The identification of pyrazolo[1,5-a]pyridines as potent p38 kinase inhibitors

Mui Cheung; Philip A Harris; Jennifer G Badiang; Gregory E Peckham; Stanley D Chamberlain; Michael J Alberti; David K Jung; Stephanie S Harris; Neal H Bramson; Andrea H Epperly; Stephen A Stimpson; Michael R Peel

doi:10.1016/j.bmcl.2008.09.040

The identification of pyrazolo[1,5-a]pyridines as potent p38 kinase inhibitors

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5428-30. doi: 10.1016/j.bmcl.2008.09.040. Epub 2008 Sep 12.

Authors

Mui Cheung¹, Philip A Harris, Jennifer G Badiang, Gregory E Peckham, Stanley D Chamberlain, Michael J Alberti, David K Jung, Stephanie S Harris, Neal H Bramson, Andrea H Epperly, Stephen A Stimpson, Michael R Peel

Affiliation

¹ GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA. mui.h.cheung@gsk.com

PMID: 18818075
DOI: 10.1016/j.bmcl.2008.09.040

Abstract

A series of pyrazolo[1,5-a]pyridine derivatives was designed and synthesized as novel potent p38 kinase inhibitors. Our approaches towards improving in vitro metabolism and in vivo pharmacokinetic properties of the series are described.

MeSH terms

Animals
Anti-Inflammatory Agents / chemical synthesis
Anti-Inflammatory Agents / pharmacology
Area Under Curve
Chemistry, Pharmaceutical / methods*
Dogs
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacokinetics*
Humans
Inhibitory Concentration 50
Leukocytes, Mononuclear / drug effects
MAP Kinase Signaling System
Pyridines / chemical synthesis*
Pyridines / pharmacokinetics
Rats
Structure-Activity Relationship
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Anti-Inflammatory Agents
Enzyme Inhibitors
Pyridines
p38 Mitogen-Activated Protein Kinases