1266331-58-1Relevant articles and documents
Optimization of pyrazole-based compounds with 1,2,4-triazole-3-thiol moiety as selective COX-2 inhibitors cardioprotective drug candidates: Design, synthesis, cyclooxygenase inhibition, anti-inflammatory, ulcerogenicity, cardiovascular evaluation, and molecular modeling studies
Abdellatif, Khaled R.A.,Abdelall, Eman K.A.,Elshemy, Heba A.H.,Philoppes, John N.,Hassanein, Emad H.M.,Kahk, Nesma M.
, (2021/07/12)
The cardiovascular side effects associated with COX-2 selective drugs were the worst for coxibs leading to their withdrawal from the market a few years after their discovery. Therefore, the design of new series of pyrazole (4a,b 5a,b, 7a,b, 9a,b, 10a-h, and 11a-f) substituted with a triazole moiety as selective COX-2 inhibitors with cardioprotective effect was aimed in this paper. The target compounds were prepared and evaluated in-vitro against COX-1 and COX-2 enzymes. Compound 5-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-4H-1,2,4-triazole-3-thiol (7a) showed the highest selectivity towards COX-2 enzyme (S.I. = 27.56) and was the most active anti-inflammatory agent. Interestingly, its cardiovascular profile showed the cardiac biomarkers (ALP, AST, CK-MB, and LDH), as well as inflammatory cytokines named (TNF-α and IL-6) nearly similar to the control. Besides, a histopathological study of the heart muscle and the stomach was also included. The results confirmed that compound 7a has a more favorable cardio profile than celecoxib. Moreover, docking simulation for the most selective compounds 4b, 7a, 10e, 11c, and 11e inside COX-2 active site was performed to explain their binding mode. Finally, an ADME study was applied and proved the promising activity of the new compounds as a new oral anti-inflammatory agent. In conclusion, the newly developed compound 7a represents a potential selective COX-2 NSAID candidate with minimum cardiovascular risks.
Synthesis and antibacterial activity of N-substituted-[1,2,4]triazoles and 1,2,4-Triazole[3,4-b][1,3,4]thiadiazines
Sanjeeva Reddy,Sanjeeva Rao,Sunitha,Nagaraj
, p. 1283 - 1289 (2015/11/25)
New series of N-[3-(5-methyl-1-phenyl-1H-4-pyrazolyl)-5- sulfanyl-4H-1,2,4-Triazol-4-yl]-N'-Arylthiourea derivatives 8a-e and 3-(5-methyl-1-phenyl-1H-4-pyrazolyl)-6-Aryl-7H-[1,2,4] triazolo[3,4- b][1,3,4]thiadiazines 9a-e have been prepared and screened for their antibacterial activity against four human pathogenic bacteria, Escherichia coli, Klebseilla pneumoniae, Shigella dysentriae and Shigella flexnei. Among the screened, compounds 8b, 8c and 8e, in which phenyl ring of isothiocyanate moiety bear 3-fluoro, 4-fluoro and 4-bromo substituents respectively, show high activity against all the micro-organisms employed. The compound 9c is highly active against all the test organisms employed. The zone of inhibition is more than what is found for the standard drug neomycin, and almost equal to the standard drug streptomycin.
