pyrimidinones and aniline

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.

Topics: Aniline Compounds; Cell Cycle Proteins; Cells, Cultured; Checkpoint Kinase 1; CSK Tyrosine-Protein Kinase; Enzyme Inhibitors; Humans; Inhibitory Concentration 50; Naphthyridines; Nuclear Proteins; Protein Kinases; Protein-Tyrosine Kinases; Pyrimidinones; Solubility; src-Family Kinases; Structure-Activity Relationship