Disubstituted pyrimidines as Lck inhibitors

We have developed a family of 4-benzimidazolyl-N-piperazinethyl-pyrimidin-2-amines that are subnanomolar inhibitors of Lck. A subset of these Lck inhibitors, with heterocyclic substituents at the benzimidazole C5, are also low-nanomolar inhibitors of cellular IL2 release.

Compound 4 was found to be a potent inhibitor of Lck activity (IC50 = 0.1 nM) and cellular IL2 release (IC50 = 8 nM).Figure optionsDownload as PowerPoint slide