Medicinal Chemistry

Synthesis and Biological Screening of New Derivatives of 2,3-dihydro quinazolin-4(1H)-one and Benzotriazepin- 5(2H)-one for Central Nervous System Activity

Abstract

Samy M Ibrahim, Abo-Kul M, Moustafa K Soltan, Waleed Barakat and Ahmed S Helal

A new syntheses of novel series of 2,3-dihydroquinazolin-4(1H)-one and benzotriazepin- 5(2H)-one derivatives, starting from the same intermediate (IIa-g). By varying the substituent on the benzamide moiety of the key intermediate (IIa-g) or the conditions of the reactions utilized in this syntheses, the reaction gives rise either quinazolin-4(1H)-one or benzotriazepine-5(2H)-one. The intermediate; 2-methylamino-N-(substituted benzoyl)benzohydrazide (IIa-g); was prepared by condensation of N-methyl-isatoic anhydride with different benzoic acid hydrazides. Constructing the intermediates (IIa-g) on different cyclo-condensation reactions; either with ethylchloroformate /potassium hydroxide or carbon disulfide/potassium hydroxide, yielded a new series of benzotriazepin-5(2H)-one (IIIa-b, IVa-d) and a new series of quinazolin4(1H)-one (Va-c, VI a-d). Pharmacological screening of the new benzotriazepinone derivatives revealed that the compounds (VI a-b, IVc-d) exhibited strong CNS depressant activity over clozapine while compounds (VIa,IVc) showed the same antipsychotic activity as clozapine with an observed neurotoxicity.