Synthesis and SAR of 4-aminocyclopentapyrrolidines as N-type Ca2+ channel blockers with analgesic activity
| Autor: | 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, Xenia Beebe |
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| Rok vydání: | 2012 |
| Předmět: |
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 |
| Zdroj: | Bioorganic & Medicinal Chemistry. 20:4128-4139 |
| ISSN: | 0968-0896 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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