Structure-activity relationships of melanocortin agonists containing the benzimidazole scaffold

Aleksandar Todorovic, Christine G. Joseph, Nicholas B. Sorensen, Michael S. Wood, Carrie Haskell-Luevano

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The melanocortin system has been implicated in regulating various physiological processes including pigmentation, energy homeostasis, obesity, steroidogenesis cardiovascular, and exocrine gland function. The five melanocortin receptors that belong to the super family of G protein-coupled receptors are stimulated by naturally occurring agonists. The aim of this research was focused on the design, synthesis, and pharmacological characterization of melanocortin ligands that contain the 1,2,5-trisubstituted benzimidazole scaffold. A series of benzimidazole analogues, with three points of diversity at positions 1, 2, and 5, were designed, synthesized, pharmacologically assayed at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R and resulted in ligands possessing a range of agonist activity from nm to no stimulation at up to 100 μM concentrations. This study demonstrates that the benzimidazole structure template can be appended with key melanocortin agonist amino acids for the design melanocortin receptor agonist ligands.

Original languageEnglish (US)
Pages (from-to)338-349
Number of pages12
JournalChemical Biology and Drug Design
Volume69
Issue number5
DOIs
StatePublished - May 2007

Keywords

  • Benzimidazole
  • Melanocortin
  • Obesity
  • Solid-phase
  • Synthesis

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