Discovery of GCC5694A: A potent and selective sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes
| Autor: | Min Ju Kim, Myung Eun Jung, Kwang-Seop Song, Young Kyu Kong, Hyeon Jung Kim, Misuk Kang |
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| Rok vydání: | 2021 |
| Předmět: |
Sodium
Clinical Biochemistry Pharmaceutical Science chemistry.chemical_element Administration Oral Type 2 diabetes Pharmacology Biochemistry Diabetes Mellitus Experimental Rats Sprague-Dawley chemistry.chemical_compound Structure-Activity Relationship Glucoside Sodium-Glucose Transporter 2 Diabetes mellitus Drug Discovery medicine Animals Humans Dapagliflozin Molecular Biology Sodium-Glucose Transporter 2 Inhibitors Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Transporter medicine.disease In vitro Rats Diabetes Mellitus Type 2 Molecular Medicine Selectivity |
| Zdroj: | Bioorganicmedicinal chemistry letters. 56 |
| ISSN: | 1464-3405 |
| Popis: | Sodium-dependent glucose co-transporter 2 (SGLT2) has emerged as a promising drug target for the treatment of type 2 diabetes, and recently, several SGLT2 inhibitors have been approved for clinical use. A series of molecules with a C-aryl glucoside scaffold was designed and synthesized for biological evaluation. Among the molecules tested, a dihydrobenzofuran-containing analog, 14g (GCC5694A), exhibited excellent in vitro activity against SGLT2 (IC50 = 0.460 nM), good selectivity for SGLT1, and good metabolic stability. Data from further evaluation of the compound in animal models showed that this molecule is a promising candidate for development as an anti-diabetic agent. |
| Databáze: | OpenAIRE |
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