Synthesis and structure-activity relationships of potent 4-fluoro-2-cyanopyrrolidine dipeptidyl peptidase IV inhibitors
| Autor: | Masato Takahashi, Koji Yamamoto, Eiji Munetomo, Akira Hiratate, Ayako Mikami, Hidetaka Saito, Yuji Takaoka, Akio Suzuki, Kiyokazu Kitano, Sumi Chonan, Masako Saito-Hori, Hiroshi Fukushima |
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| Rok vydání: | 2007 |
| Předmět: |
Blood Glucose
Male Models Molecular Pyrrolidines Dipeptidyl Peptidase 4 Clinical Biochemistry Fluorine Compounds Pharmaceutical Science Biochemistry Chemical synthesis Dipeptidyl peptidase Structure-Activity Relationship In vivo Oral administration Drug Discovery Animals Insulin Protease Inhibitors Molecular Biology chemistry.chemical_classification Dipeptidyl-Peptidase IV Inhibitors Cyanides biology Molecular Structure Chemistry Organic Chemistry In vitro Rats Enzyme Enzyme inhibitor Glycine biology.protein Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry. 16(7) |
| ISSN: | 1464-3391 |
| Popis: | Dipeptidyl peptidase IV (DPP-IV) inhibitors are promising antidiabetic drugs, and several drugs are in the developmental stage. We previously reported that the introduction of fluorine to the 4-position of 2-cyanopyrrolidine enhanced the DPP-IV inhibitory effect. In the present report, we examined the structure–activity relationship (SAR) of 2-cyano-4-fluoropyrrolidine with N-substituted glycine at the 1-position. We report the identification of a potent and stable DPP-IV inhibitor (TS-021) with a long-term persistent plasma drug concentration and a potent antihyperglycemic activity. |
| Databáze: | OpenAIRE |
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