1. Synthesis and SAR of 4-aminocyclopentapyrrolidines as N-type Ca2+ channel blockers with analgesic activity
- Author
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Andrew O. Stewart, Janel M. Boyce-Rustay, Ivan Milicic, Chang Z. Zhu, Jill M. Wetter, Timothy A. Vortherms, Michael F. Jarvis, Marian T. Namovic, Diana L. Donnelly-Roberts, Chengmin Zhong, Victoria E. Scott, Karen Kage, Rodger F. Henry, Erica Gomez, Scott J. Baker, Carol S. Surowy, Daria Darczak, Pamela H. Franklin, Gricelda H. Simler, Wende Niforatos, Richard S. Janis, Andrew M. Swensen, Kennan C. Marsh, and Xenia Beebe
- Subjects
Voltage-dependent calcium channel ,Chemistry ,Stereochemistry ,Organic Chemistry ,Clinical Biochemistry ,Analgesic ,Pharmaceutical Science ,N-type calcium channel ,Pharmacology ,Biochemistry ,chemistry.chemical_compound ,Electrophysiology ,Sulfinamide ,Drug Discovery ,Molecular Medicine ,Structure–activity relationship ,L-type calcium channel ,Channel blocker ,Molecular Biology - 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.
- Published
- 2012