title: p38MAP kinase inhibitors. Part 1: design and development of a new class of potent and highly selective inhibitors based on 3,4-dihydropyrido[3,2-d]pyrimidone scaffold.
abstract: A new class of p38 antagonists based on 3,4-dihydropyrido[3,2,-d]pyrimidine scaffold has been developed. These inhibitors exhibit unprecedented selectivity towards p38 over other very closely related kinases. Compounds 25, 33, and 34 were identified as benchmark analogues for follow-up studies. They show good potency for enzyme inhibition and excellent functional activity.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. natarajan@merck.com
authors.forename: Swaminathan R
authors.initials: SR
authors.lastname: Natarajan
authors.forename: David D
authors.initials: DD
authors.lastname: Wisnoski
authors.forename: Suresh B
authors.initials: SB
authors.lastname: Singh
authors.forename: John E
authors.initials: JE
authors.lastname: Stelmach
authors.forename: Edward A
authors.initials: EA
authors.lastname: O'Neill
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Schwartz
authors.forename: Chris M
authors.initials: CM
authors.lastname: Thompson
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Fitzgerald
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Keefe
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: Cornelis E C A
authors.initials: CE
authors.lastname: Hop
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Zaller
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Schmatz
authors.forename: James B
authors.initials: JB
authors.lastname: Doherty
mesh_terms: D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D011725:Pyridines; D011744:Pyrimidinones; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases