Design of novel quinazoline derivatives and related analogues as potent and selective ALK5 inhibitors |
| |
| Authors: | F Gellibert M-H Fouchet V-L Nguyen R Wang G Krysa A-C de Gouville S Huet N Dodic |
| |
| Institution: | 1. GlaxoSmithKline, 25-27 Avenue du Québec, 91951 Les Ulis, France;2. GlaxoSmithKline, Research Triangle Park, NC 27703, USA |
| |
| Abstract: | Starting from quinazoline 3a, we designed potent and selective ALK5 inhibitors over p38MAP kinase from a rational drug design approach based on co-crystal structures in the human ALK5 kinase domain. The quinazoline 3d exhibited also in vivo activity in an acute rat model of DMN-induced liver fibrosis when administered orally at 5 mg/kg (bid). |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
