Novel Indole‑N‑glucoside, TA-1887 As a Sodium Glucose Cotransporter 2 Inhibitor for Treatment of Type 2 Diabetes

• Published in: ACS medicinal chemistry letters Vol. 5; no. 1; pp. 51 - 55
• Main Authors: Nomura, Sumihiro, Yamamoto, Yasuo, Matsumura, Yosuke, Ohba, Kiyomi, Sakamaki, Shigeki, Kimata, Hirotaka, Nakayama, Keiko, Kuriyama, Chiaki, Matsushita, Yasuaki, Ueta, Kiichiro, Tsuda-Tsukimoto, Minoru
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 09-01-2014
• Subjects: Letter; Type 2 diabetes; sodium glucose cotransporter 2 inhibitor; TA-1887; antihyperglycemic effect; urinary glucose excretion; indole-N-glucoside
• ISSN: 1948-5875; 1948-5875
• DOI: 10.1021/ml400339b

Inhibition of the renal sodium glucose cotransporter (SGLT) increases urinary glucose excretion (UGE) and thus reduces blood glucose levels during hyperglycemia. To explore the potential of new antihyperglycemic agents, we synthesized and determined the human SGLT2 (hSGLT2) inhibitory potential of novel substituted 3-benzylindole-N-glucosides 6. Optimization of 6 resulted in the discovery of 3-(4-cyclopropylbenzyl)-4-fluoroindole-N-glucoside 6a-4 (TA-1887), a highly potent and selective hSGLT2 inhibitor, with pronounced antihyperglycemic effects in high-fat diet-fed KK (HF-KK) mice. Our results suggest the potential of indole-N-glucosides as novel antihyperglycemic agents through inhibition of renal SGLT2.