Aminimides as Potential CNS Acting Agents. I. Design, Synthesis, and Receptor Binding of 4′-Aryl Aminimide Analogues of Clozapine as Prospective Novel Antipsychotics

Ben Capuano; Ian T. Crosby; Edward J. Lloyd; Juliette E. Neve; David A. Taylor

doi:10.1071/CH07197

RESEARCH ARTICLE

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Aminimides as Potential CNS Acting Agents. I. Design, Synthesis, and Receptor Binding of 4′-Aryl Aminimide Analogues of Clozapine as Prospective Novel Antipsychotics

Ben Capuano ^A , Ian T. Crosby ^A ^D , Edward J. Lloyd ^A , Juliette E. Neve ^A ^B and David A. Taylor ^C

+ Author Affiliations

- Author Affiliations

^A Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Vic. 3052, Australia.

^B Current address: Natural Product Discovery, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan, Qld 4111, Australia.

^C Department of Pharmaceutical Biology, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Vic. 3052, Australia.

^D Corresponding author. Email: ian.crosby@vcp.monash.edu.au

Australian Journal of Chemistry 60(9) 673-684 https://doi.org/10.1071/CH07197
Submitted: 12 June 2007 Accepted: 25 July 2007 Published: 11 September 2007

Abstract

A series of substituted 1-[4-(8-chloro-5H-dibenzo[b,e][1,4]diazepin-11-yl)-1-methylhexahydropyrazin-1-ium]-1-aminimide derivatives were designed on the basis of the physicochemical properties of the aminimide functional group and synthesized as potential antipsychotic agents for the treatment of schizophrenia. The target compounds were readily prepared in two steps from clozapine (8-chloro-11-(4-methylpiperazino)-5H-dibenzo[b,e][1,4]diazepine) and involved N-acylation of a common hydrazinium salt intermediate by an acyl chloride or activated ester in the presence of a strong base. The aminimides were tested for in vitro activity at the dopamine D₄ and serotonin 5-HT_2A receptors and were found to possess modest affinity for both receptor systems.

Acknowledgement

The receipt of a Monash Graduate Scholarship (J.E.N.) for support of this research is gratefully acknowledged.

References

Aminimides as Potential CNS Acting Agents. I. Design, Synthesis, and Receptor Binding of 4′-Aryl Aminimide Analogues of Clozapine as Prospective Novel Antipsychotics

Abstract

Acknowledgement

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