3-[5-(4,5-dihydro-1H-imidazol-2-yl)-furan-2-yl]phenylamine (Amifuraline), a promising reversible and selective peripheral MAO-A inhibitor

J Med Chem. 2006 Sep 7;49(18):5578-86. doi: 10.1021/jm060605r.

Abstract

On the basis of the observation that the central side effects of MAO inhibitors may represent a major limit for their use in pathological processes involving peripheral MAOs, we investigated the possibility of generating novel inhibitors able to target specifically peripheral MAOs. To address this issue, we designed compounds 7-28. From biological results, the 2-(5-phenyl-furan-2-yl)-4,5-dihydro-1H-imidazole (Furaline, 17) proved to be a suitable lead. In fact, in enzyme assays on homogenate preparation from rat liver and HEK cells expressing MAO-A or MAO-B, compounds possessing the frame of 17 behaved as selective and reversible MAO-A inhibitors. Interestingly, in in vivo studies the amino derivative 21 (Amifuraline), endowed with good hydrophilic character, was able to significantly inhibit liver but not brain MAO-A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemical synthesis*
  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology
  • Animals
  • Brain / enzymology
  • Cell Line
  • Furans / chemical synthesis*
  • Furans / chemistry
  • Furans / pharmacology
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Isoenzymes / antagonists & inhibitors
  • Liver / enzymology
  • Male
  • Monoamine Oxidase Inhibitors / chemical synthesis*
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / pharmacology
  • Organ Specificity
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Aniline Compounds
  • Furans
  • Imidazoles
  • Isoenzymes
  • Monoamine Oxidase Inhibitors
  • amifuraline