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; Pan Li

doi:10.1021/jm0492249

CH...O and CH...N hydrogen bonds in ligand design: a novel quinazolin-4-ylthiazol-2-ylamine protein kinase inhibitor

J Med Chem. 2005 Feb 24;48(4):1278-81. doi: 10.1021/jm0492249.

Authors

Albert C Pierce¹, Ernst ter Haar, Hayley M Binch, David P Kay, Sanjay R Patel, Pan Li

Affiliation

¹ Vertex Pharmaceuticals, Inc., 130 Waverly Street, Cambridge, Massachusetts 02139, USA. [email protected]

PMID: 15715498
DOI: 10.1021/jm0492249

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.

MeSH terms

Drug Design
Glycogen Synthase Kinase 3 / antagonists & inhibitors*
Glycogen Synthase Kinase 3 / chemistry*
Hydrogen Bonding
Isomerism
Ligands
Models, Molecular
Molecular Conformation
Quinazolines / chemical synthesis*
Quinazolines / chemistry
Structure-Activity Relationship
Thiazoles / chemical synthesis*
Thiazoles / chemistry

Substances

Ligands
Quinazolines
Thiazoles
Glycogen Synthase Kinase 3