title: Synthesis and biological activity of 2H-quinolizin-2-one based p38alpha MAP kinase inhibitors.
abstract: The development and synthesis of potent p38alpha MAP kinase inhibitors containing a 2H-quinolizin-2-one platform is described. Evolution of the 2H-quinolizin-2-one series from an early lead to solving off target activity and pharmacokinetic issues is also discussed.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. Robert_tynebor@merck.com
authors.forename: Robert M
authors.initials: RM
authors.lastname: Tynebor
authors.forename: Meng-Hsin
authors.initials: MH
authors.lastname: Chen
authors.forename: Swaminathan R
authors.initials: SR
authors.lastname: Natarajan
authors.forename: Edward A
authors.initials: EA
authors.lastname: O'Neill
authors.forename: James E
authors.initials: JE
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: James B
authors.initials: JB
authors.lastname: Doherty
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D002460:Cell Line; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011807:Quinolizines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D047428:Protein Kinase Inhibitors; D011807:Quinolizines; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases