Synthesis and pharmacology of novel anxiolytic agents derived from 2-[(dialkylamino)methyl-4H-triazol-4-yl]benzophenones and related heterocyclic benzophenones

Abstract

A series of novel [(dialkylamino)methyl-4H-1,2,4,-triazol-4-yl]benzophenones and related compounds was prepared via total synthesis from substituted aminodiphenylmethanes or by hydrolysis and subsequent methylation of triazolobenzodiazepines. These new triazole compounds have potent sedative and muscle relaxing activity in mice (i.e., these compounds depressed the traction and dish reflexes). These compounds also antagonized the clonic convulsions induced in mice by the administration of pentylenetetrazole (Metrazol, 85 mg/kg), with ED50 varying from 2.0-23.0 mg/kg, and the lethality induced by thiosemicarbazide, with ED50 varying from 0.02-9.0 mg/kg. In several biological tests, the potency of 7 new benzophenone derivatives approached or exceeded that of diazepam or its glycylaminobenzophenone analogue.