3,5,6-trisubstituted naphthostyrils as CDK2 inhibitors

被引：31

作者：

Liu, JJ

Dermatakis, A

Lukacs, C

Konzelmann, F

Chen, Y

Kammlott, U

Depinto, W

Yang, H

Yin, XF

Chen, YS

Schutt, A

Simcox, ME

Luk, KC

机构：

[1] Hoffmann La Roche Inc, Dept Discovery Chem, Nutley, NJ 07110 USA

[2] Hoffmann La Roche Inc, Dept Oncol, Nutley, NJ 07110 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 15期

关键词：

D O I：

10.1016/S0960-894X(03)00488-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of 3,5,6-trisubstituted naphthostyril analogues was designed and synthesized to study the structure-activity relationship for inhibition of cyclin-dependent kinase 2 (CDK2). These compounds, particularly molecules with side-chain modifications providing additional hydrogen bonding capability, were demonstrated to be potent CDK2 inhibitors with cellular activities consistent with CDK2 inhibition. These molecules inhibited tumor cell proliferation and G1-S and G2-M cell-cycle progression in vitro. The X-ray crystal structure of a 2-aminoethyleneamine derivative bound to CDK2, refined to 2.5A resolution, is presented. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：2465 / 2468

页数：4

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