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：317

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

共 31 条

[1]

CRISPINO G, 2004, Patent No. 2004063209

[2]

DEETJEN P, 1995, TXB NEPHROLOGY, V1, P90

[3]

Deshpande P P., 2008, [No title captured], Patent No. [US 7375213 B2, 7375213, 7375213B2]

[4]

ELLSWORTH B, 2002, Patent No. 6414126

[5]

Ellsworth B. A., 2001, [No title captured], Patent No. [WO01/27128, 0127128, WO, 0127128]

[6] C-Arylglucoside synthesis:: triisopropylsilane as a selective reagent for the reduction of an anomeric C-phenyl ketal [J].

Ellsworth, BA ;

Doyle, AG ;

Patel, M ;

Caceres-Cortes, J ;

Meng, W ;

Deshpande, PP ;

Pullockaran, A ;

Washburn, WN .

TETRAHEDRON-ASYMMETRY, 2003, 14 (20) :3243-3247

[7] Type 2 diabetes market [J].

Gershell, L .

NATURE REVIEWS DRUG DISCOVERY, 2005, 4 (05) :367-368

[8] Sodium glucose co-transporter 2 (SGLT2) inhibitors as potential antidiabetic agents [J].

Handlon, AL .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2005, 15 (11) :1531-1540

[9] SYNTHETIC ROUTES TO HIGHER-CARBON SUGARS - REACTION OF LACTONES WITH 2-LITHIO-1,3-DITHIANE [J].

HORTON, D ;

PRIEBE, W .

CARBOHYDRATE RESEARCH, 1981, 94 (01) :27-41

[10] A new approach towards the yellowing inhibition of mechanical pulps.: Part I:: Selective removal of α-hydroxyl and α-carbonyl groups in lignin model compounds [J].

Hu, TQ ;

Leary, G ;

Wong, D .

HOLZFORSCHUNG, 1999, 53 (01) :43-48

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