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ID: ALA1145310

Journal: Bioorg Med Chem Lett

Title: Isothiazolopyrimidines and isoxazolopyrimidines as novel multi-targeted inhibitors of receptor tyrosine kinases.

Authors: Ji Z, Ahmed AA, Albert DH, Bouska JJ, Bousquet PF, Cunha GA, Glaser KB, Guo J, Li J, Marcotte PA, Moskey MD, Pease LJ, Stewart KD, Yates M, Davidsen SK, Michaelides MR.

Abstract: A series of isothiazolopyrimidines and isoxazolopyrimidines were synthesized and identified as potent KDR inhibitors. SAR studies led to isothiazolopyrimidine urea analogs that potently inhibit VEGFR tyrosine kinases (KDR enzymatic and cellular IC(50) values below 10 nM) as well as cKIT and TIE2. The selected compounds 8 and 13 display 56% and 48% oral bioavailability in mice, respectively.

CiteXplore: 16735117

DOI: 10.1016/j.bmcl.2006.05.057