1,5-DIARYL-2-ALKYLPYRROLE-3-SUBSTITUTED NITRO ESTERS, SELECTIVE COX-2 INHIBITORS AND NITRIC OXIDE DONORS

摘要

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, CH3, CF3, OCH3, SCH3, 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 (CHR3), Y is an oxygen atom or the group NR3 and Z is a carbonyl or a group (CHR3), or a [CH(COOH)] group, or a group (NR3), W is an aliphatic chain substituted with one or two (ONO2) groups, R2 is: H, OH, OCH3, or NHR3. R3 is: H, CH3, CH2CH3, [CH2(CH3)2]. R is methylsulphonyl or sulphonamido. Pharmaceutical formulations and methods of making an using such formulations are also provided.