Synthesis of 3 H, 2 H4 , and 14 C-MK 3814 (preladenant)

J Labelled Comp Radiopharm. 2017 Apr;60(4):194-199. doi: 10.1002/jlcr.3490. Epub 2017 Mar 17.

Abstract

MK 3814 is a potent and selective antagonist of the A2a receptor. A2a receptor antagonists have the potential for the treatment of Parkinson disease. Three distinct isotopically labelled forms of MK 3814 were synthesized. [3 H]MK 3814 was prepared for a preliminary absorption, distribution, metabolism, and excretion data (ADME) evaluation of the compound and [14 C]MK 3814 for more definitive ADME work, including an absorption, metabolism, and excretion study in man. In addition, [2 H4 ]MK 3814 was prepared as an internal standard for a liquid chromatography mass spectrometry bioanalytical method. This paper discusses the synthesis of 3 isotopically labelled forms of MK 3814.

Keywords: carbon-14; deuterium; ruthenium catalyst; tritium exchange.

MeSH terms

  • Carbon Radioisotopes / chemistry*
  • Chemistry Techniques, Synthetic
  • Deuterium / chemistry*
  • Isotope Labeling
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry*
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry*
  • Tritium / chemistry*

Substances

  • Carbon Radioisotopes
  • Pyrimidines
  • Triazoles
  • Tritium
  • 2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine
  • Deuterium