3,5-Disubstituted quinolines as novel c-Jun N-terminal kinase inhibitors

Rong Jiang; Derek Duckett; Weiming Chen; Jeff Habel; Yuan Yuan Ling; Philip LoGrasso; Theodore M Kamenecka

doi:10.1016/j.bmcl.2007.08.054

3,5-Disubstituted quinolines as novel c-Jun N-terminal kinase inhibitors

Bioorg Med Chem Lett. 2007 Nov 15;17(22):6378-82. doi: 10.1016/j.bmcl.2007.08.054. Epub 2007 Aug 26.

Authors

Rong Jiang¹, Derek Duckett, Weiming Chen, Jeff Habel, Yuan Yuan Ling, Philip LoGrasso, Theodore M Kamenecka

Affiliation

¹ Department of Medicinal Chemistry, Scripps Florida, 5353 Parkside Drive, RF-2, Jupiter, FL 33458, USA. rjiang@scripps.edu

PMID: 17911023
DOI: 10.1016/j.bmcl.2007.08.054

Abstract

The structure-based design and synthesis of a novel series of c-Jun N-terminal kinase (JNK) inhibitors with selectivity against p38 is reported. The unique structure of 3,5-disubstituted quinolines (2) was developed from the previously reported 4-(2,7-phenanthrolin-9-yl)phenol (1). The X-ray crystal structure of 16a in JNK3 reveals an unexpected binding mode for this new scaffold with protein.

MeSH terms

Crystallography, X-Ray
Drug Design*
Drug Evaluation, Preclinical
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
Molecular Structure
Phenanthrolines / chemical synthesis
Phenanthrolines / chemistry
Phenanthrolines / pharmacology
Protein Binding / drug effects
Quinolines / chemistry*
Quinolines / pharmacology*
Structure-Activity Relationship
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors

Substances

Phenanthrolines
Quinolines
JNK Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases