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(8 beta)-6-methylergoline amide derivatives as serotonin antagonists: N1-substituent effects on vascular 5HT2 receptor activity.

Abstract：

:A series of (8 beta)-6-methylergoline amide derivatives was synthesized with various alkyl substituents in the N1-position in order to evaluate their effectiveness in blocking vascular 5HT2 receptors. The influence of both the N1 substituent and amide derivative proved to be of great importance on binding affinities to vascular 5HT2 receptors. Within each series of amides, however, maximum affinity was achieved with an N1-isopropyl substituent (14, 18, 26, 38, and 41; all with 2.7-50 times greater affinity than their N1-H analogues), with the exception of two cases (22 and 37) in the cyclohexylamide derivatives wherein N1-methyl equalled the isopropyl in potency. Other than these exceptions, affinities followed the pattern of H less than Me less than Et less than iPr, with potencies falling off with larger alkyl substituents.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Misner JW,Garbrecht WL,Marzoni G,Whitten KR,Cohen ML

doi

10.1021/jm00164a029

subject

Has Abstract

pub_date

1990-02-01 00:00:00

pages

652-6

issue

2

eissn

0022-2623

issn

1520-4804

journal_volume

33

pub_type

杂志文章

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