Chemical modifications of nimesulide

Abstract

As modificações químicas da nimesulida via N-acilação direta ou através de um processo em duas etapas, envolvendo redução do grupo nitro seguida da acilação/sulfonilação regiosseletiva da arilamina resultante são descritas. A etapa da acilação do segundo método foi mais rápida do que a acilação da nimesulida. Uma série de derivados N-acilados e N-sulfonilados de N-(4-amino-2-fenóxi fenil)metanossulfonamida, obtidos a partir de nimesulida foram convenientemente preparados com bons a excelentes rendimentos. Alguns dos compostos sintetizados foram testados para inibição da ciclooxigenase e poucos mostraram seletividade para COX-2.We describe here the chemical modifications of nimesulide either via direct N-acylation or via a two-step process involving reduction of the nitro group followed by regioselective acylation/ sulfonylation of the resulting arylamine. The acylation step of the second approach was found to be faster than acylation of nimesulide. A number of N-acylated and N-sulfonylated derivatives of N-(4-amino-2-phenoxy phenyl)methanesulfonamide obtained from nimesulide were conveniently prepared in good to excellent yields. Some of the compounds synthesized were tested for cyclooxygenase inhibition and few of them showed selectivity for COX-2.

N-(4-Methylsulfonamido-3-phenoxyphenyl)-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboximide

“…The starting compound 1 (N-(4-amino-2-phenoxy-phenyl)-methane sulfonamide) required for our study was prepared [14] in quantitative yield from N-(4-nitro-2-phenoxy phenyl)methane sulfonamide B, (nimesulide) via reducing its nitro group as shown in Scheme 2. To a mixture of aromatic amine, (N-(4-amino-2-phenoxy-phenyl)-methane sulfonamide) 1 (278 mg, 1.0 mmol) and 9,10-dihydroanthracene 9,10-endo-α,β-succinic anhydride (2) (276 mg, 1.0 mmol) in glacial acetic acid (3 mL) was added anhydrous sodium acetate (100 mg, 1.2 mmol) and the mixture was allowed to reflux for 20 min.…”

“…Because of their common anti-inflammatory properties and our interest in nimesulide (N-(4-nitro-2-phenoxy phenyl)methane sulfonamide) derivatives [14][15][16][17][18] as potential anti-inflammatory agents we decided to prepare compound C having structural features of both A and B (Scheme 1).…”

Palladium‐mediated synthesis of novel nimesulide derivatives

“…[5] In our effort [6,7] to develop novel anti-inflammatory agents derived from existing and well-known NSAIDs we have reported synthesis and COX-2 inhibitory properties of a series of diaryl ethers generated from nimesulide recently. [8] In further continuation of our previous work we now wish to report a palladiummediated approach [9,10] to introduce unsaturated moieties at the C-4 position of 1 in place of the nitro group (Scheme 1). To the best of our knowledge preparation of nimesulide analogs via C-C bond forming reactions under palladium catalysis has not been reported earlier.…”

Predictions and correlations of structure activity relationship of some aminoantipyrine derivatives on the basis of theoretical and experimental ground

“…Owing to its low pK a value and small degree of plasma protein binding, antipyrine is distributed in total body water. In view of their high medicinal value and due to our interest in the synthesis of compounds of potential pharmacological interest (Pericherla et al, 2007;Pal et al, 2007;Jayaselli et al, 2008), we became interested in constructing a library based on pyrazolone scaffold. Azomethine belong to a widely used group of organic intermediates important for production of specialty chemicals, e.g., pharmaceuticals, or rubber additives (Macho et al, 2004) and as amino protective groups in organic synthesis (Bey and Vevert, 1977;Lucas et al, 1960;Bezas and Zervas, 1961).…”