C-Glucosides with heteroaryl thiophene as novel sodium-dependent glucose cotransporter 2 inhibitors

Yuichi Koga, Shigeki Sakamaki, Mitsuya Hongu, Eiji Kawanishi, Toshiaki Sakamoto, Yasuo Yamamoto, Hirotaka Kimata, Keiko Nakayama, Chiaki Kuriyama, Yasuaki Matsushita, Kiichiro Ueta, Minoru Tsuda-Tsukimoto, Sumihiro Nomura

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Canagliflozin (1), a novel inhibitor for sodium-dependent glucose cotransporter 2 (SGLT2), has been developed for the treatment of type 2 diabetes. To investigate the effect of replacement of the phenyl ring in 1 with heteroaromatics, C-glucosides 2 were designed, synthesized, and evaluated for their inhibitory activities against SGLT2. Of these, 3-pyridyl, 2-pyrimidyl or 5-membered heteroaryl substituted derivatives showed highly potent inhibitory activity against SGLT2, while 5-pyrimidyl substitution was associated with slightly reduced activity. In particular, 2g (TA-3404) had remarkable anti-hyperglycemic effects in high-fat diet fed KK (HF-KK) mice.

Original languageEnglish
Pages (from-to)5561-5572
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number17
DOIs
Publication statusPublished - Sep 1 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Koga, Y., Sakamaki, S., Hongu, M., Kawanishi, E., Sakamoto, T., Yamamoto, Y., Kimata, H., Nakayama, K., Kuriyama, C., Matsushita, Y., Ueta, K., Tsuda-Tsukimoto, M., & Nomura, S. (2013). C-Glucosides with heteroaryl thiophene as novel sodium-dependent glucose cotransporter 2 inhibitors. Bioorganic and Medicinal Chemistry, 21(17), 5561-5572. https://doi.org/10.1016/j.bmc.2013.05.048