Potent and selective non-cysteine-containing inhibitors of protein farnesyltransferase

被引：45

作者：

Augeri, DJ

O'Connor, SJ

Janowick, D

Szczepankiewicz, B

Sullivan, G

Larsen, J

Kalvin, D

Cohen, J

Devine, E

Zhang, HC

Cherian, S

Saeed, B

Ng, SC

Rosenberg, S

机构：

[1] Abbott Labs, Dept Canc Res, Abbott Pk, IL 60064 USA

[2] Abbott Labs, Dept Combinatorial Chem, Abbott Pk, IL 60064 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1998年 / 41卷 / 22期

关键词：

D O I：

10.1021/jm980298s

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Potent and selective non-thiol-containing inhibitors of protein farnesyltransferase are described. FTI-276 (1) was transformed into pyridyl ether analogue 19. The potency of pyridyl ether 19 was improved by modification of the biphenyl core to that of an o-tolyl substituted biphenyl core to give 29. In addition to 0.4 nM in vitro potency, 29 displayed 350 nM potency in whole cells as the parent carboxylic acid. The o-tolyl biphenyl core dramatically and unexpectedly enhanced the potency of other compounds as exemplified by 46, 47, 48, and 49.

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页码：4288 / 4300

页数：13

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