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Buspirone analogues. 1. Structure-activity relationships in a series of N-aryl- and heteroarylpiperazine derivatives.

Abstract：

:A series of analogues of buspirone was synthesized in which modifications were made in the aryl moiety, alkylene chain length, and cyclic imide portion of the molecule. These compounds were tested in vitro for their binding affinities to rat brain membrane sites labeled by either the dopamine antagonist [3H]spiperone or the alpha 1-adrenergic antagonist [3H]WB-4101. Compounds were also tested in vivo for tranquilizing properties and induction of catalepsy. Potency at the [3H]spiperone binding site was affected by alkylene chain length and imide portion composition. Nonortho substituents on the aryl moiety had little effect on [3H]spiperone binding affinity. Structure-activity relationships of ortho substituents demonstrated only modest correlations between the receptor binding data and physical parameters of the substituents. The complex nature of the drug-receptor interactions may be understood in terms of the fit of buspirone to a hypothetical model of the dopamine receptor.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Yevich JP,Temple DL Jr,New JS,Taylor DP,Riblet LA

doi

10.1021/jm00356a014

subject

Has Abstract

pub_date

1983-02-01 00:00:00

pages

194-203

issue

2

eissn

0022-2623

issn

1520-4804

journal_volume

26

pub_type

杂志文章

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