FADROZOLE HYDROCHLORIDE - A POTENT, SELECTIVE, NONSTEROIDAL INHIBITOR OF AROMATASE FOR THE TREATMENT OF ESTROGEN-DEPENDENT DISEASE

被引：213
作者：
BROWNE, LJ
GUDE, C
RODRIGUEZ, H
STEELE, RE
BHATNAGER, A
机构：
[1] CIBA GEIGY CORP,DIV PHARMACEUT,RES DEPT,SUMMIT,NJ 07901
[2] CIBA GEIGY AG,DIV PHARMACEUT,RES DEPT,CH-4002 BASEL,SWITZERLAND
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 02期
关键词：
D O I：
10.1021/jm00106a038
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A new class of potent, selective, nonsteroidal inhibitors of aromatase have been discovered. The most potent member of this series is fadrozole hydrochloride, CGS 16949 A, 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile monohydrochloride, 26a. In addition, the 6,7-dihydropyrrolo[1,2-c]imidazole (21a) and the 6,7,8,9-tetrahydroimidazo[1,5-a]azepine (21b) analogues were synthesized and evaluated. CGS 16949 A's ability to selectively inhibit aromatase (IC50 = 4.5nM) over other cytochrome P-450 enzymes and suppress estrogen production when administered orally make it a suitable candidate to test the potential of an aromatase inhibitor in estrogen-dependent diseases including breast cancer.
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收藏
页码：725 / 736
页数：12
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