Discovery of Canagliflozin, a Novel C-Glucoside with Thiophene Ring, as Sodium-Dependent Glucose Cotransporter 2 Inhibitor for the Treatment of Type 2 Diabetes Mellitus

被引：305

作者：

Nomura, Sumihiro ^{[1
]}

Sakamaki, Shigeki ^{[1
]}

Hongu, Mitsuya ^{[1
]}

Kawanishi, Eiji ^{[1
]}

Koga, Yuichi ^{[1
]}

Sakamoto, Toshiaki ^{[1
]}

Yamamoto, Yasuo ^{[1
]}

Ueta, Kiichiro ^{[2
]}

Kimata, Hirotaka ^{[2
]}

Nakayama, Keiko ^{[2
]}

Tsuda-Tsukimoto, Minoru ^{[3
]}

机构：

[1] Mitsubishi Tanabe Pharma Corp, Med Chem Res Labs, Toda, Saitama, Japan

[2] Mitsubishi Tanabe Pharma Corp, Pharmacol Res Labs, Toda, Saitama, Japan

[3] Mitsubishi Tanabe Pharma Corp, DMPK Res Labs, Toda, Saitama, Japan

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 17期

关键词：

ANTIDIABETIC AGENTS; SGLT2; INHIBITORS; DERIVATIVES; PREVALENCE; REDUCTION; MECHANISM;

D O I：

10.1021/jm100332n

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We discovered that C-glucosides 4 bearing a heteroaromatic ring formed metabolically more stable inhibitors for sodium-dependent glucose cotransporter 2 (SGLT2) than the O-glucoside, 2 (T-1095). A novel thiophene derivative 4b-3 (canagliflozin) was a highly potent and selective SGLT2 inhibitor and showed pronounced anti-hyperglycemic effects in high-fat diet fed KK (HF-KK) mice.

引用

页码：6355 / 6360

页数：6

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