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ID: ALA1153090

Journal: Bioorg Med Chem

Title: 5-Vinyl-3-pyridinecarbonitrile inhibitors of PKCtheta: optimization of enzymatic and functional activity.

Authors: Tumey LN, Bhagirath N, Brennan A, Brooijmans N, Lee J, Yang X, Boschelli DH.

Abstract: PKCtheta is a serine/threonine kinase involved in the regulation of IL2 production in T cells. It has recently become an attractive therapeutic target for a variety of immunological disorders. We describe the optimization of the enzymatic and cellular potency of a series of 5-vinyl-3-pyridinecarbonitrile inhibitors of PKCtheta. A binding model was developed that explains much of the SAR observed for this series, including the enzymatic potency observed for 19. An analysis of functional potency against various physiochemical parameters suggests that cellular potency is correlated with LogD(7.4), but not with cLogP, PAMPA permeability, or TPSA.

CiteXplore: 19884013

DOI: 10.1016/j.bmc.2009.10.020