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Updated: Aug 24, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Chiral, nonracemic (piperazin-2-yl)methanol derivatives with sigma-receptor affinity
Stephan Bedürftig1, Bernhard Wünsch
1Pharmazeutisches Institut der Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, D-79104 Freiburg i. Br., Germany.
Abstract:
Starting with the proteinogenic amino acid (S)-serine a series of chiral nonracemic (piperazin-2-yl)methanols 3 with various N-4 substituents is described. The key step in the synthesis of 3 is the reaction of the chloroacetamide 5 with various primary amines to yield the diastereomeric bicyclic piperazinediones cis-6 and trans-6. The scope and limitation of this transformation is thoroughly investigated. The alpha1- and sigma2-receptor affinities of the piperazines 3 are determined in receptor binding studies with guinea pig brain and rat liver membrane preparations using [3H]-labeled (+)-pentazocine and ditolylguanidine, respectively. It was found, that an additional phenyl residue in the N-4 substituent is favorable to high sigma1-receptor affinity. In this series the p-methoxybenzyl substituted piperazine 3d reveals the highest sigma1-receptor affinity (Ki=12.4 nM) with selectivity toward sigma2-, NMDA-, kappa-opioid, and mu-opioid receptors.
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