Synthesis and activity of new aryl- and heteroaryl- substituted pyrazole inhibitors of the transforming growth factor-b type I receptor kinase domain

被引：213

作者：

Sawyer, JS ^{[1
]}

Anderson, BD

Beight, DW

Campbell, RM

Jones, ML

Herron, DK

Lampe, JW

McCowan, JR

McMillen, WT

Mort, N

Parsons, S

Smith, ECR

Vieth, M

Wier, LC

Yan, L

Zhang, FM

Yingling, JM

机构：

[1] Lilly Corp Ctr, Discovery Chem Res & Technol, Canc Res & Lead Optimizat Biol, Div Eli Lilly & Co,Lilly Res Labs, Indianapolis, IN 46285 USA

[2] Lilly Res Labs, Div Eli Lilly & Co, Res Triangle Pk, NC 27709 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 19期

关键词：

D O I：

10.1021/jm0205705

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Pyrazole-based inhibitors of the transforming growth factor-beta type I receptor kinase domain (TbetaR-I) are described. Examination of the SAP, in both enzyme- and cell-based in vitro assays resulted in the emergence of two subseries featuring differing selectivity versus p38 MAP kinase. A common binding mode at the active site has been established by successful cocrystallization and X-ray analysis of potent inhibitors with the TbetaR-I receptor kinase domain.

引用

页码：3953 / 3956

页数：4

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