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

Abstract

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.

Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain

“…The following synthesis is based on that reported in [41]. Step 1: To a solution of 2-chloro-3-nitropyridine (95.0 g, 0.600 mol) and ethyl 4-aminobenzoate (99.0 g, 0.600 mol) in toluene (3 L) was added K 2 CO 3 (166 g, 1.20 mol), BINAP (7.40 g, 11.8 mmol), Pd(OAc) 2 (2.80 g, 12.5 mmol), and NaI (2.70 g, 18.0 mmol).…”

6-Bromo-1-[2-(2-oxo-1,3-oxazolidin-3-yl)ethyl]-1H-imidazo[4,5-b]pyridin-2(3H)-one

“…For the medicinal properties of imidazo [4,5-b]pyridines, see: Barraclough et al (1990); Bianchi et al (1983); Clark et al (1978); Janssens et al (1985); Temple et al (1987). Mo K radiation = 3.26 mm À1 T = 173 K 0.40 Â 0.20 Â 0.05 mm…”

Design and One-Pot Synthesis of (1H, 3H) Imidazo[4,5-b] Pyridines: Novel Therapeutic Agents Against M. Tuberculosis

“…The potent biological activity and the prevalence of 1-desazapurines in both natural products and pharmaceuticals have inspired significant interest in the synthesis of these heterocycles. Compounds that belong to the imidazo [4,5-b]pyridin-2-one class have been shown to be nonsteroidal anti-inflammatory and analgesic agents [14][15][16][17] and to possess antidepressant [15][16][17][18] , antiphlogistic [7][8][9][10][11][12][13][14][15][16][17][18][19] , cardiotonic [17][18][19][20] , hypotensive and anti-arrhythmic activity [18][19][20][21] . In addition certain members of this class had been reported to be a potent inhibitor of Aurora-A 22 , adenosine deaminase (ADA) inhibitors 23 , potent inhibitors of inosine 5'-monophosphate dehydrogenase (IMPDH) 24 .…”