Structural modifications of N-arylamide oxadiazoles: Identification of N-arylpiperidine oxadiazoles as potent and selective agonists of CB2

Bioorg Med Chem Lett. 2008 Aug 1;18(15):4267-74. doi: 10.1016/j.bmcl.2008.06.096. Epub 2008 Jul 3.

Abstract

Structural modifications to the central portion of the N-arylamide oxadiazole scaffold led to the identification of N-arylpiperidine oxadiazoles as conformationally constrained analogs that offered improved stability and comparable potency and selectivity. The simple, modular scaffold allowed for the use of expeditious and divergent synthetic routes, which provided two-directional SAR in parallel. Several potent and selective agonists from this novel ligand class are described.

MeSH terms

  • Animals
  • Combinatorial Chemistry Techniques
  • Humans
  • Microsomes, Liver / metabolism*
  • Molecular Conformation
  • Molecular Structure
  • Oxadiazoles* / chemical synthesis
  • Oxadiazoles* / chemistry
  • Oxadiazoles* / pharmacokinetics
  • Oxadiazoles* / pharmacology
  • Rats
  • Receptor, Cannabinoid, CB2 / agonists*
  • Structure-Activity Relationship

Substances

  • Oxadiazoles
  • Receptor, Cannabinoid, CB2