Fluorinated 2-Arylcyclopropan-1-amines - A new class of sigma receptor ligands

Bioorg Med Chem. 2020 Nov 15;28(22):115726. doi: 10.1016/j.bmc.2020.115726. Epub 2020 Sep 1.

Abstract

Stereoisomeric 2-aryl-2-fluoro-cyclopropan-1-amines have been discovered as a new class of σ receptor ligands showing different selectivity for the two subtypes of the receptor. Generally, compounds substituted in 4-position are much more active than corresponding 3-substituted isomers. trans-2-Fluoro-2-(4-methoxyphenyl)cyclopropan-1-amine (19a) was the most potent (Ki = 4.8 nM) σ1 receptor ligand, while cis-2-fluoro-2-(4-trifluoromethylphenyl)cyclopropan-1-amine (20b) was the most potent (Ki = 95 nM) σ2 receptor ligand.

Keywords: Arylcyclopropanamines; Fluorine; Stereoselective synthesis; Structure-affinity-relationship; Tranylcypromine; σ Receptor ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Amines / pharmacology*
  • Animals
  • Cyclopropanes / chemistry
  • Cyclopropanes / pharmacology*
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Halogenation
  • Ligands
  • Molecular Structure
  • Rats
  • Receptors, sigma / metabolism*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amines
  • Cyclopropanes
  • Ligands
  • Receptors, sigma
  • sigma-2 receptor