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.
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, (1)H-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 ED(50) of 17.0 mg/kg, TD(50) 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.
Zhang
Li-Qiu
LQ
College of Pharmacy, Yanbian University, Zhoushan 316004, P. R. China.
Guan
Li-Ping
LP
Wei
Cheng-Xi
CX
Deng
Xian-Qing
XQ
Quan
Zhe-Shan
ZS
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D007274:Injections, Intraperitoneal; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects*; D045442:Rotarod Performance Test / Q000379:methods; D012640:Seizures / Q000188:drug therapy*; D013237:Stereoisomerism; D013843:Thiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000927:Anticonvulsants; D013843:Thiazines