Design, synthesis, and pharmacological effects of structurally simple ligands for MT(1) and MT(2) melatonin receptors

Bioorg Med Chem. 2010 Sep 1;18(17):6496-511. doi: 10.1016/j.bmc.2010.06.100. Epub 2010 Jul 3.


A series of phenoxyalkyl and phenylthioalkyl amides were prepared as melatoninergic ligands. Modulation of affinity of the newly synthesized compound by applying SARs around the terminal amide moiety, the alkyl chain, and the methoxy group on the aromatic ring provides compounds with nanomolar affinity for both melatonin receptor subtypes. Affinity towards MT(1) and MT(2) receptors were modulated also exploiting chirality. The investigation of intrinsic activity revealed that all the tested compounds behave as full or partial agonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology*
  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Drug Design
  • Ligands
  • Melatonin / chemistry
  • Receptor, Melatonin, MT1 / metabolism*
  • Receptor, Melatonin, MT2 / metabolism*
  • Structure-Activity Relationship


  • Amides
  • Ligands
  • Receptor, Melatonin, MT1
  • Receptor, Melatonin, MT2
  • Melatonin