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.
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.
Natarajan
Swaminathan R
SR
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. natarajan@merck.com
Wisnoski
David D
DD
Singh
Suresh B
SB
Stelmach
John E
JE
O'Neill
Edward A
EA
Schwartz
Cheryl D
CD
Thompson
Chris M
CM
Fitzgerald
Catherine E
CE
O'Keefe
Stephen J
SJ
Kumar
Sanjeev
S
Hop
Cornelis E C A
CE
Zaller
Dennis M
DM
Schmatz
Dennis M
DM
Doherty
James B
JB
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
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D011725:Pyridines; D011744:Pyrimidinones; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases