Novel reversible monoamine oxidase A inhibitors: highly potent and selective 3-(1H-pyrrol-3-yl)-2-oxazolidinones

J Med Chem. 2011 Dec 8;54(23):8228-32. doi: 10.1021/jm201011x. Epub 2011 Nov 7.

Abstract

Monoamine oxidases (MAOs) are involved in various psychiatric and neurodegenerative disorders; hence, MAO inhibitors are useful agents in the therapy of Parkinson's disease, Alzheimer's dementia, and depression syndrome. Herein we report a novel series of 3-(1H-pyrrol-3-yl)-2-oxazolidinones 3-7 as reversible, highly potent and selective anti-MAO-A agents. In particular, 4b, 5b, and 4c showed a K(i-MAO-A) of 0.6, 0.8, and 1 nM, respectively, 4c being 200000-fold selective for MAO-A with respect to MAO-B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • In Vitro Techniques
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / chemical synthesis*
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / pharmacology
  • Oxazolidinones / chemical synthesis*
  • Oxazolidinones / chemistry
  • Oxazolidinones / pharmacology
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Isoenzymes
  • Monoamine Oxidase Inhibitors
  • Oxazolidinones
  • Pyrroles
  • Monoamine Oxidase