Synthesis and Anticonvulsant Activity of Some 7-Alkoxy-2H-1,4-benzothiazin-3(4H)-ones and 7-Alkoxy-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazines

• Published in: Chemical & Pharmaceutical Bulletin Vol. 58; no. 3; pp. 326 - 331
• Main Authors: Zhang, Li-Qiu, Guan, Li-Ping, Wei, Cheng-Xi, Deng, Xian-Qing, Quan, Zhe-Shan
• Format: Journal Article
• Language: English; Japanese
• Published: TOKYO The Pharmaceutical Society of Japan 01.03.2010; Pharmaceutical Society of Japan; Pharmaceutical Soc Japan; Japan Science and Technology Agency
• Subjects: Animals; anticonvulsant; Anticonvulsants - chemical synthesis; Anticonvulsants - chemistry; Anticonvulsants - pharmacology; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Drug Evaluation, Preclinical; Injections, Intraperitoneal; Life Sciences & Biomedicine; maximal electroshock; Mice; Molecular Structure; Motor Activity - drug effects; Pharmacology & Pharmacy; Physical Sciences; Rotarod Performance Test - methods; Science & Technology; Seizures - drug therapy; Stereoisomerism; thiamine; Thiazines - chemical synthesis; Thiazines - chemistry; Thiazines - pharmacology; triazole; thiamine; AGENTS; anticonvulsant; maximal electroshock; triazole
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.58.326

A series of 7-alkoxy-2H-1,4-benzothiazin-3(4H)-ones and a new series of 7-alkoxy-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazine derivatives were synthesized using 5-methoxybenzo[d]thiazol-2-amine as starting material. The structures of the compounds were elucidated by IR, 1H-NMR spectroscopic data and microanalyses. The anticonvulsant activity of these compounds was evaluated by maximal electroshock (MES) test and rotarod test following intraperitoneal injection in KunMing mice. Among the synthesized compounds 3a—v, 7-(hexyloxy)-2H-benzo[b][1,4]thiazin-3(4H)-one (3f) could be considered potentially the most useful and safe therapeutic compound. Among the synthesized compounds 4a—u, compound 7-(2-fluorobenzyloxy)-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazine (4k) was the most active compound with an ED50 of 17.0 mg/kg, TD50 of 243.9 mg/kg and protective index (PI) of 14.3. Its neurotoxicity was lower than all the other synthesized compounds and also markedly lower than that of the reference drug carbamazepine.