Imidazole-containing diarylether and diarylsulfone inhibitors of farnesyl-protein transferase

被引:82
作者
Dinsmore, CJ [1 ]
Williams, TM
O'Neill, TJ
Liu, DM
Rands, E
Culberson, JC
Lobell, RB
Koblan, KS
Kohl, NE
Gibbs, JB
Oliff, AI
Graham, SL
Hartman, GD
机构
[1] Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
[2] Merck Res Labs, Dept Canc Res, W Point, PA 19486 USA
[3] Merck Res Labs, Dept Mol Syst, W Point, PA 19486 USA
关键词
D O I
10.1016/S0960-894X(99)00605-8
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The design and syntheses of non-thiol inhibitors of farnesyl-protein transferase are described. Optimization of cysteine-substituted diarylethers led to highly potent imidazole-containing diarylethers and diarylsulfones. Polar diaryl linkers dramatically improved potency and gave highly cell active compounds. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:3301 / 3306
页数:6
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