The synthesis and biological evaluation of 2-(3-methyl or 3-phenylisoxazol-5-yl)-3-aryl-8-thiabicyclo[3.2.1]octanes.

Cocaine, a potent stimulant of the central nervous system, owes its reinforcing and stimulant properties to its ability to inhibit monoamine uptake systems such as the Dopamine Transporter (DAT), and the Serotonin Transporter (SERT) located on presynaptic neurons in the striatum. The search for pharmacotherapies for cocaine addiction has focused on the design of compounds that bind selectively to the DAT and manifest slow onset of stimulatory action with long duration of action. We had reported that 3-aryl-2-carbomethoxy-8-thiabicyclo[3.

The synthesis of bivalent 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)-8-heterobicyclo[3.2.1]octanes as probes for proximal binding sites on the dopamine and serotonin transporters.

3-Aryltropanes have been widely explored for potential medications for remediation of cocaine abuse. Research has focused predominantly on 8-azatropanes and it is now well recognized that these compounds can be designed to manifest varied selectivity and potency for inhibition of the dopamine, serotonin, and norepinephrine uptake systems. We had reported that the 8-nitrogen atom present in the 3-aryltropanes is not essential for tropanes to bind to monoamine uptake systems.

Synthesis of 8-thiabicyclo[3.2.1]octanes and their binding affinity for the dopamine and serotonin transporters.

Cocaine is a potent stimulant of the central nervous system. Its reinforcing and stimulant properties have been associated with inhibition of the dopamine transporter (DAT) on presynaptic neurons. In the search for medications for cocaine abuse, we have prepared 2-carbomethoxy-3-aryl-8-thiabicyclo[3.

Synthesis of 8-thiabicyclo[3.2.1]oct-2-enes and their binding affinity for the dopamine and serotonin transporters.

The reinforcing and stimulant properties of cocaine have been primarily associated with its propensity to bind to monoamine transport systems, in particular the dopamine transporter. Inhibition of the dopamine transporter then leads to an increase of synaptic dopamine with substantial pharmacological consequences. The search for medications for cocaine abuse has had a particular focus on tropane analogs of cocaine, and the interchange of nitrogen for oxygen in this class has led to potent and selective inhibitors of monoamine transport.