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Synthesis and SAR of 4-aminocyclopentapyrrolidines as N-type Ca²⁺ channel blockers with analgesic activity.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2012 Jul 01; Vol. 20 (13), pp. 4128-39. Date of Electronic Publication: 2012 May 04. - Publication Year :
- 2012
-
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.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Acetamides pharmacology
Acetamides therapeutic use
Analgesics pharmacology
Analgesics therapeutic use
Animals
Behavior, Animal drug effects
Calcium Channel Blockers pharmacology
Calcium Channel Blockers therapeutic use
Calcium Channels, N-Type metabolism
Disease Models, Animal
Male
Pain drug therapy
Pyrrolidines pharmacology
Pyrrolidines therapeutic use
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship
Acetamides chemical synthesis
Analgesics chemical synthesis
Calcium Channel Blockers chemical synthesis
Calcium Channels, N-Type chemistry
Pyrrolidines chemical synthesis
Pyrrolidines chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 20
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 22626552
- Full Text :
- https://doi.org/10.1016/j.bmc.2012.04.057