ChemInform Abstract: N-Aryl-N′-Benzylpiperazines as Potential Antipsychotic Agents (original) (raw)

N-Aryl-N'-Benzylpiperazines as Potential Antipsychotic Agents. -The N1-(2-alkoxyphenyl)piperazine title compounds, e.g. (I)-(III), carrying an additional substituted N4-benzyl group, are synthesized and evaluated in the conditioned avoidance response (CAR) test predictive of clinical antipsychotic activity and in in vitro receptor-binding assays. Structures of the type (II) with meta substitution such as (IIa) display better biological activity than the corresponding ortho-or para-substituted congeners. Only the hydantoin derivative (IIb) attached via N1 has good biological activity, whereas those hydantoins substituted via N3 or C5 are inactive. Several of the smaller acetylated derivatives, e.g. (IIc) and (IId), have fair in vivo activity, which is lost in the case of the larger benzoyl analogue. Benzylamine compounds of type (III) display moderate CAR activity, but have surprising receptor affinity. Derivatives of the type (I) are more active than those of class (III) and also exhibit excellent in vivo activity in the CAR test with modest D2 and 5-HT1A receptor binding. -(REITZ, A. B.; BAXTER, E. W.; BENNETT, D. J.; CODD, E. E.; JORDAN, A. D.; MALLOY, E. A.; MARYANOFF, B. E.; MCDONNELL, M. E.; ORTEGON, M. E.; RENZI, M. J.; SCOTT, M. K.; SHANK, R. P.; SHERRILL, R. G.; VAUGHT, J. L.; WUSTROW, D. J.; J.