Structure-Activity Relationship Of N-Methyl-N-Aralkyl-Peptidylamines As Novel N-Type Calcium Channel Blockers

Selective N-type voltage sensitive calcium channel (VSCC) blockers have shown efficacy in several animal models of stroke and pain. In the process of searching for small molecule N-type calcium channel blockers, we have identified a series of N-methyl-N-aralkyl-peptidylamines with potent functional activity at N-type VSCCs. The most active compound discovered in this series is PD 173212 (11, IC50 = 36 nM in the IMR-32 assays). SAR and pharmacological evaluation of this series are described, (C) 1999 Elsevier Science Ltd. All rights reserved.