Synthesis and structure-activity relationships of potent 1-(2-substituted-aminoacetyl)-4-fluoro-2-cyanopyrrolidine dipeptidyl peptidase IV inhibitors
| Autor: | Koji Yamamoto, Hidetaka Saito, Yuji Takaoka, Kiyokazu Kitano, Hiroshi Fukushima, Masato Takahashi, Eiji Munetomo, Masako Saito-Hori, Akira Hiratate |
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| Rok vydání: | 2008 |
| Předmět: |
Glucose lowering
Dipeptidyl-Peptidase IV Inhibitors Proline Valine General Chemistry General Medicine Pharmacology Crystallography X-Ray Pyrrolidine Dipeptidyl peptidase chemistry.chemical_compound Mice Structure-Activity Relationship chemistry Biochemistry Diabetes Mellitus Type 2 In vivo Drug Discovery Animals Enzyme Inhibitors |
| Zdroj: | Chemicalpharmaceutical bulletin. 56(8) |
| ISSN: | 0009-2363 |
| Popis: | Dipeptidyl peptidase IV (DPP-IV) inhibitors have attracted attention as potential drugs for use in the treatment of type 2 diabetes because they prevent the degradation of glucagon-like peptide-1 (GLP-1) and extend its duration of action. We previously reported that 2-cyano-4-fluoropyrrolidines act as potent DPP-IV inhibitors and have been modifying the 1-position of pyrrolidine to obtain more useful inhibitors. An L-tert-butylglycine derivative was found to be a stable and potent DPP-IV inhibitor that exhibits a glucose lowering effect in vivo. Here, we report the synthesis of and biological data on the aforementioned derivatives. |
| Databáze: | OpenAIRE |
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