Title of article :
Synthesis, structural analysis, and SAR studies of triazine derivatives as potent, selective Tie-2 inhibitors
Author/Authors :
Brian L. Hodous، نويسنده , , Stephanie D. Geuns-Meyer، نويسنده , , Paul E. Hughes، نويسنده , , Brian K. Albrecht، نويسنده , , Steve Bellon، نويسنده , , Sean Caenepeel، نويسنده , , Victor J. Cee، نويسنده , , Stuart C. Chaffee، نويسنده , , Maurice Emery، نويسنده , , Jenne Fretland، نويسنده , , Paul Gallant، نويسنده , , Yan Gu، نويسنده , , Rebecca E. Johnson، نويسنده , , Joseph L. Kim، نويسنده , , Alexander M. Long، نويسنده , , Michael Morrison، نويسنده , , Philip R. Olivieri، نويسنده , , Vinod F. Patel، نويسنده , , Anthony Polverino، نويسنده , , Paul Rose، نويسنده , , et al.، نويسنده ,
Abstract :
A novel class of selective Tie-2 inhibitors was derived from a multi-kinase inhibitor 1. By reversing the amide connectivity and incorporating aminotriazine or aminopyridine hinge-binding moieties, excellent Tie-2 potency and KDR selectivity could be achieved with 3-substituted terminal aryl rings. X-ray co-crystal structure analysis aided inhibitor design. This series was evaluated on the basis of potency, selectivity, and rat pharmacokinetic parameters.
Keywords :
Oncology , Small molecule kinase inhibitors , triazine , Tie-2 kinase , kdr
