(E)-4-(2-[[3-(INDOL-5-YL)-L-OXO-2-BUTENYL]AMINO]PHENOXY)BUTYRIC ACID-DERIVATIVES - A NEW CLASS OF STEROID 5-ALPHA-REDUCTASE INHIBITORS IN THE RAT PROSTATE .1.

被引：15

作者：

KUMAZAWA, T ^{[1
]}

TAKAMI, H ^{[1
]}

KISHIBAYASHI, N ^{[1
]}

ISHII, A ^{[1
]}

NAGAHARA, Y ^{[1
]}

HIRAYAMA, N ^{[1
]}

OBASE, H ^{[1
]}

机构：

[1] KYOWA HAKKO KOGYO CO LTD,TOKYO RES LABS,MACHIDA,TOKYO 194,JAPAN

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 15期

关键词：

D O I：

10.1021/jm00015a011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of (E)-4-{2-[[3-(indol-5-yl)-1-oxo-2-butenyl]amino]phenoxy}butyric acid derivatives was prepared, and the derivatives were demonstrated to be potent inhibitors of steroid 5 alpha-reductase in the rat prostate. The structure-activity relationships were as follows. An alpha-branched alkyI or benzyl substituent of proper size at position I of the indole is crucial for optimal enzyme inhibitory activity. N-Methylation of the amide NH resulted in complete loss of activity. Thus, coplanarity of the benzene ring and amide moiety is essential for such activity. Among the compounds prepared, (E)-4-(2-[[3-[1-[bis(4-fluorophenyl)methyl]indol-5-yl]-1-oxo-2-butenyl]amino]phenoxy)butyric acid (57, KF18678) was one of the most potent compounds (rat prostate 5 alpha-reductase IC50 = 3.3 nM).

引用

页码：2887 / 2892

页数：6

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