1. Na(+)-glucose cotransporter inhibitors as antidiabetic agents. II. Synthesis and structure-activity relationships of 4'-dehydroxyphlorizin derivatives.
- Author
-
Hongu M, Tanaka T, Funami N, Saito K, Arakawa K, Matsumoto M, and Tsujihara K
- Subjects
- Animals, Blood Glucose analysis, Glucose metabolism, Glucosides blood, Glycosuria urine, Hypoglycemic Agents pharmacology, Kidney drug effects, Kidney metabolism, Male, Phlorhizin pharmacology, Rats, Rats, Sprague-Dawley, Sodium metabolism, Sodium-Glucose Transporter 1, Structure-Activity Relationship, Hypoglycemic Agents chemical synthesis, Membrane Glycoproteins antagonists & inhibitors, Monosaccharide Transport Proteins antagonists & inhibitors, Phlorhizin analogs & derivatives
- Abstract
A novel series of 4'-dehydroxyphlorizin derivatives was synthesized and the effects of these compounds on urinary glucose excretion were evaluated in rats. There was a strict structural requirement for activity. Introduction of a small substituent or a flat ring at the 3- and/or the 4-position on the A ring was permissible, but any change at the bridge part between the A and B rings or in the sugar moiety resulted in complete loss of activity. The 6'-OH group on the B ring was also necessary, and even small structural modifications of the 6'-OH group reduced the activity considerably. Among the compounds synthesized, the 5-benzofuryl derivative 25 was the most potent and was selected as a new lead for further structure-activity relationship investigations.
- Published
- 1998
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