Synthesis of new 1,2-Benzothiazin-3-one Derivatives Designed as Dual Cyclooxygenase-2 and 5-Lipooxygenase Inhibitors

• Autor(a) principal: Teixeira,Lis Helena P.
• Data de Publicação: 1998
• Outros Autores: Fraga,Carlos A.M., Barreiro,Eliezer J.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50531998000200003
• topic: 1,2-Benzothiazin-3-one 1,1-dioxide derivatives; diastereoselective Knoevenagel-Doebner condensation; dual COX-2/5-LO inhibitors; NSAID candidates

In the scope of a research program aiming at the synthesis of new nonsteroidal anti-inflammatory drugs (NSAIDs) acting on the enzymes of the arachidonic acid cascade, we describe in this paper the synthesis of two new series of functionalized alpha,beta-unsaturated 1,2-benzothiazin-3-one derivatives (3a-10a) and (3b-10b), structurally designed as dual cyclooxigenase-2 and 5-lipooxygenase inhibitors by applying rational principles of molecular modification and hybridization. The target compounds (3a-10a) and (3b-10b) were prepared in good overall yields, exploring as the key step of the synthetic route a Knoevenagel-Doebner condensation between substituted benzaldehydes (e.g. 4-methoxy-benzaldehyde) and corresponding 1,2-benzothiazin-3(4H)-one 1,1-dioxide derivatives (17a) and (17b).