New ligands of the ghrelin receptor based on the 1,2,4-triazole scaffold by introduction of a second chiral center

Bioorg Med Chem Lett. 2016 May 15;26(10):2408-2412. doi: 10.1016/j.bmcl.2016.04.003. Epub 2016 Apr 4.

Abstract

Introducing a second chiral center on our previously described 1,2,4-triazole, allowed us to increase diversity and elongate the 'C-terminal part' of the molecule. Therefore, we were able to explore mimics of the substance P analogs described as inverse agonists. Some compounds presented affinities in the nanomolar range and potent biological activities, while one exhibited a partial inverse agonist behavior similar to a Substance P analog.

Keywords: 1,2,4-Triazole scaffold; Antagonist; Chirality; Ghrelin receptor (GHS-R1a); Inverse agonist; Structural modulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fluorescence Resonance Energy Transfer
  • Indoles / chemistry
  • Indoles / pharmacology
  • Inhibitory Concentration 50
  • Ligands
  • Receptors, Ghrelin / agonists
  • Receptors, Ghrelin / metabolism*
  • Structure-Activity Relationship
  • Substance P / chemistry
  • Triazoles / chemistry*
  • Tryptophan / analogs & derivatives
  • Tryptophan / chemistry
  • Tryptophan / pharmacology

Substances

  • Indoles
  • Ligands
  • Receptors, Ghrelin
  • Triazoles
  • 1,2,4-triazole
  • Substance P
  • macimorelin
  • Tryptophan