1. Synthesis and biological evaluation of N-glucosyl indole derivatives as sodium-dependent glucose co-transporter 2 inhibitors.
- Author
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Chu KF, Song JS, Chen CT, Yeh TK, Hsieh TC, Huang CY, Wang MH, Wu SH, Yao CH, Chao YS, and Lee JC
- Subjects
- Animals, Benzhydryl Compounds pharmacology, CHO Cells, Cricetulus, Glucosides chemical synthesis, Glucosides chemistry, Glucosides pharmacokinetics, Humans, Indoles chemical synthesis, Indoles chemistry, Indoles pharmacokinetics, Molecular Structure, Rats, Sprague-Dawley, Sodium-Glucose Transporter 2 Inhibitors chemical synthesis, Sodium-Glucose Transporter 2 Inhibitors chemistry, Sodium-Glucose Transporter 2 Inhibitors pharmacokinetics, Structure-Activity Relationship, Glucosides pharmacology, Indoles pharmacology, Sodium-Glucose Transporter 2 metabolism, Sodium-Glucose Transporter 2 Inhibitors pharmacology
- Abstract
Sodium-dependent glucose co-transporter 2 (SGLT2) inhibition has been demonstrated to efficiently control hyperglycemia via an insulin secretion-independent pathway. The unique mode of action eliminates the risk of hypoglycemia and makes SGLT2 inhibitors an attractive option for the treatment of type 2 diabetes. In a continuation of our previous studies on SGLT2 inhibitors bearing different sugar moieties, sixteen new N-glucosyl indole derivatives were designed, synthesized, and evaluated for their inhibitory activity against hSGLT2. Of these sixteen, acethydrazide-containing N-glucosyl indole 9d was found to be the most potent SGLT2 inhibitor, and caused a significant elevation in urine glucose excretion in rats at 50 mg/kg, relative to the vehicle control., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2019
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