Synthesis of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl carbamate analogs as σ2 receptor ligands

A series of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamate analogs was prepared and their affinities for sigma (σ1 and σ2) 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 σ2 versus σ1 receptors. These compounds were also used in the preparation of biotinylated and fluorescent probes of the σ2 receptor.

Synthesis and in vitro binding of a series of molecular probes for studying the function of the σ2 receptor.Figure optionsDownload as PowerPoint slide