Novel analgesic/anti-inflammatory agents: diarylpyrrole acetic esters endowed with nitric oxide releasing properties.

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Biava M, Porretta GC, Poce G, Battilocchio C, Alfonso S, Rovini M, Valenti S, Giorgi G, Calderone V, Martelli A, Testai L, Sautebin L, Rossi A, Papa G, Ghelardini C, Di Cesare Mannelli L, Giordani A, Anzellotti P, Bruno A, Patrignani P, Anzini M

Novel analgesic/anti-inflammatory agents: diarylpyrrole acetic esters endowed with nitric oxide releasing properties.

J Med Chem. 2011 Nov 24;54(22):7759-71. doi: 10.1021/jm200715n. Epub 2011 Oct 31.

PubMed ID

21992176 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Celecoxib	Prostaglandin G/H synthase 2	IC 50 (nM)	540	N/A	N/A	Details