Synthesis and structure-activity relationships of N-substituted spiropiperidines as nociceptin receptor ligands: part 2

Bioorg Med Chem Lett. 2009 Feb 15;19(4):1164-7. doi: 10.1016/j.bmcl.2008.12.092. Epub 2008 Dec 29.

Abstract

A series of N-8 substituted analogs based upon the spiropiperidine core of the original lead compound 1 was synthesized. This lead has been elaborated to compounds to give compounds 2 and 3 (R=H) that exhibited high NOP binding affinity as well as selectivity against other known opioid receptors. These two series have been further functionalized at the amido nitrogen. The synthesis and structure-activity relationship (SAR) of these and related compounds are discussed.

MeSH terms

  • Animals
  • Binding Sites
  • Capsaicin / pharmacology
  • Combinatorial Chemistry Techniques
  • Cough / chemically induced
  • Disease Models, Animal
  • Drug Design
  • Guinea Pigs
  • Molecular Structure
  • Nociceptin Receptor
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Receptors, Opioid / drug effects*
  • Receptors, Opioid / metabolism
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • Piperidines
  • Receptors, Opioid
  • Spiro Compounds
  • Capsaicin
  • Nociceptin Receptor