Syntheses of Isotope-Labeled SGLT2 Inhibitor Canagliflozin (JNJ-28431754)

J Labelled Comp Radiopharm. 2017 Nov;60(13):616-623. doi: 10.1002/jlcr.3542. Epub 2017 Sep 18.

Abstract

Canagliflozin (Invokana, JNJ-28431754) is an orally bioavailable and selective SGLT2 (subtype 2 sodium-glucose transport protein) inhibitor approved for the treatment of type 2 diabetes. Herein, we report the synthesis of 13 C and 14 C-labeled canagliflozin. Stable isotope-labeled [13 C6 ]canagliflozin was synthesized in 4 steps starting from [13 C6 ]-labeled glucose. The [14 C]-Labeled canagliflozin was synthesized by incorporation of [14 C] into the benzylic position between the thiophene and benzene rings of the compound. Detailed synthesis of the isotope-labeled compounds is reported.

Keywords: SGLT2 inhibitor; canagliflozin; isotope label; synthesis.

MeSH terms

  • Canagliflozin / chemical synthesis*
  • Canagliflozin / chemistry*
  • Canagliflozin / pharmacology
  • Carbon Isotopes / chemistry
  • Carbon Radioisotopes / chemistry
  • Chemistry Techniques, Synthetic
  • Isotope Labeling
  • Sodium-Glucose Transporter 2 Inhibitors*

Substances

  • Carbon Isotopes
  • Carbon Radioisotopes
  • Sodium-Glucose Transporter 2 Inhibitors
  • Canagliflozin
  • Carbon-14
  • Carbon-13