Structure–activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1

A Bach, N Stuhr-Hansen, TS Thorsen, N Bork…

Index: Bach, Anders; Stuhr-Hansen, Nicolai; Thorsen, Thor S.; Bork, Nicolai; Moreira, Irina S.; Frydenvang, Karla; Padrah, Shahrokh; Christensen, S. Brogger; Madsen, Kenneth L.; Weinstein, Harel; Gether, Ulrik; Stromgaard, Kristian Organic and Biomolecular Chemistry, 2010 , vol. 8, # 19 p. 4281 - 4288

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Citation Number: 17

Abstract

Recently, we described the first small-molecule inhibitor,(E)-ethyl 2-cyano-3-(3, 4- dichlorophenyl) acryloylcarbamate (1), of the PDZ domain of protein interacting with Cα- kinase 1 (PICK1), a potential drug target against brain ischemia, pain and cocaine addiction. Herein, we explore structure–activity relationships of 1 by introducing subtle modifications of the acryloylcarbamate scaffold and variations of the substituents on this scaffold. The ...

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