Synthesis and biological activity of pyridopyridazin-6-one p38α MAP kinase inhibitors. Part 2

Robert M Tynebor; Meng-Hsin Chen; Swaminathan R Natarajan; Edward A O'Neill; James E Thompson; Catherine E Fitzgerald; Stephen J O'Keefe; James B Doherty

doi:10.1016/j.bmcl.2012.07.035

Synthesis and biological activity of pyridopyridazin-6-one p38α MAP kinase inhibitors. Part 2

Bioorg Med Chem Lett. 2012 Sep 15;22(18):5979-83. doi: 10.1016/j.bmcl.2012.07.035. Epub 2012 Aug 2.

Authors

Robert M Tynebor¹, Meng-Hsin Chen, Swaminathan R Natarajan, Edward A O'Neill, James E Thompson, Catherine E Fitzgerald, Stephen J O'Keefe, James B Doherty

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. robert_tynebor@merck.com

PMID: 22901390
DOI: 10.1016/j.bmcl.2012.07.035

Abstract

This manuscript concludes the Structure Activity Relationship (SAR) on the pyridazinone scaffold and identifies a compound with subnanomolar p38α activity and 24h coverage in the rat arthritis efficacy model.

MeSH terms

Animals
Dogs
Dose-Response Relationship, Drug
Haplorhini
Humans
Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
Mitogen-Activated Protein Kinase 14 / metabolism
Molecular Structure
Protein Kinase Inhibitors / administration & dosage
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / pharmacology*
Pyridazines / administration & dosage
Pyridazines / chemical synthesis*
Pyridazines / pharmacology*
Pyridines / administration & dosage
Pyridines / chemical synthesis*
Pyridines / pharmacology*
Rats
Structure-Activity Relationship

Substances

Protein Kinase Inhibitors
Pyridazines
Pyridines
pyridopyridazin-6-one
Mitogen-Activated Protein Kinase 14