New 1-aryl-4-(biarylmethylene)piperazines as potential atypical antipsychotics sharing dopamine D(2)-receptor and serotonin 5-HT(1A)-receptor affinities.
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.
Feenstra
R W
RW
Solvay Pharmaceuticals, Research Laboratories, PO Box 900, 1380 DA, Weesp, The Netherlands. rolf.feenstra@solvay.com
de Moes
J
J
Hofma
J J
JJ
Kling
H
H
Kuipers
W
W
Long
S K
SK
Tulp
M T
MT
van der Heyden
J A
JA
Kruse
C G
CG
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001058:Apomorphine / Q000009:adverse effects; D001522:Behavior, Animal / Q000187:drug effects; D001583:Benzoxazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D051379:Mice; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology; D013134:Spiperone / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
C442388:7-(4-(3-phenylbenzyl)piperazin-1-yl)-1H-benzoxazol-2-one; D014150:Antipsychotic Agents; D001583:Benzoxazoles; D018492:Dopamine Antagonists; D010879:Piperazines; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D013134:Spiperone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001058:Apomorphine