlorophenyl-2-amino-4-methylamino 2- (2 -Chlorophenyl) ethylamino 3-chlorophenyl 2-amino-4-ranyl 2- (2-chlorophenyl) ethylamino 2-chlorophenyl 2-amino-4-yl 2- (2-Chlorophenyl) ethylamino 4-tolyl 2-amino-4-ranoyl 2- (2-chlorophenyl) ethylamino 3-tolyl 2-amino-4-ran Yodo 2- (2-chlorophenyl) ethylamino (Please read the precautions on the back before filling this page)

、1T #Ί. -51 - 本紙張尺度適用中國國家標準（CNS ) Α4規格（2】0Χ297公釐） 520362 A7 B7 五、發明説明（49 ) 經濟部中央標準局員工消費合作社印製 2-甲苯基 2-胺基-4_喊淀基 2-(2-氯苯基)乙胺基 4-三氟甲基苯基 2-胺基-4-喊淀基 2-(2-氣苯基)乙胺基 3-三氟甲基苯基 2-胺基-4_喃淀基 2-(2-氯苯基)乙胺基 2,6-二氣本基 2-胺基-4-喃淀基 2-(2-氯苯基)乙胺基 2,6·二甲基苯基 2-胺基密淀基 2-(2-氯苯基)乙胺基 2,4-二氣本基 2-胺基-4-喃淀基 2-(2-氯苯基)乙胺基 2,4-二甲基苯基 2-胺基-4-喃淀基 2-(2-氯苯基)乙胺基 苯基 4-π比淀基 2-(4-氟苯基)乙胺基 4-氟苯基 4-吡啶基 2-(4-氟苯基)乙胺基 3-氣本基 4-吡啶基 2-(4-氟苯基)乙胺基 2-氟苯基 :4·ρ比淀基 2-(4-氣苯基)乙胺基 4-氯苯基 4-ρ比淀基 2-(4-氟苯基)乙胺基 3-氯苯基 4-口比淀基 2-(4-氣苯基)乙胺基 2-氯苯基 4-ρ比淀基 2_(4·氟苯基)乙胺基 4-甲苯基 4-ρ比淀基 2-(4-氟苯基)乙胺基 3-甲苯基 4-ρ比淀基 2-(4-氟苯基)乙胺基 2-甲苯基 4-峨淀基 2-(4-氟苯基)乙胺基 4·三氟甲基苯基 4-口比淀基 2-(4-氣苯基)乙胺基 3-三氟甲基苯基 4-ρ比淀基 2—(4_氟苯塞)乙胺基 2,6-二氣本基 4-峨淀基 2-(4-氟苯基)乙胺基 (請先閱讀背面之注意事項再填寫本頁)、 1T # Ί. -51-This paper size applies to Chinese National Standard (CNS) A4 specification (2) 0 × 297 mm 520362 A7 B7 V. Description of the invention (49) 2-Toluene printed by the staff consumer cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 2-Amino-4_amino group 2- (2-chlorophenyl) ethylamino 4-trifluoromethylphenyl 2-amino-4-amino group 2- (2-aminophenyl) Ethylamino 3-trifluoromethylphenyl 2-amino-4-anhydro-2-yl 2- (2-chlorophenyl) ethylamino 2,6-diaminobenzyl 2-amino-4-nan 2- (2-chlorophenyl) ethylamino 2,6, dimethylphenyl 2-aminomylide 2- (2-chlorophenyl) ethylamino 2,4-diaminobenzyl 2 -Amino-4-ranyl 2- (2-chlorophenyl) ethylamino 2,4-dimethylphenyl 2-amino-4-ranyl 2- (2-chlorophenyl) ethyl Aminophenyl 4-π is better than 2- (4-fluorophenyl) ethylamino 4-fluorophenyl 4-pyridyl 2- (4-fluorophenyl) ethylamino 3-aminobenzyl 4- Pyridyl 2- (4-fluorophenyl) ethylamino 2-fluorophenyl: 4 · ρ than yodoyl 2- (4-fluorophenyl) ethylamino 4-chlorophenyl 4-ρ ypyridyl 2 -(4-fluorophenyl) ethylamino 3-chlorophenyl 4-methylpyridyl 2- (4-fluorophenyl) ethylamino 2-chlorophenyl 4-ρpyridyl 2- (4-fluoro Phenyl) ethylamino 4-Tolyl 4-ρ ratio ylidene 2- (4-fluorophenyl) ethylamino 3-tolyl 4-ρ ratio ylidene 2- (4-fluorophenyl) ethylamino 2-tolyl 4- Edoyl 2- (4-fluorophenyl) ethylamino 4 · trifluoromethylphenyl 4-orbitoyl 2- (4-fluorophenyl) ethylamino 3-trifluoromethylphenyl 4 -ρ ratio Yodo-based 2- (4-fluorophenylene) ethylamino 2,6-difluorobenzyl 4-amido-based 2- (4-fluorophenyl) ethylamino (Please read the precautions on the back first (Fill in this page again)

、1T -52- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（5〇 ) 經濟部中央標準局員工消費合作社印製 2,6-二甲基苯基 4-吡啶基 2-(4-氟苯基)乙胺基 2,4-二氯苯基 4-p比淀基 2-(4-氟苯基)乙胺基 2,4-二甲基苯基 4-p比淀基 2-(4-氟苯基)乙胺基 苯基 2_胺基_4·吡啶基 2-(4-氣本基)乙胺基 4-氟苯基 2-胺基基 2-(4-氟苯基)乙胺基 3-鼠苯基 2-胺基-4-p比淀基 2-(4-氟苯基)乙胺基 2-氣苯基 2-胺基-4-P比1基 2-(4-氟苯基)乙胺基 4-氯苯基 2-胺基-4-p比淀基 2-(4-氟苯基)乙胺基 3-氯苯基 2-胺基-4-p》ls淀基 2-(4-氟苯基)乙胺基 2-氯苯基 2-胺基-4-1?比症_基 2-(4-鼠本基)乙胺基 4-甲苯基 2-胺基-4-p比淀基 2-(4·氟苯基)乙胺基 3-甲苯基 2-胺基_4_p比淀基 2-(4-氟苯基)乙胺基 2-甲苯基 2·胺基-4-吡啶基 2-(4_氟苯基)乙胺基 4-二鼠甲基苯基 2-胺基-4-吡啶基 2-(4-氟苯基)乙胺基 3-三氟甲基苯基 2-胺基-4-p比症_基 2-(4·氟苯基)乙胺基 2,6-二氣本基 2-胺基-4-p比淀基 2-(4-鼠苯基)乙胺基 2,6-二甲基苯基 2-胺基-4-^比^^基 2-(4-氟苯基)乙胺基 2,4-二氣本基 2-胺基·4_ρ比淀基 2-(4-氟苯基)乙胺基 2,4-二甲基苯基 2-胺基-4-^7比淀基 2-(4-氟苯基)乙胺基 苯基 2-乙醯胺基-4-吡啶基 2-(4-氟苯基)乙胺基 (請先閱讀背面之注意事項再填寫本頁)、 1T -52- This paper size applies to Chinese National Standard (CNS) A4 specification (210X 297mm) 520362 A7 B7 V. Description of invention (50) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Phenylphenyl 4-pyridyl 2- (4-fluorophenyl) ethylamino 2,4-dichlorophenyl 4-p than phenyl 2- (4-fluorophenyl) ethylamino 2,4-di Methylphenyl 4-p is 2- (4-fluorophenyl) ethylaminophenyl 2-amino-4-pyridyl 2- (4-aminobenzyl) ethyl 4-fluorophenyl 2-amino 4- (4-fluorophenyl) ethylamino 3-muryl 2-amino-4-p than 2- (4-fluorophenyl) ethylamino 2-phenyl 2-Amino-4-P to 1-yl 2- (4-fluorophenyl) ethylamino 4-chlorophenyl 2-amino-4-p to 2-amino- (4-fluorophenyl) ethylamine 3-Chlorophenyl 2-amino-4-p >> ls 2- (4-fluorophenyl) ethylamino 2-chlorophenyl 2-amino-4-1? (4-Merbenyl) Ethylamino 4-tolyl 2-amino-4-p than Yodo 2- (4-fluorophenyl) ethylamino 3-tolyl 2-amino-4_p 2- (4-fluorophenyl) ethylamino 2-tolyl 2.amino-4-pyridyl 2- (4-fluorophenyl) ethylamino 4-dimurylphenyl 2-amino- 4-pyridyl 2- (4-fluorophenyl) Amino 3-trifluoromethylphenyl 2-amino-4-p ratio_yl 2- (4-fluorophenyl) ethylamino 2,6-diaminobenzyl 2-amino-4-p Biyenyl 2- (4-murylphenyl) ethylamino 2,6-dimethylphenyl 2-amino-4- ^ biphenyl 2- (4-fluorophenyl) ethylamino 2, 4-Diaminobenzyl 2-amino group 4-p-pyridyl 2- (4-fluorophenyl) ethylamino 2,4-dimethylphenyl 2-amino 4- ^ 7 (4-fluorophenyl) ethylaminophenyl 2-acetamido-4-pyridyl 2- (4-fluorophenyl) ethylamino (Please read the precautions on the back before filling this page)

、1T -^wi. -53- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（51 ) 經濟部中央標準局員工消費合作社印製 4-氟苯基 2-乙廳胺基-4-p比基 2·(4-氟苯基)乙胺基 3-氟苯基 2-乙酸胺基-4·ρ比淀基 2-(4-氟苯基)乙胺基 2-氟苯基 2-乙驢胺基-4-p比淀基 2-(4-氟苯基)乙胺基 4-氯苯基 2-乙醯胺基-4·吡啶基 2-(4-氟苯基)乙胺基 3-氯苯基 2-乙醯胺基-4-吡啶基 2-(4-氟苯基)乙胺基 2-氯苯基 2-乙醯胺基-4-吡啶基 2-(4-氟苯基)乙胺基 4-甲苯基 2_乙醯胺基-4-吡啶基 2-(4-氟苯基)乙胺基 3-曱苯基 2_乙醯胺基·4-吡啶基 2-(4-氟苯基)乙胺基 2-甲苯基 2·乙醯胺基_4·吡啶基 2-(4-氣苯基)乙胺基 4-三氟甲基苯基 2-乙醯胺基-4-吡啶基 2_(4_氟苯基)乙胺基 3-三氟甲基苯基 2-乙醯胺基-4-吡啶基 2-(4-氟苯基)乙胺基 2,6-二氣豕基 2-乙酿胺基-4-ρ比淀基 2-(4-氟苯基)乙胺基 2,6-二甲基苯基 2-乙醯胺基-4-ρ比咬基 2-(4·氟苯基)乙胺基 2,4-二氯苯基 2_乙醯胺基_4_吡啶基 2-(4-鼠苯基)乙胺基 2,4-二甲基苯基 2-乙醯胺基4-吡啶基 2-(4-氟苯基)乙胺基 苯基 2-胺基-4-喊淀基 2-(4-氟苯基)乙胺基 4-氟苯基 2-胺基-4-喃淀基 2-(4-氣苯基)乙胺基 3-氟苯基 2-胺基-4-喃淀基 2-(4-氟苯基)乙胺基 2-鼠苯基 2-胺基-4-喊淀基 2-(4-氣苯基)乙胺基 4-氯苯基 2-胺基-4-喃淀基 2-(4-氟苯基)乙胺基 (請先閲讀背面之注意事項再填寫本頁) 訂 -^wl. -54- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（52 ) 經濟部中央標準局員工消費合作社印製 3-氯苯基 2·胺基-4-p密淀基 2-(4-氟苯基)乙胺基 2-氯苯基 2-胺基-4-喊淀基 2-(4-鼠本基)乙胺基 4-曱苯基 2·胺基·4_喃淀基 2-(4-氟苯基)乙胺基 3-甲苯基 2-胺基_4_墙淀基 2-(4-氟苯基)乙胺基 2-甲苯基 2-胺基-4-癌淀基 2-(4-氟苯基)乙胺基 4-三氟甲基苯基 2-胺基-4-喃淀基 2-(4-氟苯基)乙胺基 3-三氟甲基苯基 2-胺基-4-喊淀基 2-(4_氟苯基)乙胺基 2,6-二氣本基 2-胺基-4-ρ密淀基 2-(4-氟苯基)乙胺基 2,6-二甲基苯基 2-胺基-4-^1密淀基 2-(4-氟苯基)乙胺基 2,4-二氯苯基 2-胺基-4-喃基 2-(4-氟苯基)乙胺基 2,4-二甲基苯基 2-胺基-4-喊症基 2-(4-氟苯基)乙胺基 苯基 4-口比淀基 3-苯基丙胺基 4-氟苯基 4-外b淀基 3-苯基丙胺基 3-氟苯基 4-p比淀基 3-苯基丙胺基 2-氣苯基 4-p比淀基 3-苯基丙胺基 4-氯苯基 4-p比淀基 3-苯基丙胺基 3-氯苯基 4-峨啶基 3-苯基丙胺基 2-氯苯基 4-p比淀基 3·苯基丙胺基 4-甲苯基 4-峨淀基 3-苯基丙脖基 3-甲苯基 4-峨淀基 3-苯基丙胺基 (請先閱讀背面之注意事項再填寫本頁)、 1T-^ wi. -53- This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) 520362 A7 B7 V. Description of Invention (51) 4-Fluorine printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Phenyl 2-Ethylamino-4-p-pyridyl 2. (4-fluorophenyl) ethylamino 3-fluorophenyl 2-acetamido-4 · ρpyridyl 2- (4-fluorobenzene (Ethyl) ethylamino 2-fluorophenyl 2-ethylammonyl-4-p than yodoyl 2- (4-fluorophenyl) ethylamino 4-chlorophenyl 2-acetamido-4 · pyridine 2- (4-fluorophenyl) ethylamino 3-chlorophenyl 2-acetamido-4-pyridyl 2- (4-fluorophenyl) ethylamino 2-chlorophenyl 2-acetamidine Amino-4-pyridyl 2- (4-fluorophenyl) ethylamino 4-tolyl 2-acetamido-4-pyridyl 2- (4-fluorophenyl) ethylamino 3-fluorenyl 2-Acetylamido 4-pyridyl 2- (4-fluorophenyl) ethylamino 2-tolyl 2-acetamido-4pyridyl 2- (4-aminophenyl) ethylamine 4-trifluoromethylphenyl 2-acetamido-4-pyridyl 2- (4-fluorophenyl) ethylamino 3-trifluoromethylphenyl 2-acetamido-4-pyridyl 2- (4-fluorophenyl) ethylamino 2,6-diaziridinyl 2-ethylamino-4-p-pyridyl 2- (4-fluorophenyl) ethylamino 2,6 -Dimethylphenyl 2-ethenylamino-4-p ratio than 2- (4-fluorophenyl) ethylamino 2,4-dichlorophenyl 2-ethenylamino-4_pyridyl 2- (4-muryl) ethylamino 2,4-dimethylphenyl 2-acetamido 4-pyridyl 2- (4-fluorophenyl) ethylaminophenyl 2-amino- 4-Hydroyl 2- (4-fluorophenyl) ethylamino 4-fluorophenyl 2-amino-4-anyl 2- (4-fluorophenyl) ethylamino 3-fluorophenyl 2 -Amino-4-ranoyl 2- (4-fluorophenyl) ethylamino 2-muranyl 2-amino-4-oxoyl 2- (4-aminophenyl) ethylamino 4- Chlorophenyl 2-amino-4-ranoyl 2- (4-fluorophenyl) ethylamino (Please read the precautions on the back before filling this page) Order-^ wl. -54- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A7 B7 V. Description of invention (52) 3-Chlorophenyl 2 · amino-4-p dense lake base printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs -(4-Fluorophenyl) ethylamino 2-chlorophenyl 2-amino-4-hexyl 2- (4-muryl) ethylamino 4-amidophenyl 2.amino-4_ 2- (4-Fluorophenyl) ethylamino 3-tolyl 2-amino 4- 4-methylphenyl 2- (4-fluorophenyl) ethylamino 2-tolyl 2-amino- 4- Ondo 2- (4-fluorophenyl) ethylamino 4-trifluoromethylphenyl 2-amino-4-ranoyl 2- (4-fluorophenyl) ethylamino 3-trifluoromethyl Phenylphenyl 2-amino-4-methylamino 2- (4-fluorophenyl) ethylamino 2,6-diaminobenzyl-2-amino-4-ρ denselyl 2- (4-fluoro (Phenyl) ethylamino 2,6-dimethylphenyl 2-amino-4- ^ 1 dense lake 2- (4-fluorophenyl) ethylamino 2,4-dichlorophenyl 2-amine 4-Amino-2- (4-fluorophenyl) ethylamino 2,4-dimethylphenyl 2-amino-4-amino-2- (4-fluorophenyl) ethylaminobenzene 4-methylpyridyl 3-phenylpropylamino 4-fluorophenyl 4-pyridyl 3-phenylpropylamino 3-fluorophenyl 4-p Phenyl 4-p is 3-phenylpropylamino 4-chlorophenyl 4-p is 4-phenylpropylamino 3-chlorophenyl 4-eridyl 3-phenylpropylamino 2-chloro Phenyl 4-p is more than 3-phenylpropylamino 4-tolyl 4-etolyl 3-phenylpropyl 3-tolyl 4-tolyl 3-phenylpropylamino (please read the back first) (Notes for filling in this page)

、1T ^_wl. -55- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362、 1T ^ _wl. -55- This paper size applies to China National Standard (CNS) A4 (210X 297 mm) 520362

A 五、發明説明（53 ) 經濟部中央標準局員工消費合作社印製 2-甲苯基 4^比淀基 3-苯基丙胺基 4-三氟甲基苯基 4-p比淀基 3-苯基丙胺基 3-三氟甲基苯基 4-p比淀基 3-苯基丙胺基 2,6-二氯苯基 4-p比淀基 3-苯基丙胺基 2,6-二甲基苯基 4-峨淀基 3-苯基丙胺基 2,4_二氯苯基 4-吡啶基 3-苯基丙胺基 2,4-二甲基苯基 4-峨淀基 3-本基丙胺基 苯基 2-胺基-4-吡啶基 3-苯基丙胺基 4-氣苯基 2-胺基-4-。比1^基 3-苯基丙胺基 3-氟苯基 2-胺基-4-吡啶基 3-苯基丙胺基 2-氟苯基 2-胺基基 3-苯基丙胺基 4-氯苯基 2-胺基-4-pib咬基 3-苯基丙胺基 3-氯苯基 2-胺基-4-p比淀基 3-苯基丙胺基 2-氯苯基 2-胺基-4-pJ^淀基 3-苯基丙胺基 4·甲苯基 2-胺基基 3_苯基丙胺基 3·甲苯基 2-胺基-4-p》b淀基 3-苯基丙胺基 2-甲苯基 2-胺基淀基 3-苯基丙胺基 4-三氟甲基苯基 2-胺基·4-ρ比淀基 3-苯基丙胺基 3-三氟甲基苯基 2-胺基-4_p比淀基 3-苯基丙胺基 2,6·二鼠本基 2-胺基基 3-苯基丙胺基 (請先閱讀背面之注意事項再填寫本頁) -口 -56- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（54 ) 經濟部中央標準局員工消費合作社印製 2,6-二甲基苯基 2-胺基-4-吡啶基 3-苯基丙胺基 2,4-二氣豕基 2-胺基-4-p比淀基 3-苯基丙胺基 2,4-二甲基苯基 2-胺基-4-ptb淀基 3-苯基丙胺基 苯基 2-乙S盛胺基基 3-苯基丙胺基 4-鼠苯基 2-乙醯胺基-4-p比淀基 3-苯基丙胺基 3-氣苯基 2-乙醯胺基-4-吡啶基 3-苯基丙胺基 2-氣苯基 2-乙醯胺基-4-p比淀基 3-苯基丙胺基 4-氯苯基 2-乙酿胺基-4-峨淀基 3-苯基丙胺基 3-氯苯基 2-乙醯胺基-4-吡啶基 3-苯基丙胺基 2-氣豕基 2·乙醯胺基-4-吡啶基 3-苯基丙胺基 4-甲苯基 2-乙酿胺基-4_^比^^基 3-苯基丙胺基 3-甲苯基 2-乙醯胺基-4-吡淀基 3-苯基丙胺基 2-甲苯基 2-乙醯胺基-4-吡啶基 3-苯基丙胺基 4-三氟甲基苯基 2-乙醯胺基-4-吡淀基 3-苯基丙胺基 3-三氟甲基苯基 2-乙醯胺基-4-吡啶基 3-苯基丙胺基 2,6-—氣本基 2-乙酿胺基-4-p比淀基 3-苯基丙胺基 2,6_二甲基苯基 2-乙醯胺基-4-吡啶基 3-苯基丙胺基 2,4-二氯苯基 2-乙醯胺基-4-吡啶基 3-苯基丙胺基 2,4-二甲基苯基 2-乙醯胺基-4-吡啶基 3-苯基丙胺基 苯基 2-胺基-4-喊淀基 3_苯基丙胺基 (請先閱讀背面之注意事項再填寫本頁) 訂 ^wi. -57- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 7 Β 五、發明説明（55 ) 經濟部中央標準局員工消費合作社印製 4-氣苯基 2-胺基-4-喊淀基 3-苯基丙胺基 3-氟苯基 2-胺基-4-ρ密淀基 3-苯基丙胺基 2-氟苯基 2-胺基-4-哺淀基 3-苯基丙胺基 4-氯苯基 2-胺基-4-喊淀基 3-苯基丙胺基 3-氯苯基 2-胺基-4-喊淀基 3-苯基丙胺基 2-氯苯基 2-胺基-4-喃淀基 3-苯基丙胺基 4-甲苯基 2-胺基-4-墙淀基 3-苯基丙胺基 3-甲苯基 2_胺基-4-喊淀基 3-苯基丙胺基 2-甲苯基 2-胺基_4_喃淀基 3-苯基丙胺基 4-二氣甲基苯基 2-胺基-4-喊淀基 3-苯基丙胺基 3-三氟甲基苯基 2-胺基-4-癌淀基 3-苯基丙胺基 2,6-二鼠表基 2-胺基-4-p密淀基 3-苯基丙胺基 2,6-二甲基苯基 2-胺基-4-喊淀基 3-苯基丙胺基 2,4-二氯苯基 2-胺基-4-喃淀基 3-苯基丙胺基 2,4-二甲基苯基 2-胺基-4-喃淀基 3-苯基丙胺基 苯基 4-p比淀基 3-咪唑基丙胺基 4-氟苯基 4_p比淀基 3_咪唑基丙胺基 3-鼠苯基 4-p比淀基 3_咪唑基丙胺基 2-氟苯基 4-p比淀基 3-咪唑基丙胺基 4-氣苯基 4-1?比淀基 3-咪唑基丙胺基 (請先閱讀背面之注意事項再填寫本頁)A 5. Description of the invention (53) 2-Tolyl 4-pyridyl 3-phenylpropylamino 4-trifluoromethylphenyl 4-p-pyridyl 3-benzene printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Propylpropylamino 3-trifluoromethylphenyl 4-p than yodoyl 3-phenylpropylamino 2,6-dichlorophenyl 4-p ypyridyl 3-phenylpropylamino 2,6-dimethyl Phenyl 4-etheryl 3-phenylpropylamino 2,4-dichlorophenyl 4-pyridyl 3-phenylpropylamino 2,4-dimethylphenyl 4-etheryl 3-benzylpropylamine Phenyl 2-amino-4-pyridyl 3-phenylpropylamino 4-aminophenyl 2-amino-4-. Than 1 ^ yl 3-phenylpropylamino 3-fluorophenyl 2-amino-4-pyridyl 3-phenylpropylamino 2-fluorophenyl 2-amino 3-phenylpropylamino 4-chlorobenzene 2-Amino-4-pib, 3-phenylpropylamino, 3-chlorophenyl 2-amino-4-p, 2-amino-4-phenyl, 3-phenylpropylamino 2-chlorophenyl, 2-amino-4 -pJ ^ yl 3-phenylpropylamino 4-tolyl 2-amino 4-phenylpropylamino 3-tolyl 2-amino-4-p "b Tolyl 2-amino-based 3-phenylpropylamino 4-trifluoromethylphenyl 2-amino -4_p than yodoyl 3-phenylpropylamino 2,6 · dimuryl 2-amino 3-phenylpropylamino (Please read the precautions on the back before filling this page) Paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A7 B7 V. Description of invention (54) 2,6-Dimethylphenyl 2-amino group printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs- 4-pyridyl 3-phenylpropylamino 2,4-diaziridinyl 2-amino-4-p than pyrido3-phenylpropylamino 2,4-dimethylphenyl 2-amino-4 -ptbYendyl 3-phenylpropylamine 2-Phenylphenyl 2-ethoxyamino 3-phenylpropylamino 4-murylphenyl 2-ethylamino-4-p Amino-4-pyridyl 3-phenylpropylamino 2-phenyl-2-acetamido-4-p is more than 3-phenylpropylamino 4-chlorophenyl 2-ethylamino-4 -Yodoyl 3-phenylpropylamino 3-chlorophenyl 2-acetamido-4-pyridyl 3-phenylpropylamino 2-aziridinyl 2-acetamido-4-pyridyl 3- Phenylalanyl 4-tolyl 2-ethylamino-4, 4-phenylalanyl 3-phenylpropylamino 3-tolyl 2-acetamido-4-pyridyl 3-phenylpropylamino 2 -Tolyl 2-acetamido-4-pyridyl 3-phenylpropylamino 4-trifluoromethylphenyl 2-acetamido-4-pyridyl 3-phenylpropylamino 3-trifluoro Methylphenyl 2-acetamido-4-pyridyl 3-phenylpropylamino 2,6--aminobenzyl-2-ethylamino-4-p than pyrido3-phenylpropylamino 2, 6-dimethylphenyl 2-acetamido-4-pyridyl 3-phenylpropylamino 2,4-dichlorophenyl 2-acetamido-4-pyridyl 3-phenylpropylamino 2 , 4-Dimethylphenyl 2-acetamido-4-pyridyl 3-phenylpropylaminophenyl 2-amino-4-amino (Please read the notes on the back before filling this page) Order ^ wi. -57- This paper size is applicable to China National Standard (CNS) A4 specification (210X 297 mm) 520362 7 Β 5. Description of the invention (55 ) Printed by 4-Phenyl 2-Amino-4-Amino- 3-phenylphenylamino 3-fluorophenyl 2-Amino-4-ρ-Milide 3- Phenylpropylamino 2-fluorophenyl 2-amino-4-amyl 3-phenylpropylamino 4-chlorophenyl 2-amino-4-dimethylamino 3-phenylpropylamino 3-chlorobenzene 2-Amino-4-amino-4-phenylpropylamino 2-chlorophenyl 2-amino 4-aminopropyl 4-phenylpropylamino 4-tolyl 2-amino-4-wall Yodo 3-phenylpropylamino 3-tolyl 2-amino-4-amino 4-hydroxypropyl 3-phenylpropylamino 2-tolyl 2-amino 4- 4-amino Digas methylphenyl 2-amino-4-amino- 3-phenylpropylamino 3-trifluoromethylphenyl 2-amino-4-carbo 3-phenylpropylamino 2,6- Dimuryl 2-amino-4-p memidido 3-phenylpropylamino 2,6-dimethylphenyl 2-amino-4-hydroxypropyl 3-phenylpropylamino 2,4- Dichlorophenyl 2-amino-4-anilino 3-benzene Propylamino 2,4-dimethylphenyl 2-amino-4-ranyl 3-phenylpropylaminophenyl 4-p 3_imidazolylpropylamino 3-muryl 4-p to yttrium Yodo 3-imidazolyl propylamine (Please read the precautions on the back before filling this page)

、1T #1. -58- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 520362 A7 B7 五、發明説明（56 ) 經濟部中央標準局員工消費合作社印製 3-氯苯基 4-p比淀基 3-咪唑基丙胺基 2-氯苯基 4-p比淀基 3-味峻基丙胺基 4-甲苯基 4-p比淀基 3-咪唑基丙胺基 3-甲苯基 4-p比淀基 3-咪唑基丙胺基 2-甲苯基 4-p比淀基 3-咪唑基丙胺基 4-三氟甲基苯基 4-p比淀基 3-咪唑基丙胺基 3-三氟甲基苯基 4-p比淀基 3-咪唑基丙胺基 2,6-二氯本基 4·^比淀基 3-咪唑基丙胺基 2,6-二甲基苯基 4-p比淀基 3-咪唑基丙胺基 2,4-—氣秦基 4-p比淀基 3-咪唑基丙胺基 2,4-二甲基苯基 4_p比淀基 3-咪唑基丙胺基 苯基 2-胺基-4-p比淀基 3-咪唑基丙胺基 4-氟苯基 2-胺基淀基 3·咪唑基丙胺基 3-氣苯基 2-胺基-4-p比淀基 3_咪唑基丙胺基 2-氟苯基 2-胺基-4-p比基 3-咪唑基丙胺基 4-氯苯基 2-胺基-4-吡啶基 3-咪唑基丙胺基 3-氣笨基 2-胺基-4-p比淀基 3-咪唑基丙胺基 2-氯苯基 2·胺基-4-p比淀基 3-咪唑基丙胺基 4-甲苯基 2-胺基-4-p比淀基 3-咪唑基丙'胺基 3-甲苯基 2-胺基-4-p比淀基 3-咪吐基丙胺基 (請先閱讀背面之注意事項再填寫本頁) -59- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362、 1T # 1. -58- This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297mm) 520362 A7 B7 V. Description of invention (56) 3-chlorophenyl printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 4-p-pyridyl 3-imidazolyl-propylamino 2-chlorophenyl 4-p-pyridyl 3-imidylpropylamino 4-tolyl 4-p-pyridyl 3-imidazolylpropylamino 3-tolyl 4-p-pyridyl 3-imidazolyl-propylamino 2-tolyl 4-p-pyridyl 3-imidazolyl-propylamino 4-trifluoromethylphenyl 4-p-pyridyl 3-imidazolyl-propylamino 3- Trifluoromethylphenyl 4-p-pyridyl 3-imidazolylpropylamino 2,6-dichlorobenzyl 4-pyridyl 3-imidazolylpropylamino 2,6-dimethylphenyl 4-p Bidinoyl 3-imidazolyl propylamino 2,4--pyridinyl 4-p Bidinoyl 3-imidazolyl propylamino 2,4-dimethylphenyl 4-Pyridyl 3-imidazolyl propylaminophenyl 2-amino-4-p ratio ylidene 3-imidazolyl propylamino 4-fluorophenyl 2-amine yl 3 · imidazolyl propyl amine 3-aminophenyl 2-amino-4-p pyridyl 3-imidazolyl propylamino 2-fluorophenyl 2-amino-4-p than 3-imidazolyl propylamino 4-chlorophenyl 2-amino-4-pyridyl 3-imidazolyl Amino 3-Aminobenzyl 2-Amino-4-p ratio Amidyl 3-imidazolylpropylamino 2-chlorophenyl 2 · Amino-4-p ratio Amino 3-imidazolylpropylamino 4-tolyl 2-Amino-4-p ratio of 3-amino-imidazolyl'amino 3-tolyl 2-amino-4-p ratio of 3-amino-imidylpropyl (Please read the precautions on the back first (Fill in this page) -59- This paper size applies to China National Standard (CNS) A4 (210X 297mm) 520362

AA

7 B 五、發明説明（57 ) 經濟部中央標準局員工消費合作社印製 2-甲苯基 2-胺基-4-p比淀基 3-咪唑基丙胺基 4-三氣甲基苯基 2-胺基-4-p比淀基 3-咪唑基丙胺基 3-二氟甲基苯基 2-胺基-4_p比淀基 3-咪唑基丙胺基 2,6-二氣豕基 2-胺基比淀基 3_咪峻基丙胺基 2,6-二曱基苯基 2-胺基-4-峨淀基 3 -味峻基丙胺基 2,4-二氯苯基 2-胺基-4-p比淀基 3-咪唑基丙胺基 2,4-二甲基苯基 2-胺基-4-吡啶基 3-咪唑基丙胺基 苯基 2-乙醯胺基-4-吡啶基 3-咪峻基丙胺基 4-氟苯基 2-乙醯胺基-4-吡啶基 3-咪峻基丙胺基 3-氟苯基 2-乙醯胺基_4·吡啶基 3-咪唑基丙胺基 2_氟苯基 2_乙醯胺基_4_吡啶基 3-咪唑基丙胺基 4-氯苯基 2-乙醯胺基-4-吡啶基 3-味峻基丙胺基 3-鼠本基 2·乙醯胺基-4-吡啶基 3-咪唑基丙胺基 2-氯苯基 2_乙酿胺基-4-p比淀基 3-咪唑基丙胺基 4-甲苯基 2-乙醯胺基-4_吡啶基 3-咪唑基丙胺基 3-甲苯基 2-乙酸胺基-4-^比^^基 3-咪峰基丙胺基 2-甲苯基 2-乙醯胺基-4-吡啶基 3-咪唑基丙胺基 4-二氣甲基苯基 2-乙醯胺基_4·吡啶基 3-咪唑基丙胺基 3-三氟甲基苯基 2-乙醯胺基-4·吡啶基 3 -味峻基丙胺基 2,6-二氣豕基 2-乙酿胺基-4-?比淀基 3-咪峻基丙胺基 (請先閲讀背面之注意事項再填寫本頁) 訂 -60- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 五、發明説明（58 ) 經濟部中央標準局員工消費合作社印製 2,6·二甲基苯基 2·乙醯胺基-4-吡啶基 3-咪唑基丙胺基 2,4-二氣本基 2-乙醯胺基-4-p比啶基 3-咪唑基丙胺基 2,4-二甲基苯基 2-乙醯胺基-4_吡啶基 3-咪唑基丙胺基 苯基 2-胺基-4-癌淀基 3-咪唑基丙胺基 4-鼠苯基 2-胺基-4-喊淀基 3-咪唑基丙胺基 3-鼠本基 2-胺基-4-p密淀基 3-咪唑基丙胺基 2-氟苯基 2_胺基-4-喊淀基 3-咪唑基丙胺基 4-氯苯基 2-胺基-4-癌淀基 3-咪唑基丙胺基 3-氯苯基 2-胺基-4-喊淀基 3-咪唑基丙胺基 2-氣苯基 2-胺基-4_癌淀基 3-咪唑基丙胺基 4-甲苯基 2-胺基-4-喊淀基 3-咪唑基丙胺基 3-甲苯基 2-胺基-4-喃淀基 3-咪唑基丙胺基 2-甲苯基 2-胺基-4-喊淀基 3-咪唑基丙胺基 4-三氟甲基苯基 2-胺基-4-喃淀基 3-咪峻基丙胺基 3·三氟甲基苯基 2-胺基-4-喊淀基 3-咪唑基丙胺基 2,6-二氣豕基 2-胺基-4-喊淀基 3-咪唑基丙胺基 2,6-二甲基苯基 2-胺基-4-喊淀基 3-咪唑基丙胺基 2,4·二氯苯基 2-胺基-4-喊淀基 3-咪唑基丙胺基 2,4-二甲基苯基 2-胺基-4-^淀基 3-咪唑基丙'胺基 4-氟苯基 4-p比淀基 4-氟爷基胺基 (請先閱讀背面之注意事項再填寫本頁) -61 - 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 5203627 B V. Description of the invention (57) Printed by 2-tolyl 2-amino-4-p-pyridyl 3-imidazolylpropylamino 4-trimethylolphenyl 2- Amino-4-p ratio of 3-amino-imidazolyl-propylamino 3-difluoromethylphenyl 2-amino-4_p ratio of 3-amino-imidazolyl-propylamino 2,6-diaziridinyl 2-amino Titanyl 3-imidylpropylamino 2,6-difluorenylphenyl 2-amino-4-gadolide 3-amidinopropylpropylamino 2,4-dichlorophenyl 2-amino-4 -p than yodoyl 3-imidazolyl propylamino 2,4-dimethylphenyl 2-amino-4-pyridyl 3-imidazolyl propylaminophenyl 2-acetamido-4-pyridyl 3- Imidylpropylamino 4-fluorophenyl 2-acetamido-4-pyridyl 3-imidylpropylamino 3-fluorophenyl 2-acetamido-4_pyridyl 3-imidazolylpropylamino 2_fluorophenyl 2_acetamido-4_pyridyl 3-imidazolylpropylamino 4-chlorophenyl 2-acetamido-4-pyridyl 3-amidinopropylamino 3-muryl 2 · Ethylamino-4-pyridyl 3-imidazolylamino-2-chlorophenyl 2-ethynylamino-4-p ratio Ethyl 3-imidazolylpropylamino 4-tolyl-2-acetamidamine 4-pyridyl 3-imidazolyl propylamino 3 -Tolyl 2-acetamido-4-^^^^ 3-imidylpropylamino 2-tolyl 2-acetamido-4-pyridyl 3-imidazolylpropylamino 4-difluoromethyl Phenyl 2-ethenylamino-4.pyridyl 3-imidazolylpropylamino 3-trifluoromethylphenyl 2-ethenylamino-4.pyridyl 3 -amidinopropylamino Pyridyl 2-Ethylamine 4-? Biydyl 3-Imidylpropylamine (Please read the precautions on the back before filling this page) Order -60- This paper size applies to Chinese National Standards (CNS) A4 specification (210X 297 mm) 520362 V. Description of the invention (58) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 2,6 · dimethylphenyl-2-acetamido-4-pyridyl 3-imidazolyl Propylamino 2,4-diaminobenzyl 2-acetamido-4-p than pyridyl 3-imidazolylpropylamino 2,4-dimethylphenyl 2-acetamido-4_pyridyl 3 -Imidazolyl alanyl phenyl 2-amino-4-carbodianyl 3-imidazolyl propylamino 4-muryl phenyl 2-amino 4-amidyl 3-imidazolyl propyl amino 3-muryl 2 -Amino-4-p denselyl 3-imidazolylpropylamino 2-fluorophenyl 2-amino-4-imidyl 3-imidazolylpropylamino 4-chlorophenyl 2-amino-4- Yodo 3-imidazolyl propylamino 3-chlorophenyl 2-amino-4-amino 4-Tolyl 2-amino-4-amino-imidyl 3-imidazolyl-propylamino 3-tolyl 2-amino 4-amino-imidyl 3-imidazolyl-propylamino 2-tolyl 2-amino-4 -Hydroyl 3-imidazolylpropylamino 4-trifluoromethylphenyl 2-amino-4-anhydrolyl 3-imidylpropylamino 3.trifluoromethylphenyl 2-amino-4- Alkyl 3-imidazolyl propylamino 2,6-diaziridinyl 2-amino-4-amino Dynamyl 3-imidazolyl propylamino 2,4-dichlorophenyl 2-amino-4-yl -3-imidazolyl-propyl'amino 4-fluorophenyl 4-p than dianyl 4-fluoromethylamino (Please read the precautions on the back before filling this page) -61-This paper size applies to Chinese national standards (CNS) A4 size (210X 297 mm) 520362

7 7 A B 五、發明説明（59 ) 經濟部中央標準局員工消費合作社印製 4-氟苯基 2-乙醯胺基-4-p比啶基 4-氟苄基胺基 4-氟苯基 2-胺基-4-p密淀基 4-氟爷基胺基 4-氟苯基 4-峨淀基 (2-(2-氯苯基-1-曱基）乙基)胺基 4-鼠苯基 2·乙醯胺基_4_吡啶基 (2-(2-氯苯基小甲基)乙基)胺基 4-氟苯基 2-胺基-4-墙淀基 (2-(2·氯苯基小甲基)乙基)胺基 4-氟苯基 4-p比淀基 (3-(4-氟苯基)·丙基)胺基 4-氟苯基 2-乙醯胺基·4·吡啶基 (3-(4-氟苯基)-丙基)胺基 4-氟苯基 2-胺基-4-喊淀基 (3-(4-氟苯基)-丙基)胺基 4-氟苯基 4-ρ比淀基 (3-(4-氟苯基)-1甲基丙基)胺基 4-氣苯基 2-乙醯胺基-4-吡啶基 (3-(4-氟苯基)-1-甲基-丙基)胺基 4-氣苯基 2-胺基-4_喃淀基 (3-(4-氣豕基)-1-甲基-丙基)胺基 4-氟苯基 4-ρ比淀基 (1，1_二甲基-3-(4-氟苯基)-丙基)胺基 4-氟苯基 2-乙醯胺基-4-吡啶基 (U-二甲基-3-(4-氟苯基)_丙基)胺基 4-氟苯基 2-胺基-4_喊淀基 (1，1-二甲基-3-(4-氟苯基)_丙基)胺基 4-氟苯基 4-ρ比淀基 (3 -(2-氣苯基)丙基)胺基 4-氟苯基 2-乙醯胺基-4-吡啶基 (3 -(2-氣苯基)丙基)胺基 4-氟苯基 2_胺基-4·喊淀基 (3-(2-氟苯基)丙基)胺基 4-氣苯基 4-口比淀基 (3-曱基-3-苯基丙基)胺基 4-鼠苯基 2·乙酿胺基_4·^比淀基 (3-甲基-3-苯基丙基)胺基 4-氟苯基 2-胺基-4-喊淀基 (3-甲基-3-苯基丙基)胺基 (請先閱讀背面之注意事項再填寫本頁) -62- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 5203627 7 AB 5. Description of the invention (59) 4-fluorophenyl 2-acetamido-4-p than pyridyl 4-fluorobenzylamino 4-fluorophenyl printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 2-Amino-4-p denselyl 4-fluoromethylamino 4-fluorophenyl 4-etoyl (2- (2-chlorophenyl-1-fluorenyl) ethyl) amino 4- Murine phenyl 2-acetamido-4-pyridyl (2- (2-chlorophenyl small methyl) ethyl) amino 4-fluorophenyl 2-amino-4-wallediyl (2- (2 · Chlorophenyl small methyl) ethyl) amino 4-fluorophenyl 4-p than yodo (3- (4-fluorophenyl) propyl) amino 4-fluorophenyl 2-ethyl醯 Amino · 4 · Pyridyl (3- (4-fluorophenyl) -propyl) amino 4-fluorophenyl 2-amino-4-amino (3- (4-fluorophenyl)- Propyl) amino 4-fluorophenyl 4-p-pyridyl (3- (4-fluorophenyl) -1 methylpropyl) amino 4-phenyl 2-acetamido-4-pyridine (3- (4-fluorophenyl) -1-methyl-propyl) amino 4-aminophenyl 2-amino-4-amino (3- (4-fluoromethyl) -1- Methyl-propyl) amino 4-fluorophenyl 4-p.pyridyl (1,1-dimethyl-3- (4-fluorophenyl) -propyl) amino 4-fluorophenyl 2- Acetylamino-4-pyridyl (U-dimethyl-3- (4-fluorophenyl) _propyl) amino 4-fluorobenzene 2-Amino-4_amino (1,1-dimethyl-3- (4-fluorophenyl) _propyl) amino 4-fluorophenyl 4-ρ ratio (3--(2 -Phenyl) propyl) amino 4-fluorophenyl 2-acetamido-4-pyridyl (3- (2-phenyl) propyl) amino 4-fluorophenyl 2-amino -4 · Hydroyl (3- (2-fluorophenyl) propyl) amino 4-Phenyl 4-Hydroxyphenyl 4- (3-Fluoro-3-phenylpropyl) amino 4-Mor Phenyl-2-ethylamino-4_ ^ pyridyl (3-methyl-3-phenylpropyl) amino 4-fluorophenyl 2-amino-4-yl (3-methyl -3-phenylpropyl) amino group (please read the precautions on the back before filling this page) -62- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) 520362

7 B 經濟部中央標準局員工消費合作社印製 A7 、發明説明（60 ) „ 4-氟苯基 4_p比淀基 (2-甲基-3-泰基-丙基)胺基 4-氟苯基 2-乙醯胺基-4-吡啶基 (2-曱基-3-苯基-丙基)胺基 4-氟苯基 2-胺基-4_續淀基 (2-甲基-3-苯基-丙基)胺基 及 R2 其中R2爲-OH及R11，R12及R1爲下表列舉之任一種組合： R11 R12 R1 苯基 4-吡啶基 4-峨啶基 4-氣苯基 4-外b淀基 4-p比淀基 3-氟苯基 比淀基 4-p比淀基 2-氟苯基 4-p比啶基 4-p比淀基 4-氯苯基 4-口比淀基 4-p比淀基 3-氯苯基 4-吡啶基 4-p比淀基 2-氯苯基 4-峨淀基 4-说淀基 4-甲苯基 4-口比淀基 4_p比淀基、 3-甲苯基 4-p比淀基 4-外I:淀基 2-甲苯基 4-p比淀基 4-ρ比淀基 (請先閱讀背面之注意事項再填寫本頁) -63- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 5203627 B Printed by A7, Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, Description of Invention (60) -Ethylamino-4-pyridyl (2-fluorenyl-3-phenyl-propyl) amino 4-fluorophenyl 2-amino-4-oxoyl (2-methyl-3-benzene -Propyl) amino and R2 where R2 is -OH and R11, R12 and R1 are any combination listed in the table below: R11 R12 R1 Phenyl 4-pyridyl 4-eridyl 4-aminophenyl 4- Outer b-Dianyl 4-p ratio Dianyl 3-fluorophenyl ratio Dianyl 4-p ratio Dianyl 2-fluorophenyl 4-p ratio pyridyl 4-p ratio Dianyl 4-chlorophenyl 4-port ratio Yodo-based 4-p ratio Yodo-based 3-chlorophenyl 4-pyridyl 4-p ratio Yodo-based 2-chlorophenyl 4-eodoyl 4-group Yodo-based 4-tolyl 4-port ratio Yodo-based 4-p ratio Yodo, 3-tolyl 4-p than Yodo 4-external I: Yodo 2-tolyl 4-p than Yodo 4-ρ than Yodo (please read the precautions on the back before filling this page)- 63- This paper size is applicable to China National Standard (CNS) A4 (210X 297mm) 520362

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7 B 五、發明説明（61 ) 經濟部中央標準局員工消費合作社印製 4·三氟甲基苯基 4-峨淀基 4-p比淀基 3_三氟甲基苯基 4-吡啶基 4-p比淀基 2,6-—鼠冬基 4-p比淀基 4-p比淀基 2,6-二甲基苯基 4-峨淀基 4-p比淀基 2,4-二氯苯基 4-t1比淀基 4-p比淀基 2,4-二甲基苯基 4-p比淀基 4-p比淀基 本基 2_胺基-4-p比淀基 4-吡啶基 4·氟苯基 2-胺基-4-p比淀基 4-p比淀基 3-鼠苯基 2-胺基-4-吡啶基 4-p比淀基 2-氣苯基 2-胺基-4·ρ比基 4-p比淀基 4-氯苯基 2-胺基-4_吡啶基 4-p比淀基 3-氯苯基 2-胺基-4-ρ比淀基 4-p比淀基 2-氯苯基 2-胺基-4-0比淀基 4-p比淀基 4-甲苯基 2_胺基-4-ρ比淀基 4-p比淀基 3-甲苯基 2-胺基-4-ρ比淀基 4-p比淀基 2-甲苯基 2-胺基-4-ρ比淀基 4-峨淀基 4-三氟甲基苯基 2-胺基-4-ρ比症基 4-ρ比淀基 3-三氟甲基苯基 2-胺基淀基 4-p比淀基 2,6-—氣冬基 2-胺基-4-p比淀基 4-峨淀基' 2,6-二甲基苯基 2-胺基-4-p比淀基 4-p比淀基 (請先閱讀背面之注意事項再填寫本頁) 訂 ^wl. -64- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 Β7 五、發明説明（62 ) 經濟部中央標準局員工消費合作社印製 2,4-二氯苯基 2-胺基-4-说啶基 4-ρ比淀基 2,4-二甲基苯基 2-胺基-4-吡啶基 4-Ρ比淀基 苯基 2_乙醯胺基-4-ρ比啶基 4-ρ比淀基 4-氟苯基 2-乙醯胺基-4-吡啶基 4-ρ比淀基 3-氟苯基 2-乙醯胺基-4-吡啶基 4-ρ比淀基 2-氟苯基 2-乙醯胺基-4-吡啶基 4-口比淀基 4-氯苯基 2-乙醯胺基-4-吡啶基 4-ρ比淀基 3-氯苯基 2-乙醯胺基-4-说啶基 4-ρ比淀基 2-鼠苯基 2-乙酸胺基-4-?比淀基 4-ρ比淀基 4-甲苯基 2-乙醯胺基_4-吡啶基 4-ρ比症基 3-甲苯基 2-乙醯胺基-4-吡淀基 4·ρ比淀基 2-甲苯基 2-乙醯胺基-4-吡淀基 4-叶b淀基 4-三氟甲基苯基 2-乙醯:胺基_4_外(:淀基 4-p比淀基 3-二鼠甲基本基 2-乙醯胺基-4-吡啶基 4-外b淀基 2,6-—氣表基 2·乙醯胺基-4-吡啶基 4-p比淀基 2,6-二甲基苯基 2·乙醯胺基-4-吡啶基 4-p比淀基 2,4-二氯苯基 2-乙醯胺基·4·吡啶基 4-p比淀基 2,4-二甲基苯基 2-乙醯胺基-4-吡啶基 4·ρ比淀基 苯基 2·胺基-4·17密淀基 4-ρ比淀基 4-氟苯基 2-胺基-4-喊淀基 4-ρ比淀基 (請先閱讀背面之注意事項再填寫本頁)7 B V. Description of the invention (61) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs. 4-p ratio yttrium 2,6 --- Rhodonyl 4-p ratio yttrium 4-p ratio yttrium 2,6-dimethylphenyl 4-eodolyl 4-p ratio ythyl 2,4- Dichlorophenyl 4-t1 is more than 4-based than p-based 2,4-dimethylphenyl 4-p is more than 4-based than p-based is 2-amido-4-p than 4 -Pyridyl 4-fluorophenyl 2-amino-4-p ratio ytyl 4-p ratio ylidene 3-murylphenyl 2-amino-4-pyridyl 4-p ratio ylideyl 2-aminophenyl 2-amino-4 · ρ-pyridyl 4-p ratio yodoyl 4-chlorophenyl 2-amino 4-pyridyl 4-p ratio yodoyl 3-chlorophenyl 2-amino-4-ρ ratio Yodo-based 4-p ratio Yodo-based 2-chlorophenyl 2-amino-4-0 ratio Yodo-based 4-p ratio Yodo-based 4-tolyl 2-amino-4-ρ ratio Yodo-based 4-p ratio Benzyl 3-tolyl 2-amino-4-ρ than yodoyl 4-p ytyl 2-tolyl 2-amino-4-ρ ytyl 4-eodoyl 4-trifluoromethylphenyl 2-Amino-4-p ratio, 4-p ratio ratio, 3-trifluoromethylphenyl 2-amino ratio, 4-p ratio, 2,6-aspartyl, 2-amino- 4-p ratio Yodo base 4-Edo base '2,6- Dimethylphenyl 2-amino-4-p ratio dianyl 4-p ratio dianyl (Please read the precautions on the back before filling this page) Order ^ wl. -64- This paper size applies to Chinese national standards ( CNS) A4 specification (210X 297 mm) 520362 B7 V. Description of the invention (62) Printed by 2,4-dichlorophenyl 2-amino- 4-pyridyl 4-r Pyridyl 2,4-dimethylphenyl 2-amino-4-pyridyl 4-P than Pyridylphenyl 2-acetamido-4-p-pyridyl 4-p-pyridyl 4- Fluorophenyl 2-acetamido-4-pyridyl 4-ρ than yl 3-fluorophenyl 2-acetamido-4-pyridyl 4-ρ than yl 2-fluorophenyl 2-ethyl Fluorenyl-4-pyridyl 4-pyridyl 4-chlorophenyl 2-ethylpyridyl 4-pyridyl 4-pyridyl 4-chlorophenyl 2-ethylphenyl Say pyridyl 4-ρ is more than 2-pyridyl-2-acetamido-4-? Than yridyl 4-ρ is more than 4-methyl-tolyl 2-acetamido-4-pyridyl 4-ρ Pyridyl 3-tolyl 2-acetamido-4-pyridyl 4-pyridyl 2-tolyl 2-acetamido-4-pyridyl 4-pyridyl 4-tribenzyl 4-tri Fluoromethylphenyl 2-acetamidine: amino-4_exo (: 4-yl Murine methylbenzyl 2-acetamido-4-pyridyl 4-exo-b-yl 2,6--epoxyepiyl-2. Acetamido-4-pyridyl 4-p-pyridyl 2,6- Dimethylphenyl 2-acetamido-4-pyridyl 4-p is more than 2,4-dichlorophenyl 2-acetamido 4-pyridyl 4-p than 2,4 -Dimethylphenyl 2-acetamido-4-pyridyl 4 · ρ than yodophenyl 2 · amino-4 · 17 denselyl 4-ρ than 4-fluorophenyl 2-amine Base-4-shodo lake 4-4-bado lake (please read the precautions on the back before filling this page)

、1T -65- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） 520362、 1T -65- This paper size is applicable to China National Standard (CNS) A4 specification (210 × 297 mm) 520362

B 五、發明説明（63 ) 經濟部中央標準局員工消費合作社印製 3-氟苯基 2-胺基-4-喃淀基 4-ρ比淀基 2-氟苯基 2-胺基基 4-ρ比淀基 4-氯苯基 2-胺基-4-喃淀基 4-ρ比淀基 3-氯苯基 2-胺基-4-喊淀基 4-ρ比淀基 2-氯苯基 2-胺基-4-4淀基 4^比淀基 4-甲苯基 2-胺基-4-喊淀基 4-ρ比淀基 3-甲苯基 2-胺基-4-癌淀基 4-ρ比淀基 2-甲苯基 2-胺基_4-ρ密淀基 4-ρ比淀基 4·三氟甲基苯基 2-胺基-4-哺淀基 4-ρ比淀基 3-三氟甲基苯基 2-胺基-4-17密淀基 4_ρ比淀基 2,6-二氯苯基 2-胺基-4-ρ密淀基 4-ρ比淀基 2,6-二甲基苯基 2-胺基-4-喃淀基 4-ρ比淀基 2,4-—氣冬基 2-胺基_4_喊淀基 4-ρ比淀基 2,4_二甲基苯基 2-胺基-4-喃淀基 4-ρ比淀基 苯基 4-ρ比淀基 4-甲基亞橫S蠢基苯基 4-氣苯基 4-吡啶基 4-甲基亞磺醯基苯基 3-氟苯基 4-峨淀基 4-甲基亞磺醯基苯基 2-鼠苯基 4-ρ比淀基 4-甲基亞磺醯基苯基 4-氯苯基 4-ρ比淀基 4-甲基亞續'酸基苯基 3-氯苯基 4-ρ比淀基 4-甲基亞磺醯基苯基 (請先閱讀背面之注意事項再填寫本頁)B V. Description of the invention (63) 3-Fluorophenyl 2-Amino-4-Hydroxy-4-phenyl ratio 4-pyridyl 2-Fluorophenyl 2-Amino 4 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs -ρ ratio ylidene 4-chlorophenyl 2-amino-4-anhydroxyl 4-ρ ratio ylidene 3-chlorophenyl 2-amino-4-yl cyanide 4-ρ bieline 2-chloro Phenyl 2-amino-4-4yl radical 4 ^ Bierlyl 4-tolyl 2-amino 4-amino- 4-yl- 4-hydroxyl 4-methyl 2-tolyl 2-amino-4-carbohydrate The ratio of 4-phenyl group 2-tolyl 2-amino group 4-4-pyridyl group 4-ρ ratio 4-phenyl group Yodo-based 3-trifluoromethylphenyl 2-amino-4-17 densely-based 4-ρ-pyridyl 2,6-dichlorophenyl 2-amino- 4-pylyl-pyridyl 4-ρ-pyridyl 2,6-Dimethylphenyl 2-amino-4-anhydro4-4-pyridyl 2,4--aspartyl 2-amino 4-4-pyridyl 4-ρ-pyridyl 2 , 4-Dimethylphenyl 2-amino-4-ranoyl 4-ρ than yodophenyl 4-ρ Pyridyl 4-methylsulfinamidinylphenyl 3-fluorophenyl 4-amidoyl 4-methylsulfinamidinylphenyl 2-murylphenyl 4-r Phenyl 4- Chlorophenyl 4-ρ is more than 4-methylidene's 4-phenyl phenyl 3-chlorophenyl 4-chloro is 4-phenyl than 4-methylsulfenylphenyl (please read the precautions on the back first) (Fill in this page)

、1T ^wl. -66- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362、 1T ^ wl. -66- This paper size applies to China National Standard (CNS) A4 (210X297 mm) 520362

AA

7 B 五、發明説明（64 ) 經濟部中央標準局員工消費合作社印製 2-氣本基 4-口比淀基 4-甲基亞磺醯基苯基 4-甲苯基 4-p比淀基 4-甲基亞續酿基苯基 3-甲苯基 4-p比淀基 4-甲基亞續S&基苯基 2-甲苯基 4-吡啶基 4-甲基亞磺醯基苯基 4-三氟甲基苯基 4-p比淀基 4-甲基亞磺醯基苯基 3-三氟甲基苯基 4-口比淀基 4-甲基亞續醯：基苯基 2,6·二氯苯基 4-p比淀基 4-甲基亞磺醯基苯基 2,6-二甲基苯基 4-p比淀基 4-甲基亞磺醯基苯基 2,4-二氣豕基 4-吡啶基 4-甲基亞續S盛基苯基 2,4-二甲基苯基 4-p比淀基 4-甲基亞續酿基苯基 苯基 2-胺基-4-p比基 4-甲基亞磺醯基苯基 4-鼠苯基 2-胺基-4-p比啶基 4-甲基亞磺醯基苯基 3-鼠苯基 2-胺基-4-0比淀基 4-甲基亞磺醯基苯基 2-氣苯基 2-胺基基 4-甲基亞磺醯基苯基 4-氯苯基 2_胺基-4-吡啶基 4-甲基亞磺醯基苯基 3-氯苯基 2-胺基-4·吡啶基 4-甲基亞磺醯基苯基 2-氯苯基 2-胺基_4-p比淀基 4-甲基亞磺醯基苯基 4-甲苯基 2-胺基·4_ρ比1•基 4-甲基亞磺醯基苯基 3_甲苯基 2-胺基-4-#b ^^基 4-甲基亞磺'醯基苯基 2-甲苯基 2·胺基-4-吡啶基 4-甲基亞磺醯基苯基 (請先閱讀背面之注意事項再填寫本貢)7 B V. Description of the invention (64) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs, 2-Gasyl 4-Methylsulfonylphenyl 4-methylsulfinylphenyl 4-tolyl 4-p 4-methylidenephenyl 3-tolyl 4-p than 4-methylidene 4-methylidene S & phenylphenyl 2-tolyl 4-pyridyl 4-methylsulfinylphenyl 4 -Trifluoromethylphenyl 4-p-pyridyl 4-methylsulfinamidinylphenyl 3-trifluoromethylphenyl 4-pyridyl 4-methylsulfinyl: phenyl 2, 6 · Dichlorophenyl 4-p than Yodo 4-methylsulfinamidophenyl 2,6-dimethylphenyl 4-p than Yodo 4-methylsulfinamidophenyl 2,4 -Dioxanyl 4-pyridyl 4-methylidene sulfonylphenyl 2,4-dimethylphenyl 4-p than yodoyl 4-methylidene phenylphenyl 2-amine Methyl-4-p than 4-methylsulfinamidinylphenyl 4-murylphenyl 2-amino 4-p than pyridinyl 4-methylsulfinamidinylphenyl 3-murylphenyl 2- Amino-4-0 than Yodo 4-methylsulfinamidinylphenyl 2-phenyl 2-aminophenyl 4-methylsulfinamidinylphenyl 4-chlorophenyl 2-amino-4 -Pyridyl 4-methylsulfinamidinylphenyl 3-chlorophenyl 2-amino-4 -pyridyl 4-methyl Sulfonylphenyl 2-chlorophenyl 2-amino_4-p ratio than 4-methylsulfinylphenyl 4-tolyl 2-amino group Sulfonylphenyl 3-tolyl-2-amino-4- # b ^ 4-methylsulfinyl'fluorenylphenyl 2-tolyl-2-amino-4-pyridyl 4-methylene Sulfonyl phenyl (please read the precautions on the back before filling in this tribute)

、1T ^wi. -67- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（65 ) 經濟部中央標準局員工消費合作社印製 4-三氟甲基苯基 2-;^基-4-?比^^基 4-甲基亞磺醯基苯基 3-三氟甲基苯基 2-胺基-4·吡啶基 4-甲基亞續S盔基苯基 2,6-—氣本基 2-胺基-4-p比淀基 4-甲基亞續S盛基苯基 2,6-二甲基苯基 2-胺基-4-吡啶基 4-甲基亞磺醯基苯基 2,4-二氯苯基 2-胺基-4-p比淀基 4-甲基亞磺醯基苯基 2,4-二甲基苯基 2-胺基-4-?比^^基 4-甲基亞續醯基苯基 苯基 2-乙酿胺基-4-p比淀基 4-甲基亞磺醯基苯基 4-氟苯基 2-乙酿胺基_4-峨淀基 4-甲基亞磺醯基苯基 3-氟苯基 2-乙醯胺基-4-吡啶基 4_甲基亞磺醯基苯基 2-氟苯基 2-乙S盛胺基-4-0比基 4-甲基亞磺醯基苯基 4-氣冬基 2_乙酿胺基-4_p比淀基 4-甲基亞磺醯基苯基 3-氯苯基 2·乙醯胺基-4-吡啶基 4-甲基亞磺醯基苯基 2-氣苯基 2-乙醯胺基-4-吡啶基 4-甲基亞確酿基苯基 4-甲苯基 2-乙S盛胺基-4-0比淀基 4-甲基亞磺醯基苯基 3-甲苯基 2-乙醯胺基-4-p比淀基 4-甲基亞磺醯基苯基 2-甲苯基 2-乙醯胺基-4-吡啶基 4-甲基亞磺醯基苯基 4-三氟甲基苯基 2-乙醯胺基-4-p比淀基 4-甲基亞磺醯基苯基 3·三氟甲基苯基 2-乙醯胺基-4·吡淀基 4-甲基亞續醯基苯基 2,6-二氣苯基 2-乙醯胺基-4-吡啶基 4-甲基亞磺k基苯基 2,6-二甲基苯基 2-乙醯胺基-4-吡淀基 4_甲基亞磺醯基苯基 (請先閱讀背面之注意事項再填寫本頁) 訂 ^_wl. -68- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 Β 五、發明説明（66 ) 經濟部中央標準局員工消費合作社印製 2,4-二氯苯基 2·乙酿胺基-4-^7比淀基 4-甲基亞續si：基苯基 2,4-二甲基苯基 2-乙S盛胺基-4_ρ比淀基 4-甲基亞磺醯基苯基 苯基 2-胺基-4-喃淀基 4-曱基亞磺醯基苯基 4-氟苯基 2-胺基-4-喊淀基 4-甲基亞續S蠢基豕基 3-氟苯基 2-胺基-4_喃淀基 4-甲基亞磺醯基苯基 2_氟苯基 2-胺基-4-喃淀基 4-甲基亞橫酿基苯基 4-氯苯基 2-胺基-4_嘧啶基 4-甲基亞續S盛基苯基 3-氯苯基 2-胺基-4-喊淀基 4-甲基亞磺醯基苯基 2-氣豕基 2-胺基-4-喊淀基 4-甲基亞磺醯基苯基 4-甲苯基 2-胺基-4-ρ密淀基 4-甲基亞續酿基苯基 3-甲苯基 2-胺基-4_喊淀基 4-甲基亞續S&基苯基 2-甲苯基 2-胺基-4-喊淀基 4-甲基亞磺醯基苯基 4-三氟甲基苯基 2-胺基-4_喊淀基 4-甲基亞磺醯基苯基 3-三氟甲基苯基 2-胺基-4-喊淀基 4-甲基亞磺醯基苯基 2,6-二氯苯基 2-胺基-4-喃淀基 4_甲基亞續酸基苯基 2,6·二甲基苯基 2-胺基-4-喊淀基 4-甲基亞磺醯基苯基 2,4-二氯苯基 2-胺基-4-喃淀基 4-甲基亞磺醯基苯基 2,4-二甲基苯基 2-胺基-4-喃淀基 4-甲基亞磺醯基苯基 苯基 4-ρ比淀基 2,6-二氯爷墓 4-氣苯基 4-ρ比淀基 2,6·二氯爷基 (請先閱讀背面之注意事項再填寫本頁)、 1T ^ wi. -67- This paper size is applicable to Chinese National Standard (CNS) A4 (210X 297 mm) 520362 A7 B7 V. Description of Invention (65) 4-Trifluoride printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Methylphenyl 2-; ^-4--4-biphenyl 4-methylsulfinamidinylphenyl 3-trifluoromethylphenyl 2-amino-4 -pyridyl 4-methylidene S helmetyl phenyl 2,6--benzyl 2-amino-4-p than yodoyl 4-methylidene S sulphenyl phenyl 2,6-dimethylphenyl 2-amino-4 -Pyridyl 4-methylsulfinamidinylphenyl 2,4-dichlorophenyl 2-amino-4-p than alkyl 4-methylsulfinamidinylphenyl 2,4-dimethylbenzene 2-Amino-4-methyl-4-methyl 4-methylidenefluorenylphenylphenyl 2-ethylamino-4-p than 4-methylsulfinylphenyl 4- Fluorophenyl 2-Ethylamino 4-4-Elideyl 4-Methylsulfenylphenyl 3-fluorophenyl 2-Ethylamino-4-pyridyl 4-methylsulfinylbenzene 2-fluorophenyl 2-ethyl S-amino-4--4-pyridyl 4-methylsulfinamidinylphenyl 4-pyroyl 2-ethynylamino-4_p Sulfonylphenyl 3-chlorophenyl 2.Ethylamido-4-pyridyl 4-methylsulfinylphenyl 2- Phenyl 2-Ethylamido-4-pyridyl 4-methylidenephenyl 4-tolyl 2-ethenylamino-4-0 than 4-methylsulfenylbenzene 2-methyl 3-tolyl 2-acetamido-4-phenyl 4-methylsulfenamidophenyl 2-tolyl 2-acetamido-4-pyridyl 4-methylsulfenamido Phenyl 4-trifluoromethylphenyl 2-acetamido-4-p than 4-methylsulfinamidophenyl 3-trifluoromethylphenyl 2-acetamido-4 · Pyridinyl 4-methylidenefluorenylphenyl 2,6-diaminophenyl 2-ethenylamino-4-pyridyl 4-methylsulfinyl phenyl 2,6-dimethyl Phenyl 2-acetamido-4-pyridyl 4-methylsulfinamidinophenyl (please read the precautions on the back before filling this page) Order ^ _wl. -68- This paper size applies to China Standard (CNS) A4 specification (210X 297 mm) 520362 Β V. Description of invention (66) Printed by 2,4-dichlorophenyl 2 · ethylethylamine 4- ^ 7 in the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Bi-Yendo 4-methylsulfinyl si: phenyl 2,4-dimethylphenyl 2-ethenylamino-4_ρ Bi-Yen 4-methylsulfinamidophenylphenyl 2-amine 4-Aminopyranyl 4-fluorenylsulfinium Phenyl 4-fluorophenyl 2-amino-4-methylidene 4-methylsulfinylsulfonyl 3-fluorophenyl 2-amino-4-pyranyl-4-methylsulfinyl 2-Phenylphenyl 2-fluorophenyl 2-amino-4-anhydrophenyl 4-methylphenylene 4-phenylphenyl 4-chlorophenyl 2-amino 4-pyrimidinyl 4-methylphenylene Phenyl 3-chlorophenyl 2-amino-4-methylsulfonyl 4-methylsulfinylphenyl Phenylphenyl 4-tolyl 2-amino-4-p-methylidene 4-methylidene 4-phenylidenephenyl 3-tolyl 2-amino-4_ylidene 4-methylidene S & s Phenylphenyl 2-tolyl 2-amino-4-methylidene 4-methylsulfinamidinylphenyl 4-trifluoromethylphenyl 2-amino-4_ylidene 4-methylidene Sulfonylphenyl 3-trifluoromethylphenyl 2-amino-4-ylamino 4-methylsulfinylphenyl 2,6-dichlorophenyl 2-amino-4-anyl 4-methyl phenylene acid phenyl 2,6 dimethylphenyl 2-amino group 4-methylsulfonyl 4-methylsulfinamidophenyl 2,4-dichlorophenyl 2- Amino-4-ranyl 4-methylsulfinamidinylphenyl 2,4-dimethylphenyl 2-amino-4-ranyl 4-methylsulfinamidinylphenylphenyl 4 -ρ ratio 2,6 -Tomb of dichlorophene 4-Phenylphenyl 4-p-pyridyl 2,6.Dichlorophenyl (Please read the precautions on the back before filling this page)

、1T 01. -69- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ 297公釐） 520362 Β7 五、發明説明（67 ) 經濟部中央標準局員工消費合作社印製 3-氣苯基 4-ρ比淀基 2,6-二氯爷基 2-氟苯基 4-ρ比淀基 2,6-二氯爷基 4-氯苯基 4-ρ比淀基 2,6-二氯字基 3-氯苯基 4_ρ比淀基 2,6-二氯苄基 2-氯苯基 4-ρ比淀基 2,6-二氯字基 4-甲苯基 4-吡啶基 2,6-二氯芊基 3_甲苯基 4-ρ比淀基 2,6-二氯爷基 2-甲苯基 4-ρ比淀基 2,6-二氯事基 4-三氟甲基苯基 4-ρ比淀基 2,6-二氯苄基 3-三氟甲基苯基 4-ρ比淀基 2,6_二氯芊基 2,6-—氣冬基 4-ρ比淀基 2,6-二氯；基 2,6-二甲基苯基 4-ρ比淀基 2,6-二氯芊基 2,4-二氣豕基 4-ρ比淀基 2,6-二氯卞基 2,4-二甲基苯基 4-ρ比淀基 2,6-二氯苄基 苯基 2_胺基·4-ρ比淀基 2,6-二氯字基 4-氟苯基 2-胺基-4_ρ比淀基 2,6-二氯爷基 3-氟苯基 2-胺基比基 2,6-二氯苄基 2-氟苯基 2-胺基基 2,6-二氯爷基 4-氯苯基 2·胺基-4-ρ比淀基 2,6-二氯爷墓 3-氯私基 2-胺基-4-峨淀基 2,6-二氯爷基 (請先閱讀背面之注意事項再填寫本頁)、 1T 01. -69- This paper size is applicable to Chinese National Standard (CNS) A4 specification (210 × 297 mm) 520362 Β7 V. Description of invention (67) 3-Gasophenyl 4 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs -ρ ratio yodoyl 2,6-dichloromethyl 2-fluorophenyl 4-ρ bispyridyl 2,6-dichloromethyl 4-chlorophenyl 4-ρ bispyridyl 2,6-dichloro 3-chlorophenyl 4-p-pyridyl 2,6-dichlorobenzyl 2-chlorophenyl 4-p-pyridyl 2,6-dichlorobenzyl 4-tolyl 4-pyridyl 2,6-di Chlorofluorenyl 3-tolyl 4-ρ is more than 2,6-dichlorobenzyl 2-tolyl 4-ρ is more than 2,6-dichloromethyl 4-trifluoromethylphenyl 4-ρ Biyenyl 2,6-dichlorobenzyl 3-trifluoromethylphenyl 4-ρ Biyenyl 2,6-dichlorofluorenyl 2,6--aspartyl 4-ρ Biyenyl 2,6 -Dichloro; radical 2,6-dimethylphenyl 4-rpyridyl 2,6-dichlorofluorenyl 2,4-difluorofluorenyl 4-rpidol 2,6-dichlorofluorenyl 2,4-Dimethylphenyl 4-p-pyridyl 2,6-dichlorobenzylphenyl 2-amino group 4-p-pyridyl 2,6-dichlorobenzyl 4-fluorophenyl 2 -Amino-4_ρ ratio than 2,6-dichlorobenzyl 3-fluorophenyl 2-amino group than 2,6-dichlorobenzyl 2-fluorophenyl 2-amino group 2,6-dichloromethyl 4-chlorophenyl 2-amino-4-ρ Yodo base 2,6-dichloroethene (Please read the precautions on the back before filling this page)

、1T 01. -70- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X 297公釐） 520362 A7 ___ B7 五、發明説明（68 ) 經濟部中央標準局員工消費合作社印製 2-氯苯基 2-胺基基 2,6-二氯爷基 4-甲苯基 2-胺基-4-p比淀基 2,6-二氯爷基 3-甲苯基 2-胺基基 2,6-二氯卞基 2-甲苯基 2-胺基基 2,6-二氯爷基 4_二鼠甲基苯基 2-胺基-4-0比淀基 2,6-二氯爷基 3-三氟甲基苯基 2-胺基-4-吡啶基 2,6-二氯芊基 2,6·二氯苯基 2-胺基-4·吡啶基 2,6-二氯字基 2,6-二甲基苯基 2-胺基-4-p比喊_基 2,6-二氯宇基 2,4-二氯苯基 2-胺基基 2,6-二氯字基 2,4-二甲基苯基 2_胺基-4_p比淀基 2,6-二氯爷基 苯基 2-乙酿胺基-4·^比淀基 2,6-二氯爷基 4-氟苯基 2-乙醯胺基-4·吡啶基 2,6-二氯爷基 3-氟苯基 2-乙醯胺基-4-吡啶基 2,6·二氯爷基 2-氣苯基 2-乙醯胺基-4-p比淀基 2,6-二氯爷基 4-氯苯基 2-乙酿胺基基 2,6-二氯卞基 3-氯苯基 2-乙醯胺基-4-吡啶基 2,6-二氯苄基 2-鼠本基 2-乙醯胺基-4-吡啶基 2,6-二氯爷基 4·甲苯基 2_乙酿胺基-4-prfs淀基 2,6·二氯爷基 3-甲苯基 2-乙醯胺基-4-吡啶基 2,6-二氯爷墓 2-甲苯基 2-乙 8¾ 胺基-基 2,6-二氯爷基 (請先閱讀背面之注意事項再填寫本頁) 訂 MWI. __ -71 - 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362、 1T 01. -70- This paper size applies to Chinese National Standard (CNS) A4 specification (210X 297 mm) 520362 A7 ___ B7 V. Description of the invention (68) 2-Chlorobenzene printed by the staff consumer cooperative of the Central Standards Bureau of the Ministry of Economic Affairs The 2-amino group 2,6-dichloromethyl 4-tolyl 2-amino group 4-p is more than the 2,6-dichloromethyl 3-tolyl 2-amino group 2,6- Dichlorofluorenyl 2-tolyl 2-amino group 2,6-dichlorobenzyl 4-dirhamylmethylphenyl 2-amino-4-0 than dianyl 2,6-dichlorobenzyl 3- Trifluoromethylphenyl 2-amino-4-pyridyl 2,6-dichlorofluorenyl 2,6 · dichlorophenyl 2-amino-4 · pyridyl 2,6-dichloro radical 2, 6-Dimethylphenyl 2-amino-4-p ratio, 2,6-dichlorobenzyl 2,4-dichlorophenyl 2-amino, 2,6-dichloro radical 2, 4-dimethylphenyl 2-amino-4_p than yodoyl 2,6-dichloromethylphenyl 2-ethylamino-4 -pyridyl 2,6-dichloromethyl 4-fluoro Phenyl 2-acetamido-4 · pyridyl 2,6-dichloromethyl 3-fluorophenyl 2-acetamido-4-pyridyl 2,6 · dichloromethyl 2-aminophenyl 2-Ethylamido-4-p-pyridyl 2,6-dichloromethyl 4-chlorophenyl 2-ethynylamino 2,6-dichloroamido 3-chlorophenyl 2-Ethylamido-4-pyridyl 2,6-dichlorobenzyl 2-ratyl 2-ethylamido-4-pyridyl 2,6-dichlorobenzyl 4-tolyl 2-ethyl Amino-4-prfsYodo, 2,6 · Dichloromethyl 3-tolyl 2-Ethylamino-4-pyridyl 2,6-dichloromethyl 2-Tolyl 2-ethyl 8¾ -Base 2,6-dichloroethene (please read the precautions on the back before filling this page) Order MWI. __ -71-This paper size is applicable to China National Standard (CNS) A4 (210X 297 mm) 520362

A B7 五、發明説明（69 ) 經濟部中央標準局員工消費合作社印製 4-三氟甲基苯基 2-乙酿胺基_4_p比淀基 2,6-二氯苄基 3-三氟甲基苯基 2-乙醯胺基-4-吡啶基 2,6-二氯爷基 2,6-二氯苯基 2-乙S盔胺基-4-p比淀基 2,6-二氯爷基 2,6-二甲基苯基 2-乙酿胺基-4-外b淀基 2,6-二氯爷基 2,4-二氯苯基 2-乙醯胺基-4_吡啶基 2,6-二氯苄基 2,4-二甲基苯基 2-乙酿胺基_4_p比淀基 2,6-二氯爷基 苯基 2-胺基-4-喊淀基 2,6·二氯爷基 4-氣苯基 2-胺基-4-喊淀基 2,6-二氯芊基 3-鼠苯基 2·胺基-4-p密淀基 2,6_二氯爷基 2-氣苯基 2-胺基-4·喊淀基 2,6-二氯爷基 4-氯苯基 2-胺基-4-癌淀基 2,6-二氯爷基 3-氯苯基 2-胺基-4-喊淀基 2,6-二氯爷基 2-氯苯基 2_胺基-4-喊淀基 2,6-二氯爷基 4-甲苯基 2-胺基-4-喊淀基 2,6-二氯爷基 3-甲苯基 2-胺基-4-喊淀基 2,6-二氯字基 2-甲苯基 2-胺基-4-喊淀基 2,6-二氯爷基 4-三氟甲基苯基 2-胺基-4-喃淀基 2,6-二氯爷基 3-三氟甲基苯基 2_胺基-4-喃淀基 2,6-二氯爷基 2,6·二氯苯基 2-胺基-4-喊淀基 2,6_二氯爷墓 2,6-二甲基苯基 2-胺基-4-喊淀基 2,6-二氯爷基 (請先閲讀背面之注意事項再填寫本頁)A B7 V. Description of the invention (69) 4-trifluoromethylphenyl 2-ethylamino-4_p than yodoyl 2,6-dichlorobenzyl 3-trifluoro Methylphenyl 2-Ethylamino-4-pyridyl 2,6-dichloroethenyl 2,6-dichlorophenyl 2-ethenylamino-4-p Chloroyl 2,6-dimethylphenyl 2-ethynylamino-4 alkynyl 2,6-dichloroethenyl 2,4-dichlorophenyl 2-ethenylamino-4_ Pyridyl 2,6-dichlorobenzyl 2,4-dimethylphenyl 2-ethylamino-4_p ratio than 2,6-dichloromethylphenyl 2-amino-4-amino 2,6-Dichloroethenyl 4-aminophenyl 2-amino-4-ylamino, 2,6-dichlorofluorenyl 3-murylphenyl 2-amino-4-p denselyl 2,6 _Dichloromethyl 2-aminophenyl 2-amino-4, 2-hydroxyphenyl 2,6-dichloromethyl 4-chlorophenyl 2-amino-4-carbodianyl 2,6-dichloromethyl 3-Chlorophenyl 2-amino-4-hexyl 2,6-dichloromethyl 2-chlorophenyl 2-amino-4-hexyl 2,6-dichloromethyl 4-toluene 2-Amino-4-Amino, 2,6-dichloromethyl 3-tolyl 2-amino 4-Amino, 2,6-dichloromethyl 2-tolyl 2-amino- 4-Hydroyl 2,6-dichloromethyl 4-trifluoromethylbenzene 2-Amino-4-ranyl 2,6-dichloromethyl 3-trifluoromethylphenyl 2-amino-4-ranyl 2,6-dichloromethyl 2,6 · di Chlorophenyl 2-amino-4-hexyl 2,6-dichlorophenyl tomb 2,6-dimethylphenyl 2-amino-4-hexyl 2,6-dichloromethyl (please (Read the notes on the back before filling out this page)

、1T -^wl. -72- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 經濟部中央標準局負工消費合作社印製 五、發明説明（70 ) 2,4-二氣本基 2-胺基-4-喊淀基 2,6-二氯苄基 2,4_二甲基苯基 2-胺基-4-喊淀基 2,6-二氯爷基 苯基 4-p比淀基 2-(4-氟苯基)乙胺基 4-氟苯基 4-p比淀基 2-(4-氟苯基)乙胺基 3-氟苯基 4-p比淀基 2-(4-氟苯基)乙胺基 2-氟苯基 4·峨淀基 2-(4-氟苯基)乙胺基 4-氯苯基 4_峨淀基 2-(4-氟苯基)乙胺基 3-氯苯基 4-p比淀基 2-(4-氟苯基)乙胺基 2-氯苯基 4-口比啶基 2-(4-氟苯基)乙胺基 4-甲苯基 4-p比淀基 2-(4-氟苯基)乙胺基 3-甲苯基 4-p比淀基 2_(4-氟苯基)乙胺基 2-甲苯基 4·ρ比淀基 2-(4·氟苯基)乙胺基 4-三氟甲基苯基 4-ρ比淀基 2-(4-氟苯基)乙胺基 3·三氟甲基苯基 4-峨淀基 2-(4-氟苯基)乙胺基 2,6-二氯苯基 4-ρ比淀基 2-(4-氟苯基)乙胺基 2,6·二甲基苯基 4»^比^^基 2-(4-氟苯基)乙胺基 2,4-二氯苯基 4_ρ比淀基 2-(4-氟苯基)乙胺基 2,4-二甲基苯基 4-峨淀基 2-(4-鼠苯基)乙胺基 苯基 2-胺基-4-吡啶基 2·(4-氟苯基5乙胺基 4-氟苯基 2-胺基-4-?比淀基 2-(4-氟苯基)乙胺基 (請先閱讀背面之注意事項再填寫本頁)、 1T-^ wl. -72- This paper size is applicable to Chinese National Standard (CNS) A4 (210X297mm) 520362 A7 B7 Printed by the Consumers ’Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (70) 2,4 -Diaminobenzyl 2-amino-4-aminobenzyl 2,6-dichlorobenzyl 2,4-dimethylphenyl 2-amino-4-hydrazyl 2,6-dichlorobenzyl Phenyl 4-p is 2- (4-fluorophenyl) ethylamino 4-fluorophenyl 4-p is 2- (4-fluorophenyl) ethylamino 3-fluorophenyl 4- p ratio Yodo-based 2- (4-fluorophenyl) ethylamino 2-fluorophenyl 4. EDYO 2- (4-fluorophenyl) ethylamino 4-chlorophenyl 4- EDYO 2- (4-fluorophenyl) ethylamino 3-chlorophenyl 4-p-pyridyl 2- (4-fluorophenyl) ethylamino 2-chlorophenyl 4-pyridyl 2- (4-fluoro Phenyl) ethylamino 4-tolyl 4-p than yodo 2- (4-fluorophenyl) ethylamino 3-tolyl 4-p than ydoyl 2- (4-fluorophenyl) ethylamino 2 -Tolyl 4 · ρ than Yodo 2- (4 · fluorophenyl) ethylamino 4-trifluoromethylphenyl 4-ρ than Yodo 2- (4-fluorophenyl) ethylamino 3.3 Fluoromethylphenyl 4-etheryl 2- (4-fluorophenyl) ethylamino 2,6-dichlorophenyl 4-ρ than yodo-2- (4-fluorophenyl) ethylamino 2, 6 · Two Phenyl 4 »^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^-^ Methylphenyl 4-etheryl 2- (4-muryl) ethylaminophenyl 2-amino-4-pyridyl 2. (4-fluorophenyl 5 ethylamino 4-fluorophenyl 2 -Amino-4-? Bito 2- (4-fluorophenyl) ethylamino (Please read the precautions on the back before filling this page)

、1T ^wl. -73- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362、 1T ^ wl. -73- This paper size is applicable to China National Standard (CNS) A4 (210X297mm) 520362

7 7 A B 五、發明説明（71 ) 經濟部中央標準局員工消費合作社印製 3-氟苯基 2-胺基-4-t1比淀基 2-(4-氟苯基)乙胺基 2-氟苯基 2_胺基-4-p比淀基 2-(4_氟苯基)乙胺基 4-氯苯基 2-胺基基 2-(4-鼠苯基)乙胺基 3-氯苯基 2-胺基-4-p比淀基 2-(4-氣苯基)乙胺基 2·氣表基 2-胺基比1基 2-(4-氣本基)乙胺基 4-甲苯基 2-胺基_4_吡啶基 2-(4-氟苯基)乙胺基 3-甲苯基 2-胺基-4-p比淀基 2-(4-氣本基)乙胺基 2-甲苯基 2-胺基-4·^比淀基 2-(4-氟苯基)乙胺基 4-三氟甲基苯基 2-胺基-4_p比淀基 2-(4-氟苯基)乙胺基 3-三氟甲基苯基 2-胺基-4-吡啶基 2-(4-氣本基)乙胺基 2,6-—氯i本基 2_胺基-4-吡啶基 2-(4-氟苯基)乙胺基 2,6·二甲基苯基 2-胺基基 2-(4-氣本基)乙胺基 2,4-二氯苯基 2-胺基_4-#b淀基 2-(4·氟苯基)乙胺基 2,4-二甲基苯基 2-胺基-4-p比淀基 2-(4-氟苯基)乙胺基 苯基 2-乙醯胺基-4·吡啶基 2-(4_氟苯基)乙胺基 4-氣苯基 2-乙醯胺基-4-吡啶基 2-(4·氟苯基)乙胺基 3-氟苯基 2-乙醯胺基-4-吡啶基 2-(4-氟苯基)乙胺基 2-氣苯基 2-乙醯胺基-4-吡啶基 2-(4-氟苯基)乙胺基 4-氯苯基 2·乙醯胺基-4·吡啶基 2_(4-氟苯基)乙胺基 3-鼠苯基 2-乙醯胺基-4-吡啶基 2-(4-氟苯基)乙胺基 (請先閱讀背面之注意事項再填寫本頁) ^_wl. -74- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X29?公釐） 520362 A7 __B7 五、發明説明（72 ) 經濟部中央標準局員工消費合作社印製 2-氯苯基 2-乙醯胺基-4-吡啶基 2-(4-氟苯基)乙胺基 4-甲苯基 2-乙S盔胺基-4-p比淀基 2-(4·氟苯基)乙胺基 3-甲苯基 2-乙酿胺基-4-?比淀基 2-(4-氟苯基)乙胺基 2-甲苯基 2·乙醯胺基_4·吡啶基 2-(4-氟苯基)乙胺基 4-三氟甲基苯基 2_乙醯胺基-4-吡啶基 2-(4-氟苯基)乙胺基 3-二鼠甲基苯基 2-乙醯胺基-4-吡啶基 2-(4-氟苯基)乙胺基 2,6-二氯苯基 2-乙醯胺基_4_吡啶基 2_(4-氟苯基)乙胺基 2,6-二甲基苯基 2-乙酿胺基淀基 2-(4-氟苯基)乙胺基 2,4-二氯本基 2·乙酸胺基_4-p比淀基 2-(4-氟苯基)乙胺基 2,4-二甲基苯基 2-乙醒胺基淀基 2-(4-氟苯基)乙胺基 苯基 2-胺基-4-癌淀基 2-(4-氟苯基)乙胺基 4-鼠苯基 2-胺基-4-喃淀基 2-(4-氟苯基)乙胺基 3-氟苯基 2-胺基-4-喊淀基 2-(4·氟苯基)乙胺基 2-氣苯基 2-胺基-4-喊淀基 2-(4-氟苯基)乙胺基 4-氯苯基 1 2-胺基-4-p密淀基 1 2-(4-氟苯基)乙胺基 3-氯苯基 2-胺基-4-喃淀基 2-(4-氟苯基)乙胺基 2-氯苯基 2_胺基-4-喃淀基 2-(4-氟苯基)乙胺基 4-甲苯基 2-胺基-4_喃淀基 2-(4-氟苯基)乙胺基 3-甲苯基 2-胺基-4-喃淀基 2-(4-氟苯;S5乙胺基 2-甲苯基 2-胺基-4-喊淀基 2-(4-氟苯基)乙胺基 (請先閱讀背面之注意事項再填寫本頁)7 7 AB V. Description of the invention (71) 3-Fluorophenyl 2-amino-4-t1 than Yodo 2- (4-fluorophenyl) ethylamino 2- Fluorophenyl 2-amino-4-p is more than 2- (4-fluorophenyl) ethylamino 4-chlorophenyl 2-amino 4- (4-muryl) ethylamino 3- Chlorophenyl 2-amino-4-p ratio 2-Yoyl 2- (4-aminophenyl) ethylamino 2 4-Tolyl 2-amino 4-pyridyl 2- (4-fluorophenyl) ethylamino 3-tolyl 2-amino-4-p Amino 2-tolyl 2-amino-4. ^ Pyridyl 2- (4-fluorophenyl) ethylamino 4-trifluoromethylphenyl 2-amino-4_p -Fluorophenyl) ethylamino 3-trifluoromethylphenyl 2-amino-4-pyridyl 2- (4-aminobenzyl) ethylamino 2,6-chloroibenzyl 2-amino -4-pyridyl 2- (4-fluorophenyl) ethylamino 2,6 · dimethylphenyl 2-amino phenyl 2- (4-aminobenzyl) ethylamino 2,4-dichlorobenzene 2-amino-4-4-bYodoyl 2- (4-fluorophenyl) ethylamino 2,4-dimethylphenyl 2-amino-4-p ratio 2-Yodoyl 2- (4-fluoro Phenyl) ethylaminophenyl 2-acetamido-4 -pyridyl 2- (4-fluorophenyl) ethyl 4-Aminophenyl 2-Ethylamino-4-pyridyl 2- (4-Fluorophenyl) ethylamino 3-fluorophenyl 2-Ethylamino-4-pyridyl 2- (4- Fluorophenyl) Ethylamino 2-Phenyl 2-Ethylamido-4-pyridyl 2- (4-fluorophenyl) ethylamino 4-chlorophenyl 2.Ethylamino-4Pyridine 2- (4-fluorophenyl) ethylamino 3-murylphenyl 2-acetamido-4-pyridyl 2- (4-fluorophenyl) ethylamino (Please read the precautions on the back before filling (This page) ^ _wl. -74- This paper size is in accordance with Chinese National Standard (CNS) A4 (210X29? Mm) 520362 A7 __B7 V. Description of the invention (72) 2-Chlorine printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Phenyl 2-acetamido-4-pyridyl 2- (4-fluorophenyl) ethylamino 4-tolyl 2-ethysylamino-4-p ) Ethylamino 3-tolyl 2-ethynylamino-4-? Pyridyl 2- (4-fluorophenyl) ethylamino 2-tolyl-2 -(4-fluorophenyl) ethylamino 4-trifluoromethylphenyl 2-acetamido-4-pyridyl 2- (4-fluorophenyl) ethylamino 3-dimurylmethylphenyl 2-Ethylamino-4-pyridyl 2- (4-fluorophenyl) ethylamino 2,6-dichlorophenyl 2-ethyl Amido-4_pyridyl 2_ (4-fluorophenyl) ethylamino 2,6-dimethylphenyl 2-ethylaminoamino 2- (4-fluorophenyl) ethylamino 2, 4-dichlorobenzyl-2-acetamido 4-p ratio than 2- (4-fluorophenyl) ethylamino 2,4-dimethylphenyl 2-ethoxyamino 2- (4-fluorophenyl) ethyl 4-fluorophenyl) ethylaminophenyl 2-amino-4-carbodianyl 2- (4-fluorophenyl) ethylamino 4-murylphenyl 2-amino-4-ranyl 2- (4-Fluorophenyl) ethylamino 3-fluorophenyl 2-amino-4-dimethylamino 2- (4-fluorophenyl) ethylamino 2-aminophenyl-2-amino-4-methyl Yodo 2- (4-fluorophenyl) ethylamino 4-chlorophenyl 1 2-amino-4-p dense Yodo 1 2- (4-fluorophenyl) ethylamino 3-chlorophenyl 2 -Amino-4-ranyl 2- (4-fluorophenyl) ethylamino 2-chlorophenyl 2-amino-4-ranyl 2- (4-fluorophenyl) ethylamino 4- Tolyl 2-amino-4_anhydro-2-yl 4- (4-fluorophenyl) ethylamino 3-tolyl 2-amino-4-anyl 2- (4-fluorobenzene; S5 ethylamino 2-Tolyl 2-Amino-4-Hydroyl 2- (4-fluorophenyl) ethylamino (Please read the precautions on the back before filling this page)

、1T ____-75- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（73 ) 經濟部中央標準局員工消費合作社印製 4-三氟甲基苯基 2-胺基-4-喊淀基 2-(4-氣苯基)乙胺基 3-三氟甲基苯基 2-胺基-4-喃淀基 2-(4-氟苯基)乙胺基 2,6-二氣參基 2-胺基-4-喊淀基 2-(4-氟苯基)乙胺基 2,6-二甲基本基 2-胺基-4-喊淀基 2-(4-氟苯基)乙胺基 2,4-二氯苯基 2-胺基-4_喃淀基 2-(4-氟苯基)乙胺基 2,4-二甲基苯基 2-胺基-4-喃淀基 2-(4·氟苯基)乙胺基 苯基 4-p比淀基 3-苯基-丙胺基 4-鼠本基 4-峨淀基 3-苯基-丙胺基 3-氟苯基 4-p比淀基 3-苯基-丙胺基 2-氟苯基 4-口比淀基 3-冬基-丙胺基 4-鼠豕基 4-p比淀基 3-苯基-丙胺基 3-氯苯基 4-p比淀基 3-豕基_丙胺基 2-氯苯基 4-外b淀基 3-苯基-丙胺基 4·甲苯基 4-p比淀基 3-苯基-丙胺基 3-甲苯基 4-p比淀基 3-苯基-丙胺基 2-甲苯基 4-口比淀基 3-苯基-丙胺基 4-三氟甲基苯基 4-p比淀基 3-苯基-丙胺基 3-二氣甲基苯基 4-峨淀基 3-苯基-丙胺基 2,6-二氣豕基 4-吡啶基 3基-丙胺基 2,6-二甲基苯基 4-p比淀基 3-苯基-丙胺基 -76- 本纸張夂度適用中國國家標準（CNS ) A4規格（210X 297公釐） (請先閱讀背面之注意事項再填寫本頁) 4. 520362 Μ Β7 五、發明説明（74 ) 經濟部中央標準局員工消費合作社印製 2,4-二氣本基 4-ρ比淀基 3-苯基-丙胺基 2,4-二甲基苯基 4-ρ比淀基 3-本基-丙胺基 苯基 2-胺基-4-?比淀基 3-苯基-丙胺基 4-氟苯基 2-胺基-4-峨淀基 3_豕基-丙胺基 3-氟苯基 2·胺基-4-吡啶基 3-苯基-丙胺基 2-氟苯基 2-胺基-4-?比淀基 3-豕基-丙胺基 4-氯苯基 2-胺基-4-ρ比淀基 3-苯基-丙胺基 3-氣本基 2_胺基-4-ρ比淀基 3-豕基-丙胺基 2-氯苯基 2-胺基-4-吡啶基 3-本基-丙胺基 4-甲苯基 2-胺基_4-峨淀基 3-苯基-丙胺基 3-甲苯基 2-胺基-4-吡啶基 3-苯基-丙胺基 2-甲苯基 2-胺基-4-吡啶基 3-苯基-丙胺基 4_三氟甲基苯基 2-胺基-4-吡啶基 3-苯基_丙胺基 3·三氟甲基苯基 2-胺基基 3-苯基-丙胺基 2,6-二氯豕基 2-胺基-4-ρ比基 3-秦基-丙胺基 2,6-二甲基苯基 2-胺基-4-峨淀基 3-苯基-丙胺基 2,4-二氯苯基 2-胺基-4-ρ比淀基 3_苯基-丙胺基 2,4-二甲基苯基 2-胺基基 3-苯基-丙胺基 苯基 2-乙酿胺基基 3-本基-丙胺基 4-氟苯基 2-乙醯胺基-4-吡啶基 3_苯基·丙胺基 ---------0------1Τ-------0— (請先閱讀背面之注意事項再填寫本頁) -77- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X29?公釐） 520362、 1T ____- 75- This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) 520362 A7 B7 V. Description of the invention (73) 4-Trifluoromethyl printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Phenyl 2-Amino-4-Hydroyl 2- (4-Gaphenyl) Ethylamino 3-trifluoromethylphenyl 2-Amino-4-ranyl 2- (4-fluorophenyl ) Ethylamino 2,6-digassinyl 2-amino-4-dimethylamino 2- (4-fluorophenyl) ethylamino 2,6-dimethylbenzyl 2-amino-4-dimethylamino 2- (4-fluorophenyl) ethylamino 2,4-dichlorophenyl 2-amino-4 -pyranyl 2- (4-fluorophenyl) ethylamino 2,4-dimethyl Phenyl 2-amino-4-anyl-2- (4-fluorophenyl) ethylaminophenyl 4-p is more than 3-phenyl-propylamino 4-muryl 4-eodoyl 3 -Phenyl-propylamino 3-fluorophenyl 4-p than yodoyl 3-phenyl-propylamino 2-fluorophenyl 4-pyridyl 3-dongyl-propylamino 4-muridine 4-p Pyridyl 3-phenyl-propylamino 3-chlorophenyl 4-p Pyridyl 3-fluorenyl-propylamino 2-chlorophenyl 4-exo-b-yl 3-phenyl-propylamine 4-tolyl 4-p than yodoyl 3-phenyl-propylamino 3-tolyl 4-p than yodoyl 3-phenyl-propylamino 2-tolyl 4- Pyridyl 3-phenyl-propylamino 4-trifluoromethylphenyl 4-p Pyridyl 3-phenyl-propylamino 3-difluoromethylphenyl 4-eodoyl 3-phenyl-propylamine 2,6-Diaerofluorenyl 4-pyridyl 3-yl-propylamino 2,6-dimethylphenyl 4-p than Yenyl 3-phenyl-propylamino-76- This paper is compatible with Chinese national standards (CNS) A4 size (210X 297 mm) (Please read the notes on the back before filling out this page) 4. 520362 Μ Β7 V. Description of the invention (74) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 2,4- Diphenylbenzyl 4-ρ ratio Yodo-based 3-phenyl-propylamino 2,4-dimethylphenyl 4-ρ ratio Yodoyl 3-benzyl-propylaminophenyl 2-amino-4-? Ratio Yodo 3-phenyl-propylamino 4-fluorophenyl 2-amino-4-gadolide 3- 3-fluorenyl-propylamino 3-fluorophenyl 2-amino-4-pyridyl 3-phenyl- Propylamino 2-fluorophenyl 2-amino-4-? Pyridyl 3-fluorenyl-propylamino 4-chlorophenyl 2-amino-4-ppyridyl 3-phenyl-propylamino 3- 2-benzyl-4-amino than 2-amino-pyridyl 3-propyl-propylamino 2-chlorophenyl 2-amino-4-pyridyl 3-benzyl-propylamino 4-tolyl 2-amino _4-Edianyl 3-phenyl-propylamino 3-methyl 2-amino-4-pyridyl 3-phenyl-propylamino 2-tolyl 2-amino 4-pyridyl 3-phenyl-propylamino 4-trifluoromethylphenyl 2-amino- 4-pyridyl 3-phenyl-propylamino 3.trifluoromethylphenyl 2-amino 3-phenyl-propylamino 2,6-dichlorofluorenyl 2-amino-4-ρ -Qinyl-propylamino 2,6-dimethylphenyl 2-amino-4-gadolide 3-phenyl-propylamino 2,4-dichlorophenyl 2-amino-4-ρ 3-phenyl-propylamino 2,4-dimethylphenyl 2-amino 3-phenyl-propylaminophenyl 2-ethylaminoamino 3-benzyl-propylamino 4-fluorophenyl 2-Ethylamino-4-pyridyl 3-phenyl · propylamino --------- 0 ------ 1T ------- 0— (Please read the Please fill in this page again for the matters needing attention) -77- This paper size applies to China National Standard (CNS) Α4 specification (210X29? Mm) 520362

A B 五、發明説明（75 ) 經濟部中央標隼局員工消費合作社印製 3-氣苯基 2-乙酿胺基-4-?比淀基 3-本基-丙胺基 2_氟苯基 2-乙醯胺基-4-吡啶基 3-苯基-丙胺基 4-氯苯基 2-乙酿胺基-4·ρ比淀基 3-苯基-丙胺基 3-氯苯基 2-乙酸胺基-4-ρ比淀基 3-苯基_丙胺基 2-氯苯基 2_乙醯胺基-4-吡啶基 3-木基-丙胺基 4-甲苯基 2-乙酿胺基 3-豕基-丙胺基 3-甲苯基 2-乙酿胺基-4-ρ比淀基 3-苯基-丙胺基 2-甲苯基 2_乙醯胺基-4-吡啶基 3-本基-丙胺基 4-三氟曱基苯基 2-乙酿胺基基 3-苯基-丙胺基 3-三氟甲基苯基 2-乙醯胺基-4-峨淀基 3-豕基-丙胺基 2,6-二氣本基 2-乙醯胺基-4_吡啶基 3-苯基_丙胺基 2,6-二甲基苯基 2-乙醯胺基-4-吡啶基 3-苯基-丙胺基 2,4-二氯苯基 2-乙S盛胺基·4-ρ比淀基 3-冬基l-丙胺基 2,4-二曱基苯基 2·乙酸胺基-4-ρ比淀基 3-豕基-丙胺基 苯基 2-胺基-4-喃淀基 3-苯基-丙胺基 4-氣苯基 2-胺基-4_喃淀基 3-冬基·丙胺基 3-氟苯基 2-胺基-4-喊淀基 3-苯基-丙胺基 2-氟苯基 2-胺基-4-喊淀基 3-苯基-丙胺基 4-氯苯基 2-胺基-4-喃淀基 3-苯基-丙胺基 3-氯苯基 2-胺基-4-喃淀基 3-苯基-丙胺基 (請先閱讀背面之注意事項再填寫本頁) 訂 -^1. -78- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362AB V. Description of the invention (75) 3-Phenyl-2-ethylamino-4-? Pyridyl 3-benzyl-propylamino 2-fluorophenyl 2 -Ethylamino-4-pyridyl 3-phenyl-propylamino 4-chlorophenyl 2-ethylamino-4 · ρ-pyridyl 3-phenyl-propylamino 3-chlorophenyl 2-acetic acid Amino-4-p ratio than phenyl 3-phenyl_propylamino 2-chlorophenyl 2-acetamido-4-pyridyl 3-muyl-propylamino 4-tolyl 2-ethylamino 3 -Methenyl-propylamino 3-tolyl 2-ethylamino-4-p-pyridyl 3-phenyl-propylamino 2-tolyl 2-ethylamido-4-pyridyl 3-benzyl- Propylamino 4-trifluorofluorenylphenyl 2-ethylaminoamino 3-phenyl-propylamino 3-trifluoromethylphenyl 2-ethylfluorinyl-4-amidoyl 3-fluorenyl-propylamine 2,6-Diaminobenzyl-2-acetamido-4-pyridyl 3-phenyl_propylamino 2,6-dimethylphenyl 2-acetamido-4-pyridyl 3-benzene Propyl-propylamino 2,4-dichlorophenyl 2-ethylaminoamine 4-4-pyridyl 3-dongyl 1-propylamino 2,4-difluorenylphenyl 2.acetamido-4 -ρ ratio ylidene 3-fluorenyl-propylaminophenyl 2-amino-4-ranyl 3-phenyl-propylamino 4- Phenyl 2-Amino-4_Amino-Dynamyl 3-Hydroxypropylamino 3-Fluorophenyl 2-Amino-4-Hydroyl 3-phenyl-propylamino 2-fluorophenyl 2-amino 4-Hydroxy-3-phenyl-propylamino 4-chlorophenyl 2-amino-4-anyl 3-phenyl-propylamino 3-chlorophenyl 2-amino-4-anyl 3-phenyl-propylamino (please read the precautions on the back before filling this page) Order-^ 1. -78- This paper size applies to China National Standard (CNS) A4 (210X 297 mm) 520362

7 B 五、發明説明（76 ) 經濟部中央標準局員工消費合作社印製 2-氯苯基 2-胺基-4_喃淀基 3-苯基-丙胺基 4·甲苯基 2-胺基-4-喊淀基 3-苯基-丙胺基 3-甲苯基 2-胺基_4-喊淀基 3-苯基-丙胺基 2-甲苯基 2_胺基_4-喊淀基 3-苯基-丙胺基 4-三氟甲基苯基 2-胺基-4-喊淀基 3-苯基-丙胺基 3-三氟甲基苯基 2-胺基-4-喃淀基 3-苯基·丙胺基 2,6·二鼠冬基 2-胺基·4-喊淀基 3-苯基-丙胺基 2,6-二甲基苯基 2-胺基-4-喊淀基 3-本基-丙胺基 2,4-二氣本基 2-胺基-4-哺淀基 3_苯基-丙胺基 2,4-二甲基苯基 2-胺基-4-喊淀基 3-苯基-丙胺基 苯基 4-ρ比淀基 (1-甲基-3-本基)丙胺基 4-氟苯基 4-ρ比淀基 (1_甲基-3-苯基)丙胺基 3_氣豕基 4-外b淀基 (1_甲基_3_苯基)丙胺基 2-氟苯基 4-p比淀基 (1-甲基-3-苯基)丙胺基 4-氯苯基 4_p比淀基 (1-甲基-3-苯基)丙胺基 3-氯苯基 4-p比淀基 (1-甲基-3-苯基)丙胺基 2-氯苯基 4-p比淀基 (1-甲基_3_苯基)丙胺基 4-甲苯基 4-外b淀基 (1-甲基-3-苯基)丙胺基 3-甲苯基 4-p比淀基 (i甲基-3-笨基)丙胺基 2-曱苯基 4-p比淀基 (i-甲基·3·苯基)丙胺基 (請先閲讀背面之注意事項再填寫本頁) 訂 -79- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（77 ) 經濟部中央標準局員工消費合作社印製 4-三氟甲基苯基 4-p比症基 (i-甲基-3-苯基)丙胺基 3-二氣甲基苯基 4·ρ比淀基 (1-甲基_3_苯基)丙胺基 2,6-—氣冬基 4-ρ比淀基 (μ甲基-3-苯基)丙胺基 2,6·二甲基苯基 4-口比淀基 (1-甲基-3-苯基)丙胺基 2,4-二鼠泰基 4·ρ比淀基 (1—甲基-3-苯基)丙胺基 2,4-二甲基苯基 4-ρ比淀基 (1-甲基-3-苯基)丙胺基 苯基 2-胺基-4-ρ比淀基 (1-甲基-3-苯基)丙胺基 4-氟苯基 2-胺基-4-ρ比淀基 (1-甲基-3-苯基)丙胺基 3-氟苯基 2_胺基-4-峨淀基 (μ甲基-3-苯基)丙胺基 2-氟苯基 2·胺基-4-ρ比淀基 (1-甲基-3-苯基)丙胺基 4-氯苯基 2-胺基_4-ρ比淀基 (1_甲基_3·苯基)丙胺基 3-氯苯基 2-胺基-4-吡啶基 (1-甲基-3-苯基)丙胺基 2-氯苯基 2-胺基-4-0比咬^基 (1-甲基各苯基)丙胺基 4-甲苯基 2-胺基基 (1-甲基_3_苯基)丙胺基 3-甲苯基 2-胺基_4-说淀基 (1-甲基-3-苯基)丙胺基 2-甲苯基 2_胺基-4-吡啶基 (1-甲基_3·苯基)丙胺基 4-三氟甲基苯基 2_胺基-4-吡啶基 (i-甲基_3_苯基)丙胺基 3-三氟甲基苯基 2-胺基淀基 (i-甲基_3_苯基)丙胺基 2,6-二氯苯基 2-胺基-4_p比淀基 (i甲基-3-苯基)丙胺基 2,6-二甲基苯基 2-胺基-4-p比淀基 (μ甲基_3-苯基)丙胺基 (請先閲讀背面之注意事項再填寫本頁)7 B V. Description of the invention (76) 2-Chlorophenyl 2-Amino-4_pyranyl 3-phenyl-propylamine 4-tolyl 2-amino- 4-Hydroxy 3-phenyl-propylamino 3-tolyl 2-amino group 4- 4-Hydroxy 3-phenyl-propylamino 2-tolyl 2-amino group 4- 4-Hydroxy 3-benzene Propyl-propylamino 4-trifluoromethylphenyl 2-amino-4-ylamino 3-phenyl-propylamino 3-trifluoromethylphenyl 2-amino-4-pyranyl 3-benzene Propylamino, 2,6-dimyridyl 2-amino, 4-aminoalkyl 3-phenyl-propylamino 2,6-dimethylphenyl 2-amino-4-amino Benzoyl-propylamino 2,4-diaminobenzyl 2-amino-4-pyridyl 3-phenyl-propylamino 2,4-dimethylphenyl 2-amino-4-ylamino 3 -Phenyl-propylaminophenyl 4-r-pyridyl (1-methyl-3-benzyl) propylamino 4-fluorophenyl 4-r-pyridyl (1-methyl-3-phenyl) propylamine 3-Aminomethyl 4-pyridyl 4- (b-methyl-3-phenyl) propylamino 2-fluorophenyl 4-p -Chlorophenyl 4-p-pyridyl (1-methyl-3-phenyl) propylamino 3-chlorophenyl 4-p Bipyridyl (1-methyl-3-phenyl) propylamino 2-chlorophenyl 4 -p-pyridyl (1-methyl_3-phenyl) propylamino 4-tolyl 4-exo-b-yl (1-methyl-3-phenyl) propylamino 3-tolyl 4-p-pyridyl (Imethyl-3-benzyl) alanyl 2-fluorenyl 4-p than ylide (i-methyl · 3 · phenyl) alanyl (please read the precautions on the back before filling this page) ORDER-79- This paper size applies Chinese National Standard (CNS) A4 (210X 297 mm) 520362 A7 B7 V. Description of the invention (77) 4-trifluoromethylphenyl printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 4-p-pyridyl (i-methyl-3-phenyl) alanyl 3-difluoromethylphenyl 4.ρpyridyl (1-methyl_3-phenyl) alanyl 2,6- --Pyroyl 4-p-pyridyl (μmethyl-3-phenyl) propylamino 2,6 · dimethylphenyl 4-lipidyl (1-methyl-3-phenyl) propylamino 2,4-Dimethynyl 4-p-pyridyl (1-methyl-3-phenyl) alanyl 2,4-dimethylphenyl 4-p-pyridyl (1-methyl-3-benzene (Propyl) propylaminophenyl 2-amino-4-p.pyridyl (1-methyl-3-phenyl) propylamino 4-fluorophenyl 2-amino-4-p.pyridyl (1-methyl Phenyl-3-phenyl) propylamino 3-fluorophenyl 2-amino-4-gadolide (μmethyl-3-phenyl) propyl Amino 2-fluorophenyl 2-amino-4-p-pyridyl (1-methyl-3-phenyl) propylamino 4-chlorophenyl 2-amino_4-ppyridyl (1_ (Methyl-3.phenyl) propylamino 3-chlorophenyl 2-amino-4-pyridyl (1-methyl-3-phenyl) propylamino 2-chlorophenyl 2-amino-4-0 Titanyl (1-methyl each phenyl) propylamino 4-tolyl 2-amino (1-methyl_3-phenyl) propylamino 3-tolyl 2-amino_4- (1-methyl-3-phenyl) propylamino 2-tolyl 2-amino-4-pyridyl (1-methyl-3-phenyl) propylamino 4-trifluoromethylphenyl 2_ Amino-4-pyridyl (i-methyl_3-phenyl) propylamino 3-trifluoromethylphenyl 2-aminoalkyl (i-methyl_3-phenyl) propylamine 2,6 -Dichlorophenyl 2-amino-4_p than amino (imethyl-3-phenyl) propylamino 2,6-dimethylphenyl 2-amino-4-p than amino (μmethyl _3-Phenyl) propylamine (Please read the precautions on the back before filling this page)

、1T ^_wl. -80- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（78 ) 經濟部中央樣準局員工消費合作社印製 2,4-二氣本基 2-胺基-4-p比基 (1-甲基-3-苯基)丙胺基 2,4-二甲基苯基 2_胺基-4-吡啶基 (1-甲基-3-苯基)丙胺基 苯基 2-乙醯胺基-4-p比淀基 (1_甲基_3-苯基)丙胺基 4-氟苯基 2-乙酿胺基-4-p比淀基 (1-曱基-3-苯基)丙胺基 3-氟苯基 2-乙醯胺基-4-吡啶基 (1-甲基-3-苯基)丙胺基 2-氟苯基 2-乙醯胺基-4-P比淀基 (1-甲基-3-苯基)丙胺基 4-氯苯基 2-乙醯胺基-4-吡啶基 (1-甲基各苯基)丙胺基 3-氯苯基 2-乙酿胺基-4-峨淀基 (1·甲基-3_苯基)丙胺基 2-氯苯基 2_乙酿胺基-4-0比淀基 (1_甲基-3-苯基)丙胺基 4-甲苯基 2-乙醯胺基_4_吡啶基 (1-甲基-3-苯基)丙胺基 3-甲苯基 2-乙酿胺基-4-p比淀基 (1-甲基-3-苯基)丙胺基 2-甲苯基 2-乙醯胺基-4-吡啶基 (1·甲基-3_苯基)丙胺基 4-二氣甲基苯基 2-乙醯胺基-4-p比淀基 (i曱基_3·苯基)丙胺基 3-三氟甲基苯基 2-乙醯胺基-4·ρ比淀基 (1-甲基·3-苯基)丙胺基 2,6-二氣本基 2-乙醯胺基-4-吡啶基 (1-甲基-3_苯基)丙胺基 2,6-二甲基苯基 2-乙醯胺基-4-外I:淀基 (1-甲基-3-本基)丙胺基 2,4-二氯苯基 2-乙醯胺基-4-吡啶基 (1_甲基-3-苯基)丙胺基 2,4-二甲基苯基 2-乙酿胺基-4-p比淀基 (1-甲基-3-苯基)丙胺基 苯基 2_胺基-4-喃淀基 (1-甲基-3-束基)丙胺基 4-氟苯基 2-胺基-4-喃淀基 (i•甲基_3_苯基)丙胺基 (請先閲讀背面之注意事項再填寫本頁) 訂 4. -81 - 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（79 ) 經濟部中央標準局員工消費合作社印製 3-氟苯基 2-胺基-4-0密淀基 (1-甲基-3-苯基)丙胺基 2-氣苯基 2-胺基-4-嘧啶基 (1-甲基-3-苯基)丙胺基 4-氣苯基 2-胺基-4-嘧啶基 (1-甲基-3-苯基)丙胺基 3-氯苯基 2-胺基-4-嘧啶基 (1-甲基-3-苯基)丙胺基 2-氯苯基 2-胺基-4-嘧啶基 (1·甲基-3-苯基)丙胺基 4-甲苯基 2-胺基-4-嘧啶基 (1_甲基-3-苯基)丙胺基 3-甲苯基 2_胺基·4-ρ密淀基 (1-甲基-3-苯基)丙胺基 2-甲苯基 2-胺基-4-喃淀基 (1·甲基-3-苯基)丙胺基 4-三氟甲基苯基 2-胺基-4-嘧啶基 (1-甲基-3-苯基)丙胺基 3-三氟甲基苯基 2-胺基_4_嘧啶基 (1-甲基-3-苯基)丙胺基 2,6-二氯苯基 2-胺基-4-嘧啶基 (1·甲基-3·苯基)丙胺基 2,6-二甲基苯基 2-胺基-4-嘧啶基 (1_甲基-3-苯基)丙胺基 2,4-二氯苯基 2-胺基-4-嘧啶基 (1-甲基_3_苯基)丙胺基 2,4-二甲基苯基 2-胺基-4-嘧啶基 (1-甲基_3_苯基)丙胺基 4-氣苯基 4-外(：淀基 4·氣卞基胺基 4-氟苯基 2-乙醯胺基-4-Ρ比淀基 4-氟苄基胺基 4-氣苯基 2-胺基-4-嘧啶基 4-氟爷基胺基 4-氣苯基 4-0比淀基 (2-(4·氟苯基-1-甲基-乙基)胺基 4-鼠苯基 2-乙醯胺基-4-吨淀基 (2-(4-鼠苯墓-1 -甲基·乙基)胺基 4-氟苯基 2-胺基-4-Ρ密淀基 (2·(Φ·氟苯基-1-甲基·乙基)胺基 -82- (請先閱讀背面之注意事項再填寫本頁) 訂 ^wi. 0 1= - 本紙張尺度適用中國國家標準（CNS ) A4規格（21〇X297公釐） 520362 A7 B7 五、發明説明（8〇 ) 經濟部中央標準局員工消費合作社印製 4-氣苯基 4-p比淀基 (1，1-二甲基-2-(4-氟苯基)-乙基)胺基 4_氟苯基 2-乙醯胺基-4·吡啶基 (1，1-二甲基-2-(4-氣苯基)-乙基)胺基 4-氣苯基 2-胺基-4-喊淀基 (1，1-二甲基-2-(4-氟苯基)-乙基)胺基 4-氟苯基 4-p比淀基 (2-(4-氟苯基)-2-甲基·乙基)胺基 4-氟苯基 2-乙S盛胺基-4-p比淀基 (2-(4-氟苯基)-2-甲基乙基)胺基 4-氟苯基 2_胺基-4-喊淀基 (2-(4-氟苯基)-2-甲基·乙基)胺基 4-氟苯基 4-p比淀基 (2-甲基-2-苯基乙基)胺基 4-氟苯基 2-乙酸胺基-4-p比淀基 (2-甲基-2-苯基乙基)胺基 4-氟苯基 2-胺基-4-喊淀基 (2·甲基·2·苯基乙基)胺基 4-氟苯基 4-峨淀基 甲基-(2-苯基乙基)胺基 4-氟苯基 2-乙酿胺基-4-p比淀基 甲基-(2-苯基乙基)胺基 4-氟苯基 2-胺基-4-喊淀基 甲基-(2-苯基乙基)胺基 4-氟苯基 4-p比淀基 (2-(4-三氟甲基苯基)乙基)胺基 4-氟苯基 2·乙醯胺基-4-吡啶基 (2-(4-三氟甲基苯基)乙基)胺基 4-氣苯基 2-胺基-4-喊淀基 (2-(4-三氟甲基苯基)乙基)胺基 4-鼠苯基 4-p比淀基 (2-(4-甲苯基)乙基胺基 4-氣苯基 2-乙醯胺基-4-吡啶基 (2-(4-甲苯基)乙基胺基 4-氟苯基 2-胺基-4-喊淀基 (2-(4_甲苯基)乙基胺基 4-氣苯基 4-p比淀基 (2-(3-氟苯基)乙基)胺基 4-鼠苯基 2-乙醯胺基-4-P比淀基 (2-(3-氟苯基)乙基)胺基 (請先閱讀背面之注意事項再填寫本頁) -83- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（81 ) 經濟部中央標準局員工消費合作社印製 4-氟苯基 2-胺基-4-喊淀基 (2-(3-氟苯基)乙基)胺基 4-氟苯基 4-ρ比淀基 (2-(2-氟苯基)乙基)胺基 4-氟苯基 2-乙醯胺基-4-p比淀基 (2-(2-氣苯基)乙基)胺基 4-氟苯基 2_胺基-4-喃淀基 (2-(2-氟苯基)乙基)胺基 4-氟苯基 4-p比淀基 甲基-(2-(2-吡啶基)乙基)胺基 4-氟苯基 2-乙酿胺基·4_ρ比淀基 甲基-(2-(2-吡啶基)乙基)胺基 4-氟苯基 2-胺基-4-喃淀基 甲基-(2_(2_吡啶基)乙基)胺基 4-氟苯基 4-峨淀基 (1，1-二甲基-3-苯基_丙基)胺基 4-氣苯基 2-乙醯胺基-4-吡啶基 (U-二甲基_3_苯基-丙基)胺基 4-氟苯基 2-胺基-4-喊淀基 (1，1-二甲基-3-苯基·丙基)胺基 4-氟苯基 4-ρ比淀基 (3-(4_氟苯基)-丙基)胺基 4-氟苯基 2-乙醯胺基-4-吡啶基 (3-(4-氟苯基)-丙基)胺基 4-氟苯基 2_胺基-4-瘤淀基 (3-(4-氟苯基)-丙基)胺基 4-氟苯基 4-ρ比淀基 (3_(4-氟苯基)-1-甲基-丙基)胺基 4-氟苯基 2-乙醯胺基-4-吡啶基 (3-(4-鼠苯基)-1-甲基-丙基)胺基 4-氟苯基 2-胺基-4-喃淀基 (3-(4-氣本基)-1-甲基-丙基)胺基 4-氟苯基 4-ρ比淀基 (1，1-二甲基-3-(4-氣本基)-丙基)胺基 4-氟苯基 2-乙醯胺基-4-ρ比淀基 (1，1-二甲基-3-(4-氟苯基)-丙基)胺基 4-氟苯基 2-胺基-4-喃淀基 (1,1-二甲基<-3-(4-氟苯基)-丙基)胺基 4-氟苯基 4-吨淀基 (3_(2_氟苯基)·丙基)胺基 (請先閲讀背面之注意事項再填寫本頁) -84- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（82 ) 經濟部中央標準局員工消費合作社印製 4-鼠苯基 2-乙醯胺基-4-吡啶基 (3-(2-氟苯基丙基)胺基 4-氟苯基 2-胺基_4_喊淀基 (3-(2-氟苯基)-丙基)胺基 4-氟苯基 4-吨淀基 (3-甲基-3-苯基-丙基)胺基 4-氟苯基 2-乙醯胺基-4-吡啶基 (3-甲基_3_苯基-丙基)胺基 4-氟苯基 2-胺基-4-p密淀基 (3-甲基-3-苯基丙基)胺基 4-氟苯基 4-p比淀基 (2-甲基-3-苯基-丙基)胺基 4-氟苯基 2-乙醯胺基-4-吡啶基 (2_甲基-3-苯基-丙基)胺基 4-氟苯基 2-胺基-4_癌淀基 (2-甲基；苯基-丙基)胺基 4-氟苯基 4-p比淀基 (3,3·二甲基丁基)胺基 4-氟苯基 2-乙醯胺基-4-p比淀基 (3,3·二甲基丁基)胺基 4-氟苯基 2-胺基-4-p密淀基 (3,3·二甲基丁基)胺基 4-氟苯基 4-p比淀基 異戊基胺基 4-氣苯基 2-乙醯胺基-4-吡啶基 異戊基胺基 4-氟苯基 2-胺基-4-喊淀基 異戊基胺基 4-氟苯基 4-p比淀基 戊基胺基 4-氣苯基 2-乙醯胺基-4-吡啶基 戊基胺基 4-氟苯基 2-胺基-4-喊淀基 戊基胺基 4-氟苯基 4-p比淀基 (2,5_二甲基)戊基胺基 4-氟苯基 2-乙醯胺基-4-吡啶基 (2,5-二甲基)戊基胺基 4-氟苯基 2_胺基-4-喊淀基 (2,5-二甲基)戊基胺基 (請先閱讀背面之注意事項再填寫本頁) 訂 -85- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362、 1T ^ _wl. -80- This paper size is applicable to Chinese National Standard (CNS) A4 (210X 297 mm) 520362 A7 B7 V. Description of the invention (78) Printed by the Consumer Cooperative of the Central Procurement Bureau of the Ministry of Economic Affairs 2,4 -Diaminobenzyl 2-amino-4-p than (1-methyl-3-phenyl) propylamino 2,4-dimethylphenyl 2-amino-4-pyridyl (1-methyl Phenyl-3-phenyl) propylaminophenyl 2-acetamido-4-p than yodo (1-methyl_3-phenyl) propylamino 4-fluorophenyl 2-ethylamino-4 -p than yodo (1-fluorenyl-3-phenyl) propylamino 3-fluorophenyl 2-acetamido-4-pyridyl (1-methyl-3-phenyl) propylamino 2-fluoro Phenyl 2-acetamido-4-P is better than (1-methyl-3-phenyl) propylamino 4-chlorophenyl 2-acetamido-4-pyridyl (1-methyl each (Phenyl) propylamino 3-chlorophenyl 2-ethylamino-4-eodoyl (1-methyl-3_phenyl) propylamino 2-chlorophenyl 2-ethylamino-4-0 Titanyl (1-methyl-3-phenyl) propylamino 4-tolyl 2-acetamido-4_pyridyl (1-methyl-3-phenyl) propylamino 3-tolyl 2- Ethylamino-4-p than amino (1-methyl-3-phenyl) propylamino 2-tolyl 2-acetamido-4-pyridyl (1-methyl-3-phenyl ) Propylamino 4-difluoromethylphenyl 2-acetamido-4-p than ydoyl (ifluorenyl-3-phenyl) propylamino 3-trifluoromethylphenyl 2-acetamido -4.p.pyridyl (1-methyl · 3-phenyl) propylamino 2,6-diaminobenzyl-2-acetamido-4-pyridyl (1-methyl-3_phenyl) Propylamino 2,6-dimethylphenyl 2-ethenylamino-4-exogen I: ylide (1-methyl-3-benzyl) propylamino 2,4-dichlorophenyl 2-ethenyl Amino-4-pyridyl (1-methyl-3-phenyl) propylamino 2,4-dimethylphenyl 2-ethylamino-4-p Phenyl) propylaminophenyl 2-amino-4-ranyl (1-methyl-3-bundyl) propylamino 4-fluorophenyl 2-amino-4-ranyl (imethyl _3_Phenyl) propylamine (please read the notes on the back before filling this page) Order 4. -81-This paper size is applicable to China National Standard (CNS) A4 (210X 297 mm) 520362 A7 B7 V. Description of the Invention (79) 3-Fluorophenyl 2-amino-4-0 denselyl (1-methyl-3-phenyl) alanine 2-aerophenyl 2 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs -Amino-4-pyrimidinyl (1-methyl-3-phenyl) propylamino 4-aminophenyl 2-amino-4-pyrimidinyl (1-methyl Phenyl-3-phenyl) propylamino 3-chlorophenyl 2-amino-4-pyrimidinyl (1-methyl-3-phenyl) propylamino 2-chlorophenyl 2-amino-4-pyrimidinyl (1-methyl-3-phenyl) propylamino 4-tolyl 2-amino-4-pyrimidinyl (1-methyl-3-phenyl) propylamino 3-tolyl 2-amino ρ denselyl (1-methyl-3-phenyl) alaninyl 2-tolyl 2-amino-4-ranyl (l.methyl-3-phenyl) alaninyl 4-trifluoromethyl Phenyl 2-amino-4-pyrimidinyl (1-methyl-3-phenyl) propylamino 3-trifluoromethylphenyl 2-amino-4_pyrimidinyl (1-methyl-3-benzene (Propyl) propylamino 2,6-dichlorophenyl 2-amino-4-pyrimidinyl (1methyl-3phenyl) propylamino 2,6-dimethylphenyl 2-amino-4- Pyrimidinyl (1-methyl-3-phenyl) propylamino 2,4-dichlorophenyl 2-amino-4-pyrimidinyl (1-methyl-3-phenyl) propylamino 2,4-di Methylphenyl 2-amino-4-pyrimidinyl (1-methyl-3_phenyl) alaninyl 4-phenyl 4-exo (: Yodoyl 4-pyridinylamino 4-fluorophenyl Ratio of 2-acetamido-4-P to 4-aminobenzyl 4-fluorophenyl 4-aminophenyl 4-aminobenzyl 4-pyrimidinyl 4-fluoromethylamino 4-phenyl Yodo (2- (4-fluorophenyl-1-methyl-ethyl) amino 4-rat 2-Ethylamido-4-tonylamino (2- (4-rhamtophenone-1 -methylethyl) amino 4-fluorophenyl 2-amino-4-P denselyl ( 2 · (Φ · fluorophenyl-1-methyl · ethyl) amino-82- (Please read the precautions on the back before filling this page) Order ^ wi. 0 1 =-This paper size applies to Chinese national standards (CNS) A4 specification (21 × 297 mm) 520362 A7 B7 V. Description of the invention (80) 4-Phenylphenyl 4-p-pyridyl (1, 1- 2) printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Methyl-2- (4-fluorophenyl) -ethyl) amino 4-fluorophenyl 2-acetamido-4 · pyridyl (1,1-dimethyl-2- (4-phenylbenzene) (Amino) -ethyl) amino 4-aminophenyl 2-amino-4-amino (1,1-dimethyl-2- (4-fluorophenyl) -ethyl) amino 4-fluoro Phenyl 4-p-pyridyl (2- (4-fluorophenyl) -2-methyl.ethyl) amino 4-fluorophenyl 2-ethylamido-4-p-pyridyl (2 -(4-fluorophenyl) -2-methylethyl) amino 4-fluorophenyl 2-amino-4-amino (2- (4-fluorophenyl) -2-methylethyl (Amino) amino 4-fluorophenyl 4-p than amino (2-methyl-2-phenylethyl) amino 4-fluorophenyl 2-acetamido-4-p Methyl-2-phenylethyl) amino 4-fluorobenzene 2-Amino-4-amino (2-methyl-2phenylphenyl) amino 4-fluorophenyl 4-eodoylmethyl- (2-phenylethyl) amino 4 -Fluorophenyl 2-ethylamino-4-p than yodomethyl- (2-phenylethyl) amino 4-fluorophenyl 2-amino-4-hydroxymethyl- (2 -Phenylethyl) amino 4-fluorophenyl 4-p bis (2- (4-trifluoromethylphenyl) ethyl) amino 4-fluorophenyl 2 acetamido-4 -Pyridyl (2- (4-trifluoromethylphenyl) ethyl) amino 4-aminophenyl 2-amino-4-amino (2- (4-trifluoromethylphenyl) ethyl (Amino) 4-aminophenyl 4-muryl 4-pyridyl (2- (4-tolyl) ethylamino Tolyl) ethylamino 4-fluorophenyl 2-amino-4-amino (2- (4-tolyl) ethylamino 4-aminophenyl 4-p 3-fluorophenyl) ethyl) amino 4-murylphenyl 2-acetamido-4-P than yodo (2- (3-fluorophenyl) ethyl) amino (please read the Please fill in this page again for the matters needing attention) -83- This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297mm) 520362 A7 B7 V. Description of invention (81) Employees' Cooperatives of Central Bureau of Standards, Ministry of Economic Affairs 4-fluorophenyl 2-amino-4-amino (2- (3-fluorophenyl) ethyl) amino 4-fluorophenyl 4-r (Yl) ethyl) amino 4-fluorophenyl 2-acetamido-4-p than yodo (2- (2-aminophenyl) ethyl) amino 4-fluorophenyl 2-amino- 4-Aminoalkyl (2- (2-fluorophenyl) ethyl) amino 4-fluorophenyl 4-p is more than methyl- (2- (2-pyridyl) ethyl) amino 4- Fluorophenyl 2-Ethylamino 4- 4-p-Hydroxymethyl- (2- (2-pyridyl) ethyl) amino 4-Fluorophenyl 2-amino-4-anhydromethyl- ( 2- (2-pyridyl) ethyl) amino 4-fluorophenyl 4-gadolide (1,1-dimethyl-3-phenyl_propyl) amino 4-phenyl 2-acetamidine Amino-4-pyridyl (U-dimethyl_3-phenyl-propyl) amino 4-fluorophenyl 2-amino-4-amino (1,1-dimethyl-3- Phenylpropyl) amino 4-fluorophenyl 4-p-pyridyl (3- (4-fluorophenyl) -propyl) amino 4-fluorophenyl 2-acetamido-4-pyridine (3- (4-fluorophenyl) -propyl) amino 4-fluorophenyl 2-amino-4-tumino (3- (4-fluorophenyl) -propyl) amino 4- Fluorophenyl 4-r-pyridyl (3- (4-fluorophenyl) -1-methyl-propyl) amino 4-fluorophenyl 2-acetamido-4-pyridyl (3- (4 -mouse Phenyl) -1-methyl-propyl) amino 4-fluorophenyl 2-amino-4-ranyl (3- (4-aminobenzyl) -1-methyl-propyl) amino 4-Fluorophenyl 4-ρ is phenyl (1,1-dimethyl-3- (4-aminobenzyl) -propyl) amino 4-fluorophenyl 2-acetamido-4-ρ Titanyl (1,1-dimethyl-3- (4-fluorophenyl) -propyl) amino 4-fluorophenyl 2-amino-4-ranyl (1,1-dimethyl < -3- (4-fluorophenyl) -propyl) amino 4-fluorophenyl 4-tonyl (3- (2-fluorophenyl) propyl) amino (Please read the note on the back first Please fill in this page for more details) -84- This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297mm) 520362 A7 B7 V. Description of invention (82) 4-Rubberbenzene printed by Employees' Cooperative of Central Standards Bureau of Ministry of Economic Affairs 2-Ethylamido-4-pyridyl (3- (2-fluorophenylpropyl) amino 4-fluorophenyl 2-amino-4_yl (3- (2-fluorophenyl ) -Propyl) amino 4-fluorophenyl 4-tonyl (3-methyl-3-phenyl-propyl) amino 4-fluorophenyl 2-acetamido-4-pyridyl ( 3-methyl-3_phenyl-propyl) amino 4-fluorophenyl 2-amino-4-p dense lake (3-methyl-3-phenylpropyl) amino 4-fluorobenzene 4-Phenyl group (2-methyl-3- Phenyl-propyl) amino 4-fluorophenyl 2-acetamido-4-pyridyl (2-methyl-3-phenyl-propyl) amino 4-fluorophenyl 2-amino- 4-Adenyl (2-methyl; phenyl-propyl) amino 4-fluorophenyl 4-p than yodo (3,3 · dimethylbutyl) amino 4-fluorophenyl 2- Ethylamino-4-p than yodo (3,3 · dimethylbutyl) amino 4-fluorophenyl 2-amino-4-p denselyl (3,3 · dimethylbutyl) ) Amino 4-fluorophenyl 4-p is higher than ydoyl isoamylamino 4-airphenyl 2-acetamido-4-pyridylisopentylamino 4-fluorophenyl 2-amino- 4-Hydroyl isoamylamino 4-fluorophenyl 4-p is higher than ylylamylpentylamino 4-airphenyl 2-acetamido-4-pyridylpentylamino 4-fluorophenyl 2-Amino-4-ylaminopentylamino 4-fluorophenyl 4-p is higher than that of (2,5-dimethyl) pentylamino 4-fluorophenyl 2-acetamido- 4-pyridyl (2,5-dimethyl) pentylamino 4-fluorophenyl 2-amino-4 (4-methyl) pentyl (2,5-dimethyl) pentylamino (please read the back first) Please note this page, please fill out this page) Order -85- This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 520362

B 五、發明説明（83 ) 經濟部中央標準局員工消費合作社印製 4-氣苯基 4-p比淀基 六氫吡畊基 4_氣苯基 2-乙醯:胺基-4-p比淀基 六氫吡畊基 4-氟苯基 2-胺基-4-喃淀基 六氫吡畊基 4-氟苯基 4-p比淀基 (3-(3-氟苯基)_丙基)胺基 4-氟苯基 2-乙醯胺基-4_吡啶基 (3-(3-氟苯基)-丙基)胺基 4-氟苯基 2-胺基-4-喊淀基 (3-(3-氟苯基)-丙基)胺基 苄基 4-p比淀基 3-苯基丙胺基 芊基 4-口比淀基 2-(4-氟苯基)乙胺基 2-p塞吩基 4_p比淀基 3-苯基丙胺基 2-嘧吩基 4-外b淀基 2-(4-氟苯基)乙胺基 環己基 4-口比淀基 3-苯基丙胺基 環己基 4-p比淀基 2_(4-氣苯基)乙胺基 第三丁基 4-p比淀基 3-苯基丙胺基 第三丁基 4-p比淀基 2-(4-氣豕基)乙胺基 4-氟苯基 4-六氫p比淀基 3-苯基丙胺基 4-氣苯基 4-六氫p比淀基 2-(4-鼠苯基)乙胺基 4-氣苯基 4-喊喃基 3-苯基丙胺基 4-氟苯基 4-0瓜喃基 2-(4-氟苯基)乙胺基 苯基 4-p比淀基 3-苯基^-胺^基-丙胺基 4-鼠苯基 4·ρ比淀基 3-苯基-2-胺基-丙胺基 (請先閲讀背面之注意事項再填寫本頁) 訂 -86- 本纸張尺度適用中國國家標準（ CNS ) A4規格（210X 297公釐） 520362B. Description of the invention (83) 4-Phenylphenyl 4-p is printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. Pyridyl hexahydropyridyl 4-fluorophenyl 2-amino-4-aminopyridyl hexahydropyridyl 4-fluorophenyl 4-p bipyridyl (3- (3-fluorophenyl) _ (Propyl) amino 4-fluorophenyl 2-acetamido-4-pyridyl (3- (3-fluorophenyl) -propyl) amino 4-fluorophenyl 2-amino-4- Yodo (3- (3-fluorophenyl) -propyl) aminobenzyl 4-p than Yodo 3-phenylpropylaminofluorenyl 4-oxobido 2- (4-fluorophenyl) ethyl Amino 2-p sedenyl 4-p ratio ylidene 3-phenylpropylamino 2-pyridinyl 4-outside ylidene 2- (4-fluorophenyl) ethylaminocyclohexyl 4-pyridyl 3 -Phenylpropylaminocyclohexyl 4-p than yodoyl 2- (4-Gaphenyl) ethylamino tert-butyl 4-p 2- (4-Arylidene) ethylamino 4-fluorophenyl 4-hexahydrop-pyridyl 3-phenylpropylamino 4-aminophenyl 4-hexaphenyl p-pyridyl 2- (4-rat Phenyl) ethylamino 4-phenyl 4-hexyl 3-phenylpropylamino 4-fluorophenyl 4-0 citranyl 2- (4-fluorophenyl) ethylaminobenzene 4-Pyridyl 3-phenyl ^ -amine ^ yl-propylamino 4-murylphenyl 4-p-pyridyl 3-phenyl-2-amino-propylamino (Please read the precautions on the back first (Fill in this page again) Order-86- This paper size applies to China National Standard (CNS) A4 (210X 297mm) 520362

7 7 A B 五、發明説明（84 ) 經濟部中央標準局員工消費合作社印製 3-氟苯基 4-p比淀基 3-苯基-2-胺基-丙胺基 2-氟苯基 4-p比淀基 3-苯基-2-胺基_丙胺基 4-氯苯基 4-p比淀基 3-本基-2-胺基-丙胺基 3-氯苯基 4-p比淀基 3_本基-2-胺基-丙胺基 2-氯苯基 4-p比淀基 3_苯基-2-胺基-丙胺基 4-甲苯基 4-吡啶基 3-本基-2-胺基-丙胺基 3-甲苯基 4-p比淀基 3-本基-2-胺基-丙胺基 2-甲苯基 4-p比淀基 3-苯基-2-胺基-丙胺基 4·三氟甲基苯基 4-p比淀基 3-苯基_2_胺基-丙胺基 3-三氟甲基苯基 4-p比淀基 3-奉基-2-胺基-丙胺基 2,6--一氣豕基 4-p比淀基 3-苯基-2-胺基-丙胺基 2,6-二甲基苯基 4-p比淀基 3-苯基-2-胺基-丙胺基 2,4-二氯苯基 4-p比淀基 3-本基-2-胺基-丙胺基 2,4-二甲基苯基 4-p比淀基 3-本基-2-胺基-丙胺基 苯基 4-p比淀基 3-苯基·3_胺基-丙胺基 4-氟苯基 4-p比淀基 3-表基-3-胺基-丙胺基 3-氟苯基 4-p比淀基 3-苯基-3-胺基-丙胺基 2-氟苯基 4-p比淀基 3-苯基-3-胺基-丙胺基 4-氯苯基 4-p比淀基 3-苯基丙胺基 3-氯苯基 4-p比淀基 3-苯基-3-胺基-丙胺基 (請先閲讀背面之注意事項再填寫本頁) 訂 -87- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（85 ) 2-氯苯基 4_ρ比淀基 3-苯基_3_胺基-丙胺基 4-甲苯基 4-ρ比淀基 3-本基-3-胺基-丙胺基 3-甲苯基 4-ρ比淀基 3-苯基-3-胺基-丙胺基 2-甲苯基 4-ρ比淀基 3_苯基-3-胺基-丙胺基 4-三氟甲基苯基 4-ρ比淀基 3-本基-3-胺基-丙胺基 3_三氟甲基苯基 4·峨淀基 3-豕基-3-胺基-丙胺基 2,6-二鼠豕基 4-ρ比淀基 3-秦基-3-胺基-丙胺基 2,6-二甲基苯基 4-口比淀基 3-苯基-3-胺基-丙胺基 2,4_二鼠豕基 4-ρ比淀基 3-苯基_3_胺基_丙胺基 2,4-二甲基苯基 4-峨啶基 3·苯基-3-胺基-丙胺基 (請先閲讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 更佳化合物列舉於下文實例。 如此處使用下列術語具有如下定義： ”烷基”單獨或合併使用時，表示直鏈或分支鏈烷基含有較 佳1-15個碳原子（CVCu)，更佳1-8個碳原子（Ci-Cs)，又更 佳1-6個碳原子（Ci-CJ，又更佳1-4個碳原子（CVC4)，又 更佳1-3個碳原子（CVCJ，及最佳1-2個碳原子（CVC2)。 此種基團範例包含甲基，乙基，正丙基，異丙基，正丁基 ，異丁基，第二丁基，第三丁基，戊基，異戊基，己基， 辛基等。 ”羥烷基”單獨或合併使用時，表示如上ΐ義之烷基其中至 少一個氫以經基置換，較佳1 -3個氫以轰基置換，更佳1 -2 個氫以巍基置換，及最佳1個氫以經基置換。此種基團範 -88- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ 297公釐） 經濟部中央標準局員工消費合作社印製 520362 A7 ----- B7 五、發明説明（86 ) ^ 例包含羥甲基，1_，2-羥乙基，，2-，3_羥丙基，n 二羥·2·丙基，1，3-二羥丁基，12,3,4,5,六羥_2_己基等。 π烯基π單獨或合併使用時，表示含1或多個雙键，較佳i _2 個雙键及更佳1個雙鍵之直鏈或分支鏈烴基其含有較佳2_ 15個碳原子（C2-C15)，更佳2-8個破原子（C2-C8)，又更佳 2-6個碳原子（(VC6)，又更佳2_4個碳原子（CrCj，及又更 佳2-3個碳原子（CrC3)。此種烯基範例包含乙烯基，丙缔 基，2-甲基丙烯基，1，4·丁二烯基等。 ”烷氧基"單獨或合併使用時，表示”R-0”型基團其中” R”爲 如上定義之烷基及”0，，爲氧原子。此種烷氧基範例包含甲氧 基，乙氧基，正丙氧基，異丙氧基，正丁氧基，異丁氧基 ，第二丁氧基，第三丁氧基等。 "烷氧羰基”單獨或合併使用時表示”R-O-C(O)-”型基團，其 中” R-0"爲如上定義之烷氧基及” C(O)，，爲羰基。 ”烷氧羰基胺基”單獨或合併使用時表示”R-〇-C(0)-NH-，，型 基團，其中”R-0-C(0)-”爲如上定義之烷氧羰基，其中胺基 可選擇性經取代，例如以烷基，芳基，芳基烷基，環烷基 ，環烷基烷基等取代。 ”烷硫基’’單獨或合併使用時表示”R-S-”型基團，其中”R”爲 如上定義之烷基及”S"爲硫原子。此種烷硫基範例包含甲硫 基’乙硫基’正丙硫基’異丙硫基，正丁硫基，異丁硫基 ，第二丁硫基，第三丁硫基等。 < ’’烷基亞磺醯基”單獨或合併使用時表示”R_S(〇)_”型基團， 其中’’R”爲如上定義之烷基及”S(0)n爲單氧化硫原子。此種 _ -89- 本紙張尺度適用中國國家榡準（CNS ) A4規格（210'〆297公釐） C請先閱讀背面之注意事if再填寫本頁j 訂 經濟部中央標準局員工消費合作社印製 520362 A7 B7 五、發明説明（87 ) 烷基亞磺醯基範例包含甲基亞磺醯基，乙基亞磺醯基，正 丙基亞磺醯基，異丙基亞磺醯基，正丁基亞磺醯基，異丁 基亞續驗基’弟一 丁基亞績SS基，第三丁基亞續酿基等。 ”烷基磺醯基”單獨或合併使用時表示”r-s(o)2-”型基團，其 中”R”爲如上定義之烷基及”S(0)2”爲雙氧化硫原子。此種 烷基磺醯基範例包含曱基亞磺醯基，乙基磺醯基，正丙基 磺醯基，異丙基磺醯基，正丁基磺醯基，異丁基磺醯基， 第二丁基磺醯基，第三丁基磺醯基等。 ”芳基”單獨或合併使用時，表示苯基或聯苯基其選擇性稠 合苯環或稠合雜環及其選擇性以一或多個選自下列之取代 基取代：燒基，燒氧基，_原子，護基，胺基，疊氮基， 硝基，氰基，鹵烷基，羧基，烷氧羧基，環烷基，烷醯胺 基，醯胺基，脒基，烷氧羰基胺基，N-烷基脒基，烷基胺 基，二烷基胺基，胺基烷基，烷基胺基烷基，二烷基胺基 烷基，N-烷基醯胺基，N，N-二烷基醯胺基，芳基烷氧羰基 胺基，燒硫基，燒基亞續si基，燒基橫酸基，氧基等。芳 基範例有苯基，鄰甲苯基，4-甲氧苯基，2-(第三丁氧）苯 基，3-甲基-4-甲氧苯基，2-CF3-苯基，2-氟苯基，2-氯苯 基，3_硝基苯基，3-胺基苯基，3-乙醯胺基苯基，2-胺基 -3-(胺基甲基）苯基，6_甲基-3-乙醯胺基苯基，6-甲基-2-胺基苯基，6-甲基-2,3-二胺基苯基，2-胺基-3-甲基苯基 ，4,6-二甲基-2-胺基苯基，4-羥苯基，、3-甲基-4-羥苯基 ，4-(2-甲氧苯基）苯基，2-胺基-1-莕基，2-莕基，3-胺基 -2 -莕基’ 1-甲基-3-胺基-2 -荅基，2,3 -二胺基-1-奈基’ ___ -90- 本纸張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） (請先閱讀背面之注意事項再填寫本頁) 訂 #1 經濟部中央標準局員工消費合作社印製 520362 A7 ----—-— —__°7_____ 五、發明説明（88 ) —- 4,8-二甲乳-2-奈基等。 ’’芳烷基”及”芳基烷基”單獨或合併使用時表示如上定義之 烷基，其中至少一個氫原子，較佳丨_2個氫原子由如上定 義之芳基取代，例如苄基，i_，2_苯基乙基，二苄基甲基 ，短苯基甲基，甲基苯基甲基，二苯基甲基，二氯苯基甲 基，4_甲氧苯基甲基等。 芳基坑氧基”單獨或合併使用時表示如上定義之燒氧基其 中土少一個氣原子，較佳1_2個氫原子由如上定義之芳基 取代，例如芊氧基，1-，2-苯基乙氧基，二苄基甲氧基， 幾苯基甲氧基，甲基苯基甲氧基，二氯苯基甲氧基，4_甲 氧苯基甲氧基等。 ”芳基烷氧羰基”單獨或合併使用時表示”R-0_c(〇)_”型基團 ’其中"R-0-"爲如上定義之芳基烷氧基及、C(〇)-，，爲羰基。 ”烷醯基”單獨或合併使用時表示”r_C(0)_”型基團，其中”R” 爲如上定義之烷基及” -C(O)-，’爲羰基。烷醯基範例包含乙醯 基’二氟乙醯基，護乙醯基，丙醯基，丁 g盔基，戊醯基， 4-甲基戊醯基等。 "烷醯胺基”單獨或合併使用時表示”r_C(0)-NH-”基團，其 中”R-C(O)·”爲如上定義之烷醯基，其中胺基可選擇性經取 代例如以烷基，芳基，芳基烷基，環烷基，環烷基烷基等 取代。 ”胺基羰基”單獨或合併使用時表示胺基取代羰基（胺基甲 醯基），其中胺基可選擇性經一-或二-取代，例如以烷基， 芳基，芳基烷基，環烷基，環烷基烷基，烷醯基，烷氧羧 -91 - 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） (請先閲讀背面之注意事項再填寫本頁} -訂 經濟部中央標準局員工消費合作社印製 520362 A7 --—------ B7 五、發明説明（89 ) 基’芳基烷氧羰基等取代。 月女基磺醯基’’單獨或合併使用時表示胺基取代磺醯基。 苯駢”單獨或合併使用時表示衍生自苯之二價基團C6h4 = 。’’苯耕稠合”形成環系其中苯於環烷基或芳基共用兩個碳 ’例如四氫蓁等。 雙％”用於此處表示兩個稠合環系如莕基及^卡巴啉基（p_ carbolmyl)，及取代環系例如聯苯基，苯基吡啶基及二苯基 六氫峨p井基。 %烷基”單獨或合併使用時表示飽和或部份飽和，較佳一 個雙鍵，單5幕、雙環或三環碳環系烷基，較佳爲單環，含 有車父佳5-12個碳原子（C5_Ci2)，更佳5_1〇個碳原子（CyCi〇) ，又更佳5_7個碳原子（Cs-C7)，其可爲選擇性苯駢稠合或 雜環骄稠合其可選擇性如就芳基定義所述經取代。此種環 烷基乾例包含環戊基，環己基，二羥環己基，伸乙基二氧 環5基，環庚基，/V氫莕基，四氫莕基，八氫喹啉基，二 甲氧四氫奈基，2,3_二氫·1Η·茚基，吖雙環[3.2.1]辛基等。 "雜原子”表示氮，氧及硫雜原子。 ”、雜環駢稠合”形成一個環系其巾5-6㈣成員之雜環基或 雜万基與環烷基或芳基共用兩個碳，例如吲哚，異喹啉， 四氫喹啉，亞甲基二氧苯等。 、 ”雜環表示飽和或部份未飽和，較佳含一個雙鍵之單環 或又衣幸义佳單¥系雜環基含有至少i個 <，較佳^至4個， =佳1至3個’又更佳卜2個氮’氧或硫原子環成員及各個 %較佳含3_8個環成員，更佳各個環含％8個環成員，及又 本紙張尺度適用中國 (請先閲讀背面之注意事項再填寫本頁) 、1Τ -^wl. -92- 520362 經濟部中央標準局員工消費合作社印製 A7 __ B7 五、發明説明（90 ) 更佳各個環含5-6個環成員。”雜環基”包含硫環成員之颯及 亞砜衍生物及第三氮環成員之N-氧化物，及碳環系稠合， 較佳3-6個環碳原子及更佳5-6個環碳原子，及苯駢稠合環 系。”雜環基”選擇性於至少一個，較佳1-4個，更佳1-3個 ，又更佳1 -2個碳原子由下列各基取代：鹵原子，燒基， 燒氧基，羥基’氧基，硫基，芳基，芳基燒基，雜芳基， 雜芳基燒基，脒基，N-燒基脒基，垸氧羰基胺基，燒基續 醯胺基等，及/或第二氮原子由輕基，燒基，芳基燒氧羧基 ’ k si：基’抗乳談基’雜方基纪基’芳基或芳基燒基取代 。更佳，”雜環基”單獨或合併使用時爲每個環含5-8個環成 員之單環或雙環飽和雜環系基團，其中1至3個環成員爲 氧’硫或氮雜原子’其遂擇性爲部份未飽和或苯胼網合及 選擇性由1-2個氧基或硫基取代。此種雜環基範例包含叶匕 咯啶基，六氫吡啶基，六氫吡畊基，嗎p林基，嘍嗎琳基， 4-苄基-六氫吡畊-1-基，嘧啶基，四氫呋喃基，吡唑淀酮基 ，吡唑啉基，嗒畊酮基，吡咯啶酮基，四氲嘧吩基及其亞 颯及颯衍生物，2,3 -二氫啕哚基，四氫喹啉基，丨2 3心 四氫異喹啉基，1，2,3,4-四氫-1-氧基異喹啉基，2,3_二氣 苯駢呋喃基，苯駢哌喃基，亞曱基二氧苯基，伸乙基二氧 苯基等。 1 ’’雜芳基”表示單環或雙環，較佳單環芳族雜環基，本有5 少一個，較佳1-4個，更佳1-3個，又更佳1-2個氮，氧或 硫原子環成員，其於各環較佳含5-6個環成員，其爲選擇 性飽和碳環稠合，較佳3-4個碳原子（CrC4)而形成5_6個環 -93 ---------------丁________ (請先閱讀背面之注意事項再填寫本頁) 表纸張尺度適用中國國家標準（CNS ) Μ規格（21G><297公着 520362 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（91 ) 成員環及其選擇性如前就芳基定義所述經取代。雜芳基範 例包含咪唑基，1 -芊氧羰基咪唑-4-基，吡咯基，说咬基， 吡啶基，3-(2-甲基）吡啶基，3-(4-三氟甲基）吡啶基，嘧啶 基，5-(4-三氟甲基）嘧啶基，吡畊基，***基，呋喃基， p塞吩基，崎唑基，邊唑基，峭哚基，4 4基，5,6,7,8_四氫 1(1奎淋基，5，6，7，8 -四氫異峻淋基，邊崎淋基，苯駢p塞岭基， 苯駢咬喃基，苯駢咪峻基，苯駢π号峻基等。 ’’雜芳烷基”及”雜芳基烷基”單獨或合併使用時表示如上定 義之芳基，其中至少一個氫原子，較佳1-2個氫原子由一 個如上定義之雜芳基置換，例如3 -咬喃基丙基，2 - p比洛基 丙基，氯喹啉基曱基，2-嘧吩基乙基，吡啶基甲基，i•咪 唑基乙基等。 ”卣素”及” _原子”單獨或合併使用時表示氟，氯，溴或碘。 ••鹵fe基”單獨或合併使用時表示如上定義之燒基其中至少 一個氫原子，較佳1-3個氫原子由鹵基置換，更佳氟或氯 。此種函烷基範例包含1，1，1 ·三氟乙基，氯甲基，丨·溴乙 基，氟甲基，一氟甲基，二氟甲基，武（三氟甲基）甲基等。 ”4(3H)-嘧啶酮”（A)及”4-羥嘧啶”（B)爲同種化合物之兩種互 變異構物名稱可互換使用。預期使用其中一者名稱包本另 一者。 ' -94- 本紙張尺度適用巾目g[家標準（CNS-) A4規格（210X297^5^ 訂 ~ (請先閱讀背面之注意事項再填寫本頁) 520362 A7 B7 五、發明説明（92 ) ------------7 7 AB V. Description of Invention (84) 3-Fluorophenyl 4-p printed by 3-fluorophenyl 4-p than 3-phenyl-2-amino-propylamino 2-fluorophenyl 4- p-pyridyl 3-phenyl-2-amino-propylamino 4-chlorophenyl 4-p-pyridyl 3-benzyl-2-amino-propylamino 3-chlorophenyl 4-p-pyridyl 3-benzyl-2-amino-propylamino 2-chlorophenyl 4-p than yodoyl 3-phenyl-2-amino-propylamino 4-tolyl 4-pyridyl 3-benzyl-2- Amino-propylamino 3-tolyl 4-p ratio ylidene 3-benzyl-2-amino-propylamino 2-tolyl 4-p ratio ylidene 3-phenyl-2-amino-propylamino 4 · Trifluoromethylphenyl 4-p ratio ylidene 3-phenyl-2-amino-propylamino 3-trifluoromethylphenyl 4-p ratio ylidene 3-pentyl-2-amino-propylamine Phenyl 2,6--monocarbamoyl 4-p than yodoyl 3-phenyl-2-amino-propylamino 2,6-dimethylphenyl 4-p yodoyl 3-phenyl-2-amine Propyl-propylamino 2,4-dichlorophenyl 4-p than yodoyl 3-benzyl-2-amino-propylamino 2,4-dimethylphenyl 4-p pyridyl 3-benzyl- 2-amino-propylaminophenyl 4-p ratio ylidene 3-phenyl · 3-amino-propylamino 4-fluorophenyl 4-p ratio ylidene 3-epi-3-amino-propylamino 3-fluorobenzene 4-p ratio yodoyl 3-phenyl-3-amino-propylamino 2-fluorophenyl 4-p ratio yodoyl 3-phenyl-3-amino-propylamino 4-chlorophenyl 4-p ratio Yodo 3-phenylpropylamino 3-chlorophenyl 4-p than Yodo 3-phenyl-3-amino-propylamine (Please read the precautions on the back before filling this page) Order -87- This page Standards apply to Chinese National Standard (CNS) A4 specifications (210X 297 mm) 520362 A7 B7 V. Description of the invention (85) 2-Chlorophenyl 4_ρ ratios 3-phenyl_3_amino-propylamino 4-toluene 4-Phenyl 4-phenyl 3-benzyl-3-amino-propylamino 3-tolyl 4-phenyl 4-phenyl 3-phenyl-3-amino-propylamino 2-tolyl 4-p 3-Phenyl-3-amino-propylamino 4-trifluoromethylphenyl 4-r-pyridyl 3-benzyl-3-amino-propylamino 3-trifluoromethylphenyl Yodoyl 3-fluorenyl-3-amino-propylamino 2,6-dimurinolyl 4-ρ ratio Yodoyl 3-qinyl-3-amino-propylamino 2,6-dimethylphenyl 4 -Hydroxyl 3-phenyl-3-amino-propylamino 2,4-dimuridine 4-ρ bixyl 3-phenyl-3-amino-propylamino 2,4-dimethyl Phenyl 4-eridyl 3-phenyl-3-amino-propylamino (Please read the precautions on the back first Complete this page) Ministry of Economic Affairs Bureau of Standards staff printed better consumer cooperatives compounds listed in the examples below. As used herein, the following terms have the following definitions: "Alkyl" when used alone or in combination means that a straight or branched chain alkyl group contains preferably 1-15 carbon atoms (CVCu), more preferably 1-8 carbon atoms (Ci -Cs), and more preferably 1-6 carbon atoms (Ci-CJ, more preferably 1-4 carbon atoms (CVC4), and more preferably 1-3 carbon atoms (CVCJ, and optimally 1-2 Carbon atom (CVC2). Examples of such groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, second butyl, third butyl, pentyl, isopentyl , Hexyl, octyl, etc. "Hydroxyalkyl" when used alone or in combination means that at least one hydrogen of the above-mentioned alkyl is replaced by a radical, preferably 1 to 3 hydrogens are replaced by a radical, more preferably 1-2 Each hydrogen is replaced by a Wei group, and the best one is replaced by a hydrogen group. This type of group Fan -88- This paper size applies to China National Standard (CNS) A4 specifications (210 × 297 mm) Employees of the Central Standards Bureau of the Ministry of Economic Affairs Printed by the Consumer Cooperative 520362 A7 ----- B7 V. Description of the invention (86) ^ Examples include hydroxymethyl, 1-, 2-hydroxyethyl, 2-, 3-hydroxypropyl, n-dihydroxy · 2 · Propyl, 1,3- Hydroxybutyl, 12,3,4,5, hexahydroxy-2-hexyl, etc. When used independently or in combination, πalkenylπ contains 1 or more double bonds, preferably i _2 double bonds and more preferably 1 A straight or branched hydrocarbon group with two double bonds has preferably 2-15 carbon atoms (C2-C15), more preferably 2-8 broken atoms (C2-C8), and more preferably 2-6 carbon atoms (( VC6), and more preferably 2-4 carbon atoms (CrCj, and still more preferably 2-3 carbon atoms (CrC3). Examples of such alkenyl groups include vinyl, allyl, 2-methacryl, 1,4 · Butadienyl, etc. "Alkoxy" when used alone or in combination means "R-0" type groups, where "R" is an alkyl group as defined above and "0" is an oxygen atom. Such an alkane Examples of oxy include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, second butoxy, third butoxy, etc. " Alkoxycarbonyl "" When used alone or in combination, it represents a "ROC (O)-" type group, where "R-0 " is an alkoxy group as defined above and" C (O) "is a carbonyl group." Alkoxycarbonylamino "alone Or combined use means "R-O-C (0) -NH- ,, type group, where" R-0-C (0)-"is an alkoxycarbonyl group as defined above, wherein the amine group can be optionally substituted, for example, with alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, etc. "Alkylthio" when used alone or in combination means a "RS-" type group, where "R" is an alkyl group as defined above and "S " is a sulfur atom. Examples of such alkylthio groups include methylthio 'Ethylthio' n-propylthio 'isopropylthio, n-butylthio, isobutylthio, second butylthio, third butylthio, and the like. < `` Alkylsulfinyl '' when used alone or in combination means a "R_S (〇) _" type group, where "R" is an alkyl group as defined above and "S (0) n is a sulfur monoxide Atomic. Such _ -89- This paper size applies to China National Standards (CNS) A4 specifications (210'〆297 mm) C Please read the notes on the back if you want to fill out this page. J Staff of Central Bureau of Standards, Ministry of Economic Affairs Printed by the Consumer Cooperative 520362 A7 B7 V. Description of the Invention (87) Examples of alkylsulfinyl sulfonyl include methylsulfinyl sulfonyl, ethylsulfinyl sulfinyl, n-propylsulfinyl sulfinyl, isopropylsulfinyl sulfinyl Group, n-butylsulfinylene, isobutylidene group, di-dibutylene group, SS group, third butylidene group, etc. "Alkylsulfonyl group" means when used alone or in combination. "Rs (o) 2-" type group, where "R" is an alkyl group as defined above and "S (0) 2" is a sulfur dioxide atom. Examples of such alkylsulfonyl groups include sulfenylsulfinium , Ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, second butylsulfonyl, third butylsulfonyl Base, etc. " "When used alone or in combination, it means phenyl or biphenyl which is optionally fused to a benzene ring or a fused heterocyclic ring and its selectivity is substituted by one or more substituents selected from the group consisting of: _ Atom, protecting group, amine group, azido group, nitro group, cyano group, haloalkyl group, carboxyl group, alkoxycarboxyl group, cycloalkyl group, alkylamino group, fluorenylamino group, fluorenyl group, alkoxycarbonylamine , N-alkylfluorenyl, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, N-alkylfluorenylamino, N, N-dialkylfluorenylamino, arylalkoxycarbonylamino, thiothio, thioalkylene, thioalkyl, oxy, etc. Examples of aryl include phenyl, o-tolyl, 4 -Methoxyphenyl, 2- (third butoxy) phenyl, 3-methyl-4-methoxyphenyl, 2-CF3-phenyl, 2-fluorophenyl, 2-chlorophenyl, 3- Nitrophenyl, 3-aminophenyl, 3-acetamidophenyl, 2-amino-3- (aminomethyl) phenyl, 6-methyl-3-acetamidophenyl , 6-methyl-2-aminophenyl, 6-methyl-2,3-diaminophenyl, 2-amino-3-methylphenyl, 4,6-dimethyl-2- Aminophenyl, 4-hydroxy , 3-methyl-4-hydroxyphenyl, 4- (2-methoxyphenyl) phenyl, 2-amino-1-fluorenyl, 2-fluorenyl, 3-amino-2 -fluorenyl Base '1-methyl-3-amino-2 -fluorenyl, 2,3 -diamino-1-naphthyl' ___ -90- This paper size applies to China National Standard (CNS) A4 (210X297) (%) (Please read the notes on the back before filling this page) Order # 1 Printed by the Central Consumers Bureau of the Ministry of Economic Affairs, Consumer Cooperatives 520362 A7 ----—- — —__ ° 7 _____ V. Description of Invention (88) —- 4,8-dimethyl milk-2-naphthyl and the like. "Aralkyl" and "arylalkyl" when used alone or in combination denote an alkyl group as defined above, wherein at least one hydrogen atom, preferably two hydrogen atoms, is substituted by an aryl group as defined above, such as benzyl , I_, 2-phenylethyl, dibenzylmethyl, short phenylmethyl, methylphenylmethyl, diphenylmethyl, dichlorophenylmethyl, 4-methoxyphenylmethyl Etc. "Aryloxy" alone or in combination means that the alkoxy group as defined above has one less gas atom, preferably 1_2 hydrogen atoms are replaced by an aryl group as defined above, such as fluorenyloxy, 1-, 2 -Phenylethoxy, dibenzylmethoxy, quinylmethoxy, methylphenylmethoxy, dichlorophenylmethoxy, 4-methoxyphenylmethoxy, and the like. "Arylalkoxycarbonyl" when used alone or in combination means a "R-0_c (〇) _" group 'wherein " R-0- " is an arylalkoxy group as defined above, and C (〇) -, Is a carbonyl group. "Alkyl" represents a group of the "r_C (0) _" type when used alone or in combination, where "R" is an alkyl group as defined above and "-C (O)-," is a carbonyl group. Examples of alkyl groups include Ethyl'difluoroethenyl, ethynyl, propionyl, butyl, pentamyl, 4-methylpentyl, etc. " Alkylamino " when used alone or in combination "R_C (0) -NH-" group, wherein "RC (O) ·" is an alkylamino group as defined above, wherein the amine group can be optionally substituted, for example, with alkyl, aryl, arylalkyl, ring Alkyl, cycloalkylalkyl and the like. "Aminocarbonyl" when used alone or in combination means an amine-substituted carbonyl (aminomethyl) group, wherein the amine group can be optionally mono- or di-substituted, for example, with alkyl, aryl, arylalkyl, Cycloalkyl, cycloalkylalkyl, alkylfluorenyl, alkoxycarboxyl-91-This paper size applies to China National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling in this page} -Ordered by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs to print 520362 A7 ----------- B7 V. Description of the invention (89) Substituted by 'aryl alkoxycarbonyl group, etc. Cryl sulfonyl' ' Or when used in combination, it means that the amine group is substituted for sulfonyl. "Benzene" when used alone or in combination means that the divalent group derived from benzene is C6h4 =. "Benzene is fused" to form a ring system in which benzene is in a cycloalkyl or aromatic group. Groups share two carbons, such as tetrahydrofluorene, etc. Bi% "is used herein to indicate two fused ring systems such as fluorenyl and p-carbolmyl, and substituted ring systems such as biphenyl, phenyl Pyridyl and diphenylhexahydropyryl.% Alkyl "when used alone or in combination means saturated or partially saturated , Preferably a double bond, a single 5 act, bicyclic or tricyclic carbocyclic alkyl group, preferably a single ring, containing 5-12 carbon atoms (C5_Ci2), more preferably 5-10 carbon atoms (CyCi 〇), and more preferably 5-7 carbon atoms (Cs-C7), which may be selectively benzene fused or heterocyclic fused which may optionally be substituted as described in the definition of aryl. Such cycloalkyl Dry examples include cyclopentyl, cyclohexyl, dihydroxycyclohexyl, ethoxyl 5-oxo, cycloheptyl, / Vhydrofluorenyl, tetrahydrofluorenyl, octahydroquinolinyl, dimethoxytetrahydro Nyl, 2,3_dihydro · 1Η · indenyl, acridine bicyclic [3.2.1] octyl, etc. " Heteroatom " means nitrogen, oxygen, and sulfur heteroatoms. &Quot; Heterocycle fused to form one The heterocyclic group or heterowanyl group of the member of the ring system 5-6㈣ shares two carbons with the cycloalkyl or aryl group, such as indole, isoquinoline, tetrahydroquinoline, methylene dioxobenzene, etc. "Heterocyclic ring means saturated or partially unsaturated, preferably a single ring containing a double bond or a Ying Yijia single ¥ heterocyclic group contains at least i <, preferably ^ to 4, = 佳 1 to 3 'and better 2 nitrogen' oxygen or sulfur atoms And each% preferably contains 3_8 ring members, more preferably each ring contains% 8 ring members, and the paper size is applicable to China (please read the precautions on the back before filling this page), 1T-^ wl. -92 -520362 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 __ B7 V. Description of the invention (90) It is better that each ring contains 5-6 ring members. "Heterocyclyl" includes the sulfur ring members and sulfoxide derivatives And the N-oxide of the third nitrogen ring member, and a carbocyclic ring system are fused, preferably 3-6 ring carbon atoms and more preferably 5-6 ring carbon atoms, and a phenylhydrazone fused ring system. " Is selected from at least one, preferably one to four, more preferably one to three, and more preferably one to two carbon atoms are substituted by the following groups: halogen atom, alkyl group, alkyloxy group, hydroxy'oxy group Group, thio group, aryl group, aryl alkyl group, heteroaryl group, heteroaryl alkyl group, fluorenyl group, N-alkyl fluorenyl group, fluorenyloxycarbonylamino group, carbamoyl group and the like, and / or The second nitrogen atom is substituted by a light group, an alkyl group, an arylalkyloxy carboxyl group'ksi: group, an anti-lactalyl group, a heterocyclyl group, an aryl group, or an arylalkyl group. More preferably, "heterocyclyl" when used alone or in combination is a monocyclic or bicyclic saturated heterocyclic group containing 5 to 8 ring members per ring, of which 1 to 3 ring members are oxygen 'sulfur or aza The atom's selectivity is partially unsaturated or phenylhydrazone networked and optionally substituted by 1-2 oxy or thio groups. Examples of such heterocyclyls include pyridyl, hexahydropyridyl, hexahydropyridyl, morpholinyl, morpholinyl, 4-benzyl-hexahydropyridin-1-yl, pyrimidinyl , Tetrahydrofuranyl, pyrazolidinyl, pyrazolinyl, dacrotonyl, pyrrolidinyl, tetrapyrimidinyl and its fluorene and fluorene derivatives, 2,3-dihydrofluorinyl, tetra Hydroquinolinyl, 2 3-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydro-1-oxyisoquinolinyl, 2,3_digas benzofuranyl, benazepine Uranyl, fluorenylene dioxyphenyl, ethylene dioxyphenyl and the like. 1 "Heteroaryl" means monocyclic or bicyclic, preferably monocyclic aromatic heterocyclic group, which has 5 less one, preferably 1-4, more preferably 1-3, and more preferably 1-2 Nitrogen, oxygen, or sulfur atom ring members, which preferably contain 5-6 ring members in each ring, which are fused with a selectively saturated carbocyclic ring, preferably 3-4 carbon atoms (CrC4) to form 5-6 rings- 93 --------------- 丁 ________ (Please read the notes on the back before filling out this page) The paper size of the table is applicable to the Chinese National Standard (CNS) M specification (21G > < 297 Publication 520362 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the Invention (91) The member ring and its selectivity are substituted as described above for the definition of aryl. Examples of heteroaryl groups include imidazolyl, 1- Oxocarbonyl imidazol-4-yl, pyrrolyl, pyridyl, pyridyl, 3- (2-methyl) pyridyl, 3- (4-trifluoromethyl) pyridyl, pyrimidinyl, 5- (4 -Trifluoromethyl) pyrimidinyl, pyrimidinyl, triazolyl, furanyl, p-secenyl, azazolyl, oxazolyl, adolyl, 4 4 -yl, 5, 6, 7, 8-tetrayl Hydrogen 1 (1 quinolyl, 5,6,7,8 -tetrahydroisopentyl, bisakilyl, benzene Sellingyl, benzamidine, benzamidine, benzamidine, etc. "Heteroaralkyl" and "heteroarylalkyl" when used alone or in combination represent an aryl group as defined above Where at least one hydrogen atom, preferably 1-2 hydrogen atoms, is replaced by a heteroaryl group as defined above, such as 3-alanylpropyl, 2-p-pyrrolylpropyl, chloroquinolinylfluorenyl, 2 -Pyramidylethyl, pyridylmethyl, i • imidazolylethyl, etc. “Houdin” and “_atom” when used alone or in combination represent fluorine, chlorine, bromine or iodine. Or when used in combination, it means that at least one of the hydrogen atoms of the alkyl group as defined above, preferably 1-3 hydrogen atoms are replaced by a halogen group, more preferably fluorine or chlorine. Examples of such alkyl groups include 1,1,1 · trifluoro Ethyl, chloromethyl, bromoethyl, fluoromethyl, monofluoromethyl, difluoromethyl, mar (trifluoromethyl) methyl, etc. "4 (3H) -pyrimidinone" (A) And "4-Hydroxypyrimidine" (B) is the name of two tautomers of the same compound used interchangeably. It is expected that one of the names will be used to encapsulate the other. '-94- Towel g [Home Standard (CNS-) A4 Specification (210X297 ^ 5 ^ Order ~ (Please read the precautions on the back before filling in this page) 520362 A7 B7 V. Invention Description (92) -------- ----

(A)(A)

OHOH

經濟部中央標準局員工消費合作社印製Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs

N (B) ’’藥理可接受性鹽"表示藉習知 丁+又策備之鹽且歲f農人Λ 眾所周知。”藥理可接受性鹽， · 匕口典機及有機酸之鹼性鹽 ，包含但和僅限於氫氯酸，氯溪 4 /吳鮫，石瓜鉍，磷酸，甲烷磺 故，乙烷^ ，頻果酸，乙醢 首 ^ A G鲛，卓，酒石酸，檸檬酸， '魬’反丁烯-酸’ 丁二酸，順丁烯二酸，水楊酸，苯甲 酸’苯乙酸’扁桃酸等。當本發明化合物包含一個酸官能 基如羧基時，羧基之適當醫藥可接受性陽離子對爲業界人 士眾所周知且包含鹼，鹼土，銨，第四銨陽離子等。至於，， 藥理可接受性鹽”之其它範例參見後文及Berge “ al” J. Pharm. Sci. 66，1 (1977) 〇 ”細胞激素”表示可影響其它細胞功能之分泌蛋白質，特別 有關免疫系統細胞或發炎反應細胞間之交互作用之調控。 細胞激素範例包含但非僅限於介白素l(IL-l)，較佳IL-Ιβ ，介白素6(IL-6)，介白素8(IL_8)及TNF，較佳TNF-α(腫 瘤壞死因子a)。 ”TNF，IL-1，IL-6，及/或IL-8媒介疾病或疾病狀態”表 示全部疾病狀態其中TNF，IL-1，IL_6，及/或il-8經由 TNF，IL-1，IL-6，及/或 IL-8 本身，或經由 TNF，IL-1 -95- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） (請先閲讀背面之注意事項再填寫本頁)N (B) 'Pharmacologically acceptable salt' means borrowing the knowledge of Ding + and prepared salt and the well-known farmer Λ is well known. Pharmacologically acceptable salts, · Alkaline salts of daggers and organic acids, including but not limited to hydrochloric acid, Chlorine 4 / Wushen, Shiya bismuth, phosphoric acid, methanesulfonium, ethane ^, Phenolic acid, Acetyl succinate ^ AG 鲛, Zhuo, tartaric acid, citric acid, '魬' transbutene-acid 'succinic acid, maleic acid, salicylic acid, benzoic acid' phenylacetic acid 'mandelic acid, etc. When the compound of the present invention contains an acid functional group such as a carboxyl group, a suitable pharmaceutically acceptable cation pair of the carboxyl group is well known to those skilled in the art and contains a base, alkaline earth, ammonium, a fourth ammonium cation, etc. As for, pharmacologically acceptable salts " For other examples, see below and Berge "al" J. Pharm. Sci. 66, 1 (1977). "Cytohormone" means a secreted protein that can affect other cell functions, especially the interaction between immune system cells or inflammatory response cells. Regulation of role. Examples of cytokines include, but are not limited to, interleukin-1 (IL-1), preferably IL-1β, interleukin-6 (IL-6), interleukin-8 (IL_8) and TNF, preferably TNF-α ( Tumor necrosis factor a). "TNF, IL-1, IL-6, and / or IL-8-mediated diseases or disease states" means all disease states in which TNF, IL-1, IL-6, and / or il-8 pass through TNF, IL-1, IL -6, and / or IL-8 itself, or via TNF, IL-1 -95- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page )

520362 A7 B7 五、發明説明（93 ，IL-6，及/或IL-8謗使釋放另一種細胞激素扮演某種角 色。例如，其中IL-1扮演主要角色的il- 1生產或作用係由 於TNF的結果，則該疾病狀態視爲有TNF媒介。 f’離去基”表示易有親核基團置換之基，例如胺，硫醇或醇 親核基團。此種離去基爲業界眾所周知。離去基範例包含 但非限於N-羥丁二醯亞胺，N-羥苯駢***，鹵化物，三氟 甲烷磺酸鹽，甲苯磺酸鹽等。較佳離去基於適當之處敘述。 ’’保護基’’通常表示業界眾所周知用於防止特選的反應基如 羧基，胺基，羥基，醜基等進行非期望的反應，例如親核 、親電子、氧化、還原等反應。較佳保護基於適當之處説 明。胺基保護基範例包含但非僅限於芳基烷基，取代芳基 烷基，環烯基烷基及取代環烯基烷基，烯丙基，取代晞丙 基，醯基，烷氧羰基，芳基烷氧羰基，矽烷基等。芳基烷 基範例包含但非僅限於苄基，鄰甲基；基，三苯甲基及二 苯甲基，其可選擇性以_原子，烷基，烷氧基，羥基，硝 基，醯胺基，醯基等取代，及鹽如鳞鹽及銨鹽。芳基範例 包含苯基，萘基，四氫茚基，蔥基，9_(9_苯基芴基），菲 基，1，2,4,5-四甲基苯基等。較佳含6-1〇碳原子之環烯基 坑基或取代環烯基烷基範例包含但非僅限於環己烯基甲基 等。適當酸基，烷氧羰基及芳基烷氧羰基包含芊氧羰基， 第三丁氧羰基，異丁氧羰基，苯甲醯基，取代苯甲醯基， 丁醒基’乙醯基，三氟乙醯基，三氯乙醯基，酞醯基等。 保護基混合物可用於保護相同胺基，例如第一胺基可由芳 基坑基及芳基坑氧羰基保護。胺基保户基也可與其附接之 -96- 本紙張尺度通用甲國國冢標準（CNS ) A4規格（21〇χ 297公釐） (請先閱讀背面之注意事項再填寫本頁) 、-口 經濟部中央標準局員工消費合作社印製 520362 經濟部中央標隼局員工消費合作社印製 A7 B7 五、發明説明（94 ) II形成雜環系環，例如1，2 -武（亞甲基）苯，g太二酿亞胺基， 丁二醯亞胺基，順丁烯二醯亞胺基等，及此處雜芳基又可 包含w比鄰芳基或環貌基環。此外，雜環基可經一 _，二_或 三-取代如硝基酞二醯亞胺基。胺基也可經由形成加成鹽， 如鹽酸，甲苯磺酸，三氟乙酸等保護不進行非期望的反應 ，例如氧化反應。多種胺基保護基也適合保護羧基，經基 及鏡基。例如，芳基烷基。烷基亦爲保護羥基及鲩基之適 當基’如第三丁基。 石夕烷基保護基爲選擇性由一個或多個烷基，芳基及芳基 燒基取代之矽原子。適當矽烷基保護基包含但非僅限於三 甲基矽烷基，三乙基矽烷基，三異丙基矽烷基，第三丁基 二甲基矽烷基，二甲基苯基矽烷基，^—貳（二甲基矽烷基 )苯，1，2-貳（二甲基矽烷基）乙烷及二苯基甲基矽烷基。胺 基矽烷化反應產生一-或二-矽烷基胺基。胺基醇化合物矽 坑化反應獲得Ν，Ν，0-三矽烷基衍生物。由矽烷基醚官能基 去除矽烷基官能基易使用例如金屬氫氧化物或氟化銨反應 劑，呈各別反應步驟或於與醇基反應過程中原地處理達成 。適當矽烷化劑，例如三甲基矽烷基氯，第三丁基二甲基 矽烷基氯，苯基二甲基矽烷基氯，二苯基甲基矽烷基氯或 其與咪唑或DMF之組合產物。胺之矽烷化及矽烷基保護基 去除方法爲業界人士眾所周知。此等胺衍生物由對應胺基 酸，胺基酸醯胺或胺基酸酯之製法亦爲有機化學劑，包含 胺基酸/胺基酸酯或胺基醇化學界人士眾所周知。 保護基可於不會影響分子其餘部份之條件下進行。此等 本紙張尺度適用中國國家標缚r^ CNS ) 訂 ~ (請先閲讀背面之注意事項再填寫本頁) -97- -CRxRy- -NRxRy520362 A7 B7 V. Description of the invention (93, IL-6, and / or IL-8 liberates the release of another cytokine to play a certain role. For example, IL-1 production or action in which IL-1 plays a major role is due to As a result of TNF, the disease state is considered to have a TNF mediator. "F 'leaving group" means a group that is prone to be replaced by a nucleophilic group, such as an amine, thiol or alcohol nucleophilic group. Such leaving groups are in the industry It is well known that examples of leaving groups include, but are not limited to, N-hydroxysuccinimide, N-hydroxybenzotriazole, halide, trifluoromethanesulfonate, toluenesulfonate, etc. The preferred leaving is based on the appropriate The "protecting group" generally means that it is well-known in the industry to prevent selected reactive groups such as carboxyl, amine, hydroxyl, and ugly groups from performing undesired reactions, such as nucleophilic, electrophilic, oxidation, reduction and other reactions. Preferred protection is based on where appropriate. Examples of amine protecting groups include, but are not limited to, arylalkyl, substituted arylalkyl, cycloalkenylalkyl and substituted cycloalkenylalkyl, allyl, substituted propylpropyl Alkyl, fluorenyl, alkoxycarbonyl, arylalkoxycarbonyl, silyl, etc. Examples of arylalkyl include, but are not limited to, benzyl, o-methyl; phenyl, trityl, and benzhydryl, which can optionally include _ atom, alkyl, alkoxy, hydroxyl, nitro, and fluorene Substitutes such as amine, fluorenyl, and salts such as scale and ammonium. Examples of aryl include phenyl, naphthyl, tetrahydroindenyl, allium, 9- (9-phenylfluorenyl), phenanthryl, 1, 2,4,5-tetramethylphenyl, etc. Preferred examples of cycloalkenyl pits or substituted cycloalkenylalkyl groups containing 6 to 10 carbon atoms include, but are not limited to, cyclohexenylmethyl, etc. as appropriate Acid, alkoxycarbonyl and arylalkoxycarbonyl groups include fluorenyloxycarbonyl, tert-butoxycarbonyl, isobutoxycarbonyl, benzamidine, substituted benzamidine, butylammonium'ethenyl, trifluoroethenyl , Trichloroethenyl, phthalofluorenyl, etc. The protecting group mixture can be used to protect the same amine group, for example, the first amine group can be protected by an aryl pit group and an aryl pit oxycarbonyl group. The amine group can also be attached to it Zhi-96- This paper standard is the standard of country A ’s national grave (CNS) A4 (21〇χ 297 mm) (Please read the precautions on the back before filling this page),-Ministry of Economy Printed by the Consumer Cooperatives of the Standards Bureau 520362 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (94) II forms a heterocyclic ring, such as 1,2-wu (methylene) benzene, g too Nitroimine, succinimide, cis-butenylimide, etc., and the heteroaryl group here may also contain a vicinal aryl or cyclic ring. In addition, the heterocyclic group may be _, Di_ or tri-substitution such as nitrophthalodiimide. Amine groups can also be protected from undesired reactions such as oxidation by formation of addition salts such as hydrochloric acid, toluenesulfonic acid, trifluoroacetic acid, etc. A variety of amine-protecting groups are also suitable for protecting carboxyl groups, via groups and mirror groups. For example, arylalkyl groups. Alkyl groups are also suitable groups for protecting hydroxyl groups and fluorenyl groups, such as third butyl groups. A silicon atom optionally substituted by one or more alkyl, aryl and arylalkyl groups. Suitable silyl protecting groups include, but are not limited to, trimethylsilyl, triethylsilyl, triisopropylsilyl, third butyldimethylsilyl, dimethylphenylsilyl, ^-贰(Dimethylsilyl) benzene, 1,2-fluorene (dimethylsilyl) ethane and diphenylmethylsilyl. Amine silylation reactions produce mono- or di-silylamine groups. Silicon pitting reaction of amino alcohol compounds to obtain N, N, 0-trisilyl derivatives. Removal of silyl functional groups from silyl ether functional groups is easily accomplished using, for example, metal hydroxides or ammonium fluoride reactants in individual reaction steps or in situ treatment during reaction with alcohol groups. Appropriate silylating agents, such as trimethylsilyl chloride, third butyldimethylsilyl chloride, phenyldimethylsilyl chloride, diphenylmethylsilyl chloride or a combination product thereof with imidazole or DMF . Methods for the silylation of amines and the removal of silane-based protective groups are well known in the industry. These amine derivatives are prepared from the corresponding amino acids, aminoamines, or amino acid esters, and are also organic chemical agents, which are well known to those in the chemical industry who include amino acids / amino acid esters or amino alcohols. The protecting group can be performed under conditions that will not affect the rest of the molecule. These paper sizes are applicable to the Chinese national standard r ^ CNS) Order ~ (Please read the precautions on the back before filling this page) -97- -CRxRy- -NRxRy

R I 520362 A7 --·~—— Β7 五、發明説明（95 ) —^ ~~ -- 万法爲業界眾所周知包含酸水解，氫解等。較佳方法包括 去除保護基，如使用鈀/碳於適當溶劑系統如醇，乙酸等， 或其混合物藉氫解去除爷氧羰基。第三丁氧幾基保護基可 利用無機或有機酸如鹽酸或三氟乙酸於適當溶劑系統如二 啰烷或亞甲基氯去除。所得胺基鹽可方便中和獲得自由態 胺。羧基保護基如甲基，乙基，芊基，第三丁基，4•甲氧 苯基甲基等可於業界人士眾所周知之水解或氳解條件下去 除0 前文使用之符號具如下定義： %〆 本發明化合物之原體也包含於本發明之範圍。原體爲活 性或無活性化合物，原體投予病人後經由活體内生理作用 進行化學修改，如水解、代謝等修改成本發明化合物。原 體製造及使用之相關適合性及技術爲業界人士眾所周知。 至於原體包括酯類之一般性討論參見Svensson and TunekR I 520362 A7-· ~ —— B7 V. Description of the Invention (95) — ^ ~~-Wanfa is well known in the industry and includes acid hydrolysis, hydrogenolysis and so on. Preferred methods include removal of protecting groups, such as the use of palladium / carbon in a suitable solvent system such as alcohol, acetic acid, etc., or a mixture thereof to remove the oxycarbonyl group by hydrogenolysis. The third butyloxy protecting group can be removed using an inorganic or organic acid such as hydrochloric acid or trifluoroacetic acid in a suitable solvent system such as dioxane or methylene chloride. The resulting amine salt can be conveniently neutralized to obtain a free amine. Carboxyl protecting groups such as methyl, ethyl, fluorenyl, tert-butyl, 4 • methoxyphenylmethyl, etc. can be removed under hydrolysis or decomposition conditions that are well known to those in the industry.原 The precursors of the compounds of the present invention are also included in the scope of the present invention. The protozoan is an active or inactive compound. After the protozoan is administered to a patient, chemical modifications such as hydrolysis, metabolism, etc. are made into the compound of the invention through physiological actions in vivo. The suitability and technology related to the manufacture and use of the primitives are well known in the industry. For a general discussion of primitives including esters see Svensson and Tunek

Drug Metabolism Reviews 165 (1988)及 Bundgaard Design 〇f -98- 本紙張尺度適用中國ϋ標準rCNsTA4規格（210X 297公釐）~~~' --—- . IT.Aw~ (請先閱讀背面之注意事項再填寫本頁) -C(0) -c(NR)- -S(〇）2-Drug Metabolism Reviews 165 (1988) and Bundgaard Design 〇f -98- This paper size is applicable to the Chinese standard rCNsTA4 specification (210X 297 mm) ~~~ '---.. IT.Aw ~ (Please read the note on the back first (Please fill in this page for more details) -C (0) -c (NR)--S (〇) 2-

-NR- 經濟部中央標準局員工消費合作社印製 經濟部中央標準局員工消費合作社印製 520362 A7 B7 五、發明説明（96)-NR- Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economics Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economics 520362 A7 B7 V. Description of the Invention (96)

Prodrugs，Elsevier (1985)。經遮蔽羧酸根陰離子範例包含 多種酯如烷基（如曱基乙基），環烷基（如環己基），芳基燒基 (如苄基，對甲氧苄基），及烷基羰基氧烷基（例如特戊酸亞 甲基）。遮蔽成芳基談基氧甲基取代成衍生物之胺類可藉酉旨 酶割裂而於活體内釋放自由態藥物及甲醛（BungaiTd j Med· Chem· 25 03 (1989))。又，含酸性NH基之藥物，如咪 峻，醯亞胺，吲哚等可以N-醯亞甲基遮蔽（Bundgaard Design ofProdrugs，Elsevier(1985))。羥基遮蔽成酯類及醚類。 EP 039,05 1(Sloan 及 Little，1981 年 4 月 11 曰）揭示曼尼克 -鹼羥肟酸原體，其製備及用途。 根據本發明之化合物可根據一種或多種下述方法合成。 需注意顯示一般程序因其用於製備具有非特定立體化學之 化合物。但此種程序通常可應用於具有特定立體化學之化 合物，例如有關某個基的立體化學爲（S)或（R)。此外，據有 一種立體化學之化合物（例如（R))常可使用眾所周知之方法 ，例如顚倒方法，用以生產具有相反立體化學（亦即0》之 化合物。 嘧啶類： 式ί化合物之概略製備程序包括1，3-二羰基中間物或與 含N-C_N結構式如脒IV，胍VI或脲VII進行縮合反應（反 應圖1 ;有關合成方法综論參見D.J. Brown，雜環系化合 物：嘧啶，第 3 章，1994 年，John Wiley & Sons)。 __ -99- 本紙張尺度相 ) ------^------#1 (請先閱讀背面之注意事項再填寫本頁) 520362 A7 B7 五、發明説明（97Prodrugs, Elsevier (1985). Examples of masked carboxylate anions include a variety of esters such as alkyl (such as fluorenylethyl), cycloalkyl (such as cyclohexyl), arylalkyl (such as benzyl, p-methoxybenzyl), and alkylcarbonyloxy Alkyl (eg methylene pivalate). Amines that are masked to be substituted with aryl ethoxymethyl groups can be released by free enzymes and formaldehyde in vivo by cleaving enzymes (BungaiTd j Med. Chem. 25 03 (1989)). In addition, drugs containing acidic NH groups, such as micon, arsenimine, indole, etc., can be masked by N-amidine (Bundgaard Design of Prodrugs, Elsevier (1985)). Hydroxyl masks into esters and ethers. EP 039,05 1 (Sloan and Little, April 11, 1981) discloses Mannich-base hydroxamates, their preparation and uses. The compounds according to the invention can be synthesized according to one or more of the following methods. Care should be taken to show the general procedure as it is used to prepare compounds with non-specific stereochemistry. However, this procedure can usually be applied to compounds with specific stereochemistry, for example, the stereochemistry of a group is (S) or (R). In addition, according to a stereochemical compound (such as (R)), well-known methods, such as the decantation method, can often be used to produce compounds having the opposite stereochemistry (ie, 0). Pyrimidines: Outline of the compound of formula ί The preparation procedures include 1,3-dicarbonyl intermediates or condensation reactions with N-C_N-containing structural formulas such as hydrazone IV, guanidine VI or urea VII (Reaction Figure 1; see DJ Brown for a comprehensive overview of synthetic methods, heterocyclic compounds: Pyrimidine, Chapter 3, 1994, John Wiley & Sons). __ -99- This paper is standard) ------ ^ ------ # 1 (Please read the notes on the back before filling This page) 520362 A7 B7 V. Description of the invention (97

ITIT

〇 反應圖〇 Reaction diagram

HN V, VI, VII i 此外’至於1，3 ·二談基synthon， b -二甲基胺基- a，b -未飽 和酮IX可如所述與脒V或胍VI反應（G.B. Bennett et al·，J. Med. Chem· 21，623-628，1978)(反應圖 2)。此種 b·二甲 基胺基- a，b-未飽和酮IX可經由以布瑞克氏（Bredereck’s)反 應劑，亦即，貳（二甲基胺基）甲氧甲烷進行胺基甲醯化活 性亞甲基酮 VIII 製備（H. Bredereck et al·，Chem· Ber. 101 ’ 41-50 (1968) ; G.B. Bennett et al·，J. Org. Chem· 43， 221-225 (1977))。 (請先閱讀背面之注意事項再填寫本頁)HN V, VI, VII i In addition, as for the 1,3 · dialkynyl, b-dimethylamino-a, b-unsaturated ketone IX can be reacted with hydrazone V or guanidine VI as described (GB Bennett et al., J. Med. Chem. 21, 623-628, 1978) (Reaction Figure 2). Such b · dimethylamino-a, b-unsaturated ketone IX can be subjected to aminoformamidine by using Bredereck's reagent, that is, amidine (dimethylamino) methoxymethane. Preparation of methylene ketone VIII (H. Bredereck et al., Chem. Ber. 101 '41-50 (1968); GB Bennett et al., J. Org. Chem. 43, 221-225 (1977)) . (Please read the notes on the back before filling this page)

RR

h2n 經濟部中央標準局員工消費合作社印製 -100 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐 520362 A7 B7 五、發明説明（98 反應圖2 〇h2n Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs -100 This paper size is applicable to the Chinese National Standard (CNS) A4 (210X 297 mm 520362 A7 B7) V. Description of the invention (98 Reaction Figure 2 〇

R12 VIIIR12 VIII

R11 Me2NR11 Me2N

Me2N 〇Me 〇Me2N 〇Me 〇

R 12 NM02R 12 NM02

IXIX

k2nVr1 HNk2nVr1 HN

RR

R γν V，VI12 人 Ν’ R" (請先閱讀背面之注意事項再填寫本頁) 反應圖R γν V, VI12 people Ν ’R " (Please read the notes on the back before filling this page) Reaction Diagram

F 經濟部中央標準局負工消費合作社印製 根據此種反應，反應圖3示例説明2-(4-氟苯基）-1-(4-吡 -101 - 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 Μ —_____________ 五、發明説明（99 ) 一~一~ 啶基）乙酮（VIII ; Sheldrake，合成通訊 23，1967 (1993)) 轉成烯胺IX。中間物IX可與多種脒V及胍VI縮合獲得2-取代5-(4·鼠冬基）-4-(4·ρ比淀基）-p密淀I。 又可製備酮VIII(例如根據Sheldrake，合成通訊23 ， 1967-1971 (1993))，使用其它雜芳基羧醛做爲起始物料如 2·甲基吡啶-4·羧醛，2,6-二甲基吡啶-4-羧醛（Mathes and Sauermilch，Chem. Ber. 88，1276-1283 (1955))，喹琳 _4_ 叛醛，嘧啶-4-瘦醛，6-甲基嘧啶-4-叛醛，2-甲基嘧啶-4-羧醛，2,6-二甲基嘧啶 _4_ 羧醛（Bredereck et al.，Chem. Ber. 97 ’ 3407-3417 (1964))。此外，2_硝基吡啶-4_竣醛可經由 氧化甲基（Venemalm et al.，Tet. Lett. 34 ， 5495-5496 (1993))製自 2-硝基-4-甲基吡啶（Stanonis，J. Org. Chem. 22 ，475 (1957))。進一步經由酮VIII轉化獲得2_硝基·44啶 基衍生物1(反應圖4)。催化還原硝基成爲胺基可提供I衍 生物’ R12以2-胺基-4-吡啶基表示。然後胺基以習知乙醯 化反應獲得2-乙醯胺基-4-吡啶基衍生物。 反應圖4 Φ------1Τ------0— (請先閱讀背面之注意事項再填寫本頁)F Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Based on this response, the reaction is illustrated in Figure 3 as an example of 2- (4-fluorophenyl) -1- (4-pyridine-101. ) A4 specification (210X 297 mm) 520362 M —_____________ 5. Description of the invention (99) 1 ~ 1 ~ pyridyl) ethanone (VIII; Sheldrake, Synthesis Communications 23, 1967 (1993)) is converted to enamine IX. Intermediate IX can be condensed with various amidines V and guanidine VI to obtain 2-substituted 5- (4.murdinyl) -4- (4.p.pyridyl) -p dense lake I. Ketone VIII can also be prepared (e.g., according to Sheldrake, Synthetic Communications 23, 1967-1971 (1993)), using other heteroarylcarboxaldehydes as starting materials such as 2.methylpyridine-4.carboxaldehyde, 2,6- Dimethylpyridine-4-carboxaldehyde (Mathes and Sauermilch, Chem. Ber. 88, 1276-1283 (1955)), quinine_4_ aldehyde, pyrimidine-4-lephthaldehyde, 6-methylpyrimidine-4- Betaldehyde, 2-methylpyrimidine-4-carboxaldehyde, 2,6-dimethylpyrimidine-4-carboxaldehyde (Bredereck et al., Chem. Ber. 97 '3407-3417 (1964)). In addition, 2-nitropyridine-4_endaldehyde can be produced from 2-nitro-4-methylpyridine (Stanonis via oxymethyl (Venemalm et al., Tet. Lett. 34, 5495-5496 (1993)). J. Org. Chem. 22, 475 (1957)). Further conversion via ketone VIII gave 2-nitro.44pyridyl derivative 1 (Reaction Figure 4). The catalytic reduction of a nitro group to an amine group provides the I derivative ' R12 is represented by 2-amino-4-pyridyl. The amine group is then subjected to a conventional acetylation reaction to obtain a 2-acetamido-4-pyridyl derivative. Reaction Diagram 4 Φ ------ 1Τ ------ 0— (Please read the precautions on the back before filling this page)

-102- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 520362 A7 B7 五 、發明説明（1〇〇) 如反應圖5顯示，中間物IX也可與脲VII縮合獲得2(1H)-密咳：’衍生物x。X經由與卣化劑例如磷醯氯反應轉成氯 物XI。鼠化物XI以第一及第二胺，硫醇酸鹽，醇酸鹽 處理可製備前述其它嘧啶1及尺1以取代N，S或〇基表示 同理’胼可與氯化物XI反應獲得2_肼基取代喊淀I。反應圖5 經濟部中央標準局員工消費合作社印製-102- This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A7 B7 V. Description of the invention (100) As shown in Figure 5, intermediate IX can also be condensed with urea VII to obtain 2 ( 1H)-Mimetic cough: 'derivative x. X is converted to chloride XI via a reaction with a halogenating agent such as phosphonium chloride. The rat compound XI can be treated with the first and second amines, thiolates, and alkyds to prepare the other pyrimidines 1 and 1 in place of N, S, or O. The same reasoning can be obtained by reacting with chloride XI to obtain 2 _Hydrazine is substituted for I. Response Figure 5 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs

-103- 本紙張尺度烟中規格—（21〇 X 297公釐) (請先閱讀背面之注意事項再填寫本頁) 520362 A7 B7 五、發明説明（101)-103- Specifications of this paper standard in smoke— (21〇 X 297mm) (Please read the precautions on the back before filling this page) 520362 A7 B7 V. Description of the invention (101)

具應圖6 丽2Figure 6 Li 2

R R1 R1 NR22C(〇)R21 NR 22 SO 2R 20 Φ (請先閱讀背面之注意事項再填寫本頁) 鈀或鎳催化氯化物XI與芳基二羥硼酸或芳基鋅_化物 進行交叉偶合反應獲得式I化合物其中R1爲芳基或雜芳基。 反應圖6示例説明中間物IX與胍V!反應獲得2-胺基取 代I。2-胺基I爲2-胺基進一步醯化及磺化獲得醯胺基及續 醯胺基衍生物之有用中間物。 欲合成4-羥嘧啶II，可遵循反應圖7顯示之方法（合成方 法之综論參見：D.J· Brown，雜環系化合物：喊淀，參見 上文）。此種方法包括丙烯酸酯XII與脒V間之磺化反應， 接著氧化所得二氫嘧啶酮XIII獲得Π。 -104- 本纸張尺度適用中國國家標準（CNs ) A4規格（210X297公釐） 、\\一口 經濟部中央標準局員工消費合作社印製 520362 ΚΊ B7 五、發明説明（102:R R1 R1 NR22C (〇) R21 NR 22 SO 2R 20 Φ (Please read the notes on the back before filling this page) Palladium or nickel catalyzes the cross-coupling reaction of chloride XI with aryldihydroxyboronic acid or aryl zinc oxide A compound of formula I is obtained where R1 is aryl or heteroaryl. Reaction Figure 6 illustrates the reaction of intermediate IX with guanidine V! To obtain 2-amine substitution I. 2-Amino group I is a useful intermediate for further amidation and sulfonation of 2-amino groups to obtain amine and amine derivatives. To synthesize 4-hydroxypyrimidine II, the method shown in Figure 7 can be followed (for a comprehensive overview of the synthesis methods, see: D.J. Brown, Heterocyclic Compounds: Shout Lake, see above). This method includes a sulfonation reaction between acrylate XII and amidine V, followed by oxidation of the obtained dihydropyrimidone XIII to obtain Π. -104- This paper size applies to Chinese National Standards (CNs) A4 (210X297mm), printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 520362 ΚΊ B7 5. Description of Invention

2Ύ ΝΚ XII R12Ύ ΝΚ XII R1

V πV π

'R 經濟部中央標隼局員工消費合作社印製 欲合成2-取代5_(4_顧艾苴 „ ^ (氟苯基）_6-(4_吡啶基）_4_羥-嘧啶Π( 反應圖8)，2-取代丙烯酸酯 在疋（ . 酗ΧΠ可万便地經由吡啶-4-羧醛 與4-氟苯基乙酸縮合接著 ^ 、口祛耆酉曰化製備。XII可與多種脒V於 二反應至万、ΧΙΠ轉成η之脱氯劑，適合使用亞硝酸納 /乙酸。 如此，可經由適當選用起始物料獲得其它式Η化合物其 中R12爲R12定義中之其它雜芳基環。此等起始物料包含但 非僅限於2·甲基吡啶_4_羧醛，2,6-二甲基吡啶_4_^醛 (MathesandSauermilch?Chem.Ber. 88 ^ 1276-1283 (1955)) ’喹啉-4-羧醛，嘧啶_4-羧醛，6-甲基嘧啶羧醛，2_甲 基嘴呢-4-幾齡，2,6_二甲基嘧啶羧醛（Bredereck以吐 ’ Chem· Ber· 97，3407-3417 (1964))。使用 2-硝基吡啶· 4-瘦酸可獲得式π衍生物中Ri2爲2_硝基-4_吡啶基。硝基 催化還原成胺基獲得2_胺基_4_吡啶基衍生物Η。反應圖8 所示方法可用於其它芳基乙酸獲得具有不同芳基做爲R 之式II化合物。 11 (請先閱讀背面之注意事項再填寫本頁) -105- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X 297公釐 520362 A7 ~_____ B7 五、發明説明（103) 反應圖8 〇'R Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs to synthesize 2-substituted 5_ (4_ 顾 艾 苴 „^ (fluorophenyl) _6- (4_pyridyl) _4_hydroxy-pyrimidineΠ (Reaction Figure 8 ), 2-substituted acrylates can be easily prepared by condensing pyridine-4-carboxaldehyde with 4-fluorophenylacetic acid followed by hydration. XII can be used with a variety of The dechlorination agent that reacts to 10,000 and XII to η is suitable for using sodium nitrite / acetic acid. In this way, other compounds of formula VII can be obtained through appropriate selection of starting materials, where R12 is other heteroaryl ring in the definition of R12. Other starting materials include, but are not limited to, 2 · methylpyridine_4_carboxaldehyde, 2,6-dimethylpyridin_4_ ^ aldehyde (MathesandSauermilch? Chem. Ber. 88 ^ 1276-1283 (1955)) 'quine Porphyrin-4-carboxaldehyde, pyrimidine_4-carboxaldehyde, 6-methylpyrimidinecarboxaldehyde, 2-methylcarbazine-4-years old, 2,6_dimethylpyrimidinecarboxaldehyde (Bredereck to vomit 'Chem · Ber · 97, 3407-3417 (1964)). The use of 2-nitropyridine · 4-leptic acid to obtain a π derivative of the formula π is 2-nitro-4_pyridyl. The nitro group catalyzes the reduction to an amino group. The 2-amino-4-pyridyl derivative Η was obtained. The method shown in Figure 8 can be used for other arylacetic acids to obtain compounds of formula II with different aryl groups as R. 11 (Please read the precautions on the back before filling out this page) -105- This paper size applies to Chinese national standards (CNS ) Α4 specifications (210X 297mm 520362 A7 ~ _____ B7 V. Description of the invention (103) Reaction Figure 8 〇

(請先閱讀背面之注意事項再填寫本頁} 經濟部中央標準局員工消費合作社印製 另一種可獲得5,6-二芳基-4-¾嘧啶之方法（反應圖9)包 括以硫脲環化b·酮基酯XIV獲得硫尿喊淀衍生物XV。χν 可S-單甲基化成XVI。XVI與第一及第二胺反應獲得2-胺 基取代4-羥-嘧啶II。經由以烷基_烷化XV可獲得其它2-硫脒衍生物具有RkSR21。XV或XVI以阮尼鎳及H2處理 獲得結構式II化合物其中R1爲Η。 -106-(Please read the notes on the back before filling out this page} Another method for obtaining 5,6-diaryl-4-¾pyrimidine by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs (Reaction Figure 9) includes thiourea Cyclized b · ketoester XIV to obtain thiourea derivatives XV. Χν can be S-monomethylated to XVI. XVI reacts with the first and second amines to obtain 2-amino-substituted 4-hydroxy-pyrimidine II. Via Alkyl-alkylated XV can be used to obtain other 2-thizone derivatives having RkSR21. XV or XVI is treated with Raney nickel and H2 to obtain compounds of formula II where R1 is fluorene. -106-

本紙張尺度適用中國國家標準（CNS )_Α4規格（2丨OX 297:i"TThis paper size applies to China National Standard (CNS) _Α4 specifications (2 丨 OX 297: i " T

JZUJOZ 五、發明説明（1〇4: A7 B7JZUJOZ V. Description of the invention (104: A7 B7

'OEt'OEt

XIVXIV

工工Workers

IT 工工R' = SR. 21 (請先閱讀背面之注意事項再填寫本頁) 雖然反應圖9示例説明其中R 12 ^ ,, 馬4 -卩比咬基之合成，作你 經濟部中央標準局員工消費合作社印製 由通當選擇起始物料此種方法 1一 ^ 万决冋寺適用於R12定義中之饪 何其Έ雜芳基環。此等起始物# ^ 寸物枓包含但非僅限於2_甲基異IT worker R '= SR. 21 (Please read the notes on the back before filling out this page) Although the reaction diagram 9 illustrates the synthesis of R 12 ^ ,, Ma 4-卩 bibitate, as the central standard of your Ministry of Economic Affairs The Bureau ’s Consumer Cooperatives printed the method of selecting starting materials by Tongdang. This method is applicable to the heteroaryl ring in the definition of R12. These starting materials include, but are not limited to, 2-methyliso

菸鹼酸乙酯（Efimovsky and Rumpf, Bull s〇c Chim FR 648_649 (1954))，嘧啶·4_羧酸甲酯，2-甲基嘧啶-4-羧酸甲 酯’ 6-甲基嘧啶_4_叛酸甲酯及2,6-二甲基嘧淀-4-複酸甲 酯（Sakasi et al·，Heterocycles 13，235 (1978))。同理，2- -107 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362Ethyl nicotinate (Efimovsky and Rumpf, Bull soc Chim FR 648_649 (1954)), pyrimidine · 4-methyl carboxylate, 2-methylpyrimidine-4-carboxylic acid methyl ester 6-methylpyrimidine_ 4-Methyl metaborate and methyl 2,6-dimethylpyridine-4-valerate (Sakasi et al., Heterocycles 13, 235 (1978)). In the same way, the paper size of 2- -107 applies to China National Standard (CNS) A4 (210X297mm) 520362

A7 B7 五、發明説明（105) 硝基異於驗酸甲酉旨（Stanonis，J. 〇rg. Chem· 22 ’ 475 (1957))可與芳基乙酸酯反應接著類似反應圖9以硫脲環化 所得b_酮基酯。隨後硝基催化還原成胺基獲得4·羥-嘧啶II 其中R12爲2-胺基-4-吡啶基（反應圖1〇)。 反應圖10A7 B7 V. Description of the invention (105) Nitro is different from formic acid (Stanonis, J. Org. Chem. 22 '475 (1957)) can be reacted with aryl acetate and then similar reaction Figure 9 The b-ketoester obtained from urea cyclization. Subsequently, the nitro group is catalyzed and reduced to amine group to obtain 4 · hydroxy-pyrimidine II, wherein R12 is 2-amino-4-pyridyl group (Reaction Figure 10). Reaction Figure 10

R* 此外，2-乙醯胺基異菸鹼酸甲酯（反應圖11)於適當保護 酸胺基氮後可以類似反應圖9之方式反應，醯胺基氮係使 用例如第三丁基二甲基矽烷基氧甲基（Benneche et al·，ActaR * In addition, methyl 2-acetamidinyl isonicotinate (Reaction Figure 11) can be reacted in a manner similar to that shown in Figure 9 after appropriately protecting the acid amine nitrogen. Methylsilyloxymethyl (Benneche et al., Acta

Chem. Scand. B 42 3 84-3 89 (198 8))，第三丁 基二甲基矽烷 基，苄氧甲基，苄基等（Pi)保護。 反應圖1 1 (請先閲讀背面之注意事項再填寫本頁)Chem. Scand. B 42 3 84-3 89 (198 8)), tert-butyldimethylsilyl, benzyloxymethyl, benzyl, etc. (Pi) are protected. Reaction diagram 1 1 (Please read the notes on the back before filling in this page)

1T ii. 經濟部中央標準局員工消費合作社印製1T ii. Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs

CO 2MeCO 2Me

C02Me 然後使用適當反應劑（例如於Ρι爲第三丁基二甲基矽烷 -108- 本紙張尺度鄉巾關家標準（CNS ) A视格 經濟部中央標準局員工消費合作社印製 520362 A7 —------ - B7 五、發明説明（) 一 ^ 〜一 一 基氧甲基之例使用氟化四丁銨）去除所得嘧啶n之保護基 Pi後可獲得嘧啶II具有Rik2_乙醯胺基-4_吡啶基。無庸待 言，對氟苯基乙酸乙酯可於反應圖9示例説明之程序中以 任一種芳基乙酸烷酯取代獲得式Π化合物具有不同的Rl i 芳基取代基。C02Me is then printed with a suitable reactant (for example, Ter is butyl dimethyl silane-108- this paper standard Country Standard for Household Towels (CNS) A printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A520 — A7 —- ------B7 V. Explanation of the invention () Example of ^ ~~ 1-oxymethyl group using tetrabutylammonium fluoride) After removing the protecting group Pi of pyrimidine n, pyrimidine II can be obtained with Rik2_acetamidine 4-pyridyl. Needless to say, p-fluorophenyl ethyl acetate can be substituted with any of aryl alkyl acetates in the procedure illustrated in the reaction of FIG. 9 to obtain compounds of formula II having different R i i aryl substituents.

另一方法中，嘧啶II化合物可經由適當XVIII衍生物（L 爲離去基，如_基等，P2爲保護基如苄基等）與適當芳基相 當物偶合製備。In another method, the pyrimidine II compound can be prepared by coupling an appropriate XVIII derivative (L is a leaving group, such as — group, etc., P2 is a protecting group such as benzyl, etc.) and an appropriate aryl equivalent.

XVIII 此種芳基/雜芳基偶合反應爲業界人士眾所周知，包括有 機金屬成份供與第二化合物之反應性衍生物，如_衍生物 ，於催化劑存在下反應。金屬有機物種可由嘧啶酮提供， 該種情況下，芳基成份提供反應性_相當物，或嘧淀酮呈 反應性5-自基衍生物形式與金屬有機芳基化合物反應。如 此，5-溴及5-碘衍生物XVIII(L=Br，I)可以芳基烷基錫化 合物，例如三甲基錫烷基苯，於惰性溶劑如四氫呋喃，於 鈀催化劑如二氣化二（三苯基膦）鈀（II)存在下處理。（Peters et al” J. Heterocyclic Chem. 27，2165-2173 (1990))。另外 ，鹵衍生物XVIII可經由與例如三丁基錫烷基氯反應轉成 三烷基錫衍生物（L = Bu3Sn)接著以丁基鋰鋰化然後與芳基 -109- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 1·、訂------ (請先閲讀背面之注意事項再填寫本頁) 520362 五、發明説明（107) 鹵於催化劑存在下反應（Sandosham and Undheim，Acta Chem. Scand. 43，684-689 (1989))。兩種方法皆可獲得 口密 啶II其中R11二芳基及雜芳基。 如參考文獻報告（Kabbe，Lieb· Ann· Chem. 704， 144 (1967);德國專利1271 1 16 (1968))並顯示於反應圖12，5-芳基_2,6-二吡啶基-4_羥嘧啶（II)可於一步驟式合成經由氰 基吡啶與芳基乙醯基酯，如苯基乙酸乙酯於甲氧化鈉存在 下反應製備。 反應圖12XVIII This aryl / heteroaryl coupling reaction is well known to those in the industry, and it includes an organic metal component for a reactive derivative, such as a derivative, that reacts in the presence of a catalyst. The metal organic species can be provided by pyrimidinone, in which case the aryl component provides a reactive equivalent, or the pyrimone reacts with the metal organic aryl compound in the form of a reactive 5-self radical derivative. Thus, the 5-bromo and 5-iodine derivatives XVIII (L = Br, I) can be arylalkyltin compounds, such as trimethylstannylbenzene, in an inert solvent such as tetrahydrofuran, and in a palladium catalyst such as digas. Treatment with (triphenylphosphine) palladium (II). (Peters et al "J. Heterocyclic Chem. 27, 2165-2173 (1990)) In addition, the halogen derivative XVIII can be converted to a trialkyltin derivative by reacting with, for example, tributyltin alkyl chloride (L = Bu3Sn). Lithified with butyl lithium and then with aryl-109- This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 1. · Order ------ (Please read the precautions on the back before (Fill in this page) 520362 V. Description of the invention (107) Halogens are reacted in the presence of catalysts (Sandosham and Undheim, Acta Chem. Scand. 43, 684-689 (1989)). Both methods can be used to obtain orimidine II of which R11 Diaryl and heteroaryl, as shown in the reference report (Kabbe, Lieb · Ann · Chem. 704, 144 (1967); German Patent 1271 1 16 (1968)) and shown in the reaction diagram 12, 5-aryl_2 , 6-Dipyridyl-4-hydroxypyrimidine (II) can be synthesized in one step via the reaction of cyanopyridine with an arylacetamyl ester, such as ethyl phenylacetate, in the presence of sodium methoxide. Reaction Figure 12

Cr 類似地，如前文報告（Kabbe，參見上文）並顯示於反應圖 13，4_胺基-5-(芳基）-2,6-二吡啶基·嘧啶XIX係於一步驟 式合成經由氰基吡啶與芳基乙腈，如4-氟苯乙腈反應獲得。 反應圖13 ------1Τ------- (請先閲讀背面之注意事項再填寫本頁)Cr is similar, as previously reported (Kabbe, see above) and shown in the reaction FIG. 13, 4-amino-5- (aryl) -2,6-dipyridyl · pyrimidine XIX is synthesized in one step via Cyanopyridine is obtained by reaction with arylacetonitrile, such as 4-fluorophenylacetonitrile. Reaction Diagram 13 ------ 1Τ ------- (Please read the notes on the back before filling this page)

0H0H

C〇2Et 經濟部中央標準局員工消費合作社印製 αC〇2Et Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs α

-110 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 520362 A7 五、發明説明（108) 、、’二由异磷醯氯反應（反應圖14)轉成氯衍生物XX可修改 密疋II之4士置（式I之R2)。4_燒氧衍生物X幻可由氯衍 :物XX、經由以烷氧化物進行親核取代製備。另外，替代 氯基可使用其匕離去基，例如甲苯磺酸根，甲烷磺酸根等 又離去基也可由胺基，硫醇酸根，醇酸根等親核基團 替代。例如，氯衍生物xx可藉催化氫化反應還原獲得嘧 疋I此處R爲Η，或可與烷基或芳基二氫硼酸或烷基或 芳基自化鋅反應獲得嘧啶ί此處R2爲烷基或芳基。 反應圖14 (請先閱讀背面之注意事項再填寫本頁) ΟΗ-110 This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A7 V. Description of the invention (108), '' is converted from the reaction of isophosphonium chloride (reaction figure 14) to chlorine derivative XX Modified 4 Shiji of Key II (R2 of Formula I). The 4-oxo-oxygen derivative X may be prepared from a chloro derivative: XX via nucleophilic substitution with an alkoxide. In addition, the chloro group can be replaced by its leaving group, such as toluenesulfonate, methanesulfonate and the like. The leaving group can also be replaced by amine groups such as amine group, thiolate group, and alkylate group. For example, the chlorine derivative xx can be reduced by catalytic hydrogenation to obtain pyrimidine I, where R is hydrazone, or can be reacted with alkyl or aryl dihydroboric acid or alkyl or aryl zinc to obtain pyrimidine, where R2 is Alkyl or aryl. Reaction Figure 14 (Please read the notes on the back before filling in this page) ΟΗ

R*R *

XX IT = C1 XXI R2 =〇MeXX IT = C1 XXI R2 = 〇Me

II

R Η 經濟部中央榡準局員工消費合作衽印製 反應圖15中，本發明式XXX化合物易經由w 物XXXI與胺NHR5R21反應，例如經由較佳於高於ϋ t 了 更佳於150-210 °C溫度加熱混合物製備。另外，式χχχ化 合物易經由甲烷磺醯中間物XXXH與胺 ’、 反應，例 如經由於高於4(TC，更佳50-210。(：溫度加熱混合物製備。 甲基硫中間 •I. -111 本紙張尺度適用中 (CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（1〇9; 反應圖15 OH:¾R 消费 Consumer cooperation of the Central Associate Bureau of the Ministry of Economic Affairs 衽 Printed response In Figure 15, the compound of formula XXX of the present invention easily reacts with the amine NHR5R21 via the substance XXXI, for example, it is better than 150-210. Prepared by heating the mixture at a temperature of ° C. In addition, compounds of formula χχχ are easily reacted with amines via the methanesulfonium intermediate XXXH, for example, via a temperature higher than 4 (TC, more preferably 50-210. (: Prepared by heating the mixture at a temperature. Methyl sulfur intermediate • I. -111 This paper size is applicable (CNS) A4 size (210X 297 mm) 520362 A7 B7 V. Description of the invention (109; Reaction Figure 15 OH: ¾

IT R1-，^r、SMe XXXIIT R1-, ^ r, SMe XXXI

R OH R 12R OH R 12

XXXXXX

經濟部中央標準局員工消費合作社印製 式NHR5R21胺爲市面可得或易由業界人士由市面可得起 始物料製備。例如，醯胺基，硝基或氰基可於還原條件下 例如於鋁氫化鋰等還原劑存在下還原生成對應胺。胺基之 烷化及醯化反應爲業界人士眾所周知。光學活性及非光學 活性取代胺可由光學活性胺基酸及胺基酸醯胺（例如烷基 ’芳基’雜芳基，環坑基’芳基燒基，雜芳基燒基，環燒 基燒基等取代甘胺酸，β-丙胺酸等）使用業界人士眾所周知之方法製備，例如 Η. Brunner，P. Hankofer，U. Holzinger，Β. Treittinger and H. Schoenenberger, Eur. J. Med. Chem. 25 ’ 35-44 ’ 1990 ; M.Freibergerand R.B.Hasbrouck，J· Am. Chem. Soc. 82 ? 696-698 ? 1960 ; Dornow and Fust ? Chem· Ber· 87，984，1954 ; M. Kojima and J· Fujita， Bull. Chem· Soc. Jpn. 55，1454-1459，1982 ; W· Wheeler and D. O’Bannon，標記化合物及放射性藥品期刊xxxi， 306，1992 ;及 S. Davies，Ν· Garrido，0. Ichihara and I.Walters, J. Chem. Soc., Chem. Commun. 1153，1993。 下列實例僅供舉例説明之用，而絕非視爲限制本發明。 業界人士了解可未侵害本發明之精髓與範圍對此處揭示之 -112- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） (請先閱讀背面之注意事項再填寫本頁)The NHR5R21 amine printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs is commercially available or can be readily prepared by industry professionals from commercially available materials. For example, amidino, nitro or cyano can be reduced to the corresponding amine under reducing conditions such as in the presence of a reducing agent such as lithium aluminohydride. The alkylation and tritiation of amino groups are well known in the industry. Optically active and non-optically active amines can be selected from optically active amino acids and amidoamines (such as alkyl'aryl'heteroaryl, cyclohexyl'arylalkyl, heteroarylalkyl, cycloalkyl) Substituted glycine, β-alanine, etc.) are prepared using methods well known to those in the industry, such as Η. Brunner, P. Hankofer, U. Holzinger, Β. Treittinger and H. Schoenenberger, Eur. J. Med. Chem 25 '35-44' 1990; M. Freiberger and RB Hasbrouck, J. Am. Chem. Soc. 82? 696-698? 1960; Dornow and Fust? Chem. Ber. 87, 984, 1954; M. Kojima and J. Fujita, Bull. Chem. Soc. Jpn. 55, 1454-1459, 1982; W. Wheeler and D. O'Bannon, Journal of Labeled Compounds and Radiopharmaceuticals xxxi, 306, 1992; and S. Davies, N. Garrido, 0. Ichihara and I. Walters, J. Chem. Soc., Chem. Commun. 1153, 1993. The following examples are for illustrative purposes only and are not to be considered as limiting the invention in any way. People in the industry understand that the essence and scope of the present invention may not be infringed upon. -112- This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page)

^20362 A7^ 20362 A7

五、發明説明（11〇) 化合物做出變化及修改 實例 實例 2-取代5-(4 -氟苯基）-4-(4-峨淀基）-喊淀之概略製備程序 IjjlC二甲基胺基）_2_(4_氣苯基比淀基）·3_丙燦_〗_酿| : (根據 Bennett et al.，J· 〇rg. Chem. 43，221 (1977))。V. Description of the invention (11) Examples of changes and modifications of the compound Examples 2-Substituted 5- (4-fluorophenyl) -4- (4-eodoyl) -synthesis IjjlC dimethylamine Group) _2_ (4_Gaphenyl group). 3_Bingcan ___ brewing |: (according to Bennett et al., J. 〇rg. Chem. 43, 221 (1977)).

F 2-(4-氟苯基）-i-(4_吡啶基）乙酮（3 〇〇毫克，i 39毫莫耳）及 武（二甲基胺基）甲氧甲烷（300毫克，1.95毫莫耳）之混合物 於110 C於氬氣下加熱1.5小時。蒸發，黃色結晶殘餘物於 用於隨後反應之前於油泵眞空脱水。MS(m/z): 270.8(M + H)+ ; C16H15FN20 要求値 270.3。W-NMI^CDCh) :d 8.57，7.25(2 m，各個 2H，吡啶），7.36(s，1H， CH = )，7·13，6.99(2m，各個 2H，PhF)，3.00(bs，6H ，2 CH3)。 ·概略程序： (根據 Bennett et al., J. Med. Chem. 21，623 (1978))。 -113-F 2- (4-fluorophenyl) -i- (4-pyridyl) ethanone (300 mg, i 39 mmol) and dimethyl (dimethylamino) methoxymethane (300 mg, 1.95 The mixture was heated at 110 C for 1.5 hours under argon. Evaporate and the yellow crystalline residue is dehydrated on an oil pump before being used in subsequent reactions. MS (m / z): 270.8 (M + H) +; C16H15FN20 requires 値 270.3. W-NMI ^ CDCh): d 8.57, 7.25 (2 m, each 2H, pyridine), 7.36 (s, 1H, CH =), 7.13, 6.99 (2m, each 2H, PhF), 3.00 (bs, 6H , 2 CH3). • Outline procedure: (according to Bennett et al., J. Med. Chem. 21, 623 (1978)). -113-

I n I n ^ I n 111 (請先閱讀背面之注意事項再填寫本頁J 經濟部中央榡準局員工消費合作社印製 本紙張尺度適用中國國家標準 (CNS)A4規格（ 210X 297公釐） 520362 A7 -----—______ B7 五、發明説明（111)I n I n ^ I n 111 (Please read the notes on the back before filling in this page. J Printed by the Central Consumers ’Association of the Ministry of Economic Affairs, Employee Consumer Cooperatives. 520362 A7 -----—______ B7 V. Description of the invention (111)

經濟部中央標準局員工消費合作社印製 3-(—甲基胺基）-2-(4·氟苯基）_i_(4-吡啶基）-3•丙烯-卜酮 (1.39毫莫耳）於絕對乙醇（9毫升）之溶液移入由鈉（167毫 莫耳）及脒或胍鹽酸鹽（167毫莫耳）製備之尺1_ C(NH)CH2(1.67笔莫耳）於乙醇（2毫升）之溶液。回流加熱 1_5至24小時後，經蒸發及所得物料直接施於矽膠柱（卜5 %甲醇/二氯甲烷）或攝取於二氯甲烷接著以水洗滌，脱水 有機溶液及蒸發隨後進行柱式層析。 下列嘧啶係根據此種概略程序經由3 -(二甲基胺基）-2-(4-氟苯基）-1-(4-吡啶基）_3_丙烯-1-酮於脒反應製備： 卜1 5-(4 -氟苯基）-2 -甲基- 4- (4 -ρ比咬基喊淀：MS (m/z)： 266.0 (M + H)+ ; C16H12FN3 要求値 265.3。W-NMK^CDCU) :d 8.70(d，1H，H-6，。密淀），8.59，7.32(2m，各個 2H，吡啶），7.20-7.00(m，4H，PhF)，2.88(s，3H， CH3) 〇 Ri = CH3- 1-2 5 -(4·氣苯基）-2-兴丙基 4 (4- p比淀基）-癌淀：MS (m/z) ·· 294.4(M + H)+ ; CigH16FN3 要求値 293.4 。 NMR(CDC13) : d 8.73(s ， 1H ，H-6 ，嘧啶），8·60 ， -114- 本紙張尺度適用中國國家標準（CNS ) Α4規格（21〇X 297公釐） (請先聞讀背面之注意事項#填寫本買)Printed by 3-(— methylamino) -2- (4 · fluorophenyl) _i_ (4-pyridyl) -3 • propene-butanone (1.39 mmol) in the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A solution of absolute ethanol (9 ml) was transferred to a ruler 1_ C (NH) CH2 (1.67 pen moles) prepared in sodium (167 mmol) and tritium or guanidine hydrochloride (167 mmol) in ethanol (2 ml) ) Solution. After heating under reflux for 1-5 to 24 hours, after evaporation and the resulting material is directly applied to a silica gel column (5% methanol / dichloromethane) or taken up in dichloromethane and then washed with water, the organic solution is dehydrated and evaporated followed by column chromatography. . The following pyrimidines were prepared according to this general procedure via 3- (dimethylamino) -2- (4-fluorophenyl) -1- (4-pyridyl) _3_propen-1-one in a hydrazone reaction: 1 5- (4-Fluorophenyl) -2 -methyl- 4- (4 -ρ ratio): MS (m / z): 266.0 (M + H) +; C16H12FN3 requires 値 265.3. W- NMK ^ CDCU): d 8.70 (d, 1H, H-6,. Dense lake), 8.59, 7.32 (2m, each 2H, pyridine), 7.20-7.00 (m, 4H, PhF), 2.88 (s, 3H, CH3) 〇Ri = CH3- 1-2 5-(4-phenyl) -2-oxopropyl 4 (4-p ratio) -Audun: MS (m / z) ·· 294.4 (M + H) +; CigH16FN3 requires 値 293.4. NMR (CDC13): d 8.73 (s, 1H, H-6, pyrimidine), 8.60, -114- This paper size is applicable to China National Standard (CNS) A4 specification (21〇X 297 mm) (please listen first Read the notes on the back #Fill in this purchase)

，1T 520362 A7 B7 五、發明説明（112) 7.35(2m，各個 2H，吡啶），7.20-7.04(m，4H，PhF)， 3.37(m，1H，CH(CH3)2)，1.50，1.4f(2s，各個 3H，2 CH3) 〇1T 520362 A7 B7 V. Description of the invention (112) 7.35 (2m, each 2H, pyridine), 7.20-7.04 (m, 4H, PhF), 3.37 (m, 1H, CH (CH3) 2), 1.50, 1.4f (2s, each 3H, 2 CH3).

Ri - (CH3)2CH. 1-3 2-第三丁基_5-(4-氟苯基）-4-(4-吡啶基V嘧啶： MS(m/z) : 307·8(Μ + Η)+; C19H18FN3 要求値 307·4。iH-NMR(CDC13) · d 8.72(s ， 1H ，H-6 ，嘧啶），8.59 ， 7.38(2m，各個 2H，p比淀），7.21-7.06(m，4H，PhF)， 1.52(s，9H，3 CH3) 〇 Ri = (CH3)3C- 1-4 2-(1-氣-2-甲氧乙基-氣苯基）-4-(4 -峨淀基）-p密淀 _· MS(m/z) ·· 344·2(Μ + Η)+ ; C18H15C1FN30 要求値 343.8。 lU^MR(COCU) ： d 8.81(s，1Η，H-6，嘧啶），8·61， 7.35(2m，各個 2H，吡啶），7.22-7.08(m，4H，PhF)， 5.29(dd，1H，CHC1)，4.31，4.04(2dd，各個 1H，CH20) ，3.47(s，3H，CH30) o Ri = CH30CH2CH(C1)- 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 1-5 2 -（壤丙基氣苯基）-4-(4-口比淀基）-口密淀：MS(m/z、 :292.0(M + H)+ ； C18H14FN3 要求値 291.3 。 'H- NMR(CDC13) : d 8.60(s ， 1H ，H-6 ，嘧啶），8.57 ， 7.32(2m，各個 2H，吡啶），7.16-7.00(m，4H，PhF)， 2.32(m，1H，-CH-)，1.2，l.l(2m，各個 2H，2CH2)。 R1= t>~ -115- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐）Ri-(CH3) 2CH. 1-3 2-Third-butyl-5- (4-fluorophenyl) -4- (4-pyridyl V-pyrimidine: MS (m / z): 307 · 8 (Μ + Η) +; C19H18FN3 requires 値 307 · 4. IH-NMR (CDC13) · d 8.72 (s, 1H, H-6, pyrimidine), 8.59, 7.38 (2m, each 2H, p ratio), 7.21-7.06 ( m, 4H, PhF), 1.52 (s, 9H, 3 CH3) 〇Ri = (CH3) 3C- 1-4 2- (1-Gas-2-methoxyethyl-Gaphenyl) -4- (4 -Edianji) -p dense lake_ · MS (m / z) ·· 344 · 2 (Μ + Η) +; C18H15C1FN30 requires 値 343.8. LU ^ MR (COCU): d 8.81 (s, 1Η, H- 6, pyrimidine), 8.61, 7.35 (2m, each 2H, pyridine), 7.22-7.08 (m, 4H, PhF), 5.29 (dd, 1H, CHC1), 4.31, 4.04 (2dd, each 1H, CH20) , 3.47 (s, 3H, CH30) o Ri = CH30CH2CH (C1)-Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) 1-5 2-(Polypropyl Gas Phenyl) -4- (4-port ratio) -port dense lake: MS (m / z,: 292.0 (M + H) +; C18H14FN3 requires 値 291.3. 'H-NMR (CDC13): d 8.60 ( s, 1H, H-6, pyrimidine), 8.57, 7.32 (2m, each 2H, pyridine), 7.16-7.00 (m, 4 H, PhF), 2.32 (m, 1H, -CH-), 1.2, ll (2m, each 2H, 2CH2). R1 = t > ~ -115- This paper size applies to China National Standard (CNS) A4 specification (210X297 Mm)

520362 A7 _ B7 五、發明説明（113 ) 卜6 2-(金_烷基）·5-(4_ 4苯基吡啶基V嘧啶： MS(m/z): 386.0(M + H)+; C25H24FN3 要>値 385.5。 NMR(CDC13) : d 8.76(s ， 1H，H-6，嘧啶），8.61 ， 7·51(2ιη ’ 各個 2H，p比淀），7·22·7·08(πι，4H，PhF)， 〜1.9-1.5(^，15H，CH2，CH)〇 R1 二 1·7 2_ 芊基-5_(4_ 氟苯基）-4·(4-ρ比淀基）-p密咬：MSTm/z^ ： 342·2(Μ + Η)+ ; C22H16FN3 要求値 341.4。iH-NMR^CDCL) :d 8.71(s，1H，H-6，嘧啶），8·60，7.48(2m，各個 2H，吡啶），7.42-7.04(m，9H，PhF，Ph)，4.42(s，2H ，CH2Ph)。 (請先閱讀背面之注意事項再填寫本頁) -訂520362 A7 _ B7 V. Description of the invention (113) BU 6 2- (gold_alkyl) · 5- (4_ 4 phenylpyridinyl V pyrimidine: MS (m / z): 386.0 (M + H) +; C25H24FN3 Key> 5.5385.5. NMR (CDC13): d 8.76 (s, 1H, H-6, pyrimidine), 8.61, 7.51 (2 ′ each 2H, p ratio), 7.22 · 7 · 08 (πι , 4H, PhF), ~ 1.9-1.5 (^, 15H, CH2, CH) 〇R1 di 1.7 2_ fluorenyl-5_ (4_fluorophenyl) -4 · (4-ρ than yodo) -p dense Bite: MSTm / z ^: 342.2 (M + Η) +; C22H16FN3 requires 値 341.4. IH-NMR ^ CDCL): d 8.71 (s, 1H, H-6, pyrimidine), 8.60, 7.48 (2m , Each 2H, pyridine), 7.42-7.04 (m, 9H, PhF, Ph), 4.42 (s, 2H, CH2Ph). (Please read the notes on the back before filling this page)-Order

經濟部中央標準局員工消費合作社印製 1-8 2·(2,6-二氯字基）-5-(4-氟苯基）-4-(4 -p比淀基）-癌淀： MS(m/z): 410·2(Μ)+; C22H14C12FN3 要求値410.3。111-NMR(CDC13) : d 8.68(s，1H，H-6，喊淀），8.57(d，2H ，口比淀），7.44-7.03(m，9H，口比淀，PhF，PhCl2) 9 4.93(s ，2H，CH2)。Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs of the People's Republic of China 1-8 2 · (2,6-dichlorobenzene) -5- (4-fluorophenyl) -4- (4-p-pyridyl) -Ondian: MS (m / z): 410.2 (Μ) +; C22H14C12FN3 requires 値 410.3. 111-NMR (CDC13): d 8.68 (s, 1H, H-6, Diandian), 8.57 (d, 2H, mouth ratio Lake), 7.44-7.03 (m, 9H, Kipido Lake, PhF, PhCl2) 9 4.93 (s, 2H, CH2).

Cl _Cl _

R1 二 -116- 本紙張尺度適用中國國家標率（CNS ) A4規格（210X 297公釐） 520362 Α7 Β7 五、發明説明（114 9 5-(4-氟苯基）-2-苯氧甲基-4-(4- 17比淀基ρ密淀 MS(m/z) : 358·2(Μ + Η). ; C22H16FN30 姜求値 357.4。111-NMR(CDC13) : d8.83(s，1H，H-6, 口密淀），8.60(m，2H ，外匕淀），7.36_6.98(m，11H，叶匕淀，PhF，Ph)，5.43(s ，2H，CH2)。 R1 a 1-10 5_(4-氟苯基）-2•苯硫甲基-4-(4·ρ比淀基密淀： MS(m/z): 374·2(Μ + Η)+; C22H16FN3S 要求値 373.5。 NMR(CDCl3) : d 8.72(s ’ 1H ’ H-6，口密淀），8.56 ， 7.49(2m，各個 2H，峨淀），7.32-7.02(m，9H，PhF， Ph)，4.50(s，2H，CH2) 〇 R1 a: (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局負工消費合作社印製 1-11 5-(4-氟苯基）_2_苯基_4·(4-吡啶基嘧啶：MSfm/z、: 328.2(M + H)+ ; C21H14FN3 要求値 327.4。h-NMI^CDClO :d8.85(s，1H，H-6，口密淀），8.63，7.4(2m，各個 2H ，吡啶），8.56，7.6-7.5，7.25-7.05(m，9H，PhF，Ph)。 R1 σ 1-12 5-(4-氣苯基）晒2-(4-經苯基）-4-（4-口比淀基）-口密喊 ： -117 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） 520362 A7 B7 五、發明説明（115 MS(m/z): 344.2(M + H)+; C21H14FN30 要求値 343.4。4· NMR(DMSO-d6) : d 10.2(bs，1H，OH)，8.90(s，1H， H-6，嘧啶，嘧啶），8.60，7.42(2m，务個 2H，吡啶）， 8.35，7.40-6.92(m，8H，PhF，PhOH) 〇 R1 1 _ 13 I : MS(m/z): 343·2(Μ + Η)+; C21H15FN4 要求値 342.4。4. NMR(CDC13) : d 8.75(s ， 1H ， H-6 ，口密淀），8.60, 7.41(2m，各個 2H，吡啶），8·40，7.22-6.79(m，8H，R1 II-116- This paper size applies to China National Standards (CNS) A4 specifications (210X 297 mm) 520362 A7 B7 V. Description of the invention (114 9 5- (4-fluorophenyl) -2-phenoxymethyl -4- (4- 17 specific ratio ρ dense lake MS (m / z): 358.2 (Μ + Η).; C22H16FN30 Jiang Qiu 357.4. 111-NMR (CDC13): d8.83 (s, 1H , H-6, mouth dense lake), 8.60 (m, 2H, outer Dian lake), 7.36_6.98 (m, 11H, Ye Dian lake, PhF, Ph), 5.43 (s, 2H, CH2). R1 a 1-10 5_ (4-fluorophenyl) -2 • phenylthiomethyl-4- (4 · ρ than yodoside dense lake: MS (m / z): 374 · 2 (Μ + Η) +; C22H16FN3S requirements値 373.5. NMR (CDCl3): d 8.72 (s'1H'H-6, Komiyodo), 8.56, 7.49 (2m, each 2H, Edo), 7.32-7.02 (m, 9H, PhF, Ph), 4.50 (s, 2H, CH2) 〇R1 a: (Please read the notes on the back before filling in this page) Printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives 1-11 5- (4-fluorophenyl) _2_ Phenyl-4 · (4-pyridylpyrimidine: MSfm / z ,: 328.2 (M + H) +; C21H14FN3 requires 値 327.4. H-NMI ^ CDClO: d8.85 (s, 1H, H-6, mouth tight Lake), 8.63, 7.4 (2m, each 2H, pyridine), 8.56, 7.6- 7.5, 7.25-7.05 (m, 9H, PhF, Ph). R1 σ 1-12 5- (4-Gaphenyl) photo 2- (4-Vinyl) -4- (4-Methyl) -Spoken secretly: -117 This paper size applies to Chinese National Standard (CNS) A4 specification (210 × 297 mm) 520362 A7 B7 V. Description of invention (115 MS (m / z): 344.2 (M + H) +; C21H14FN30 requirements値 343.4.4 NMR (DMSO-d6): d 10.2 (bs, 1H, OH), 8.90 (s, 1H, H-6, pyrimidine, pyrimidine), 8.60, 7.42 (2m, 2H, pyridine), 8.35, 7.40-6.92 (m, 8H, PhF, PhOH) 〇R1 1 _ 13 I: MS (m / z): 343 · 2 (Μ + Η) +; C21H15FN4 requires 値 342.4. 4. NMR (CDC13): d 8.75 (s, 1H, H-6, Komiyodo), 8.60, 7.41 (2m, each 2H, pyridine), 8.40, 7.22-6.79 (m, 8H,

PhF，Ph)，4.00(bs，2H，NH2) 〇 (請先閱讀背面之注意事項再填寫本頁) R1PhF, Ph), 4.00 (bs, 2H, NH2) 〇 (Please read the precautions on the back before filling this page) R1

H，>TH, > T

14 氟苯基）-2-(3_ p比淀基）3-(4- p比啶基）_ p密咬： MS(m/z) : 329.0(M + H) ; CaoHnFls^ 要求値 328.4。4- NMR(CDC13) : d 9.80(bs，H-2，比淀），$ 9〇(s，ih 經濟部中央標準局員工消費合作社印製 ，H-6,嘧啶），8.84，8.80(2m，各個 ih，3-吡啶），8.66 ，7.45(2m，各個 2H，4_ 吡啶），7.5〇(m，1H，3-吡啶） ，7.28-7.10(m，4H，PhF)。14 Fluorophenyl) -2- (3-p ratio than yl) 3- (4-p ratio than pyridyl) _p dense bite: MS (m / z): 329.0 (M + H); CaoHnFls ^ requires 値 328.4. 4- NMR (CDC13): d 9.80 (bs, H-2, Hitachi), $ 90 (s, ih Printed by the Consumer Cooperative of the Central Standards Bureau, Ministry of Economic Affairs, H-6, pyrimidine), 8.84, 8.80 (2m , Each ih, 3-pyridine), 8.66, 7.45 (2m, each 2H, 4-pyridine), 7.50 (m, 1H, 3-pyridine), 7.28-7.10 (m, 4H, PhF).

R1 -118 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（116 1-15 5-(4·氟苯基）_2-(2-峨淀基比淀基）-p密淀： MS(m/z): 329·0(Μ + Η)+; C2〇H13FN4< 求値 328.4。111-NMR(CDC13) : d 9.0 l(s，1Η，H-6，,淀），8·92，8·66 ，7.94，7.48(4m，各個 1Η，2-外t：淀），8.66，7.47(2m ，各個 2H，4-峨淀），7·26，7.14(2m，各個 2H，PhF)。 R1 α 1-16 5-(4-氟苯基）-2-(2 -?比p井基）-4-(4-峨淀基喃淀： MS(m/z): 330·2(Μ + Η)+; C19H12FN5 要求値 329.3。 NMR(CDCl3) : 9.84(m，1H，Η_3，ρ比口井），9.01(s，1H ’ H-6，墙淀），8.84 9 8.76(2m，各個 1H，H-5，H-6 ，峨 口井），8.65，7.44(2m，各個 2H，峨淀），7.26，7.13(2m ，各個 2H，PhF)。 R1 (請先閲讀背面之注意事項再填寫本頁)R1 -118 This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A7 B7 V. Description of the invention (116 1-15 5- (4 · fluorophenyl) _2- (2-Edian base ratio (Yenji) -p dense lake: MS (m / z): 329 · 0 (Μ + Η) +; C20H13FN4 < Find 値 328.4. 111-NMR (CDC13): d 9.0 l (s, 1Η, H- 6, Yodo), 8.92, 8.66, 7.94, 7.48 (4m, each 1Η, 2-out t: Yodo), 8.66, 7.47 (2m, each 2H, 4-Edo), 7.26, 7.14 (2m, each 2H, PhF). R1 α 1-16 5- (4-fluorophenyl) -2- (2-? Ratio p-well-based) -4- (4-Edo-based glutamate: MS ( m / z): 330 · 2 (Μ + Η) +; C19H12FN5 requires 値 329.3. NMR (CDCl3): 9.84 (m, 1H, Η_3, ρ than a well), 9.01 (s, 1H 'H-6, wall Lake), 8.84 9 8.76 (2m, each 1H, H-5, H-6, Eguchi), 8.65, 7.44 (2m, each 2H, Edo), 7.26, 7.13 (2m, each 2H, PhF). R1 (Please read the notes on the back before filling this page)

、1T 經濟部中央標準局員工消費合作社印製 1-17 5·(4 -轨苯基）-2_(2 -甲基p塞峻_4 -基）-4-(4 -峨淀基）-口密淀 J_MS(m/z) ： 349·0(Μ + Η)+ ; C19H13FN4S 要求値 348.4。 ^-NMRCCDCls) : d 8.90(s，1H，H-6，嘧啶），8.63， 7.42(2m，各個 2H，峨淀），8.32(s，1H，H-5，p塞唑）， 7.22，7.10(2m，各個 2H，PhF)，2.88(s，3H，CH3)。 119- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） -Φ. 經满部中央標準局員工消費合作社印製 520362 A7 —__ .____B7 五、發明説明（117 ), 1T Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs of the People's Republic of China 1-17 5 · (4- orbital phenyl) -2_ (2-methyl psajun _4-yl) -4- (4-Edianji)- J_MS (m / z): 349.0 (Μ + Η) +; C19H13FN4S requires 値 348.4. ^ -NMRCCDCls): d 8.90 (s, 1H, H-6, pyrimidine), 8.63, 7.42 (2m, each 2H, Edo), 8.32 (s, 1H, H-5, petazole), 7.22, 7.10 (2m, each 2H, PhF), 2.88 (s, 3H, CH3). 119- This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) -Φ. Printed by the Consumer Standards Cooperative of the Central Bureau of Standards 520362 A7 —__ .____ B7 V. Description of the Invention (117)

卜18 ·5·(4_氟苯基）_4_(4_吡^基）_2-(2·嘍吩基）·嘧啶： MS(m/z): 334·2(Μ + Η)+; C19H12FN3S 要求値 333.4。4-NMR(CDC13) : d 8.74(s， 1H，H-6，嘧啶），8.63 ， 7.41(2m，各個 2H，吡啶），8 13，7 55(2ϊη，各個 iH， 嘧吩），7.20(m，3H，PhF，噻吩），7.10(m，2H，PhF)。 … 下列嘧淀係根據概略程序經由3-(二甲胺基）-2-(4-氟苯基）· 1-(4-吡啶基）-3-丙晞·1-酮與胍反應製備： 1-19 2-胺基-5-(4-氟苯基吡啶基）-嘧啶：MSim/z、: 267.0(M + H)+ ; C15HnFN4 要求値 266.3。111以^111(0以80-d6) : d8.54 ’ 7.26(2m，各個 2H，峨淀），8.35(s，1H， H-6，口密啶），7.22-7.12(m，4H，PhF)，6.97(s，2H， NH2) 〇 R1 = NH2Bu 18 · 5 · (4_fluorophenyl) _4_ (4_pyridinyl) _2- (2 · fluorenyl) · pyrimidine: MS (m / z): 334 · 2 (Μ + Η) +; C19H12FN3S Requirement 333.4. 4-NMR (CDC13): d 8.74 (s, 1H, H-6, pyrimidine), 8.63, 7.41 (2m, each 2H, pyridine), 8 13, 7 55 (2ϊη, each iH, pyrimidine ), 7.20 (m, 3H, PhF, thiophene), 7.10 (m, 2H, PhF). … The following pyrimide is prepared by reacting 3- (dimethylamino) -2- (4-fluorophenyl) · 1- (4-pyridyl) -3-propanone · 1-one with guanidine according to the outline procedure: 1-19 2-Amino-5- (4-fluorophenylpyridyl) -pyrimidine: MSim / z ,: 267.0 (M + H) +; C15HnFN4 requires 値 266.3. 111 to ^ 111 (0 to 80-d6 ): d8.54 '7.26 (2m, each 2H, Edo), 8.35 (s, 1H, H-6, orimidine), 7.22-7.12 (m, 4H, PhF), 6.97 (s, 2H, NH2 ) 〇R1 = NH2

1-20 2-乙基胺基-5-(4-氟苯基峨淀基）喊淀： MS(m/z): 295·0(Μ + Η)+; C17H15FN4 要求値 294.3。111-NMR(CDC13) : d8.56，7.32(m，各個 2H，吡啶），8.36(s ，111，11-6，嘧啶），7.12-6.99(111，411，？1^)，5.33(未 光學分割，1H，NH)，3.58(s，2H，CH2)，1.32(t，3H -120 - 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） " (請先閱讀背面之注意事項再填寫本頁)1-20 2-Ethylamino-5- (4-fluorophenylgadolide): MS (m / z): 295 · 0 (Μ + Η) +; C17H15FN4 requires 値 294.3. 111-NMR (CDC13): d8.56, 7.32 (m, each 2H, pyridine), 8.36 (s, 111, 11-6, pyrimidine), 7.12-6.99 (111, 411,? 1 ^), 5.33 (not optically divided, 1H, NH), 3.58 (s, 2H, CH2), 1.32 (t, 3H -120-This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) " (Please read the precautions on the back before (Fill in this page)

、1T -ΑΎ. 520362 A7 — B7 五、發明説明（118) ，ch3) 〇 R1 = CH3CH2-NH- 1-21 5-(4_氟苯基）·4·(4·吡啶基）-2-(2-磺基乙基胺基V嘧啶 :MS(m/z) : 375.2(M + H)+ ; C17H15FN403S 要求値 374.4。 iH-NMR^DMSO-dd : d 8.51，7.25(2d，各個 2H，吡啶） ，8.36(s，1H，H-6，嘧啶），7.32〇，111，^^11)，7.2· 7.1(m，4H，PhF)，3.62(q，2H，CH2N)，2.72(t，2H ，CH2) 〇 R1 = H03S-CH2-CH2-NH- 1-22 2-(2-二乙基胺基乙基胺基）-5-(4-氟苯基）-4-(4-吡啶某 )-嘧啶：MS(m/z) : 365·8(Μ + Η)+ ; C21H24FN5 要求値 365·5 。iH-NMRCCDCU) : d 8·55，7.28(2m，各個 2Η，吡啶） ，8.34(s，1H，H-6，嘧啶），7·08，7.01(2m，各個 2H ，PhF)，5.95(bs，1H，NH)，3.60(q，2H，CH2N)， 2.76(t，2H，CH2)，2.65(q，4H，2 CH2CH3)，l.〇8(t ，6H，2 CH3) 〇 R1 二（CH3CH2)2NCH2CH2NH- 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 1-23 (4-氟苯基）-4-(4-吡啶基V2_(硫脲基V嘧啶：MS(m/z) :326.2(M + H)+ ; C16H12FN5S 要求値 325.4 。 NMR(DMSO-d6) : d 10.84，10.11，9.20(3s，各個 1H， NH，SH)，8.75(s，1H，H-6，嘧啶），8.59，7,32(2m ，各個 2H，吡啶），7.28，7.21(2m，各個 2H，PhF)。 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（119) R1 1-24 2-(2,6-二氯苯基胺基）-5-(4-氟苯基）-444-吡啶基）-嘧 淀· MS(m/z) _· 410·8(Μ)+ ; CnHuChF]^ 要求値 411·3。 ^-NMRCCDCls) · d 8·54，7.30(2m，各個 2H，吡啶）， 8.45(s，1H，H-6,嘧啶），7.45(d，2H，PhCl2)，7.21(t ，1H，PhCl2)，7·12，7.04 (2m，各個 2H，PhF)。520362 A7 — B7 5. Explanation of the invention (118), ch3) 〇R1 = CH3CH2-NH- 1-21 5- (4-fluorophenyl) · 4 · (4 · pyridyl) -2- (2-sulfoethylamino V-pyrimidine: MS (m / z): 375.2 (M + H) +; C17H15FN403S requires 値 374.4. IH-NMR ^ DMSO-dd: d 8.51, 7.25 (2d, each 2H, Pyridine), 8.36 (s, 1H, H-6, pyrimidine), 7.32〇, 111, ^^ 11), 7.2 · 7.1 (m, 4H, PhF), 3.62 (q, 2H, CH2N), 2.72 (t, 2H, CH2) 〇R1 = H03S-CH2-CH2-NH- 1-22 2- (2-diethylaminoethylamino) -5- (4-fluorophenyl) -4- (4-pyridine (A) -Pyrimidine: MS (m / z): 365 · 8 (Μ + Η) +; C21H24FN5 requires 値 365 · 5. iH-NMRCCDCU): d 8.55, 7.28 (2m, each 2H, pyridine), 8.34 (s, 1H, H-6, pyrimidine), 7.08, 7.01 (2m, each 2H, PhF), 5.95 (bs , 1H, NH), 3.60 (q, 2H, CH2N), 2.76 (t, 2H, CH2), 2.65 (q, 4H, 2 CH2CH3), 1.08 (t, 6H, 2 CH3) 〇R1 two ( CH3CH2) 2NCH2CH2NH- Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) 1-23 (4-fluorophenyl) -4- (4-pyridyl V2_ (thioureido V pyrimidine: MS (m / z): 326.2 (M + H) +; C16H12FN5S requires 値 325.4. NMR (DMSO-d6): d 10.84, 10.11, 9.20 (3s, each 1H, NH, SH), 8.75 (s , 1H, H-6, pyrimidine), 8.59, 7, 32 (2m, each 2H, pyridine), 7.28, 7.21 (2m, each 2H, PhF). This paper size applies to China National Standard (CNS) A4 specifications (210X297) (Mm) 520362 A7 B7 V. Description of the invention (119) R1 1-24 2- (2,6-dichlorophenylamino) -5- (4-fluorophenyl) -444-pyridyl) -pyrimidine · MS (m / z) _ · 410 · 8 (Μ) +; CnHuChF] ^ requires 値 411 · 3. ^ -NMRCCDCls) · d 8 · 54, 7.30 (2m, each 2H, pyridine), 8.45 (s, 1H H-6, pyrimidine), 7.45 (d, 2H, PhCl2), 7.21 (t, 1H, PhCl2), 7 · 12,7.04 (2m, each 2H, PhF).

(請先閱讀背面之注意事項再填寫本頁) R1 1-25 2_(2,6_二甲基苯基胺基）-5-(4-氟苯基V4-M-吡啶基）-口密淀：MS(m/z) : 371 ·0(Μ + Η)+ ; C23H19FN4 要求値 370.4 。^-NMRCCDCls) : d 8.56，7.32(2d，各個 2H，吡啶） ，8.40(s，1H，H-6,嘧啶），7.20(s，3H，PhCl2)，7.11 ，7.04(2m，各個 2H，PhF)，6.66(s，1H，NH)，2.20(s ，6H，2CH3)。(Please read the precautions on the back before filling out this page) R1 1-25 2_ (2,6_dimethylphenylamino) -5- (4-fluorophenyl V4-M-pyridyl) -closed Lake: MS (m / z): 371 · 0 (Μ + Η) +; C23H19FN4 requires 値 370.4. ^ -NMRCCDCls): d 8.56, 7.32 (2d, each 2H, pyridine), 8.40 (s, 1H, H-6, pyrimidine), 7.20 (s, 3H, PhCl2), 7.11, 7.04 (2m, each 2H, PhF ), 6.66 (s, 1H, NH), 2.20 (s, 6H, 2CH3).

Me 經濟部中央標準局員工消費合作社印製Printed by Me Consumer Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs

R1 = > 1-26 5-(4-氣苯基比症基）-p密淀：MS(m/z): 373.0(M + H)+ ； C22H17FN40 要求値 372.4 。 4- NMR(CDC13): d8.62，7.40(2m，各個 2H，吡啶），8.60(m ，1H，PhOMe)，8.52(s，1H，H-6，喊淀），7,99(s， 122- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（120) 1H，NH)，7·18-6·94〇，7H，PhF，PhOMe)，3.96(s ，3H，CH30)。 V 〇Me R1 =R1 = > 1-26 5- (4-Phenylphenyl) -p dense lake: MS (m / z): 373.0 (M + H) +; C22H17FN40 requires 値 372.4. 4- NMR (CDC13): d8.62, 7.40 (2m, each 2H, pyridine), 8.60 (m, 1H, PhOMe), 8.52 (s, 1H, H-6, yodo), 7,99 (s, 122- This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) 520362 A7 B7 V. Description of the invention (120) 1H, NH), 7 · 18-6 · 94〇, 7H, PhF, PhOMe) , 3.96 (s, 3H, CH30). V 〇Me R1 =

S' 1-27 5_(4·氟苯基）-2-(4-氟苯基胺基）-4-(4-吡啶基）-嘧啶： MS(m/z): 361·0(Μ + Η)+; C21H14F2N4 要求値 360.4。4- NMR(CDC13) : d 8.58，7·32(χη，2H，吡啶），8.46(s， 1H，H-6，嘧啶），7.62(m，2H，PhF)，7.24(bs，1H ，NH)，7.13-7.00(m，6H，PhF)。 s、 (請先閲讀背面之注意事項再填寫本頁) R1 1-28 2-(4-乙基苯基胺基）-5-(4-氟苯基吡啶基V嘧啶 ：MS(m/z) ·· 371·2(Μ + Η)+ ; C23H19FN4 要求値 370.4。 ^-NMRCCDCU) : d 8·61，7.41(2m，各個 2H，吡啶）， 8.49 (s，1H，H-6，嘧啶），7.60，7.23 (2d，各個 2H， PhEth)，〜7·28(ΝΗ)，7.13，7.06(2m，各個 2H，PhF)， 2.67(q，2H，CH2)，1.27(t，3H，CH3)〇S '1-27 5_ (4 · fluorophenyl) -2- (4-fluorophenylamino) -4- (4-pyridyl) -pyrimidine: MS (m / z): 361 · 0 (Μ + Η) +; C21H14F2N4 requires 値 360.4. 4-NMR (CDC13): d 8.58, 7.32 (χη, 2H, pyridine), 8.46 (s, 1H, H-6, pyrimidine), 7.62 (m, 2H, PhF ), 7.24 (bs, 1H, NH), 7.13-7.00 (m, 6H, PhF). s, (Please read the precautions on the back before filling in this page) R1 1-28 2- (4-ethylphenylamino) -5- (4-fluorophenylpyridyl V-pyrimidine: MS (m / z ) · 371.2 (M + Η) +; C23H19FN4 requires 値 370.4. ^ -NMRCCDCU): d 8.61, 7.41 (2m, each 2H, pyridine), 8.49 (s, 1H, H-6, pyrimidine) , 7.60, 7.23 (2d, each 2H, PhEth), ~ 7 · 28 (NΗ), 7.13, 7.06 (2m, each 2H, PhF), 2.67 (q, 2H, CH2), 1.27 (t, 3H, CH3) 〇

、1T 1·· 經濟部中央標準局員工消費合作社印製 S' R1 29 5-(4 -氟苯基）-4-(4 -p比淀基）-2-(3-二氟甲基苯基胺基 -123- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X2W公釐） 520362 A7 B7 經濟部中央標率局員工消費合作社印製 五、發明説明（121) 嘧啶：MS(m/z) : 411·0(Μ+Η)+ ; C22H14F4N4 要求値 410.4 。iH-NMR^CDCU) : d 8·60，7.35(2mv，各個 2H，峨淀） ，8.52(s，1H，H-6，嘧啶），8.23，？·73，7.46(s，dd ，t，各個 1H，PI1CF3)，7.44(s，1H，NH)，7.3i(dd， 1H，PhCF3)，7.13，7.05(2m，各個 2H，PhF)。 R1, 1T 1 ·· Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs, S 'R1 29 5- (4-fluorophenyl) -4- (4-p than Yodoyl) -2- (3-difluoromethylbenzene Amino-123- This paper size applies to Chinese National Standard (CNS) A4 specification (210X2W mm) 520362 A7 B7 Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (121) Pyrimidine: MS (m / z): 411.0 (M + Η) +; C22H14F4N4 requires 値 410.4. iH-NMR ^ CDCU): d 8.60, 7.35 (2mv, each 2H, Edo), 8.52 (s, 1H, H-6 , Pyrimidine), 8.23 ,? 73, 7.46 (s, dd, t, each 1H, PI1CF3), 7.44 (s, 1H, NH), 7.3i (dd, 1H, PhCF3), 7.13, 7.05 (2m, each 2H, PhF). R1

1-30 2-(芊基胺基）-5-(4-氟苯基）-4-(4-吡啶某嘧啶： MS(m/z): 357.0(M + H)+; C22H17FN4 要求値 356·4。iH-NMR(CDC13) : d 8.55 ^ 7.28(2m，各個 2H，吡啶），8.36(s ，1H，H-6，。密淀），7·44-7·28(ιη，5H，Ph)，7·〇9， 7.02(2m，各個 2H，PhF)，5.71(t，1H，NH)，4.75(d ，1H，CH2)。 R11-30 2- (fluorenylamino) -5- (4-fluorophenyl) -4- (4-pyridine): MS (m / z): 357.0 (M + H) +; C22H17FN4 requires 値 356 · 4. iH-NMR (CDC13): d 8.55 ^ 7.28 (2m, each 2H, pyridine), 8.36 (s, 1H, H-6, dense lake), 7.44-7 · 28 (ιη, 5H, Ph), 7.09, 7.02 (2m, each 2H, PhF), 5.71 (t, 1H, NH), 4.75 (d, 1H, CH2). R1

(T S' 3 1 5-(4 -鼠苯基）-2_(2 -苯基乙基胺基）-4-(4 -p比淀基）-u密淀 _MS(m/z) : 371.0(M + H)+ ; C23H19FN4 要求値 370.4 。 iH-NMRCCDCh) : d 8.56(m，2H，吡啶），8.35(s，1H， H-6，嘧啶），7·38-7·22(πι，7H，Ph，吡啶），7.08， 7.02(2m，各個 2H，PhF)，5.32(t，1H，NH)，3.80(q ，2H，CH2N)，2.92(t，2H，CH2)。 -124 (請先閱讀背面之注意事項再填寫本頁)(TS '3 1 5- (4-Methenyl) -2_ (2-phenylethylamino) -4- (4-p ratio) -u dense lake_MS (m / z): 371.0 (M + H) +; C23H19FN4 requires 値 370.4. IH-NMRCCDCh): d 8.56 (m, 2H, pyridine), 8.35 (s, 1H, H-6, pyrimidine), 7.38-7 · 22 (πι, 7H, Ph, pyridine), 7.08, 7.02 (2m, each 2H, PhF), 5.32 (t, 1H, NH), 3.80 (q, 2H, CH2N), 2.92 (t, 2H, CH2). -124 (Please read the notes on the back before filling this page)

本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 ___ B7 五、發明説明（122) R1This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 520362 A7 ___ B7 V. Description of the invention (122) R1

“32 5-(4-鼠本基）-4_(4·ρ比淀基）-2-峨洛咬基- π密淀： MS(m,z) ·· 312·2(Μ + Η)+ ; C19H17FN4 要求値^❹]。1!!· NMR(CDC13) : d8.54，7.32(2d，各個 2H，P比旬，8.37(S ，iH，H-6 "密淀），7·〇ό，7 〇〇(2m，各個 ，phF) ，3.68，2.05(2m，各個 4H，4 CH2)。 Ν' (請先閱讀背面之注意事項再填寫本頁) R1 1 "33 5-(4-氟苯基）_2_嗎 p林基-4-(4-峨淀基淀：MS(m/z) :337.2(M + H)+ ; C19H17FN40 要求値 336.4 。 ιΗ_ NMR(CDC13) ·· d 8·56，7.31(2m，各個 2H，吡啶），8.40(s ’ 1H，H-6 ’ 癌淀），7·10，7.03(2m，各個 2H，PhF) ，3.94，3.83(2m，各個 4H，4 CH2)。 R1 〇 N· 經濟部中央標準局員工消費合作社印製 1-3 4 2-(3，5_二甲基外1：峻基）-5-(4-氟苯基）-4-(4 -p比咬基）—p密 啶：MS(m/z) ： 346.0(M + H)+ ; C2〇H16FN5 要求値 345.4。 ^-NMRCCDCls) : d 8.80(s，1H，H-6，嘧啶），8.60， 7.35(2m，各個 2H，吡啶），7.18，7.08(2m，各個 2H， PhF)，6.08(s，1H，p比峻），2.70，2.30(2s，各個 3H , -125- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 R1 五、發明説明（123) 2CH3) 〇 ,Ν-"32 5- (4-ratyl) -4_ (4 · ρbiyodoyl) -2-erotetrayl-π dense lake: MS (m, z) ··· 312 · 2 (Μ + Η) + C19H17FN4 requires 値 ^ ❹]. 1 !! · NMR (CDC13): d8.54, 7.32 (2d, each 2H, P ratio, 8.37 (S, iH, H-6 " dense lake), 7. · 〇 ό, 7 〇〇 (2m, each, phF), 3.68, 2.05 (2m, each 4H, 4 CH2). Ν '(Please read the precautions on the back before filling this page) R1 1 " 33 5- (4 -Fluorophenyl) _2_morphin 4- (4-Edian): MS (m / z): 337.2 (M + H) +; C19H17FN40 requires 値 336.4. ΙΗ_ NMR (CDC13) ·· d 8.56, 7.31 (2m, each 2H, pyridine), 8.40 (s '1H, H-6' cancer lake), 7.10, 7.03 (2m, each 2H, PhF), 3.94, 3.83 (2m, each 4H , 4 CH2). R1 〇N · Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 1-3 4 2- (3,5_dimethylexcept 1: Junji) -5- (4-fluorophenyl)- 4- (4-p ratio) -p-pyrimidine: MS (m / z): 346.0 (M + H) +; C20H16FN5 requires 値 345.4. ^ -NMRCCDCls): d 8.80 (s, 1H, H -6, pyrimidine), 8.60, 7.35 (2m, each 2H, pyridine), 7.18, 7.08 (2m, each 2H, PhF), 6.08 (s, 1H, p ratio), 2.70, 2.30 (2s, each 3H, -125-) This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 520362 A7 B7 R1 V. Description of the Invention (123) 2CH3) 〇, Ν-

Me 1-35 5·(4-氟苯基）-4-(4-吡啶基）-2-「3,5-貳（三氟甲基）苯胺 基磺醯基 1-嘧啶： MS(m/z) ·· 542·8(Μ + Η)+ ； C23H13F7N402S 要求値 542.4 。 j-NMR^DMSO-dd : d 8.63(s，1H，H-6，喊淀），8.56(m，2H，p比淀），8.49 ，8.43(2s，2H，1H，Ph(CF3)2)，7.26-7· 15(m，6H， PhF，吡啶）。 (請先閱讀背面之注意事項再填寫本頁)Me 1-35 5 · (4-fluorophenyl) -4- (4-pyridyl) -2- "3,5-fluoren (trifluoromethyl) anilinesulfonamido1-pyrimidine: MS (m / z) ·· 542 · 8 (Μ + Η) +; C23H13F7N402S requires 値 542.4. j-NMR ^ DMSO-dd: d 8.63 (s, 1H, H-6, yodo), 8.56 (m, 2H, p ratio Lake), 8.49, 8.43 (2s, 2H, 1H, Ph (CF3) 2), 7.26-7 · 15 (m, 6H, PhF, pyridine). (Please read the precautions on the back before filling this page)

FiC R1 v° cf3 經濟部中央標準局員工消費合作社印製FiC R1 v ° cf3 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs

1-36 2_『4_胺基苯胺基續S盛基1-5"(4-氣I基)麵4一(4-卩比 < 基)-嘧啶：MS(m/z) : 421·8(Μ + Η)+ ; C21H16FN502S 要求値 421.5。iH-NMR^DMSO-dd : d8.58(s，1H，H-6，嘧啶） ，8.575(m，2H，吡啶），7.64，6.56(2d，各個 2H，PhNH2) ，7.28-7.15(m，6H，PhF，吡啶），5.99(s，2H，NH2)。 R1 Η,Ν -126- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（124) 1-37 2-(2-二甲基胺基乙基硫基）-5·(4·氟苯基）-4-(4-吡啶基 )-嘧啶係根據概略程序經由3-(二甲基腠基）-2-(4-氟苯基）- 1- (4-吡啶基）-3-丙烯-1-酮與S-(2-二甲棊胺基乙基）異硫脲 反應製備。MS(m/z) : 355·2(Μ + Η)+ ; C19H19FN4S 要求値 354·5。iH-NMRCCDCU) : d 8.59，7.32(2m，各個 2H， 吡啶），8.58(s，1H，H-6，嘧啶），7·16，7.08(2m，各 個 2H，PhF)，3.40，2.76(2m，各個 2H，2 CH2)，2.3 7(s ，6H，2 CH3)。 R1 = (CH3)2NCH2CH2S- 實例2 2- N取代2-胺基-5-(4-氟苯基）-4_(4-吡啶基）-嘧啶之概略製 備程序 a_.5_(4·氟苯基）-4-(4-吡啶基）-2(lHV嘧啶酮： ----------—·裝-- (請先閱讀背面之注意事項再填寫本頁)1-36 2_ "4-Amine aniline group continued S Shengji 1-5 " (4-Ga I group) surface 4-a (4-A ratio < group)-pyrimidine: MS (m / z): 421 · 8 (Μ + Η) +; C21H16FN502S requires 値 421.5. iH-NMR ^ DMSO-dd: d8.58 (s, 1H, H-6, pyrimidine), 8.575 (m, 2H, pyridine), 7.64, 6.56 (2d, each 2H, PhNH2), 7.28-7.15 (m, 6H, PhF, pyridine), 5.99 (s, 2H, NH2). R1 Η, N -126- This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A7 B7 V. Description of the invention (124) 1-37 2- (2-dimethylaminoethylsulfur) Group) -5 · (4 · fluorophenyl) -4- (4-pyridyl) -pyrimidine system via 3- (dimethylfluorenyl) -2- (4-fluorophenyl)-1- (4-Pyridyl) -3-propen-1-one is prepared by reacting S- (2-dimethylamidoethyl) isothiourea. MS (m / z): 355.2 (Μ + Η) +; C19H19FN4S requires 値 354.5. iH-NMRCCDCU): d 8.59, 7.32 (2m, each 2H, pyridine), 8.58 (s, 1H, H-6, pyrimidine), 7.16, 7.08 (2m, each 2H, PhF), 3.40, 2.76 (2m , Each 2H, 2 CH2), 2.3 7 (s, 6H, 2 CH3). R1 = (CH3) 2NCH2CH2S- Example 2 General procedure for the preparation of 2-N-substituted 2-amino-5- (4-fluorophenyl) -4_ (4-pyridyl) -pyrimidine a_.5_ (4 · fluorophenyl ) -4- (4-pyridyl) -2 (lHV pyrimidinone: ------------ · pack-(Please read the precautions on the back before filling this page)

NH,NH,

經濟部中央標準局員工消費合作社印製 尿素（0.67克，1 1. 15毫莫耳）添加至經攪摔的乙醇系〇 62 N 乙氧化鈉溶液（15毫升）。添加3-(二甲基胺基）-2-(4-氟苯基 )_ 1-(4-吡哫基）-3-丙烯-1·酮（9.29毫莫耳）之乙醇系溶液（60 耄升）及混合物回流隔夜。經蒸發接著柱式層析（5 %甲醇/ 二氯甲坑至100 %甲醇）。以二氯甲烷/甲醇處理所得產物獲 ___________ - 127- 本紙張尺度適用中國國家標準（CNS ) ( 210X297公襲) --- 520362 A7 B7 五、發明説明（125) 得晶體（推定爲脲）經過濾出。濾液經蒸發及殘餘物於矽膠 柱再層析（氯仿/甲醇/水=70 : 20 : 1/獲得標題化合物呈 黃色發泡體。 λ MS(m/z): 268.2(M + H)+; C15H10FN3O 要求値 267.3。11 NMR(DMSO-d6) : d 8·55，7.24(2m，各個 2H，吡啶）， 8.22(bs，1H，H-6，嘧啶），7.20-7.10(m，4H，PhF)。 b · 2 -氣-5 _ ( 4 _氣苯基）-4 - ( 4 _ p比淀基）_ p密淀：Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. Urea (0.67 g, 11.15 mmol) was added to a stirred ethanol-based 62 N sodium ethoxide solution (15 ml). Adding 3- (dimethylamino) -2- (4-fluorophenyl) _ 1- (4-pyridyl) -3-propene-1 · one (9.29 mmol) to an ethanol-based solution (60耄) and the mixture was refluxed overnight. Evaporation followed by column chromatography (5% methanol / dichloromethane to 100% methanol). The product obtained by dichloromethane / methanol treatment is ___________-127- This paper size is applicable to Chinese National Standard (CNS) (210X297 public attack) --- 520362 A7 B7 V. Description of the invention (125) Crystal obtained (presumed to be urea) Filtered out. The filtrate was evaporated and the residue was rechromatographed on a silica gel column (chloroform / methanol / water = 70: 20: 1 / to obtain the title compound as a yellow foam. Λ MS (m / z): 268.2 (M + H) +; C15H10FN3O requires 値 267.3.11 NMR (DMSO-d6): d 8.55, 7.24 (2m, each 2H, pyridine), 8.22 (bs, 1H, H-6, pyrimidine), 7.20-7.10 (m, 4H, PhF ). B · 2 -Ga-5 _ (4 _Gaphenyl)-4-(4 _ p ratio than yodo) _ p dense lake:

(請先閱讀背面之注意事項再填寫本頁) 5-(4 -氟苯基）-4_(4_p比淀基）_2(1H)-喃淀酮（2·41毫莫耳）與 磷醯氯（3毫升）之混合物回流加熱45分鐘。於浴溫大於 5 0 C蒸發至乾。燒瓶於冰浴中冷卻及添加冰水。若發現ρ η 値仍爲酸性，則混合物以5 〇/。氫氧化銨水溶液中和。以二 氯甲坑萃取’接著有機溶液以氯化納水溶液洗〉條，脱水及 經濟部中央標準局員工消費合作社印製 备發獲彳于標題化合物呈黃色發泡體，其未經進一步純化即 供使用。 MS(m/z)·· 286.1(M + H)+，· C15H19C1FN3 要求値“乂？。^-NMR(CDC13): d8.68(s， 1H，Η·6，嘧啶），8 62， 7.42(2m，各個 2Η，吡啶），7.23-7.1〇(m，4Η，phF)。 _- 128- 本紙張尺度適用中國國家標準（CNS ) A4規格（21 OX 297公釐） 520362 A7 B7 五、發明説明（126) c.概略程序(Please read the precautions on the back before filling out this page) 5- (4-Fluorophenyl) -4_ (4_pBiYodo) _2 (1H) -pyranone (2.41 mmol) and phosphonium chloride (3 ml) of the mixture was heated at reflux for 45 minutes. Evaporate to dryness at a bath temperature greater than 50 ° C. The flask was cooled in an ice bath and ice water was added. If it is found that ρ η 酸性 is still acidic, the mixture is reduced by 50%. Neutralize with aqueous ammonium hydroxide. Extraction with dichloromethane, followed by washing the organic solution with aqueous sodium chloride solution>, dehydration and printing by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, and obtained the title compound as a yellow foam, which was not further purified For use. MS (m / z) ·· 286.1 (M + H) +, · C15H19C1FN3 requires "値"? ^-NMR (CDC13): d8.68 (s, 1H, Η · 6, pyrimidine), 8 62, 7.42 (2m, each 2Η, pyridine), 7.23-7.10 (m, 4Η, phF). _- 128- This paper size applies to China National Standard (CNS) A4 (21 OX 297 mm) 520362 A7 B7 V. Invention Explanation (126) c. Outline procedure

經濟部中央標準局員工消費合作社印製 2-氯-5-0-氟苯基）_4_(4_吡啶基）_嘧啶（5〇_12〇毫克， (M8-0.42毫莫耳）與胺’ hnr5r21〇 〇毫升）之混合物於⑽ C加熱5·30分鐘（薄層層析檢查）。混合物直接施加至矽膠 柱，柱以甲醇/二氯甲烷展開。 實例2-6 , 2_U，2_12，2_2〇及2_26之例使用以乙醇 做溶劑之替代程序。 下列嘧啶係根據此種程序使用適當胺製備： 2·1 2_(2-fe基乙基胺基）-5-(4-氟苯基）二吡啶基嘧啶鹽 莖_鹽：,· MS(m/z) : 310·2(Μ + Η)+ ; C17H16FN5_HC1 要求値 309.4 + 36.5。iH-NMR^CDsOD) : d 8.84，8.10(2m，各個 2H，外匕淀），8.58(s，1H，H-6，喃唉），7.28，7.15(2m ，各個 2H，PhF)，3.83(t，2H，CH2)，3.27(t，2H， CH2)。 R1 = NH2CH2CH2NH- 2-2 2-(3-胺基丙基胺基）-5-(4 -氟苯基）-4-(4-pr比淀基）-p密淀鹽 酸鹽：MS(m/z) : 324·0(Μ + Η)+ ; C18H18FN5_HC1 要求値 323.4 + 36.5。iH-NMR^CDsOD) : d 8·85，8· 10(m，2H， ρ比淀），8.54(s，1Η，Η·6，喊淀），7.27，7.14(2m，各 -129- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） (請先閲讀背面之注意事項再填寫本頁) 訂_ 1· 520362 A7 B7 經濟部中央標準局員工消費合作社印製 五、發明説明（127)個 2H，PhF)，3.84，3.68(2t，各個 2H，2 CH2N)，2·18(πι ，2Η，CH2)。 R1 = NH2CH2CH2CH2NH- 2-3 2 — (4 -月安基丁基月安基)晒5-(4_氣苯基)一4-(4 -口比 < 基)一口密 < 鹽 酸鹽：MS(m/z) : 338·0(Μ + Η)+ ; C19H20FN5-HC1 要求値 337.4 + 36.5。iH-NMR^CDsOD) : d 8.80，8.05(2m，各個 2H，吡啶），8.50(s，1H，H-6，嘧啶），7.25，7.14(2m ，各個 2H，PhF)。3.58(bt，2H，CH2)，3.02(bt，1H ，CH2)，1.80(m，4H，2CH2) 〇 R1 二 NH2CH2CH2CH2CH2NH- 2-4 2-(2-二甲基胺基乙基胺基）-5-(4-氟苯基）-4-(4-吡啶某V 嘧啶鹽酸鹽：MS(m/z) : 338.2(M + H)+ ; C19H2〇FN5 要求値 337.4。 iH-NMRCCDCh) : d 8.57，7.30(2m，各個 2H， 吡啶），8.37(s，1H，H-6，嘧啶），7.10，7.03(2m，各 個 2H，PhF)，6.00(t，1H，NH)，3.66(q，2H，CH2) ，2.71(t，2H，CH2)，2.41(s，6H，2CH3)。 R1 = (ch3)2nch2ch2nh- 2-5 5-(4-氟苯基）-2-(2-苯基胺基乙基胺基）-4-(4-吡啶基嘧 啶鹽酸鹽：MS(m/z) : 386(M + H)+ ; C23H2〇FN5 要求値 385.5。 iH-NMRCCDCU) : d 8.57，7.28(m，2H，吡啶） ，8.36(s，1H，H-6，嘧啶），7.18(t，2H，Ph)，7.08 ，7.02(2m，各個 2H，PhF)，6.73(t，1H，Ph)，6.64(d ，2H，Ph)，5.62(bt，1H，NH)，3.80(q，2H，CH2) ，3.47(t，2H，CH2)。_-130- _____ 本紙張尺度適用中國國家標準（CNS ) A4規格（21〇X：297公釐） (請先閱讀背面之注意事項再填寫本頁} -裝. 訂 i# 520362 A7 B7 五、發明説明（128 R1 σ ΗΝ. Ν Κ 2-6 5-(4-氟苯基）-2-『2-(4-氟苯基胺基乙基胺基1·4-(4·吡 淀基）-喊淀：2•氯- 5- (4-氟苯基）-4-(4-0比淀基）-喊淀（103毫 克，0.36毫莫耳）及Ν-(4-氟苯基）伸乙基二胺（1毫升）於乙 醇（1毫升）回流加熱3小時。蒸發接著柱式層析（3 %甲醇/ 二氯甲烷）獲得標題化合物呈黃色固體。MS(m/z): 404.2(M + H)+ ; C23H19F2N5 要求値 403.4。iH-NMRCCDCU) :8.60，7.31(2m，各個 2H，吡啶），8.40(s，1H，H-6 ，嘧淀），7.11-7.02(2m，各個 2H，PhF)，6.90，6,60(t ，dd，各個 2H，PhF)，5.62(t，1H，NH)，3.82(q，2H ，CH2)，3.44(t，2H，CH2)。 R1 (請先閲讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印裂 2-7 5-(4 -氟苯基）-2-(4 -甲基爷基胺基）-4-(4 -p比淀基）·喃淀： MS(m/z): 371·2(Μ + Η)+，· C23H19FN4 要求値]?。^。1!!-NMR(CDC13): d8.55 ， 7.34(2m，各個 2H，口比淀），8.36(s ，1Η，H-6，嘧啶），7.30，7.18(2d，各個 2H，PhMe) ，7.08，7.02(2m，各個 2H，PhF)，5.69(bs，1H，NH) ，4.69(d，2H，CH2)，2.36(s，3H，CH3) 〇 -131 - 本紙張尺度適用中國國家標準（CNS ) A4規格（2l0X297公釐） 520362 A7 B7 五、發明説明（129 ) R1 ϊί 2-8 5 (4_氣苯基）-2·『2-(4 -氣本基）-乙基胺基1麵4-(4-¾匕淀基） 嘧啶：MS(m/z) : 389.2(M + H)+ ; C23H18F2N4 要求値 388·4 。iH-NMRCCDCh) : d 8.57(m，2Η，吡啶），8.36(s，1H ，H-6，嘧啶），7.32-7.20，7·12-6·98(2ιη，10H，2PhF ，吡啶），5.37(bt，1H，NH)，3.79(q，2H，CH2N)， 2.97(t，2H，CH2)。 R1Printed by the Consumers 'Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 2-Chloro-5-0-fluorophenyl) _4_ (4_pyridyl) _pyrimidine (50-20 mg, (M8-0.42 mmol) and amine' hnr5r2100 ml) mixture was heated at ⑽ C for 5.30 minutes (thin layer chromatography examination). The mixture was applied directly to a silica gel column, and the column was developed with methanol / dichloromethane. Examples 2-6, 2_U, 2_12, 2_20 and 2_26 use ethanol as a solvent replacement procedure. The following pyrimidines were prepared according to this procedure using appropriate amines: 2 · 1 2_ (2-feylethylamino) -5- (4-fluorophenyl) dipyridylpyrimidine salt stem_salt :, MS (m / z): 310 · 2 (Μ + Η) +; C17H16FN5_HC1 requires 値 309.4 + 36.5. iH-NMR ^ CDsOD): d 8.84, 8.10 (2m, each 2H, outer ridge), 8.58 (s, 1H, H-6, muffled), 7.28, 7.15 (2m, each 2H, PhF), 3.83 ( t, 2H, CH2), 3.27 (t, 2H, CH2). R1 = NH2CH2CH2NH- 2-2 2- (3-Aminopropylamino) -5- (4-fluorophenyl) -4- (4-pr ratio) -p dense lake hydrochloride: MS ( m / z): 324 · 0 (Μ + Η) +; C18H18FN5_HC1 requires 値 323.4 + 36.5. iH-NMR ^ CDsOD): d 8 · 85, 8 · 10 (m, 2H, ρ biyodo), 8.54 (s, 1Η, Η · 6, yodo), 7.27, 7.14 (2m, each -129- Paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read the notes on the back before filling out this page) Order _ 520362 A7 B7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (127) 2H, PhF), 3.84, 3.68 (2t, each 2H, 2 CH2N), 2.18 (π, 2Η, CH2). R1 = NH2CH2CH2CH2NH- 2-3 2 — (4-Methanylbutyl month anion) 5- (4-Gasphenyl) -4- (4-Mole ratio < yl) Mastic < hydrochloride : MS (m / z): 338 · 0 (Μ + Η) +; C19H20FN5-HC1 requires 値 337.4 + 36.5. iH-NMR (CDsOD): d 8.80, 8.05 (2m, each 2H, pyridine), 8.50 (s, 1H, H-6, pyrimidine), 7.25, 7.14 (2m, each 2H, PhF). 3.58 (bt, 2H, CH2), 3.02 (bt, 1H, CH2), 1.80 (m, 4H, 2CH2) 〇R1 diNH2CH2CH2CH2CH2NH- 2-4 2- (2-dimethylaminoethylethylamino)- 5- (4-fluorophenyl) -4- (4-pyridine V pyrimidine hydrochloride: MS (m / z): 338.2 (M + H) +; C19H2〇FN5 requires 値 337.4. IH-NMRCCDCh): d 8.57, 7.30 (2m, each 2H, pyridine), 8.37 (s, 1H, H-6, pyrimidine), 7.10, 7.03 (2m, each 2H, PhF), 6.00 (t, 1H, NH), 3.66 (q , 2H, CH2), 2.71 (t, 2H, CH2), 2.41 (s, 6H, 2CH3). R1 = (ch3) 2nch2ch2nh- 2-5 5- (4-fluorophenyl) -2- (2-phenylaminoethylethylamino) -4- (4-pyridylpyrimidine hydrochloride: MS (m / z): 386 (M + H) +; C23H2〇FN5 requires 値 385.5. iH-NMRCCDCU): d 8.57, 7.28 (m, 2H, pyridine), 8.36 (s, 1H, H-6, pyrimidine), 7.18 (t, 2H, Ph), 7.08, 7.02 (2m, each 2H, PhF), 6.73 (t, 1H, Ph), 6.64 (d, 2H, Ph), 5.62 (bt, 1H, NH), 3.80 (q , 2H, CH2), 3.47 (t, 2H, CH2). _-130- _____ This paper size applies to China National Standard (CNS) A4 (21〇X: 297mm) (Please read the precautions on the back before filling this page}-Binding. Order i # 520362 A7 B7 V. Description of the invention (128 R1 σ ΗN. Ν 2K 5--6- (4-fluorophenyl) -2- "2- (4-fluorophenylaminoethylethylamino1 · 4- (4 · pyridyl) ) -Xiaodian: 2 • Chloro-5- (4-fluorophenyl) -4- (4-0 than Dianji) -Xiaodian (103 mg, 0.36 mmol) and N- (4-fluorophenyl ) Ethylenediamine (1 ml) was heated at reflux for 3 hours in ethanol (1 ml). Evaporation followed by column chromatography (3% methanol / dichloromethane) gave the title compound as a yellow solid. MS (m / z): 404.2 (M + H) +; C23H19F2N5 requires 403.4. IH-NMRCCDCU): 8.60, 7.31 (2m, each 2H, pyridine), 8.40 (s, 1H, H-6, pyrimide), 7.11-7.02 (2m, Each 2H, PhF), 6.90, 6,60 (t, dd, each 2H, PhF), 5.62 (t, 1H, NH), 3.82 (q, 2H, CH2), 3.44 (t, 2H, CH2). R1 (Please read the notes on the back before filling this page) 2-7 5- (4-fluorophenyl) -2- (4-methyl Aminoamino group) -4- (4-p ratio), Nanato: MS (m / z): 371.2 (M + Η) +, C23H19FN4 requires 値]? ^. 1 !!-NMR (CDC13): d8.55, 7.34 (2m, each 2H, Hipido), 8.36 (s, 1H, H-6, pyrimidine), 7.30, 7.18 (2d, each 2H, PhMe), 7.08, 7.02 (2m , Each 2H, PhF), 5.69 (bs, 1H, NH), 4.69 (d, 2H, CH2), 2.36 (s, 3H, CH3) 〇-131-This paper size applies to China National Standard (CNS) A4 specifications ( 2l0X297 mm) 520362 A7 B7 V. Description of the invention (129) R1 ϊί 2-8 5 (4-Gaphenyl) -2 · 『2- (4-Gabenyl) -ethylamino 1-sided 4- ( 4-¾Dianyl) Pyrimidine: MS (m / z): 389.2 (M + H) +; C23H18F2N4 requires 値 388 · 4. IH-NMRCCDCh): d 8.57 (m, 2Η, pyridine), 8.36 (s, 1H, H-6, pyrimidine), 7.32-7.20, 7.12-6.98 (2m, 10H, 2PhF, pyridine), 5.37 (bt, 1H, NH), 3.79 (q, 2H, CH2N), 2.97 ( t, 2H, CH2). R1

(請先閲讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 2-9 2 -『2-(4-氯苯基)罐乙基胺基苯基)一4-(4 -这比 < 基) 嘧啶：MS(m/z) : 405·0(Μ+Η)+ ; C23H18C1FN4 要求値 404·9 。W-NMR^CDCh) : d 8.56(bs，2Η，吡啶），8.34(s，1H ，H-6，嘧啶），7.29(m，d，4H，p比啶，PhCl)，7.20(d ，2H，PhCl)，7.08，7.02(2m，各個 2H，PhF)，5.35(t ，1H，NH)，3.78(q，CH2N)，2.96(t，2H，CH2) 〇 R1(Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs 2-9 2-"2- (4-chlorophenyl) tank ethylaminophenyl)-4- ( 4-This ratio is < yl) pyrimidine: MS (m / z): 405.0 (M + Η) +; C23H18C1FN4 requires 値 404 · 9. W-NMR ^ CDCh): d 8.56 (bs, 2H, pyridine), 8.34 (s, 1H, H-6, pyrimidine), 7.29 (m, d, 4H, p-pyridine, PhCl), 7.20 (d, 2H , PhCl), 7.08, 7.02 (2m, each 2H, PhF), 5.35 (t, 1H, NH), 3.78 (q, CH2N), 2.96 (t, 2H, CH2) 〇R1

2-10 2-『2_(4-溴苯基V乙基胺基1-5-(4_氟苯基）-4-(4-毗啶基 -132- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（130) 密淀：MS(m/z) : 449.0(M)+ ; CwKh8BrFN4 要求値 449.3 。iH-NMR^CDCh) :· d8.58，7.47(m，2H，p比淀），8.37(s ’ 1H，Η·6，口密淀），7.29，7.17(2d，各個 2H，PhCl) ，7,10，7.02(2d，各個 2H，PhF)，5.34(t，1H，NH) ，3.80(q，2H，CH2N)，2.97(t，2H，CH2)〇 R12-10 2- 『2_ (4-Bromophenyl Vethylamino 1-5- (4_fluorophenyl) -4- (4-pyridinyl-132- This paper size applies to Chinese National Standards (CNS ) A4 specification (210X297 mm) 520362 A7 B7 V. Description of the invention (130) Dense lake: MS (m / z): 449.0 (M) +; CwKh8BrFN4 requires 値 449.3. IH-NMR ^ CDCh): · d8.58 , 7.47 (m, 2H, p ratio lake), 8.37 (s' 1H, Η · 6, Komiyoto), 7.29, 7.17 (2d, each 2H, PhCl), 7,10, 7.02 (2d, each 2H, PhF), 5.34 (t, 1H, NH), 3.80 (q, 2H, CH2N), 2.97 (t, 2H, CH2) .R1

·裝-- (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 2-11 5-(4 -氟苯基）_2-『 2-(4-¾苯基）·乙基胺基）-4-(4·峨淀基 )-p密淀：2 •氣- 5- (4 -氟苯基）-4-(4-峨淀基）-喃淀（61毫克， 0.21毫莫耳），赂胺鹽酸鹽（186毫克，1.01毫莫耳）及碳酸 氫鈉（90毫克，1.07毫莫耳）於乙醇水溶液（1毫升）之混合 物回流加熱1小時。蒸發去除溶劑接著柱式層析（5 %甲醇/ 一氣甲统）獲付標題化合物呈黃色固體。MS(m/z): 387·2(Μ + Η)+ ; C23H19FN40 要求値 386.4 。 'H- NMR(DMSO_d6) : d 9· 12(bs，1H，OH)，8.54，7.26(2m ，各個 2H，p比淀），8.38(s，1H，H-6，。密淀），7.52(t ，1H，NH)，7.20-7.10(m，4H，PhF)，7.05，6.69(2d ，各個 2H，PhOH)，3.52(q，2H，CH2N)，2.78(t，2H ，CH2)。 R1· Packing-(Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economy 2-11 5- (4-fluorophenyl) _2- 『2- (4-¾phenyl ) · Ethylamino) -4- (4 · Edianyl) -p dense lake: 2 • Gas 5- (4-fluorophenyl) -4- (4-Edianyl) -nan Lake (61 (Mg, 0.21 mmol), bridamine hydrochloride (186 mg, 1.01 mmol) and sodium bicarbonate (90 mg, 1.07 mmol) in an aqueous ethanol solution (1 ml) were heated at reflux for 1 hour. The solvent was removed by evaporation followed by column chromatography (5% methanol / monogas) to afford the title compound as a yellow solid. MS (m / z): 387.2 (Μ + Η) +; C23H19FN40 requires 値 386.4. 'H-NMR (DMSO_d6): d 9 · 12 (bs, 1H, OH), 8.54, 7.26 (2m, each 2H, p ratio), 8.38 (s, 1H, H-6, dense dense), 7.52 (t, 1H, NH), 7.20-7.10 (m, 4H, PhF), 7.05, 6.69 (2d, each 2H, PhOH), 3.52 (q, 2H, CH2N), 2.78 (t, 2H, CH2). R1

-133- 本紙張尺度適用中國國家標準（CNS ) A4規格（21 OX 297公釐） 、11 · 520362 A7 _ ______ _B7 五、發明説明（131 ) 2-12 2-丨2-M-胺基苯基）-乙基胺基1-5-(4-氟苯基）_4-(4-毗啶 基）-喊喊 : 2 -氣-5 - ( 4 -氣；^基）-4 ( 4 -卩比基）-喊淀（7 1毫克 ，0.25毫莫耳）及2-(4-胺基苯基）乙基胺(〇·5毫升，3.80毫 莫耳）於乙醇（1.5笔升）之落液回流加熱2 0分鐘。蒸發及隨 後於矽膠柱層析（2 %甲醇/二氯甲烷）獲得標題化合物呈黃 色糖漿狀物。MS(m/z): 386.4(M + H)+; C23H2〇FN5 要求値 385·5。iH-NMRCCDCU) : d 8.56，7.32(2m，各個 2H， p 比啶），8.35(s，1H，Η·6，嘧淀），7.12-6.99(m，6H， PhF，PhNH2)，6.68(d，2H，PhNH2)，5.37(t，1H， NH)，3.75(q，2H，CH2N)，2.88(t，2H，CH2)〇 (讀先閱讀背面之注意事項再填寫本頁) R1-133- This paper size applies to China National Standard (CNS) A4 (21 OX 297 mm), 11 · 520362 A7 _ ______ _B7 V. Description of the invention (131) 2-12 2- 丨 2-M-aminobenzene ) -Ethylamino 1-5- (4-fluorophenyl) _4- (4-pyridinyl) -shout: 2 -Ga-5-(4 -Ga; ^ yl) -4 (4- Stilbene)-shouting lake (71 mg, 0.25 mmol) and 2- (4-aminophenyl) ethylamine (0.5 ml, 3.80 mmol) in ethanol (1.5 strokes) The falling liquid was heated under reflux for 20 minutes. Evaporation and subsequent silica gel column chromatography (2% methanol / dichloromethane) gave the title compound as a yellow syrup. MS (m / z): 386.4 (M + H) +; C23H20FN5 requires 値 385.5. iH-NMRCCDCU): d 8.56, 7.32 (2m, each 2H, p-pyridine), 8.35 (s, 1H, Η · 6, pyrimidine), 7.12-6.99 (m, 6H, PhF, PhNH2), 6.68 (d , 2H, PhNH2), 5.37 (t, 1H, NH), 3.75 (q, 2H, CH2N), 2.88 (t, 2H, CH2). (Read the precautions on the back before filling this page) R1

H，NH, N

經濟部中央標準局員工消費合作社印製Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs

2-13 5-(4-氣本基）-2-f2-(2_氣豕基）_乙基月安基1_4·(4_ρ比淀基 )-嘧啶：MS(m/z) : 389·2(Μ + Η)+ ; CwHi8F2N4 要求値 388·4。iH-NMRCCDCU) : 8·57(m，2H，吡啶），8.35(s ，1H，H-6，嘧啶），7·34-7·20，7.14-7.00(2m，10H， 2PhF，吡啶），5.42(bt，1H，NH)，3.82(q，2H，CH2N) ，3.05(t，2H，CH2)。 R1 -134- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（132 ) 2-14 2-Γ2-(2-氯苯基）-乙基胺基1-5-(4-鼠苯基）-4_(4-p比淀基 )-p密淀：M S(m/z) ： 405·0(Μ + Η)+ ; C23H18CIFN4 要求値 404.9。h-NMi^CDCU) : d 8.57(m，2Η，吡啶），8.36(s ，1H，H-6，嘧啶），7.40-7.00(m，10H，PhF，PhCl2 ，吡啶），5.44(bt，1H，NH)，3.84(q，2H，CH2N)， 3.15(t，2H，CH2)。 R12-13 5- (4-Gabenzyl) -2-f2- (2_Arylidene) _ethyl monthanyl 1_4 · (4_ρbidianyl) -pyrimidine: MS (m / z): 389 · 2 (Μ + Η) +; CwHi8F2N4 requires 値 388 · 4. iH-NMRCCDCU): 8.57 (m, 2H, pyridine), 8.35 (s, 1H, H-6, pyrimidine), 7.34-7.20, 7.14-7.00 (2m, 10H, 2PhF, pyridine), 5.42 (bt, 1H, NH), 3.82 (q, 2H, CH2N), 3.05 (t, 2H, CH2). R1 -134- This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 520362 A7 B7 V. Description of the invention (132) 2-14 2-Γ2- (2-chlorophenyl) -ethylamino 1-5- (4-muryl) -4_ (4-p ratio) -p dense lake: MS (m / z): 405.0 (M + Η) +; C23H18CIFN4 requires 値 404.9. h-NMi ^ CDCU): d 8.57 (m, 2Η, pyridine), 8.36 (s, 1H, H-6, pyrimidine), 7.40-7.00 (m, 10H, PhF, PhCl2, pyridine), 5.44 (bt, 1H , NH), 3.84 (q, 2H, CH2N), 3.15 (t, 2H, CH2). R1

2-15 5-(4-氟苯基）-2-丨2-(2-甲氧苯基V乙基胺基1-4-(4-吡啶 基嘧啶：MS(m/z) : 401.2(M + H)+ ； C24H2iFN40 要求値 400.5。iH-NMRCCDCh) : d 8.56，7.30(2m，各個 2H， 吡啶），8.34(s，1H，H-6，嘧啶），7.24，7·08，7.02 ，6.92(4m，各個 2H，PhF，PhOMe)，5.50(bt，1H， NH)，3.87(s，3H，CH3)，3.78(q，2H，CH2N)，3.02(t ，2H，CH2)。 R1 (請先閱讀背面之注意事項再填寫本頁) ^衣-- I 訂 經濟部中央標準局員工消費合作社印製2-15 5- (4-fluorophenyl) -2- 丨 2- (2-methoxyphenyl V ethylamino 1-4- (4-pyridylpyrimidine: MS (m / z): 401.2 ( M + H) +; C24H2iFN40 requires 値 400.5. IH-NMRCCDCh): d 8.56, 7.30 (2m, each 2H, pyridine), 8.34 (s, 1H, H-6, pyrimidine), 7.24, 7.08, 7.02, 6.92 (4m, each 2H, PhF, PhOMe), 5.50 (bt, 1H, NH), 3.87 (s, 3H, CH3), 3.78 (q, 2H, CH2N), 3.02 (t, 2H, CH2). R1 ( (Please read the notes on the back before filling out this page) ^ Clothing-I Order Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

〇Me〇Me

2-16 2_[2·(2,4·二氣豕基）_乙基月安基1-5-(4麵鼠冬基）-4_(4_外匕 啶基嘧啶：MSim/z) : 439.0(M)+ ; C23H17C12FN4 要求値 439.3。iH-NMRCCDCU) : 8.56(bs，2H，吡啶），8.34(s ，1H，H-6,嘧啶），7.37(s，1H，PhCl)，7.30(bd，2H -135- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（133) ，吡啶），7.22-7.15(m，2H，PhCl)，7·08，7.05(2m， 各個 2H，PhF)，5.40(t，1H，NH)V，3.80(q，2H， CH2N)，3.10(t，2H，CH2)。2-16 2_ [2 · (2,4 · Diaziridinyl) _Ethyl monthanyl 1-5- (4-faced murinoyl) -4_ (4_exopyridinylpyrimidine: MSim / z): 439.0 (M) +; C23H17C12FN4 requires 439.3. iH-NMRCCDCU): 8.56 (bs, 2H, pyridine), 8.34 (s, 1H, H-6, pyrimidine), 7.37 (s, 1H, PhCl), 7.30 (bd, 2H -135- This paper is applicable to China Standard (CNS) A4 specification (210X297 mm) 520362 A7 B7 V. Description of the invention (133), pyridine), 7.22-7.15 (m, 2H, PhCl), 7.08, 7.05 (2m, each 2H, PhF), 5.40 (t, 1H, NH) V, 3.80 (q, 2H, CH2N), 3.10 (t, 2H, CH2).

(請先閱讀背面之注意事項再填寫本頁) R1 2-17 2-「2-(2,6_二氯苯基）-乙基胺基1-5_(4-氟苯基）-4-(4，吡 基）-嘧啶：MS(m/z) : 439·0(Μ)+ ; CwHi7C12FN4 要求値 439.3。iH-NMRCCDCU) : 8.57(m，2H，吡啶），8.36(s ，1H，H-6,嘧啶），7.35(d，2H，PhCl)，7.11(m，3H ，PhF，PhCl)，7.03(m，2H，PhF)，5.45(t，1H，NH) ，3.86(q，2H，CH2N)，3.38(t，2H，CH2)。(Please read the notes on the back before filling this page) R1 2-17 2- 「2- (2,6_dichlorophenyl) -ethylamino 1-5_ (4-fluorophenyl) -4- (4, pyridyl) -pyrimidine: MS (m / z): 439.0 (M) +; CwHi7C12FN4 requires 値 439.3. IH-NMRCCDCU): 8.57 (m, 2H, pyridine), 8.36 (s, 1H, H -6, pyrimidine), 7.35 (d, 2H, PhCl), 7.11 (m, 3H, PhF, PhCl), 7.03 (m, 2H, PhF), 5.45 (t, 1H, NH), 3.86 (q, 2H, CH2N), 3.38 (t, 2H, CH2).

R1 經濟部中央標準局員工消費合作社印製 2-18 5-(4-氟苯基V2-丨2-(3-甲氧苯基）·乙基胺基吡啶 基）·嘧啶：MS(m/z) : 401.2(M + H)+ ; C24H21FN40 要求値 400.5。h-NMRCCDCh) : d8.56(m，2H，吡啶），8.34(s ，1H，H-6,嘧啶），7.32-7.22，7.11-6.98，6.89-6.77(3m ，10H，PhF，PhOMe，吡啶），5.38(t，1H，NH)， 3.82(m，5H，CH2N，CH3)，2.96(t，2H，CH2) 〇 -136· 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五 '發明説明（ 134 R1 〇Me 2 · 19 2 -『2-(3-氣豕基）-乙基胺基1-5-(4 -氣私基）-4-(4-^比淀基 啶：MS(m/z) : 405.4(M+H)+ ; C23H18C1FN4 要求値 404.9。h-NMRCCDCh) : d 8.60(d，2H，口比啶），8.38(s ，1H ^ H-6，嘧啶），7.32-7.24(m，5H，吡啶，PhCl) ，7.18(m，1H，PhCl)，7.11，7·04(2ιη，各個 2H，PhF) ，5.35(t，1H，NH)，3.83(q，2H，CH2N)，3.00(t， 2H，CH2)。 Ν' ·(請先閱讀背面之注意事項再填寫本頁)R1 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 2-18 5- (4-fluorophenyl V2- 丨 2- (3-methoxyphenyl) · ethylaminopyridyl) · Pyrimidine: MS (m / z): 401.2 (M + H) +; C24H21FN40 requires 値 400.5. h-NMRCCDCh): d8.56 (m, 2H, pyridine), 8.34 (s, 1H, H-6, pyrimidine), 7.32-7.22, 7.11-6.98, 6.89-6.77 (3m, 10H, PhF, PhOMe, pyridine ), 5.38 (t, 1H, NH), 3.82 (m, 5H, CH2N, CH3), 2.96 (t, 2H, CH2) 〇-136 · This paper size applies to China National Standard (CNS) A4 specifications (210X297 mm) ) 520362 A7 B7 Five 'Invention Description (134 R1 〇Me 2 · 19 2-"2- (3-Azofluorenyl) -ethylamino 1-5-(4-Phenyl) -4- (4- ^ Pyridylidine: MS (m / z): 405.4 (M + H) +; C23H18C1FN4 requires 値 404.9. H-NMRCCDCh): d 8.60 (d, 2H, bipyridine), 8.38 (s, 1H ^ H -6, pyrimidine), 7.32-7.24 (m, 5H, pyridine, PhCl), 7.18 (m, 1H, PhCl), 7.11, 7.04 (2 μm, each 2H, PhF), 5.35 (t, 1H, NH) , 3.83 (q, 2H, CH2N), 3.00 (t, 2H, CH2). Ν '· (Please read the precautions on the back before filling this page)

HH

Rl=Rl =

Cl 經濟部中央標準局員工消費合作社印製 2-20 5-(4-氣苯基）-2_『（2-¾ -2 -參基）-乙基胺基1-4-(4 -p比淀 基）·p密淀：2-氯- 5- (4_氣苯基）-4-(4-ρ比淀基）_p密淀（87毫克 ，0.31毫莫耳）及2-胺基_1_苯基乙醇（300毫克，2.19毫莫 耳）於乙醇（2毫升）之混合物回流加熱2小時。蒸發隨後於 矽膠柱層析（4 %甲醇/二氯甲烷）獲得標題化合物呈黃色發 泡體。MS(m/z): 387·0(Μ+Η)+; C23H19FN40 要求値 386.4 。iH-NMR^CDCU) : d 8.58(d，2H，p比淀），8.38(s，1H ，H-6,喊淀），7.47(d，2H，Ph)，7.41(t，2H，Ph)，7.34(t ，1H，Ph)，7.28(d，2H，口比淀），7.10，7.02(2m，2H， -137- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X：297公釐） 520362 A7 B7 i、發明説明（135 )Cl Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs of the People's Republic of China 2-20 5- (4-Gasphenyl) -2 _ 『(2-¾ -2 -Phenyl) -ethylamino 1-4- (4-p Group) · p dense lake: 2-chloro-5-(4-phenylphenyl) -4- (4-ρ ratio lake) _p dense lake (87 mg, 0.31 mmol) and 2-amino group_1 A mixture of phenylethanol (300 mg, 2.19 mmol) in ethanol (2 ml) was heated at reflux for 2 hours. Evaporation followed by silica gel column chromatography (4% methanol / dichloromethane) gave the title compound as yellow foam. MS (m / z): 387.0 (Μ + Η) +; C23H19FN40 requires 値 386.4. iH-NMR ^ CDCU): d 8.58 (d, 2H, p ratio), 8.38 (s, 1H, H-6, yodo), 7.47 (d, 2H, Ph), 7.41 (t, 2H, Ph) , 7.34 (t, 1H, Ph), 7.28 (d, 2H, mouth ratio lake), 7.10, 7.02 (2m, 2H, -137-) This paper size applies to China National Standard (CNS) A4 specifications (210X: 297 mm) ) 520362 A7 B7 i. Description of the invention (135)

PhF)，5.72(t，1H，NH)，5.06(m，CHOH)，4.02-3.92(m ，2H，OH，1 CH2)，3.72(ddd，1H，、CH2)。PhF), 5.72 (t, 1H, NH), 5.06 (m, CHOH), 4.02-3.92 (m, 2H, OH, 1 CH2), 3.72 (ddd, 1H ,, CH2).

OHOH

(請先閱讀背面之注意事項再填寫本頁) R1 = 2-21 5-(4-氟苯基）-2-丨甲基-(2-苯基乙基胺基1-4-(4-吡啶 基）-嘧啶：MS(m/z) : 385·0(Μ + Η)+ ; C24H21FN4 要求値 384·5。iH-NMRCCDCh) : d 8.57，7.35(2m，各個 2H， 吡啶），8.40(s，1H，H-6，嘧啶），7·34·7·21(ηχ，5H， Ph)，7.10，7.03(2m，2H，PhF)，3.96(t，2H，CH2N) ，3.23(s，3H，CH3)，3.00(t，2H，CH2)。 CH,(Please read the precautions on the back before filling this page) R1 = 2-21 5- (4-fluorophenyl) -2- 丨 methyl- (2-phenylethylamino1-4- (4- Pyridyl) -pyrimidine: MS (m / z): 385 · 0 (Μ + Η) +; C24H21FN4 requires 値 384 · 5. IH-NMRCCDCh): d 8.57, 7.35 (2m, each 2H, pyridine), 8.40 ( s, 1H, H-6, pyrimidine), 7.34 · 7 · 21 (ηχ, 5H, Ph), 7.10, 7.03 (2m, 2H, PhF), 3.96 (t, 2H, CH2N), 3.23 (s, 3H, CH3), 3.00 (t, 2H, CH2). CH,

R1 二 經濟部中央標準局員工消費合作社印製 2-22 5_(4_氣冬基）-2-f(3"豕基丙基）胺基1 -4-（4 口比淀基）喃 啶：MS(m/z) : 385·2(Μ + Η)+ ; C24H21FN4 要求値 384.5。 iH-NMRCCDCh) : d 8.56(m，2H，吡啶），8.34(s，1H， H-6，喊淀），7.34-7.20(m，7H，Ph，口比唉），7.08， 7.01(2m，各個 2H，PhF)，5.38(t，1H，NH)，3.58(q ，2H，CH2N) ? 2.78(t，2H，CH2)，2.03(m，2H，CH2)。 -138- 本紙張尺度適用中國國家標準（CNS ) A4規格（2l〇X 297公釐） 520362 A7 B7 五、發明説明（136 )R1 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 2-22 5_ (4_ 气 冬 基) -2-f (3 " fluorenylpropyl) amino 1-4- (4 acetonyl) pyrimidine : MS (m / z): 385 · 2 (Μ + +) +; C24H21FN4 requires 値 384.5. iH-NMRCCDCh): d 8.56 (m, 2H, pyridine), 8.34 (s, 1H, H-6, yodo), 7.34-7.20 (m, 7H, Ph, lip ratio), 7.08, 7.01 (2m, Each of 2H, PhF), 5.38 (t, 1H, NH), 3.58 (q, 2H, CH2N)? 2.78 (t, 2H, CH2), 2.03 (m, 2H, CH2). -138- This paper size is applicable to Chinese National Standard (CNS) A4 (2l0X 297mm) 520362 A7 B7 V. Description of the invention (136)

經濟部中央標準局員工消費合作社印繁 2*23 氟苯基）-2-丨Π-甲基-3-苯基丙基V胺基1-4-(4-吡 发產）_嘧啶：MS(m/z) : 399·0(Μ + Η)+ ; C25H23FN4 要求値 398.5。i-NMRCCDCls) : d8.56(m，2H，吡啶），8.32(s ，1H，H-6，嘧啶），7.32-7.17(m，7H，吡啶，Ph)， 7.〇9-7.02(2m，各個 2H，PhF)，5.16(d，1H，NH)， 4.28(m，1H，CH)，2.77(m，2H，CH2)，1.94(m，2H ，CH2)，1.34(d，3H，CH3)。 b / N H 2·24 5-(4-鼠苯基）-2 -『（3-味峻基丙基）-胺基1-4-(4 -p比淀基）_ 口密淀：MS(m/z) : 375·0(Μ + Η)+ ; · C21H19FN6 要求値 374.4 。iH-NMRCCDCh) : d 8.57，7.26(2m，各個 2H，咏淀） ，8.36(>s，1H，H-6，喊淀），7.56(s，1H，咪峻）， 7.16-6.96(m，6H，PhF，味峻），5.38(bt，1H，ΝΗ)， 4.12(t，2H，CH2N)，3.56(q，2H，CH2NH)，2.20(m， 2H，CH2)。 ri^Employees' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs of the People's Republic of China 2 * 23 Fluorophenyl) -2- 丨 Π-methyl-3-phenylpropyl Vamino 1-4- (4-pyridine) _Pyrimidine: MS (m / z): 399.0 (M + Η) +; C25H23FN4 requires 値 398.5. i-NMRCCDCls): d8.56 (m, 2H, pyridine), 8.32 (s, 1H, H-6, pyrimidine), 7.32-7.17 (m, 7H, pyridine, Ph), 7.09-7.02 (2m , Each 2H, PhF), 5.16 (d, 1H, NH), 4.28 (m, 1H, CH), 2.77 (m, 2H, CH2), 1.94 (m, 2H, CH2), 1.34 (d, 3H, CH3 ). b / NH 2 · 24 5- (4-murylphenyl) -2-"(3-trisylamino) -amino 1-4- (4-p ratio)-口 密 晶 ： MS ( m / z): 375.0 (M + Η) +; C21H19FN6 requires 値 374.4. iH-NMRCCDCh): d 8.57, 7.26 (2m, each 2H, Yongdian), 8.36 (> s, 1H, H-6, shouting), 7.56 (s, 1H, Mijun), 7.16-6.96 (m , 6H, PhF, Weijun), 5.38 (bt, 1H, NO), 4.12 (t, 2H, CH2N), 3.56 (q, 2H, CH2NH), 2.20 (m, 2H, CH2). ri ^

-139- 本紙張尺度適用中國國家標準（CNS ) A4規格（21 OX297公釐） •裝-- (請先閱讀背面之注意事項再填寫本頁)-139- This paper size applies to Chinese National Standard (CNS) A4 (21 OX297 mm) • Packing-(Please read the precautions on the back before filling this page)

、1T j·. 520362 A7 B7 五、發明説明（137 2-25 5-(4-氟苯基）-2-「（4-苯基-正丁基）_胺基]_4_{4-吡啶基）· :密啶：MS(m/z) : 399·0(Μ + Η)+ ; C25H23FN4 要求値 398.5 。iH-NMR^CDCb) : d 8.56(m，2H，4 啶），8.34(s，1H ，H-6，嘧啶），7.33-7.17(m，7H，Ph，吡啶），7·08， 7.02(2m，各個 2H，PhF)，5.33(bt，1H，NH)，3.56(q ，2H，CH2N)，2.71(t，2H，CH2)，1.76(m，4H， 2CH2) 〇 R11T j ·. 520362 A7 B7 V. Description of the invention (137 2-25 5- (4-fluorophenyl) -2-"(4-phenyl-n-butyl) _amino group] _4_ {4-pyridyl group ) :: Mididine: MS (m / z): 399.0 (M + Η) +; C25H23FN4 requires 値 398.5. IH-NMR ^ CDCb): d 8.56 (m, 2H, 4 pyridine), 8.34 (s, 1H, H-6, pyrimidine), 7.33-7.17 (m, 7H, Ph, pyridine), 7.08, 7.02 (2m, each 2H, PhF), 5.33 (bt, 1H, NH), 3.56 (q, 2H , CH2N), 2.71 (t, 2H, CH2), 1.76 (m, 4H, 2CH2) 〇R1

(請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印繁 2-26 5-(4 -氟苯基）-2-(1-六氫1^比^2井基V4_(4-峨淀基）-喊淀： 2-氯-5·(4-氟苯基）-4-(4-吡啶基）-嘧啶（71毫克，0.25毫莫 耳）及六氫毗畊（214毫克，2·48毫莫耳）於乙醇（1毫升）之混 合物回流加熱5分鐘。蒸發隨後於矽膠柱層析（5 %甲醇/二 氯甲烷）獲得標題化合物呈黃色固體。MS(m/z): 336.2(M + H)+ ; C19H18FN5 要求値 335.4。1 H-NMR(CDC13) :d 8.54，7.29(2m，各個 2H，吡啶），8.3 7(s，1H，H-6 ，嘧啶），7.08，7.00(2m，各個 2H，PhF)，3.95(t，4H ，2CH2)，3.01(t，4H，2 H2)。 R1(Please read the precautions on the back before filling out this page) Yin Fan, Staff Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs 2-26 5- (4-fluorophenyl) -2- (1-hexahydro 1 ^ 比 ^ 2 Jingji V4_ (4-Edianyl) -Xiaodian: 2-chloro-5 · (4-fluorophenyl) -4- (4-pyridyl) -pyrimidine (71 mg, 0.25 mmol) and hexahydropigenol (214 mg, 2.48 mmol) in ethanol (1 ml) was heated at reflux for 5 minutes. Evaporation followed by silica gel column chromatography (5% methanol / dichloromethane) gave the title compound as a yellow solid. MS (m / z): 336.2 (M + H) +; C19H18FN5 requires 値 335.4. 1 H-NMR (CDC13): d 8.54, 7.29 (2m, each 2H, pyridine), 8.3 7 (s, 1H, H-6, pyrimidine ), 7.08, 7.00 (2m, each 2H, PhF), 3.95 (t, 4H, 2CH2), 3.01 (t, 4H, 2 H2). R1

-K-K

K -140- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（138) MS(m/z) : 335·2(Μ+Η)+ ; CsoHbFIS^ 要求値 334.4。 NMR(CDC13) : d 8.55，7.30(2m，各個 V2H，吡啶），8.36(s ，1H，H-6,口密淀），7·08，7.01(2m，2H，PhF)，3.91(t ，4H，2 CH2N)，1·74，1 ·68(2m，6H，3 CH2) 〇 R1 N- 2-28 5_(4-氣苯基）·2_(4 -甲基-1-六鼠井基）_4-(4·ρ比淀基 嘧啶：MS(m/z) : 350.0(Μ + Η)+ ; C2()H2〇FN5 要求値 349.4 。1H-NMR(CDC13) : d 8·58，7·32(2m，各個 2Η，峨淀） ，8.40(s，1H，H-6，喊淀），7.10，7.04(2m，各個 2H ，PhF)，4.00(t，4H，2 CH2)，2.57(t，4H，2 CH2)， 2.42(s，3H，CH3)。 R1K -140- This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X 297mm) 520362 A7 B7 V. Description of the invention (138) MS (m / z): 335 · 2 (Μ + Η) +; CsoHbFIS ^ Requirement 4.4334.4. NMR (CDC13): d 8.55, 7.30 (2m, each V2H, pyridine), 8.36 (s, 1H, H-6, Komiyoto), 7.08, 7.01 (2m, 2H, PhF), 3.91 (t, 4H, 2 CH2N), 1.74, 1.68 (2m, 6H, 3 CH2) 〇R1 N- 2-28 5_ (4-Gaphenyl) · 2_ (4-methyl-1-hexamuryl) ) 4- (4 · ρ ratio of pyridyl pyrimidine: MS (m / z): 350.0 (Μ + Η) +; C2 () H2〇FN5 requires 値 349.4. 1H-NMR (CDC13): d 8.58,7 32 (2m, each 2Η, Edian), 8.40 (s, 1H, H-6, shouting), 7.10, 7.04 (2m, each 2H, PhF), 4.00 (t, 4H, 2 CH2), 2.57 ( t, 4H, 2 CH2), 2.42 (s, 3H, CH3). R1

H,C—N N- (請先閱讀背面之注意事項再填寫本頁)H, C—N N- (Please read the notes on the back before filling this page)

、1T 經濟部中央標準局員工消費合作社印t 2-29 5 -（ 4 氣私基^ ) 2 - ( 4 麵 基^ _ 1 六鼠 p比口井基^ ) - 4 ( 4 _ 口比 基^ ) _ 嘧啶：MS(m/z) : 412.2(M + H)+ ; C25H22FN5 要求値 411.5 。iH-NMRCCDCls) : d 8.58(bd，2H，吡啶），8.42(s，1H ，H_6，嘧啶），7.38-7.30(m，4H，吡啶，卩11)，7.15-7.00(m，6H，PhF，Ph)，6.94(t，1H，Ph)，4.13(t， 4H，2 CH2)，3.33(t，4H，2 CH2)。 -141 - 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（139)、 1T Consumer Cooperative Cooperatives, Central Standard Bureau of the Ministry of Economic Affairs 2-29 5-(4 air-based ^) 2-(4 surface-based ^ _ 1 six rat p than well-based ^)-4 (4 _ mouth-based ^) _ Pyrimidine: MS (m / z): 412.2 (M + H) +; C25H22FN5 requires 値 411.5. iH-NMRCCDCls): d 8.58 (bd, 2H, pyridine), 8.42 (s, 1H, H-6, pyrimidine), 7.38-7.30 (m, 4H, pyridine, hydrazone 11), 7.15-7.00 (m, 6H, PhF, Ph), 6.94 (t, 1H, Ph), 4.13 (t, 4H, 2 CH2), 3.33 (t, 4H, 2 CH2). -141-This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) 520362 A7 B7 V. Description of the invention (139)

RlRl

Or N N- 2-3 0 5-(4 -氟苯基）-2-(2 -嗎p林基乙基胺基）-4_(4-p比咬基密 % : MS(m/z) : 380·4(Μ + Η)+ ; C21H22FN50 要求値 379 4 。i-NMiUCDCh) : d 8·58，7.30(2m，各個 2H，吡啶） ，8.38(s，1H，Η·6，。密淀），7·10，7.03(2m，各個 2H ，PhF)，5.91(bs，1H，NH)，3.79(bs，4H，2 CH2)， 3.66(bs，2H，CH2)，2.71(bs，2H，CH2)，2.59(bs， 4H，2 CH2) 0Or N N- 2-3 0 5- (4-fluorophenyl) -2- (2-morphinylethylamino) -4_ (4-p is more dense than octyl): MS (m / z) : 380 · 4 (Μ + Η) +; C21H22FN50 requires 値 379 4. I-NMiUCDCh): d 8.58, 7.30 (2m, each 2H, pyridine), 8.38 (s, 1H, Η · 6, .Mi Dian ), 7.10, 7.03 (2m, each 2H, PhF), 5.91 (bs, 1H, NH), 3.79 (bs, 4H, 2 CH2), 3.66 (bs, 2H, CH2), 2.71 (bs, 2H, CH2), 2.59 (bs, 4H, 2 CH2) 0

-S (請先閱讀背面之注意事項再填寫本頁)-S (Please read the notes on the back before filling this page)

Rl 〇 N-Rl 〇 N-

、1T 經濟部中央標準局員工消費合作社印製 2-31 5-(4-氟苯基）-2-(2-六氫吡啶基乙基胺基）-4-(4-吡啶基 )-嘧啶：MS(m/z) : 378·2(Μ + Η)+ ; C22H24FN5 要求値 377.5 。W-NMRCCDCU) : d 8.54，7.27(2d，各個 2H，吡啶） ，8.34(s，1H，H-6，嘧啶），7.06，7.〇〇(2m，各個 2H ，PhF)，6.04(bt，1H，NH)，3.66(q，2H，CH2NH)， 2.74(t，2H，CH2)，2.61(bs，4H，2 CH2)，1.68(m， 4H，2 CH2)，1.50(m，2H，CH2) 0, 1T Printed by 2-31 5- (4-fluorophenyl) -2- (2-hexahydropyridylethylamino) -4- (4-pyridyl) -pyrimidine : MS (m / z): 378.2 (M + Η) +; C22H24FN5 requires 値 377.5. W-NMRCCDCU): d 8.54, 7.27 (2d, each 2H, pyridine), 8.34 (s, 1H, H-6, pyrimidine), 7.06, 7.0 (2m, each 2H, PhF), 6.04 (bt, 1H, NH), 3.66 (q, 2H, CH2NH), 2.74 (t, 2H, CH2), 2.61 (bs, 4H, 2 CH2), 1.68 (m, 4H, 2 CH2), 1.50 (m, 2H, CH2) ) 0

Rl 〇 •δ -142- 本紙張尺度適用中國國家標準（CNS ) A4規格（21 OX 297公釐） 520362 A7 B7 五、發明説明（140 ) 2-32 5-(4 -氣苯基）-4-(4 -p比淀基）-2-(2 -说洛淀基乙基胺基）-:密啶：MS(m/z) : 364.0(M + H)+ ; C21HV22FN5 要求値 363.4 。iH-NMRCCDCh) : d 8·55，7.28(2m，各個 2H，吡啶） ，8.36(s，1H，H-6，喊淀），7.08，7.02(2m，各個 2H ，PhF)，6.28(t，1H，NH)，3.86(q，2H，CH2NH)， 3.18(t，2H，CH2N)，3.10(bs，4H，2CH2N)，2.02(bs ，4H，2 CH2)。 R1 N- 2-33 5-(4-氟苯基）-2-(3-嗎啉基丙基胺基）-4-(4-吡啶某嘧 啶：MS(m/z) : 394·2(Μ + Η)+ ; C22H24FN50 要求値 393 ·5 。iH-NMRCCDCh) : d 8.54，7.27(2m，各個 2H，吡啶） ，8.33(s，1H，H-6，喃淀），7.06，7.00(2m，各個 2H ，PhF)，6.00(t，1H，NH)，3.76(t，4H，2 CH20)， 3.60(q，2H，CH2NH)，2.52(t，2H，CH2N)，2.50(m， 4H，CH2N)，1.86(m，2H，CH2)。 R1 (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製Rl 〇 • δ -142- This paper size applies to Chinese National Standard (CNS) A4 specification (21 OX 297 mm) 520362 A7 B7 V. Description of the invention (140) 2-32 5- (4-Gaphenyl) -4 -(4-p than yodoyl) -2- (2-said Luodianylethylamino)-: pyrimidine: MS (m / z): 364.0 (M + H) +; C21HV22FN5 requires 値 363.4. iH-NMRCCDCh): d 8.55, 7.28 (2m, each 2H, pyridine), 8.36 (s, 1H, H-6, yodo), 7.08, 7.02 (2m, each 2H, PhF), 6.28 (t, 1H, NH), 3.86 (q, 2H, CH2NH), 3.18 (t, 2H, CH2N), 3.10 (bs, 4H, 2CH2N), 2.02 (bs, 4H, 2 CH2). R1 N- 2-33 5- (4-fluorophenyl) -2- (3-morpholinylpropylamino) -4- (4-pyridine pyrimidine: MS (m / z): 394 · 2 ( Μ + Η) +; C22H24FN50 requires 値 393 · 5. IH-NMRCCDCh): d 8.54, 7.27 (2m, each 2H, pyridine), 8.33 (s, 1H, H-6, Nanto), 7.06, 7.00 (2m , Each 2H, PhF), 6.00 (t, 1H, NH), 3.76 (t, 4H, 2 CH20), 3.60 (q, 2H, CH2NH), 2.52 (t, 2H, CH2N), 2.50 (m, 4H, CH2N), 1.86 (m, 2H, CH2). R1 (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs

2-34 5 (4麵氣苯基）-2·『3-(2 -口比洛淀酉同-1 -基）_丙胺基1 -4-(4-p比 啶基 V.嘧啶：MS(m/z) : 392·2(Μ + Η)+ ; C22H22FN50 要求 値 391.5。i-NMI^CDCh) : d8.58，7.30(m，2H，吡啶 )，8.36(s，1H，H-6,喃淀），7·10，7·04(πι，2H，PhF) 143- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（141 ，5.88(t，1H，NH)，3.56(q，2H，CH2NH)，3.48， 3.45(2t，各個 2H，2CH2)，2.46(t，2¾，CH2)，2·08(ιη ，2H，CH2)，1.90(m，2H，CH2) 〇 R12-34 5 (4-Hexylphenyl) -2 · "3- (2--Bilopyridine with -1 -yl) _propylamino 1 -4- (4-p than pyridyl V. pyrimidine: MS (m / z): 392.2 (M + Η) +; C22H22FN50 requires 値 391.5. i-NMI ^ CDCh): d8.58, 7.30 (m, 2H, pyridine), 8.36 (s, 1H, H-6 , Nandian), 7 · 10, 7 · 04 (π, 2H, PhF) 143- This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A7 B7 V. Description of the invention (141, 5.88 ( t, 1H, NH), 3.56 (q, 2H, CH2NH), 3.48, 3.45 (2t, each 2H, 2CH2), 2.46 (t, 2¾, CH2), 2.08 (ιH, 2H, CH2), 1.90 ( m, 2H, CH2) 〇R1

經濟部中央標準局員工消費合作社印製 2-35 2-[((S)-2-胺基-3-苯基丙基）-胺基1-5-(4-氣茉某V4-M-二比淀基）_ p密淀鹽酸鹽：MS(m/z) ： 400·1(Μ + Η)+ ; C24H22FN5要求値399.5。（自由態鹼）。 R1 rr^ ΝΗ2 實例3 2-驗胺基- 5- (4-氟苯基）-4-(4 -ρ比淀基）-喊淀之概略製備程序Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 2-35 2-[(((S) -2-amino-3-phenylpropyl) -amino 1-5-(4-aseum V4-M- Bibito-based) _p dense lake hydrochloride: MS (m / z): 400 · 1 (Μ + Η) +; C24H22FN5 requires 値 399.5. (Free state base). R1 rr ^ ΝΗ2 Example 3 Schematic preparation procedure for 2-aminoamine- 5- (4-fluorophenyl) -4- (4-p-pyridyl) -dimethylamino

-144 (請先閱讀背面之注意事項再填寫本頁) Η-144 (Please read the notes on the back before filling this page) Η

、R R = R21，OR2〇 或 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7_ 五、發明説明（142 ) 氯羰基R-C(O)Cl(0.57毫莫耳）於冰浴溫度逐滴加至2-胺 基- 5- (4 -鼠苯基）-4-(4 -p比淀基）-七、淀（〇·38毫莫耳）於p比淀（3 毫升）之溶液。於室溫授摔3小時’藉薄層層析監測，倒入 冰水中，以二氯曱燒萃取，脱水及蒸發。粗產物藉石夕膠柱 式層析純化（己烷-丙酮）及由適當溶劑如乙酸乙酯再結晶。 下列化合物係根據此種程序使用適當醯氯製備： 3-1 2-乙·醯胺基-5-(4-氟苯基）-4_(4-吡啶基）·嘧啶； MS(m/z) : 309·0(Μ + Η)+; C17H13FN40 要求値 3〇8 3。ιΗ- NMR(CDC13) : d 8.63(s ， 1H ’ H-6，口密淀），8.60 ， 7.29(2m，各個 2H，p 比淀），8.26(bs，1H，NH)，7，14 ，7.08(2m，各個 2H，PhF)，2.58(s，3H，CH3CO)。 R 二 CH3- 3-2 2- 丁醯胺基_5-(4-氣笨基）-4-(4-吡啶基喊淀： 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) MS(m/z) : 337·2(Μ+Η)+; C19H17FN40 要求値 336.4。 NMR(CDC13) : d 8.64(s， 1H，H-6，。密淀），8.60， 7.31(2m，各個 2H，吡啶），8.17(bs，1H，NH)，7，14 ，7.08(2m，各個 2H，PhF)，2.80(t，2H，CH2CO)， 1.82(m，2H，CH2)，1.06(t，3H，CH3) 〇 R 二 CH3CH2CH2- 3-3 5-(4-鼠冬基）_2-特戊酿胺基-4_(4-p比淀美）_p密淀： MS(m/z): 351·0(Μ + Η)+; C2〇H19FN40 要求値 350.4。ιΗ· NMR(CDC13) : d 8.69(s，1H，H-6，口密淀），8.60， 7.35(2m，各個 2H，吡啶），8.25(bs，1H，NH)，7，15 ，7.08(2m，各個 2H , PhF)，1.4(s，9H，3 CH3)。 _____-145-_ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（143 ) R = (ch3)3c- 3_4 2·表甲酸胺基_5_(4_氣本基）-4_(4-p比咬基）_p密淀 ： MS(m/z) : 371.0(M+H)+; C22H15FN40 要求値 370.4。4-NMR(CDC13) : d 8.75(s , 2H，NH，Η·6，嘧啶），8.61 ’ 7.36(2m，各個 2Η，ρ比淀），8.00，7.63，7.55(d，t ，t，2H，1H，2H，Ph)，7·18，7.10(2m，各個 2H，, RR = R21, OR2〇 or this paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A7 B7_ V. Description of the invention (142) Chlorocarbonyl RC (O) Cl (0.57 mmol) in ice The bath temperature was added dropwise to 2-amino-5- (4-m-phenyl) -4- (4-p-pyridyl) -VII, yodo (0.38 mmol) in p-pyridine (3 ml ) Solution. Incubate at room temperature for 3 hours. 'Monitor by thin layer chromatography, pour into ice water, extract with dichloromethane, dehydrate and evaporate. The crude product is purified by column chromatography (hexane-acetone) and recrystallized from a suitable solvent such as ethyl acetate. The following compounds were prepared according to this procedure using appropriate ammonium chloride: 3-1 2-Ethylamino-5- (4-fluorophenyl) -4- (4-pyridyl) · pyrimidine; MS (m / z) : 309.0 (Μ + Η) +; C17H13FN40 requires 値 308. ιΗ-NMR (CDC13): d 8.63 (s, 1H'H-6, Komiyoto), 8.60, 7.29 (2m, each 2H, p ratio), 8.26 (bs, 1H, NH), 7, 14 7.08 (2m, each 2H, PhF), 2.58 (s, 3H, CH3CO). R DiCH3- 3-2 2- Butylamido_5- (4-airbenzyl) -4- (4-pyridylyl): Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the first Note: Please fill in this page again) MS (m / z): 337 · 2 (Μ + Η) +; C19H17FN40 requires 値 336.4. NMR (CDC13): d 8.64 (s, 1H, H-6, dense lake), 8.60, 7.31 (2m, each 2H, pyridine), 8.17 (bs, 1H, NH), 7,14, 7.08 (2m, each 2H, PhF), 2.80 (t, 2H, CH2CO), 1.82 (m, 2H, CH2), 1.06 (t, 3H, CH3) 〇R diCH3CH2CH2- 3-3 5- (4-ratyl) _2-tetramethylamino-4_ (4-p than Yomei) _p dense lake: MS (m / z): 351.0 (M + Η) +; C20H19FN40 requires 値 350.4. ι Η NMR (CDC13): d 8.69 (s, 1H, H-6, mouth dense lake), 8.60, 7.35 ( 2m, each 2H, pyridine), 8.25 (bs, 1H, NH), 7,15, 7.08 (2m, each 2H, PhF), 1.4 (s, 9H, 3 CH3). _____- 145-_ This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A7 B7 V. Description of the invention (143) R = (ch3) 3c- 3_4 2 · Epiformic acid amino group _5_ (4_Gaben) -4_ (4 -p than base) _p dense lake: MS (m / z) : 371.0 (M + H) +; C22H15FN40 requires 値 370.4. 4-NMR (CDC13): d 8.75 (s, 2H, NH, Η · 6, pyrimidine), 8.61 '7.36 (2m, each 2Η, ρ bidian) , 8.00, 7.63, 7.55 (d, t, t, 2H, 1H, 2H, Ph), 7.18, 7.10 (2m, each 2H,

PhF)PhF)

R σ 3 ·5 5_(4·氟苯基）·2_苯基乙酿胺基-4_(4·ρ比淀基）_p密淀： MS(m/z): 385·0(Μ + Η)+; C23H17FN40 要求値 384.4。4-NMR(CDCl3) : d 8.66(s， 1Η，H-6，喊淀），8.59， 7.28(2m，各個 2H，^^)，8.21(bs，lH，NH)，7.43-7.30(m，5H，Ph)，7.14，7·08 (2m，各個 2H，PhF)， 4.13(s，2H，CH2)。R σ 3 · 5 5_ (4 · fluorophenyl) · 2_phenylethylamine-4_ (4 · ρ 比 ρ 基) _p dense lake: MS (m / z): 385 · 0 (Μ + Η ) +; C23H17FN40 requires 値 384.4. 4-NMR (CDCl3): d 8.66 (s, 1Η, H-6, Xingdian), 8.59, 7.28 (2m, each 2H, ^^), 8.21 (bs, 1H, NH) ), 7.43-7.30 (m, 5H, Ph), 7.14, 7.08 (2m, each 2H, PhF), 4.13 (s, 2H, CH2).

R (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 3-6 5-(4-氟苯基）-2-氫桂皮醯胺基-4_(4-吡啶基V嘧啶： MS(m/z): 399.2(M + H)+; C24H19FN40 要求値 398.4。1^!-NMR(CDC13) : d 8.60(s，1H，H-6，喊淀），8.54(m，2H ，吡啶），8.20(bs，1H，NH)，7.31-7.16(m，7H，Ph ，吡啶），7.11，7.05(2m，各個 2H，PhF)，3.20，3.09(2t 146- 本紙張尺度適用中國國家標準（CNS ) A4規格（21 OX 297公釐） 520362 A7 B7 五、發明説明（144) ，各個 2H，2 CH2)R (Please read the notes on the back before filling out this page) 3-6 5- (4-fluorophenyl) -2-hydrocinnamylamino-4_ (4-pyridine) printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs Pyrimidine: MS (m / z): 399.2 (M + H) +; C24H19FN40 requires 値 398.4. 1 ^!-NMR (CDC13): d 8.60 (s, 1H, H-6, yodo), 8.54 ( m, 2H, pyridine), 8.20 (bs, 1H, NH), 7.31-7.16 (m, 7H, Ph, pyridine), 7.11, 7.05 (2m, each 2H, PhF), 3.20, 3.09 (2t 146- this paper Standards apply to Chinese National Standard (CNS) A4 specifications (21 OX 297 mm) 520362 A7 B7 V. Description of the invention (144), each 2H, 2 CH2)

R 實例42-取代5-(4_氟苯基）-6-(4-吡啶基）-4(3H)-嘧啶_之概略 備程序 製 〇R Example 42- Summary of Substituted 5- (4-fluorophenyl) -6- (4-pyridyl) -4 (3H) -pyrimidine_ Preparation Procedure

(請先閱讀背面之注意事項再填寫本頁) -訂· 經濟部中央標準局員工消費合作社印製 a.2-(4-氟苯吡蟓基上丙烯酸：4-氟苯基乙醯a克 ，58.4毫莫耳），4-吡啶羧醛（5.6毫升，58.6毫莫耳），吡 啶（6毫升）及乙酐毫升）之混合物於丨5〇 °C加熱1小時接著 蒸發及於水同時蒸餾。所得物料於添加乙醇時結晶。過濾 出固體及乙醇及乙酸乙醋洗滌獲得標題化合物。]Vi S(m/z) :244·0(Μ + Η)+ ; Ci4Hi〇FN02 要求値 243.2 。 lU^ 147- 表紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（145) NMR(DMSO-d6): d8.43，6.98(2d，各個 2H，叶匕淀），7.73(s ，1H，CH=)，7.21(d，4H，PhF) 〇 氟苯基）-3-(4-吡啶基）-丙烯酸乙酯：澧硫酸（2.2毫升 )小心添加至2-(4 -氟苯基）-3-(4·ρ比淀基）-丙晞酸（6.7克’ 27.5毫莫耳）於乙醇（120毫升）之懸浮液及混合物回流加熱 24小時。蒸發去除溶劑，殘餘物攝取於二氯甲烷及有機溶 液以碳酸氫鈉水液及水洗滌，接著脱水及蒸發。於矽膠急 速柱式層析（己烷-丙酮=2 : 1)獲得純標題化合物。 MS(m/z): 271·8(Μ + Η)+; C16H14FN02 要求値 271.3。4- NMR(CDC13) : 8.44，6.88(2m，各個 2H，p比淀），7.72(s ，1H，CH = )，7.16，7.06(2m，各個 2H，PhF)，4.28(q ，2H，CH2)，1.28(t，3H，CH3) 〇 經濟、部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) c. 一般程序：2-(4-氟苯基）·3_(4_吡啶基）-丙埽酸乙酯（357 毫克，1.38毫莫耳），脒鹽酸鹽（2.61毫莫耳）及甲氧化鈉 (250毫克，4.62毫莫耳）於乙醇（5毫升）之攪妥混合物於 120 °C密封管内加熱3小時。蒸發前以2Ν鹽酸中和。殘餘 物攝取於乙酸（25毫升）及以亞硝酸鈉（670毫克，9.71毫莫 耳）於44 °C處理20分鐘。蒸發後所得產物攝取於二氯甲烷 及溶液以竣酸氫鈉水液及水洗鲦隨後脱水及蒸發。產物由 甲醇再結晶純化。若亞硝酸鹽氧化之粗產物爲水溶性，如 5-(4-氟苯基）-2-甲基-6-(4-峨淀基）-4(3H)-喃淀自同所見，則 未進行水液後續處理，但蒸發所得材料施用至矽膠柱（5 % 甲醇/二氯甲烷）隨後再結晶。 下列化合物係使用適當脒鹽酸鹽據此製備·· _____ -148 - 本紙張尺度適用中國國家標準（CNS ) A4規格（210x197公釐） ~ 520362 A7 B7 五、發明説明（146) 4-1 5_(4·氟苯基V2_甲基-6-(4-吡啶基）-4(3H)-嘧啶： MS(m/z): 282.2(M + H)+; C16H12FN30 無求値281.3。111-NMR(DMSO-d6) : d 8.46(m，2H，吡嗳），7.2-7.03(m， 6H，PhF，吡啶），2.38(s，3H，CH3)。 R1 二 CH3- 4-2 5 (4麵氣苯；^ )-2_ 異丙；^ ό_(4 p比 )-4(3H) - 口备 : MS(m/z) _ 310.0(M + H)+; C18H16FN30 要求値 309.4。111-NMR(DMSO-d6) : d 8.45(m，2H，吡啶），7·21-7·03(ιη， 6H，PhF，吡啶），2·90(ιη，1H，CH(CH3)2)，1.26， 1.24(2s，各個 3H，2 CH3)。 R1 = (CH3)2CH- 4-3 2-(2,6二氯苄基）_5-(4-氟苯基）-6·(4-吡啶基）-4(3H)_ 嘧 啶：MS(m/z) ： 426.0(M)+ ; C22H14C12FN30 要求値 426.3 。iH-NMR^DMSO-dJ : d8.37(m，2H，吡啶），7.50(d， 2H，PhCl2)，7.35(t，1H，PhCl2)，7.18-7.08(m，4H ，PhF)，6.96(m，2H，吡啶），4.36(s，2H，CH2)。(Please read the precautions on the back before filling out this page)-Customized · Printed by a. 2- (4-Fluorophenylpyridinyl on acrylic acid: 4-fluorophenylethylfluorene a) , 58.4 mmol), 4-pyridinecarboxaldehyde (5.6 ml, 58.6 mmol), pyridine (6 ml) and acetic anhydride (ml) were heated at 50 ° C for 1 hour, then evaporated and distilled simultaneously with water . The resulting material crystallized when ethanol was added. The solid was filtered off and washed with ethanol and ethyl acetate to obtain the title compound. ] Vi S (m / z): 244.0 (M + Η) +; Ci4Hi〇FN02 requires 値 243.2. lU ^ 147- The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A7 B7 V. Description of the invention (145) NMR (DMSO-d6): d8.43, 6.98 (2d, each 2H, leaf Diandian), 7.73 (s, 1H, CH =), 7.21 (d, 4H, PhF) fluorophenyl) -3- (4-pyridyl) -ethyl acrylate: Sulfuric acid (2.2 ml) was carefully added to A suspension of 2- (4-fluorophenyl) -3- (4.p.pyridyl) -propionic acid (6.7 g '27.5 mmol) in ethanol (120 ml) and the mixture was heated at reflux for 24 hours. The solvent was removed by evaporation, and the residue was taken up in dichloromethane and an organic solution, washed with aqueous sodium hydrogen carbonate solution and water, and then dehydrated and evaporated. Purification by silica gel flash column chromatography (hexane-acetone = 2: 1) gave the pure title compound. MS (m / z): 271.8 (M + Η) +; C16H14FN02 requires 値 271.3. 4-NMR (CDC13): 8.44, 6.88 (2m, each 2H, p ratio), 7.72 (s, 1H, CH =), 7.16, 7.06 (2m, each 2H, PhF), 4.28 (q, 2H, CH2), 1.28 (t, 3H, CH3) 〇 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economy and Economy (please read the first Note: Please fill in this page again) c. General procedure: 2- (4-fluorophenyl) · 3_ (4-pyridyl) -propionate ethyl ester (357 mg, 1.38 mmol), hydrazone hydrochloride ( 2.61 millimoles) and sodium methoxide (250 mg, 4.62 millimoles) in ethanol (5 ml). Heat the mixture in a sealed tube at 120 ° C for 3 hours. Neutralize with 2N hydrochloric acid before evaporation. The residue was taken up in acetic acid (25 ml) and treated with sodium nitrite (670 mg, 9.71 mmol) at 44 ° C for 20 minutes. The product obtained after evaporation was taken up in dichloromethane and the solution to complete the aqueous sodium hydrogen acid solution and water washing, followed by dehydration and evaporation. The product was purified by recrystallization from methanol. If the crude product of nitrite oxidation is water-soluble, such as 5- (4-fluorophenyl) -2-methyl-6- (4-eodoyl) -4 (3H) -nando, then No subsequent treatment with water was performed, but the material obtained by evaporation was applied to a silica gel column (5% methanol / dichloromethane) and then recrystallized. The following compounds were prepared based on the appropriate hydrazone hydrochloride ... _____ -148-This paper size is applicable to Chinese National Standard (CNS) A4 (210x197 mm) ~ 520362 A7 B7 V. Description of the invention (146) 4-1 5_ (4 · fluorophenyl V2-methyl-6- (4-pyridyl) -4 (3H) -pyrimidine: MS (m / z): 282.2 (M + H) +; C16H12FN30 No requirement 281.3. 111- NMR (DMSO-d6): d 8.46 (m, 2H, pyridoxine), 7.2-7.03 (m, 6H, PhF, pyridine), 2.38 (s, 3H, CH3). R1 diCH3- 4-2 5 (4 Surface gas benzene; ^) -2_ isopropyl; ^ __ (4 p ratio) -4 (3H)-mouth preparation: MS (m / z) _ 310.0 (M + H) +; C18H16FN30 requires 309.4.111-NMR (DMSO-d6): d 8.45 (m, 2H, pyridine), 7.21-7.03 (ιη, 6H, PhF, pyridine), 2.90 (ιη, 1H, CH (CH3) 2), 1.26, 1.24 (2s, each 3H, 2 CH3) R1 = (CH3) 2CH- 4-3 2- (2,6dichlorobenzyl) _5- (4-fluorophenyl) -6 · (4-pyridyl) -4 (3H) _ pyrimidine: MS (m / z): 426.0 (M) +; C22H14C12FN30 requires 値 426.3. IH-NMR ^ DMSO-dJ: d8.37 (m, 2H, pyridine), 7.50 (d, 2H , PhCl2), 7.35 (t, 1H, PhCl2), 7.18-7.08 (m, 4H, PhF), 6.96 (m, 2H, pyridine) 4.36 (s, 2H, CH2).

ClCl

經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁)Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling this page)

4-4 5-(4-氟苯基）-2-苯基-6-(4_吡啶基）-4(3H)-嘧啶： MS(m/z): 344.2(M + H)+; C21H14FN30 要求値 343.4。111-NMR(DMSO-d6) : d 8.49(d，2H，吡啶），8.20(d，2H， Ph)，7.66-7.50(m，3H，吡啶，Ph)，7.32-7.11(m，6H _-149-_ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（147 ) ，PhF ， Ph) R1 σ 實例5 5-(4-氟苯基）-6-(4•说咬基）_2_硫燒基·4(3Ηρ密徒_之概略 製備程序 免屋...Α·2·(4-氣苯基吡啶基丙酸乙酯：4-4 5- (4-fluorophenyl) -2-phenyl-6- (4-pyridyl) -4 (3H) -pyrimidine: MS (m / z): 344.2 (M + H) +; C21H14FN30 Requirement 343.4. 111-NMR (DMSO-d6): d 8.49 (d, 2H, pyridine), 8.20 (d, 2H, Ph), 7.66-7.50 (m, 3H, pyridine, Ph), 7.32-7.11 (m , 6H _-149-_ This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A7 B7 5. Description of the invention (147), PhF, Ph) R1 σ Example 5 5- (4-fluorobenzene Radical) -6- (4 • said bitenyl) _2_sulfanyl radical · 4 (3Ηρ 密 徒 _'s general preparation procedure free house ... A · 2 · (4-aminophenylpyridyl propionate ethyl ester:

(請先閱讀背面之注意事項再填寫本頁) 經濟部中央標隼局員工消費合作社印製 81(1955)) 〇 4-氟苯基乙酸乙酯（13克，71.35毫莫耳），異於驗酸乙酯 (10.7毫升，71·4毫莫耳）及鈉鲩（1·64克，71.34毫莫耳） 之混合物於9 0 - 9 5 °C於氬下加熱。混合物開始回流且逐漸 轉成固體。2.5小時後，混合物以稀乙酸中和拌以冷卻， 接著以二氯甲烷萃取。有機溶液以水洗滌，脱水及蒸發。 於矽膠柱急速層析（己烷-丙酮=4 : 1，3 : 1，2 : 1)獲 得標題化合物呈油。MS(m/z) : 287.8(M+H)+ ; C16H14FN03 要求値 287.3。W-NMRCCDCh)，（酮··晞醇 1 : 0.33): dl3.50(s，0·3Η，OH-E)，8.81(m 2H，吡 150- 本紙張尺度適用中國國家標率（CNS ) A4規格（21〇X 297公釐） 520362 A7 B7 五、發明説明（148 ) 咬-K)，8.48(m，0.66H，冲b 淀-E)，7.72(m，2H，p比淀·(Please read the precautions on the back before filling out this page) 81 (1955) printed by the Employees' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 〇 4-fluorophenyl ethyl acetate (13 g, 71.35 mmol), different from A mixture of ethyl acetate (10.7 ml, 71.4 mmol) and sodium sulfide (1.64 g, 71.34 mmol) was heated at 90-95 ° C under argon. The mixture started to reflux and gradually turned into a solid. After 2.5 hours, the mixture was neutralized with dilute acetic acid and cooled, followed by extraction with dichloromethane. The organic solution was washed with water, dehydrated and evaporated. Flash chromatography on a silica gel column (hexane-acetone = 4: 1,3: 1,2: 1) gave the title compound as an oil. MS (m / z): 287.8 (M + H) +; C16H14FN03 requires 値 287.3. W-NMRCCDCh), (keto ·· methanol 1: 0.33): dl3.50 (s, 0 · 3OH, OH-E), 8.81 (m 2H, pyr 150-) This paper is applicable to China National Standards (CNS) A4 specification (21 × X 297 mm) 520362 A7 B7 V. Description of the invention (148) Bite-K), 8.48 (m, 0.66H, red b-Y), 7.72 (m, 2H, p than yodo ·

V K)，7.38(m，2H，PhF-K)，7.14-7.04(m，2H，PhF-K ;〜0·65Η，外匕淀-E ;〜0.65H ， PhF-E) ’ 6.96(t，0.64H， PhF-E)，5.51(s，1H，CH-K)，4·23-4·2.(ηι，CH2-K， E)，1.26(t，CH3-K，E)。 步驟B.5_(4 -氣笨基）-6-(4 -峨淀基）-2 -硫尿喊症：VK), 7.38 (m, 2H, PhF-K), 7.14-7.04 (m, 2H, PhF-K; ~ 0.65Η, Outer-E; ~ 0.65H, PhF-E) '6.96 (t, 0.64H, PhF-E), 5.51 (s, 1H, CH-K), 4.2 · 3-4 · 2.2. (Η, CH2-K, E), 1.26 (t, CH3-K, E). Step B.5_ (4 -Airbenzyl) -6- (4 -Edianji) -2 -thiourea:

(請先閲讀背面之注意事項再填寫本頁) 2-(4 -氟苯基）-3-氧基- 3-(4 -外b淀基）-丙酸乙酯（22.3克， 77.6毫莫耳）及硫脲（5.9克，77.6毫莫耳）之攪妥混合物於 19 0 °C於氬下反應4 0分鐘。任反應混合物達室溫，攝取於 丙酮及過濾沉澱獲得標題化合物。MS(m/z): 300·2(Μ + Η)+ ; C15H10FN3OS 要求値 299 3 。 1η_ NMR(DMSO-d6): d 12.74，12.65(2s，2Η)，8.51(m，2Η 經濟部中央標準局員工消費合作社印製 ，吡啶），7.26(m，2H，吡啶），7·09 及 7 〇3(2m，各個 2H，PhF)。 另外，2-(4-氟苯基）_3-氧基-3-(4-吡啶基丙酸乙酉匕 α87克’ 1〇毫莫耳）及硫脈（2·28克，30亳莫耳）懸浮於^ 水對二甲苯（50毫升）拌以極有效攪拌。混合物内加入對 苯磺酸吡啶鑌（1〇〇毫克）及使用丁史塔克裝置回流ΐ2·ΐ6 本紙張尺度適用中國國家標準（CNS ) 520362 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（149) 時摔以連績去除水（0.2毫升）。反應混合物經冷卻，暗褐色 固體使用布克納漏斗過濾。收集得之_體懸浮於丙酮（25 毫升）及過滤。經丙酮洗滌產物含有微量硫脲，其以熱水 (20-30毫升）滴定去除。產物經過濾及風乾。 步驟C.概略程序： 芳基燒基溴（0.36亳莫耳）逐滴加至5_(4_氟苯基兴6_(4_吡 哫基）-2-硫尿嘧啶（1〇〇亳克，〇 33毫莫耳）及碳酸鉀（46亳 克，0.33毫莫耳）於N，N-二甲基甲醯胺（4.6毫升）之攪拌混 合物。持續攪拌3小時接著蒸發。於矽膠柱急速層析（己烷 -丙酮二3 : 1，2 : 1，：ι : 〇及由熱甲醇再結晶獲得目 標化合物。 下列化合物係使用適當芳基烷基溴根據前述程序獲得·· 5-1 g-(4-氟苯基）_2-(2•笨基乙基）硫_6-(4-吡啶基V4(3H)-嘧 m ： MS(m/z) ·· 404·2(Μ+Η)+ ; C23H18FN3OS 要求値 403.4。h-NMR^DMSO·、）： dl3.08(bs，0·7Η)，8.49(m ，2H，吡啶），7.30-7.06(m，11H，吡啶，Ph，PhF)， 3.41(dd，2H，CH2S)，3.00(t，2H，CH2)。(Please read the precautions on the back before filling this page) 2- (4-Fluorophenyl) -3-oxy-3- (4-Exo-b-yl) -ethyl propionate (22.3 g, 77.6 mmol) Ear) and thiourea (5.9 g, 77.6 mmol) were stirred at 19 ° C for 40 minutes under argon. The reaction mixture was allowed to reach room temperature, taken up in acetone and filtered to obtain the title compound. MS (m / z): 300 · 2 (Μ + Η) +; C15H10FN3OS requires 値 299 3. 1η_NMR (DMSO-d6): d 12.74, 12.65 (2s, 2Η), 8.51 (m, 2Η Printed by the Consumer Cooperative of the Central Standards Bureau, Ministry of Economic Affairs, pyridine), 7.26 (m, 2H, pyridine), 7.09 and 〇3 (2m, each 2H, PhF). In addition, 2- (4-fluorophenyl) _3-oxy-3- (4-pyridylpropanoic acid ethyl acetate (87 g '10 mmol) and sulfur veins (2.28 g, 30 mmol) Suspend in ^ water of para-xylene (50 ml) and mix with extremely effective stirring. Pyridine p-benzenesulfonate (100 mg) was added to the mixture and refluxed using a Ding Stark device. 2 · ΐ6 This paper size applies to Chinese National Standards (CNS) 520362 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 Five 2. Description of the invention (149) When the water was dropped (0.2 ml), it was continuously dropped. The reaction mixture was cooled and the dark brown solid was filtered using a Bucherer funnel. The collected body was suspended in acetone (25 ml) and filtered. The product washed with acetone contained traces of thiourea which was removed by titration with hot water (20-30 ml). The product was filtered and air-dried. Step C. General procedure: Arylalkyl bromide (0.36 mol) is added dropwise to 5- (4-fluorophenyl oxo 6- (4-pyridyl) -2-thiouracil (100 g, 〇33mmol) and potassium carbonate (46 亳 g, 0.33mmol) in N, N-dimethylformamide (4.6ml). Stir mixture for 3 hours and then evaporate. Rapid layer on silica gel column Analytical (hexane-acetone di 3: 1,2,1 :: ι: 〇 and recrystallization from hot methanol to obtain the target compound. The following compounds were obtained according to the procedure described above using the appropriate aryl alkyl bromide. 5-1 g- (4-Fluorophenyl) _2- (2 • benzylethyl) sulfur-6- (4-pyridyl V4 (3H) -pyrimidine: MS (m / z) ·· 404 · 2 (M + Η) +; C23H18FN3OS requires 値 403.4. H-NMR ^ DMSO ·,): dl3.08 (bs, 0.7 ·), 8.49 (m, 2H, pyridine), 7.30-7.06 (m, 11H, pyridine, Ph, PhF) , 3.41 (dd, 2H, CH2S), 3.00 (t, 2H, CH2).

5-2 5·(4_氟苯基）-2-(3_苯基丙基）硫-6-(4-吡啶基V4(3H)-嘧 啶酮：MS(m/z) : 418.0(M+H)+ ; C24H2〇FN3OS 要求値 417.5 〇 iH-NMR^DMSO-H· dl3.10(bs，0.7H)，8.47(m ，2H，p比淀），7.29-7.06(m，11H，p比淀，Ph，PhF) ’ -152-____ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） #狀衣-- (請先閱讀背面之注意事項再填寫本頁)5-2 5 · (4-fluorophenyl) -2- (3-phenylpropyl) thio-6- (4-pyridyl V4 (3H) -pyrimidone: MS (m / z): 418.0 (M + H) +; C24H2〇FN3OS requires 値 417.5 〇iH-NMR ^ DMSO-H · dl3.10 (bs, 0.7H), 8.47 (m, 2H, p ratio lake), 7.29-7.06 (m, 11H, p Bidian, Ph, PhF) '-152 -____ This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) # 状 衣-(Please read the precautions on the back before filling this page)

、1T J· 5203621T J520520

A7 B7 五、發明説明（15〇 ) 3.18(t，2H，CH2S)，2.71(t，2H，CH2Ph)，2.03(m， 2H，CH2)。 v R1 5_3 5-(4_鼠豕基）-2_(2-苯氧> 乙基）硫-6-(4-p比淀基-^ 峰酮：MS(m/z) ·· 420·0(Μ+Η)+ ; C23Hi8FN302S 要求値 419.5 〇 W-NMR^DMSO-dd: dl3.20(bs，0·7Η)，8.46(m ，2H，吡啶），7.24-7.07(m，8H，吡啶，PhF，Ph)， 6.95(d，2H，Ph)，6.92(t，重疊，1H，Ph)，4.30(t， 2H，CH20)，3.58(t，2H，CH2S)。 (讀先閱讀背面之注意事項再填寫本頁) R1 u 〇、A7 B7 V. Description of the invention (15) 3.18 (t, 2H, CH2S), 2.71 (t, 2H, CH2Ph), 2.03 (m, 2H, CH2). v R1 5_3 5- (4_murinoyl) -2_ (2-phenoxy > ethyl) sulfur-6- (4-p than ydoyl- ^ peak ketone: MS (m / z) ·· 420 · 0 (Μ + Η) +; C23Hi8FN302S requires 値 419.5 MW-NMR ^ DMSO-dd: dl3.20 (bs, 0.7Η), 8.46 (m, 2H, pyridine), 7.24-7.07 (m, 8H, pyridine) , PhF, Ph), 6.95 (d, 2H, Ph), 6.92 (t, overlap, 1H, Ph), 4.30 (t, 2H, CH20), 3.58 (t, 2H, CH2S). (Read the first read on the back Please fill in this page again for attention) R1 u 〇 、

、1T 經濟部中央標準局員工消費合作社印製 5-4 5·Γ4-氟苯基）_2-(2-苯基胺基乙基）硫-6_(4_吡啶基V 4(3H)-嘧啶酮：MS(m/z) : 419·0(Μ + Η)+ ; C23H19FN4OS 要 求値 418.5。h-NMR^DMSO-dd: d 13.20(bs，0.8H)， 8.48，7.22(2m，各個 2H，吡啶），7.16，7.10(2m，各個 2H，PhF)，6.89(t，2H，Ph)，6.54(d，2H，Ph)， 6.48(t，1H，Ph)，5.90(bs，0.6H，NH)，3·43-3·25(ιη ，2 CH2)。, 1T printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 5-4 5 · Γ4-fluorophenyl) _2- (2-phenylaminoethyl) sulfur-6_ (4_pyridyl V 4 (3H) -pyrimidine Ketone: MS (m / z): 419.0 (M + Η) +; C23H19FN4OS requires 値 418.5. H-NMR ^ DMSO-dd: d 13.20 (bs, 0.8H), 8.48, 7.22 (2m, each 2H, Pyridine), 7.16, 7.10 (2m, each 2H, PhF), 6.89 (t, 2H, Ph), 6.54 (d, 2H, Ph), 6.48 (t, 1H, Ph), 5.90 (bs, 0.6H, NH ), 3.43-3.25 (ιη, 2 CH2).

RJ σ s' i# 153- 本紙張尺度適用中國國家標準（CNS ) A4規格（21〇x 297公瘦） 520362 A7 B7 五、發明说明（151 ) 實例6 2-N取代2-胺基_5_(4-氟苯基）_6-(4-吡邊基）-4(3H)-嘧啶酮 之概略製備程序： 步驟A. 5_(4 -氟表基）_2_甲基硫-6-(4 -p比淀基）-4(3H) -續淀：RJ σ s' i # 153- This paper size applies to Chinese National Standard (CNS) A4 (21 × 297 male thin) 520362 A7 B7 V. Description of the invention (151) Example 6 2-N substituted 2-amino group_5_ (4-Fluorophenyl) -6- (4-pyridyl) -4 (3H) -pyrimidinone: Preparation procedure: Step A. 5_ (4-fluoroepiyl) _2_methylsulfan-6- (4 -p than Yodo base) -4 (3H) -continuous lake:

甲基碘（90毫升，1.44毫莫耳）於冰浴溫度逐滴加至5-(4-氟苯基）-6-(4-吡啶基）-2-硫尿嘧啶（430毫克，1.44毫莫耳） 及碳酸鉀（198毫克，1.43毫莫耳）於n，N-二甲基甲醯胺（13 毫升）之攪妥混合物。40分鐘後經蒸發，粗產物於矽膠柱 藉急速層析純化（己垸-丙酮=2 : 1，1 ·· 1，1 ·· 2)獲得 標題化合物呈固體。MS(m/z) : 314·2(Μ+Η)+ ; C16H12FN3OS 要求値 313.3 。iH-NMR^DMSO-dJ : d (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 13.10(bs)，8.47，7.22(2m，各個 2H，吡啶），7.16， 7.10(2m，各個 2H，PhF)，2.56(s，3H，CH3)。 步驟B.概略程序：Methyl iodide (90 ml, 1.44 mmol) was added dropwise to the 5- (4-fluorophenyl) -6- (4-pyridyl) -2-thiouracil (430 mg, 1.44 mmol) at an ice bath Mol) and a stirred mixture of potassium carbonate (198 mg, 1.43 mmol) in n, N-dimethylformamide (13 ml). After 40 minutes of evaporation, the crude product was purified by flash chromatography on a silica gel column (hexane-acetone = 2: 1,1 ·· 1,1 ·· 2) to obtain the title compound as a solid. MS (m / z): 314.2 (M + Η) +; C16H12FN3OS requires 値 313.3. iH-NMR ^ DMSO-dJ: d (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Central Standards Bureau, Ministry of Economic Affairs 13.10 (bs), 8.47, 7.22 (2m, each 2H, pyridine), 7.16 , 7.10 (2m, each 2H, PhF), 2.56 (s, 3H, CH3). Step B. Outline procedure:

-154- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 __B7 五、發明説明（152 ) 5-(4-氟苯基）-2-甲基硫-6-(4-吡啶基）-4(3H)-嘧啶（1 〇〇毫 克，〇·32毫莫耳）及胺hnr5r21(1毫莫—耳）之混合物於ι8〇 °C加熱2小時。所得產物於矽膠柱藉急速層析純化（己燒_ 丙酮或甲醇-二氯甲燒）獲得目標化合物，及由甲醇再結晶。 下列化合物係使用前述概略程序及適當胺製備： 6-1 2-(2-(2 -氯苯基）乙基-胺基）_5-(4_氟笨某喊#其 )-4(3H)-嘧啶酮·· MS(m/z) ： 421.2(M + H)+ ; C23H18C1FN40 要求値 420.9。h-NMI^DMSO-dd: dll.24(bs)，8.44， 7.16 (2m，各個 2H，吡啶），7.43，7.38(2dd，各個 1H ，PhCl)，7·30，7.26(2dt，各個 1H，PhCl)，7.1〇-7.〇〇(m ，2H，PhF)，6.74(bs，1H，NH)，3.60(q，2H，CH2N) ，3.03(t，2H，CH2) 0-154- This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 520362 A7 __B7 V. Description of the invention (152) 5- (4-fluorophenyl) -2-methylsulfur-6- (4 -Pyridyl) -4 (3H) -pyrimidine (100 mg, 0.32 mmol) and the amine hhn5r21 (1 mmol-ear) were heated at 80 ° C for 2 hours. The obtained product was purified by flash chromatography on a silica gel column (hexane-acetone or methanol-dichloromethane) to obtain the target compound, and recrystallized from methanol. The following compounds were prepared using the outlined procedures and appropriate amines: 6-1 2- (2- (2- (chlorophenyl) ethyl-amino) _5- (4_fluoro 笨 某 叫 # 其) -4 (3H) -Pyrimidinone MS (m / z): 421.2 (M + H) +; C23H18C1FN40 requires 値 420.9. h-NMI ^ DMSO-dd: dll.24 (bs), 8.44, 7.16 (2m, each 2H, pyridine), 7.43, 7.38 (2dd, each 1H, PhCl), 7.30, 7.26 (2dt, each 1H, PhCl), 7.10-7.00 (m, 2H, PhF), 6.74 (bs, 1H, NH), 3.60 (q, 2H, CH2N), 3.03 (t, 2H, CH2) 0

H (請先閱讀背面之注意事項再填寫本頁)H (Please read the notes on the back before filling this page)

經濟部中央標準局員工消費合作社印製 6-2 5-(4-氟苯基）-2-((3-苯基丙基V胺基）-6-(4-吡啶基）-4(3H)-嘧啶酮：MS(m/z) : 401·2(Μ + Η)+ ; C24H21FN40 要 求値 400.5。iH-NMI^DMSO-dd: dll.l6(bs)，8.44， 7.14(2m，各個 2H，吡啶），7.32-7.01(m，9H，Ph，PhF) ，6.78(bs，NH)，3.36(q，2H，CH2N)，2.67(t，2H， CH2Ph)，1.89(m，2H，CH2)。 ___- 155- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐1 520362 A7 B7Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 6-2 5- (4-fluorophenyl) -2-((3-phenylpropylVamino) -6- (4-pyridyl) -4 (3H ) -Pyrimidinone: MS (m / z): 401.2 (Μ + Η) +; C24H21FN40 requires 値 400.5. IH-NMI ^ DMSO-dd: dll.16 (bs), 8.44, 7.14 (2m, each 2H , Pyridine), 7.32-7.01 (m, 9H, Ph, PhF), 6.78 (bs, NH), 3.36 (q, 2H, CH2N), 2.67 (t, 2H, CH2Ph), 1.89 (m, 2H, CH2) ___- 155- This paper size applies to China National Standard (CNS) A4 (210X297 mm 1 520362 A7 B7

五、發明説明（153 R] 6-3 5_(4_氣豕基）-2-((1-甲基-3-苯基丙基）-胺基）-6_(4-p比淀 基）-4(3HV嘧啶酮··反應於180 °C需反應時間15小時。 MS(m/z) ·· 415·0(Μ + Η)+; C25H23FN40 要求値 414.5。iH· NMR(CDC13): d8.48(m，2H，吡啶），7.28-7.08(m，9H ，吡啶，Ph，PhF)，6.94(m，2H，PhF)，5.67(bs，1H ，NH)，4.08(m，1H，CHCH3)，2.6 l(t，2H，CH2Ph) ，1.67(m，2H，CH2)，1.08(d，3H，CH3) 〇 R1 = (請先閱讀背面之注意事項再填寫本頁) CH,V. Description of the invention (153 R) 6-3 5_ (4_Arylidene) -2-((1-methyl-3-phenylpropyl) -amino group) -6_ (4-p ratio) -4 (3HV pyrimidinone ·· It takes 15 hours to react at 180 ° C. MS (m / z) ·· 415 · 0 (Μ + Η) +; C25H23FN40 requires 値 414.5. IH · NMR (CDC13): d8 .48 (m, 2H, pyridine), 7.28-7.08 (m, 9H, pyridine, Ph, PhF), 6.94 (m, 2H, PhF), 5.67 (bs, 1H, NH), 4.08 (m, 1H, CHCH3 ), 2.6 l (t, 2H, CH2Ph), 1.67 (m, 2H, CH2), 1.08 (d, 3H, CH3) 〇R1 = (Please read the precautions on the back before filling this page) CH,

經濟部中央標率局員工消費合作社印製 6-4 5-(4·氣苯基）-2-((3-味峻基丙基）-月安基）-6-(4 -p比淀基）瞧 4(3H)-嘧啶酮：MSfm/z) : 391 ·0(Μ + Η)+ ; C21H19FN60 要 求値 390.4。iH-NMR^DMSO-dd : d 11.24(bs)，8.42， 7.12(2m，各個 2H，吡啶），7.62，7.18(2s，各個 1H， 咪也），7.08-6.99(m，4H，PhF) ’ 6.88(s，1H，咪咬） ，4.02〇，2^1，（：112?^)，3.28(重疊水信號，（：11一11)， 2.00(m，2H，CH2) 0 R1Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. 6-4 5- (4-Gasphenyl) -2-((3-Weijunylpropyl) -Yueanji) -6- (4 -p Biyodo Based on 4 (3H) -pyrimidinone: MSfm / z): 391 · 0 (Μ + Η) +; C21H19FN60 requires 値 390.4. iH-NMR ^ DMSO-dd: d 11.24 (bs), 8.42, 7.12 (2m, each 2H, pyridine), 7.62, 7.18 (2s, each 1H, miya), 7.08-6.99 (m, 4H, PhF) ' 6.88 (s, 1H, microphone bite), 4.02〇, 2 ^ 1, (: 112? ^), 3.28 (overlapping water signal, (: 11-11), 2.00 (m, 2H, CH2) 0 R1

OO

H 156 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） ，362 ，362H 156 This paper size is applicable to China National Standard (CNS) A4 (210X297 mm), 362, 362

A7 i '發明説明（154) 實例7 5-(4 -氟苯基）-2-肼基- 6-(4-吡啶基）：4(3H)-嘧啶酮 5-(4 -氣豕基）-6-(4 -p比淀基）-2 -硫尿p密章（5〇〇毫克，166 毫莫耳）及肼水合物（800毫升，約14毫莫耳）之混合物於12〇 C力口熱6 0分鐘。經蒸發及反應產物由熱甲醇再結晶獲得標 題化合物。MS(m/z): 298.0(M + H)+; Ci5Hi2FN5〇 要求値 297.3。^-NMWDMSO-D: d 8·41，7·12(2ιη，各個 2H ，吡啶），7·05，7.00(2m，各個 2Η，PhF)。 R1 = NH-NH2 實例8 5-芳基-2,6-二此淀基-(3H)-嘧咬酮之概略製備程序 (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製A7 i 'Explanation of the invention (154) Example 7 5- (4-fluorophenyl) -2-hydrazino-6- (4-pyridyl): 4 (3H) -pyrimidinone 5- (4-aziridinyl) A mixture of -6- (4-p-pyridyl) -2 -thiourea p-signature (500 mg, 166 mmol) and hydrazine hydrate (800 ml, about 14 mmol) at 120 ° C Likou heat for 60 minutes. The title compound was obtained by evaporation and reaction product recrystallization from hot methanol. MS (m / z): 298.0 (M + H) +; Ci5Hi2FN50 requires 297.3. ^ -NMWDMSO-D: d 8.41, 7.12 (2m each, 2H, pyridine), 7.05, 7.00 (2m, each 2H, PhF). R1 = NH-NH2 Example 8 Schematic preparation procedure of 5-aryl-2,6-diphenyl- (3H) -pyrimidone (Please read the notes on the back before filling this page) Central Bureau of Standards, Ministry of Economic Affairs Printed by Employee Consumer Cooperative

520362 A7 ________ B7 五、發明説明（155 )520362 A7 ________ B7 V. Description of the invention (155)

8-4 · F8-4F

(請先閱讀背面之注意事項再填寫本頁) 〇Et 此等化合物係根據參考文獻製備如下（Kabbe， supra ; German Patent 1271 1 16 (1968)) ·· 苯基乙酸乙酯（3.13毫莫耳），氰基吡啶（6.24毫莫耳）及甲 氧化鈉（3.5毫莫耳）於正丁醇（1.2毫升）之攪妥混合物於11〇 °C加熱2小時。反應混合物經濃縮及溶解於水（4毫升），接 著加入飽合氯化銨水液（2毫升）。過濾出沉澱及由熱甲醇再 結晶。 下列化合物係根據此種程序使用適當起始物料製備： 8-1 5-麥基- 2,6 -武 _(4 -p比淀基）-4_(3H)-p密淀嗣：MS(m/ζ) ·· 327.2(M + H)+; C2〇H14N40 要求値 326.4。111"^]^11(〇]^180-d6) : d 8·78，8·47，8.13(3m，各個 2H，吡啶），7.40- 7.14(m，7H，Ph，峨淀）。 8-2 5-(4-氟苯基）_2,6•貳_(4·吡啶基）-4(3H)_嘧唸酮： 經濟部中央標苹局員工消費合作社印繁 MS(m/z): 345·2(Μ + Η)+; C2〇H13FN40 要求値 344.4。1{^ NMR(DMSO-d6) : d8.80，8.49，8.13(3m，各個 2H，吡 啶），7.40-7.08(m，6H，PhF，吡啶）。 8-3 2,5,6 -畚- (4 -p比淀，基）-4(3Η)-喃淀酮係根據概略程序經 由4·吡啶基乙酸乙酯與4-氰基吡啶於甲氧化鈉存在下反應 製備。MS(m/z) : 328·2(Μ + Η)+ ; C19H13N50 要求値 327 4 -158- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 —_____B7 五、發明説明（156 ) 。h-NMR^DMSO-dd : d8.65，8.45，8.35，8.18，7 25 ，7· 13(6m，各個 2H，此啶）。 v 8-4 5-(4-氟冬基）_2,6_ 武-(3-峨淀基密淀 _ : MS(m/z): 345.2(M + H)+; C20H13FN4O 要求値 344.4。ιΗ_ NMR(DMS0-d6) : d 9·34，8·77，8.54，8·48，7.78， 7·60，7.34(7m，3 X 1Η，2Η，3 X 1Η，吡啶），7 26 ，7.15(2m，各個 2Η，PhF)。 實例9 4·-胺基_5-(4_氣苯基）-2,6 -武- (4^比淀基）·ρ密淀 (請先閱讀背面之注意事項再填寫本頁}(Please read the notes on the back before filling in this page) 〇Et These compounds were prepared according to the references (Kabbe, supra; German Patent 1271 1 16 (1968)). · Ethyl phenylacetate (3.13 mmol) ), A stirred mixture of cyanopyridine (6.24 mmol) and sodium methoxide (3.5 mmol) in n-butanol (1.2 ml) was heated at 110 ° C for 2 hours. The reaction mixture was concentrated and dissolved in water (4 ml), followed by addition of a saturated aqueous ammonium chloride solution (2 ml). The precipitate was filtered off and recrystallized from hot methanol. The following compounds were prepared according to this procedure using appropriate starting materials: 8-1 5-Methyl-2,6-Wu_ (4-p than Yodo) -4_ (3H) -p dense lake: MS (m / ζ) · 327.2 (M + H) +; C2〇H14N40 requires 値 326.4. 111 " ^] ^ 11 (〇) ^ 180-d6): d 8.78, 8.47, 8.13 (3m, each 2H , Pyridine), 7.40-7.14 (m, 7H, Ph, Edian). 8-2 5- (4-fluorophenyl) _2,6 • 贰 _ (4 · pyridyl) -4 (3H) _pyrimidone: Yinfan MS (m / z) ): 345 · 2 (Μ + Η) +; C20H13FN40 requires 値 344.4.1 {^ NMR (DMSO-d6): d8.80, 8.49, 8.13 (3m, each 2H, pyridine), 7.40-7.08 (m , 6H, PhF, pyridine). 8-3 2,5,6 -fluorene- (4-p-pyridine, yl) -4 (3fluorene) -anhydroxanthone was oxidized by methylpyridinylacetate and 4-cyanopyridine in accordance with the outline procedure. Prepared by reaction in the presence of sodium. MS (m / z): 328 · 2 (Μ + Η) +; C19H13N50 requirements 値 327 4 -158- This paper size is applicable to China National Standard (CNS) A4 specification (210X297mm) 520362 A7 —_____ B7 V. Description of the invention (156). h-NMR ^ DMSO-dd: d8.65, 8.45, 8.35, 8.18, 7 25, 7.13 (6m, each 2H, this pyridine). v 8-4 5- (4-Fluorodongyl) _2,6_ Wu- (3-Edianji dense lake_: MS (m / z): 345.2 (M + H) +; C20H13FN4O requires 値 344.4.ιΗ_ NMR (DMS0-d6): d 9.34, 8.77, 8.54, 8.48, 7.78, 7.60, 7.34 (7m, 3 X 1Η, 2Η, 3 X 1Η, pyridine), 7 26, 7.15 (2m , Each 2Η, PhF). Example 9 4 · -Amino_5- (4_Phenylphenyl) -2,6-wu- (4 ^ BiYodo) · ρ dense lake (Please read the notes on the back first Fill out this page again}

胺基-5-(4·氟笨基）-2,6-貳-(4-吡啶基）-嘧啶係根據參考文 獻（Kabbe，參見上文）製備： 經濟部中央標率局員工消費合作杜印製 甲氧化鋼（180毫克，3.33毫莫耳）加至4·氰基p比淀（650 毫克，6·24毫莫耳）及4-氟苯基乙腈（375毫升，3.12毫莫 耳）於正丁醇（1.5毫升）之攪妥溶液。混合物於室溫攪掉20 分鐘隨後於110 °C加熱1.5小時。任其達室溫及加入乙醇 (2.5毫升）。過濾出沉澱及由乙酸/水（35/10毫升）再結晶獲 得標題化合物。MS(m/z) : 344·2(Μ + Η)+ ; C2〇H14FN5 要求 値 343.4。iH-NMR^DMSO-dd : 8.76，8·47，8.22(3m， -_____ - 159- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（157 ) 各個 2H，吡啶），7.4-7.16(m，6H，PhF，吡啶）Amino-5- (4 · fluorobenzyl) -2,6-fluorene- (4-pyridyl) -pyrimidine is prepared according to the reference (Kabbe, see above): Staff Spending Cooperation, Central Standards Bureau, Ministry of Economy Printed formazan steel (180 mg, 3.33 mmol) added to 4 · cyano-p-pyridine (650 mg, 6.24 mmol) and 4-fluorophenylacetonitrile (375 ml, 3.12 mmol) Stir the solution in n-butanol (1.5 ml). The mixture was stirred at room temperature for 20 minutes and then heated at 110 ° C for 1.5 hours. Allow to reach room temperature and add ethanol (2.5 ml). The precipitate was filtered off and recrystallized from acetic acid / water (35/10 ml) to obtain the title compound. MS (m / z): 344 · 2 (Μ + Η) +; C20H14FN5 requires 値 343.4. iH-NMR ^ DMSO-dd: 8.76, 8.47, 8.22 (3m, -_____-159- This paper size applies to China National Standard (CNS) A4 (210X297 mm) 520362 A7 B7 V. Description of the invention (157) Each 2H, pyridine), 7.4-7.16 (m, 6H, PhF, pyridine)

實例1 ο v 4 -甲氧-5-苯基- 2,6 -武比淀基）-癌淀Example 1 v 4 -Methoxy-5-phenyl-2,6 -wubidianyl) -Ondian

C請先閱讀背面之注意事項蒋填寫本貢) 5-苯基-2,6_貳-(4·吡啶基）-4(3H)_嘧啶酮（360毫克，1·1〇 晕莫耳）及磷醯氯（2毫升）之混合物回流加熱1.5小時。如對 製備2_氯·5·(4·氟苯基）_4-(4-吡啶基）-嘧啶所述進行後續處 理。於粗製4-氯-5_苯基-2,6-貳_(4_吡啶基）-嘧啶（250毫克 ，0.73毫莫耳）於甲醇（5毫升）之溶液内加入甲醇系〇.5Ν甲 氧化鈉（1·45毫升，0.73毫莫耳）及回流加熱1小時。蒸發 後所得材料分配於乙酸乙酯與水間。有機溶液以水洗滌， 脱水及蒸發。粗產物於矽膠拄層析（乙酸乙酯）獲得標題化 合物。MS(m/z): 341·2(Μ + Η)+ ; C21H16N40 要求値 340,4 。iH-NMRCCDCh) ·· 8·82，8.54，8.40(3m，各個 2Η， 吡啶），7.40-7.18(m，7H，Ph，吡啶），4.15(s，3H， CH30)。 實例11 5-(4 -氟苯基）-2,4-武- (4-p比淀基）-喃淀之製備程序 步驟A· 4 -氯- 5- (4 -氟苯基）-2,6 -武-(4•峨淀基）_p密喊： -160- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐）CPlease read the notes on the back first to fill out the tribute) 5-phenyl-2,6_ 贰-(4 · pyridyl) -4 (3H) _pyrimidone (360 mg, 1.1 mol) And a mixture of phosphonium chloride (2 ml) was heated at reflux for 1.5 hours. Follow-up as described for the preparation of 2-chloro · 5 · (4 · fluorophenyl) _4- (4-pyridyl) -pyrimidine. To a solution of crude 4-chloro-5_phenyl-2,6-fluorenyl (4-pyridyl) -pyrimidine (250 mg, 0.73 mmol) in methanol (5 ml) was added methanol-based 0.5N methyl formaldehyde. Sodium oxide (1.45 ml, 0.73 mmol) and heated at reflux for 1 hour. The material obtained after evaporation was partitioned between ethyl acetate and water. The organic solution was washed with water, dehydrated and evaporated. The crude product was subjected to silica gel chromatography (ethyl acetate) to obtain the title compound. MS (m / z): 341.2 (Μ + Η) +; C21H16N40 requires 値 340,4. iH-NMRCCDCh) 8.82, 8.54, 8.40 (3m, each 2H, pyridine), 7.40-7.18 (m, 7H, Ph, pyridine), 4.15 (s, 3H, CH30). Example 11 Preparation procedure of 5- (4-fluorophenyl) -2,4-wu- (4-p-pyridyl) -ranodolide A · 4-chloro-5 (4-fluorophenyl) -2 , 6-武-(4 • EDIAN JI) _p secret shout: -160- This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm)

1T 經濟部中央標準局員工消費合作社印製 520362 A7 B7 1581T Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 520362 A7 B7 158

五、發明説明（5. Description of the invention (

N 5-(4_氟本基）_2,6·武_(4_p比淀基）_4(3H) -外b淀嗣（76〇毫克 ’ 2 ·2 1耄莫耳）於磷醯氯（3亳升）之混合物回流加熱1小時 。如製備2 -鼠- 5-(4 -氟苯基）_4-(4·17比淀基）-喊淀所述進行後 續處理。部份（290毫克）所得產物（495毫克）於矽膠藉急速 層析純化（乙酸乙酯，微量三乙基胺）。MS(m/z): 363.2(M + H)+ ; C2〇H12ClFN4 要求値 362·8 。 NMR(CDC13) : d 8·84，8·60，8·38，7·30(4πι，各個 2h ，吡啶），7·22，7.13(2m，各個 2Η，PhF)。 步驟Β· 5-(4 -氟苯基比症基）-喊淀·· (請先閱讀背面之注意事項再填寫本頁jN 5- (4_fluorobenzyl) _2,6 · Wu_ (4_p than Dingji) _4 (3H) -outer B ytterbium (7660 mg '2 · 2 1 耄 mol) in phosphonium chloride (3 The mixture was heated at reflux for 1 hour. Subsequent treatment was carried out as described in the preparation of 2-murine 5- (4-fluorophenyl) _4- (4.17bitoyl) -Yodo. A portion (290 mg) of the obtained product (495 mg) was purified by flash chromatography on silica gel (ethyl acetate, triethylamine in trace amounts). MS (m / z): 363.2 (M + H) +; C20H12ClFN4 requires 値 362.8. NMR (CDC13): d 8.84, 8.60, 8.38, 7.30 (4 μm, 2 h each, pyridine), 7.22, 7.13 (2 m, 2 h each, PhF). Step Β · 5- (4-Fluorophenylpyridinyl)-Shout Lake · (Please read the precautions on the back before filling in this page j

經濟部中央標準局黃工消費合作社印製 4 -氣-5-(4 -氟苯基）_2,6 -武-(4 -p比淀基密淀（99毫克， 0.27毫莫耳）及10 %鈀/碳（70毫克）於乙醇（1〇亳升）之檀妥 混合物於氫氣氛下氫化28小時。過濾及蒸發去除溶劑彳秦著 於矽膠柱急速層析（乙酸乙酯）獲得標題化合物。 ·· 329.2(M + H)+ ; C2〇H13FN4 要求値 328.4 。〜 H- -161 - 本紙張尺度適用中國國家標準（CNS ) A4規格（2l0X297公釐） ----------- 520362 A7 B7 五、發明説明（159 ) (請先閱讀背面之注意事項再填寫本頁) NMR(CDC13) : d 8.91(s，1H，H-6，嘧啶），8.83，8.65 ’ 8.40，7.45(4m，各個 2H，吡啶），v 7.3 0-7.06(m，4H ，PhF) 0 實例12 6-取代3-苯基- 4-(4-喻淀基）_2(1 H)-响淀酮之概略製備程序 步驟A. 1-芳基- 3- (4·ρ比淀基）-2 -丙晞-1-酮之概略製備程序：Printed by 4-g-5--5- (4-fluorophenyl) _2,6-wu- (4-p-pyridyl-based dense lake (99 mg, 0.27 mmol) and 10 % Pd / carbon (70 mg) in ethanol (10 liters) of the tantalum mixture was hydrogenated under a hydrogen atmosphere for 28 hours. The solvent was filtered and evaporated. The title compound was obtained by flash chromatography (ethyl acetate) on a silica gel column · 329.2 (M + H) +; C2〇H13FN4 requires 値 328.4. ~ H- -161-This paper size is applicable to China National Standard (CNS) A4 specification (2l0X297 mm) --------- -520362 A7 B7 V. Description of the invention (159) (Please read the notes on the back before filling this page) NMR (CDC13): d 8.91 (s, 1H, H-6, pyrimidine), 8.83, 8.65 '8.40, 7.45 (4m, each 2H, pyridine), v 7.3 0-7.06 (m, 4H, PhF) 0 Example 12 of 6-Substituted 3-phenyl- 4- (4-Yudendyl) _2 (1 H) -Xylide Schematic preparation procedure Step A. Schematic preparation procedure of 1-aryl-3-(4 · ρ biydyl) -2 -propan-1-one:

於冰浴溫度混合六氫吡啶（206毫升），乙酸（206毫升）及 4-嘧啶羧醛（1.6毫升，16.6毫莫耳）。然後於室溫加入苯乙 酮（12.0毫莫耳）及混合物於1 3 0 °C加熱1 · 5小時。反應混合 物以二氯甲燒稀釋，以碳酸氫鈉水液及水洗鲦接著脱水及 蒸發。粗產物於矽膠藉急速層析純化（己烷-乙酮：=3 : 1)。 下列化合物係根據此種程序使用適當苯乙酮衍生物製備： 1-苯基-3-(4- ρ比淀基）_2丙缔-1·嗣：MS(m/z): 210.1(M + H)+ ; C14HnNO 要求値 209.3。 經濟部中央標隼局員工消費合作社印製 1-(4•甲基苯基）-3-(4_p比淀基）·2-丙晞-1-酬I : MS(m/z): 224.2(M + H)+ ; C15H13NO 要求値 223.3。 1-(4-乙基苯基）_3_(4o比淀基）-2·丙晞-1-嗣：MS(m/z): 237.8(M + H)+ ; C16H15NO 要求値 237.3。 1-(4 -異丙基苯基）_3_(4_p比淀基）_2 -丙婦-1-酉同：MS(m/z): 252.0(M + H)+; C17H17NO 要求値 251.3。 _ -162-_ 本紙張尺度剌巾關家料·（ CNS ) A4規格（21G X 297公釐) ' _ 520362 A7 B7 211·0(Μ + Η) 五、發明説明（160 ) 1-(2-甲基苯基）-3_(4 -外I:咬基）-3-丙晞-1-酮：MS(m/z): 223·8(Μ + Η)+; C15H13NO 要求値 223.3。 1-(2,4-二甲基苯基）-3-(4-p 比淀基）-2·丙晞-1-酮：MS(m/z) :238.0(M + H)+; C16H15NO 要求値 237.3。 1-(2-甲氧豕基）_3-(4·ρ比淀基）-2-丙婦-1-酉同 240.0(Μ + Η) ; C15H13NO2要求値 239.3。 1·(4-氯苯基）-3-(4-ρ比淀基）_2-丙婦-1-酉同 244·0(Μ + Η)+ ; C14H1()C1N0 要求値 243.7。 1-(4-氯基苯基）-3-(4•峨淀基）-2-丙晞-1-酉同 235·1(Μ + Η)+; C15H1()N20 要求値 234.3。 奈基）-3-(4- p比淀基）-2-丙缔-1-酉同 260.0(M + H)+; C18H13NO 要求値 259.3。 1，3 -武- (4 -p比淀基）-2 -丙稀'·1-酉同：MS(m/z): ;C13H1GN20 要求値 210.2。 3-(4_吡啶基）-1-(2_噻吩基）·2-丙烯-1-酮 216·0(Μ + Η)+; C12H9NOS 要求値 215.3。 1_(2_呋喃基）-3·(4-吡啶基）-2-丙晞-1-酮 200·0(Μ + Η)+ ; C12H9N02 要求値 199.2。 1-環己基-3-(4-吡啶基）-2-丙烯-1-酮係以相同方式使用乙 醯環己烷製備：MS(m/z): 216·2(Μ + Η)+; C“Hi7N〇 要求 値 215.3 〇 1 -第二丁基-3 _(4_17比淀基）-2 -丙缔-1-嗣：3，3 - 甲基2 酮（2.5毫升，20.0毫莫耳），4·吡啶羧醛（2.15毫升’ 22·3 毫莫耳），乙醇（7.6毫升）及4.5 %氫氧化鈉水液（4.6 %升） -163 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） ---------·裝-- (請先閲讀背面之注意事項再填寫本頁) 訂 經濟部中央標隼局員工消費合作社印製 520362 A7 B7 *— -- ----------------- ---- ---- -一—— - -----------____ 五、發明説明（161 ) 之混合物於室溫維持12小時。以二氣甲烷稀釋，以鹽酸水 液及水洗務’脱水及蒸發。隨後柱式層析（己院-乙酸乙醋 =3 : 1)獲得標題化合物。MS(m/z) : 190.4(M+H)+ ； C12H15NO 要求値 189.3 〇 步驟Β· 6·取代3 -苯基- 比淀基）-2(1Η)-ρ比淀酮類之概略 製備程序： (請先閱讀背面之注意事項再填寫本頁) i·Mix hexahydropyridine (206 ml), acetic acid (206 ml) and 4-pyrimidinecarboxaldehyde (1.6 ml, 16.6 mmol) at the temperature of the ice bath. Then acetophenone (12.0 mmol) was added at room temperature and the mixture was heated at 130 ° C for 1.5 hours. The reaction mixture was diluted with dichloromethane, washed with aqueous sodium bicarbonate solution and water, dehydrated and evaporated. The crude product was purified by flash chromatography on silica gel (hexane-ethyl ketone: = 3: 1). The following compounds were prepared according to this procedure using the appropriate acetophenone derivative: 1-phenyl-3- (4-ρ bipyridyl) _2propan-1 · 嗣: MS (m / z): 210.1 (M + H) +; C14HnNO requires 値 209.3. Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs, 1- (4 • methylphenyl) -3- (4_p than Yodo-based) · 2-Propane-1-reward I: MS (m / z): 224.2 ( M + H) +; C15H13NO requires 値 223.3. 1- (4-ethylphenyl) _3_ (4o than ydoyl) -2 · propan-1-one: MS (m / z): 237.8 (M + H) +; C16H15NO requires 値 237.3. 1- (4 -Isopropylphenyl) _3_ (4_p than yodoyl) _2 -Propane-1-isopropyl: MS (m / z): 252.0 (M + H) +; C17H17NO requires 値 251.3. _ -162-_ This paper scales towels and household materials · (CNS) A4 size (21G X 297 mm) '_ 520362 A7 B7 211.0 (M + Η) V. Description of the invention (160) 1- (2 -Methylphenyl) -3_ (4 -exo I: tetrayl) -3-propan-1-one: MS (m / z): 223.8 (M + Η) +; C15H13NO requires 値 223.3. 1- (2,4-dimethylphenyl) -3- (4-p than ydoyl) -2 · propan-1-one: MS (m / z): 238.0 (M + H) +; C16H15NO Requires 値 237.3. 1- (2-methoxyfluorenyl) _3- (4 · ρ than Yodoyl) -2-propionyl-1-fluorene with 240.0 (Μ + Η); C15H13NO2 requires 値 239.3. 1 · (4-Chlorophenyl) -3- (4-ρ than yodoyl) _2-propyl- 1- 酉 酉 Same as 244 · 0 (Μ + Η) +; C14H1 () C1N0 requires 値 243.7. 1- (4-chlorophenyl) -3- (4 • edynyl) -2-propanyl-1-fluorene is the same as 235 · 1 (Μ + Η) +; C15H1 () N20 requires 値 234.3. Nynyl) -3- (4-p than Yodoyl) -2-propan-1-one is the same as 260.0 (M + H) +; C18H13NO requires 259.3. 1,3 -Wu- (4-p than Yodo-based) -2 -propene '· 1- 酉 Same as: MS (m / z):; C13H1GN20 requires 値 210.2. 3- (4-pyridyl) -1- (2-thienyl) · 2-propen-1-one 216.0 (M + Η) +; C12H9NOS requires 値 215.3. 1_ (2-furyl) -3 · (4-pyridyl) -2-propan-1-one 200 · 0 (Μ + Η) +; C12H9N02 requires 値 199.2. 1-cyclohexyl-3- (4-pyridyl) -2-propen-1-one was prepared in the same way using acetamidine cyclohexane: MS (m / z): 216 · 2 (Μ + Η) +; C "Hi7N0 requires 値 215.3 〇1-second butyl-3 _ (4_17 than yodoyl)-2-propyl -1- 嗣: 3,3-methyl 2 ketone (2.5 ml, 20.0 mmol) , 4 · pyridinecarboxaldehyde (2.15ml '22.3mmol), ethanol (7.6ml) and 4.5% sodium hydroxide aqueous solution (4.6% liter) -163 This paper size applies to China National Standard (CNS) A4 specifications (210X297 mm) --------- · install-(Please read the notes on the back before filling this page) Order printed by the Central Consumers Bureau of the Ministry of Economy Staff Consumer Cooperatives 520362 A7 B7 *-- ----------------- ---- ---- -1-------------____ V. Description of Invention (161) The mixture was maintained at room temperature for 12 hours. It was diluted with digas methane, dehydrated and evaporated with aqueous hydrochloric acid solution and water washing. Subsequently, column chromatography (Keinin-ethyl acetate = 3: 1) was used to obtain the title compound. MS (m / z): 190.4 (M + H) +; C12H15NO requires 値 189.3 〇 Step B · 6 · Substituted 3-phenyl-pyridyl) -2 (1Η) -ρ bilidene Preparation program: (Please read the notes on the back of this page and then fill in) i ·

、1T 〇, 1T 〇

經濟部中央標準局員工消費合作社印製 鈉（40毫克，1.74毫莫斗）溶解於苯基乙醯胺（880毫克， 6.51毫莫耳）及乙醇（5毫升）之攪拌中之混合物。若溶解度 許可，則1-取代3-(4-吡啶基）-2-丙烯-ΐ_酮（5.4毫莫耳）分成 數份呈乙醇系溶液（20毫升）加至回流苯基乙醯胺溶液，或 於室溫呈固體添加。混合物回流維持1 5小時然後任其到 達室溫。2Ν鹽酸添加至pH値5接著加入數毫升水。由此 混合物結晶出產物及過遽，隨後以乙醇，水，乙醇洗鲦及 由甲醇再結晶。若產物於添加鹽酸時未有反應混合物結晶 ’則蒸發去除混合物及其餘產物攝取於二氯甲燒。有機溶 液以水洗滌，脱水及蒸發。所得產物由熱丙酮結晶及由甲 醇再結晶。 下列化合物係根據此種程序使用實例12 a•所述2-(4-吡 __ -164- 本紙張尺度家標準（CNS ) A4規格（21GXY97公楚厂 一 520362 A7 B7 五、發明説明（162 啶基）·2•丙烯-1-酮衍生物製備：12-1 ϋ二苯基-4-(4-吡啶基‘啶酮 ^ MS(m/z): 325.4(M + H)+ ; C22H16N2〇d6) : d 8·63(ιη，2H，吡啶），7.86(m，2H)，7.58-7.45 ，7.29-7.08(2m)。Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs Sodium (40 mg, 1.74 mmol) dissolved in a stirred mixture of phenylacetamide (880 mg, 6.51 mmol) and ethanol (5 ml). If the solubility permits, divide 1-substituted 3- (4-pyridyl) -2-propene-fluorenone (5.4 mmol) into several ethanol-based solutions (20 ml) and add to the refluxing phenylacetamide solution. , Or added as a solid at room temperature. The mixture was maintained at reflux for 15 hours and then allowed to reach room temperature. 2N hydrochloric acid was added to pH 値 5 followed by a few milliliters of water. The product was crystallized from the mixture and filtered, and then washed with ethanol, water, ethanol and recrystallized from methanol. If the product does not crystallize when the reaction mixture is added with hydrochloric acid, the mixture is evaporated and the remaining product is taken up in dichloromethane. The organic solution was washed with water, dehydrated and evaporated. The resulting product was crystallized from hot acetone and recrystallized from methanol. The following compounds are used according to Example 12a of this procedure. The 2- (4-pyridine__ -164- described in this paper standard (CNS) A4 specifications (21GXY97 Gongchu Factory 520362 A7 B7) V. Description of the invention (162 Pyridyl) · 2 • propylene-1-one derivative preparation: 12-1 ϋDiphenyl-4- (4-pyridyl'pyridone) MS (m / z): 325.4 (M + H) +; C22H16N2 〇d6): d 8.63 (ιη, 2H, pyridine), 7.86 (m, 2H), 7.58-7.45, 7.29-7.08 (2m).

RJ σ 12-2 6-(4•甲基苯基）·3_苯基_4·(4-ρ比淀基）_2(lH)-g比淀酮： MS(m/z) : 339·2(Μ + Η)+ ; C23H18N20 要求値 338.4。111-NMR(DMSO-d6) : d 8.44(m，2H，吡啶），7.79(d，2H) ，7.32(d，2H)，7.26-7.01(m，7H，Ph，吡啶），6.67(bs 1H) (讀先閱讀背面之注意事項再填寫本頁)RJ σ 12-2 6- (4 • methylphenyl) · 3_phenyl_4 · (4-ρ biryl) _2 (lH) -g birylone: MS (m / z): 339 · 2 (Μ + Η) +; C23H18N20 requires 値 338.4. 111-NMR (DMSO-d6): d 8.44 (m, 2H, pyridine), 7.79 (d, 2H), 7.32 (d, 2H), 7.26-7.01 ( m, 7H, Ph, pyridine), 6.67 (bs 1H) (Read the precautions on the back before filling this page)

RJ 經濟部中央標準局員工消費合作社印製 12-3 6_(4_乙基豕基） 3 _本基-4編（4口比淀基）-2( 1H) -口比淀酉同： MS(m/z): 353·0(Μ + Η)+ ; C24H2〇N20 要求値];】、。1!!-NMR(DMSO-d6) : d 8.42(m，2H，吡啶），7.79(d，2H) ，7.33(d，2H)，7·24-7·06(ιη，7H，Ph，吡啶），6.65(bs ，1H，CH二），2.66(q，2H，CH2)，1.21(t，3H，CH3)。Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs of the People's Republic of China 12-3 6_ (4_ethylfluorenyl) 3_Benji-4 (4 ports than Yodo base) -2 (1H) (m / z): 353.0 (M + Η) +; C24H2ON20 requires 値];]. 1 !!-NMR (DMSO-d6): d 8.42 (m, 2H, pyridine), 7.79 (d, 2H), 7.33 (d, 2H), 7.24-7 · 06 (ιη, 7H, Ph, pyridine ), 6.65 (bs, 1H, CH 2), 2.66 (q, 2H, CH2), 1.21 (t, 3H, CH3).

RJRJ

A 165- 本紙張尺度適用中國國家標準（CNS ) A4規格（21 OX 297公釐） 520362 A7 B7 經濟部中央標準局員工消費合作社印製 五、發明説明（163) 12-4 6-(4-異丙基苯基）-3-苯基-4-(4-吡啶基）-2(1Η)-吡啶酮 J_MS(m/z) ： 367.0(M + H)+ ; C25H22N2y〇 要求値 366·5。 iH-NMR^DMSO-dd: d8.45(m，2Η，吡啶），7.82(d，2Η) ，7.39(d，2H)，7.28-7.10(m，7H，Ph，吡啶），6.67(bs ，1H，CH二），2.98(m，1H，CH(CH3)2)，1,27，1.25(2s ，各個 3H，2 CH3)。A 165- This paper size applies to Chinese National Standards (CNS) A4 specifications (21 OX 297 mm) 520362 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (163) 12-4 6- (4- Isopropylphenyl) -3-phenyl-4- (4-pyridyl) -2 (1Η) -pyridone J_MS (m / z): 367.0 (M + H) +; C25H22N2y〇 requires 366.6 . iH-NMR ^ DMSO-dd: d8.45 (m, 2Η, pyridine), 7.82 (d, 2Η), 7.39 (d, 2H), 7.28-7.10 (m, 7H, Ph, pyridine), 6.67 (bs, 1H, CH2), 2.98 (m, 1H, CH (CH3) 2), 1,27, 1.25 (2s, each 3H, 2 CH3).

RJRJ

12-5 ό-(2-甲基豕基） 3 _表基_4 (4-口比淀基）·2( 1H) -口比淀西同： MS(m/z) : 339.2(M + H)+; C23H18N20 要求値 338.4。4-NMR(DMSO-d6) : d 8.40(m，2H，外匕淀），7.45-7.09(m， 11Η，Ph，峨淀），6.21(bs，1Η，CH = )，2.39(s，3Η， CH3) 〇12-5 ό- (2-methylfluorenyl) 3 _ Table group_4 (4-Hydroxyl) · 2 (1H) -Hydroxyl: Same as MS (m / z): 339.2 (M + H) +; C23H18N20 requires 値 338.4. 4-NMR (DMSO-d6): d 8.40 (m, 2H, outer Diandian), 7.45-7.09 (m, 11Η, Ph, Edian), 6.21 (bs, 1Η, CH =), 2.39 (s, 3Η, CH3).

RJRJ

CC 12-6 6-(2,4-二甲基苯基）-3 _苯基_4_(4- 口比淀基、一2( 1H)·口比淀 酮：MS(m/z) : 353·0(Μ + Η)+ ; C24H2〇N20 要求値 352.4。 iH-NMR^DMSO-ds): d8.42(m，2H，吡啶），7.29(d，1H) ，7.23-7.06(m，9H，Ph，外匕淀），6.17(bs，1H，CH = ) ，2.34，2.31(2s，各個 3H，2 CH3)。 -166- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） (請先閱讀背面之注意事項再填寫本頁) 520362 A7 B7 五、發明説明（164 ) R1 12-7 6-(2-甲氧苯基V3-苯基-4-(4-吡啶基）_2ΠΗ)-吡啶酮： MS(m/z): 355.0(M + H)+; C23H18N202 要求値 354.4。111- NMR(DMSO-d6) : d 8.41(m，2H，吡啶），7.49(bd，1H) ，7.44(m，1H)，7.24-7.06(m，8H，Ph，吡啶），7.02(dt ，1H)，6.32(bs，1H，CH = )，3,82(s，3H，CH3)。CC 12-6 6- (2,4-Dimethylphenyl) -3 _phenyl_4_ (4-Methylpyridyl, 1 2 (1H) · Methylpyridone: MS (m / z): 353.0 (M + Η) +; C24H2ON20 requires 値 352.4. IH-NMR ^ DMSO-ds): d8.42 (m, 2H, pyridine), 7.29 (d, 1H), 7.23-7.06 (m, 9H, Ph, outer diameter), 6.17 (bs, 1H, CH =), 2.34, 2.31 (2s, each 3H, 2 CH3). -166- This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read the notes on the back before filling this page) 520362 A7 B7 V. Description of the invention (164) R1 12-7 6- ( 2-methoxyphenyl V3-phenyl-4- (4-pyridyl) _2ΠΗ) -pyridone: MS (m / z): 355.0 (M + H) +; C23H18N202 requires 値 354.4. 111- NMR (DMSO -d6): d 8.41 (m, 2H, pyridine), 7.49 (bd, 1H), 7.44 (m, 1H), 7.24-7.06 (m, 8H, Ph, pyridine), 7.02 (dt, 1H), 6.32 ( bs, 1H, CH =), 3,82 (s, 3H, CH3).

RJ 12-8 6-(4-氯苯基V3-苯基-4-(4-峨啶基）-2(lH)-吡啶酮： MS(m/z) : 359.2(M+H)+ ; C22H15C1N20 要求値 358.8 。 iH-NMRXDMSO-dd : d 8·42(πι，2H，吡啶），7.93(bd， 2H)，7.54(m，2H)，7.26-7.08(m，7H，Ph，吡啶）， 6.80(bs， 1H，CH = )。RJ 12-8 6- (4-chlorophenylV3-phenyl-4- (4-eridinyl) -2 (lH) -pyridone: MS (m / z): 359.2 (M + H) +; C22H15C1N20 requires 値 358.8. IH-NMRXDMSO-dd: d 8.42 (π, 2H, pyridine), 7.93 (bd, 2H), 7.54 (m, 2H), 7.26-7.08 (m, 7H, Ph, pyridine), 6.80 (bs, 1H, CH =).

RJ 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁)Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs of RJ (Please read the precautions on the back before filling this page)

Cl 12-9 6-(4•氰基苯基）-3-苯基-4-(4·吡啶基）_2(1H)_吡啶酮·· MS(m/z): 350·2(Μ + Η)+; C23H15N30 要求値 349.4。111- NMR(DMSO-d6) : d 8.45(m，2H，吡啶），8.16(bd，2H) ，7.98(d，2H)，7.32-7.00(m，8H，Ph，吡啶，CH=)。 167· 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 165 五、發明説明（ R]Cl 12-9 6- (4 • cyanophenyl) -3-phenyl-4- (4 · pyridyl) _2 (1H) _pyridone · MS (m / z): 350 · 2 (Μ + Η) +; C23H15N30 requires 値 349.4. 111-NMR (DMSO-d6): d 8.45 (m, 2H, pyridine), 8.16 (bd, 2H), 7.98 (d, 2H), 7.32-7.00 (m, 8H, Ph, pyridine, CH =). 167 · The size of this paper is applicable to Chinese National Standard (CNS) A4 (210X297 mm) 520362 A7 B7 165 V. Description of the invention (R)

NC α 12-10 6-(a-各基）·3·苯基_4_(4· 口比淀基)_2( 1 ff) 口比淀酉同： MS(m/z) : 375.0(M+H)+ ; C26H18N20 要求値 374.5。4 NMR(DMSO-d6) : d 8.38(m，2H，p比淀），8·06-7·98(ιη， 3Η)，7.67(dd，1H)，7.62_7.54(m，3H)，7.25-7· 1 l(m， 7H，Ph，吡啶），6.38(bs，1H，CH二）。 R1NC α 12-10 6- (a- each group) · 3 · phenyl_4_ (4 · mouth ratio lake base) _2 (1 ff) mouth ratio lake: MS (m / z): 375.0 (M + H) +; C26H18N20 requires 値 374.5. 4 NMR (DMSO-d6): d 8.38 (m, 2H, p ratio), 8.06-7 · 98 (ιη, 3Η), 7.67 (dd, 1H), 7.62 -7.54 (m, 3H), 7.25-7 · 1 l (m, 7H, Ph, pyridine), 6.38 (bs, 1H, CH di). R1

(請先閱讀背面之注意事項再填寫本頁)(Please read the notes on the back before filling this page)

經濟部中央標準局員工消費合作社印製 12-11 3 -苯基 _4,6_^-(4-p比淀基）_2(1H)_峨淀嗣：M S f m/z) :326·0(Μ + Η)+ ; C21H15N30 要求値 325.4 。 4- NMR(DMSO-d6) : d 8·69，8.43(2m，各個 2H，吨淀）， 7.92(bs，2H)，7.28-7.05(m，8H) °Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs of the People's Republic of China 12-11 3 -Phenyl_4,6 _ ^-(4-p 比基基) _2 (1H) _Edian 嗣: MS fm / z): 326 · 0 ( Μ + Η) +; C21H15N30 requires 値 325.4. 4- NMR (DMSO-d6): d 8.69, 8.43 (2m, each 2H, ton), 7.92 (bs, 2H), 7.28-7.05 (m, 8H) °

RJRJ

NN

12-12 3 -冬基-4-(4- π比淀基）-6 (2- p塞吩基）·2( 1H)_ p比淀嗣： MS(m/z): 331.0(M+H)+; C2〇H14N2OS 要求値 330.4。4· NMR(DMSO-d6) : d8.44(m，2H，吡啶），7.90，7.70(2bd ，各個 1H)，7.28-7.08(m，9H)。12-12 3 -dongyl-4- (4- π ratio ydenyl) -6 (2- p sephenyl) · 2 (1H) _ p ratio ytterbium: MS (m / z): 331.0 (M + H) +; C20H14N2OS requires 値 330.4. NMR (DMSO-d6): d8.44 (m, 2H, pyridine), 7.90, 7.70 (2bd, each 1H), 7.28-7.08 (m, 9H).

RJ 168- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（166 ) 12-13 6-(2•咬喃基）-3 -苯基-4-(4-p比淀基）·2(1Η)-ρ比淀酬： MS(m/z): 315·0(Μ + Η)+; C2〇H14N202 要求値]^々。1!!· NMR(DMSO-d6) : d 8.44(m，2H，吡啶），7.90(s，1H) ，7.43(bs，1H)，7.27-7.08(m，7H，Ph，峨淀），6·7 l(m ，2H)。 R1RJ 168- This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) 520362 A7 B7 V. Description of the invention (166) 12-13 6- (2 • Branyl) -3 -phenyl-4- (4-p ratio): 2 (1Η) -ρ ratio: MS (m / z): 315.0 (M + Η) +; C2H14N202 requires 値] ^ 々. 1 !! · NMR (DMSO-d6): d 8.44 (m, 2H, pyridine), 7.90 (s, 1H), 7.43 (bs, 1H), 7.27-7.08 (m, 7H, Ph, Edo), 6 7 l (m, 2H). R1

12-14 6_壤己基_3表基-4-(4_ p比淀基）-2( 1H)_ 口比淀酉同 ： MS(m/z): 331.2(M + H)+; C22H22N20 要求値 330.4。111· NMR(DMSO-d6): d8.40(m，2H，吡啶），7.22-7.13， 7.10-7.03(2m，7H，Ph，p 比淀），6.04(bs，1H，CH = ) ，1.95-1.15(m，11H，環己烷）。12-14 6_lohexyl_3epi-4- (4_ p ratio Yodo base) -2 (1H) _ mouth ratio Yodo: MS (m / z): 331.2 (M + H) +; C22H22N20 requirements値 330.4.111 · NMR (DMSO-d6): d8.40 (m, 2H, pyridine), 7.22-7.13, 7.10-7.03 (2m, 7H, Ph, p ratio), 6.04 (bs, 1H, CH = ), 1.95-1.15 (m, 11H, cyclohexane).

RJ σ (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 12-15 ό弟二丁基-3 + 基 4-(4_ p比淀基）-2( 1H、· 口比淀 S同： MS(m/z): 305·0(Μ + Η)+; C2〇H2〇N20 要求値川彳义。1!!-NMR(DMSO-d6) : d 8.39(m，2H，峨淀），7·20·7·12， 7.10-7.02(2m，7Η，Ph，ρ比淀），6‘02(bs，1Η，CH = ) ，1.31(s，9H，3 CH3) 〇 Ri = (CH3)3C· 實例13 (S)-l，2·芊基伸乙基二胺之製備程序 169- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 --〜—一- _____ 五、發明説明（167)RJ σ (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 12-15 Dibutyl-3 + radical 4- (4_ p than Yodo) -2 (1H The same is true for Mouth and S: MS (m / z): 305.0 (M + Η) +; C2OH2〇N20 requires 値 川 彳 义. 1 !!-NMR (DMSO-d6): d 8.39 ( m, 2H, Edian), 7.20 · 7 · 12, 7.10-7.02 (2m, 7Η, Ph, ρ Biyodo), 6'02 (bs, 1Η, CH =), 1.31 (s, 9H, 3 CH3) 〇Ri = (CH3) 3C. Example 13 (S) -1,2, fluorenyl ethylene diamine preparation procedure 169- This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A7 B7-~ — 一-_____ V. Description of the Invention (167)

1,2-字基伸乙基二胺· 一胺係根據參考文獻（H. Brunner ’ P. Hankofer, U. Holzinger, B. Treittinger and H. Schoenenberger, Eur· J. Med. Chem. 25，35_44，（1990)) 經由以鋁氫化鋰還原L_苯基丙胺酸醯胺製備。（R)_對映異 構物係以相同方式由D-苯基丙胺酸醯胺製備。 實例14 2-(((S)_2 -乙醯胺基·3 -苯基丙基）-胺基）-5-(4_氟苯基）-3 -甲 基比淀基）-4(3Η)-_^_之概略製備程序 ·1-- (請先閱讀背面之注意事項再填寫本頁)1,2-Word-based ethylenediamine · monoamine is based on references (H. Brunner 'P. Hankofer, U. Holzinger, B. Treittinger and H. Schoenenberger, Eur · J. Med. Chem. 25, 35_44, (1990)) Prepared via reduction of L-phenylalanine amidine with lithium aluminide. The (R) -enantiomer is prepared from D-phenylalanine amidine in the same manner. Example 14 2-(((S) _2-Ethylamino · 3-phenylpropyl) -amino) -5- (4-fluorophenyl) -3 -methylpyridyl) -4 (3Η ) -_ ^ _ 's outline preparation procedure · 1-- (Please read the precautions on the back before filling this page)

，1Τ 2-(((S)-2-乙醯胺基-3-苯基丙基胺某装基）_3_甲 基-6-(4·吡啶基）-4(3H)_嘧啶酮： 2-(((S)-2-胺基-3-苯基丙基）-胺基）-5-(4-氟苯基）-3-甲基-6· (4·^比淀基）_4(3H)_嘴淀晒1(25毫克，〇.〇58毫莫斗）及乙肝 (200毫升）於甲醇（2毫升）之溶液於室溫維持1小時。蒸發 接著於矽膠柱層析所得產物（10 %甲醇/二氯甲烷）獲得標 題化合物。MS(m/z): 472·3(Μ + Η)+; C27H26FN5〇2 要求値 471.5 〇 -170- 本紙張尺度適用中國國家標準（CNS ) Α4規格(2K)X;97公釐） 1· 經濟部中央標準局員工消費合作社印製 520362 經濟部中央標準局員工消費合作社印f Α7 Β7 五、發明説明（168) 實例15 5-(4·氟苯基）-2-(((S)-2-N-異丙基胺基-3-苯基丙基）_胺基）· 3 -甲基- 6- (4-p比淀基）-4(3H)-p密淀S同鹽酸鹽之製備程序, 1T 2-(((S) -2-Ethylamino-3-phenylpropylamine) _3_methyl-6- (4 · pyridyl) -4 (3H) _pyrimidone: 2-(((S) -2-Amino-3-phenylpropyl) -amino) -5- (4-fluorophenyl) -3-methyl-6 · (4 · ^ pyridyl) _4 (3H) _ Zuidian 1 (25 mg, 0.058 mmol) and a solution of hepatitis B (200 ml) in methanol (2 ml) were maintained at room temperature for 1 hour. Evaporation was followed by silica gel column chromatography. The product (10% methanol / dichloromethane) was used to obtain the title compound. MS (m / z): 472 · 3 (Μ + Η) +; C27H26FN502 Requirement 値 471.5 〇-170- This paper size applies to Chinese national standards (CNS ) Α4 size (2K) X; 97mm) 1. Printed by the Consumers 'Cooperative of the Central Standards Bureau of the Ministry of Economics 520362 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economics f Α7 Β7 V. Description of the invention (168) Example 15 5- (4 · Fluorophenyl) -2-(((S) -2-N-isopropylamino-3-phenylpropyl) _amino) · 3-methyl-6- (4-p ratio ) -4 (3H) -p dense lake S with the preparation process of hydrochloride

5-(4-氟苯基）-2-(((SV2-N-異丙基胺基苯基丙基胺基）-g_•甲基-6-(4-吡啶基）·4(3Η)_嘧淀酮鹽酸鹽：三乙醯氧硼氫 化鈉（23毫克，0.109毫莫耳）加至2-(((S)-2-胺基-3-苯基丙 基）-胺基）-5-(4-鼠苯基）_3 -甲基- 6- (4 -p比淀基）-4(311)-。密淀 酮鹽酸鹽（50毫克，0.107毫莫耳），三乙基胺（15毫升， 0.108毫莫耳）及丙酮（7·9毫升，0.108毫莫耳）於1，2-二氯 乙烷（0·8亳升）之攪拌混合物。4小時後，藉加入飽和碳酸 氫鈉水液淬熄反應，接著於二氯甲烷萃取，脱水有機溶液 及蒸發。於矽膠柱層析（10 %甲醇/氯仿）獲得標題化合物呈 自由態鹼，其藉加入4Ν鹽酸/二崎烷（21微升，〇.〇8毫莫耳 )至其甲醇係溶液（1毫升）及隨後蒸發轉成一鹽酸鹽。 MS(m/z) : 472.1(M + H)+ ; C28H30FN5O 要求値 471 ·6(自由 態）。 實例16 5-(4_氟豕基）-2-(((S)-2-N-環己基胺基·3 -苯基丙基）-胺基）- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） ^^衣------1T------ (請先閱讀背面之注意事項再填寫本頁) -171- _ 520362 A7 B7 五 '發明説明（169) 3-甲基-6-(4-吡啶基）-4(3 H)-嘧啶酮鹽酸鹽之製備程序5- (4-fluorophenyl) -2-(((SV2-N-isopropylaminophenylphenylamino) -g_ • methyl-6- (4-pyridyl) · 4 (3Η) _ Pyrimidolone hydrochloride: sodium triacetoxyborohydride (23 mg, 0.109 mmol) added to 2-(((S) -2-amino-3-phenylpropyl) -amine) -5- (4-murylphenyl) _3-methyl-6- (4-p-pyridyl) -4 (311)-. Myronone hydrochloride (50 mg, 0.107 mmol), triethyl Stir the mixture of methylamine (15 ml, 0.108 mmol) and acetone (7.9 ml, 0.108 mmol) in 1,2-dichloroethane (0.8 mL). After 4 hours, add by borrowing The reaction was quenched with saturated aqueous sodium hydrogen carbonate solution, followed by extraction in dichloromethane, dehydration of the organic solution and evaporation. The title compound was obtained as a free base by silica gel column chromatography (10% methanol / chloroform), which was added by adding 4N hydrochloric acid / dichloromethane. Zane (21 μl, 0.08 mmol) to its methanolic solution (1 mL) and subsequent evaporation to convert to a hydrochloride salt. MS (m / z): 472.1 (M + H) +; C28H30FN5O値 471 · 6 (free state) is required. Example 16 5- (4-fluorofluorenyl) -2-((((S) -2-N-cyclohexylamino · 3-phenylpropyl) -amino)) -Paper ruler Applicable to China National Standard (CNS) Α4 specifications (210X297 mm) ^^ clothing ------ 1T ------ (Please read the precautions on the back before filling this page) -171- _ 520362 A7 B7 Five 'invention description (169) 3-methyl-6- (4-pyridyl) -4 (3 H) -pyrimidinone hydrochloride preparation procedure

經濟部中央標準局員工消費合作社印製 h甲基·6·(4-吡啶基V4(3HV嘧啶酮鹽酸鹽：使用環已酮， 5-(4-氟苯基）-2-(((S)-2-N·環己基胺基-3-苯基丙基）-胺基）-3_甲基-6-(4-吡啶基）_4(3H)·吡啶酮以5-(4·氟苯基）_2· (((S)-2-N -異丙基胺基-3-苯基丙基）-胺基）-3-甲基-6-(4-p比 淀基）-4(3H)·喊淀酮之相同方式製備·· MS(m/z)5 11.6 (M) + ;C31H34FN50 要求値 511.6(自由態）。 實例17 2_(((S)-2-N-正丁基胺基-3_苯基丙基）_胺基）·5-(4-氟苯基）-3-甲基-6-(4-吡啶基）-4(3 H)_嘧啶酮鹽酸鹽之製備程序Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs of the People's Republic of China. Methyl · ················· S) -2-N · Cyclohexylamino-3-phenylpropyl) -amino) -3-methyl-6- (4-pyridyl) _4 (3H) · pyridone with 5- (4 · Fluorophenyl) _2 · (((S) -2-N -isopropylamino-3-phenylpropyl) -amino) -3-methyl-6- (4-p ratio) 4 (3H) · Same as the preparation of MSD ·· MS (m / z) 5 11.6 (M) +; C31H34FN50 requires 値 511.6 (free state). Example 17 2 _ (((S) -2-N-positive Butylamino-3_phenylpropyl) _amino) · 5- (4-fluorophenyl) -3-methyl-6- (4-pyridyl) -4 (3H) _pyrimidinone salt Procedure

172- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、 發明説明（17Ό ) ^zlL(S)-2-N-_^ 丁基胺基·3-苯基丙某V胺基 基-6-(4_吡啶基V4(3H)-嘧啶酮鹽酸―鹽：三乙醯氧硼氫 化鈉（28毫克，0.13毫莫耳）添加至2-(/(S)-2·胺基_3_苯基 兩基）-胺基）-5-(4-氟苯基）-3•甲基·6·(4-吡啶基）-4(3H)〇密 淀酮（41毫克，0.〇95毫莫耳）及丁醛（8.5毫升，〇.〇94亳莫 耳）於1，2-二氯乙烷（0·8毫升）之攪摔混合物。2小時後，反 應藉加入飽和碳酸氫鈉水液淬熄接著以二氯甲烷萃取，脱 水有機溶液及蒸發。於矽膠柱層析（5 %甲醇/氯仿）獲得標 題化合物呈自由態鹼，其藉加入4Ν鹽酸/二唠烷（12微升， 0.048毫莫耳）至其甲醇系溶液（1毫升）及隨後蒸發轉成一鹽 酸鹽。MS(m/Z) : 486·2(Μ+Η)+ ; C29H32FN5〇 要求値 485.6(自由態鹼）。 實例1 8 (S)-2-N，N-二甲基胺基-3-苯基丙基胺之製備程序 •批衣-- (請先聞讀背面之注意事項再填寫本頁) -訂172- This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) 520362 A7 B7 V. Description of the invention (17Ό) ^ zlL (S) -2-N -_ ^ Butylamino · 3-phenyl Propionylamino-6- (4-pyridyl V4 (3H) -pyrimidone hydrochloride-salt: sodium triacetoxyborohydride (28 mg, 0.13 mmol) added to 2-(/ (S) -2 · amino_3-phenyldiyl) -amino) -5- (4-fluorophenyl) -3 · methyl · 6 · (4-pyridyl) -4 (3H) (41 mg, 0.095 mmol) and a mixture of butyraldehyde (8.5 ml, 0.094 mmol) in 1,2-dichloroethane (0.8 ml). After 2 hours, the reaction was quenched by the addition of saturated aqueous sodium bicarbonate and then extracted with dichloromethane. The organic solution was dehydrated and evaporated. Chromatography on a silica gel column (5% methanol / chloroform) gave the title compound as a free base by adding 4N hydrochloric acid / dioxane (12 μl, 0.048 mmol) to its methanol solution (1 mL) and subsequently Evaporation turned into a hydrochloride. MS (m / Z): 486 · 2 (M + Η) +; C29H32FN50 requires 値 485.6 (free state base). Example 1 8 (S) -2-N, N-dimethylamino-3-phenylpropylamine preparation procedure • Batch coating-(Please read the precautions on the back before filling this page)-Order

經濟部中央標準局員工消費合作社印製 (SV2-N.N- /\ /\ 胺基-2-苯基丙基胺=三乙醯氧氫化鈉 (13.0克，61.3毫莫耳）添加至苯基丙胺酸醯胺（36克， 21.9晕莫耳）及37 %甲酸溶液（4·4毫升，58.7毫莫耳）於 1，2 - —氣乙( 7 7毫升）之擾摔中之混合物。攪摔2小時後， 反應藉加入飽和碳酸氫鈉水液淬熄。然後加入氫氧化钾丸 粒接著以二氯甲燒萃取，脱水有機溶液及蒸發。所得（s)_ 173- 本紙張尺度適用中國國家標準（CMS ) A4規格（210X 297公釐） I# 經濟部中央榡準局員工消費合作社印製 固 步 520362 A7 ________ B7 五、發明説明（171 ) 2-]Si，N -二甲基胺基-3-苯基丙基酿胺以叙氯化鐘根據參考文 獻（H· Brunner，P. Hankofer，U. HolzingeV，B. Treittinger and H. Schoenenberger，Eur. J· Med· Chem. 25，35-44 > (1990)) 還原獲得標題化合物。 實例19 2-(((S)-2-N，N-二甲基胺基-3-苯基丙基）·胺基）_5_(4_氟苯基 -3-甲基-6-(4-吡啶基）-4(3 H)-嘧啶酮鹽酸鹽之製備程序Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (SV2-NN- / \ / \ Amino-2-phenylpropylamine = triethylammonium hydride (13.0 g, 61.3 mmol) added to phenylpropylamine Mixture of ammonium acid (36 g, 21.9 mol) and 37% formic acid solution (4.4 ml, 58.7 mmol) in 1,2-acetone (77 ml). Stir After 2 hours, the reaction was quenched by the addition of saturated aqueous sodium bicarbonate solution. Then potassium hydroxide pellets were added, followed by extraction with dichloromethane, dehydration of the organic solution and evaporation. The resulting (s) _ 173- This paper is for China Standard (CMS) A4 specification (210X 297 mm) I # Printed by the Consumers' Cooperative of the Central Government Bureau of the Ministry of Economic Affairs 520362 A7 ________ B7 V. Description of the invention (171) 2-] Si, N-dimethylamino group According to the reference (H. Brunner, P. Hankofer, U. HolzingeV, B. Treittinger and H. Schoenenberger, Eur. J. Med. Chem. 25, 35- 44 > (1990)) reduction to obtain the title compound. Example 19 2-(((S) -2-N, N-dimethylamino-3-phenylpropyl) · amino) _5_ (4_fluoro -3-methyl-6- (4-pyridyl) -4 (3 H) - pyrimidinone hydrochloride The procedure

步驟A. 5 - ( 4 •氣苯基）-3 -甲基-2 -甲基崎6盛基-6 - (4 - p比淀基1·ϋ· 全（3HV嘧啶酮：5-(4-氟苯基）-3-甲基-2-甲基硫-6-(4-吡症 基）_4(3H)_嘧啶酮（400毫克，1·22毫莫耳）及奥松（〇x〇neR)( 過氧一硫酸鉀，2.3克，3.74毫莫耳）於甲醇（100毫升）及 水（45毫升）之混合物攪拌13小時。溶劑濃縮至约50毫升 ，接著以二氣甲烷萃取，脱水有機溶液及蒸發。所得白色 體未經純化即用於次一步驟。 驟B. 2-(((S)_2-M N-二甲基胺基-3_苯基丙基胺基上红 -174 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 0装------1Τ------ (請先聞讀背面之注意事項再填寫本頁) 520362 Α7 Β7 經濟部中央標準局員工消費合作社印製 五、發明説明（172) 氣苯基·3·甲基-6·(4-吡啶基）-4(3HV嘧啶酮鹽酸鹽：粗製 5-(4-氟苯基）-3 -甲基-2 -甲基橫醯基- 6-(4-^淀基）-4(3 H)-嘧 咬酮（430毫克，1.19毫莫耳）&(S)-2_N，N_二甲基胺基_3_ 苯基丙基胺（600微升，約3.4毫莫耳）之混合物於室溫攪拌 1小時然後於50 °C簡短溫熱。於矽膠柱式層析（3乃％甲醇/ 氯仿）獲得標題化合物呈自由態驗，其藉添加4N鹽酸/二口号 烷（160微升，0.64毫莫耳）至其甲醇系溶液（4毫升）及隨後 蒸發轉成一鹽酸鹽。MS(m/z) : 458.0(M + H)+ ; C27H28FN50要求値457.5(自由態鹼）。 實例20 5-(4-氟苯基）-6-(4-(2-乙醯胺基）-吡啶基）-2-硫烷基-4(3H)- 喊淀酮 童^. Α. 2·(4_氟苯基）_3_氧基_3·(4_(2·乙醯胺基吡啶基 丙酸乙酯： 2-氯異菸鹼酸（25·〇克，0.16莫耳）於65毫升濃氫氧化銨溶 液於剛密閉室内加熱至205 °C歷72小時。冷卻至23。<：後， 溶液使用6N鹽酸酸化至pH 1及隨後過濾去除未反應之起 始物料。溶液眞空濃縮至原先容積之四分之一（約2〇〇亳升 )，及小心使用IN NaOH調整至pH 6。混濁溶液於〇 °C儲 存20小時後，過濾出所需2_胺基異菸鹼酸。2_胺基異菸鹼 於乙醇（600¾升）之懸浮液内加入47.1¾升4N無水鹽酸 於二嘮烷。溫熱至達到回流歷20小時，又加入47· 1亳升 4N無水鹽酸於二呤烷及反應又回流溫熱20小時。於罩斗 内於氮流濃縮接著進一步眞空濃縮，剩餘固體以飽和碳酸 本紙張尺度適用中國國家標準（CNS ) A4規格（21〇χ297公襲） (請先閱讀背面之注意事項再填寫本頁} >裝_ -訂 · 520362 Α7 Β7 五、發明说明（173) 氫鹽（200耄升）稀釋，以乙酸乙酯（2 X 200毫升）萃取，脱 水（硫酸鈉）。眞空濃縮後，獲得所需2_胺基異菸鹼酸乙醋 。於0 °C於氬氣氛下於2-胺基異菸鹼酸乙酯於吡啶（45毫升 )之溶液内以5分鐘時間逐滴加入乙醯氯。於〇 Ό經2小時 後，反應倒至冰300克上，以乙酸乙酯（2 X 300毫升）萃取 ，以水（2 X 100毫升）洗綠’接著以鹽水（2 X 1 毫升）洗(條 及脱水（硫酸鈉）。眞空濃縮後，殘餘物藉急速層析純化（梯 度乙酸乙醋：己燒1 : 4然後乙酸乙酿：己貌1 : 1)獲得2 _ 乙醯胺基異菸鹼酸乙酯。 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁} 於二異丙基胺（14.15毫升，101毫莫耳）及THF (40毫升） 於-7 8 °C之溶液内以5分鐘時間逐滴加入正丁鐘（3 8 · 1毫升 ，95毫莫耳）。10分鐘後，加入4-氟苯基乙酸乙酯（17.3 克，95毫莫耳）於40毫升無水THF。1〇分鐘後，加入2-乙醯胺基異菸鹼酸乙酯（6.0克，29亳莫耳）於20毫升無水 THF。任反應溫熱至23 °C隔夜，然後一次加入乙酸（95毫 莫耳）。反應經眞空濃縮然後重覆分配於飽和碳酸氫鹽（200 毫升）及醚（300亳升），合併碳酸氫鹽層以1〇 %檸檬酸中和 及以乙酸乙酯（2 X 300毫升）萃取。有機層經脱水（硫酸鈉） ，眞空濃縮獲得2-(4·氟苯基）-3·氧基-3-(4-(2-乙醯胺基）-ρ比淀基）-丙酸乙@旨。 步骤Β. 5-(4·氟苯基）·6-(4-(2-乙醯胺基）吡啶基）-2-硫尿嘧 啶： 2-(4-氟苯基）-3-氧基-3-(4-(2-乙醯胺基）吡啶基）-丙酸乙酯 (1·3克，3.78毫莫耳）及硫脲（863毫克，11.3毫莫耳）懸浮 ____-176- ____ 本&張尺度適5中國標準（CNS ) Α4規格（210X297公釐） ' 520362 A7 ———-------____ 五、發明説明（174) 於無水對二甲苯（15毫升）摔以極爲有效擾掉。混合物内加 入對甲苯磺酸吡啶鑕（38毫克）及使用τ史塔克裝置回流 12_ 16小時連續去，除水（〇·1亳升）。反應混合物經冷卻，使 用布克納漏斗過濾出暗褐色固體。收集之固體懸浮於丙酮 (25亳升）及過濾。丙酮洗滌後產物含微量硫脲，硫脲經由 與熱水（20-30毫升）研製去除。產物經過濾及風乾繼以與甲 苯共沸蒸餾。 實例2 1 (S)-2-N-乙基胺基-3-苯基丙基胺之製備程序 (請先閱讀背面之注意事項再填寫本頁) 〇Step A. 5-(4 • Phenylphenyl) -3 -methyl-2 -methylazine 6 Shengji-6-(4 -p than yodoyl 1. ··· (3HV pyrimidinone: 5- (4 -Fluorophenyl) -3-methyl-2-methylsulfan-6- (4-pyridino) _4 (3H) _pyrimidone (400 mg, 1.22 mol) and oxone (〇x 〇neR) (potassium peroxymonosulfate, 2.3 g, 3.74 mmol) was stirred in a mixture of methanol (100 ml) and water (45 ml) for 13 hours. The solvent was concentrated to about 50 ml, followed by extraction with methane gas. The organic solution was dehydrated and evaporated. The resulting white body was used in the next step without purification. Step B. 2-((((S) _2-M N-dimethylamino-3_phenylpropylamino) on red -174 This paper size applies to Chinese National Standard (CNS) A4 specification (210X 297 mm) 0 pack ------ 1T ------ (Please read the precautions on the back before filling this page) 520362 Α7 Β7 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (172) Gasoline · 3 · methyl-6 · (4-pyridyl) -4 (3HV pyrimidinone hydrochloride: crude 5- ( 4-fluorophenyl) -3 -methyl-2 -methylpyridinyl-6- (4- ^ ethyl) -4 (3 H) -pyrimidone (430 mg, 1.19 mmol) & a mp; (S) -2_N, N_dimethylamino_3_phenylpropylamine (600 microliters, about 3.4 millimoles) was stirred at room temperature for 1 hour and then briefly warmed at 50 ° C. The title compound was obtained in a silica gel column chromatography (3% methanol / chloroform) in a free form. The title compound was added by adding 4N hydrochloric acid / di-moxa (160 μl, 0.64 mmol) to its methanol solution (4 ml). And subsequent evaporation to convert to a hydrochloride salt. MS (m / z): 458.0 (M + H) +; C27H28FN50 requires 457.5 (free state base). Example 20 5- (4-fluorophenyl) -6- ( 4- (2-Ethylamido) -pyridyl) -2-sulfanyl-4 (3H) -xanthone ^. Α. 2 · (4_fluorophenyl) _3_oxy_3 · (4- (2. Acetaminopyridyl propionate ethyl ester: 2-chloroisonicotinic acid (25.0 g, 0.16 mol) in 65 ml of concentrated ammonium hydroxide solution and heated to 205 ° C in a freshly sealed room Over 72 hours. Cool to 23. <: After that, the solution was acidified with 6N hydrochloric acid to pH 1 and then filtered to remove unreacted starting materials. The solution was emptied and concentrated to a quarter of the original volume (about 200 liters) ), And carefully adjust the pH to 6 with IN NaOH. Store the turbid solution at 0 ° C for 20 hours. After that time, the desired 2-aminoisonicotinic acid was filtered. 2-Aminoisonicotine was added to a suspension of ethanol (600¾ liters) with 47.1¾ liters of 4N anhydrous hydrochloric acid in dioxane. Warm to reflux for 20 hours, add 47.1 liters of 4N anhydrous hydrochloric acid to the dipurinane, and allow the reaction to reflux for another 20 hours. Concentrated in the nitrogen stream in the hood and then further concentrated in the air. The remaining solids are saturated with carbonic acid. This paper applies the Chinese National Standard (CNS) A4 specification (21〇χ297 public attack). (Please read the precautions on the back before filling this page} > Packing _-Order · 520362 Α7 Β7 V. Description of the invention (173) Hydrogen salt (200 耄 L) diluted, extracted with ethyl acetate (2 X 200ml), dehydrated (sodium sulfate). After concentrating, obtain Ethyl 2-aminoisonicotinate is required. Acetyl chloride is added dropwise over 5 minutes in a solution of ethyl 2-aminoisonicotinate in pyridine (45 ml) at 0 ° C in an argon atmosphere. After 2 hours at 0 ° C, the reaction was poured onto 300 g of ice, extracted with ethyl acetate (2 X 300 mL), washed with water (2 X 100 mL) and then washed with brine (2 X 1 mL). (Strips and dehydrated (sodium sulfate). After condensing in the air, the residue was purified by flash chromatography (gradient ethyl acetate: hexane 1: 4 then ethyl acetate: hexane 1: 1)) to obtain 2 _ acetamidine Ethyl nicotinate. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the note on the back first) Fill out this page again} Add n-butyl bell (3 8 ·) to a solution of diisopropylamine (14.15 ml, 101 mmol) and THF (40 ml) at -78 ° C for 5 minutes. 1 ml, 95 mmol). After 10 minutes, 4-fluorophenylethyl acetate (17.3 g, 95 mmol) was added to 40 ml of anhydrous THF. After 10 minutes, 2-acetamidoisopropyl Ethyl nicotinate (6.0 g, 29 μmol) in 20 ml of anhydrous THF. The reaction was allowed to warm to 23 ° C overnight, and then acetic acid (95 mmol) was added in one portion. The reaction was concentrated in vacuo and then repeatedly partitioned between Saturated bicarbonate (200 mL) and ether (300 mL), combined bicarbonate layers were neutralized with 10% citric acid and extracted with ethyl acetate (2 X 300 mL). The organic layer was dehydrated (sodium sulfate) , And condensed to obtain 2- (4 · fluorophenyl) -3 · oxy-3- (4- (2-acetamido) -r-pyridyl) -ethyl propionate. Step B. 5- (4 · fluorophenyl) · 6- (4- (2-acetamido) pyridyl) -2-thiouracil: 2- (4-fluorophenyl) -3-oxy-3- (4 -(2-Ethylamino) pyridyl) -ethyl propionate (1.3 g, 3.78 mmol) and thiourea (863 Milligram, 11.3 millimolar) Suspension ____- 176- ____ This & Zhang scale is 5 Chinese Standard (CNS) A4 Specification (210X297 mm) '520362 A7 ———-------____ V. Invention Note (174) It is extremely effective to dissolve it in anhydrous p-xylene (15 ml). Add pyridinium p-toluenesulfonate (38 mg) to the mixture and use a τ Stark device to reflux for 12_16 hours, and remove the water ( 〇 · 1 亳 liter). The reaction mixture was cooled and a dark brown solid was filtered off using a Buckner funnel. The collected solid was suspended in acetone (25 ml) and filtered. After washing with acetone, the product contains a small amount of thiourea, which is removed by trituration with hot water (20-30 ml). The product was filtered and air-dried followed by azeotropic distillation with toluene. Example 2 1 (S) -2-N-ethylamino-3-phenylpropylamine preparation procedure (Please read the precautions on the back before filling this page) 〇

經濟部中央標準局員工消費合作社印製 (S)-2-N·乙基胺基-3-苯基丙基胺：乙奸（1.2毫升，12.7毫 莫耳）添加至L-苯基丙胺酸醯胺（1.0克，6.10毫莫耳）於甲 醇（25毫升）之攪拌溶液。於室溫經1.5小時後蒸發及繼以於 油泵眞空脱水。所得L-N -乙基苯基丙胺酸醯胺（6· 1毫莫耳） 於55°C以鋁氫化鋰（570毫克，15.0毫莫耳）於四氫嗅喃（65 微升）還原4小時。反應混合物倒入飽和碳酸氫鈉水液及以 二氯甲燒萃取’脱水及蒸發。於石夕膠柱式層析（氯仿：甲醇 :三乙胺=90 : 7 : 3)獲得胺呈黃色油。: 179.1(Μ + Η)+ ; (：ηΗ18Ν2 要求値 178.3。 -177- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） 520362 A7 一 ___ B7 五、發明説明（175 ) 實例22 2 ·胺基-2 -甲基-3 -表基丙基胺之製備程序 NH2 ，， U^-2-甲基-3-_萎基丙基胺二市售D，L_a-甲基苯基丙胺酸 甲酯（5.0克，25·7毫莫耳）於28%氫氧化銨水溶液（5〇毫升 )之溶液於室溫維持3日。所得D，L-a-甲基苯基丙胺酸醯胺 白色沉澱經過濾及脱水（2.5克）。此物料（2.〇克，11.22毫 莫耳）以鋁氫化鋰（1.3克，34.26毫莫耳）於沸四氫呋喃還原 24小時。反應藉加入硫酸鈉十水合物於冰浴溫度淬媳。過 濾出鹽，接著蒸發留下標題化合物呈油。MS(m/z): 165· 1(M + H)+ ; C1()H16N2要求値164.2。替代製法報告於μ. Freiberger and R· B. Hasbrouck，J. Am· Chem. Soc. 82， 696-698(1960)。 實例23 2-甲基-3-苯基丙基胺之製備程序 nh2(S) -2-N · Ethylamino-3-phenylpropylamine printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs: Ethane (1.2 ml, 12.7 mmol) added to L-phenylalanine A stirred solution of amidine (1.0 g, 6.10 mmol) in methanol (25 ml). After 1.5 hours at room temperature, it was evaporated and then dewatered by an oil pump. The obtained L-N-ethylphenylalanine ammonium amine (6.1 mmol) was reduced at 55 ° C with lithium aluminum hydride (570 mg, 15.0 mmol) in tetrahydrosulfan (65 µl) for 4 hours. The reaction mixture was poured into a saturated aqueous solution of sodium bicarbonate and extracted with methylene chloride 'to dehydrate and evaporate. Yu Shixue column chromatography (chloroform: methanol: triethylamine = 90: 7: 3) gave the amine as a yellow oil. : 179.1 (Μ + Η) +; (: ηΗ18N2 requires 値 178.3. -177- This paper size applies to the Chinese National Standard (CNS) A4 specification (210 × 297 mm) 520362 A7 ___ B7 V. Description of the invention (175) Examples 22 2 · Procedure for the preparation of amine-2 -methyl-3 -epipropylamine NH2, U ^ -2-methyl-3-_cumylpropylamine di-commercially available D, L_a-methylbenzene A solution of methyl alanine (5.0 g, 25.7 mmol) in a 28% aqueous solution of ammonium hydroxide (50 ml) was maintained at room temperature for 3 days. The resulting D, La-methylphenylalanine ammonium The white precipitate was filtered and dehydrated (2.5 g). This material (2.0 g, 11.22 mmol) was reduced with lithium aluminum hydride (1.3 g, 34.26 mmol) in boiling tetrahydrofuran for 24 hours. The reaction was added by adding sodium sulfate ten The hydrate was quenched at an ice bath temperature. The salt was filtered off and then evaporated to leave the title compound as an oil. MS (m / z): 165.1 (M + H) +; C1 () H16N2 requires 値 164.2. Alternative production method report In μ. Freiberger and R. Hasbrouck, J. Am. Chem. Soc. 82, 696-698 (1960). Example 23 Preparation procedure of 2-methyl-3-phenylpropylamine nh2

(請先閱讀背面之注意事項再填寫本頁) >裝· 訂 經濟部中央標準局員工消費合作社印製(Please read the notes on the back before filling out this page) > Binding and binding Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

2-甲基-3-苯基丙基胺：市售2_甲基-3-苯基丙基胺（4.32克 ，26.5毫莫耳）及鋁氫化鋰（1.3克，34.3毫莫耳）於四氫呋 喃（1 8 4毫升）之混合物於室溫擅;摔5小時。倒入飽和硫酸鋼 _ __·178- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） '— 520362 A7 〜_______B7__ 五、發明説明（176 ) 水液内及以二氯甲烷萃取接著脱水有機溶液及蒸發獲得胺 呈油。也曾報告其它合成方法例如Doriiow and Fust，Chem. Ber. 87，984 (1954) 0 實例24 5-(4 -氟苯基）-3 -甲基- 2- ((2 -甲基-3-苯基丙基）胺基）-6-(4 -p比 啶基）-4(3H)-嘧啶酮鹽酸鹽之製備程序2-methyl-3-phenylpropylamine: commercially available 2-methyl-3-phenylpropylamine (4.32 g, 26.5 mmol) and lithium aluminum hydride (1.3 g, 34.3 mmol) Tetrahydrofuran (184 ml) mixture at room temperature; drop for 5 hours. Pour into saturated sulfuric acid steel _ __178-This paper size is applicable to Chinese National Standard (CNS) A4 (210X297 mm) '— 520362 A7 ~ _______ B7__ 5. Description of the invention (176) Extraction in water and dichloromethane The organic solution was dehydrated and evaporated to give an amine as an oil. Other synthetic methods have also been reported such as Doriiow and Fust, Chem. Ber. 87, 984 (1954) 0 Example 24 5- (4-fluorophenyl) -3-methyl-2- ((2-methyl-3- Preparation of phenylpropyl) amino) -6- (4-p than pyridyl) -4 (3H) -pyrimidinone hydrochloride

5-(4 -氟苯基）-3 -甲基- 2- ((2 -甲基-3-苯基丙基）胺基比 啶基）-4(3Η)·嘧啶酮鹽酸鹽：粗5_(4·氟苯基）·3_甲基_2•甲 基續醯基- 6- (4 -ρ比淀基）-4(3Η)·ρ密淀酮（520毫克，1.45毫莫 耳）及2 -甲基-3-苯基丙基胺（1.5克’ 10.1毫莫耳）之混合物 經濟部中央標率局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 於50 °C加熱3 0分鐘。於石夕膠柱式層析（2-5 %甲醇/二氯甲 烷；己烷·丙酮=2 : 1)獲得標題化合物。MS(m/z；| : 429.4(M + H)+ ; C26H25FN40 要求値 428.5(自由態鹼）。 實例25 1·苯基-1，3 -丙坑一胺之製備程序5- (4-fluorophenyl) -3 -methyl-2-((2-methyl-3-phenylpropyl) amino group than pyridyl) -4 (3Η) · pyrimidinone hydrochloride: crude 5_ (4 · Fluorophenyl) · 3_Methyl_2 · Methyl fluorenyl-6- (4-p-pyridyl) -4 (3Η) · p-mylidene (520 mg, 1.45 mmol) ) And a mixture of 2-methyl-3-phenylpropylamine (1.5 g '10.1 mmol) printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) at Heat at 50 ° C for 30 minutes. The title compound was obtained by column chromatography on Shixi gel (2-5% methanol / dichloromethane; hexane · acetone = 2: 1). MS (m / z; |: 429.4 (M + H) +; C26H25FN40 requires 値 428.5 (free state base). Example 25 Preparation procedure of 1 · phenyl-1,3-propanilamine

-179- 本紙張尺度適用中國國家標準（CMS ) A4規格（210X297公釐） 520362 Α7 Β7 五、 發明説明（ 177-179- This paper size applies Chinese National Standard (CMS) A4 specification (210X297mm) 520362 Α7 Β7 V. Description of the invention (177

•CH3 基_1,3_丙燒二胺：3 -苯基胺基丙酸（S.G. Cohen and S Υ· Weinstein，J· Am. Chem· Soc. 86 ’ 725-728 ’ 1964) 如參考文獻（M. Kojima and J. Fujita, Bi^ll· Chem· Soc. Jpn. 55，1454-1459 (1982))報告轉成 1_ 苯基·1，3_ 丙烷二胺。 實例26 3-乙基-5-(4-氟苯基）-2-甲基硫-6-(4-吡啶基）-4(3H)-嘧啶酮 之製備程序• CH3 group_1,3-propanediamine: 3-phenylaminopropionic acid (SG Cohen and S. Weinstein, J. Am. Chem. Soc. 86 '725-728' 1964) As reference ( M. Kojima and J. Fujita, Bi ^ ll · Chem · Soc. Jpn. 55, 1454-1459 (1982)) reported conversion to 1-phenyl · 1,3-propanediamine. Example 26 Preparation of 3-ethyl-5- (4-fluorophenyl) -2-methylsulfan-6- (4-pyridyl) -4 (3H) -pyrimidone

3 -乙基- 5- (4 -氣苯基）-2·甲基硫-6-(4·外淀基密淀酉同 乙基溴（600毫升，8.03毫莫耳）於室溫添加至5-(4-氟苯 基）-2-甲基硫_6_(4_吡啶基）_4(3H)·嘧啶酮（1.8克，5.97毫 莫耳）及氫化鈉（60 %油懸浮液，320毫克，8毫莫耳）與 N，N-二甲基甲醯胺（60毫升）之攪妥混合物。經2及3·5小時 後加入更多乙基溴（2 X 600毫升，2 X 8.03毫莫耳）。8小 時後，反應混合物以乙酸中和及蒸發。殘餘物攝取於二氯 甲烷，有機溶液以水洗滌，脱水及蒸發。於矽膠柱急速層 析（己烷-丙酮二3 ·· 1，2 : 1)於第二主要溶離分獲得標題 化合物呈固體。 實例27 3·乙基-5-(4-氟苯基）_2-甲基磺醯基-6_(4-吡啶基）-4(311)-嘧 -180- 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） I I j i—a - I—1 ?-- ........士 -11-- -I I— — II -- - I II - - (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 ^0362 A7 ^^___________B7 五、發明説明（178 ) 啶酮之製備程序3 -Ethyl-5- (4-Gaphenyl) -2 · methylsulfan-6- (4 · Widedo-based dense lake with ethyl bromide (600ml, 8.03mmol) was added at room temperature to 5- (4-fluorophenyl) -2-methylsulfan-6_ (4_pyridyl) _4 (3H) · pyrimidone (1.8 g, 5.97 mmol) and sodium hydride (60% oil suspension, 320 Milligram, 8 millimolar) in a stirred mixture with N, N-dimethylformamide (60 ml). After 2 and 3.5 hours more ethyl bromide (2 X 600 ml, 2 X 8.03) Mmol). After 8 hours, the reaction mixture was neutralized and evaporated with acetic acid. The residue was taken up in dichloromethane, the organic solution was washed with water, dehydrated and evaporated. Flash chromatography on a silica gel column (hexane-acetone di 3 · · 1,2: 1) The title compound was obtained as a solid in the second major fraction. Example 27 3 · Ethyl-5- (4-fluorophenyl) _2-methylsulfonyl-6- (4-pyridyl) -4 (311) -Pyrimid-180- This paper size is applicable to Chinese National Standard (CNS) A4 specification (210 × 297 mm) II ji—a-I—1?-........ 士 -11- --II— — II--I II--(Please read the notes on the back before filling out this page) Central Bureau of Standards, Ministry of Economic Affairs Consumer cooperative work printed ^ 0362 A7 ^^ ___________ B7 V. invention is described in (178) following the procedure of piperidinone

兔题：3 _乙基·5-(4_氟苯基）-2-甲基硫-6-(4-吡啶基）-4(3H)-嘧啶酮（300毫克，0.88毫莫耳）及奥松（過氧一硫酸鉀， 2.54克，4.14毫莫耳）於甲醇（71毫升）及水（33毫升）之混合 物攪拌14小時。溶劑濃縮至約35毫升，接著以二氯甲烷 萃取，脱水及蒸發。所得白色固體未經進一步純化即用於 次一步驟。 實例28 2-(((S)-2-胺基_3_苯基丙基）·胺基）-3-乙基-5-(4-氟苯基 (4-吡啶基）-4(3H)-嘧啶酮鹽酸鹽之製備程序 (請先閱讀背面之注意事項再填寫本頁) 訂· 經濟部中央標準局員工消費合作社印製Rabbit question: 3_ethyl · 5- (4-fluorophenyl) -2-methylsulfan-6- (4-pyridyl) -4 (3H) -pyrimidinone (300 mg, 0.88 mmol) and Oxon (potassium peroxymonosulfate, 2.54 g, 4.14 mmol) was stirred in a mixture of methanol (71 ml) and water (33 ml) for 14 hours. The solvent was concentrated to about 35 ml, followed by extraction with dichloromethane, dehydration and evaporation. The resulting white solid was used in the next step without further purification. Example 28 2-(((S) -2-Amino-3_phenylpropyl) · amino) -3-ethyl-5- (4-fluorophenyl (4-pyridyl) -4 (3H ) -Preparation procedure of pyrimidinone hydrochloride (please read the notes on the back before filling this page)

2-(((S)_2 -胺基-3-苯基丙基）-胺基V3 -乙基- 5- (4-氟苯基 (4·吡啶基V4(3HV嘧啶酮鹽酸鹽：3-乙基_5_(4_氟苯基 甲基硫-6-(4•吡啶基）-4(3H)-嘧啶酮（15〇毫克，0.44毫莫耳 -181 - 本紙張尺度適用中國國家標準（CNS ) A4規格（21〇X 297公釐） ♦ 520362 A7 B7 五 、發明説明（ 179 )及（S)-l，2-苄基伸乙基二胺（200毫升，約1.3毫莫耳）之混 合物於l9〇°C加熱4.5小時。於艾司托灸（latrobeadsR)柱式 層析（氯仿：甲醇：三乙胺=90 : 7 : 3)獲得標題化合物 呈自由態鹼，自由態鹼藉加入2N鹽酸（165毫升，0.33毫 莫耳）及甲醇（1.5毫升）轉成結晶一鹽酸鹽。過濾、獲得標題化 合物。MS(m/z) : 444.0(M+H)+ ; C265H27FN50 要求値 443.5(自由態鹼）。 實例29 3 -乙基- 5- (4 -氟苯基）-2_((2·甲基-3-苯基丙基）胺基）-6_(4 -口比 啶基）-4(3H)-嘧啶酮鹽酸鹽之製備程序 (讀先閱讀背面之注意事項再填寫本頁)2-(((S) _2-Amino-3-phenylpropyl) -amino V3 -ethyl- 5- (4-fluorophenyl (4 · pyridyl V4 (3HV pyrimidinone hydrochloride: 3 -Ethyl_5_ (4-fluorophenylmethylsulfan-6- (4 • pyridyl) -4 (3H) -pyrimidinone (15 mg, 0.44 mmol) -181-This paper size applies to Chinese national standards (CNS) A4 specification (21 × 297 mm) ♦ 520362 A7 B7 V. Description of the invention (179) and (S) -1,2-benzylethylene diamine (200 ml, about 1.3 mmol) The mixture was heated at 190 ° C for 4.5 hours. Column chromatography (chloroform: methanol: triethylamine = 90: 7: 3) was performed on latrobeadsR to obtain the title compound as a free base. The free base was added by 2N hydrochloric acid (165 ml, 0.33 millimoles) and methanol (1.5 ml) were converted into crystalline monohydrochloride. The title compound was obtained by filtration. MS (m / z): 444.0 (M + H) +; C265H27FN50 requires 値 443.5 (Free state base). Example 29 3-ethyl-5- (4-fluorophenyl) -2-((2-methyl-3-phenylpropyl) amino) -6_ (4-pyridyl) ) -4 (3H) -Pyrimidinone hydrochloride preparation procedure (read the precautions on the back before filling this page)

經濟部中央標隼局員工消費合作社印製 I-乙基- 5- (4 -氟苯基-甲基-3_笨基丙基）胺基-外匕 啶基嘧啶酮鹽酸鹽：粗製3-乙基-5-(4-氟苯基）-2-甲基續醯基-6_(4-ρ比咤基）-4(3Η)-ρ密淀酮（320毫克，0.89毫 莫耳）及2-甲基-3-苯基丙基胺（600毫升，約4毫莫耳）之混 合物於60 °C加熱2小時。於矽膠柱式層析（己烷-丙酮=2 .1’2-5%甲醇/一鼠甲坑）獲得標題化合物。^8(111/2：): 443_2(M + H)+ ; C27H27FN40 要求値 442.5。 實例3 0 3_(2_甲基苯基）丙基胺之製備程序 -182- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（180 )Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs, I-Ethyl-5- (4-fluorophenyl-methyl-3_benzylpropyl) amino-exopyridinylpyrimidinone hydrochloride: crude 3 -Ethyl-5- (4-fluorophenyl) -2-methylcontinyl-6- (4-ρ than fluorenyl) -4 (3Η) -ρ melidene (320 mg, 0.89 mmol) A mixture of 2-methyl-3-phenylpropylamine (600 ml, about 4 mmol) was heated at 60 ° C for 2 hours. The title compound was obtained by silica gel column chromatography (hexane-acetone = 2.1'2-5% methanol / one rat pit). ^ 8 (111/2 :): 443_2 (M + H) +; C27H27FN40 requires 値 442.5. Example 3 0 3_ (2_methylphenyl) propylamine preparation procedure -182- This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 520362 A7 B7 V. Description of the invention (180)

g-(2_甲基苯基）丙基胺：氰臬甲签_鸸二λ酷（5·〇毫升， 30.9毫莫耳）於氬下添加至氫化鈉（6〇。/。油懸浮液，1.24克 ，3 1毫莫耳）於四氫呋喃（50亳升）之攪妥懸浮液。30分鐘 後，加入2-甲基苯甲醛（3.6毫升，31.ι毫莫耳）及持續攪拌 1小時。反應藉加速淬熄及以二氯甲烷萃取接著脱水及蒸 發去除有機溶液。柱式層析（己烷；己烷：乙酸乙酯=3 : 1)獲得2-(2 -甲基苯基）丙烯腈呈油。此種物料（3 8克），1〇 %細/碳（3·8克）及12Ν鹽酸（ΐι·8毫升，！42毫莫耳）於甲醇 (125尾升）於大氣壓以氫氫化2曰。過濾去除催化劑及蒸發 去除落劑。所得物料分配於二氯甲烷與水。水層以丨〇Ν氫 氧化鈉調整爲鹼性及以二氯甲烷萃取，接著脱水及蒸發。 所得物料於矽膠柱純化（氯仿：甲醇：三乙胺=85 : 1〇 : 5 )獲得標題化合物呈油。 實例3 1 2 -胺基- 3- (2 -氟本基）-丙基胺之製備程序 (請先閱讀背面之注意事項再填寫本頁} 一裴g- (2-Methylphenyl) propylamine: cyanocyanine methylacetate-co-diλco (5.0 ml, 30.9 mmol) was added to sodium hydride (60% oil suspension under argon). (1.24 g, 31 mmol) in a stirred suspension of tetrahydrofuran (50 ml). After 30 minutes, 2-methylbenzaldehyde (3.6 ml, 31. mil) was added and stirring was continued for 1 hour. The reaction was quenched and extracted with dichloromethane followed by dehydration and evaporation to remove the organic solution. Column chromatography (hexane; hexane: ethyl acetate = 3: 1) gave 2- (2-methylphenyl) acrylonitrile as an oil. This material (38 g), 10% fines / carbon (3.8 g) and 12N hydrochloric acid (ΐ8 ml,! 42 mmol) in methanol (125 liters) were hydrogenated with hydrogen at atmospheric pressure. . The catalyst is removed by filtration and the falling agent is evaporated. The resulting material was partitioned between dichloromethane and water. The aqueous layer was adjusted to basic with sodium hydroxide and extracted with dichloromethane, followed by dehydration and evaporation. The obtained material was purified on a silica gel column (chloroform: methanol: triethylamine = 85: 10: 5) to obtain the title compound as an oil. Example 3 1 2 -Amino-3-(2-fluorobenzyl) -propylamine preparation procedure (Please read the precautions on the back before filling this page} Yi Pei

、1T 經濟部中央標準局員工消費合作社印製, 1T Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs

堂胺基-3-(2-氟一苯基）丙酸甲克（27 3毫莫耳 )(D，L)_(2 -氟-苯基）丙胺酸懸浮於5〇亳并甲_ 毛升ψ %系鹽酸及於 183- 表紙張尺度適用中國國家標準（CNS ) A4規袼（2Ι〇χ297公釐） .I- I : 1— _ 0 «ϋϋ —ϋ 520362 Α7 Β7 五、發明説明（181 ) 室溫攪拌3日。反應混合物經眞空濃縮及脱水獲得黃色油 。MS(m/z) : 198(M + H)+ ; C1()H12FN20 要求値 197.2。 步驟B. 2-胺基-3-Γ2_1笨基）丙醯胺：2-胺基-3·(2·氟1某） 丙酸甲酯懸浮於5 0毫升3 0 %氫氧化銨及於室溫攪拌1 8小 時。混合物經過遽，以冷水洗務及收集2 -胺基-3 - ( 2 -氣苯基 )丙醯胺呈白色固體。MS(m/z) : 183·1(Μ + Η)+ ; C9HnFN20 要求値 182.2。 步驟C. 2-胺基-3-(2-氣笨基丙基胺：2-胺基-3-(2-氟苯基 )丙醯胺於氬下小心加至LAH( 1.0克’ 26.3毫莫耳）及20¾ 升THF之急冷（5 °C )混合物。然後反應回流加熱1 〇小時。 反應冷卻至5 °C及以硫酸鈉十水合物小心處理。所得混合 物攪拌18小時然後過濾去除固體。濾液經眞空濃縮獲得琥 珀色油。MS(m/z) : 169(M+H)+ ; C9H13FN2 要求値 168.19。 實例32 表I-II顯示化合物可使用實例U1程序製備。 (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 _- 184二 本紙張尺度適用中國國家標準（CNS ) A4規格(2丨〇'〆297公ϋ 520362 A7 B7 五、發明説明（182)Donamino-3- (2-fluoromonophenyl) propanoic acid methyl gram (27 3 mol) (D, L) _ (2-fluoro-phenyl) alanine suspended in 50% pyrene-methyl Liter ψ% is hydrochloric acid and it is applicable to Chinese National Standard (CNS) A4 Regulation (2Ι〇χ297mm) on the 183-sheet paper scale. I- I: 1— _ 0 «ϋϋ —ϋ 520362 Α7 Β7 V. Description of the invention ( 181) Stir at room temperature for 3 days. The reaction mixture was concentrated under reduced pressure and dehydrated to obtain a yellow oil. MS (m / z): 198 (M + H) +; C1 () H12FN20 requires 値 197.2. Step B. 2-Amino-3-Γ2_1benzyl) propanamine: 2-amino-3 · (2 · fluoro1) methyl propionate is suspended in 50 ml of 30% ammonium hydroxide and the chamber Stir for 18 hours. The mixture was washed with hydrazone, washed with cold water and collected 2-amino-3-(2- phenylphenyl) propanilamine as a white solid. MS (m / z): 183.1 (Μ + Η) +; C9HnFN20 requires 値 182.2. Step C. 2-Amino-3- (2-aminobenzylpropylamine: 2-amino-3- (2-fluorophenyl) propanamide is carefully added to LAH (1.0 g '26.3 mmol) under argon Mol) and a quenched (5 ° C) mixture of 20¾ liters of THF. The reaction was then heated at reflux for 10 hours. The reaction was cooled to 5 ° C and carefully treated with sodium sulfate decahydrate. The resulting mixture was stirred for 18 hours and then filtered to remove solids. The filtrate was concentrated in vacuo to obtain an amber oil. MS (m / z): 169 (M + H) +; C9H13FN2 requires 値 168.19. Example 32 Table I-II shows that the compounds can be prepared using the example U1 procedure. (Please read the back Note: Please fill in this page again.) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs _ 184 Two paper sizes are applicable to China National Standard (CNS) A4 specifications (2 丨 〇297〆 520362 A7 B7 V. Description of the invention ( 182)

表I 經濟部中央標準局員工消費合作社印製Table I Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs

(請先閱讀背面之注意事項再填寫本頁) -185- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（183 ) 經濟部中央標準局員工消費合作社印製(Please read the precautions on the back before filling this page) -185- This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) 520362 A7 B7 V. Description of Invention (183) Employees of the Central Standards Bureau of the Ministry of Economic Affairs Printed by Consumer Cooperatives

(請先閱讀背面之注意事項再填寫本頁) -186- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 B7 五、發明説明（184 ) 經濟部中央標準局員工消費合作社印製(Please read the precautions on the back before filling this page) -186- This paper size is applicable to Chinese National Standard (CNS) A4 size (210X 297 mm) 520362 A7 B7 V. Description of invention (184) Employees of the Central Standards Bureau of the Ministry of Economic Affairs Printed by Consumer Cooperatives

(請先閱讀背面之注意事項再填寫本頁) -187- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（185 )(Please read the precautions on the back before filling this page) -187- This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 520362 Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (185)

表IITable II

(請先閱讀背面之注意事項再填寫本頁) -188- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（186) 經濟部中央標準局員工消費合作社印製(Please read the precautions on the back before filling out this page) -188- This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 520362 A7 B7 V. Description of Invention (186) Staff Consumption of Central Standards Bureau, Ministry of Economic Affairs Printed by a cooperative

(請先閱讀背面之注意事項再填寫本頁) -189- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 五、發明説明（187 ) 實例33 生物檢定分析 下列檢定分析用以特徵化本發明化合物抑制TNF-α及 IL-1 β的生產能力。第二檢定分析測量小鼠投予口服試驗化 合物後TNF-a及/或IL-Ιβ之抑制作用。第三檢定分析爲試管 試驗檢定分析中，升糖素結合抑制作用，可用以特徵化本 發明化合物用以抑制升糖素結合的能力。第四檢定分析爲 環氧化酶（C0X-1及C0X-2)於試管試驗檢定分析之抑制活 性，可用以特徵化本發明化合物抑制C0X-1及/或C0X-2 之能力。 脂多醣活化單核細胞TNF生產檢定分析 單核細胞之分離 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 試驗化合物於試管試驗評估其抑制由以細菌性脂多_ (LPS)活化單核細胞生產TNF。新鮮殘餘白血球來源（血小 板電泳副產物）由當地血庫獲得，周邊血液單核細胞 (PBMCs)係藉密度梯度離心於 Ficol_Paque Plus(Pharmacia) 分離。PBMCs以2 x 106/毫升懸浮於DMEM，DMEM補充 含有2 % FCS 10 mM，0.3毫克/毫升麩胺酸酯，100單位/ 毫升青徼素G及100毫克/毫升鏈徵素硫酸鹽（完整培養基） 。細胞接種於Falcon平底96孔培養平板（200微升/孔）及於 37 °C及6 %二氧化碳培育隔夜。以200微升/孔新鮮培養基 洗滌去除未黏著細胞。含黏著細胞（約70 %單核細胞）之孔 補充10 0微升新鮮培養基。 -190- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 Α7 Β7 五、發明説明（188 ) 試驗化合物備用溶液之製備 試驗化合物溶解於DMZ。製備試驗化合物備用溶液至初 濃度10-50 μΜ。備料最初於完全培養基稀釋至20-200 μΜ 。然後於完整培養基製備各種化合物一系列九次兩倍稀釋 液。 細胞以試驗化合物處理及TNF生產以脂多醣活化(Please read the precautions on the back before filling this page) -189- This paper size is applicable to the Chinese National Standard (CNS) A4 size (210X297 mm) 520362 A7 B7 V. Description of the invention (187) Example 33 Biological test analysis The following test The analysis was used to characterize the ability of the compounds of the invention to inhibit TNF-α and IL-1 β production. The second assay was used to measure the inhibitory effect of TNF-a and / or IL-Ιβ on mice after oral administration of test compounds. The third test analysis is a test tube test test analysis, in which the glucagon binding inhibitory effect can be used to characterize the ability of the compound of the present invention to inhibit glucagon binding. The fourth assay is the inhibitory activity of cyclooxygenases (C0X-1 and COX-2) in a test tube assay, which can be used to characterize the ability of the compounds of the present invention to inhibit COX-1 and / or COX-2. Lipopolysaccharide-activated monocyte TNF production assay Analysis of monocyte isolation Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) Test compounds are tested in test tubes to evaluate their inhibition by bacterial Lipopolysaccharide (LPS) activates monocytes to produce TNF. The source of fresh residual leukocytes (byproducts of platelet electrophoresis) was obtained from the local blood bank. Peripheral blood mononuclear cells (PBMCs) were separated by density gradient centrifugation at Ficol_Paque Plus (Pharmacia). PBMCs were suspended in DMEM at 2 x 106 / ml, and DMEM supplemented with 2% FCS 10 mM, 0.3 mg / ml glutamate, 100 units / ml berberine G and 100 mg / ml streptavidin sulfate (complete medium ). Cells were seeded on Falcon flat-bottomed 96-well culture plates (200 μl / well) and incubated overnight at 37 ° C and 6% carbon dioxide. Wash with 200 μl / well of fresh medium to remove non-adherent cells. Wells with adherent cells (approximately 70% monocytes) were supplemented with 100 μl of fresh medium. -190- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210X 297 mm) 520362 A7 B7 V. Description of the invention (188) Preparation of test compound standby solution The test compound is dissolved in DMZ. Prepare a test compound stock solution to an initial concentration of 10-50 μM. The preparation was initially diluted to 20-200 μM in complete medium. A series of nine two-fold dilutions of each compound were then prepared in complete medium. Cells treated with test compounds and TNF production activated with lipopolysaccharide

100微升各試驗化合物稀釋液添加至含黏著單核細胞及 100微升完全培養基之微力價孔。單核細胞於試驗化合物 培養60分鐘，此時25微升完全培養基含30塵克/毫升得自 大腸桿菌Κ532之脂多醣添加至各孔。孔又培養4小時。然 後移出培養上清液，及上清液中TNF含量使用ELIS Α定量。 TNF ELISA 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 平底96孔康寧高度結合ELIS A平板以150微升/孔3微克 /毫升鼠抗人 TNF-α MAb(R&D Systems #MAB210)塗覆隔夜 (4 °C )。然後孔於室溫以200微升/孔不含二氯化鈣ELIS A 之緩衝液封阻1小時，緩衝液經補充而含有20毫克/毫升 BSA(標準 ELISA 緩衝液：20 mM，150 mM NaCl，2 mM CaCl2，0.15 mM柳硫汞，pH 7.4)。平板經洗滌及補充100 微升試驗上清液（稀釋1 : 3)或標準品。標準品包括一系列 十一次1.5倍得自1塵克/毫升重組人TNF(R&D Systems)備 料稀釋液。平板於室溫於軌道機振搖（300 rpm)培育1小時 ，洗滌及補充100微升/孔0.5微克/毫升山羊抗人TNF-a (R&D systems #ΑΒ-210·ΝΑ)以4 : 1之比生物素化。平板 培育40分鐘，洗滌及以0.02微克/毫升補充100微升/孔鹼 -191 - 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 520362 A7 B7 五、發明説明（189 經濟部中央標準局員工消費合作社印製 性騎酸酶共輛接合鏈球菌 N囷抗生物素（Jackson ImmunoResearch #0 16-050-084、〇 t 、 ； 干板培育30分鐘，洗滌 及補充200微升/孔1毫克/毫升噂酸對硝基苯基酯。3〇分 後’平板於Vmax平板閱項機於4〇5 nm閱讀。資料分析 〜 標準曲線資料配合第2級多项式及解出濃度方程式由 OD決定未知之TNF-a濃度。然後TNF_a濃度使用第2級多 項式相對於試驗化合物濃度作圖。然後方程式用於算出試 驗化合物濃度使TNF-a產量降低5〇 %。 本發明化合物藉業界人士眾所周知之方法測量IL_ 1 β， IL-6及/或IL-8濃度也顯示可抑制Lps_謗生由單核細胞釋 放出IL-Ιβ，IL-6及/或IL-8。以類似前述有關Lps_謗生單 核細胞釋放TNF-a之檢定分析之相同方式，本發明化合物 藉業界人士眾所周知方法經由測量IL_ip，IL_6及/或IL_8 ;辰度也顯示可抑制LPS_謗生由單核細胞釋放 及/或IL-8。如此，本發明化合物可降低TNF_a，IL-1，IL-6 ’及IL-8之升高濃度。此等發炎性細胞激素升高的濃度降 低土基本濃度或以下’有利於控制、減慢進展及改善多種 病態。全部化合物皆可用於疾病治療方法，其中TNF_a， α-ΐβ ’ IL_6，及IL-8於該疾病扮演角色至此處所述TNF-a媒介病定義之完整程度。 於小鼠抑制LPS-謗生TNF-a之生產 雄DBA/1LACJ小鼠於注射脂多醣（2毫克/千克靜脈注射） 前30分鐘給予媒劑或試驗化合物於媒劑（媒劑包括0.5 %西 192 表紙張尺度適用中國國家榇準（CNS ) A4規格（2ίϋχ297公襲) (請先閱讀背面之注意事項再填寫本頁) _裝_ -?口 1· 520362 A7 ___ B7 五、發明説明（190 ) ~^^' 黃蓍膠於0.03N鹽酸）。LPS注射後90分鐘，採集血液及藉 ELISA分析血清之TNF濃度。 下列化合物於單核細胞檢定分析（LPS謗生TNF釋放）具 有活性，IC5〇値爲20 μΜ或以下·· 5_(4_氟苯基）-2-(4-ρ比淀基）-4-(4-ρ比淀基）_喊淀 5-(4-氣苯基）_2-(2 -曱基ρ塞峻·4_基）-4-(4-ρ比淀基）-口密淀 5-(4 -氟苯基）-4-(4-0比淀基）-2·(2_ρ塞吩基）-喃淀 2-(2 -二乙基胺基乙基胺基）·5-(4·氣苯基）-4_(4-ρ比淀基）-νι密 淀 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 2-(2-胺基乙基胺基）-5-(4-氣苯基）-4-(4 -外ts症基咬 2-(3-胺基丙基胺基）-5-(4-氟苯基）-4-(4-吡啶基）-嘧啶 2-(4-胺基丁基胺基）-5-(4-氟苯基）-4-(4-吡啶基）-嘧啶 2-(2,6-二氯字基）-5_(4-氟*苯基）-4-(4-p比淀基）_p密淀 2-(2,6-二氯苯基胺基）-5-(4-氟苯基）-4-(4-吡啶基）-嘧啶 2_(2,6-二甲基苯基胺基）-5-(4-氟苯基）-4-(4-吡啶基）-嘧啶 5-(4-氟苯基）-2-(2-甲氧苯基胺基）-4-(4-吡啶基）-嘧啶 5-(4_氟苯基）-2-(4-氟苯基胺基）-4-(4-吡啶基）-嘧啶 5 - (4 -氣苯基）-2 -苯基硫甲基-4 - (4 - π比淀基）-♦淀 2-(爷基胺基）-5-(4-氣苯基）-4-(4 -p比淀基< 5-(4-氟苯基）-2-(2-苯基乙基胺基）-4-(4-吡啶基）-嘧啶 5-(4-氟苯基）-2-(甲基-(2-苯基乙基）-胺基）-心（4-吡啶基）-嘧 啶 5-(4-氟苯基）-2-((2-羥-2-苯基-乙基）胺基）-4-(4-吡啶基）·嘧 淀 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） -193- _ 520362 A7 _ B7 五、發明説明（191 ) 5_(4_氟苯基）-2-(2-(4-羥苯基）乙基-胺基）-4-(4-吡啶基）·嘧 啶 2-(2-(4-胺基苯基）乙基-胺基）-5-(4-氟苯基）-4-(4-吡啶基）_ 嘧啶 5-(4-氟苯基）-2-(2-(4-氟苯基）乙基-胺基）-4-(4-吡啶基）_嘧 啶 5-(4-氟苯基）-2-(2-(2-氟苯基）乙基-胺基）-4-(4-吡啶基）〃密 啶 2-(2-(2-氯苯基）乙基-胺基）·5-(4-氟苯基）-4-(4-吡啶基）_口密 啶 2-(2-(4-氯苯基）乙基-胺基）-5-(4-氟苯基）-4-(4·吡啶基）_癌 淀 2-(2-(3-氯苯基）乙基-胺基）-5-(4-氟苯基）-4-(4-吡啶基）_喊 2-(2-(2,4-二氯苯基）乙基-胺基）-5-(4-氟苯基）-4-(4-吡淀基 嘧啶 2-(2-(4-溴苯基）乙基-胺基）-5-(4-氟苯基）-4-(4-吡啶基）·癌 啶 經濟部中央標率局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 5-(4-氟苯基）-2-(2-(2-甲氧苯基）乙基-胺基）-4-(4^比淀基）_ 嘧啶 5-(4-氟苯基）-2-(2-(3-甲氧苯基）乙基-胺基）-4-(4-吡淀基）_ 癌淀 5-(4-氟苯基）-2-((3 -苯基丙基）胺基）-4-(4-吡啶基）-嘧啶 5-(4-氟苯基）-2-((1-甲基-3-苯基丙基）-胺基）-4-(4-吡啶基）- __- 194- _ 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X 297公釐） 520362 經濟部中央標準局員工消費合作社印製 Α7 Β7 五、發明説明（192) 口密淀 2-(((S)-2-胺基-3-苯基丙基）-胺基）-5-(4-氟苯基）-4-(4-吡啶 基）-,淀 5-(4-氟苯基）-2-(2-苯基胺基乙基胺基）-4-(4-吡啶基）-嘧啶 5-(4-氟苯基）-2-((3-咪峻基丙基）-胺基）-4-(4-p比淀基）-喃淀 5-(4-氟苯基）-2-((4-苯基丁基）-胺基）-4-(4-吡啶基）-嘧啶 5-(4 -氟苯基）-4-(4-说淀基）_2-峨洛啶基-嘧啶 5-(4-氟苯基）-2-嗎啉基-4-(4-吡啶基）-嘧啶 5_(4_氟苯基）-2-((1-六氫吡畊基）-4-(4-吡啶基）-嘧啶 5 ^4-氟苯基）-4-(4-吡啶基）-2-(2-吡咯啶基乙基胺基）-嘧唆 5-(4 -鼠本基）-2-(2 -嗎1(7林基乙基胺基）-4-(4 -p比淀基）-p密咬 5*"(4 -氟苯基）-2-(2 -六氫峨淀基乙基胺基）-4-(4-p比淀基 啶 5-(4-氟苯基）-2-(3_(2-吡咯啶酮-1-基）丙基-胺基）-4·(4-Ρ比咬 基）_嘧啶 2-(2,6·二氯苄基）_5-(4_ 氟苯基）·6-(4·吡啶基）·4(3Η)_,咬 酮 5-(4-氟苯基）-2_(2·苯基乙基）硫-6-(4_吡啶基）_4(3Η)-,咬 酮 5-(4-氟苯基）-2-(3-苯基丙基）硫-6-(4-吡啶基）-4(3Η)_,唆 酮 5-(4_氟苯基）-2-(2-苯氧乙基）硫_6-(4-ρ比淀基）-4(3Η)_,咬 酮 -氟笨基）-2_(2_苯基胺基乙基）硫_6·(4·ρ比淀基）_4(3只） -----195- _ 本紙張尺度適用中國ϋ：標準（CNS ) Α4規格（2lOX:7公釐） (請先閱讀背面之注意事項再填寫本頁，> 琴裝 -訂' 經濟部中央標準局員工消費合作社印製 520362 A7 __ B7 五、發明説明（193) 嘧啶酮 2-(2-(2-氯苯基）乙基-胺基）-5-(4-氟苯基）-6-(4-吡啶基）-4(3H)-喊淀酮 5-(4-氟苯基）-2-((3-苯基丙基）胺基）-6-(4-吡啶基）-4(3H)-嘧 啶酮 5-(4-氟苯基）-2-((1-甲基-3-苯基丙基）_胺基）-6_(4-吡啶基）-4(3H) -喊淀酉同 5-(4·氣苯基）-2-((3·味峻基丙基）胺基）-6-(4-p比淀基）-4(3H)· 嘧咬酮 下列化合物於單核細胞檢定分析（LPS謗生TNF釋放）具 有IC5〇値爲5 μΜ或以下： 2-(2-胺基乙基胺基）-5-(4-氟苯基）-4_(4-吡啶基）-嘧啶 2-(3-胺基丙基胺基）-5-(4-氟苯基）-4-(4-吡啶基）-嘧啶 2-(苄基胺基）-5-(4-氟苯基）-4-(4-吡啶基）·嘧啶 5-(4-氟苯基）-2-(2-苯基乙基胺基）-4-(4-吡啶基）·嘧啶 5-(4-氟苯基）-2-(1^-甲基->^(2-苯基乙基）胺基）-4-(4-吡啶基 嘧啶 5 - ( 4 ·鼠冬基）-2 - ( 2 -經-2 _苯基-乙基）胺基-4 - ( 4 - ρ比淀基）_ ρ密 啶 5-(4-氟苯基）-2-(2-(4-羥苯基）乙基胺基）-4-(4-吡啶基）_嘧 啶 5-(4-鼠苯基）-2-(2_(4-氟苯基）乙基胺基）-4_(4-π比淀基密 啶 5-(4-氟苯基）_2·(2-(2·氣苯基）乙基胺基）-4-(4 -π比淀基）_口密 ___- 196-__ 本紙張尺度適用中國國家標準（CNS ) Α4規格（2lOX297公釐^ ' «批衣-- (請先閱讀背面之注意事項再填寫本頁) 、11 520362 A7 B7 五、發明説明（194 ) 啶 2-(2-(2-氯苯基）乙基胺基）-5-(4-氣苯基）-4-(4 -p比淀基）-口密 啶 2-(2-(4 -氯苯基）乙基胺基）-5-(4 -氣苯基）-4-(4 -p比淀基）-喃 啶 2-(2-(2,4-二氯苯基）乙基胺基）-5-(4-氟苯基）-4-(4-吡啶基）- p密淀 5-(4-氟苯基）-2-(3-苯基丙基）胺基-4-(4-吡啶基）-嘧啶 2-((S)-2-胺基-3-苯基丙基）胺基-5-(4_氟苯基）-4-(4-吡啶基 密淀 5-(4-氟苯基）-2-(2_苯基胺基乙基胺基）_4-(4-吡啶基）-嘧啶 5-(4-氟苯基）_2_(3-咪唑基丙基）胺基-4-(4-吡啶基）-嘧啶 5-(4 -氟苯基）-4-(4-p比淀基）-2-各淀基密淀 5-(4-氟苯基）-2-(1-六氫井基）-4-(4-p比淀基）-喊淀 5-(4-氟苯基）-2-(2-苯基乙基）硫-6-(4-吡啶基）-4(3H)-嘧啶 酮 5-(4-氟苯基）-2-(3 -苯基丙基）硫-6-(4-吡啶基）-4(3H)-嘧啶 酮 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 2-(2-(2-氯苯基）乙基-胺基）-5-(4-氟苯基）-6-(4-吡啶基）-4(3H)-喊淀酮 5_(4_氟苯基）-2-(3-苯基丙基）胺基-6-(4-吡啶基）-4(3H)-嘧 淀酮 5-(4-氟苯基）-2-(1-甲基-3-苯基丙基）胺基-6-(4-吡啶基）-4(3H)-喊淀酮 __- 197- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 經濟部中央標準局員工消費合作社印製 A7 ___B7 五、發明説明（195 ) 本發明化合物於動物發炎模式顯示具有抗炎性質，動物 發炎模式包含鹿角菜膠踱水腫，膠原謗生關節炎及佐藥關 節炎例如鹿角菜膠疏水腫模式（C.A. Winter et al Proc. Soc. Exp. Biol. Med. (1962) vol 111，p 544 ; K.F· Swingle，in R· A. Scherrer and M. W. Whitehouse, Eds”100 microliters of each test compound dilution was added to the microvalence wells containing adherent monocytes and 100 microliters of complete medium. Monocytes were incubated with the test compound for 60 minutes, at which time 25 microliters of complete medium containing 30 g / ml of lipopolysaccharide from E. coli K532 was added to each well. The wells were incubated for another 4 hours. The culture supernatant was then removed and the TNF content in the supernatant was quantified using ELIS A. TNF ELISA Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) Flat-bottomed 96-well Corning highly integrated ELIS A plate at 150 μl / well 3 μg / ml mouse anti-human TNF-α MAb (R & D Systems # MAB210) was coated overnight (4 ° C). The wells were then blocked at room temperature with 200 μl / well of calcium chloride-free ELIS A buffer for 1 hour. The buffer was supplemented with 20 mg / ml BSA (standard ELISA buffer: 20 mM, 150 mM NaCl , 2 mM CaCl2, 0.15 mM thiomersal, pH 7.4). The plate was washed and supplemented with 100 μl of test supernatant (diluted 1: 3) or standard. Standards consisted of a series of eleven 1.5-fold dilutions of 1 g / ml recombinant human TNF (R & D Systems) stock dilutions. The plate was incubated at room temperature for 1 hour on an orbital shaker (300 rpm), washed and supplemented with 100 μl / well 0.5 μg / ml goat anti-human TNF-a (R & D systems # ΑΒ-210 · ΝΑ) at 4: 1 ratio biotinylated. The plate was incubated for 40 minutes, washed and supplemented with 0.02 μg / ml and supplemented with 100 μl / pore base -191-This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A7 B7 V. Description of the invention (189 Ministry of Economic Affairs) Central Standards Bureau Consumers' Cooperative Printed Saccharase Enzyme Conjugated Streptococcus N 囷 Avidin (Jackson ImmunoResearch # 0 16-050-084, 0t,; Incubate dry plates for 30 minutes, wash and replenish 200 μl / Well 1 mg / ml p-nitrophenyl gallate. After 30 minutes, the plate was read on a Vmax plate reader at 405 nm. Data analysis ~ The standard curve data was combined with a second-order polynomial and the concentration equation was solved by The OD determines the unknown TNF-a concentration. The TNF_a concentration is then plotted against the concentration of the test compound using a second-order polynomial. The equation is then used to calculate the concentration of the test compound to reduce the TNF-a production by 50%. The compounds of the invention are well known to those in the industry The method of measuring the concentration of IL-1 β, IL-6 and / or IL-8 has also been shown to inhibit the release of IL-1β, IL-6 and / or IL-8 from monocytes. _Study List In the same way as the assay for TNF-a release from cells, the compounds of the present invention measure IL_ip, IL_6, and / or IL_8 by well-known methods in the industry; Chen degree has also been shown to inhibit the release of LPS_flame from monocytes and / or IL- 8. In this way, the compounds of the present invention can reduce the elevated concentrations of TNF_a, IL-1, IL-6 'and IL-8. These elevated concentrations of inflammatory cytokines reduce the basic concentration of soil or below' which is conducive to control, reduce Slow progression and improvement of various pathologies. All compounds can be used in the treatment of diseases, in which TNF_a, α-ΐβ'IL_6, and IL-8 play a role in the disease to the full extent of the definition of TNF-a vector disease described herein. Yu Xiao Rats inhibited LPS-proliferating TNF-a production. Male DBA / 1LACJ mice were given vehicle or test compound 30 minutes before injection of lipopolysaccharide (2 mg / kg intravenously) (vehicle included 0.5% West 192 paper) Zhang scale is applicable to China National Standards Standard (CNS) A4 (2 ϋ 297297 attack) (Please read the precautions on the back before filling this page) _ 装 _-? 口 1 · 520362 A7 ___ B7 V. Description of the invention (190) ~ ^^ 'tragacanth in 0.03N hydrochloric acid). LPS Ninety minutes after the injection, blood was collected and the serum TNF concentration was analyzed by ELISA. The following compounds were active in a monocyte assay (LPS S TNF release) with IC50 of 20 μM or less. 5_ (4_fluorobenzene ) -2- (4-ρ ratio ytyl) -4- (4-ρ ratio ydyl) _Xiaodian 5- (4-Gaphenyl) _2- (2-fluorenyl ph ) -4- (4-ρ ratio phenyl group) -Komi dense lake 5- (4-fluorophenyl) -4- (4-0 ratio phenyl group) -2 · (2_ρ Cephenyl) -Nanji 2- (2-Diethylaminoethylamino) · 5- (4 · Phenylphenyl) -4_ (4-ρBiYodo)-printed by the Consumer Cooperative of the Central Standards Bureau of the Midian Economic Ministry (please first Read the notes on the back and fill in this page again) 2- (2-Aminoethylamino) -5- (4-Gaphenyl) -4- (4-Exyttriol 2- (3-Amino) Propylamino) -5- (4-fluorophenyl) -4- (4-pyridyl) -pyrimidine 2- (4-aminobutylamino) -5- (4-fluorophenyl) -4 -(4-pyridyl) -pyrimidine 2- (2,6-dichloro group) -5_ (4-fluoro * phenyl) -4- (4-p than ydoyl) _p dense lake 2- (2, 6-dichlorophenylamino) -5- (4-fluorophenyl) -4- (4-pyridyl) -pyrimidine 2_ (2,6-dimethylphenylamino) -5- (4- Fluorophenyl) -4- (4-pyridyl ) -Pyrimidine 5- (4-fluorophenyl) -2- (2-methoxyphenylamino) -4- (4-pyridyl) -pyrimidine 5- (4-fluorophenyl) -2- (4 -Fluorophenylamino) -4- (4-pyridyl) -pyrimidine 5-(4-Phenylphenyl) -2 -phenylthiomethyl-4-(4-π ratio)-♦ 2 -(Lethylamino) -5- (4-phenyl) -4- (4-p than Phenyl < 5- (4-fluorophenyl) -2- (2-phenylethylamino) ) -4- (4-pyridyl) -pyrimidine 5- (4-fluorophenyl) -2- (methyl- (2-phenylethyl) -amino) -heart (4-pyridyl) -pyrimidine 5- (4-fluorophenyl) -2-((2-hydroxy-2-phenyl-ethyl) amino) -4- (4-pyridyl) · pyrimido This paper is sized to the Chinese National Standard (CNS ) A4 specification (210X297 mm) -193- _ 520362 A7 _ B7 V. Description of the invention (191) 5_ (4_fluorophenyl) -2- (2- (4-hydroxyphenyl) ethyl-amine) -4- (4-pyridyl) · pyrimidine 2- (2- (4-aminophenyl) ethyl-amino) -5- (4-fluorophenyl) -4- (4-pyridyl) _ Pyrimidine 5- (4-fluorophenyl) -2- (2- (4-fluorophenyl) ethyl-amino) -4- (4-pyridyl) _pyrimidine 5- (4-fluorophenyl)- 2- (2- (2-fluorophenyl) ethyl-amino) -4- (4-pyridyl) pyrimidin 2- (2- (2-chlorophenyl) ethyl- ) · 5- (4-fluorophenyl) -4- (4-pyridyl) _oripidine 2- (2- (4-chlorophenyl) ethyl-amino) -5- (4-fluoro Phenyl) -4- (4 · pyridyl) _Ondo 2- (2- (3-chlorophenyl) ethyl-amino) -5- (4-fluorophenyl) -4- (4-pyridine ) __ 2- (2- (2,4-dichlorophenyl) ethyl-amino) -5- (4-fluorophenyl) -4- (4-pyridylpyrimidine 2- (2- (4-Bromophenyl) ethyl-amino) -5- (4-fluorophenyl) -4- (4-pyridyl) · Printed by the Employees' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (Please read first Note on the back, please fill out this page again) 5- (4-Fluorophenyl) -2- (2- (2-methoxyphenyl) ethyl-amino) -4- (4 ^ bidianyl) _ Pyrimidine 5- (4-fluorophenyl) -2- (2- (3-methoxyphenyl) ethyl-amino) -4- (4-pyridyl) _ Ondo 5- (4-fluorophenyl ) -2-((3-phenylpropyl) amino) -4- (4-pyridyl) -pyrimidine 5- (4-fluorophenyl) -2-((1-methyl-3-phenyl Propyl) -amino) -4- (4-pyridyl)-__- 194- _ This paper size applies to China National Standard (CNS) A4 specification (210X 297 mm) 520362 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Preparation A7 B7 V. Description of the invention (192) Mouth dense lake 2-(( (S) -2-Amino-3-phenylpropyl) -amino) -5- (4-fluorophenyl) -4- (4-pyridyl)-, 5- (4-fluorophenyl) ) -2- (2-phenylaminoethylethylamino) -4- (4-pyridyl) -pyrimidine 5- (4-fluorophenyl) -2-((3-imidylpropyl)- Amino group) -4- (4-p than Yodo group) -rano 5- (4-fluorophenyl) -2-((4-phenylbutyl) -amino group) -4- (4-pyridyl group ) -Pyrimidine 5- (4-fluorophenyl) -4- (4-Saidyl) _2-erlotidyl-pyrimidine 5- (4-fluorophenyl) -2-morpholinyl-4- (4 -Pyridyl) -pyrimidine 5_ (4-fluorophenyl) -2-((1-hexahydropyridyl) -4- (4-pyridyl) -pyrimidine 5 ^ 4-fluorophenyl) -4- ( 4-pyridyl) -2- (2-pyrrolidinylethylamino) -pyrimidine 5- (4-murylbenzyl) -2- (2-morpho-1 (7linylethylamino) -4 -(4 -p 比基基) -p dense bite 5 * " (4-fluorophenyl) -2- (2-hexahydroetoylethylamino) -4- (4-pbito Pyridine 5- (4-fluorophenyl) -2- (3_ (2-pyrrolidinone-1-yl) propyl-amino) -4 · (4-P ratio) -pyrimidine 2- (2, 6 · Dichlorobenzyl) _5- (4_fluorophenyl) · 6- (4 · pyridyl) · 4 (3Η) _, keto 5- (4-fluorophenyl) -2_ (2 · phenylethyl ) Sulfur-6- (4-pyridyl) _4 (3Η)-, keto 5- (4-fluorophenyl -2- (3-phenylpropyl) thio-6- (4-pyridyl) -4 (3Η) _, fluorenone 5- (4-fluorophenyl) -2- (2-phenoxyethyl) Sulfur 6- (4-ρ than yodoyl) -4 (3Η) _, keto-fluorobenzyl) -2_ (2_phenylaminoethyl) sulfur -6 · (4 · ρ yodoyl) _4 (3 pcs) ----- 195- _ This paper size applies to Chinaϋ: Standard (CNS) Α4 size (2lOX: 7mm) (Please read the precautions on the back before filling this page, > Musical equipment -Order 'Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 520362 A7 __ B7 V. Description of the invention (193) Pyrimidone 2- (2- (2-chlorophenyl) ethyl-amino) -5- (4- Fluorophenyl) -6- (4-pyridyl) -4 (3H) -Hydroxylone 5- (4-fluorophenyl) -2-((3-phenylpropyl) amino) -6- ( 4-pyridyl) -4 (3H) -pyrimidinone 5- (4-fluorophenyl) -2-((1-methyl-3-phenylpropyl) _amino) -6_ (4-pyridyl ) -4 (3H) -Yodo-Yen with 5- (4-Phenylphenyl) -2-((3 · Weijipropyl) amino) -6- (4-p than yodo) -4 ( 3H) · The following compounds have an IC50 of 5 μM or less in a monocyte assay (LPS TNF release): 2- (2-aminoethylethylamino) -5- (4-fluoro Phenyl) -4_ (4-pyridyl -Pyrimidine 2- (3-aminopropylamino) -5- (4-fluorophenyl) -4- (4-pyridyl) -pyrimidine 2- (benzylamino) -5- (4-fluoro Phenyl) -4- (4-pyridyl) · pyrimidine 5- (4-fluorophenyl) -2- (2-phenylethylamino) -4- (4-pyridyl) · pyrimidine 5- ( 4-Fluorophenyl) -2- (1 ^ -methyl- > ^ (2-phenylethyl) amino) -4- (4-pyridylpyrimidine 5-(4 · Ruetyl) -2 -(2 -Ethyl-2 -phenyl-ethyl) amino-4-(4 -r than pyridyl) _ r pyrimidine 5- (4-fluorophenyl) -2- (2- (4-hydroxy Phenyl) ethylamino) -4- (4-pyridyl) _pyrimidine 5- (4-murylphenyl) -2- (2- (4-fluorophenyl) ethylamino) -4_ (4- π than ytmidyl 5- (4-fluorophenyl) _2 · (2- (2 · Gaphenyl) ethylamino) -4- (4 -π than ytyl) _ mouth dense ___- 196 -__ This paper size is in accordance with Chinese National Standard (CNS) A4 specification (2lOX297mm ^ '«Batch-(Please read the precautions on the back before filling this page), 11 520362 A7 B7 V. Description of the invention (194) Pyrimidine 2- (2- (2-chlorophenyl) ethylamino) -5- (4-phenyl) -4- (4-p-pyridyl) -oripidine 2- (2- (4 -Chlorophenyl) ethylamino) -5- (4-phenyl) -4- (4-p -Pyrimidine 2- (2- (2,4-dichlorophenyl) ethylamino) -5- (4-fluorophenyl) -4- (4-pyridyl) -p dense lake 5- (4 -Fluorophenyl) -2- (3-phenylpropyl) amino-4- (4-pyridyl) -pyrimidine 2-((S) -2-amino-3-phenylpropyl) amino -5- (4_fluorophenyl) -4- (4-pyridyl dense lake 5- (4-fluorophenyl) -2- (2-phenylaminoethylethylamino) _4- (4-pyridine ) -Pyrimidine 5- (4-fluorophenyl) _2_ (3-imidazolylpropyl) amino-4- (4-pyridyl) -pyrimidine 5- (4-fluorophenyl) -4- (4- p-specific phenyl group) -2- each crystalline group densely deposited 5- (4-fluorophenyl) -2- (1-hexahydro well group) -4- (4-p specific crystalline group) -shodo 5- ( 4-fluorophenyl) -2- (2-phenylethyl) thio-6- (4-pyridyl) -4 (3H) -pyrimidinone 5- (4-fluorophenyl) -2- (3- Phenylpropyl) sulfur-6- (4-pyridyl) -4 (3H) -pyrimidinone Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling this page) 2- (2 -(2-Chlorophenyl) ethyl-amino) -5- (4-fluorophenyl) -6- (4-pyridyl) -4 (3H) -dimethylammonone 5_ (4_fluorophenyl) 2- (3-phenylpropyl) amino-6- (4-pyridyl) -4 (3H) -pyrimidolone 5- (4-fluorophenyl) -2- (1-methyl-3 -Phenylpropyl) amino-6- ( 4-pyridyl) -4 (3H) -Xiaodianone __- 197- This paper size is applicable to China National Standard (CNS) A4 (210X 297 mm) 520362 Printed by A7 ___B7, Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs V. Description of the invention (195) The compounds of the present invention show anti-inflammatory properties in animal inflammatory modes. The animal inflammatory modes include carrageenan edema, collagen-induced arthritis and adjuvant arthritis such as carrageenan hydrophobic edema (CA Winter et al Proc. Soc. Exp. Biol. Med. (1962) vol 111, p 544; KF · Swingle, in R · A. Scherrer and MW Whitehouse, Eds "

Antiinflammatory Agents，Chemistry and Pharmacology，Vol· 13-11，Academic，New York，1974，ρ·33)及膠原謗生關 節炎（D.E. Trentham et al J. Exp· Med. (1977) vol. 146，p 857 ; J. S· Courtenay，Nature (New Biol.) (1980)，Vol 283 ，p 666) o 使用CHO/hGLUR細胞進行125I-升糖素結合篩檢 檢定分析述於WO 97/16442(併述於此以供參考）。 反應劑Antiinflammatory Agents, Chemistry and Pharmacology, Vol. 13-11, Academic, New York, 1974, p. 33) and collagen osteoarthritis (DE Trentham et al J. Exp. Med. (1977) vol. 146, p 857 J. S. Courtenay, Nature (New Biol.) (1980), Vol 283, p 666) o 125I-glucagon binding screening assay assay using CHO / hGLUR cells is described in WO 97/16442 (also described in For reference). Reactant

反應劑製備如下：（a)製備新鮮1M鄰菲繞啉 (Aldrich)(198.2毫克/毫升乙醇）；（b)製備新鮮〇 5M DTT(Sigma) ; (c)蛋白酶抑制劑混合物（looox) : 5毫克 leupeptin，10毫克苯甲脒，40毫克bacitracin及5毫克大 豆胰蛋白酶抑制劑/毫升DMSO及液份儲存於_2〇。(： ；（d)250 μΜ人升糖素（peninsuia) ·· 〇 5毫克小瓶溶解於575微升 0· 1N乙酸（1微升於非特異性結合檢定分析獲得1 μΜ終濃 度）及以整份儲存於-20 °C，·（e)檢定分析緩衝液·· 20 mMThe reagents were prepared as follows: (a) Preparation of fresh 1M phenanthroline (Aldrich) (198.2 mg / ml ethanol); (b) Preparation of fresh 05M DTT (Sigma); (c) Protease inhibitor mixture (looox): 5 Mg of leupeptin, 10 mg of benzamidine, 40 mg of bacitracin, and 5 mg of soy trypsin inhibitor / ml of DMSO and the aliquots were stored at -20. (:; (D) 250 μM human glycinin (peninsuia) ·················································· The microcapsules were dissolved in 575 µl · 0.1N acetic acid (1 µl in non-specific binding assay to obtain a final concentration of 1 µM). Store at -20 ° C, (e) Assay Buffer, 20 mM

Tris(pH 7.8)，1 mM DTT 及 3 mM 鄰菲繞琳；（f)含 〇 ι % BSA之檢定分析緩衝液（僅稀釋標記；檢定分析終濃度〇 〇1 %): 10微升10% BSA(加熱失活化）及99〇微升檢定分析 _____ - 198 - 本紙張尺度適用中賴家標準（CNS ) A4規格（21GX297公釐)~-----*- (請先閱讀背面之注意事項再填寫本頁} 擎裝· 520362 A7 B7 五、發明説明（196 ) 緩衝液；（g)125I-升糖素（NEN，受體級，2200 Ci/毫莫耳） :於含B S A之檢定分析緩衝液（檢定分析中終濃度約爲 5ΟρΜ)稀釋至 50,000 cpm/25 微升。 收獲CHO/hGLUR細胞供檢定分析 1. 由融合燒瓶移出培養基然後以PBS(不含鈣，鎂）及不含 酶之解離流體（Specialty Media, Inc.)清洗一次。 2. 添加10毫升不含酶之解離流體及於37 °C維持約4分鐘。 3 .溫和敲擊細胞，研製，取出液分供計算及離心機於1000 rpm離心5分鐘至殘餘物。 4.以75 000細胞/100微升再懸浮丸粒於檢定分析緩衝液。 CHO/hGLUR細胞之膜製品用於相同檢定分析容積替代 全細胞。膜製品之終蛋白質濃度係以每批基準測定。 檢定分析 升糖素結合抑制測定可經由測量於式I化合物存在下於 125I-升糖素結合下降進行。反應劑之組合如下： 化合物/媒介 250 μΜ升糖素 125Ι-升糖素 CHO/hGLUR 細胞 全邵結合 -/5微升 — 25微升 100微升 +化合物 5微升/— — 25微升 100微升 非特異性結合 -/5微升 1微升 25微升 100微升 經滴部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 混合物於22 °C於275 rpm振搖機上培育60分鐘。混合物使 用Innotech收獲機或Tomtec收獲機於預先浸泡（0.5 %聚乙 基亞胺（PEI))GF/C濾墊過濾，使用冰冷20mM Tris緩衝液 _- 199-_ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 520362 A7 -------- B7 五、發明説明（197 ) (pH 7.8)洗四次。濾墊之放射活性係藉珈侷閃爍計數器測定。 (請先閱讀背面之注意事項再填寫本頁) 如此，本發明化合物也顯示可抑制升糖素結合至升糖素 受體。 環氧化酶活性檢定分析 人單核細胞白血病細胞系THP- 1，藉暴露於佛爾醇酯區 別出僅表現COX-1 ;人骨肉瘤細胞系i43B主要表現COX-2 。THP-1細胞例行於補充10 % fbs之RPMI完全培養基培 養，人類骨肉瘤細胞（HOSC)於補充1〇 %胎牛血清（MEM-10 % FBS)之最低必須培養基培養；全部細胞培育皆於37 °C於 5 %二氧化碳之濕化環境進行。 COX-1檢定分析 經濟部中央標準局員工消費合作社印製 準備COX-1檢定分析時，ΤΗΡ·1細胞生長至融合，*** 1 : 3至含2 % FBS及10mM佛耳醇12 -肉豆蔻酸酯13 -乙酸 酯（TPA)之RPMI，及於振搖機培育48小時預防附接。細胞 經造粒及再懸浮於含漢克氏緩衝鹽水（HBS)濃度爲2.5 X 106細胞/毫升及以密度5 X 105細胞/毫升接種於96孔培養 平板。試驗化合物於HBS稀釋及添加至所需終濃度及細胞 又培育4小時。花生四烯酸添加至終濃度3 0 mM，細胞於 3 7 °C培育20分鐘及如下述測定酶活性。 C0X-2檢定分析 欲進行C0X-2檢定分析，次融合HOSC經胰蛋白酶處理 及以3 X 1〇6細胞/毫升再懸浮於含1塵克人IL-lb/毫升之 MEM-FBS，以3 X 104細胞/孔密度接種於96孔組織培養 平板，於振搖機培育1小時而均勻分布細胞，接著又進行2 _____-200- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 ----—_— B7 五、發明説明（198 ) 小時靜悲培Θ使其附著。培養基更換成MEM含2 〇/。 FBS(MEM-2 % FBS)& i塵克人IL_lb/毫升，及細胞培育 18-22小時。以19〇毫升MEM更換培養基後，1〇毫升於 HBS稀釋之試驗化合物經添加而達成所需濃度及細胞培育 4小時。移出上清液及更換含3〇mM花生四烯酸之mem， 細胞於37 °C培育20分鐘及如下式測定酶活性。 測量COX活性 於與花生四烯酸培育後，反應藉加入1N鹽酸中止，接著 以1N氫氧化鈉中和及離心來使細胞碎屑形成丸粒。於 HOSC及THP-1細胞上清液之環氧化酶活性係使用市售 ELISA(Ne〇gen#404110)測量 PGe2 濃度測定。pGE2標準曲 線用於校準’市售COX-1及COX-2抑制劑包含做爲標準對 照品。 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁} 如此，本發明化合物或其醫藥組成物可用於預防及治療 類風濕性關節炎，巴吉特氏病，鬆骨病，多發性骨體瘤， 葡萄膜炎’急性及慢性骨髓原性白血病，胰臟β細胞破壞， 骨關節炎，類風濕性脊椎炎，痛風性關節炎，發炎性腸病 ’成人呼吸窘迫症候群（ARDS)，乾癖，柯恩氏病，過敏性 鼻炎’潰瘍性結腸炎，無防衛性過敏，接觸性皮炎，氣喘 ’肌肉退化’惡病質’萊特氏症候群，第I型及第Η型糖 尿病，骨質吸收病，移植物對寄主反應，缺血性再灌流傷 害，動脈粥瘤硬化，腦創傷，阿茲海默氏病，中風，心肌 梗塞，多發性硬化，腦癔，敗血病，敗血性休克，中毒性 休克症候群，發燒及感染引起肌痛。HIV-1 ，HIV-2 ， ___________-201 本紙張尺度適用中國國家標準（CNS ) Α4規格（210x197公餐） 經濟部中央標準局員工消費合作社印製 520362 A7 -----B7__ 五、發明説明（199 ) 、-—Tris (pH 7.8), 1 mM DTT and 3 mM orthophenanthrene; (f) assay assay buffer containing 〇 ％% BSA (only dilution label; final assay assay concentration of 0.01%): 10 microliters 10% BSA (heat deactivation) and analysis of 99 microliters _____-198-This paper size is applicable to CNS A4 specification (21GX297 mm) ~ ----- *-(Please read the back first Please note this page before filling in this page} Engine installation · 520362 A7 B7 V. Description of the invention (196) Buffer solution; (g) 125I-glucagon (NEN, receptor grade, 2200 Ci / mmol): Included in BSA The assay assay buffer (final concentration in the assay is approximately 50 ρΜ) is diluted to 50,000 cpm / 25 microliters. CHO / hGLUR cells are harvested for assay analysis. 1. Remove the culture medium from the fusion flask and use PBS (without calcium and magnesium) and Wash the enzyme-free dissociation fluid (Specialty Media, Inc.) once. 2. Add 10 ml of enzyme-free dissociation fluid and maintain it at 37 ° C for about 4 minutes. 3. Gently tap the cells, develop, and remove the liquid for supply. Calculate and centrifuge at 1000 rpm for 5 minutes to the residue. 4. Resuspend pellet at 75 000 cells / 100 μl in assay assay buffer The membrane preparation of CHO / hGLUR cells is used to replace whole cells with the same assay volume. The final protein concentration of the membrane product is determined on a per-batch basis. The assay analysis of the glucagon binding inhibition assay can be measured in the presence of a compound of formula I at 125I -Glycein binding declines. The combination of reactants is as follows: Compound / vehicle 250 μM glycin 125 125-glucagon CHO / hGLUR Full cell binding-5 µl-25 µl 100 µl + compound 5 µ Liters / —25 microliters 100 microliters of non-specific binding-/ 5 microliters 1 microliter 25 microliters 100 microliters Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Distillation (Please read the precautions on the back before filling in this Page) The mixture was incubated on a shaker at 275 rpm for 60 minutes at 22 ° C. The mixture was filtered using an Innotech harvester or Tomtec harvester in a pre-soaked (0.5% polyethylimine (PEI)) GF / C filter pad, using Ice-cold 20mM Tris buffer _- 199-_ This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) 520362 A7 -------- B7 V. Description of the invention (197) (pH 7.8) Wash four times. The radioactivity of the filter pad is borrowed Measuring scintillation counter. (Read Notes on the back and then fill the page) As such, compounds of the present invention is also shown to inhibit glucagon binding to the glucagon receptor. Cyclooxygenase activity assay analysis The human mononuclear leukemia cell line THP-1 showed only COX-1 by exposure to phoritol esters; the human osteosarcoma cell line i43B mainly showed COX-2. THP-1 cells are routinely cultured in RPMI complete medium supplemented with 10% fbs, and human osteosarcoma cells (HOSC) are cultured in the minimum necessary medium supplemented with 10% fetal bovine serum (MEM-10% FBS); all cell cultures are performed in 37 ° C in a humidified environment with 5% carbon dioxide. COX-1 assay analysis When printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs to prepare for the COX-1 assay, TP · 1 cells grow to confluence and divide 1: 3 to contain 2% FBS and 10 mM phorol 12-myristic acid Esters 13-acetate (TPA) RPMI, and incubated for 48 hours on a shaker to prevent attachment. Cells were pelleted and resuspended in Hank's buffered saline (HBS) at a concentration of 2.5 X 106 cells / ml and seeded at a density of 5 X 105 cells / ml in 96-well culture plates. Test compounds were diluted in HBS and added to the desired final concentration and cells were incubated for an additional 4 hours. Arachidonic acid was added to a final concentration of 30 mM, and the cells were incubated at 37 ° C for 20 minutes and the enzyme activity was determined as described below. COX-2 assay For COX-2 assay, the fusion HOSC was trypsinized and resuspended at 3 X 106 cells / ml in MEM-FBS containing 1 g of human IL-lb / ml. X 104 cells / well density were seeded on a 96-well tissue culture plate, incubated for 1 hour on a shaker to uniformly distribute the cells, and then performed 2 _____- 200- This paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) ) 520362 A7 ----—_— B7 V. Description of the invention (198) Hours of quiet grief Θ make it adhere. The medium was changed to MEM containing 20 /. FBS (MEM-2% FBS) & i g human IL-lb / ml, and cell incubation for 18-22 hours. After changing the medium with 190 ml of MEM, 10 ml of the test compound diluted in HBS was added to achieve the required concentration and the cells were incubated for 4 hours. The supernatant was removed and the mem containing 30 mM arachidonic acid was replaced. The cells were incubated at 37 ° C for 20 minutes and the enzyme activity was determined as follows. Measurement of COX activity After incubation with arachidonic acid, the reaction was stopped by adding 1N hydrochloric acid, followed by neutralization with 1N sodium hydroxide and centrifugation to pelletize the cell debris. The cyclooxygenase activity in the supernatant of HOSC and THP-1 cells was determined by measuring the PGe2 concentration using a commercially available ELISA (Neogen # 404110). The pGE2 standard curve is used to calibrate ‘commercially available COX-1 and COX-2 inhibitors included as a standard reference. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page). In this way, the compound of the present invention or its pharmaceutical composition can be used for the prevention and treatment of rheumatoid arthritis, Baget ’s disease, Osteoporosis, multiple osteoma, uveitis 'acute and chronic myelogenous leukemia, destruction of pancreatic beta cells, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease' adult breathing Distress Syndrome (ARDS), dry addiction, Cohen's disease, allergic rhinitis, ulcerative colitis, non-defensive allergies, contact dermatitis, asthma 'muscle degeneration' cachexia 'Wright's syndrome, types I and Η Diabetes, bone resorption disease, graft response to host, ischemic reperfusion injury, atherosclerosis, brain trauma, Alzheimer's disease, stroke, myocardial infarction, multiple sclerosis, cerebral palpitations, sepsis, Septic shock, toxic shock syndrome, myalgia caused by fever and infection. HIV-1, HIV-2, ___________- 201 This paper size applies to China National Standard (CNS) Α4 specifications 210x197 male meal) Ministry of Economic Affairs Bureau of Standards employees consumer cooperatives printed 520362 A7 ----- B7__ V. Description (199) invention -

HiV-3，細胞巨病毒（CMV)，流行性感冒病毒，腺病毒，疱 疹病毒（包含HSV_1，HSV_2)，及帶狀疱疹，全部皆對TNf α ’及/或IL- 1抑制或升糖素拮抗作用敏感，也受本發明化 合物及方法之正面影響。 本發明化合物也具有止痛性故可用於治療疼痛病症，例 如因IL-1過量造成痛覺過敏。本發明化合物也經由抑制人 類花生四烯酸/***素路徑之酶，包含環氧化酶而防止前 列腺素的產生（WO 90/〇3387，併述於此以供參考）。 因本發明化合物可降低TNF-α及IL-1濃度或抑制升糖素 結合至其受體，本發明化合物也可做爲研究阻斷此等作用 相關生理的研究工具。 本發明方法包括投予有效劑量之本發明化合物，其醫藥 可接受性鹽，或其醫藥組成物給需要降低TNF-a，IL-1， IL-6及/或IL-8濃度及/或降低血漿葡萄糖濃度之個體（亦即 動物，較佳哺乳類，最佳人類）及/或患有下列疾病之個體 :類風濕性關節炎，巴吉特氏病，鬆骨病，多發性骨髓瘤 ’葡萄膜炎，急性及慢性骨髓原性白血病，胰臟β細胞破壞 ’骨關節炎，類風濕性脊椎炎，痛風性關節炎，發炎性腸 病’成人呼吸窘迫症候群（ARDS)，乾癬，柯恩氏病，過敏 性鼻炎’潰瘍性結腸炎，無防衛性過敏，接觸性皮炎，氣 喘’肌肉退化，惡病質，萊特氏症候群，第I型及第U型 糖尿病，骨質吸收病，移植物對寄主反應，缺血性再灌流 傷害’動脈粥瘤硬化，腦創傷，阿茲海默氏病，中風，心 肌梗塞’多發性硬化’腦癔，敗血病，敗血性休克，中毒 ______- 9Ω9 . 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） --------I.衣-------、玎------· (請先閱讀背面之注意事項再填寫本頁} A7 B7 經濟部中央標準局員工消費合作社印製 520362HiV-3, cytomegalovirus (CMV), influenza virus, adenovirus, herpes virus (including HSV_1, HSV_2), and shingles, all of which inhibit TNf α 'and / or IL-1 or glucagon Antagonism is sensitive and also positively affected by the compounds and methods of the invention. The compounds of the present invention are also analgesic and can be used to treat painful conditions, such as hyperalgesia caused by excessive IL-1. The compounds of the present invention also prevent prostaglandin production via enzymes that inhibit the human arachidonic acid / prostaglandin pathway, including cyclooxygenase (WO 90 / 〇3387, which is incorporated herein by reference). Since the compounds of the present invention can reduce the concentrations of TNF-α and IL-1 or inhibit the binding of glucagon to its receptors, the compounds of the present invention can also be used as research tools to study the physiological effects of blocking these effects. The method of the present invention comprises administering an effective dose of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof to a patient who needs to reduce the concentration and / or decrease of TNF-a, IL-1, IL-6 and / or IL-8. Plasma glucose concentrations in individuals (ie animals, preferably mammals, best humans) and / or individuals with the following diseases: rheumatoid arthritis, Baget's disease, osteoporosis, multiple myeloma 'Grape Meningitis, acute and chronic myelogenous leukemia, pancreatic beta cell destruction 'osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease' adult respiratory distress syndrome (ARDS), psoriasis, Cohen's Disease, allergic rhinitis, ulcerative colitis, non-defensive allergies, contact dermatitis, asthma, muscle degeneration, cachexia, Wright syndrome, type I and type U diabetes, bone resorption disease, graft response to host, Ischemic reperfusion injury 'atherosclerosis, brain trauma, Alzheimer's disease, stroke, myocardial infarction' multiple sclerosis' brain palpitations, sepsis, septic shock, poisoning ______- 9Ω9. This paper ruler Applicable to China National Standard (CNS) A4 specification (210X297 mm) -------- I. Clothing -------, 玎 ------ · (Please read the precautions on the back first Refill this page} A7 B7 Printed by the Staff Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs 520362

五、發明説明（2QQ 性休克症候群，發燒及感㈣起肌痛，或該個體受献] HIV-2，HIV·3，細胞巨病毒（CMv)，流行性感冒病毒 ，腺病毒，祕病毒（包含刪]，HsV-2)，或帶狀痕珍 感染。 另一態樣中，本發明包括使用本發明化合物，或立醫藥 可接受性鹽，用於製造急性或慢性ΤΝρ_α，Κ_ΐβ，^^及 /或IL-8媒介病態之治療用藥，包含前述者。又，本發明化 ^物可用於製造止痛藥物及治療疼痛$纟，如_覺過敏用 2。本發明化合物也可用於製造經由抑制人類花生四烯酸/ 岫列腺素路极之酶而防止***素產生用藥。 又另一態樣中，本發明提供一種醫藥組成物，包括有效 IL-Ιβ，IL_6&^tlL-8降低用量及/或有效血漿葡 萄糖濃度下降用量之本發明化合物及醫藥可接受性載劑或 稀釋劑，及若有所需其它活性成份。本發明化合物可藉任 何適田路；L，車父佳適合此種路徑之醫藥組成物劑型，及以 可有政治療用劑量投藥。停止疾病相關組織傷害之進展或 防止、、且織知害所需本發明化合物之治療有效劑量亦由業界 人士使用標準方法確定。 供治療TNF-a，IL-Ιβ，IL-6及/或^-8媒介病及/或高血 糖，本發明化合物可經口、腸外、藉吸入噴霧、直腸或局 邵以含有習知醫藥可接受性载劑、佐劑及媒劑之單位劑量 配方投藥。此處使用腸外一詞包含皮下、靜脈、肌肉、胸 骨内、輸注技術或腹内投藥。 使用本發明化合物及/或本發明組成物治療TNF-a，IL-1 (请先閱讀背面之注意事項再填寫本頁)V. Description of the Invention (2QQ Shock Syndrome, Fever and Sensation of Myalgia, or Donation of the Individual] HIV-2, HIV · 3, Cytomegalovirus (CMv), Influenza Virus, Adenovirus, Mysterious Virus ( Including deletion], HsV-2), or banded trace infection. In another aspect, the present invention includes the use of a compound of the present invention or a pharmaceutically acceptable salt for the manufacture of acute or chronic TNρ_α, Κ_ΐβ, ^^ And / or IL-8-mediated pathological treatment, including the foregoing. In addition, the compounds of the present invention can be used in the manufacture of analgesic drugs and the treatment of pain, such as anaphylaxis 2. The compounds of the present invention can also be used to manufacture via inhibition Human arachidonic acid / prostaglandin pathway enzymes are used to prevent prostaglandin production. In yet another aspect, the present invention provides a medicinal composition comprising effective IL-Ιβ, IL-6 & tltl-8 And / or effective plasma glucose concentration reduction of the compound of the present invention and a pharmaceutically acceptable carrier or diluent, and if other active ingredients are required. The compound of the present invention can be borrowed from any Shida Road; L, Che Fujia is suitable for this Path of Medicine The dosage form of the product and administration at a therapeutically effective dose. The therapeutically effective dose of the compound of the present invention required to stop the progression or prevention of disease-related tissue injury and to prevent harm is also determined by the industry using standard methods. For the treatment of TNF -a, IL-1β, IL-6 and / or ^ -8 vector disease and / or hyperglycemia, the compounds of the present invention can be administered orally, parenterally, by inhalation spray, rectum or locally to contain conventional medical acceptability Unit-dose formulations for vehicles, adjuvants and vehicles. The term parenteral is used herein to include subcutaneous, intravenous, intramuscular, intrasternal, infusion techniques, or intraperitoneal administration. Treatment with a compound of the invention and / or a composition of the invention TNF-a, IL-1 (Please read the notes on the back before filling this page)

520362 A7 B7 經濟部中央標準局員工消費合作社印製 五、發明説明（2Q1 IL-6及IL-8媒介病及/或高血糖 闵鲁而宗，勺入、、 。又用法用量係基於多種 因素而疋，包含疾病類型，病人年 |•主、p 产卜主抑4 ^ 體重、性別、醫療 h況，病情嚴重程度，投藥路徑 阳、土面旦-r去* W用特疋化合物。如此 ，用法用f可有廣泛變化，但可使 滅丨旦的Λ n】古土 率万法例行決定。 釗里約〇·〇1笔克至30毫克/千克體重 in古m古 ^ 里/曰，較佳0.1毫克至 10笔克/千克，更佳約〇·25毫克至i 揭示之各種方法。 克/千克可用於此處 本發明之醫藥活性化合物可根據習知製藥方法生產而生 產供投予病人，包含人類及其它喷乳類用藥劑。 :口服投藥，醫藥組成物可呈例如膠囊、錠劑、懸浮液 劑或屣劑。醫樂組成物較佳製造成含特定量活性成份之單 位劑型。例如，含有活性成份約i至 佳 至500毫克，更佳約5至15〇毫克。 兄杈1 ，] A A 口叫曰1厂 人大員或其它哺乳類之適 语母日劑Ϊ可依病人情況及其它因素 例行方法決定。 活性成份可呈含適當載劑如鹽水，葡萄糖或水之組成物 注射投藥。每日腸外用量爲約〇 1至 ^ ^ .1 土約3〇耄克/千克總體重 ，較佳約0」至約10毫克/千克，更佳約〇 25毫克至i毫 /千克。 注射劑如無菌注射水或由懸浮液劑可根據已知方法使用 通當分散或濕潤劑或懸浮劑配方。無菌注射劑亦可爲無菌 注射落液劑或懸敎劑於無毒腸外可接受性稀釋劑或溶劑 ，例如於1，3-丁二醇之溶液。#用的可接受性媒劑及溶劑 包括水，林格氏液，及等張氯化鈉溶液。此外，無菌固定 本紙張尺度適用中國國家標準（CNS ) A4規格 (請先閱讀背面之注意事項再填寫本頁)520362 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the invention (2Q1 IL-6 and IL-8 vector disease and / or hyperglycemia Min Lu Erzong, scooped into, and. The dosage is based on a variety of factors And 疋, including the type of disease, the patient's year | • main, p, 产, 抑 4 ^ weight, sex, medical status, the severity of the disease, the route of administration of Yang, Tumen Dan -r to * W with special compounds. The usage of f can be widely changed, but it can be determined routinely by the law of the ancient soil rate. Zhaoli about 0.01 gram to 30 mg / kg body weight in ancient m ancient ^ li / That is, preferably from 0.1 mg to 10 g / kg, more preferably from about 0.25 mg to i. Various methods disclosed. G / kg The pharmaceutically active compound that can be used herein The present invention can be produced by conventional pharmaceutical methods and produced It is administered to patients, including human and other milk-spraying agents.: For oral administration, the pharmaceutical composition can be in the form of capsules, tablets, suspensions, or elixirs. The medical composition is preferably manufactured to contain a specific amount of active ingredients. A unit dosage form. For example, contains about i to about 5 00 mg, more preferably about 5 to 150 mg. Brother1,] AA mouth is called a suitable mother-to-day dosage of the 1st factory people's congress or other mammals. It can be determined routinely according to the patient's situation and other factors. The active ingredient can be It is administered by injection with a composition containing an appropriate carrier such as saline, dextrose or water. The daily parenteral dosage is about 0.01 to ^ ^ .1 about 30 g / kg of total weight, preferably about 0 "to about 10 Mg / kg, more preferably about 025 mg to 1 m / kg. Injectables such as sterile injectable water or suspensions can be formulated according to known methods with Tong Dang dispersing or wetting agents or suspensions. Sterile injections can also be sterile injections Liquids or suspensions are in non-toxic parenterally acceptable diluents or solvents, such as solutions in 1,3-butanediol. Acceptable vehicles and solvents include water, Ringer's solution, and Isotonic sodium chloride solution. In addition, the size of this paper is aseptically fixed to Chinese National Standard (CNS) A4 (please read the precautions on the back before filling this page)

、1T ,· 204-1T 204-

、發明説明（2〇2 ) A7 B7 油白7用做落劑或懸浮介質。供此目的，可使用任何品牌固 油’包含合成一-或二甘油酯。此外，脂肪酸如油酸可用 於製備注射劑。 ,直腸投藥用栓劑可經由藥物與適當非刺激性賦形劑混合 製備’該賦形劑如可可脂及聚乙二醇類其於常溫爲固體但 毛直腸溫度爲液體因此可於直腸内溶化並釋出藥物。 本發明化合物之適當局部活性成份劑量爲0.1毫克至150 毫克，每日投藥1至4次，較佳1或2次。供局部投藥用， 活性成份包括0.00 1。/。至10 % w/w，例如1。/。至2 %之重 量比配方，但包括高達1〇 % w/w，但較佳不超過5 % w/w ，及更佳0.1 %至1 %配方。 適合局部投藥用配方包含適合滲透通過皮膚之液體或半 液體直徑（例如油膏劑，乳液劑，軟膏劑，乳膏劑或硬膏劑 )及適合投予眼、耳或鼻之滴劑。 供投藥用，本發明化合物通常合併一種或多種適合指示 投藥路徑之佐劑。化合物可與乳糖，蔗糖，澱粉，烷酸之 纖維素酯，硬脂酸，滑石，硬脂酸鎂，氧化鎂，磷酸及硫 酸之鈉及鈣鹽，***膠，明膠，藻蛋白酸鈉，聚乙晞基 吡咯啶，及/或聚乙烯醇混合並打錠及包膠供以習知方式投 藥。另外，本發明化合物可溶解於鹽水，水，聚乙二醇， 丙二醇’乙醇’玉米油，花生油，棉籽油，芝麻油，西黃 蓍膠及多種缓衝液。其它佐劑及投藥模式爲製藥業界眾所 周知。載劑或稀釋劑包含延遲物質，如單獨一硬脂酸甘油 酯或二硬脂酸甘油酯或混合蠟，或其它業界眾所周知材料。 205- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） ---------•裝-- (請先閱讀背面之注意事項再填寫本頁}Description of the invention (202) A7 B7 Oil White 7 is used as a dropper or suspension medium. For this purpose, any brand of solid oil ' may be used including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid can be used in the preparation of injectables. Rectal pharmaceutical suppositories can be prepared by mixing the drug with an appropriate non-irritating excipient.The excipients such as cocoa butter and polyethylene glycols are solid at normal temperature but the hair rectal temperature is liquid so they can be dissolved in the rectum and Release the drug. A suitable topical active ingredient dose of a compound of the present invention is from 0.1 mg to 150 mg, administered 1 to 4 times a day, preferably 1 or 2 times. For topical administration, active ingredients include 0.001. /. Up to 10% w / w, for example 1. /. To 2% weight ratio formula, but including up to 10% w / w, but preferably not more than 5% w / w, and more preferably 0.1% to 1% formula. Formulations suitable for topical administration include liquid or semi-liquid diameters suitable for penetration through the skin (such as ointments, emulsions, ointments, creams or plasters) and drops suitable for administration to the eyes, ears or nose. For administration, the compounds of the present invention typically incorporate one or more adjuvants suitable for indicating the route of administration. Compounds are compatible with lactose, sucrose, starch, cellulose esters of alkanoic acid, stearic acid, talc, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric acid and sulfuric acid, gum arabic, gelatin, sodium alginate, Acetylpyrrolidine and / or polyvinyl alcohol are mixed and tabletted and encapsulated for administration in a conventional manner. In addition, the compound of the present invention can be dissolved in saline, water, polyethylene glycol, propylene glycol 'ethanol' corn oil, peanut oil, cottonseed oil, sesame oil, tragacanth gum and various buffer solutions. Other adjuvants and modes of administration are well known in the pharmaceutical industry. The carrier or diluent contains a delaying substance, such as glyceryl monostearate or glyceryl distearate or a mixed wax, or other materials well known in the industry. 205- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210X297mm) --------- • Installation-(Please read the precautions on the back before filling this page}

、1T ί·^ 經滴部中央標準局員工消費合作社印製 520362 A7 五、發明説明（2〇3 醫^組成物可製造成固體劑型（包含粒劑，散劑，或拾劑 )=展㈣j型⑽D溶液劑，懸浮液劑或乳液劑）。醫藥組成 —y接又白知醫藥作業例如滅菌及/或含有習知佐劑如保 賊劑，安定劑，濕潤劑，乳化劑及緩衝劑等。 口服投藥用固體劑型包含膠囊劑，錠劑，丸劑，散劑及 粒劑。此種固體劑型中，活性化合物可混合至少一種惰性 稀釋劑如薦糖，乳糖或殿粉。此種劑型如同正常實務，亦 包括惰性稀釋劑以外之其它物質，例如潤滑劑如硬脂酸鎂 以知囊劑，錠劑及丸劑爲例，劑型亦包括緩衝劑。錠劑 及丸劑可額外製備附有腸衣。 口服投藥用之液體劑型包含醫藥可接受性乳液劑，溶液 劑，懸浮液劑，糖漿劑，及_含有業界常用之惰性稀釋 劑如水。此等組成物也包括佐劑如濕潤劑，甜味劑，矯味 劑及香味劑。 本發明化合物具有一或多個非對稱碳原子，因此可呈光 學異構物形式及外消旋或非外消旋混合物形式存在。光學 異構物可經由根據習知方法光學分割外消旋混合物獲得， 例2生產非對應異構物鹽，以旋光性酸或鹼處理。適當酸 之範例爲酒石酸，二乙醯基酒石酸，二苯甲醯基酒石酸， 二甲苯甲醯基酒石酸，及樟腦磺酸，然後經由結晶分離非 對應兴構物混合物。接著由鹽釋放出旋光性鹼。光學異構 物之不同分離方法包括使用光學活性層析柱其經最適當選 擇而可獲得對應異構物之最大分離效果。又另一種方法包 括經由本發明化合物與光學純質酸呈活性形式或光學純質 ··裝-- (請先閱讀背面之注意事項再填寫本頁) 訂 1· 經濟部中央標準局員工消費合作社印製， 1T ί · ^ Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Labor 520362 A7 V. Description of the invention (203 medical composition can be made into solid dosage forms (including granules, powders, or pick-ups) = Zhanji type (D solution, suspension or emulsion). Medicinal composition — It is known that pharmaceutical operations such as sterilization and / or contain conventional adjuvants such as thieves, stabilizers, wetting agents, emulsifiers and buffers. Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In this solid dosage form, the active compound may be mixed with at least one inert diluent such as saccharose, lactose or gluten. This dosage form, like normal practice, also includes substances other than inert diluents, such as lubricants such as magnesium stearate. Taking capsules, tablets, and pills as examples, the dosage form also includes buffering agents. Lozenges and pills can be additionally prepared with casing. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and inert diluents such as water commonly used in the industry. These compositions also include adjuvants such as wetting agents, sweeteners, flavoring agents, and flavoring agents. The compounds of the invention have one or more asymmetric carbon atoms and can therefore exist as optical isomers and as racemic or non-racemic mixtures. Optical isomers can be obtained by optically separating racemic mixtures according to conventional methods. Example 2 produces non-corresponding isomer salts and is treated with optically active acids or bases. Examples of suitable acids are tartaric acid, diethylfluorenyl tartaric acid, dibenzyl tartaric acid, xylylene tartaric acid, and camphorsulfonic acid, and then the non-corresponding mixture of compounds is separated by crystallization. The optically active base is then released from the salt. Different methods of separation of optical isomers include the use of optically active chromatography columns, which are most appropriately selected to obtain the maximum separation of the corresponding isomers. Yet another method involves the active form or optical purity of the compound and optically pure acid via the compound of the present invention. (Please read the precautions on the back before filling out this page) Order 1 · Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Print

520362 經濟部中央標準局員工消費合作社印製 、發明説明（204 ) =氰酸@旨反應合成共價非對應異構物分子。合成的非對應 兴構物可藉習知手段分離，例如層析，蒸餘，肖晶或昇華 ，然後水解釋放成對應異構純質化合物。本發明之旋光性 化合物同理可使用活性起始物料獲得。此等異構物可呈自 由怨故’自由態驗，自旨或鹽形式。 本發明化a物可主衍生自有機或無機酸之鹽形式使用。 鹽包含但非限於下列：乙酸鹽，己二酸鹽，藻蛋白酸鹽， 檸檬酸鹽，天冬酸鹽，苯甲酸鹽，苯磺酸鹽，硫酸氫鹽， 丁酸鹽’樟腦酸鹽’樟腦磺酸鹽，二葡萄酸鹽，環戊烷丙 酸鹽’十一基硫酸鹽’乙燒續酸鹽，葡萄糖庚酸鹽，甘油 基蹲酸鹽，半硫酸鹽，庚酸鹽，己酸鹽，反丁烯二酸鹽， 氫氯酸鹽’氫溴酸鹽，氫破酸鹽，2-輕乙烷續酸鹽，乳酸 鹽’順丁烯二酸鹽，甲烷磺酸鹽，菸鹼酸鹽，2_莕磺酸鹽 ’草酸鹽，棕櫚酸鹽，果膠酸鹽，過硫酸鹽，八苯基丙酸 鹽’苦味酸鹽，特戊酸鹽，丙酸鹽，丁二酸鹽，酒石酸鹽 ，硫氰酸鹽，甲苯磺酸鹽，甲烷磺酸鹽，及十二酸鹽。又 ，驗性含氮基可以下列化學劑第四化，例如低碳烷基鹵化 物如甲基，乙基，丙基及丁基氯，溴及碘；二烷基硫酸酯 例如二甲基，二乙基，二丁基及二戊基硫酸酯，長鏈鹵化 物如癸基，月桂基，肉豆蔻基及硬脂基氯、溴及碘，芳烷 基鹵化物例如苄基及苯乙基溴，及其它。如此獲得水或油 溶性或分散性產物。 可用於形成醫藥可接受性酸加成鹽之酸範例包含無機酸 如鹽酸，硫酸及磷酸及有機酸如草酸，順丁烯二酸，丁二 (請先閱讀背面之注意事項再填寫本頁} >裝·520362 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs, and Description of Invention (204) = Cyanate @ Purpose Reaction to synthesize covalent non-corresponding isomer molecules. Synthetic non-corresponding compounds can be separated by conventional means, such as chromatography, distillation, Xiaojing or sublimation, and then hydrolyzed to release the corresponding isomeric pure compounds. The optically active compounds of the present invention can be similarly obtained using active starting materials. These isomers can be in the form of free complaints, free intentions, or salt forms. The compounds of the present invention can be used mainly in the form of salts derived from organic or inorganic acids. Salts include but are not limited to the following: acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, hydrogen sulfate, butyrate'camphorate 'Camphor sulfonate, digluconate, cyclopentanepropionate' undecyl sulfate 'ethanoate, glucoheptanoate, glyceryl squatate, hemisulfate, heptanoate, hexane Acid salt, fumarate, hydrochloride 'hydrobromide, hydrochloride, 2-light ethanesalt, lactate' maleate, methanesulfonate, smoke Alkaline, 2'-sulfonate 'oxalate, palmitate, pectate, persulfate, octaphenylpropionate' picrate, pivalate, propionate, succinic acid Acid salt, tartrate, thiocyanate, tosylate, methane sulfonate, and dodecanoate. In addition, the experimental nitrogen-containing group can be quaternized with the following chemical agents, such as lower alkyl halides such as methyl, ethyl, propyl and butyl chloride, bromine and iodine; dialkyl sulfates such as dimethyl, Diethyl, dibutyl and dipentyl sulfate, long chain halides such as decyl, lauryl, myristyl and stearyl chloride, bromine and iodine, aralkyl halides such as benzyl and phenethyl Bromine, and others. This gives a water or oil soluble or dispersible product. Examples of acids that can be used to form pharmaceutically acceptable acid addition salts include inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid, and organic acids such as oxalic acid, maleic acid, and succinic acid (Please read the notes on the back before filling this page} > Outfit ·

、1T J· -207- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 520362 A7 B7 205 合物 同持間 五、發明説明（ 酸及檸檬酸。其它例包含與鹼金屬或鹼土金屬如鈉，鉀 药或鍰或與其它驗生成之鹽。 雖然本發明化合物可呈唯一活性藥劑投藥，但亦町與 種或多種本發明化合物或其它藥劑合併使用。當昱 投藥時，治療劑可調配成個別組成物而同時或於不 投藥，或治療劑可成單一組成物投藥。 W文僅供舉例説明本發明而決非意圖限制本發明於揭$ 的化合物。業界人士顯然易知之多種變化預期揭示於隨附 之申請專利範圍之界定之本發明之範圍及性質。 由丽文説明，業界人士容易確定本發明之要義特徵，可 未背離其精髓及範圍做出本發明之多種變化與修改而適合 多種用途及病情。 口 广请先閱讀背面之注意事項真填寫本買)、 1T J · -207- This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297mm) 520362 A7 B7 205 Compounds of the same kind 5. Description of invention (acid and citric acid. Other examples include Alkaline earth metals such as sodium, potassium or thorium or other test salts. Although the compound of the present invention can be administered as the sole active agent, it is also used in combination with one or more compounds of the present invention or other agents. When Yu is administered, treatment The agent can be formulated into individual compositions without or at the same time, or the therapeutic agent can be administered as a single composition. The text is only for illustration of the present invention and is not intended to limit the compounds disclosed in the present invention. It is obvious to those skilled in the art Various changes are expected to be disclosed in the scope and nature of the invention as defined in the scope of the accompanying patent application. As explained by Liwen, the industry can easily determine the essential features of the invention, and can make various changes to the invention without departing from its essence and scope. And modify it to suit a variety of uses and conditions. Guangkou, please read the precautions on the back to fill in this purchase)

-----IT ·· 經濟部中央標準局員工消費合作社印製 -208- 本紙張尺度適用中國國家標準（CMS ) Α4規格（210Χ297公釐） 公告秦 申請曰期 86. 12. 04 案 號 086118244 類 別 (以上各櫚由本局填註） A4 中文說明書替換頁(91年12月） 雪|專利説明書 520362 中 文 、翁！名稱 英 文 姓 名 國 籍 經取代之嘧啶化合物及含彼之醫藥組成物----- IT ·· Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs -208- This paper size applies to the Chinese National Standard (CMS) A4 specification (210 × 297 mm) Announcement Qin application date 86. 12. 04 Case number 086118244 Category (The above palms are filled by this bureau) A4 Chinese manual replacement page (December 91) Snow | Patent specification 520362 Chinese, Weng! Name English Name First Name Nationality Substituted pyrimidine compounds and pharmaceutical compositions containing them

SUBSTITUTED PYRIMIDINE COMPOUNDS AND PHARMACEUTICAL COMPOSITION COMPRISING SAME 1. 悠里克D·史伯爾 2. 麥克J.馬龍3. 納坦B.曼特羅 1.加拿大 2.3.均美國 -、發明 +創作 人 住、居所 1 ·美國科羅拉多州伯德市格蘭武德路2925號 2·美國科羅拉多州伯德市古伯瑞路6054H號 3·美國科羅拉多州萊夫瓦特市基尼路2538號 % 姓 名 (名稱了 美商安美基公司 Μ 國 籍 美國 三、申請人 美國加州千橡市德哈威蘭路1840號 湯瑪士·E ·渥克曼二世 本紙張尺度適财s s家襟準(CNS) Α4規格(2lG χ 297公羡)SUBSTITUTED PYRIMIDINE COMPOUNDS AND PHARMACEUTICAL COMPOSITION COMPRISING SAME 1. Uric D. Spar 2. Mike J. Malone 3. Nathan B. Mantero 1. Canada 2.3. All American-, Invention + Creator, Residence 1 2925 Granville Road, Bird, Colorado, U.S. 2 # 6054H, Guberi Road, Bird, Colorado, U.S. 3 # 2538, Gini Road, Lefwater, Colorado, U.S. %% Nationality US III. Applicant Thomas E. Walkman II, 1840 De Havilland Road, Thousand Oaks, California, USA Paper size suitable for wealth ss Family standard (CNS) Α4 size (2lG x 297 public envy)

Claims (1)

520362 8 8 8 8 A B c D 第086118244號專利申請案 中文申請專利範圍修正本(91年11月) 公告泰 1. 一種下式化合物 R2520362 8 8 8 8 A B c D Patent Application No. 086118244 Chinese Patent Application Amendment (November 91) Bulletin Thai 1. A compound of formula R2 或其醫藥可接受性鹽；其中 Ri為OH、自素、胺基、C3_8環烷基苯基、苄基、SH、 C 1 -6燒基、说症、嗎淋、六氫说淀、遠峻、p塞吩、莕基、 胺基- Cl -坑胺基、胺基- Ci-4坑基、二-(Ci_4)挺胺基（Ci-4) 烷胺基、Cid烷基二唑基、硫醯基-Cw烷胺基、 MeOr a pharmaceutically acceptable salt thereof; wherein Ri is OH, autogen, amine, C3_8 cycloalkylphenyl, benzyl, SH, C 1-6 alkyl, rheumatism, morphine, hexahydrochloride, far Jun, p-phene, fluorenyl, amine-Cl-pit amine, amine-Ci-4 pit, di- (Ci_4) amidinyl (Ci-4) alkylamino, Cid alkyldiazolyl , Thio-Cw alkylamino, Me MeMe H2N S02H2N S02 苯硫甲基、苯氧甲基、2-甲基-咪唑-4-基、嘧 啶、六氫吡畊-1-基、4-苯基-六氫吡畊-1-基、4-甲基-六氫吡畊-1-基、3-咪唑基丙胺基、2-(嗎啉-4-基）乙胺 基，2-(六氫吡啶基）乙胺基、2-(吡咯烷基）乙胺基、Phenylthiomethyl, phenoxymethyl, 2-methyl-imidazol-4-yl, pyrimidine, hexahydropyrim-1-yl, 4-phenyl-hexahydropyrim-1-yl, 4-methyl -Hexahydropyrimyl-1-yl, 3-imidazolylpropylamino, 2- (morpholin-4-yl) ethylamino, 2- (hexahydropyridyl) ethylamino, 2- (pyrrolidinyl) Ethylamino, 、、苯乙硫基、苯丙 nh2 硫基、2 -苯氧基乙硫基、2 -苯胺基乙硫基、爷基經二個 鹵素取代、苯基經一個OH、NH2、鹵素、OMe、CN、 本紙張尺度適用中國國家標準(CNS) A4規格(210 x 297公釐) 520362 A8 B8 C8 D8 申请專利範圍 Ci·4燒基、或二個鹵素或ph-(CH2)n-NH·所取代（其中 苯環上可經一或二個鹵素、C1 -4燒基甲氧基、胺基、 〇H或CF3取代，或—NH上的Η被Cu烷基取代，或 CH2上的Η被OH或Me取代）； η 為 〇 _ 4 ; R2 為 Η、OH、C1 或 〇me ;,, phenethylthio, phenylpropyl nh2 thio, 2-phenoxyethylthio, 2-anilinoethylthio, hexyl substituted with two halogens, phenyl with one OH, NH2, halogen, OMe, CN, This paper size applies to China National Standard (CNS) A4 specification (210 x 297 mm) 520362 A8 B8 C8 D8 Patent application scope Ci · 4 base, or two halogen or ph- (CH2) n-NH · Substitution (where the benzene ring may be substituted with one or two halogens, C1-4 alkyl, methoxy, amine, 0H or CF3, or-Η on NH is replaced by Cu alkyl, or Η on CH2 OH or Me substitution); η is 0-4; R2 is Η, OH, C1 or 0me; 裝 Rii為4 -氟苯基、未經取代之苯基、π比咬-4-基，及 R12 為 p 比1- 4 ·基。 2.如申請專利範圍第1項之化合物，其為： 5-(4_氟苯基）-2-(4-吡啶基）-4-(4_吡啶基）_嘧啶， 5-(4-氟苯基）-2-(2-甲基嘧唑-4-基）-4-(4-吡啶基）-嘧啶， 5-(4 -獻苯基）-4_(4-p比淀基）-2-(2-魂吩基）_p密淀’ 2-〇二乙基胺基乙基胺基）-5_(4_氟苯基）_4_(4·吡啶 基）-喊淀， 線Let Rii be 4-fluorophenyl, unsubstituted phenyl, π-ratio-4-yl, and R12 be p-ratio 1-4. 2. The compound according to item 1 of the patent application scope, which is: 5- (4-fluorophenyl) -2- (4-pyridyl) -4- (4-pyridyl) _pyrimidine, 5- (4- Fluorophenyl) -2- (2-methylpyrazol-4-yl) -4- (4-pyridyl) -pyrimidine, 5- (4-methylphenyl) -4_ (4-p ratio) -2- (2-Homophenyl) _p dense lake '2-〇diethylaminoethylamino) -5_ (4_fluorophenyl) _4_ (4 · pyridyl) -Houdian, line 2-(4-胺基丁基胺基）-5-(4-氟苯基）-4-(4-p比咬基）_喊淀， 2-(2,6-二氯苄基）-5-(4-氟苯基）-4-(4-吡啶基）-嘧啶， 2_(2,6·二氯苯基胺基）-5-(4-氟苯基吡啶基）-嘧啶， 2-(2,6-二甲基苯基胺基）-5-(4-氟苯基）-4-(4-吡啶基>嘧 淀， 5-(4-氟苯基）-2-(2-甲氧苯基胺基）-4-(4-吡啶基）-嘧啶， 5-(4 -氟苯基）-2-(4 -氟苯基胺基）-4-(4-^7比淀基密咬， 5-(4-氟苯基）-2-苯基硫甲基-4-(4-吡啶基）-嘧啶， 2_(2_(4·胺基苯基）乙基-胺基）-5_(4-氟苯基）-4-(4-吡啶 基）-喊淀， -2 - 本紙張尺度適用中國國家標準(CNS) A4規格(210 X 297公釐) 520362 ABCD 六、申請專利範圍 2_(2-(2-氯苯基）乙基-胺基）_5-(4-氟苯基）-4-(4-吡啶 基）-喊咬， 2-(2·(4_氯苯基）乙基-胺基）·5-(4_氟苯基）_4_(4-吡啶 基）-喃淀， 2_(2_(3-氯苯基）乙基-胺基）-5-(4_氟苯基）_4_(4·吡啶 基）-喊淀， 2-(2-(2，4-二氯苯基）乙基-胺基）-5-(4-氟琴基）_4-(4-外匕 淀基）-喃淀， 2·(2·(4-溪苯基）乙基-胺基）·5-(4_氣本基）·4-(4-ρ比淀 基）·喃咬， 5_(4_氟苯基）-2-(2-(2-甲氧苯基）乙基-胺基）_4_(4_吡啶 基）-喊淀， 5_(4·氟苯基）·2_(2_(3- Τ氧苯基）乙基-胺基）-4_(4-吡啶 基）-喊淀， 5-(4 -氟苯基）-2-((1-甲基-3_苯基丙基）-胺基）·4-(4_ρ比淀 基）-喊淀， 5-(4-氟苯基）-2-((4-苯基·丁基）-胺基）-4-(4-吡啶基）-嘧啶， 5-(4-氟苯基）-2-嗎啉基-4_(4-吡啶基）·嘧啶， 5-(4-氟苯基）-4-(4-吡啶基）_2_(2_吡咯啶基乙基胺基）- 口密淀， 5-(4_氣本基）-2-(2-嗎111林基乙基胺基）-4-(4-ρ比淀基）-喊淀’ 5-(4_氟苯基）-2-(2-六氫吡啶基乙基胺基）-4-(4_吡啶 基）-喊淀， 5-(4 -氟苯基）-2-(3-(2-^ρ各淀酮-1-基）丙基胺基）-4-(4- -3- 本紙張尺度適用中國國家標準(CNS) Α4規格(210X297公釐） 520362 A8 B8 C8 D8 六、申請專利範圍 叶匕淀基）-喊症， 5-(4-氟苯基）-2-(2-苯氧乙基）硫-6-(4-吡啶基）-4_羥-嘧 淀， 5-(4·氟苯基）-2-(2-苯基胺基乙基）硫-6·(4-吡啶基）-4·羥 -嘧啶， 2_(2_胺基乙基胺基）-5-(4-氟苯基）-4-(4-吡遠基）-嘧啶， 2-(3-胺基丙基胺基）-5-(4-氟苯基）-4-(4-吡啶基）-嘧啶， 2-(苄基胺基）-5-(4-氟苯基）-4-(4-吡啶基）_嘧啶， 5-(4_氟苯基）-2-(2-苯基乙基胺基）-4-(4-吡啶基）-嘧啶， 5_(4_氟苯基）-2-(Ν-甲基-Ν-(2_苯基乙基）-胺基）·4_(4·吡 淀基）-喃咬， 5-(4-氟苯基）-2-(2-羥·2-苯基-乙基）胺基-4-(4-吡啶基）-Ρ密淀， 5-(4-氟苯基）-2-(2_(4-羥苯基）乙基-胺基）-4_(4_吡啶 基）-喊咬， 5-(4-氟苯基）-2-(2_(4_氟苯基）乙基-胺基）_4-(4-说食 基）-續淀， 5-(4_氟苯基）-2-(2-(2-氟苯基）乙基-胺基）-4_(4 -π比淀 基嘧啶， 5-(4-氟苯基）-2-((3-苯基丙基）-胺基）-4-(4-吡啶基）-喊淀， 2-((2(S)-胺基-3-苯基丙基）-胺基）-5-(4_氟苯基）-4-(4-口比 啶基）-嘧啶， 5-(4-氟苯基）-2-(2-苯基胺基乙基胺基）-4-(4-吡啶基）-嘧啶， -4- 本紙張尺度適用中國國家標準(CNS) A4規格(210X297公釐)2- (4-Aminobutylamino) -5- (4-fluorophenyl) -4- (4-p specific octyl group) _Xiaodian, 2- (2,6-dichlorobenzyl)- 5- (4-fluorophenyl) -4- (4-pyridyl) -pyrimidine, 2_ (2,6 · dichlorophenylamino) -5- (4-fluorophenylpyridyl) -pyrimidine, 2 -(2,6-dimethylphenylamino) -5- (4-fluorophenyl) -4- (4-pyridyl > pyrimido, 5- (4-fluorophenyl) -2- ( 2-methoxyphenylamino) -4- (4-pyridyl) -pyrimidine, 5- (4-fluorophenyl) -2- (4-fluorophenylamino) -4- (4- ^ 7 Than Yendyl, 5- (4-fluorophenyl) -2-phenylthiomethyl-4- (4-pyridyl) -pyrimidine, 2- (2- (4-aminophenyl) ethyl-amine ) -5_ (4-fluorophenyl) -4- (4-pyridyl) -Yodo, -2-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 520362 ABCD Patent application scope 2_ (2- (2-chlorophenyl) ethyl-amino) _5- (4-fluorophenyl) -4- (4-pyridyl) -snake, 2- (2 · (4_ Chlorophenyl) ethyl-amino) · 5- (4_fluorophenyl) _4_ (4-pyridyl) -amino lake, 2_ (2_ (3-chlorophenyl) ethyl-amino) -5- (4_fluorophenyl) _4_ (4 · pyridyl) -Hyoto, 2- (2- (2,4-dichlorophenyl) ethyl-amine ) -5- (4-Fluorenyl) _4- (4-Exoalkyl) -Nanto, 2 · (2 · (4-Bromophenyl) ethyl-amino) · 5- (4_Ga BenQ) · 4- (4-ρBiYodo) · Branch, 5- (4-fluorophenyl) -2- (2- (2-methoxyphenyl) ethyl-amino) _4_ (4_ Pyridyl) -Xiaodian, 5_ (4 · fluorophenyl) · 2_ (2_ (3-Toxophenyl) ethyl-amino) -4_ (4-pyridyl) -Xiaodian, 5- (4- Fluorophenyl) -2-((1-methyl-3_phenylpropyl) -amino) · 4- (4_ρ Biyenyl) -Hyoden, 5- (4-fluorophenyl) -2- ((4-phenyl · butyl) -amino) -4- (4-pyridyl) -pyrimidine, 5- (4-fluorophenyl) -2-morpholinyl-4_ (4-pyridyl) · Pyrimidine, 5- (4-fluorophenyl) -4- (4-pyridyl) _2_ (2_pyrrolidinylethylamino) -Komimitsu, 5- (4_Gabenyl) -2- ( 2-? 111-Linylethylamino) -4- (4-ρBiYenyl) -Xiaodian '5- (4-fluorophenyl) -2- (2-hexahydropyridylethylamino) -4- (4_pyridyl) -dimethylamino, 5- (4-fluorophenyl) -2- (3- (2- ^ ρ each keto-1-yl) propylamino) -4- ( 4- -3- This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 520362 A8 B8 C8 D8 VI. Patent application Periphyllyl) -hypertensive disease, 5- (4-fluorophenyl) -2- (2-phenoxyethyl) thio-6- (4-pyridyl) -4_hydroxy-pyrimidine, 5- (4 · fluorophenyl) -2- (2-phenylaminoethyl) thio-6 · (4-pyridyl) -4 · hydroxy-pyrimidine, 2_ (2-aminoethylethylamino) -5 -(4-fluorophenyl) -4- (4-pyridyl) -pyrimidine, 2- (3-aminopropylamino) -5- (4-fluorophenyl) -4- (4-pyridine ) -Pyrimidine, 2- (benzylamino) -5- (4-fluorophenyl) -4- (4-pyridyl) _pyrimidine, 5- (4-fluorophenyl) -2- (2- Phenylethylamino) -4- (4-pyridyl) -pyrimidine, 5- (4-fluorophenyl) -2- (N-methyl-N- (2-phenylethyl) -amino) 4- (4-pyridyl) -pyridine, 5- (4-fluorophenyl) -2- (2-hydroxy · 2-phenyl-ethyl) amino-4- (4-pyridyl)- Pichi Lake, 5- (4-fluorophenyl) -2- (2- (4-hydroxyphenyl) ethyl-amino) -4_ (4-pyridyl) -snake, 5- (4-fluorobenzene Group) -2- (2_ (4-fluorophenyl) ethyl-amino group) _4- (4-soryl) -continuous lake, 5- (4-fluorophenyl) -2- (2- (2 -Fluorophenyl) ethyl-amino) -4_ (4-pi ratio pyridylpyrimidine, 5- (4-fluorophenyl) -2-((3-phenylpropyl) -amino) -4- (4-Pyridyl) -Hydrogenates, 2-((2 (S) -Amino-3-phenylpropyl) -amino) -5- (4-fluorophenyl) -4- (4-ringpyridyl) -pyrimidine, 5- (4-fluorophenyl ) -2- (2-phenylaminoethylethylamino) -4- (4-pyridyl) -pyrimidine, -4- This paper size applies to China National Standard (CNS) A4 specifications (210X297 mm) 訂Order 520362 A8 B8 C8 申請專利範圍 5_(4·氟苯基）-2-((3-咪唑基丙基）_胺基）-4-(4-吡啶基）- 口密咬， 5一（4_氟苯基）·4·(4·吡啶基）-2-吡咯啶基-嘧啶， 5-(4·氟苯基）_2_(1-六氫ρ比ρ井基、‘（‘吨淀基兴喊淀， 2-(2,6-二氯爷基）-5-(4-氟苯基）-6-(4-峨違基）-4-幾-喊淀'， 5 (4-鼠表基）-2-(2_表基乙基）硫-6_(4-ρ比淀基）_4_經-口密 淀， 5-(4·氟苯基）-2-(3-苯基丙基）硫-6-(4-吡啶基）-4-羥-嘧 啶， 2_(2-(2-氯苯基）乙基-胺基）_5_(4-氟苯基）-6-(4-吡啶 基）-4•經-ρ密淀， 5_(4_氟苯基）_2_((3·苯基丙基）-胺基）-6-(4·吡啶基）-4-幾·喃淀， 5_(4_氟苯基）-2-((1-甲基-3-苯基丙基）-胺基）-6-(4-峨啶 基）-4-經-嘧咬，或 2·(2-(2-氯苯基）乙基·胺基）_5·(4_氟苯基）_6气仁吡啶 基）_4-經-喊淀， 或其醫藥可接受性鹽。 3· —種預防或治療發炎之醫藥組成物，包括有效量之申 請專利範圍第1或2項之化合物。 4. 一種於哺乳動物體預防或治療下列疾病之醫藥組成 物：類風濕性關節炎，巴吉特氏病，鬆骨病，多發性 骨髓瘤，葡萄膜炎，急性及慢性骨髓原性白血病，胰 臟β細胞破壞，骨關節炎，類風濕性脊椎炎，痛風性關 -5- 本紙張尺度適用中國國家標準(CNS) Α4規格(210 X 297公釐) 六、申請專利範圍 節炎，發炎性腸病，成人呼吸窘迫症候群（ARDS)，乾 癬’柯恩氏病，過敏性鼻炎，潰瘍性結腸炎，無防衛 性過敏，接觸性皮炎，氣喘，肌肉退化，惡病質，萊 特氏症候群，第I型糖尿病，第Η型糖尿病，骨質吸 收病’移植物對寄主反應，阿茲海默氏病，中風，心 肌梗塞’缺血性再灌流傷害，動脈粥瘤硬化，腦創傷， 多發性硬化，腦癔，敗血病，敗血性休克，中毒性休 克症候群，發燒，因HIV-1，HIV_2，HIV_3，細胞巨病 毒（CMV)，流行性感冒病毒，腺病毒，疱疹病毒或帶狀 癌療感染導致的肌痛’該方法包括投與有效量之如申 請專利範圍第1或2項之化合物。 5. y種，低TNF-^n^中之任_者或二者之血聚濃度 之醫藥組成物，包括有效量之申請專利範圍第丨或2 項之化合物。 6. -料低IL_6lIL_8中之任一者或二者之血聚濃度之 醫藥组成物，包括有效量之申請專利範圍第丨或2項 之化合物。 7· 一種於哺乳動物體預防或治療糖尿病之醫藥组成物， 包括有效量之申請專利範圍第i 2戈2項之化合物而產 生升糖素拮抗劑效果。 8. —種於哺乳動物體預防或治療疼痛病症之醫藥組成 物，包括有效量之如申請專利範固第工或2項之化合 物。 、 9. 一種於哺乳動物體減少***素之產生之醫藥組成 -6- 520362 8 8 8 8 A BCD 々、申請專利範圍 物，包括有效量之申請專利範圍第1或2項之化合物。 10. —種於哺乳動物體降低環氧化酶活性之醫藥組成物， 包括有效量之申請專利範圍第1或2項之化合物。 11. 如申請專利範圍第10項之醫藥組成物，其中該環氧化 酶為COX-2 〇 本紙張尺度適用中國國家標準(CNS) A4規格(210X 297公釐)520362 A8 B8 C8 Patent application scope 5_ (4 · fluorophenyl) -2-((3-imidazolylpropyl) _amino) -4- (4-pyridyl)-Oral bite, 5 (4_ Fluorophenyl) · 4 · (4 · Pyridyl) -2-pyrrolidinyl-pyrimidine, 5- (4 · Fluorophenyl) _2_ (1-hexahydroρ ratio ρ Well group, '(' Tondo Keixing Jiaodian, 2- (2,6-dichloroethenyl) -5- (4-fluorophenyl) -6- (4-amidonyl) -4-Ji-Xiaodian ', 5 (4-rat table ) -2- (2_epiylethyl) sulfur-6_ (4-ρ than yodoyl) _4_Jing-kou dense lake, 5- (4 · fluorophenyl) -2- (3-phenylpropyl ) Sulfur-6- (4-pyridyl) -4-hydroxy-pyrimidine, 2- (2- (2-chlorophenyl) ethyl-amino) _5_ (4-fluorophenyl) -6- (4- Pyridyl) -4 • Via -ρ dense lake, 5_ (4_fluorophenyl) _2 _ ((3 · phenylpropyl) -amino) -6- (4 · pyridyl) -4-kiran , 5- (4-fluorophenyl) -2-((1-methyl-3-phenylpropyl) -amino) -6- (4-eridinyl) -4-via-pyrimidine, or 2 · (2- (2-chlorophenyl) ethyl · amino group) _5 · (4_fluorophenyl) _6 gasopyridyl group) _4-Jing-Xiaodian, or a pharmaceutically acceptable salt thereof. 3 · — Pharmaceutical composition for preventing or treating inflammation, including application of effective amount The compounds of the scope of interest 1 or 2. 4. A medicinal composition for preventing or treating the following diseases in mammals: rheumatoid arthritis, Baget's disease, osteoporosis, multiple myeloma, uveal membrane Inflammation, acute and chronic myelogenous leukemia, pancreatic β-cell destruction, osteoarthritis, rheumatoid spondylitis, gouty -5- This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) ) 6. Scope of patent application: Arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis' Cohen's disease, allergic rhinitis, ulcerative colitis, non-defensive allergy, contact dermatitis, asthma, muscle Degeneration, cachexia, Wright's syndrome, type 1 diabetes, type 2 diabetes, bone resorption disease 'graft response to host, Alzheimer's disease, stroke, myocardial infarction' ischemic reperfusion injury, atheroma Sclerosis, brain trauma, multiple sclerosis, cerebral palpitations, sepsis, septic shock, toxic shock syndrome, fever, HIV-1, HIV_2, HIV_3, cytomegalovirus (CMV), epidemic Myalgia caused by cold virus, adenovirus, herpes virus, or band cancer treatment of infection 'This method involves administering an effective amount of a compound such as those in the scope of patent application No. 1 or 2. 5. Type y, low TNF- ^ n ^ The pharmaceutical composition of blood concentration of either or both of them includes an effective amount of the compound in the scope of patent application No. 1 or 2. 6.-A pharmaceutical composition with low blood concentration of any one or both of IL_6lIL_8, including an effective amount of a compound in the scope of patent application No. 丨 or 2. 7. A medicinal composition for preventing or treating diabetes in a mammal, comprising an effective amount of a compound in the scope of patent application Nos. I 2 to 2 to produce a glucagon antagonist effect. 8. —Medical composition for the prevention or treatment of painful conditions in mammals, including effective amounts of compounds such as the patent application No. 2 or No. 2. 9. A medicinal composition that reduces the production of prostaglandins in mammals-6-520362 8 8 8 8 A BCD 々, patented substances, including effective amounts of the compounds in the scope of patent applications 1 or 2. 10.-A pharmaceutical composition for reducing cyclooxygenase activity in mammals, including an effective amount of a compound in the scope of claims 1 or 2 of the patent application. 11. If you apply for a pharmaceutical composition under the scope of patent application No. 10, where the cyclooxygenase is COX-2 〇 This paper size is applicable to China National Standard (CNS) A4 (210X 297 mm)
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