Novel thienopyrimidine and thiazolopyrimidine kinase inhibitors with activity against Tie-2 in vitro and in vivo

…, P Ballard, D Buttar, L Campbell, J Curwen…

Index: Luke, Richard W.A.; Ballard, Peter; Buttar, David; Campbell, Leonie; Curwen, Jon; Emery, Steve C.; Griffen, Alison M.; Hassall, Lorraine; Hayter, Barry R.; Jones, Cliff D.; McCoull, William; Mellor, Martine; Swain, Mike L.; Tucker, Julie A. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 23 p. 6670 - 6674

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Citation Number: 20

Abstract

The SAR and improvement in potency against Tie2 of novel thienopyrimidine and thiazolopyrimidine kinase inhibitors are reported. The crystal structure of one of these compounds bound to the Tie-2 kinase domain is consistent with the SAR. These compounds have moderate potency in cellular assays of Tie-2 inhibition, good physical properties, DMPK, and show evidence of in vivo inhibition of Tie-2.