Novel antiobesity agents: synthesis and pharmacological evaluation of analogues of Rimonabant and of LH21

Bioorg Med Chem. 2013 Apr 1;21(7):1708-16. doi: 10.1016/j.bmc.2013.01.055. Epub 2013 Feb 4.

Abstract

Searching for novel antiobesity agents, a series of cannabinoid LH21 and of Rimonabant-fatty acid amide analogues have been prepared. Synthesis of pyrazoles 2a-2c was achieved by a two steps simple methodology via α,β-unsaturated ketones. Carboxamides 8a-8h were obtained in good yields from esters 7a-7c by a one-pot procedure which takes place under mild conditions. New compounds have been evaluated in vivo as anorectic agents. Some of them showed interesting properties reducing food intake in rats by a mechanism which does not involve the endocannabinoid system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Obesity Agents / chemical synthesis
  • Anti-Obesity Agents / chemistry*
  • Anti-Obesity Agents / pharmacology*
  • Cannabinoids / chemical synthesis
  • Cannabinoids / chemistry*
  • Cannabinoids / pharmacology*
  • Eating / drug effects*
  • Humans
  • Male
  • Piperidines / chemical synthesis
  • Piperidines / chemistry*
  • Piperidines / pharmacology*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / metabolism
  • Rimonabant

Substances

  • Anti-Obesity Agents
  • Cannabinoids
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Rimonabant