Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, United States.
Bioorg Med Chem. 2012 Jul 1;20(13):4128-39. doi: 10.1016/j.bmc.2012.04.057. Epub 2012 May 4.
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.
我们发现了一系列新型的 4-氨基环戊并吡咯烷类 N 型钙通道阻滞剂。使用 N-叔丁基亚磺酰胺化学可以实现 4-氨基环戊并吡咯烷的对映选择性合成。SAR 研究表明，这些化合物对 L 型钙通道具有选择性。使用电生理记录技术证实了 N 型钙通道的阻断作用。化合物 25 是一种 N 型钙通道阻滞剂，在炎症和伤害性疼痛模型中具有镇痛作用，且没有心血管或运动方面的副作用。
