1346223-13-9Relevant articles and documents
1,5-Diaryl-2-alkylpyrrole-3-Substituted Nitro Esters, Selective COX-2 Inhibitors and Nitric Oxide Donors
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Paragraph 0194; 0197, (2013/07/05)
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 (—O—NO2) 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.
Novel analgesic/anti-inflammatory agents: Diarylpyrrole acetic esters endowed with nitric oxide releasing properties
Biava, Mariangela,Porretta, Giulio Cesare,Poce, Giovanna,Battilocchio, Claudio,Alfonso, Salvatore,Rovini, Michele,Valenti, Salvatore,Giorgi, Gianluca,Calderone, Vincenzo,Martelli, Alma,Testai, Lara,Sautebin, Lidia,Rossi, Antonietta,Papa, Giuseppina,Ghelardini, Carla,Di Cesare Mannelli, Lorenzo,Giordani, Antonio,Anzellotti, Paola,Bruno, Annalisa,Patrignani, Paola,Anzini, Maurizio
, p. 7759 - 7771 (2012/01/03)
The design of compounds that are able to inhibit cyclooxygenase (COX) and to release nitric oxide (NO) should give rise to drugs endowed with an overall safer profile for the gastrointestinal and cardiovascular systems. Herein we report a new class of pyrrole-derived nitrooxy esters (11a-j), cyclooxygenase-2 (COX-2) selective inhibitors endowed with NO releasing properties, with the goal of generating new molecules able to both strongly inhibit this isoform and reduce the related adverse side effects. Taking into account the metabolic conversion of nitrooxy esters into corresponding alcohols, we also studied derivatives 12a-j. All compounds proved to be very potent and selective COX-2 inhibitors; nitrooxy derivatives displayed interesting ex vivo NO-dependent vasorelaxing properties. Compounds 11c, 11d, 12c, and 12d were selected for further in vivo studies that highlited good anti-inflammatory and antinociceptive activities. Finally, two selected compounds (11c and 12c) tested in human whole blood (HWB) assay proved to be preferential inhibitors of COX-2.
