Pharmacological Evaluation of Novel Quinazoline Derivatives for Their Anti-Convulsant and CNS Depressant Activities

Abstract

The present study attempted to design and synthesise isomeric new series of quinazoline-4-one/4-thione derivatives, based on the pharmacophoric model of CNS activity by structural modifications retaining the essential structural features for the activity and evaluated for their anticonvulsant and CNS depressant properties. Epilepsy, a disorder of unprovoked seizures is a multifaceted disease affecting individuals of all ages with a particular predilection for the very young and old. In addition to seizures, many patients often report cognitive and psychiatric problems associated with both the seizures themselves and its therapy.  A series of 7-chloro-3-[substituted (amino/phenylamino)]-2-phenyl quinazolin-4 (3H)-one/thione derivatives and 1-(7-chloro-4-oxo/-2-phenylquinazoline-3 (4H-yl)) substituted urea derivatives were synthesized. The reaction scheme proceeds through the intermediate 7-chloro-2-phenyl-4H-benzo[d] [1, 3] oxazin-4-one. The newly synthesized compounds were characterized by infrared (IR), ¹H nuclear magnetic resonance (NMR) and mass spectra (m/z) and elemental analysis. The maximum electroshock (MES) seizure test and Porsolt's behavioural despair test (forced swimming) were used to examine the anti-convulsant and CNS depressant activity, respectively. To evaluate any potential alterations in motor coordination brought on by the test compounds, the rota-rod test was conducted. The synthesis of quinazoline derivatives with a common skeleton was unequivocally confirmed by the physicochemical and spectroscopic data. The synthesised compounds were evaluated for their anticonvulsant and CNS depressant properties. Six compounds (IIc, IIg, IIj, IIIc, IIIg, IIIj) exhibited a good activity profile in CNS depressant activity. Five compounds (IIc, IIg, IIj, IIIg, IIIh) showed protection against MES-induced seizures. Compounds IIc, IIg, IIj, IIIc, IIIg, IIIj, and IIIh were found to be a potent compound which may be effective as a potential source for the development of CNS depressant and anti-convulsant drugs with lesser side effects.