Search

Your search keyword '"Kawanishi, Eiji"' showing total 4 results
Start Over Author "Kawanishi, Eiji" Topic sodium-glucose transporter 2 inhibitors
4 results on '"Kawanishi, Eiji"'

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

Author

Yamamoto Y, Kawanishi E, Koga Y, Sakamaki S, Sakamoto T, Ueta K, Matsushita Y, Kuriyama C, Tsuda-Tsukimoto M, and Nomura S

Subjects
Animals, Glucose metabolism, Glucosides chemical synthesis, Glucosides pharmacokinetics, Half-Life, Humans, Indoles chemical synthesis, Indoles pharmacokinetics, Protein Binding, Rats, Sodium-Glucose Transporter 2 metabolism, Structure-Activity Relationship, Glucosides chemistry, Indoles chemistry, Sodium-Glucose Transporter 2 Inhibitors
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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
Full Text
View/download PDF

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

Author

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, and Nomura S

Subjects
Animals, Blood Glucose analysis, CHO Cells, Canagliflozin, Cell Line, Cricetinae, Cricetulus, Diet, High-Fat, Glucosides chemical synthesis, Glucosides pharmacokinetics, Half-Life, Humans, Hypoglycemic Agents chemical synthesis, Hypoglycemic Agents pharmacokinetics, Male, Mice, Monosaccharides chemical synthesis, Monosaccharides pharmacokinetics, Protein Binding, Pyridines chemical synthesis, Pyridines pharmacokinetics, Rats, Rats, Sprague-Dawley, Sodium-Glucose Transporter 1 antagonists & inhibitors, Sodium-Glucose Transporter 1 genetics, Sodium-Glucose Transporter 1 metabolism, Sodium-Glucose Transporter 2 genetics, Sodium-Glucose Transporter 2 metabolism, Glucosides chemistry, Hypoglycemic Agents chemistry, Monosaccharides chemistry, Pyridines chemistry, Sodium-Glucose Transporter 2 Inhibitors, Thiophenes chemistry
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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
Full Text
View/download PDF

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

Author

Sakamaki S, Kawanishi E, Koga Y, Yamamoto Y, Kuriyama C, Matsushita Y, Ueta K, and Nomura S

Subjects
Animals, Body Weight drug effects, CHO Cells, Cricetinae, Cricetulus, Glucosides chemical synthesis, Glucosides pharmacology, Humans, Hypoglycemic Agents chemistry, Hypoglycemic Agents pharmacology, Male, Rats, Rats, Sprague-Dawley, Sodium-Glucose Transporter 2 metabolism, Sorbitol chemical synthesis, Sorbitol chemistry, Sorbitol pharmacology, Structure-Activity Relationship, Glucose metabolism, Glucosides chemistry, Hypoglycemic Agents chemical synthesis, Sodium-Glucose Transporter 2 Inhibitors, Sorbitol analogs & derivatives, Thiophenes chemistry
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
Full Text
View/download PDF

4. 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

Nomura S, Sakamaki S, Hongu M, Kawanishi E, Koga Y, Sakamoto T, Yamamoto Y, Ueta K, Kimata H, Nakayama K, and Tsuda-Tsukimoto M

Subjects
Animals, Biological Availability, Canagliflozin, Carbonates pharmacology, Glucosides pharmacokinetics, Glucosides pharmacology, Humans, Hypoglycemic Agents pharmacokinetics, Hypoglycemic Agents pharmacology, Male, Mice, Rats, Rats, Sprague-Dawley, Stereoisomerism, Structure-Activity Relationship, Thiophenes pharmacokinetics, Thiophenes pharmacology, Diabetes Mellitus, Type 2 drug therapy, Glucosides chemical synthesis, Hypoglycemic Agents chemical synthesis, Sodium-Glucose Transporter 2 Inhibitors, Thiophenes chemical synthesis
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
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results