Efficient Synthesis and Docking Analysis of Selective CDK9 Inhibitor NVP-2
文献类型：期刊论文
| 作者 | Saidahmatov, Abdusaid; Liang, Xue-Wu; Shi, Yuqiang; Han, Xu; Liu, Hong
|
| 刊名 | Pharmaceutical Fronts
 |
| 出版日期 | 2021-09-02 |
| 期号 | 3页码:E50-E55 |
| 关键词 | NVP-2 CDK9 inhitor efficient synthesis docking analysis |
| ISSN号 | 2628-5088 |
| DOI | 10.1055/s-0041-1735144 |
| 英文摘要 | NVP-2 (1), a potent and selective inhibitor of cyclin-dependent kinase 9 (CDK9), showed potent antitumor activity in preclinical studies. In this work, we designed and adopted a convergent synthetic route to efficiently synthesize NVP-2 (1). The key intermediate (7) was synthesized from malononitrile (2) and 1-bromo-2-(2-bromoethoxy)ethane (3) by successive cyclization, reduction, nucleophilic substitution with 2-bromo-6-fluoropyr idine, and Suzuki–Miyaura reaction with (5-chloro-2-fluoropyridin-4-yl)boronic acid. Another key intermediate (11) was synthesized from (S)-1-methoxypropan-2-ol (8) by reaction with TsCl, electrophilic substitution reaction with tert-butyl ((1r,4r)-4-amino cyclohexyl)carbamate, and then by deprotection of Boc. Finally, a substitution reaction by the key intermediates (7) and (11) to afford the target product NVP-2 (1). The reaction conditions of the whole synthesis process were simple and mild, free of harsh conditions such as the microwave reaction and dangerous reagents in the original patent, and realized the efficient synthesis of NVP-2. In addition, we analyzed the binding mode of NVP-2 in the active pocket of CDK9 to provide reasonable design ideas for subsequent discovery of novel CDK9 inhibitors. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309252]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Liu, Hong |
| 作者单位 | State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China |
| 推荐引用方式 GB/T 7714 | Saidahmatov, Abdusaid,Liang, Xue-Wu,Shi, Yuqiang,et al. Efficient Synthesis and Docking Analysis of Selective CDK9 Inhibitor NVP-2[J]. Pharmaceutical Fronts,2021(3):E50-E55. |
| APA | Saidahmatov, Abdusaid,Liang, Xue-Wu,Shi, Yuqiang,Han, Xu,&Liu, Hong.(2021).Efficient Synthesis and Docking Analysis of Selective CDK9 Inhibitor NVP-2.Pharmaceutical Fronts(3),E50-E55. |
| MLA | Saidahmatov, Abdusaid,et al."Efficient Synthesis and Docking Analysis of Selective CDK9 Inhibitor NVP-2".Pharmaceutical Fronts .3(2021):E50-E55. |
入库方式： OAI收割
来源：上海药物研究所
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