The synthesis of [(14) C]AZD5122. Incorporation of an IV (14) C-microtracer dose into a first in human study to determine the absolute oral bioavailability of AZD5122

J Labelled Comp Radiopharm. 2016 May 30;59(6):245-9. doi: 10.1002/jlcr.3385.

Abstract

AZD5122, N-(2-(2,3-difluorobenzylthio)-6-((2R,3R)-3,4-dihydroxybutan-2-ylamino)pyrimidin-4-yl)azetidine-1-sulfonamide was under investigation as a potential chemokine receptor CXCR2 antagonist for the treatment for inflammatory diseases. To gain a better understanding of the human pharmacokinetic profile, an exploratory phase I IV microtracer study was conducted using carbon-14 radiolabelled AZD5122. [(14) C]AZD5122 was carbon-14 labelled in the pyrimidine ring in five steps in an overall radiochemical yield of 19% from [(14) C]thiourea. The absolute oral bioavailability of AZD5122 was assessed in healthy subjects by an oral administration of AZD5122, followed by a concomitant intravenous [(14) C]AZD5122 microdose.

Keywords: AZD5122; IV Microtracer; carbon-14.

MeSH terms

  • Administration, Oral
  • Azetidines / administration & dosage
  • Azetidines / chemical synthesis*
  • Azetidines / chemistry
  • Azetidines / pharmacokinetics*
  • Biological Availability
  • Carbon Radioisotopes / chemistry*
  • Chemistry Techniques, Synthetic
  • Half-Life
  • Humans
  • Injections, Intravenous
  • Radioactive Tracers
  • Sulfonamides / administration & dosage
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacokinetics*

Substances

  • AZD5122
  • Azetidines
  • Carbon Radioisotopes
  • Radioactive Tracers
  • Sulfonamides