（1-苄基吲哚-3-基）链烷酸；新型甾体5α-还原酶非甾体抑制剂（I）。

(1-Benzylindole-3-yl)alkanoic acids; novel nonsteroidal inhibitors of steroid 5 alpha-reductase (I).

作者信息

Sawada K, Hirai H, Golden P, Okada S, Sawada Y, Hashimoto M, Tanaka H

机构信息

Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Tsukuba, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1998 Nov;46(11):1683-7. doi: 10.1248/cpb.46.1683.

DOI:10.1248/cpb.46.1683

Abstract

A novel series of indole-3-alkanoic acids with varied N-benzyl substituents were synthesized as nonsteroidal inhibitors of steroid 5 alpha-reductase. The structure-activity relationships in this series were studied and the optimum carboxylic acid side chain was butyric acid. Furthermore, compounds with a diaryl substituent at the 1-position of the indole ring displayed strong inhibitory activities in vitro. Amongst these derivatives, 4-[1-(6,6-dimethyl-6H-dibenzo[b,d]pyran-3-yl)methylindol-3-yl]b uty ric acid (FR119680) displayed very high inhibitory activity in vitro against rat prostatic 5 alpha-reductase (IC50 = 5.0 nM) and good in vivo activity in the castrated young rat model.

摘要

合成了一系列新型的带有不同N-苄基取代基的吲哚-3-链烷酸，作为甾体5α-还原酶的非甾体抑制剂。研究了该系列化合物的构效关系，最佳的羧酸侧链为丁酸。此外，在吲哚环1位带有二芳基取代基的化合物在体外显示出较强的抑制活性。在这些衍生物中，4-[1-(6,6-二甲基-6H-二苯并[b,d]吡喃-3-基)甲基吲哚-3-基]丁酸(FR119680)在体外对大鼠前列腺5α-还原酶表现出非常高的抑制活性(IC50 = 5.0 nM)，并且在去势幼鼠模型中具有良好的体内活性。

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