Regioselective synthesis of 1,3- and 1,5-substituted pyrazoles and pyrazolynes analogous of Celecoxib

Regioselective synthesis of 1,3- and 1,5-substituted pyrazoles and pyrazolynes analogous of Celecoxib

Zanatta, Nilo; Lobo, Marcio M.; Canova, Bruna; Bonacorso, Helio G.; Martins, Marcos A. P.

Abstract:

The analgesic action of pyrazoles is widely studied and among the commercially available drugs containing the pyrazoline nucleus can be highlighted dipyrone and Celecoxib. Celecoxib (CelebrexTM) is a non-steroidal anti-inflammatory used in the treatment of diseases such as rheumatoid arthritis. It was the first selective inhibitor of cyclooxygenase 2 (COX-2) launched in the world, however, there are several questions about their toxicity, especially with regard to the cardiovascular system. Some methodologies for the synthesis of Celecoxib have been described, but often resulting an isomeric mixture of pyrazoles (1,3- and 1,5-substituited) difficult to separate. 4-alkoxyvinyl trifluoromethyl ketones are important precursors blocks. From these ketones is possible to synthesize a series of heterocycles, including pyrazoles and, therefore, this work aims to regioselective synthesize a series of 1,3- and 1,5- substituted sulfamidophenyl pyrazoles.

The analgesic action of pyrazoles is widely studied and among the commercially available drugs containing the pyrazoline nucleus can be highlighted dipyrone and Celecoxib. Celecoxib (CelebrexTM) is a non-steroidal anti-inflammatory used in the treatment of diseases such as rheumatoid arthritis. It was the first selective inhibitor of cyclooxygenase 2 (COX-2) launched in the world, however, there are several questions about their toxicity, especially with regard to the cardiovascular system. Some methodologies for the synthesis of Celecoxib have been described, but often resulting an isomeric mixture of pyrazoles (1,3- and 1,5-substituited) difficult to separate. 4-alkoxyvinyl trifluoromethyl ketones are important precursors blocks. From these ketones is possible to synthesize a series of heterocycles, including pyrazoles and, therefore, this work aims to regioselective synthesize a series of 1,3- and 1,5- substituted sulfamidophenyl pyrazoles.

Palavras-chave:

DOI: 10.5151/chempro-15bmos-BMOS2013_20138818469

Referências bibliográficas

• [1] 1 Gaulier, S. M.; McKay, R.; Swain, Swain, N. A. Tetrahedron, 2011, 52, 6000.
• [2] 2 Fitzgerald, G.A. N. Engl. J. Med. 2004, 351, 1709.
• [3] 3 Cunico, W.; Cechinel, C. A.; Bonacorso, H. G.; Martins, M. A. P.; Zanatta, N.; de Souza, M. V. N.; Freitas, I. O.; Soares, R. P. P.; Krettli, A. U. Bioorg. Med. Chem. Lett. 2006, 16, 649.

Como citar:

Zanatta, Nilo; Lobo, Marcio M.; Canova, Bruna; Bonacorso, Helio G.; Martins, Marcos A. P.; "Regioselective synthesis of 1,3- and 1,5-substituted pyrazoles and pyrazolynes analogous of Celecoxib", p-9-9. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_20138818469