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

2009; Elsevier BV; Volume: 19; Issue: 23 Linguagem: Inglês

10.1016/j.bmcl.2009.10.001

1464-3405

Richard Luke, Peter Ballard, David Buttar, Leonie Campbell, Jon Curwen, Steve Emery, Alison M. Griffen, Lorraine Hassall, Barry R. Hayter, Cliff Jones, William McCoull, Martine J. Mellor, Mike L. Swain, Julie A. Tucker,

Quinazolinone synthesis and applications

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.