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7-[3-(1-piperidinyl)propoxy]chromenones as potential atypical antipsychotics.

Abstract：

:Compound 1 (1-benzyl-3-methyl-4-[4-(4-fluorophenyl)-4-oxobutyl]piperazine), a synthetic intermediate identified as a potential atypical antipsychotic, was selected as the starting point for pharmacological improvement. From 1, sequential structural variations were conducted in order to improve its potency and oral bioavailability. These variations included a series of piperazine, ethanediamine, and piperidine derivatives. The piperidine series afforded some orally potent compounds in the inhibition of apomorphine-induced climbing and hyperactivity in mice, which are regarded as behavioral models predictive of antipsychotic efficacy. Further optimization of these structures led to the highly potent 7-[3-(1-piperidinyl)propoxy]chromenones. Inhibition of stereotypies and induction of catalepsy in rats at doses substantially higher than required for inhibition of climbing suggest an atypical antipsychotic profile, which is assumed to predict a reduced induction of extrapyramidal side effects in humans.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Bolós J,Gubert S,Anglada L,Planas JM,Burgarolas C,Castelló JM,Sacristán A,Ortiz JA

doi

10.1021/jm950894b

subject

Has Abstract

pub_date

1996-07-19 00:00:00

pages

2962-70

issue

15

eissn

0022-2623

issn

1520-4804

pii

jm950894b

journal_volume

39

pub_type

杂志文章

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