Design, synthesis and anticonvulsant evaluation of N-(benzo[d]thiazol-2-ylcarbamoyl)-2-methyl-4-oxoquinazoline-3(4H)-carbothioamide derivatives: A hybrid pharmacophore approach (original) (raw)

2013, European Journal of Medicinal Chemistry

INTRODUCTION Epilepsy is the fourth most common neurological problem affecting human population after migrane, stroke and Alzheimer's disease (Epilepsy foundation). Epilepsy belongs to a group of neurological disorders showing neuronal hyperexcitability characterized by recurrent seizures in different parts of the brain [1]. According to WHO, it is estimated that the condition affects approximately 50 million people worldwide, 80 % of which resides in developing countries. Enormous AEDs belonging to different classes are used nowadays to treat epilepsy including phenytoin, carbamazepine, valproic acid, topiramate, gabapentin, felbamate, levetiracetam, etc. [2]. However, the current therapy using the presently available antiepileptic drugs shows limitations viz. insufficient, seizure control, unpredictability of effect and its loss, poor efficacy, inadequate information about the receptors involved, etc. Moreover AEDs do not prevent epilepsy in persons at risk of drug-resistance. Further, long term therapy with these drugs pose an array of side effects which includes but is not limited to drowsiness, ataxia, gastrointestinal disturbances, megaloblasticanaemia and hirsutism [3,4]. Hence there exists the continuous need for the discovery and development of new antiepileptic agents with higher activity, minimal or negligible toxicity and side effects. A number of heterocyclic derivatives possessing nitrogen has been reported to play an important role in pharmaceutical Design, Synthesis and Anticonvulsant Evaluation of N-[(Substituted 1H-pyrazol-3-yl)amino]-2-(4-methylphenyl)quinazolin-4(3H)-one Derivatives