Synthesis and biological activity of pyridopyridazin-6-one p38 MAP kinase inhibitors. Part 1

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.2010.10.128

Synthesis and biological activity of pyridopyridazin-6-one p38 MAP kinase inhibitors. Part 1

Bioorg Med Chem Lett. 2011 Jan 1;21(1):411-6. doi: 10.1016/j.bmcl.2010.10.128. Epub 2010 Oct 30.

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: 21084192
DOI: 10.1016/j.bmcl.2010.10.128

Abstract

The development and synthesis of potent p38α MAP kinase inhibitors containing a pyridazinone platform is described. Evolution of the p38α selective pyridopyridazin-6-one series from the p38α/β dual inhibitor 2H-quinolizin-2-one series will be discussed in full detail.

MeSH terms

Animals
Binding Sites
Catalytic Domain
Computer Simulation
Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
Mitogen-Activated Protein Kinase 14 / metabolism
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacokinetics
Protein Structure, Tertiary
Pyridazines / chemical synthesis
Pyridazines / chemistry*
Pyridazines / pharmacokinetics
Rats
Structure-Activity Relationship

Substances

Protein Kinase Inhibitors
Pyridazines
Mitogen-Activated Protein Kinase 14