Synthesis and analgesic activity of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones and 3-(substituted phenyl)-1,2,3-triazolo[4,5-b]pyridines.
In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the pain thresholds of both the inflamed and normal foot were elevated. This is not commonly observed with nonsteroidal antiinflammatory agents. The most active compounds were 1,3-dihydro-3[3,4-(methylenedioxy)phenyl]imidazo[4,5-b]pyridin-2-one (I-15) and its N-allyl (I-21) and N-isopropyl (I-121) derivatives. In the triazole series the 3-(2-fluoro- and 2,4-difluorophenyl)triazolo[4,5-b]pyridines (T-1 and T-8) were the best. The imidazole compounds were somewhat superior in analgesic activity to codeine and d-propoxyphene without showing any narcotic characteristics. Some of the compounds also possessed activity against carrageenan-induced foot edema in the rat, so these compounds represent a new class of nonnarcotic analgesic antiinflammatories, capable of producing a greater degree of analgesia than that obtainable with other nonsteroidal antiinflammatory agents.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D013329:Structure-Activity Relationship; D013375:Substance Withdrawal Syndrome / Q000139:chemically induced
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011725:Pyridines; D011728:Pyridones; D009270:Naloxone