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研究生:石美玲
研究生(外文):Shih Mei-Ling
論文名稱:1(或2)-(取代芐基)-3-(4-甲基苯基)-1(或2)氫-吲唑類化合物之合成及其抗血小板、抗血管增生與細胞致毒活性
論文名稱(外文):Synthesis, Antiplatelet, Antiangiogenesis and Cytotoxicity Activity of 1(or 2)-(Substituted benzyl)-3-(4-methylphenyl)-1(or 2)H-indazoles
指導教授:郭盛助郭盛助引用關係黃麗嬌黃麗嬌引用關係
指導教授(外文):Kuo Sheng-ChuHuang Li-Jiau
學位類別:碩士
校院名稱:中國醫藥學院
系所名稱:藥物化學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:132
中文關鍵詞:抗血小板凝集抗血管增生細胞致毒YD-3 衍生物唑類衍生物
外文關鍵詞:antiplateletantiangiogenesiscytotoxicityYD-3 derivativesindazole derivatives
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為了得到強力的抗血小板與抗血管增生之化合物,所以著者以3-(4-methylphenyl)-1H-indazole (6)為key intermediate,從事其衍生物的合成。
利用1-N-嗎福啉基環己烯與4-甲基苯甲醯氯在三乙基胺的存在下反應,接著以鹽酸水溶液水解即可得2-oxocyclohexyl 4- methylphenyl ketone (4)。將化合物4與聯胺進行反應,可以得到3-(4-methylphenyl)-4,5,6,7-tetrahydro-1H-indazole (5)。繼而以Pd/C之催化脫氫反應將化合物5氧化成3-(4-methylphenyl)-1H-indazole (6)。最後將化合物6與各種取代的芐基氯進行benzylation 後,形成兩類主要的衍生物;1-(substituted benzyl)-3-(4-methylphenyl)-1H-indazole (7、9、11、13、15、16、18)與2-(substituted benzyl)-3-(4-methylphenyl)-2H-indazole (8、10、12、14、17、19 - 21)。
將化合物6及其相關化合物進行生物活性之評估。結果發現大部份N2取代性衍生物(8、10、12、14、17、19 - 21)比N1取代性衍生物(9、11、13、15、16)具有較顯著的抗血小板活性。而在N2取代性衍生物中,2-(4-chlorobenzyl)-3-(4-methylphenyl)-2H-indazole (8), 2-(4-methylbenzyl)-3-(4-methylphenyl)-2H-indazole (14) 以及 2-(4-methoxybenzyl)-3-(4-methylphenyl)-2H-indazole (19)具有顯著的抗血管增生活性,值得進一步探討。

In order to search novel compounds with potent antiplatelet and antiangiogenesis activities, 3-(4-methylphenyl)-1H-indazole (6) was used as the key intermediate and its derivatives were synthesized.
In the presence of triethylamine, 1-(N-morpholino)cyclohexene was reacted with 4-methylbenzoyl chloride. Followed by hydrolysis using dil. hydrochloric acid, 2-oxocyclohexyl 4-methylphenyl ketone (4) was obtained. 3-(4-Methylphenyl)-4,5,6,7-tetrahydro-1H-indazole (5) was gained after reaction of compound 4 and hydrazine. The product, 3-(4-methyl phenyl)-1H-indazole (6), was obtained after compound 5 was oxygenated by catalytic dehydrogenation on Pd/C. Finally, benzylation of compound 6 with various substituted benzyl chloride produced the derivatives, 1-(substituted benzyl)-3-(4-methylphenyl)-1H-indazoles (7、9、11、13、15、16、18) and 2-(substituted benzyl)-3-(4-methyl phenyl)-2H-indazoles (8、10、12、14、17、19 - 21).
Compound 6 and its related compounds were evaluated for their biological activities. Most of N2-substituted derivatives (8、10、12、14、17、19、20、21) showed more prominent antiplatelet activity than N1-substituted derivatives (9、11、13、15、16). Among these N2-substituted derivatives, 2-(4-chlorobenzyl)-3-(4-methylphenyl)-2H-indazole (8), 2-(4-methylbenzyl)-3-(4-methylphenyl)-2H-indazole (14) and 2-(4-methoxybenzyl)-3-(4-methylphenyl)-2H-indazole (19) showed significant antiangiogenesis and worthy for further investigation.

中文摘要
英文摘要
第一章 緒論
第一節 血小板(platelet)之生理及病理角色……………… 1
第二節 癌症………………………………………………… 4
第三節 凝血酶(thrombin)之主要生理功能……………… 7
第四節 吲唑類(indazole)化合物之合成方法……………… 9
第五節 YD-3之研究概況………………………………… 11
第六節 研究動機與目的…………………………………… 13
第二章 結果與討論
第一節 化學合成
I、標的化合物的合成概述……………………………… 16
第二節 藥理活性試驗結果
I、抗血小板凝集活性…………………………………… 59
II、抑制血管增生之活性………………………………… 63
III、細胞致毒活性………………………………………… 68
第三章 結論…………………………………………………… 71
第四章 實驗部份
第一節 試藥………………………………………………… 73
第二節 重要儀器…………………………………………… 75
第三節 各化合物之製備…………………………………… 77
第四節 藥理試驗方法……………………………………… 91
參考文獻………………………………………………………… 94
圖譜………………………………………………………….… 99
圖譜目錄
圖4-1,圖4-2 化合物4之MS圖譜及IR光譜圖………………. 19
圖4-3 化合物4之1H-NMR (CDCl3, 200 MHz)圖譜…………. 20
圖4-4a 化合物4之1H-1H cosy (CDCl3, 200 MHz)圖譜……… 20
圖4-4b 化合物4之1H-1H cosy (CDCl3, 200 MHz)圖譜……… 21
圖4-5 化合物4之13C-NMR (CDCl3, 50 MHz)圖譜…………… 21
圖4-6a 化合物4之HMQC (CDCl3)圖譜……………………….. 22
圖4-6b 化合物4之HMQC (CDCl3)圖譜……………………….. 22
圖5-1,圖5-2 化合物5之MS圖譜及IR光譜圖………………. 24
圖5-3 化合物5之1H-NMR (CDCl3, 200 MHz)圖譜…………... 25
圖5-4 化合物5之13C-NMR (CDCl3, 50 MHz)圖譜…………… 25
圖5-5a 化合物5之13C-1H cosy (CDCl3)光譜………………… 26
圖5-5b 化合物5之13C-1H cosy (CDCl3)圖譜………………… 26
圖6-1,圖6-2 化合物6之MS圖譜及IR光譜圖………………. 29
圖6-3 化合物6之1H-NMR (CDCl3, 300 MHz)圖譜…………... 30
圖6-4 化合物6之1H-1H cosy (CDCl3, 300 MHz)圖譜………. 30
圖6-5 化合物6之13C-NMR (CDCl3, 75 MHz)圖譜…………… 31
圖6-6 化合物6之HMQC (CDCl3)圖譜………………………... 31
圖6-7 化合物6之HMBC (CDCl3)圖譜………………………... 32
圖18-1,圖18-2 化合物18之MS圖譜及IR光譜圖…………... 38
圖18-3 化合物18之1H-NMR (DMSO-d6, 400 MHz)圖譜……. 39
圖18-4 化合物18之1H-1H cosy (DMSO-d6, 400 MHz)圖譜… 39
圖18-5 化合物18之13C-NMR (DMSO-d6, 50 MHz)光譜…….. 40
圖18-6 化合物18之HMQC (DMSO-d6)圖譜…………………. 40
圖18-7 化合物18之HMBC (DMSO-d6)圖譜…………………. 41
圖19-1,圖19-2 化合物19之MS圖譜及IR光譜圖…………... 44
圖19-3 化合物19之1H-NMR (DMSO-d6, 400 MHz)圖譜……. 45
圖19-4 化合物19之1H-1H cosy (DMSO-d6, 400 MHz)圖譜… 45
圖19-5 化合物19之13C-NMR (DMSO-d6, 50 MHz)圖譜…….. 46
圖19-6 化合物19之HMQC (DMSO-d6)圖譜…………………. 46
圖19-7a 化合物19之HMBC (DMSO-d6)圖譜…………………. 47
圖19-7b 化合物19之HMBC (DMSO-d6)圖譜………………… 48
圖22-1,圖22-2 化合物22之MS圖譜及IR光譜圖…………... 53
圖22-3 化合物22之1H-NMR (CDCl3, 400 MHz)圖譜………... 54
圖22-4 化合物22之1H-1H cosy (CDCl3, 400 MHz)圖譜……. 54
圖22-5 化合物22之13C-NMR (CDCl3, 50 MHz)圖譜………… 55
圖22-6 化合物22之HMQC (CDCl3)圖譜……………………... 55
圖22-7a 化合物22之HMBC (CDCl3)圖譜…………………….. 56
圖22-7b 化合物22之HMBC (CDCl3)圖譜…………………….. 57
圖7-1,圖7-2 化合物7之MS圖譜及IR光譜圖………………. 99
圖7-3 化合物7之1H-NMR (CDCl3, 200 MHz)圖譜…………... 100
圖7-4 化合物7之13C-NMR (CDCl3, 50 MHz)圖譜…………… 100
圖8-1,圖8-2 化合物8之MS圖譜及IR光譜圖………………. 101
圖8-3 化合物8之1H-NMR (CDCl3, 200 MHz)圖譜…………... 102
圖8-4 化合物8之13C-NMR (CDCl3, 50 MHz)圖譜…………… 102
圖9-1,圖9-2 化合物9之MS圖譜及IR光譜圖………………. 103
圖9-3 化合物9之1H-NMR (CDCl3, 200 MHz)圖譜…………... 104
圖9-4 化合物9之13C-NMR (CDCl3, 50 MHz)圖譜…………… 104
圖10-1,圖10-2 化合物10之MS圖譜及IR光譜圖…………… 105
圖10-3 化合物10之1H-NMR (CDCl3, 200 MHz)圖譜……….. 106
圖10-4 化合物10之13C-NMR (CDCl3, 50 MHz)圖譜………… 106
圖11-1,圖11-2 化合物11之MS圖譜及IR光譜圖…………... 107
圖11-3 化合物11之1H-NMR (CDCl3, 200 MHz)圖譜……….. 108
圖11-4 化合物11之13C-NMR (CDCl3, 50 MHz)圖譜………… 108
圖12-1,圖12-2 化合物12之MS圖譜及IR光譜圖…………... 109
圖12-3 化合物12之1H-NMR (CDCl3, 200 MHz)圖譜……….. 110
圖12-4 化合物12之13C-NMR (CDCl3, 50 MHz)圖譜………… 110
圖13-1,圖13-2 化合物13之MS圖譜及IR光譜圖…………... 111
圖13-3 化合物13之1H-NMR (CDCl3, 200 MHz)圖譜………... 112
圖13-4 化合物13之13C-NMR (CDCl3, 50 MHz)圖譜………… 112
圖14-1,圖14-2 化合物14之MS圖譜及IR光譜圖…………... 113
圖14-3 化合物14之1H-NMR (CDCl3, 200 MHz)圖譜………... 114
圖14-4 化合物14之13C-NMR (CDCl3, 50 MHz)圖譜………… 114
圖15-1,圖15-2 化合物15之MS圖譜及IR光譜圖…………... 115
圖15-3 化合物15之1H-NMR (CDCl3, 200 MHz)圖譜………... 116
圖15-4 化合物15之13C-NMR (CDCl3, 50 MHz)圖譜………… 116
圖16-1,圖16-2 化合物16之MS圖譜及IR光譜圖…………... 117
圖16-3 化合物16之1H-NMR (CDCl3, 200 MHz)圖譜………... 118
圖16-4 化合物16之13C-NMR (CDCl3, 50 MHz)圖譜………… 118
圖17-1,圖17-2 化合物17之MS圖譜及IR光譜圖…………... 119
圖17-3 化合物17之1H-NMR (CDCl3, 200 MHz)圖譜……….. 120
圖17-4 化合物17之13C-NMR (CDCl3, 50 MHz)圖譜………… 120
圖20-1,圖20-2 化合物20之MS圖譜及IR光譜圖…………... 121
圖20-3 化合物20之1H-NMR (CDCl3, 200 MHz)圖譜………... 122
圖20-4 化合物20之13C-NMR (CDCl3, 50 MHz)圖譜………… 122
圖21-1,圖21-2 化合物21之MS圖譜及IR光譜圖…………... 123
圖21-3 化合物21之1H-NMR (CDCl3, 200 MHz)圖譜………... 124
圖21-4 化合物21之13C-NMR (CDCl3, 50 MHz)圖譜………… 124
圖I-1,圖I-2 化合物I之MS圖譜及IR光譜圖…………….. 125
圖I-3 化合物I之1H-NMR (CDCl3, 200 MHz)圖譜…………. 126

1. Murray, R. K.; Granner, D. K.; Mayes, P. A.; Rodwell, V. W. Harper’s Biochemistry, 24th ed.; Prentice-Hall International, INC.: London, 1996; p 707-731.
2. Gonzalez, E. R. Antiplatelet Therapy in Atherosclerotic Cardiovascular Disease. Clin. Therapeutics. 1998, 20, supplement 2, B18-41.
3. Bang, N. U.; Wilson, D. B. Normal Platelet Function and Antiplatelet Drugs. ACC Cur. J. Rev. 1999, 8, 13-16.
4. Haskell,C. M. Cancer Treatment, 5th ed.; W. B. Saunders Co.: Philadelphia, 2001; p 2-29, 98-99, 480-481.
5. Abeloff, M. D.; Armitage, J. O.; Lichter, A. S.; Niederhuber, J. E. Clinical Oncology, 2th ed.; Churchill Livingstone: Philadelphia, 2000; p 10-53, 242-250.
6. DeVita Jr, V. T.; Hellman, S.; Rosenberg, S. A. Cancer Principles & Practice of Oncology, 6th ed.; Lippincott Williams & Wilkins: Philadelphia, 2001; p 137-147.
7. Goldsack, N. R.; Chambers, R. C.; Dabbagh, K.; Laurent. G. J. Molecules in Focus Thrombin. Intern. J. Biochem. & Cell Biol. 1998, 30, 641-646.
8. Ray, A.; Hegde, L. G.; Gupta, J. B. Related Articles Thrombin Receptor: A Novel Target for Antiplatelet Drug Development. Thromb. Res. 1997, 87, 37-50.
9. Macfarlane, S. R.; Seatter, M. J.; Kanke, T.; Hunter, G. D.; Plevin, R.
Related Articles Proteinase-activated Receptors. Pharmacol. Rev. 2001, 53, 245-282.
10.Dery, O.; Corvera, C. U.; Steinhoff, M.; Bunnett, N. W. Related Articles Proteinase-activated Receptors: Novel Mechanisms of Signaling by Serine Proteases. Am. J. Physiol. 1998, 274, c1429-1452.
11.Cupit, L. D.; Schmidt, V. A.; Bahou, W. F. Related Articles Proteolytically Activated Receptor-3. A Number of an Emerging Gene Family of Protease Receptors Expressed on Vascular Endothelial Cells and Platelets. Trends Cardiovasc. Med. 1999, 9, 42-48.
12.Xu, W. F.; Andersen, H.; Whitmore, T, E.; Presnell, S. R.; Yee, D. P.; Ching, A.; Gilbert, T.; Davie, E. W.; Foster, D. C. Related Articles, Nucleotide, OMIM, Free in PMC, Protein Cloning and Characterization of Human Protease-activated Receptor 4. Proc. Natl. Acad. Sci. Sua. 1998, 95, 6642-6646.
13.Kahn, M. L.; Zheng, T. W.; Huang, W.; Bigornia, V.; Zeng, D.; Moff, S.; Farese Jr, R. V.; Tam, C.; Coughlin, S. R. Related Articles, Nucleotide, OMIM, Protein a Dual Thrombin Receptor Sysem for Platelet Activation. Nature. 1998, 394, 690-694.
14.Kahn, M. L.; Nakanishi-Matsui, M.; Shapiro, M. J.; Ishihara, H.; Coughlin, S. R. Related Articles, Protein Protease-activated Receptors 1 and 4 Mediate Activation of Human Platelets by Thrombin. J. Clin. Invest. 1999, 103, 879-887.
15.Hannig, E.; Kollmorgen, C.; Geipel, I. The Preparation of Some Derivatives of 5-Methylindazole-3-carboxylic Acid. Pharmazie. 1973, 28, 720-723.
16.Hannig, E.; Kollmorgen, C.; Dressel, M. Various Derivatives of 1-Benzyl-6- aminoindazole. Pharmazie. 1974, 29, 685-687.
17.Ina, S.; Inoue, S.; Noguchi, T. N-heterocyclic Compounds. I. Facile Synthesis of 5,6-dialkoxy-2-aryI-2H-indazoles (author's transl). Yakugaku Zasshi. 1975, 95, 1245- 1249.
18.Corsi, G.; Palazzo, G. 1-Halobenzyl-lH-indazole-3-carboxylic Acid. A New Class of Antispermatogenic agents. J. Med. Chem. 1976, 19, 778-783.
19.Bistocchi, G. A.; De Meo, G.; Pedini, M.; Ricci, A.; Brouilhet, H.; Boucherie, S.; Rabaud, M.; Jacquignon, P. N1-Substituted 1H-indazole-3-ethyl Carboxylates and 1H-Indazole-3-hydroxamic Acids. Farmaco —Edizione Scientifica. 1981, 36, 315-333.
20.Conway, G. A.; LoefEler, L. J.; Hall, I. H. Synthesis and Antitumor Evaluation of Selected 5,6-Disubstituted 1(2)H-indazole-4,7-diones. J. Med. Chem. 1983, 26, 876-884.
21.Cecchi, L.; Melani, E; Filacchioni, G.; Tredici, M. Synthesis and Biological Activity of Some 3-(Pyrazol-l'-yl)indazole Derivatives. Farmaco - Edizione Scientifica. 1984, 39, 945-952.
22.Mosti, L.; Menozzi, G.; Schenone, P.; Molinario, L.; Conte, F.; Montanario, C.; Marmoe, E. Acetic Acids Bearing the 1-Phenyl-1H-indazole Nucleus with Analgesic and Anti-inflammatory Activity. Farmaco - Edizione Scientifica. 1988, 43, 763-774.
23.Mosti, L; Menozzi, G.; Schenone, P.; Cervo, D.; Esposito, G.; Marmoe, E. 4-Substituted 1-Phenyl-1H-indazoles with Analgesic, Anti-innammatory, Antipyretic and Local Anesthetic Activities. Farmaco. 1990, 45, 415-429.
24.Robertson, D. W.; Bloomquist, W.; Cohen, M. L.; Reid, L. R.; Schenck, K.; Wong, D. T. Synthesis and Biochemical Evaluation Tritium-labeled 1-Methyl-N- (8-methyl-8-azabicyclo[3.2.l]oct-3-yl)-1H-indazole-3-carboxamide, A Useful Radioligand for 5-HT3 Receptors. J. Med Chem. 1990, 33, 3176-3181.
25.Wrzeciono, U.; Linkowska, E.; Majewska, K.; Gzella, A.; Stochla, K. Synthesis and Anti-inflammatory Activity of Some Indazole Derivatives. 36. Azoles. Pharmazie. 1993, 48, 582-584.
26.Perni, R. B.; Wentland, M. P.; Huang, J. I.; Powles, R. Aldous, G.; S.; Klingbeil, K. M.; Peverly, A. D.; Robinson, R. G.; Corbett, T. H.; Jones, J. L.; Mattes, K. C.; Rake, J. B; Coughlin, S. A. Synthesis and Antitumor Activity of 4-Aminomethylthioxanthenone and 5-Aminomethylbenzothiopyrano-indazole Derivatives. J. Med. Chem. 1998, 41, 3645-3654.
27.Andronati, S.; Sava, V.; Makan, S.; Kolodeev, G. Synthesis of 3-Aryl-l- [(4-phenyl-l-piperazinyl)butyl]indazole Derivatives and Their Affinity to 5-HT1A Serotonin and Dopamine D1 receptors. Pharmazie. 1999, 54, 99-101.
28.Song, J. J.; Yee, N. K. A Novel Synthesis of 2-Aryl-2H-indazoles via a Palladium-catalyzed Intramolecular Amination Reaction. Org. Lett. 2000, 2, 519-521.
29.Isin, E. M.; de Jonge, M.; Jr. Castagnoli, N. Studies on Synthetic Approaches to
1H- and 2H-Indazolyl Derivatives. J. Org. Chem. 2001, 66, 4220-4226.
30.Richard, H. W. Pyrazoles, Pyrazolines, Pyrazolidines, Indazoles and Condensed Rings.; Interscience Publishers: New York, 1967, Pt. 3, p 289-382.
31.Gladstone, W. A. F. J. Chem. Soc. 1965, 3048-3050.
32.Yashina, S.; Tanaka, A.; Kuo, S. C. Yakugaku Zasshi. 1977, 97, 955-961.
33.Lee, F. Y.; Lien, J. C.; Huang, L. J.; Huang, T. M.; Tsai, S. C.; Teng, C. M.; Wu, C. C.; Cheng, F. C.; Kuo S. C. Synthesis of 1-Benzyl-3-(5'-hydroxymethyl-2'- furyl)indazole Analogues as Novel Antiplatelet Agents. J. Med. Chem. 2001, 44, 3746-3749.
34.Wu, C. C.; Huang, S. W.; Hwang T. L.; Kuo S. C.; Lee F. Y.; Teng C. M. YD-3, A Novel Inhibitor of Protease-induced Platelet Activation. Br. J. Pharmacol. 2000, 130, 1289-1296.
35.Seiler, S. M. Related Articles Thrombin Receptor Antagonists. Semi. Thromb. Hemost. 1996, 22, 223-231.
36.Wu, C. C.; Hwang, T. L.; Liao, C. H.; Kuo, S. C.; Lee, F. Y.; Lee, C. Y.; Teng, C. M. Selective Inhibition of Protease-activated Receptor 4-dependent Platelet Activation by YD-3, Thromb. Haemost. 2002, 87, 1026-33.
37.McCrae, W. Basic Organic Reaction.; Heyden & Son INC.: New York, 1973;
p 80-82.
38.Norman, R. Organic Synthesis, 2th ed.; John Wiley & Sons, INC.: New York, 1967; Col. Vol. 4. p 536-539.
39.李芳裕,3-(5'-羥甲基-2'-呋喃基)-1-苯甲基吲唑類緣化合物之合成及其抗血小板活性,中國醫藥學院藥物化學研究所博士論文,1997。
40.Horning, E. C. Organic. Synthesis.; John Wiley & Sons, INC.: New York, 1957; Col. Vol. 3. p 740-741.
41.Blatt, A. H. Organic Synthesis, 7th ed.; John Wiley & Sons, INC.: New York, 1955; Col. Vol. 2. p 135-136.
42.a) Wuehrmenn, H. Ger. Patent 2, 307, 292, 1973.
b) Matsude, H.; Mori H. and Matoba, H. Jpn. Patent 2,263, 879 , 1973.
c) Rosenberg, R. Ger. Patent 2, 115, 945, 1971.
d) Chu , V. and Cohen, A. Fr. Patent 2, 001, 923, 1969.
43.Howell, J. B. L.; Altounyan, R. E. C. Lancet. 1967, 2, 539.
44.Teng, C. M.; Chen, W. Y.; Ko, W.C.; Ouyang, C. Antiplatelet Effect of Butylindenephthalide. Biochem. Biophys. Acta. 1987, 924, 375-382.
45.Lopez-Lluch, G.; Buron, M. I.; Alcain, F. J.; Quesada, J. M.; Navas, P. Redox Regulation of Camp Levels by Ascorbate in 1,25-Dihydroxy-vitamine D3-induced Differentication of HL-60 Cells. Biochem. J. 1998, 331(Pt. 1), 21-27.
46.He, Q.; Jiang, D. A Novel Aminosteroid is Active for Proliferation Inhibition and Differentiation Induction of Human Acute Myeloid Leukemia HL-60 Cells. Leuk. Res. 1999, 23(4), 369-372.
47.Berridge, M. V.; Tan, A. S. Characterization of the Cellular Reduction of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide (MTT): Subcellular Localization, Substrate Dependence, and Involvement of Mitochondrial Electron Transport in MTT Reduction. Arch. Biochem. Biophys. 1993, 303, 474-482.

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