Synthesis of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl carbamate analogs as σ 2 receptor ligands

Abstract

A series of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamate analogs was prepared and their affinities for sigma (σ 1 and σ 2) receptors were measured in vitro. The results of their structure–activity relationship study identified two new compounds, N-(9-(4-aminobutyl)-9-azabicyclo[3.3.1]nonan-3α-yl)- N′-(2-methoxy-5-methylphenyl)carbamate and N-(9-(6-aminohexyl)-9-azabicyclo[3.3.1]nonan-3α-yl)- N′-(2-methoxy-5-methylphenyl)carbamate, having a high affinity and selectivity for σ 2 versus σ 1 receptors. These compounds were also used in the preparation of biotinylated and fluorescent probes of the σ 2 receptor.