Structure-activity relationships and CoMFA of N-3 substituted phenoxypropyl piperidine benzimidazol-2-one analogues as NOP receptor agonists with analgesic properties

Bioorg Med Chem. 2008 Mar 15;16(6):2829-51. doi: 10.1016/j.bmc.2008.01.005. Epub 2008 Jan 10.

Abstract

The N-3 position of a series of 3-phenoxypropyl piperidine benzimidazol-2-one analogues was optimised using the predictive power of a CoMFA model. The model was used to prioritise compounds for synthesis culminating in the triazole (+)-24. (+)-24 was found to be a high affinity, potent NOP agonist and demonstrated both antinociceptive and antiallodynic effects when administered iv to rodents.

MeSH terms

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

Substances

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