Synthesis and anticonvulsant activity of 3-(6-substituted-benzothiazol-2-yl)-6-phenyl-[1, 3]-xazinane-2-thiones.
A new series of 3-(6-substituted-benzothiazol-2-yl)-6-phenyl-[1, 3]-oxazinane-2-thiones (4a-j) has been synthesised using an appropriate synthetic route (Scheme 1) and characterised by elemental analyses and spectral (IR, (1)HNMR, (13)C NMR, and EI MS) data. The anticonvulsant activity of all the title compounds (4a-j) was evaluated against Maximal Electroshock (MES) induced seizures and furthermore the most potent compounds were evaluated against subcutaneous pentylenetetrazole (sc PTZ) induced seizures model in mice. The neurotoxicity was assessed using the rotorod procedure. All the test compounds were administered intraperitoneally at various dose levels ranging from 30-200 mg/kg body wt and the median effective dose (ED(50)), median toxic dose (TD(50)), and protection index (PI) values were determined (Table 2). Among the compounds tested, the 3-(6-dimethylaminobenzothiazol-2-yl)-6-phenyl-[1, 3]-oxazinane-2-thiones (4j) was found to be the most potent (ED(50): 9.85 and 14.8 in MES model and 12 and 17 in scPTZ model at t = 0.5 h and 4 h, respectively, and TD(50) 42.8 and 44 at t = 0.5 h and 4 h, respectively, which has been found to be significant at p < 0.01 with respect to reference standard phenytoin) with protection index (PI) 4.85.
Chopade
Rajendra S
RS
Department of Pharmaceutical Sciences, Nagpur University, Nagpur-440010 (M.S), India.
Bahekar
Rajesh H
RH
Khedekar
Pramod B
PB
Bhusari
Kishore P
KP
Rao
Akkinpalli Raghu Ram
AR
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D052160:Benzothiazoles; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003292:Convulsants / Q000494:pharmacology; D004597:Electroshock; D005260:Female; D008297:Male; D051379:Mice; D008970:Molecular Weight; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D004856:Postural Balance / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity
D000927:Anticonvulsants; D052160:Benzothiazoles; D003292:Convulsants; D013844:Thiazoles; C005465:benzothiazole; D010433:Pentylenetetrazole