Syntheses of isotope‐labeled SGLT2 inhibitor canagliflozin (JNJ‐28431754). (18th September 2017)

• Record Type: Journal Article
• Authors: Lin, Ronghui; Hoerr, David C.; Weaner, Larry E.; Salter, Rhys
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 60:Number 13(2017)
• Page Start: 616
• Page End: 623
• Publication Date: 2017-09-18
• Subjects: canagliflozin -- isotope label -- SGLT2 inhibitor -- synthesis; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3542
• Languages: English
• ISSNs: 0362-4803

Abstract

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.