Structure-activity relationship studies of N-sulfonyl analogs of cocaine: role of ionic interaction in cocaine binding.

Six new N-sulfonylated analogs of cocaine have been prepared, and these compounds have been evaluated for their ability to inhibit [3H]mazindol binding and [3H]dopamine uptake into striatal synaptosomes. The N-sulfonyl compounds still inhibited binding and uptake at low micromolar concentrations despite the neutral character of the tropane nitrogen, thus suggesting that the binding of cocaine to the dopamine transporter may not require protonation of its nitrogen and ionic interaction with its recognition site.