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

共 50 条

[21] Exploration of Novel C-Glucoside Formation and Application for SGLT2 Inhibitors -Discovery of Canagliflozin as a SGLT2 Inhibitor-
Sakamaki, Shigeki
Kawanishi, Eiji
Nomura, Sumihiro
JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN, 2016, 74 (09) : 877 - 884
[22] Synthesis and Biological Evaluation of Thiophene-C-glucosides as Sodium-Dependent Glucose Cotransporter 2 Inhibitors
Sakamaki, Shigeki
Kawanishi, Eiji
Koga, Yuichi
Yamamoto, Yasuo
Kuriyama, Chiaki
Matsushita, Yasuaki
Ueta, Kiichiro
Nomura, Sumihiro
CHEMICAL & PHARMACEUTICAL BULLETIN, 2013, 61 (10) : 1037 - 1043
[23] Diabetic Ketoacidosis With Canagliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, in Patients With Type 1 Diabetes
Peters, Anne L.
Henry, Robert R.
Thakkar, Payal
Tong, Cindy
Alba, Maria
DIABETES CARE, 2016, 39 (04) : 532 - 538
[24] Metabolic and hemodynamic effects of sodium-dependent glucose cotransporter 2 inhibitors on cardio-renal protection in the treatment of patients with type 2 diabetes mellitus
Kashiwagi, Atsunori
Maegawa, Hiroshi
JOURNAL OF DIABETES INVESTIGATION, 2017, 8 (04) : 416 - 427
[25] Empagliflozin: A sodium-glucose cotransporter 2 inhibitor for treatment of type 2 diabetes
Dixit, Divisha
Yoon, Youngmin
Volino, Lucio R.
Mansukhani, Rupal Patel
AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY, 2015, 72 (22) : 1943 - 1954
[26] Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes
Hedrington, Maka S.
Davis, Stephen N.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2015, 11 (04) : 613 - 623
[27] Novel L-Xylose Derivatives as Selective Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitors for the Treatment of Type 2 Diabetes
Goodwin, Nicole C.
Mabon, Ross
Harrison, Bryce A.
Shadoan, Melanie K.
Almstead, Zheng Y.
Xie, Yiling
Healy, Jason
Buhring, Lindsey M.
DaCosta, Christopher M.
Bardenhagen, Jennifer
Mseeh, Faika
Liu, Qingyun
Nouraldeen, Amr
Wilson, Alan G. E.
Kimball, S. David
Powell, David R.
Rawlins, David B.
JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (20) : 6201 - 6204
[28] Sodium Glucose Cotransporter 2 Inhibition by Canagliflozin Attenuates Intrarenal Angiotensinogen Augmentation in Type 2 Diabetes Mellitus.
Woods, T. Cooper
Satou, Ryousule
Miyata, Kayoko
Katsurada, Akemi
Dugas, Courtney M.
Lightell, Daniel, Jr.
Navar, L. Gabriel
HYPERTENSION, 2017, 70
[29] Discovery of potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor SGL5213 for type 2 diabetes treatment
Kuroda, Shoichi
Kobashi, Yohei
Oi, Takahiro
Kawabe, Kenichi
Shiozawa, Fumiyasu
Okumura-Kitajima, Lisa
Sugisaki-Kitano, Mami
Io, Fusayo
Yamamoto, Koji
Kakinuma, Hiroyuki
BIOORGANIC & MEDICINAL CHEMISTRY, 2019, 27 (02) : 394 - 409
[30] Beneficial Effects of Sodium Glucose Cotransporter 2 Inhibition by Canagliflozin Independent of its Glucose Lowering Effects in Type 2 Diabetes Mellitus
Woods, T. Cooper
Sato, Ryosuke
Miyata, Kayoko
Katsurada, Akemi
Lightell, Daniel
Navar, L. Gabriel
FASEB JOURNAL, 2017, 31

← 1 2 3 4 5 →