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ID: ALA2046441

Journal: Bioorg Med Chem

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

Authors: Beebe X, Darczak D, Henry RF, Vortherms T, Janis R, Namovic M, Donnelly-Roberts D, Kage KL, Surowy C, Milicic I, Niforatos W, Swensen A, Marsh KC, Wetter JM, Franklin P, Baker S, Zhong C, Simler G, Gomez E, Boyce-Rustay JM, Zhu CZ, Stewart AO, Jarvis MF, Scott VE.

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.

CiteXplore: 22626552

DOI: 10.1016/j.bmc.2012.04.057