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A series of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1 H -imidazoles, 7a-c , 11a-h , and 16a-h has been synthesised and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Incorporation of a quinoxalin-6-yl moiety and a methylene linker at the 4- and 2-position of the imidazole ring, respectively, and a m- CONH 2 substituent in the phenyl ring generated a highly potent and selective ALK5 inhibitor 11e . Docking model of ALK5 in complex with 11e showed that it fitted well in the ATP-binding pocket with favourable interactions.

Protein tyrosine phosphatase (PTP) is the family of enzymes that are key players in cellular signal transduction system and perturbation in their functioning is implicated in many disease-states. Diverse chemical compounds are being synthesized and evaluated as PTP inhibitors. This review presents a brief account of various enzymes of the PTP family and their inhibitors. Peculiar features of these enzymes and their roles in various diseases are summarized along with important inhibitors developed in recent years.