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

A new syntheses of novel series of 2,3-dihydroquinazolin-4(1H)-one and benzotriazepin- 5(2H)-one derivatives, starting from the same intermediate (II _a-g ). By varying the substituent on the benzamide moiety of the key intermediate (II _a-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 (II _a-g ); was prepared by condensation of N-methyl-isatoic anhydride with different benzoic acid hydrazides. Constructing the intermediates (II _a-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 (IV _a-d , VI _a-c ) and a new series of quinazolin 4(1H)-one (III _a-d , V _a-d ). Pharmacological screening of the new benzotriazepinone derivatives revealed that the compounds (VI _b,c , IV _a,c,d ) exhibited strong CNS depressant activity over clozapine while compounds (VI _b , IV _c ) showed the same antipsychotic activity as clozapine with an observed neurotoxicity.