SAR of 3,4-dihydropyrido[3,2-d]pyrimidone p38 inhibitors

Luping Liu; John E Stelmach; Swaminathan R Natarajan; Meng-Hsin Chen; Suresh B Singh; Cheryl D Schwartz; Catherine E Fitzgerald; Stephen J O'Keefe; Dennis M Zaller; Dennis M Schmatz; James B Doherty

doi:10.1016/j.bmcl.2003.08.059

SAR of 3,4-dihydropyrido[3,2-d]pyrimidone p38 inhibitors

Bioorg Med Chem Lett. 2003 Nov 17;13(22):3979-82. doi: 10.1016/j.bmcl.2003.08.059.

Authors

Luping Liu¹, John E Stelmach, Swaminathan R Natarajan, Meng-Hsin Chen, Suresh B Singh, Cheryl D Schwartz, Catherine E Fitzgerald, Stephen J O'Keefe, Dennis M Zaller, Dennis M Schmatz, James B Doherty

Affiliation

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

PMID: 14592489
DOI: 10.1016/j.bmcl.2003.08.059

Abstract

Development for a class of potent 3,4-dihydropyrido(3,2-d)pyrimidone inhibitors of p38a MAP kinase is described. Modification of N-1 aryl and C-6 arylsulfide in 3,4-dihydropyrido(3,2-d)pyrimidone analogues for the interaction with the hydrophobic pockets in p38 active site is also discussed.

MeSH terms

Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Kinetics
Mitogen-Activated Protein Kinases / antagonists & inhibitors*
Molecular Structure
Pyrimidinones / chemical synthesis*
Pyrimidinones / pharmacology
Structure-Activity Relationship
p38 Mitogen-Activated Protein Kinases

Substances

3,4-dihydropyrido(3,2-d)pyrimidone
Enzyme Inhibitors
Pyrimidinones
Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases