| 咪唑酮并[4,5-c]喹啉衍生物的 合成及体外生物活性 |
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| 引用本文： | 李艳杰,王恩思,邵晓玮,张兴民,牛生秀,杨丽娟,武毅.咪唑酮并[4,5-c]喹啉衍生物的 合成及体外生物活性[J].高等学校化学学报,2019,40(12):2502. |
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| 作者姓名： | 李艳杰 王恩思 邵晓玮 张兴民 牛生秀 杨丽娟 武毅 |
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| 作者单位： | 吉林大学药学院,长春130012;长春中医药大学药学院,长春130117;吉林大学药学院,长春,130012;北京富龙泰康生物技术有限公司,北京,101111 |
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| 基金项目： | 吉林大学(中国)高新技术(集团)有限公司基金资助. |
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| 摘 要： | 为了合成含有咪唑并喹啉结构骨架的高效PI3K/mTOR抑制剂, 以4-氯喹啉与苯胺的芳香亲核取代(SNAr)反应、 芳香二胺与三光气Traube缩合反应以及双芳基的Suzuki交叉偶联反应等为关键步骤, 合成了15个结构新颖的咪唑酮并4,5-c]喹啉衍生物(8Aa~8Ae, 8Ba~8Be和8Ca~8Ce). 经核磁共振波谱(NMR)和高分辨质谱(HRMS)分析确证了关键中间体和目标化合物的结构. 采用ADP-Glo激酶试剂盒和TR-FRET mTOR试剂盒法检测了目标化合物对PI3K/mTOR的体外抑制活性, 发现所有化合物均表现出较强的活性.
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| 关 键 词： | 咪唑酮并喹啉 Traube反应 Suzuki反应 PI3K/mTOR双重抑制剂 |
| 收稿时间： | 2019-10-21 |
Synthesis and Biological Activity in vitro of Imidazo[4,5-c]quinoline Derivatives ? |
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| Yanjie LI,Ensi WANG,Xiaowei SHAO,Xingmin ZHANG,Shengxiu NIU,Lijuan YANG,Yi WU.Synthesis and Biological Activity in vitro of Imidazo[4,5-c]quinoline Derivatives ?[J].Chemical Research In Chinese Universities,2019,40(12):2502. |
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| Authors: | Yanjie LI Ensi WANG Xiaowei SHAO Xingmin ZHANG Shengxiu NIU Lijuan YANG Yi WU |
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| Institution: | 1. College of Pharmacy, Jilin University, Changchun 130012, China;2. College of Pharmacy, Changchun University of Traditional Chinese Medicine, Changchun 130117, China;3. Beijing Foreland Pharma Biological Technology Co., Ltd., Beijing 101111, China |
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| Abstract: | In search of new and efficient PI3K/mTOR inhibitor based on the imidazoquinoline structural framework, 15 novel imidazo4,5-c] quinoline were synthesized via SNAr reaction of 4-chloroquinoline with aniline, the Traube condensation reaction of aromatic diamine with triphosgene and the Suzuki coupling reaction of bromo-compounds with 3-quinoline boronic acid. The structures of the key intermediates and target compounds were confirmed by 1H NMR, 13C NMR and HRMS. Imidazo4,5-c] quinolin analogues(8Aa—8Ae, 8Ba—8Be, 8Ca—8Ce) were evaluated for their in vitro activities against PI3Kα/mTOR by ADP-Glo kinase assay and TR-FRET assay, all compounds displayed strong activities. |
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| Keywords: | Imidazoquinoline Traube reaction Suzuki reaction PI3K/mTOR Dual inhibitor |
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