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Synthesis and alpha-adrenoreceptor blocking properties of phenoxybenzamine-related (2-chloroethyl)-(2,3-dihydrobenzo[1,4]dioxin- 2-ylmethyl)-(2-phenoxyethyl) amines.

Abstract：

:A series of beta-chloroethylamines, structural hybrids of WB 4101, a competitive alpha 1-adrenoreceptor antagonist, and phenoxybenzamine, an irreversible alpha-adrenoreceptor antagonist, has been synthesized and tested in isolated rat vas deferens alpha-adrenoreceptors. Although, for all compounds, apparent blocking potency and alpha 1-selectivity are quite similar to those of phenoxybenzamine, affinity values calculated by taking into account the actual concentration of aziridinium ion in solution, reveal that compounds bearing a 1,4-benzodioxan-2-ylmethyl moiety, display a significantly higher potency for both alpha 1- and alpha 2-adrenoreceptors than compounds having a benzyl group. In addition, two of the compounds, having both methyl and methoxy groups in their structure, show a marked discontinuity in the alpha 1-adrenoreceptor concentration-inhibition curve, with a plateau in the range 30-100 nM. Stereochemical aspects are also shown to play an important role in the binding. The biological results suggest that the two irreversible antagonists may be able to discriminate between two alpha 1-adrenoreceptor subtypes, which are both involved in the noradrenaline-induced contraction of the epididymal portion of rat vas deferens.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Giardinà D,Crucianelli M,Marucci G,Paparelli F,Melchiorre C

doi

10.1016/0968-0896(94)00150-2

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

85-94

issue

1

eissn

0968-0896

issn

1464-3391

pii

0968089694001502

journal_volume

3

pub_type

杂志文章

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