Combining monoamine oxidase B and semicarbazide-sensitive amine oxidase enzyme inhibition to address inflammatory disease

Bioorg Med Chem Lett. 2022 Oct 15:74:128942. doi: 10.1016/j.bmcl.2022.128942. Epub 2022 Aug 13.

Abstract

The discovery of a dual MAO-B/SSAO inhibitor PXS-5131 is reported. The compound offers a compact and rigid three-dimensional structure with superior selectivity over MAO-A. Potency and selectivity are linked to both the double bond geometry and stereochemistry of the allylamine moiety, highlighting the importance of optimal set up of these features in the class of amine oxidase inhibitors. PXS-5131 possesses an attractive preclinical pharmacokinetic profile and has anti-inflammatory properties in models of acute inflammation and neuroinflammation.

Keywords: Amine oxidase; MAO-A; MAO-B; SSAO; VAP-1; Vinyl fluoride.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amine Oxidase (Copper-Containing)*
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Monoamine Oxidase
  • Monoamine Oxidase Inhibitors / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Monoamine Oxidase Inhibitors
  • Amine Oxidase (Copper-Containing)
  • Monoamine Oxidase