General role of the amino and methylsulfamoyl groups in selective cyclooxygenase(COX)-1 inhibition by 1,4-diaryl-1,2,3-triazoles and validation of a predictive pharmacometric PLS model

European Journal of Medicinal Chemistry
Maria Grazia PerroneAntonio Scilimati

Abstract

A novel set of 1,4-diaryl-1,2,3-triazoles were projected as a tool to study the effect of both the heteroaromatic triazole as a core ring and a variety of chemical groups with different electronic features, size and shape on the catalytic activity of the two COX isoenzymes. The new triazoles were synthesized in fair to good yields and then evaluated for their inhibitory activity towards COXs arachidonic acid conversion catalysis. Their COXs selectivity was also measured. A predictive pharmacometric Volsurf plus model, experimentally confirmed by the percentage (%) of COXs inhibition at the concentration of 50 μM and IC50 values of the tested compounds, was built by using a number of isoxazoles of known COXs inhibitory activity as a training set. It was found that two compounds {4-(5-methyl-4-phenyl-1H-1,2,3-triazol-1-yl)benzenamine (18) and 4-[1-(4-methoxyphenyl)-5-methyl-1H-1,2,3-triazole-4-yl]benzenamine (19)} bearing an amino group (NH2) are potent and selective COX-1 inhibitors (IC50 = 15 and 3 μM, respectively) and that the presence of a methylsulfamoyl group (SO2CH3) is not a rule to have a Coxib. In fact, 4-(4-methoxyphenyl)-5-methyl-1-[4-(methylsulfonyl)phenyl]-1H-1,2,3-triazole (23) has COX-1 IC50 = 23 μM and was found...Continue Reading

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Citations

Apr 26, 2016·Medicinal Research Reviews·Paola VitaleMaria Grazia Perrone
Oct 3, 2018·SAR and QSAR in Environmental Research·Y XiA Yan
Jun 3, 2020·International Journal of Molecular Sciences·Ching-Yi ChengMuhammad S Khan
May 3, 2016·ChemMedChem·Maria Grazia PerroneAntonio Scilimati
Apr 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xunan ZhengDawei Zhang
Aug 20, 2019·Current Medicinal Chemistry·Maria Grazia PerroneAntonio Scilimati

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