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

doi:10.1016/j.bmc.2013.05.048

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 journal › Article › peer-review

26 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 language	English
Pages (from-to)	5561-5572
Number of pages	12
Journal	Bioorganic and Medicinal Chemistry
Volume	21
Issue number	17
DOIs	https://doi.org/10.1016/j.bmc.2013.05.048
Publication status	Published - Sept 1 2013
Externally published	Yes

All Science Journal Classification (ASJC) codes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmc.2013.05.048

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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

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, vol. 21, no. 17, pp. 5561-5572. https://doi.org/10.1016/j.bmc.2013.05.048

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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.",

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AU - Koga, Yuichi

AU - Sakamaki, Shigeki

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AU - Kawanishi, Eiji

AU - Sakamoto, Toshiaki

AU - Yamamoto, Yasuo

AU - Kimata, Hirotaka

AU - Nakayama, Keiko

AU - Kuriyama, Chiaki

AU - Matsushita, Yasuaki

AU - Ueta, Kiichiro

AU - Tsuda-Tsukimoto, Minoru

AU - Nomura, Sumihiro

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AB - 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.

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

Abstract

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