Aminopyridine carboxamides as c-Jun N-terminal kinase inhibitors: targeting the gatekeeper residue and beyond

Gang Liu; Hongyu Zhao; Bo Liu; Zhili Xin; Mei Liu; Christi Kosogof; Bruce G Szczepankiewicz; Sanyi Wang; Jill E Clampit; Rebecca J Gum; Deanna L Haasch; James M Trevillyan; Hing L Sham

doi:10.1016/j.bmcl.2006.08.097

Aminopyridine carboxamides as c-Jun N-terminal kinase inhibitors: targeting the gatekeeper residue and beyond

Bioorg Med Chem Lett. 2006 Nov 15;16(22):5723-30. doi: 10.1016/j.bmcl.2006.08.097. Epub 2006 Sep 12.

Authors

Gang Liu¹, Hongyu Zhao, Bo Liu, Zhili Xin, Mei Liu, Christi Kosogof, Bruce G Szczepankiewicz, Sanyi Wang, Jill E Clampit, Rebecca J Gum, Deanna L Haasch, James M Trevillyan, Hing L Sham

Affiliation

¹ Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. [email protected]

PMID: 16971120
DOI: 10.1016/j.bmcl.2006.08.097

Abstract

The structure-activity relationships of 5,6-positions of aminopyridine carboxamide-based c-Jun N-terminal Kinase (JNK) inhibitors were explored to expand interaction with the kinase specificity and ribose-binding pockets. The syntheses of analogues and the impact of structural modification on in vitro potency and cellular activity are described.

MeSH terms

Amides / chemistry
Amides / pharmacology*
Aminopyridines / chemistry
Aminopyridines / pharmacology*
Crystallography, X-Ray
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Inhibitory Concentration 50
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
Protein Binding
Ribose / metabolism
Structure-Activity Relationship
Substrate Specificity

Substances

Amides
Aminopyridines
Enzyme Inhibitors
Ribose
JNK Mitogen-Activated Protein Kinases