Design of novel quinazoline derivatives and related analogues as potent and selective ALK5 inhibitors.
Gellibert F, Fouchet MH, Nguyen VL, Wang R, Krysa G, de Gouville AC, Huet S, Dodic N.
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).