Antinociceptive properties of new coumarin derivatives bearing substituted 3,4-dihydro-2H-benzothiazines

BACKGROUND: Coumarins are an important class of widely distributed heterocyclic natural products exhibiting a broad pharmacological profile. In this work, a new series of coumarins bearing substituted 3,4-dihydro-2H-benzothiazines were described as potential analgesic agents. The clinical use of NSAIDs as traditional analgesics is associated with side effects such as gastrointestinal lesions and nephrotoxicity. Therefore, the discovery of new safer drugs represents a challenging goal for such a research area. RESULTS: The target compounds 3-(3-methyl-3,4-dihydro-2H-benzo[b][1,4]thiazin-3-yl)-2H-chromen-2-ones 2a-u were synthesized and characterized by spectral data. The antinociceptive properties of target compounds were determined by formalin-induced test and acetic acid-induced writhing test in mice. Among the tested compounds, compound 2u bearing 2-(4-(methylsulfonyl)benzoyl)- moiety on benzothiazine ring and 4-(methylsulfonyl)phenacyloxy- group on the 7 position of coumarin nucleus showed better profile of antinocecieption in both models. It was more effective than mefenamic acid during the late phase of formalin-induced test as well as in the acetic acid-induced writhing test. CONCLUSION: Considering the significant antinoceciptive action of phenacyloxycoumarin derivatives, compound 2u prototype might be further used as model to obtain new more potent analgesic drugs.