Synthesis and anticonvulsant activity of 7-alkoxy-triazolo-[3, 4-b]benzo[d]thiazoles.
The present study describes the chemical synthesis and anticonvulsant activity evaluation of a series of 7-alkoxy-triazolo-[3, 4-b]benzo[d]thiazoles. Most compounds exhibited good anticonvulsant activity in the Maximal electroshock (MES) test. And the structure-activity relationships (SAR) were analyzed. Among the compounds studied, 7-octyloxy-triazolo-[3, 4-b]benzo[d]thiazole (5g) was found to be the most potent compound with a median effective dose (ED(50)) value of 8.0 mg/kg and a protective index (PI) value of 15.0, possessing better anticonvulsant activity and higher safety than marketed drugs carbamazepine and phenytoin. The mechanism study of compound 5g showed that it displayed broad spectrum activity in several models, and it is likely to have several mechanisms of action (including inhibiting voltage-gated ion channels and GABAergic activity).
Deng
Xian-Qing
XQ
College of Pharmacy, Yanbian University, No. 977 Park Road, Yanji, Jilin, China.
Song
Ming-Xia
MX
Wei
Cheng-Xi
CX
Li
Fu-Nan
FN
Quan
Zhe-Shan
ZS
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002220:Carbamazepine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010672:Phenytoin / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000927:Anticonvulsants; D052160:Benzothiazoles; D014230:Triazoles; D002220:Carbamazepine; D010672:Phenytoin