Structural Modifications of the Triazolo-thiadiazole Derivatives as DOT1L Inhibitors and Their Activities
文献类型：期刊论文
| 作者 | Xu Xiaoming2; Guo Siqi1,3; Zhang Jing2; Chen Yantao1; Kang Yaqing2; Liu Na2; Liu Junfang2; Luo Cheng1 ; Chen Shijie1; Chen Hua2
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| 刊名 | CHINESE JOURNAL OF ORGANIC CHEMISTRY
 |
| 出版日期 | 2020-05-25 |
| 卷号 | 40期号:5页码:1345-1354 |
| 关键词 | DOT1L inhibitor ttriazolo-thiadiazole structural modification hydrophobic substituent structure-activity analysis |
| ISSN号 | 0253-2786 |
| DOI | 10.6023/cjoc201911012 |
| 通讯作者 | Chen Shijie(shijiechen@simm.ac.cn) ; Chen Hua(hua-todd@163.com) |
| 英文摘要 | A series of novel derivatives containing triazolo-thiadiazole moiety have been synthesized by structural modifications on a lead disruptor of telomeric silencing 1-like (DOT1L) inhibitor 8. All the compounds have been evaluated for their DOT1L inhibitory activities at the concentration of 50 mu mol/L. The results showed that the tested compounds showed certain DOT1L inhibitory activities. Among them, N,N-dimethyl-4-(6-methyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl)aniline (14b) and (R)-tert-butyl (1-((3-(4-(dimethylamino)phenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)methyl)-piperidin-3-yl)carbamate (16a) were the best ones with IC50 values of 7.37 and 7.84 mu mol/L, respectively, near that of the positive control 8. The structure-activity analysis showed that when the triazolo-thiadiazole moiety occupied the binding-site of S-adenosylmethionine (SAM) in DOT1L and R-1 group was 4-N,N-dimethyl, the hydrophobic substituents as the tailed R-2 groups would be accommodated into the DOT1L binding site, and the sizes of the substituents seemed no effects on their DOT1L inhibitory activities of the compounds. |
| WOS关键词 | ACCURATE DOCKING ; LEUKEMIA-CELLS ; POTENT ; DESIGN ; GLIDE ; DISRUPTOR ; DISCOVERY |
| 资助项目 | Natural Science Interdisciplinary Research Program of Hebei University[DXK201903] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000550196500026 |
| 出版者 | SCIENCE PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/292000]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Chen Shijie; Chen Hua |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Hebei Univ, Coll Chem & Environm Sci, Key Lab Chem Biol Hebei Prov, Baoding 071002, Hebei, Peoples R China 3.Nanchang Univ, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu Xiaoming,Guo Siqi,Zhang Jing,et al. Structural Modifications of the Triazolo-thiadiazole Derivatives as DOT1L Inhibitors and Their Activities[J]. CHINESE JOURNAL OF ORGANIC CHEMISTRY,2020,40(5):1345-1354. |
| APA | Xu Xiaoming.,Guo Siqi.,Zhang Jing.,Chen Yantao.,Kang Yaqing.,...&Chen Hua.(2020).Structural Modifications of the Triazolo-thiadiazole Derivatives as DOT1L Inhibitors and Their Activities.CHINESE JOURNAL OF ORGANIC CHEMISTRY,40(5),1345-1354. |
| MLA | Xu Xiaoming,et al."Structural Modifications of the Triazolo-thiadiazole Derivatives as DOT1L Inhibitors and Their Activities".CHINESE JOURNAL OF ORGANIC CHEMISTRY 40.5(2020):1345-1354. |
入库方式： OAI收割
来源：上海药物研究所
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