Abstract
We optimized the structure of an active metabolite (1) of WAY-123783, which was obtained from mouse urine after oral administration, to improve selectivity for SGLT2 and oral bioavailability. O-glucoside derivative 24 (remogliflozin etabonate) was subsequently identified as a potent, highly selective, and orally available SGLT2 inhibitor.
Keywords:
O-glucoside; Remogliflozin etabonate; SGLT2 inhibitor; Type 2 diabetes mellitus.
Copyright © 2021 Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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COS Cells
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Chlorocebus aethiops
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Drug Discovery
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Glucosides / chemistry*
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Glucosides / pharmacology*
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Glycosuria
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Mice
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Molecular Structure
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Pyrazoles / chemistry*
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Pyrazoles / metabolism
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Pyrazoles / pharmacology*
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Sodium-Glucose Transporter 2 / genetics
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Sodium-Glucose Transporter 2 / metabolism
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Sodium-Glucose Transporter 2 Inhibitors / chemistry*
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Sodium-Glucose Transporter 2 Inhibitors / metabolism
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Sodium-Glucose Transporter 2 Inhibitors / pharmacology*
Substances
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Glucosides
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Pyrazoles
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SLC5A2 protein, human
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Sodium-Glucose Transporter 2
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Sodium-Glucose Transporter 2 Inhibitors
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WAY 123783
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remogliflozin etabonate