《氮雜芳甲氨基二硫代甲酸酯類新型抗腫瘤藥物研究》是葛澤梅為項目負責人，北京大學為依託單位的面上項目。
基本介紹
- 中文名：氮雜芳甲氨基二硫代甲酸酯類新型抗腫瘤藥物研究
- 項目類別 ：面上項目
- 項目負責人：葛澤梅
- 依託單位 ：北京大學
科研成果,項目摘要,
科研成果
序號 | 標題 | 類型 | 作者 |
|---|---|---|---|
1 | 雙氨基二硫代甲酸酯類抗肝癌化合物LRD-22的發現 | 會議論文 | - |
2 | Discovery of new pyridin-3-ylmethyl dithiocarbamic acid esters as activators of pyruvate kinase M2 | 會議論文 | - |
3 | Propylene oxide assisted one-pot, tandem synthesis of substituted-1,3,4-oxadiazole-2(3H)-ones in water | 期刊論文 | Yuanqiang Wang|Tieming Cheng|Zemei Ge|Runtao Li| |
4 | Discovery of novel dithiocarbamic acid ester HGWJ11C with significant anticancer action | 期刊論文 | Jun Wei,|Yiqiang Wang|Zemei Ge *|Runtao Li| |
5 | Palladium catalyzed amide-oxazoline directed C–H acetoxylation of arenes | 期刊論文 | Xuhu Huang|Xin Wang|Zemei Ge|Runtao Li| |
6 | IC-4, a new irreversible EGFR inhibitor, exhibits prominent anti-tumor and anti-angiogenesis activities | 期刊論文 | Ze-Mei Ge|De-Min Zhou|Yi-Tao Wang|Run-Tao Li| |
7 | A convenient four-component one-pot synthesis of 2-amino-1,3,4-thiadiazoles in water | 期刊論文 | Yuan-Qiang Wang|Ze-Mei Ge|Tie-Ming Cheng|Run-Tao Li| |
8 | Novel Dithiocarbamic Acid Esters Derived from 6-Aminomethyl-4-anilinoquinazolines and 6-Aminomethyl-4-anilino-3-cyanoquinolines as Potent EGFR Inhibitors | 期刊論文 | Ge, Zemei|Zhang, Liangren|Cheng, Tieming|Li, Runtao| |
9 | Novel atom-economic reaction: comprehensive utilization of S-alkylisothiouronium salt in the synthesis of thioethers and guanidinium salts | 期刊論文 | Qi Sun|Xin Wang|Zemei Ge|Runtao Li| |
10 | An efficient three-component, one-pot synthesis of 2-alkylthio-4-amino-5-cyano-6-aryl(alkyl)pyrimidines in water | 期刊論文 | Qiao-Yan Li|Ze-Mei Ge|Tie-Ming Cheng|Run-Tao Li| |
11 | Novel Dithiocarbamic Acid Esters Derived from 6-Aminomethyl-4-anilinoquinazolines and 6-Aminomethyl-4-anilino-3-cyanoquinolines as Potent EGFR Inhibitors | 期刊論文 | Zemei Ge|Liangren Zhang|Tieming Cheng|Runtao Li| |
12 | CovalentDock: Automated Covalent Docking with Parameterized Covalent Linkage Energy Estimation and Molecular Geometry Constraints | 期刊論文 | Chinh Tran To Su|Zemei Ge|Runtao Li|Chee Keong Kwoh| |
13 | Discovery of novel dithiocarbamic acid ester HGWJ11C with significant anticancer action | 期刊論文 | Jun Wei|Yiqiang Wang|Zemei Ge|Runtao Li| |
14 | CovalentDock Cloud: a web server for automated covalent docking | 期刊論文 | Shuo Zhou|Zemei Ge|Runtao Li|Chee Keong Kwoh| |
15 | Novel atom-economic reaction: comprehensive utilization of S-alkylisothiouronium salt in the synthesis of thioethers and guanidinium salts | 期刊論文 | Qi Sun|Xin Wang|Zemei Ge|Runtao Li| |
16 | 氨基二硫代甲酸酯類化合物的合成及生物活性研究進展 | 期刊論文 | 李日東|王元強|葛澤梅|李潤濤| |
17 | CovalentDock Cloud: a web server for automated covalent docking | 期刊論文 | Zhou, Shuo|Ge, Zemei|Li, Runtao|Kwoh, Chee Keong| |
18 | A convenient four component one pot synthesis of 2-amino-1,3,4-thiadiazoles in water | 期刊論文 | Wang, Yuan-Qiang;|Ge, Ze-Mei|Tie-Ming Cheng|Run-Tao Li| |
19 | An efficient three-component, one-pot synthesis of 2-alkylthio-4-amino-5-cyano-6-aryl(alkyl)pyrimidines in water | 期刊論文 | 2） Qiao-Yan Li • Ze-Mei Ge • Tie-Ming Cheng • Run-| |
20 | CovalentDock: Automated covalent docking with parameterized covalent linkage energy estimation and molecular geometry constraints | 期刊論文 | Su, Chinh Tran To|Ge, Zemei|Li, Runtao|Kwoh, Chee Keong| |
21 | Discovery and optimization of novel dual dithiocarbamates as potent anticancer agents | 期刊論文 | Xin Wang|Yi-Tao Wang|Ze-Mei Ge|Run-Tao Li| |
22 | IC-4, a new irreversible EGFR inhibitor, exhibits prominent anti-tumor and anti-angiogenesis activities | 期刊論文 | Ze-Mei Ge|De-Min Zhou|Yi-Tao Wang|Run-Tao Li| |
23 | New pyridin-3-ylmethyl carbamodithioic esters activate pyruvate kinase M2 and potential anticancer lead compounds | 期刊論文 | Zhenming Liu|Zemei Ge|Runtao Li|Yuxin Yin| |
24 | Propylene oxide assisted one-pot, tandem synthesis of substituted-1,3,4-oxadiazole-2(3H)-ones in water | 期刊論文 | Xu Yan, Shuo Zhou, Yuanqiang Wang, Zemei Ge *, | |
項目摘要
以我們發現的、抗腫瘤活性明顯、結構全新的呋喃甲氨基二硫代甲酸酯類化合物A為先導物，經第一輪結構最佳化，得到抗腫瘤活性更好的吡啶甲氨基二硫代甲酸酯類化合物A1-A5，研究表明，此類化合物很可能是一類結構新穎的EGFR/ ErbB-2抑制劑。其中A3不僅抗腫瘤活性更好，且克服了第一代先導物溶解度差、不易成藥的缺點。本課題將以A3為第二代先導物，依據第一輪篩選總結的構效關係，首先對吡啶環進行結構最佳化，選擇10類氮雜芳環或取代氮雜芳環，藉助於計算機輔助藥物設計，對化合物與表皮生長因子激酶域的結合情況進行模擬實驗，以便發現和利用與該靶點蛋白結合好的氮雜芳環代替A3中的吡啶環，然後選擇合適的氮雜芳環固定不變，對A3的另一端進行結構修飾。合成約100個化合物進行抗腫瘤活性評價及構效關係研究。有望發現1-2個具有自主智慧財產權、結構新穎、可進入臨床前研究的候選化合物，為開發結構全新的EGFR抑制劑奠定基礎。
