Anticonvulsant and Toxicity Evaluation of Newly Synthesized 1-[2-(3,4-disubstituted phenyl) -3-chloro-4-oxoazetidin-1-yl]-3-(6-substituted -1,3-benzothiazol-2-yl)ureas

Nadeem Siddiqui,a,* Arpana Rana,a Suroor A. Khan,a Syed Ehtaishamul Haque,b M. Shamsher Alam,a Waquar Ahsana and M. Faiz Arshada

a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi-110062, India
b Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi-110062, India
* Corresponding author: E-mail:,
Phone: 91-11-26059688 - Ext. 5639

A number of new 1-[2-(3,4-disubstituted phenyl)-3-chloro-4-oxoazetidin-1-yl]-3-(6-substituted-1,3-benzothiazol-2-yl)urea compounds (5a-t) were synthesized and evaluated for their anticonvulsant, hepatotoxic and neurotoxic properties. The titled compounds (5a-t) were obtained by cyclization of 3,4-disubstituted benzaldehyde-N-(6-substituted-1,3- benzothiazol-2-yl)semicarbazones (4a-t) in presence of DMF/triethylamine and chloroacetylchloride. All the newly synthesized compounds were screened for their anticonvulsant activity in i.p. Maximal Electroshock Seizure (MES) model and were compared with the standard drug phenytoin. Interestingly, compounds 5f, 5n, and 5p exhibited 100% protection in the MES test. In the neurotoxicity and hepatotoxicity screening, all the compounds were devoid of toxicity at the dose of 30 mg/kg body weight. The study showed that introduction of F, CH3 at the 6- position of benzothiazole moiety with H, OCH3 at the 3-position and OH, OCH3 at 4-position of the distant phenyl ring led to increased activity. Introduction of F, NO2, CH3, OCH3 substituents at the 6-position of the benzothiazole moiety and unsubstituted distant phenyl ring showed moderate decrease in activity.

Keywords: Azetidine, benzothiazole, maximal electroshock seizure test, anticonvulsant activity, neurotoxicity, hepatotoxicity