Bioorganic & Medicinal Chemistry Letters 2009-10-15

First generation 5-vinyl-3-pyridinecarbonitrile PKCtheta inhibitors.

Chuansheng Niu, Diane H Boschelli, L Nathan Tumey, Niala Bhagirath, Joan Subrath, Jaechul Shim, Yan Wang, Biqi Wu, Clark Eid, Julie Lee, Xiaoke Yang, Agnes Brennan, Divya Chaudhary, Chuansheng Niu, Diane H. Boschelli, L. Nathan Tumey, Niala Bhagirath, Joan Subrath, Jaechul Shim, Yan Wang, Biqi Wu, Clark Eid, Julie Lee, Xiaoke Yang, Agnes Brennan, Divya Chaudhary

Index: Bioorg. Med. Chem. Lett. 19 , 5829, (2009)

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Abstract

A series of 5-vinyl-3-pyridinecarbonitriles were synthesized and evaluated as PKCtheta inhibitors. The systematic optimization of 4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-phenylvinyl]-3-pyridinecarbonitrile 3 resulted in the identification of compound 23e as a potent PKCtheta inhibitor with good selectivity over PKCdelta.