Design and synthesis of naphthalenic dimers as selective MT1 melatoninergic ligands

J Med Chem. 2003 Mar 27;46(7):1127-9. doi: 10.1021/jm0255872.

Abstract

We report the synthesis and binding properties at MT(1) and MT(2) receptors of the first example of agomelatine (N-[2-(7-methoxynaphth-1-yl)ethyl]acetamide) dimers in which two agomelatine moieties are linked together through their methoxy substituent by a polymethylene side chain according to the "bivalent ligand" approach. Some of these compounds behave as MT(1)-selective ligands. The most selective one (5) behaves as an antagonist.

MeSH terms

  • Acetamides / chemistry*
  • Acetamides / pharmacology
  • Animals
  • Cell Line
  • Cricetinae
  • Dimerization
  • Drug Design
  • Humans
  • Ligands
  • Melatonin / metabolism*
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology
  • Radioligand Assay
  • Receptors, Cell Surface / agonists
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / drug effects*
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / drug effects*
  • Receptors, Melatonin
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Ligands
  • Naphthalenes
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Melatonin
  • agomelatine
  • Melatonin