Synthesis and anticonvulsant activity evaluation of 7-alkoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-ones.
A new series of 7-alkoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-ones were synthesized and evaluated for their anticonvulsant activities. Among these compounds, 7-propoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-one (4c) and 7-butoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-one (4d) showed the highest activity against maximal electroshock (MES)-induced tonic extension [effective dose (ED)50 : 11.4 and 13.6 mg/kg, respectively]. It is worth mentioning that compound 4d showed especially low neurotoxicity, which led to a high protective index (PI >51). The orally anticonvulsant activity data of compound 4d further confirmed its efficacy, in an MES test, and its high safety with a PI value of 50.2. In addition, the potency of compound 4h against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline in the chemical-induced seizure tests suggested that compound 4d may exert its anticonvulsant activity through affecting the GABAergic system.
College of Pharmacy, Yanbian University, Yanji, Jilin, China.
Da-Chuan
DC
Liu
Xian-Qing
XQ
Deng
Shi-Ben
SB
Wang
Zhe-Shan
ZS
Quan
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004597:Electroshock; D051379:Mice; D020258:Neurotoxicity Syndromes / Q000209:etiology; D012640:Seizures / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D013844:Thiazoles; D005680:gamma-Aminobutyric Acid
Anticonvulsant activity; Benzothiazole; Maximal electroshock; Pentylenetetrazole; Triazolone