Amino acid amide derivatives of 2-[3-(aminomethyl)-4H-1,2,4-triazol-4-yl]benzophenones, a novel class of annelated peptidoaminobenzophenones.

A series of the title compounds was prepared via condensation of the 3-(aminomethyl)triazolylbenzophenone (5) with N-protected amino acids, followed by deprotection, amination of the 3-[(chloroacetamido)methyl]triazolylbenzophenone (6a,b), or reduction of the relevant azide derivative (6c). Some of the title compounds were also derived directly from the quinazolines 3 or 4 by acid-induced rearrangement, followed by deprotection. These new amino acid amide derivatives of the triazolylbenzophenones (2) were evaluated for central nervous system (CNS) activity. Members of this class of compounds exhibited a high level of CNS activities. For example, 2',5-dichloro-2-[3-[(glycylamino)methyl]-5-methyl-4H-1,2,4-triazol-4-yl] benzophenone (2c) was as active as triazolam, with an ED50 of 0.58 mg/kg (mice, po), against antifighting activity in the foot shock-induced fighting test. Other triazolylbenzophenone derivatives (2a-f) showed similar pharmacological activities.