Synthesis and evaluation of N-3 substituted phenoxypropyl piperidine benzimidazol-2-one analogues as NOP receptor agonists with analgesic and sedative properties

Bioorg Med Chem. 2007 Feb 15;15(4):1828-47. doi: 10.1016/j.bmc.2006.11.030. Epub 2006 Nov 19.

Abstract

A series of 3-phenoxypropyl piperidine benzimidazol-2-one analogues have been discovered as novel NOP receptor agonists. Structure-activity relationships have been explored via N-3 substitution of the benzimidazol-2-one with a range of functionality. The N-methyl acetamide derivative (+)-7f was found to be a high-affinity, potent NOP agonist with greater than 100-fold selectivity over the MOP receptor. Furthermore (+)-7f was shown to be both antinociceptive and sedative when administered iv to rodents.

MeSH terms

  • Analgesics / chemical synthesis*
  • Animals
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / pharmacology*
  • Hypnotics and Sedatives / chemical synthesis*
  • Nociceptin Receptor
  • Receptors, Opioid / agonists*
  • Rodentia
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Benzimidazoles
  • Hypnotics and Sedatives
  • Receptors, Opioid
  • benzimidazol-2-one
  • Nociceptin Receptor