Benzimidazolone p38 inhibitors.
The synthesis and in vitro p38 alpha activity of a novel series of benzimidazolone inhibitors is described. The p38 alpha SAR is consistent with a mode of binding wherein the benzimidazolone carbonyl serves as the H-bond acceptor to Met109 of p38 alpha in a manner analogous to the pyridine nitrogen of prototypical pyridylimidazole p38 inhibitors. Potent p38 alpha activity comparable to that of several previously reported p38 inhibitors is observed for this novel chemotype.
Dombroski
Mark A
MA
Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA.
Letavic
Michael A
MA
McClure
Kim F
KF
Barberia
John T
JT
Carty
Thomas J
TJ
Cortina
Santo R
SR
Csiki
Csilla
C
Dipesa
Alan J
AJ
Elliott
Nancy C
NC
Gabel
Christopher A
CA
Jordan
Crystal K
CK
Labasi
Jeff M
JM
Martin
William H
WH
Peese
Kevin M
KM
Stock
Ingrid A
IA
Svensson
Linne
L
Sweeney
Francis J
FJ
Yu
Chul H
CH
D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D048308:Mitogen-Activated Protein Kinase 14; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D011725:Pyridines / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D007093:Imidazoles; C490855:L-790070; D011725:Pyridines; D048308:Mitogen-Activated Protein Kinase 14; D020928:Mitogen-Activated Protein Kinases