Novel Indole-N-glucoside, TA-1887 As a Sodium Glucose Cotransporter 2 Inhibitor for Treatment of Type 2 Diabetes
| Autor: | Shigeki Sakamaki, Kiyomi Ohba, Keiko Nakayama, Hirotaka Kimata, Sumihiro Nomura, Yasuo Yamamoto, Chiaki Kuriyama, Yosuke Matsumura, Yasuaki Matsushita, Kiichiro Ueta, Minoru Tsuda-Tsukimoto |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Indole test
medicine.medical_specialty business.industry Urinary system Sodium Organic Chemistry chemistry.chemical_element Type 2 diabetes medicine.disease Biochemistry Excretion chemistry.chemical_compound Endocrinology Glucoside chemistry Internal medicine Drug Discovery medicine Sodium-Glucose Cotransporter 2 Inhibitor Cotransporter business |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|