Synthesis and biological evaluation of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2-carbonitrile derivatives as dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes
文献类型：期刊论文
| 作者 | Wang, Jiang ; Feng, Ying; Ji, Xun; Deng, Guanghui; Leng, Ying; Liu, Hong
|
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2013-12-01 |
| 卷号 | 21期号:23页码:7418-7429 |
| ISSN号 | 0968-0896 |
| 关键词 | Pyrrolidine-2-carbonitrile 4-Fluoropyrrolidine-2-carbonitrile Dipeptidyl peptidase-4 inhibitor Oral glucose tolerance test Type 2 diabetes |
| DOI | 10.1016/j.bmc.2013.09.048 |
| 文献子类 | Article |
| 英文摘要 | A novel series of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2-carbonitrile derivatives was designed, synthesized, and found to act as dipeptidyl peptidase-4 (DPP-4) inhibitors. From this series of compounds, compound 17a was identified as an efficacious, safe, and selective inhibitor of DPP-4. In vivo studies in ICR and KKAy mice showed that administration of this compound resulted in decreased blood glucose in these mice after an oral glucose challenge. Compound 17a showed high DPP-4 inhibitory activity (IC50 = 0.017 mu M), moderate selectivity against DPP-4 (selective ratio: DPP-8/DPP-4 = 1324; DPP-9/DPP-4 = 1164), and good efficacy in oral glucose tolerance tests in ICR and KKAy mice. These in vivo anti-diabetic properties and its desirable pharmacokinetic profile in Sprague-Dawley rats demonstrate that compound 17a is a promising candidate for development as an anti-diabetic agent. (C) 2013 Elsevier Ltd. All rights reserved. |
| WOS关键词 | GLUCAGON-LIKE PEPTIDE-1 ; MEDICINAL CHEMISTRY ; IV INHIBITOR ; DPP-4 INHIBITOR ; HIGHLY POTENT ; FLUORINE ; PHARMACEUTICALS ; DISCOVERY ; GLUCOSE |
| 资助项目 | National Natural Science Foundation of China[21021063] ; National Natural Science Foundation of China[81025017] ; National S&T Major Projects[2012ZX09103101-072] ; National S&T Major Projects[2012ZX09301001-005] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| WOS记录号 | WOS:000326374600016 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277366]  |
| 专题 | 药物化学研究室 药理学第一研究室 |
| 通讯作者 | Leng, Ying |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Jiang,Feng, Ying,Ji, Xun,et al. Synthesis and biological evaluation of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2-carbonitrile derivatives as dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2013,21(23):7418-7429. |
| APA | Wang, Jiang,Feng, Ying,Ji, Xun,Deng, Guanghui,Leng, Ying,&Liu, Hong.(2013).Synthesis and biological evaluation of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2-carbonitrile derivatives as dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes.BIOORGANIC & MEDICINAL CHEMISTRY,21(23),7418-7429. |
| MLA | Wang, Jiang,et al."Synthesis and biological evaluation of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2-carbonitrile derivatives as dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes".BIOORGANIC & MEDICINAL CHEMISTRY 21.23(2013):7418-7429. |
入库方式： OAI收割
来源：上海药物研究所
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