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
| Autor: | Robert L. Clark, Arsenio A. Pessolano, Lars M. Flataker, Howard Jones, Victor J. Lotti, David P. Jacobus, Tsung-Ying Shen |
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| Rok vydání: | 1978 |
| Předmět: |
Pyridines
Pyridones Analgesic Triazole Alkylation Medicinal chemistry Methylenedioxy chemistry.chemical_compound Mice Structure-Activity Relationship Drug Discovery medicine Reaction Time Structure–activity relationship Imidazole Animals Humans Foot edema Inflammation Naloxone Codeine Anti-Inflammatory Agents Non-Steroidal Rats Substance Withdrawal Syndrome chemistry Molecular Medicine Female medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 21(9) |
| ISSN: | 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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