Lambrecht G, Feifel R, Moser U, Wagner-Röder M, Choo L K, Camus J, Tastenoy M, Waelbroeck M, Strohmann C, Tacke R
Trends Pharmacol Sci. 1989 Dec;Suppl:60-4.
A series of hexahydro-difenidol (HHD) and hexahydro-sila-difenidol (HHSiD) analogues modified in the amino group, the phenyl ring and in the alkylene chain were investigated for their binding and functional properties at muscarinic M1, M2 and M3 receptors. Novel muscarinic receptor antagonists were obtained which exhibited different receptor selectivity profiles from the parent compounds HHD and HHSiD (M1 congruent to M3 greater than M2), e.g. HHD and HHSiD methiodides, M1 greater than M2 congruent to M3; p-fluoro-HHSiD, M3 greater than M1 greater than M2; trans-hexbutenol, M1 greater than M3 greater than M2; and (s)-p-fluoro-hexbutinol, M3 greater than M2 congruent to M1. Stereoselectivity ratios [(R)/(S)] for the enantiomers of HHD, hexbutinol and p-fluoro-hexbutinol were highest at M1, intermediate at M3 and lowest at M2 receptors.
研究了一系列在氨基、苯环和亚烷基链上进行修饰的六氢二苯哌啶（HHD）和六氢硅二苯哌啶（HHSiD）类似物在毒蕈碱M1、M2和M3受体上的结合和功能特性。获得了新型毒蕈碱受体拮抗剂，它们表现出与母体化合物HHD和HHSiD不同的受体选择性特征（M1等同于M3大于M2），例如HHD和HHSiD甲碘化物，M1大于M2等同于M3；对氟-HHSiD，M3大于M1大于M2；反式己烯醇，M1大于M3大于M2；以及（S）-对氟己醇，M3大于M2等同于M1。HHD、己醇和对氟己醇对映体的立体选择性比率[（R）/（S）]在M1受体上最高，在M3受体上居中，在M2受体上最低。
