CH···O and CH···N Hydrogen Bonds in Ligand Design: A Novel Quinazolin-4-ylthiazol-2-ylamine Protein Kinase Inhibitor

Albert C. Pierce ,* Ernst ter Haar , Hayley M. Binch , David P. Kay , Sanjay R. Patel , and Pan Li

Vertex Pharmaceuticals, Inc., 130 Waverly Street, Cambridge, Massachusetts 02139

J. Med. Chem., 2005, 48 (4), pp 1278–1281

DOI: 10.1021/jm0492249

Publication Date (Web): January 25, 2005

Abstract

Aryl CH hydrogen bonds play an important role in the binding of several analogues of a pyrazol-3-ylquinazolin-4-ylamine inhibitor of glycogen synthase kinase 3 (GSK3). Understanding the importance of these CH···O and CH···N hydrogen bonds allowed the design of a novel quinazolin-4-ylthiazol-2-ylamine inhibitor of GSK3 with a structurally confirmed CH···O hydrogen bond to the protein.

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Brief Article

CH···O and CH···N Hydrogen Bonds in Ligand Design: A Novel Quinazolin-4-ylthiazol-2-ylamine Protein Kinase Inhibitor

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