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Muscarinic subtypes profile modulation within a series of new antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine.

Abstract：

:A set of new muscarinic antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine (1), was synthesized and tested to evaluate their affinity and selectivity for M(1), M(2), M(3) and M(4) receptor subtypes. The conformational constraint of 1 in a bicyclic structure, and the variation in distance and stereochemistry of the active functions allowed us to modulate the selectivity of interaction with the M(1)-M(3) receptor subtypes. The most interesting compound was (cis,trans)-2-(2,2-diphenylethyl)-5-methyl-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole oxalate (6), which is equipotent with Pirenzepine on rabbit vas deferens (M(1)-putative) but shows a better selectivity profile.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Piergentili A,Gentili F,Ghelfi F,Marucci G,Pigini M,Quaglia W,Giannella M

doi

10.1016/s0968-0896(03)00431-0

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

3901-11

issue

18

eissn

0968-0896

issn

1464-3391

pii

S0968089603004310

journal_volume

11

pub_type

杂志文章

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