Development of potential selective and reversible pyrazoline based MAO-B inhibitors as MAO-B PET tracer precursors and reference substances for the early detection of Alzheimer's disease

Bioorg Med Chem Lett. 2014 Sep 15;24(18):4490-4495. doi: 10.1016/j.bmcl.2014.07.085. Epub 2014 Aug 7.

Abstract

Since high MAO-B levels are present in early stages of AD, the MAO-B system can be designated as an appropriate and prospective tracer target of molecular imaging biomarkers for the detection of early AD. According to the preceding investigations of Mishra et al. the aim of this work was the development of a compound library of selective and reversible MAO-B inhibitors by performing bioisosteric modifications of the core structure of 3-(anthracen-9-yl)-5-phenyl-4,5-dihydro-1H-pyrazoles. In conclusion, 13 new pyrazoline based derivatives have been prepared, which will serve as precursor substances for future radiolabeling as well as reference compounds for the investigation of increased MAO-B levels in AD.

Keywords: Alzheimer’s disease; MAO-B; Molecular imaging; PET; Pyrazoline derivatives.

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / enzymology
  • Alzheimer Disease / metabolism
  • Dose-Response Relationship, Drug
  • Early Diagnosis
  • Humans
  • Molecular Structure
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors* / chemistry
  • Monoamine Oxidase Inhibitors* / pharmacology
  • Positron-Emission Tomography*
  • Pyrazoles* / chemistry
  • Pyrazoles* / pharmacology
  • Reference Standards
  • Structure-Activity Relationship

Substances

  • Monoamine Oxidase Inhibitors
  • Pyrazoles
  • Monoamine Oxidase