Novel thienopyrimidine and thiazolopyrimidine kinase inhibitors with activity against Tie-2 in vitro and in vivo
详细信息 查看全文
- 作者：Richard W.A. Luke ; Peter Ballard ; David Buttar ; Leonie Campbell ; Jon Curwen ; Steve C. Emery ; Alison M. Griffen ; Lorraine Hassall ; Barry R. Hayter ; Cliff D. Jones ; William McCoull ; Martine Mellor ; Mike
- 关键词：Kinase ; Tie-2 ; TEK ; Inhibition ; Angiogenesis ; Small molecule
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2009
- 出版时间：1 December 2009
- 年：2009
- 卷：19
- 期：23
- 页码：6670-6674
- 全文大小：851 K
文摘
The SAR and improvement in potency against Tie2 of novel thienopyrimidine and thiazolopyrimidine kinase inhibitors are reported. The crystal structure of one of these compounds bound to the Tie-2 kinase domain is consistent with the SAR. These compounds have moderate potency in cellular assays of Tie-2 inhibition, good physical properties, DMPK, and show evidence of in vivo inhibition of Tie-2.