Structure-activity relationship of N-methyl-N-aralkyl-peptidylamines as novel N-type calcium channel blockers

  • Bioorg Med Chem Lett. 1999 Aug 2;9(15):2151-6. doi: 10.1016/s0960-894x(99)00359-5.
L Y Hu  1 ,  T R Ryder ,  M F Rafferty ,  D J Dooley ,  J J Geer ,  S M Lotarski ,  G P Miljanich ,  E Millerman ,  D M Rock ,  S J Stoehr ,  B G Szoke ,  C P Taylor ,  M G Vartanian
Affiliations
  • 1. Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
PMID: 10465535 DOI: 10.1016/s0960-894x(99)00359-5
Abstract

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.

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