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

Luke R.W., Ballard P., Buttar D., Campbell L., Curwen J., Emery S.C., Griffen A.M., Hassall L., Hayter B.R., Jones C.D., McCoull W., Mellor M., Swain M.L., Tucker J.A.

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.

Bioorg. Med. Chem. Lett. 19:6670-6674(2009) [PubMed] [Europe PMC]

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