Synthesis and SAR of 2-phenoxypyridines as novel c-Jun N-terminal kinase inhibitors

Xinyi Song; Weimin Chen; Li Lin; Claudia H Ruiz; Michael D Cameron; Derek R Duckett; Theodore M Kamenecka

doi:10.1016/j.bmcl.2011.09.090

Synthesis and SAR of 2-phenoxypyridines as novel c-Jun N-terminal kinase inhibitors

Bioorg Med Chem Lett. 2011 Dec 1;21(23):7072-5. doi: 10.1016/j.bmcl.2011.09.090. Epub 2011 Sep 29.

Authors

Xinyi Song¹, Weimin Chen, Li Lin, Claudia H Ruiz, Michael D Cameron, Derek R Duckett, Theodore M Kamenecka

Affiliation

¹ Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.

PMID: 22004719
DOI: 10.1016/j.bmcl.2011.09.090

Abstract

The design and synthesis of a novel series of c-jun N-terminal kinase (JNK3) inhibitors is described. The development and optimization of the 2-phenoxypyridine series was carried out from an earlier pyrimidine series of JNK1 inhibitors. Through the optimization of the scaffold 2, several potent compounds with good in vivo profiles were discovered.

MeSH terms

Drug Design*
Enzyme Activation / drug effects
Inhibitory Concentration 50
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
Models, Molecular
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Pyridines / chemical synthesis*
Pyridines / chemistry
Pyridines / pharmacology
Pyrimidines / chemical synthesis*
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Structure-Activity Relationship

Substances

Protein Kinase Inhibitors
Pyridines
Pyrimidines
JNK Mitogen-Activated Protein Kinases