Discovery of potent, selective, and orally bioavailable 3H-spiro[isobenzofuran-1,4'-piperidine] based melanocortin subtype-4 receptor agonists

Bioorg Med Chem Lett. 2010 Aug 15;20(16):4895-900. doi: 10.1016/j.bmcl.2010.06.068. Epub 2010 Jun 17.

Abstract

Design, synthesis, and SAR of a series of 3H-spiro[isobenzofuran-1,4'-piperidine] based compounds as potent, selective and orally bioavailable melanocortin subtype-4 receptor (MC4R) agonists are disclosed.

MeSH terms

  • Administration, Oral
  • Animals
  • Brain / metabolism
  • Crystallography, X-Ray
  • Drug Evaluation, Preclinical
  • Humans
  • Molecular Conformation
  • Piperidines / chemical synthesis
  • Piperidines / chemistry*
  • Piperidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Melanocortin, Type 4 / agonists*
  • Receptor, Melanocortin, Type 4 / metabolism
  • Spiro Compounds / chemistry
  • Structure-Activity Relationship

Substances

  • Piperidines
  • Receptor, Melanocortin, Type 4
  • Spiro Compounds
  • piperidine