1,3,4-Oxadiazole, 1,3,4-thiadiazole, and 1,2,4-triazole analogs of the fenamates: in vitro inhibition of cyclooxygenase and 5-lipoxygenase activities

Abstract

N-Arylanthranilic acids, known generically as the fenamates, are nonsteroidal antiinflammatory drugs (NSAIDs) that block the metabolism of arachidonic acid by the enzyme cyclooxygenase (CO). Substitution of the carboxylic acid functionality of several fenamates with acidic heterocycles provided dual inhibitors of CO and 5-lipoxygenase (5-LO) activities when tested in an intact rat basophilic leukemia (RBL-1) cell line. Compound 5b (IC50 = 0.77 microM (5-LO), 0.27 microM (CO)) which contains an 1,3,4-oxadiazole-2-thione replacement and 10b (IC50 = 0.87 microM (5-LO), 0.85 microM (CO)) which contains a 1,3,4-thiadiazole-2-thione are the most potent inhibitors of 5-LO and CO activities from these series. Both of these heterocyclic analogs of flufenamic acid are also active in carageenin-induced rat footpad edema (CFE), a model of acute inflammation. When dosed orally the ID50s for 5b and 10b in CFE are 8.5 and 4.7 mg/kg, respectively.

Biological Evaluation of 2, 5-Di (4 Aryloylaryloxy Methyl) - 1, 3, 4-Oxadiazoles Derivatives as Antimicrobial Agents

“…The compounds with the backbone of benzophenones have been reported to possess various biological activities such as anticancer [8] antimicrobial [9] antioxidant [10]. 1,3,4-Oxadiazole ring is associated with many types of biological properties such as anti-inflammatory [11][12][13], hypoglycemic [14], antifungal and antibacterial [15][16][17][18][19] activities. 1,3,4-Oxadiazoles and its derivatives have a broad range of biological and pharmacological properties and are widely used as starting materials for the synthesis of a broad range of heterocyclic compounds and substrates for the drug synthesis.…”

Synthesis and Pharmacological Evaluation of Certain Novel Oxadiazole Derivatives Containing Substituted Phenylimidazole Moiety

“…The tendency of many acidic drugs to accumulate in the stomach walls soon after oral absorption, as evidenced by radio autography, has been considered as a contributory factor for GI irritation 2 . It has been reported in the literature that certain five membered heterocyclic compounds possess interesting antiinflammatory activity with lesser GI effect 3,4 . Among heterocyclic compounds, imidazole bearing nucleus have been reported to have significant anti-inflammatory activity 5,6 .…”

Solvent-Free Synthesis and Assessment of Substituent Effects from IR & NMR Spectra of some Substituted Benzylidene-5-Ethyl-1,3,4-Thiadiazole-2-Amines

“…Therefore chemists and researchers paid more attentions for synthesis of heterocyclic compounds by synthetic routes or naturally occurring methods [1]. Some of the important biological activities of these thiadiazoles are antitumor agent [2], potent inhibitors of 5-lipoxygenase and cyclooxygenase [3], antimicrobials [4], anti-tuberculosis [5,6], antiinflammatory [7], antidepressant and anxiolytics [8], anticancer [9,10], anthelmintic [11] and antimicrobial [1]. Numerous solvent-free methods and solvent assisted methods were reported for the synthesis of heterocyclics [1,[12][13][14].…”