M. Langlois et al., DERIVATIVES OF QUINUCLIDINE AS 5-HT3 RECEPTOR ANTAGONISTS - INFLUENCEOF AN ADDITIONAL CARBONYL GROUP ON THE RECOGNITION OF CHIRALITY BY THE RECEPTOR, Bioorganic & medicinal chemistry letters, 3(8), 1993, pp. 1555-1558
The influence of the aromatic moiety on the recognition of the (R) or
(S) chirality of the quinuclidine framework by 5-HT3 receptors was eva
luated in a series of simple o-alkoxy benzamide and naphthalene deriva
tives. In all the derivatives, the highest potency resided in the (S)
isomers, as seen with zacopride, and depended upon the hydrophobic pro
perties of the substituent. It was demonstrated that an intramolecular
hydrogen bond as not implicated in the activity and the introduction
of an additional carbonyl function, as in 1,2-naphthalimide, brought a
bout an inversion of the enantioselectivity. The existence of a second
ary hydrogen donor group in the receptor site as suggested.