Synthesis, characterization and pharmacological evaluation of 1-(2-chloro-6-fluorophenyl)-5-methylindolin-2-one: a new anti-inflammatory compound with reduced gastric ulceration properties |
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Authors: | dos Santos Jean Leandro Chelucci Rafael Chiquetto Richard Chung Man Chin Campos Michel Leandro Peccinini Rosangela Gonçalves |
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Affiliation: | Lapdesf-Laboratório de Pesquisa e Desenvolvimento de Fármacos, Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas-UNESP Rodovia Araraquara Jaú Km. 01, 14801-902, Araraquara, SP, Brazil. santosjl@fcfar.unesp.br |
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Abstract: | The new compound 1-(2-chloro-6-fluorophenyl)-5-methylindolin-2-one (1), designed using the prodrug approach, was easily obtained in 85% yield and characterized by nuclear magnetic resonance, elemental analysis, mass spectrometry and infrared spectroscopy. The lactam 1 showed anti-inflammatory and analgesic activity comparable to that of the COX-2 inhibitor lumiracoxib, without gastro-ulceration effects. Stability studies demonstrated that the lactam function was stable and did not hydrolyze in pH 1.2 or 7.4. Furthermore, using a thioglycollate-induced peritonitis model, compound 1 was shown to inhibit cell migration by 50.4%, while lumiracoxib inhibited it by 18%. This compound represents a new non-ulcerogenic prototype for the treatment of chronic inflammatory diseases. |
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