RESUMO
The aldimine-directed C-H amidation of various arenes with N-acyl azides as amidation surrogates under cationic iridium(III) catalysis is described. This transformation efficiently provides a range of 2-aminobenzaldehyde derivatives with excellent site selectivity and functional group compatibility. The resulting 2-aminobenzaldehyde framework provides facile access to a range of biologically interesting heterocycles. In addition, all synthetic compounds were screened for anti-inflammatory activity against interleukin-1ß (IL-1ß) and tumor necrosis factor alpha (TNF-α) with lipopolysaccharide (LPS)-induced RAW264.7 cells. Generally, a range of ortho-amidated benzaldehydes displayed promising inhibitory activity against IL-1ß and TNF-α compared to dexamethasone as a positive control. Notably, compounds (3ae and 4ac) were found to exhibit potent anti-inflammatory activity stronger than that of dexamethasone.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Azidas/química , Benzaldeídos/farmacologia , Iminas/química , Interleucina-1beta/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Amidas/síntese química , Amidas/química , Amidas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Benzaldeídos/síntese química , Benzaldeídos/química , Catálise , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Irídio/química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Compostos Organometálicos/química , Células RAW 264.7RESUMO
The iridium(III)-catalyzed ortho-C-H amidation of benzoic acids with sulfonyl azides is described. These transformations allow the facile generation of N-sulfonyl anthranilic acids, which are known as crucial scaffolds found in biologically active molecules. In addition, all synthetic products were evaluated for in vitro anti-inflammatory activity against interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2) with lipopolysaccharide (LPS)-induced RAW264.7 cells. Notably, compounds 4c and 4d, generated from p-OMe- and p-Br-sulfonyl azides, were found to display potent anti-inflammatory property stronger than that of well-known NSAIDs ibuprofen.
