Pyridine analogues of nimesulide: design, synthesis, and in vitro and in vivo pharmacological evaluation as promising cyclooxygenase 1 and 2 inhibitors.

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Renard JF, Arslan D, Garbacki N, Pirotte B, de Leval X

Pyridine analogues of nimesulide: design, synthesis, and in vitro and in vivo pharmacological evaluation as promising cyclooxygenase 1 and 2 inhibitors.

J Med Chem. 2009 Oct 8;52(19):5864-71. doi: 10.1021/jm900702b.

PubMed ID

19791801 [ View in PubMed

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Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) represent one of the most prescribed medications, although the chronic use of such pharmacological agents is commonly associated with numerous side effects. The demonstration that the use of COX-2 selective or preferential inhibitors is associated with a better tolerability opened new horizons in the search of safer drugs for the management of inflammation. In the present study, we report the synthesis and the pharmacological evaluation of pyridine analogues of nimesulide, a COX-2 preferential inhibitor. The cyclooxygenases (COXs) inhibitory activities were evaluated in vitro using a human whole blood model. According to the in vitro results, a selection of compounds exhibiting moderate to high COX-2/COX-1 selectivity ratio (from weak COX-2 preferential inhibitors to compounds displaying a celecoxib-like selectivity profile) were further evaluated in vivo in a model of lambda carrageenan-induced pleurisy in rats. Some of the selected compounds displayed similar or improved anti-inflammatory properties when compared to nimesulide and celecoxib.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Celecoxib	Prostaglandin G/H synthase 2	IC 50 (nM)	350	N/A	N/A	Details
Nimesulide	Prostaglandin G/H synthase 2	IC 50 (nM)	700	N/A	N/A	Details