Discovery of novel 2,3-dihydro-1H-inden-1-amine derivatives as selective monoamine oxidase B inhibitors

Bioorg Med Chem Lett. 2019 May 1;29(9):1090-1093. doi: 10.1016/j.bmcl.2019.02.030. Epub 2019 Feb 27.

Abstract

Inhibition of MAO-B has been an effective strategy for the treatment of Parkinson's disease. To find more potent and selective MAO-B inhibitors with novel chemical scaffold, we designed and synthesized a series of new 2,3-dihydro-1H-inden-1-amine derivatives on basis of our previous study. Furthermore, the corresponding structure-activity relationship (SAR) of these compounds is detailedly discussed. Compounds L4 (IC50 = 0.11 μM), L8 (IC50 = 0.18 μM), L16 (IC50 = 0.27 μM) and L17 (IC50 = 0.48 μM) showed similar MAO-B inhibitory activity as Selegiline. Moreover, L4, L16 and L17 also exhibited comparable selectivity with Selegiline, indicating that L4, L16 and L17 could be promising selective MAO-B inhibitors for further study.

Keywords: 2,3-Dihydro-1H-inden-1-amine; Monoamine oxidase B; Selectivity; Structure activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiparkinson Agents / chemical synthesis*
  • Antiparkinson Agents / chemistry
  • Antiparkinson Agents / pharmacology*
  • Clorgyline / chemistry
  • Clorgyline / pharmacology
  • Drug Design
  • Humans
  • Molecular Structure
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / chemical synthesis*
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Protein Conformation
  • Selegiline / chemistry
  • Selegiline / pharmacology
  • Structure-Activity Relationship

Substances

  • Antiparkinson Agents
  • Monoamine Oxidase Inhibitors
  • Selegiline
  • Monoamine Oxidase
  • Clorgyline