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.
MeSH terms
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Animals
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Biological Availability
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Canagliflozin
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Carbonates / pharmacology
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Diabetes Mellitus, Type 2 / drug therapy*
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Glucosides / chemical synthesis*
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Glucosides / pharmacokinetics
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Glucosides / pharmacology
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Humans
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Hypoglycemic Agents / chemical synthesis*
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Hypoglycemic Agents / pharmacokinetics
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Hypoglycemic Agents / pharmacology
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Male
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Mice
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Rats
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Rats, Sprague-Dawley
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Sodium-Glucose Transporter 2 Inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
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Thiophenes / chemical synthesis*
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Thiophenes / pharmacokinetics
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Thiophenes / pharmacology
Substances
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Carbonates
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Glucosides
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Hypoglycemic Agents
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Sodium-Glucose Transporter 2 Inhibitors
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T 1095
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Thiophenes
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Canagliflozin