Synthesis and biological activity of pyridopyridazin-6-one p38α MAP kinase inhibitors. Part 2.
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.
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. robert_tynebor@merck.com
Robert M
RM
Tynebor
Meng-Hsin
MH
Chen
Swaminathan R
SR
Natarajan
Edward A
EA
O'Neill
James E
JE
Thompson
Catherine E
CE
Fitzgerald
Stephen J
SJ
O'Keefe
James B
JB
Doherty
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D000882:Haplorhini; D006801:Humans; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D011724:Pyridazines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D011724:Pyridazines; D011725:Pyridines; C576866:pyridopyridazin-6-one; D048308:Mitogen-Activated Protein Kinase 14