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ID: ALA1143513

Journal: Bioorg Med Chem Lett

Title: Structure-activity relationships for 2-anilino-6-phenylpyrido[2,3-d]pyrimidin-7(8H)-ones as inhibitors of the cellular checkpoint kinase Wee1.

Authors: Palmer BD, Smaill JB, Rewcastle GW, Dobrusin EM, Kraker A, Moore CW, Steinkampf RW, Denny WA.

Abstract: A series of 2-anilino-6-phenylpyrido[2,3-d]pyrimidin-7(8H)-ones were synthesized and evaluated for their inhibitory properties against the non-receptor kinase c-Src and the G2/M checkpoint kinase Wee1. Overall, the compounds were 10-100-fold more potent inhibitors of c-Src than Wee1, and variation of substituents on the 6-phenyl ring did not markedly alter this preference. Solubilizing substituents off the 2-anilino ring in many cases increased Wee1 activity, thus lowering this preference to about 10-fold. 5-Alkyl substituted analogs were generally Wee1 selective, but at the expense of absolute potency.

CiteXplore: 15780636

DOI: 10.1016/j.bmcl.2005.01.079