Inhibition of monoamine oxidase by indole and benzofuran derivatives

Eur J Med Chem. 2010 Oct;45(10):4458-66. doi: 10.1016/j.ejmech.2010.07.005. Epub 2010 Jul 31.

Abstract

Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. A series of indole and benzofuran derivatives were synthesised and evaluated as inhibitors of the two MAO isoforms, MAO-A and MAO-B. In general, the derivatives were found to be selective MAO-B inhibitors with K(i) values in the nanoMolar (nM) to microMolar (microM) concentration range. The most potent MAO-B inhibitor, 3,4-dichloro-N-(2-methyl-1H-indol-5-yl)benzamide, exhibited a K(i) value of 0.03 microM and was 99 fold more selective for the B isoform. We conclude that these indole and benzofuran derivatives are promising reversible MAO-B inhibitors with a possible role in the treatment of neurodegenerative diseases such as Parkinson's disease (PD).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzofurans / chemical synthesis
  • Benzofurans / chemistry*
  • Benzofurans / pharmacology*
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacology*
  • Models, Molecular
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry*
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Parkinson Disease / drug therapy
  • Structure-Activity Relationship

Substances

  • Benzofurans
  • Indoles
  • Monoamine Oxidase Inhibitors
  • Monoamine Oxidase