National Center for
2OO8: Synthesis, Structural Analysis, And Sar Studies Of Triazine Derivatives As Potent, Selective Tie-2 Inhibitors
Synthesis, structural analysis, and SAR studies of triazine derivatives as potent, selective Tie-2 inhibitors
Bioorg. Med. Chem. Lett. (2007) 17 p.2886-2889
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.