Discovery of a new class of 4-anilinopyrimidines as potent c-Jun N-terminal kinase inhibitors: Synthesis and SAR studies

Mei Liu; Sanyi Wang; Jill E Clampit; Rebecca J Gum; Deanna L Haasch; Cristina M Rondinone; James M Trevillyan; Cele Abad-Zapatero; Elizabeth H Fry; Hing L Sham; Gang Liu

doi:10.1016/j.bmcl.2006.10.093

Discovery of a new class of 4-anilinopyrimidines as potent c-Jun N-terminal kinase inhibitors: Synthesis and SAR studies

Bioorg Med Chem Lett. 2007 Feb 1;17(3):668-72. doi: 10.1016/j.bmcl.2006.10.093. Epub 2006 Nov 2.

Authors

Mei Liu¹, Sanyi Wang, Jill E Clampit, Rebecca J Gum, Deanna L Haasch, Cristina M Rondinone, James M Trevillyan, Cele Abad-Zapatero, Elizabeth H Fry, Hing L Sham, Gang Liu

Affiliation

¹ Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6098, USA. mei.liu@abbott.com

PMID: 17107797
DOI: 10.1016/j.bmcl.2006.10.093

Abstract

A new series of 4-anilinopyrimidines has been synthesized and evaluated as JNK1 inhibitors. SAR studies led to the discovery of potent JNK1 inhibitors with good enzymatic activity as well as cellular potency represented by compound 2b. Kinase selectivity profile and the crystal structure of 2b are also described.

MeSH terms

Aniline Compounds / chemical synthesis*
Aniline Compounds / pharmacology*
Crystallography, X-Ray
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Indicators and Reagents
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Conformation
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology*
Structure-Activity Relationship

Substances

Aniline Compounds
Enzyme Inhibitors
Indicators and Reagents
Pyrimidines
JNK Mitogen-Activated Protein Kinases