SYNTHESIS OF NEW 1,2-BENZOTHIAZIN-3-ONE DERIVATIVES DESIGNED AS DUAL CYCLOOXYGENASE-2 AND 5-LIPOOXYGENASE INHIBITORS

In the scope of a research program aiming at the synthesis of new nons teroidal 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-benzothiaz in-3-one derivatives (3a-10a) and (3b-10b), structurally designed as d ual cyclooxigenase-2 and 5-lipooxygenase inhibitors by applying ration al 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-benzal dehyde) and corresponding 1,2-benzothiazin-3(4H)-one 1,1-dioxide deriv atives (17a) and (17b).