Synthesis and anticonvulsant activity of various Mannich and schiff bases of 1,5-benzodiazepines

Abstract

Benzodiazepines have a various behavioural effects in addition to their anxiolytic action . There is every reason to believe that the BZ/GABA receptor complex is involved in these effects since gabamimetic manipulations modify the effect of BZ in tests of convulsive activity, motor function, and appetitive behavior. 1, 5- benzodiazepines are biologically important molecules and are extensively used clinically as analgesic, hypnotic, sedative and antidepressive agents. Hence 1,5-benzodiazepines were synthesized by condensation of o-phenylenediamine and ketones e.g., cyclohexanone and acetone in presence of Sulfated Zirconia (catalyst).Mannich bases were synthesized with acetophenone, p-nitroacetophenone, p-chloroacetophenone and formaldehyde. Schiff bases were synthesized using Mannich base of 1,5-benzodiazepines with p-chloroaniline and p-chlorophenylsemicarbazide in presence of glacial acetic acid. All the synthesized compounds were characterized by 1H NMR and IR spectral analysis. All the synthesized derivatives were evaluated at the dose of 30mg/kg b.w for anticonvulsant activity by isoniazid induced convulsion model and the compounds NBZD-3 & NBZD-8 were found to be most active among all compounds . Among all the synthesized derivatives, compounds NBZD-13, NBZD-17 were found to be most active among all compounds using thiosemicarbazide induced model. NBZD-8, NBZD-10, NBZD-18 are the compounds which had shown good anticonvulsant activity and have advantage over that, they were not sedative.