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 Combining double low line 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 Combining double low line 23 μM and was found inactive towards COX-2.

Autore Pugliese

• Scilimati Antonio , Perrone Maria Grazia , Vitale Paola

Tutti gli autori

• PANELLA A.;SCILIMATI A.;PERRONE M.G.;VITALE P.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2015

ISSN

0223-5234

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

17

Ultimo Aggiornamento Citazioni

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Settori ERC

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Codici ASJC

Non Disponibile