Synthesis, structure-activity relationship, and biological studies of indolocarbazoles as potent cyclin D1-CDK4 inhibitors

被引：105

作者：

Zhu, GX ^{[1
]}

Conner, SE ^{[1
]}

Zhou, X ^{[1
]}

Shih, C ^{[1
]}

Li, TC ^{[1
]}

Anderson, BD ^{[1
]}

Brooks, HB ^{[1
]}

Campbell, RM ^{[1
]}

Considine, E ^{[1
]}

Dempsey, JA ^{[1
]}

Faul, MM ^{[1
]}

Ogg, C ^{[1
]}

Patel, B ^{[1
]}

Schultz, RM ^{[1
]}

Spencer, CD ^{[1
]}

Teicher, B ^{[1
]}

Watkins, SA ^{[1
]}

机构：

[1] Eli Lilly & Co, Lilly Res Labs, Lilly Corp Ctr, Indianapolis, IN 46285 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 11期

关键词：

DEPENDENT KINASE INHIBITORS; CELL-CYCLE; ANTICANCER AGENTS; CDK2; PAULLONES; DESIGN; ARREST; PHASE;

D O I：

10.1021/jm0256169

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel substituted indolocarbazoles were synthesized, and their kinase inhibitory capability was evaluated in vitro. 6-Substituted indolocarbazoles 4 were found to be potent and selective D1/CDK4 inhibitors. 4d and 4h exhibited potent and ATP-competitive D1/CDK4 activities with IC50 values of 76 and 42 nM, respectively. Both compounds had high selectivity against the other kinases. These D1/CDK4 inhibitors inhibited tumor cell growth, arrested tumor cells at the G1 phase, and inhibited pRb phosphorylation.

引用

页码：2027 / 2030

页数：4

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