Orally active and brain permeable proline amides as highly selective 5HT2c agonists for the treatment of obesity

Bioorg Med Chem Lett. 2010 Apr 1;20(7):2365-9. doi: 10.1016/j.bmcl.2010.01.107. Epub 2010 Jan 25.

Abstract

Brain-penetrable proline amides were developed as 5HT2c agonists with more than 1000-fold binding selectivity against 5HT2b receptor. After medicinal chemistry optimization and SAR studies, orally active proline amides with robust efficacy in a rodent food intake inhibition model were uncovered.

MeSH terms

  • Administration, Oral
  • Amides / pharmacokinetics
  • Amides / pharmacology
  • Amides / therapeutic use
  • Animals
  • Anti-Obesity Agents / pharmacokinetics*
  • Anti-Obesity Agents / pharmacology
  • Anti-Obesity Agents / therapeutic use*
  • Brain / metabolism
  • Dogs
  • Eating / drug effects
  • Humans
  • Obesity / drug therapy*
  • Proline / analogs & derivatives
  • Proline / pharmacokinetics*
  • Proline / pharmacology
  • Proline / therapeutic use*
  • Rats
  • Receptor, Serotonin, 5-HT2C / metabolism
  • Serotonin 5-HT2 Receptor Agonists*
  • Structure-Activity Relationship

Substances

  • Amides
  • Anti-Obesity Agents
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT2 Receptor Agonists
  • Proline