Synthesis of new benzotriazepin-5(2H)-one derivatives of expected antipsychotic activity

A new series of 3,4-dihydro-1H-benzo{[}e]{[}1,2,4]triazepin-5(2H)-one derivatives were synthesized by cyclocondensation of benzohydrazides (II, IX), derived from the reaction of N-methyl-isatoic anhydride with phenyl hydrazine and isonicotinic acid hydrazide, respectively, with formaldehyde, aromatic aldehydes in acidic medium or with carbon disulfide in alkaline medium, the last reaction was only carried out with benzohydrazide II. Benzotriazepinone derivatives IV,V (a-h) ,VI, and XI were subjected to ptosis test using clozapine as a reference drug to evaluate their antipsychotic activity. It was found that 2-thioxobenzotriazepinone VI had the same antipsychotic activity as reference drug clozapine but with lesser side effects whereas it showed nonsignificant CNS depressant activity upon using forced swim pool test as well as no neurotoxicity when tested in mice using rotarod or horizontal screen tests. A new series of benzotriazepin-5(2H)-ones (IV,V (a-h) , VI, and XI) were prepared starting from isatoic anhydride and their antipsychotic activity revealed that 2-thioxobenzotriazepinone VI was superior to the reference drug clozapine.