Rottapharm Biotech S.r.l.

International Society for Drug Development S.r.l.

Vincenzo Calderone

Lucio C Rovati

Antonio Giordani

Maurizio Anzini

Mariangela Biava

Claudia Martini

Lucio Claudio Rovati

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&#x2033; are: &#x2014;H, &#x2014;F, &#x2014;Cl, &#x2014;Br, &#x2014;CH, &#x2014;CF, &#x2014;OCH, &#x2014;SCH, R1 is methyl, ethyl, trifluoromethyl, hydroxymethyl, methoxymethyl and the substituent in position &#x2212;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 &#x2014;(CHR)&#x2014;, Y is an oxygen atom or the group &#x2014;NR&#x2014; and Z is a carbonyl or a group &#x2014;(CHR)&#x2014;, or a [&#x2014;CH(COOH)&#x2014;] group, or a group &#x2014;(NR)&#x2014;, W is an aliphatic chain substituted with one or two (&#x2014;O&#x2014;NO) groups, R2 is: &#x2014;H, &#x2014;OH, &#x2014;OCH, or &#x2014;NHR. Ris: &#x2014;H, &#x2014;CH, &#x2014;CHCH, [&#x2014;CH(CH)]. R&#x2032;&#x2033; is methylsulphonyl or sulphonamido. Pharmaceutical formulations and methods of making an using such formulations are also provided.

1,5-Diary1-2-alkylpyrrole-3-substituted nitro esters, selective COX-2 inhibitors and nitric oxide donors

Growing community of inventors

Massa, Italy

Vincenzo Calderone