Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors

Abstract

Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine based JAK2 inhibitors with higher potency (IC₅₀ of 0.7nM) and selectivity (>30 fold) to JAK3 kinase than tofacitinib.

Keywords: 4,5,6,7-Tetrahydro-furo[3,2-c]pyridine; 4-(2-Furanyl)pyrimidin-2-amine; JAK2 inhibitor; Kinase selectivity.