Design of novel quinazoline derivatives and related analogues as potent and selective ALK5 inhibitors

  • Bioorg Med Chem Lett. 2009 Apr 15;19(8):2277-81. doi: 10.1016/j.bmcl.2009.02.087.
F Gellibert  1 ,  M-H Fouchet ,  V-L Nguyen ,  R Wang ,  G Krysa ,  A-C de Gouville ,  S Huet ,  N Dodic
Affiliations
PMID: 19285388 DOI: 10.1016/j.bmcl.2009.02.087
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 5mg/kg (bid).