Syntheses of isotope‐labeled SGLT2 inhibitor canagliflozin (JNJ‐28431754). (18th September 2017) - Lin, Ronghui
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. Abstract : Canagliflozin (Invokana, JNJ‐28431754) is an orally bioavailable and selective 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.