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7 results on '"Shigeki, Sakamaki"'

1. Exploration of Novel C-Glucoside Formation and Application for SGLT2 Inhibitors —Discovery of Canagliflozin as a SGLT2 Inhibitor

Author

Shigeki Sakamaki, Eiji Kawanishi, and Sumihiro Nomura

Subjects
Canagliflozin, medicine.medical_specialty, 010405 organic chemistry, Chemistry, Phlorizin, Organic Chemistry, Type 2 diabetes, 010402 general chemistry, medicine.disease, 01 natural sciences, 0104 chemical sciences, chemistry.chemical_compound, Endocrinology, Internal medicine, medicine, medicine.drug
Published
2016
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2. Synthesis and Biological Evaluation of Thiophene-C-glucosides as Sodium-Dependent Glucose Cotransporter 2 Inhibitors

Author

Yuichi Koga, Kiichiro Ueta, Eiji Kawanishi, Chiaki Kuriyama, Yasuaki Matsushita, Sumihiro Nomura, Shigeki Sakamaki, and Yasuo Yamamoto

Subjects
biology, Chemistry, Chinese hamster ovary cell, General Chemistry, General Medicine, Carbohydrate metabolism, Inhibitory postsynaptic potential, biology.organism_classification, Excretion, chemistry.chemical_compound, Biochemistry, Drug Discovery, Thiophene, Structure–activity relationship, Cricetulus, Cotransporter
Abstract

The synthesis and structure-activity relationship (SAR) of thiophene-C-glucosides have been explored, and the human sodium-dependent glucose cotransporter 2 (hSGLT2) inhibitory activities and rat urinary glucose excretion (UGE) effects of 3a-f were evaluated. As a result, they showed good hSGLT2 inhibitory activities and rat UGE effects. In particular, the chlorothiophene derivative 3f showed remarkable inhibitory activity against hSGLT2.

Published
2013
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3. Aryl-β-C-glucosidation using glucal boronate: application to the synthesis of tri-O-methylnorbergenin

Author

Tsutomu Ishikawa, Sumihiro Nomura, Shigeki Sakamaki, and Eiji Kawanishi

Subjects
chemistry.chemical_compound, chemistry, Aryl, Organic Chemistry, Drug Discovery, Bergenin, Biochemistry, Glucal, Combinatorial chemistry, Derivative (chemistry)
Abstract

Novel aryl-β-C-glucosidation method using glucal boronate was developed. This protocol can offer several advantages including use of non-toxic, easily handling glucal boronate as a crystalline solid and storable at room temperature for several months. Tri-O-methylnorbergenin (8,10-di-O-methylbergenin), an anti-HIV active bergenin derivative, was concisely synthesized by application of the aryl-β-C-glucosidation method.

Published
2012
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4. Novel Indole-N-glucoside, TA-1887 As a Sodium Glucose Cotransporter 2 Inhibitor for Treatment of Type 2 Diabetes

Author

Shigeki Sakamaki, Kiyomi Ohba, Keiko Nakayama, Hirotaka Kimata, Sumihiro Nomura, Yasuo Yamamoto, Chiaki Kuriyama, Yosuke Matsumura, Yasuaki Matsushita, Kiichiro Ueta, and Minoru Tsuda-Tsukimoto

Subjects
Indole test, medicine.medical_specialty, business.industry, Urinary system, Sodium, Organic Chemistry, chemistry.chemical_element, Type 2 diabetes, medicine.disease, Biochemistry, Excretion, chemistry.chemical_compound, Endocrinology, Glucoside, chemistry, Internal medicine, Drug Discovery, medicine, Sodium-Glucose Cotransporter 2 Inhibitor, Cotransporter, business
Abstract

Inhibition of the renal sodium glucose cotransporter (SGLT) increases urinary glucose excretion (UGE) and thus reduces blood glucose levels during hyperglycemia. To explore the potential of new antihyperglycemic agents, we synthesized and determined the human SGLT2 (hSGLT2) inhibitory potential of novel substituted 3-benzylindole-N-glucosides 6. Optimization of 6 resulted in the discovery of 3-(4-cyclopropylbenzyl)-4-fluoroindole-N-glucoside 6a-4 (TA-1887), a highly potent and selective hSGLT2 inhibitor, with pronounced antihyperglycemic effects in high-fat diet-fed KK (HF-KK) mice. Our results suggest the potential of indole-N-glucosides as novel antihyperglycemic agents through inhibition of renal SGLT2.

Published
2013

5. Synthesis and biological evaluation of thiophene-C-glucosides as sodium-dependent glucose cotransporter 2 inhibitors

Author

Shigeki, Sakamaki, Eiji, Kawanishi, Yuichi, Koga, Yasuo, Yamamoto, Chiaki, Kuriyama, Yasuaki, Matsushita, Kiichiro, Ueta, and Sumihiro, Nomura

Subjects
Male, Body Weight, CHO Cells, Thiophenes, Rats, Rats, Sprague-Dawley, Structure-Activity Relationship, Cricetulus, Glucose, Glucosides, Sodium-Glucose Transporter 2, Cricetinae, Animals, Humans, Hypoglycemic Agents, Sorbitol, Sodium-Glucose Transporter 2 Inhibitors
Abstract

The synthesis and structure-activity relationship (SAR) of thiophene-C-glucosides have been explored, and the human sodium-dependent glucose cotransporter 2 (hSGLT2) inhibitory activities and rat urinary glucose excretion (UGE) effects of 3a-f were evaluated. As a result, they showed good hSGLT2 inhibitory activities and rat UGE effects. In particular, the chlorothiophene derivative 3f showed remarkable inhibitory activity against hSGLT2.

Published
2013

6. N-Glucosides as human sodium-dependent glucose cotransporter 2 (hSGLT2) inhibitors

Author

Yuichi Koga, Eiji Kawanishi, Shigeki Sakamaki, Toshiaki Sakamoto, Yasuaki Matsushita, Sumihiro Nomura, Minoru Tsuda-Tsukimoto, Kiichiro Ueta, Chiaki Kuriyama, and Yasuo Yamamoto

Subjects
medicine.medical_specialty, Indoles, Clinical Biochemistry, Pharmaceutical Science, Biochemistry, Excretion, chemistry.chemical_compound, Structure-Activity Relationship, Glucoside, Glucosides, Sodium-Glucose Transporter 2, In vivo, Internal medicine, Drug Discovery, medicine, Potency, Structure–activity relationship, Animals, Humans, Molecular Biology, IC50, Sodium-Glucose Transporter 2 Inhibitors, Chemistry, Organic Chemistry, In vitro, Rats, Endocrinology, Glucose, Molecular Medicine, Cotransporter, Half-Life, Protein Binding
Abstract

Inhibition of renal sodium-dependent glucose cotransporter 2 (SGLT2) increases urinary glucose excretion (UGE), and thus reduces blood glucose levels in hyperglycemia. A series of N-glucosides was synthesized for biological evaluation as human SGLT2 (hSGLT2) inhibitors. Among these compounds, N-glucoside 9d possessing an indole core structure showed good in vitro activity (IC50=7.1 nM against hSGLT2). Furthermore, 9d exhibited favorable in vivo potency with regard to UGE in rats based on good pharmacokinetic profiles.

Published
2013

7. 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

Author

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

Subjects
Male, medicine.medical_specialty, Carbonates, Biological Availability, Thiophenes, Pharmacology, Rats, Sprague-Dawley, chemistry.chemical_compound, Mice, Structure-Activity Relationship, Glucoside, Glucosides, Internal medicine, Diabetes mellitus, Drug Discovery, medicine, Thiophene, Structure–activity relationship, Animals, Humans, Hypoglycemic Agents, Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Chemistry, Type 2 Diabetes Mellitus, Stereoisomerism, medicine.disease, Rats, Endocrinology, Diabetes Mellitus, Type 2, Molecular Medicine, SGLT2 Inhibitor, Cotransporter, medicine.drug
Abstract

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.

Published
2010

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