Substituted 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-ones as potential antiinflammatory agents.
A series of analogues based on the 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one ring system have been synthesized and shown to possess oral antiinflammatory activity in both the reverse passive Arthus reaction (RPAR) pleural cavity assay in rats and in the adjuvant-induced arthritic rat model (AAR). Several members of this series additionally exhibit an inhibitory effect on the in vivo production of prostaglandin- and leukotriene-derived products or arachidonic acid metabolism although these compounds exhibit no significant inhibitory activity against the cyclooxygenase and 5-lipoxygenase enzymes in vitro. Structure-activity relationships in this series are discussed.
Ting
P C
PC
Department of Chemistry, Schering-Plough Research, Bloomfield, New Jersey 07003.
Kaminski
J J
JJ
Sherlock
M H
MH
Tom
W C
WC
Lee
J F
JF
Bryant
R W
RW
Watnick
A S
AS
McPhail
A T
AT
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis*; D001169:Arthritis, Experimental / Q000188:drug therapy; D001183:Arthus Reaction; D001792:Blood Platelets / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors; D004341:Drug Evaluation; D006801:Humans; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D009504:Neutrophils / Q000201:enzymology; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011728:Pyridones; D011758:Pyrroles