Synthesis and SAR of 4-aminocyclopentapyrrolidines as orally active N-type calcium channel inhibitors for inflammatory and neuropathic pain.

Abstract

A novel series of N-type calcium channel inhibitors have been discovered. Optimization of potency and HT-ADME properties provides 4-aminocyclopentapyrrolidines with analgesic efficacy after oral dosing.

• Authors: Xenia Beebe, Clinton M Yeung, Daria Darczak, Shashank Shekhar, Timothy A Vortherms, Loan Miller, Ivan Milicic, Andrew M Swensen, Chang Z Zhu, Patricia Banfor, Jill M Wetter, Kennan C Marsh, Michael F Jarvis, Victoria E Scott, Michael R Schrimpf, Chih-Hung Lee
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 17 Pg. 4857-61 (Sep 01 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 23876987 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Analgesics
• Calcium Channel Blockers
• Calcium Channels, N-Type

Topics

• Administration, Oral
• Analgesics (chemical synthesis, chemistry, metabolism, therapeutic use)
• Animals
• Calcium Channel Blockers (chemical synthesis, chemistry, metabolism, therapeutic use)
• Calcium Channels, N-Type (metabolism)
• Humans
• Microsomes (metabolism)
• Neuralgia (drug therapy)
• Rats
• Structure-Activity Relationship