Synthesis and SAR of 4-aminocyclopentapyrrolidines as N-type Ca2+ channel blockers with analgesic activity

Abstract A novel 4-aminocyclopentapyrrolidine series of N-type Ca 2+ channel blockers have been discovered. Enantioselective synthesis of the 4-aminocyclopentapyrrolidines was enabled using N-tert -butyl sulfinamide chemistry. SAR studies demonstrate selectivity over L-type Ca 2+ channels. N-type Ca 2+ channel blockade was confirmed using electrophysiological recording techniques. Compound 25 is an N-type Ca 2+ channel blocker that produces antinociception in inflammatory and nociceptive pain models without exhibiting cardiovascular or motor liabilities.