Synthesis of 2,6-dicarbethoxy-3,5-diaryltetrahydro-1,4-thiazine-1,1-dioxide derivatives as potent anticonvulsant agents

• 3,5-Diaryltetrahydro-1,4-thiazine-1,1-dioxide derivatives were synthesized.
• The newly synthesized compounds have been tested for anticonvulsant activity.
• From the present study, seven compounds have emerged as the lead compounds.
• Compound 4d exhibits a protective index (TD50/ED50) of 28.3 in the MES test.

An efficient synthesis of 2,6-dicarbethoxy-3,5-diaryltetrahydro-1,4-thiazine-1,1-dioxide derivatives has been achieved under aqueous medium for the first time in good to excellent yields. All the synthesized compounds were tested for anticonvulsant activity using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) screens, which are the most broadly employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotarod test. Seven compounds 4a, 4d, 4f, 4h, 4o, 4p and 4q showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 4d showed the MES-induced seizures with ED50 value of 10.2 mg/kg and TD50 value of 288.6 mg/kg after intraperitoneal injection to mice, which provided compound 4d with a protective index (TD50/ED50) of 28.3 in the MES test.

In the present study, synthesis and anticonvulsant activity of 2,6-dicarbethoxy-3,5-diaryltetrahydro-1,4-thiazine-1,1-dioxide derivatives have been described.Figure optionsDownload as PowerPoint slide