Identification of a novel class of androgen receptor antagonists based on the bicyclic-1H-isoindole-1,3(2H)-dione nucleus

被引：38

作者：

Salvati, ME

Balog, A

Wei, DD

Pickering, D

Attar, RM

Geng, JP

Rizzo, CA

Hunt, JT

Gottardis, MM

Weinmann, R

Martinez, R

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Oncol Chem, Princeton, NJ 08543 USA

[2] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Discovery Biol, Princeton, NJ 08543 USA

[3] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Chem Synth, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 02期

关键词：

androgen receptor; prostate cancer; antagonist;

D O I：

10.1016/j.bmcl.2004.10.051

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of isoindoledione based compounds were identified as potent antagonists of the androgen receptor (AR). SAR around this series revealed dramatic differences in binding and function in mutant variants (MT) of the AR as compared to the wild type (WT) receptor. Optimization of the aniline portion revealed substitution patterns, which yielded potent antagonist activity against the WT AR as well as the MT AR found in the LNCaP and PCa2b human prostate tumor cell lines. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：389 / 393

页数：5

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