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Synthesis and Anticonvulsant Activity of 3‐(6‐Substituted‐benzothiazol‐2‐yl)‐6‐phenyl‐[1, 3]‐xazinane‐2‐thiones
Author(s) -
Chopade Rajendra S.,
Bahekar Rajesh H.,
Khedekar Pramod B.,
Bhusari Kishore P.,
Ram Rao Akkinpalli Raghu
Publication year - 2002
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/1521-4184(200211)335:8<381::aid-ardp381>3.0.co;2-s
Subject(s) - anticonvulsant , chemistry , stereochemistry , combinatorial chemistry , epilepsy , medicine , psychiatry
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.