Synthesis and Biological Evaluation of Thiophene-C-glucosides as Sodium-Dependent Glucose Cotransporter 2 Inhibitors

• Published in: Chemical & pharmaceutical bulletin Vol. 61; no. 10; pp. 1037 - 1043
• Main Authors: Sakamaki, Shigeki, Kawanishi, Eiji, Koga, Yuichi, Yamamoto, Yasuo, Kuriyama, Chiaki, Matsushita, Yasuaki, Ueta, Kiichiro, Nomura, Sumihiro
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01-10-2013; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Animals; Body Weight - drug effects; CHO Cells; Cricetinae; Cricetulus; glucal-boronate; Glucose - metabolism; Glucosides - chemical synthesis; Glucosides - chemistry; Glucosides - pharmacology; Humans; Hypoglycemic Agents - chemical synthesis; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Male; Rats; Rats, Sprague-Dawley; sodium-dependent glucose cotransporter; Sodium-Glucose Transporter 2 - metabolism; Sodium-Glucose Transporter 2 Inhibitors; Sorbitol - analogs & derivatives; Sorbitol - chemical synthesis; Sorbitol - chemistry; Sorbitol - pharmacology; Structure-Activity Relationship; thiophene-C-glucoside; Thiophenes - chemistry
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c13-00407

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.