| Autor: |
Peng Sun, Weiliang Zhu, Yuren Zhou, Xiangrui Jiang, Qiang Shao, Jingshan Shen, Zhen Wang, Jianming Zhu, Bo Li, Chen Zhuxi, Tao Jiang, He-Yao Wang, Qiang Zhang |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
Archiv der Pharmazie. 348:399-407 |
| ISSN: |
0365-6233 |
| DOI: |
10.1002/ardp.201500082 |
| Popis: |
The optimization of a series of fused β-homophenylalanine inhibitors of dipeptidyl peptidase-4 (DPP-4) is described. Modification on the P2-binding moiety of 6 (IC50 = 10 nM) led to the discovery of β-homophenylalanine derivatives containing pyrrolidin-2-ylmethyl amides. The introduction of a sulfamine in the meta position of the phenyl ring improved the potency against DPP-4 (6-12-fold increase). Compound 14k showed DPP-4 inhibitory activity with an IC50 value of 0.87 nM. Meanwhile, in vivo experiments exhibited that 14h had an efficiency comparable to sitagliptin at the dose of 10 mg/kg. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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