Thienopyridine ureas as dual inhibitors of the VEGF and Aurora kinase families
详细信息 查看全文
- 作者：Michael L. Curtin ; mike.curtin@abbott.com ; Robin R. Frey ; H. Robin Heyman ; Niru B. Soni ; Patrick A. Marcotte ; Lori J. Pease ; Keith B. Glaser ; Terrance J. Magoc ; Paul Tapang ; Daniel H. Albert ; Donald J. Osterling ; Amanda M. Olson ; Jennifer J. Bouska ; Zhiwen Guan ; Lee C. Preusser ; James S. Polakowski ; Kent D. Stewart ; Chris Tse ; Steven K. Davidsen ; Michael R. Michaelides
- 关键词：Aurora kinase inhibitors ; KDR kinase inhibitors ; Thienopyridine ureas ; Pyrazoles ; Antitumor activity ; ABT-348
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：1 May, 2012
- 年：2012
- 卷：22
- 期：9
- 页码：3208-3212
- 全文大小：930 K
文摘
In an effort to identify multi-targeted kinase inhibitors with a novel spectrum of kinase activity, a screen of Abbott proprietary KDR inhibitors against a broad panel of kinases was conducted and revealed a series of thienopyridine ureas with promising activity against the Aurora kinases. Modification of the diphenyl urea and C7 moiety of these compounds provided potent inhibitors with good pharmacokinetic profiles that were efficacious in mouse tumor models after oral dosing. Compound 2 (ABT-348) of this series is currently undergoing Phase I clinical trials in solid and hematological cancer populations.