Phenylaminopyrimidines as inhibitors of Janus kinases (JAKs)

A series of phenylaminopyrimidines has been identified as inhibitors of Janus kinases (JAKs). Development of this initial series led to the potent JAK2/JAK1 inhibitor CYT387 (N-(cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]-benzamide). Details of synthesis and SAR studies of these compounds are reported.

Graphical abstractDetails of SAR studies leading to CYT387, a potent and selective dual JAK1 and JAK2 inhibitor, are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide