New 1-aryl-4-(biarylmethylene)piperazines as potential atypical antipsychotics sharing dopamine D(2)-receptor and serotonin 5-HT(1A)-receptor affinities

R W Feenstra; J de Moes; J J Hofma; H Kling; W Kuipers; S K Long; M T Tulp; J A van der Heyden; C G Kruse

doi:10.1016/s0960-894x(01)00425-5

New 1-aryl-4-(biarylmethylene)piperazines as potential atypical antipsychotics sharing dopamine D(2)-receptor and serotonin 5-HT(1A)-receptor affinities

Bioorg Med Chem Lett. 2001 Sep 3;11(17):2345-9. doi: 10.1016/s0960-894x(01)00425-5.

Authors

R W Feenstra¹, J de Moes, J J Hofma, H Kling, W Kuipers, S K Long, M T Tulp, J A van der Heyden, C G Kruse

Affiliation

¹ Solvay Pharmaceuticals, Research Laboratories, PO Box 900, 1380 DA, Weesp, The Netherlands. rolf.feenstra@solvay.com

PMID: 11527728
DOI: 10.1016/s0960-894x(01)00425-5

Abstract

This paper describes the syntheses of several 1-aryl-4-(biarylmethylene)piperazines and the results of the determination of their affinity for D(2) and 5-HT(1A) receptors. A selection of these compounds was evaluated in vivo, resulting in the identification of a drug candidate which is being clinically evaluated as a potential atypical antipsychotic with reduced extrapyrimidal side effects.

Publication types

Evaluation Study

MeSH terms

8-Hydroxy-2-(di-n-propylamino)tetralin / metabolism
8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
Animals
Antipsychotic Agents / chemistry*
Antipsychotic Agents / metabolism
Antipsychotic Agents / pharmacology*
Apomorphine / adverse effects
Behavior, Animal / drug effects
Benzoxazoles / chemistry*
Benzoxazoles / metabolism
Benzoxazoles / pharmacology*
Dopamine Antagonists / metabolism
Dopamine Antagonists / pharmacology
Drug Design
Drug Evaluation, Preclinical
Mice
Piperazines / chemistry*
Piperazines / metabolism
Piperazines / pharmacology*
Rats
Receptors, Dopamine D2 / drug effects
Receptors, Dopamine D2 / metabolism*
Receptors, Serotonin / drug effects
Receptors, Serotonin / metabolism*
Receptors, Serotonin, 5-HT1
Serotonin Receptor Agonists / metabolism
Serotonin Receptor Agonists / pharmacology
Spiperone / metabolism
Spiperone / pharmacology
Structure-Activity Relationship

Substances

7-(4-(3-phenylbenzyl)piperazin-1-yl)-1H-benzoxazol-2-one
Antipsychotic Agents
Benzoxazoles
Dopamine Antagonists
Piperazines
Receptors, Dopamine D2
Receptors, Serotonin
Receptors, Serotonin, 5-HT1
Serotonin Receptor Agonists
Spiperone
8-Hydroxy-2-(di-n-propylamino)tetralin
Apomorphine