1,5-diary1-2-alkylpyrrole-3-substituted nitro esters, selective cox-2 inhibitors and nitric oxide donors

Abstract

1,5-diaryl-2-alkylpyrrole-3-substituted nitro esters, of Formula (I) are provided. Such compounds are potent and selective COX-2 inhibitors which are able to release NO in concentrations that make it possible to counteract the side effects due to selective COX-2 inhibition, without giving rise to hypotensive effects. Formula (I) includes compounds wherein the groups R' and R″ are: —H, —F, —Cl, —Br, —CH, —CF, —OCH, —SCH, R1 is methyl, ethyl, trifluoromethyl, hydroxymethyl, methoxymethyl and the substituent in position −3 of the pyrrole ring is a chain, where the groups X, Y, Z, W and R2 are: X is a carbonyl or a group —(CHR)—, Y is an oxygen atom or the group —NR— and Z is a carbonyl or a group —(CHR)—, or a [—CH(COOH)—] group, or a group —(NR)—, W is an aliphatic chain substituted with one or two (—O—NO) groups, R2 is: —H, —OH, —OCH, or —NHR. Ris: —H, —CH, —CHCH, [—CH(CH)]. R′″ is methylsulphonyl or sulphonamido. Pharmaceutical formulations and methods of making an using such formulations are also provided.