Washington University

Rebecca Aft

Robert H Mach

Zhude Tu

William G Hawkins

Richard S Hotchkiss

Wenhua Chu

Suwanna Vangveravong

A series of N-substituted 9-azabicyclo[3.3.1]nonan-3&#x3b1;-yl phenylcarbamate analogs are disclosed, as well as methods of their preparation. Their affinities for sigma (&#x3c3;1 and &#x3c3;2) receptors are described. Two new compounds, N-(9-(4-aminobutyl)-9-azabicyclo[3.3.1]nonan-3&#x3b1;-yl)-N'-(2-methoxy-5-methylphenyl)carbamate and N-(9-(6-aminohexyl)-9-azabicyclo[3.3.1]nonan-3&#x3b1;-yl)-N&#x2032;-(2-methoxy-5-methylphenyl)carbamate, are shown to have a high affinity and selectivity for &#x3c3;2 versus &#x3c3;1 receptors. Among the disclosed compounds are biotinylated and fluorescent analogs. These compounds can serve as probes to the &#x3c3;2 receptor. In addition, some disclosed compounds can induce apoptotic cell death by both caspase-dependent and caspase-independent mechanisms, and are effective for treatment of tumors. The compounds can be used as chemotherapeutics or chemosensitizers in the treatment of a wide variety of solid tumors.

Therapeutic uses of bicyclic ligands of sigma 2 receptor

Sigma 2 receptor ligands and therapeutic uses therefor

Growing community of inventors

Chesterfield, MO, United States of America

Rebecca Aft