| 15158798 |
Bedurftig S, Wunsch B: Chiral, nonracemic (piperazin-2-yl) methanol derivatives with sigma-receptor affinity. Bioorg Med Chem. 2004 Jun 15;12(12):3299-311.
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. |
81(1,1,1,1) |