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中文别名 GS5734,瑞德沙韦
英文别名 Remdesivir; GS-5734; GS 5734; GS5734, Prodrug of GS-441524; Prodrug of GS441524; Prodrug of GS441524;
CAS号 1809249-37-3
SMILES CCC(CC)COC(=O)C(C)NP(=O)(OCC1C(C(C(O1)(C#N)C2=CC=C3N2N=CN=C3N)O)O)OC4=CC=CC=C4
Inchi InChI=1S/C27H35N6O8P/c1-4-18(5-2)13-38-26(36)17(3)32-42(37,41-19-9-7-6-8-10-19)39-14-21-23(34)24(35)27(15-28,40-21)22-12-11-20-25(29)30-16-31-33(20)22/h6-12,16-18,21,23-24,34-35H,4-5,13-14H2,1-3H3,(H,32,37)(H2,29,30,31)/t17-,21+,23+,24+,27-,42-/m0/s1
InchiKey RWWYLEGWBNMMLJ-YSOARWBDSA-N
分子式 Molecular Weight C27H35N6O8P
分子量 Formula 602.6g/mol
闪点 FP NA
熔点 Melting point NA
沸点 Boiling point NA
物理属性 Physical property powder
密度 Density NA
蒸汽压 Vapor Pressure NA
溶解度Solubility
化学性质Characters Solid powder
储藏条件 Storage conditions Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
产品说明 瑞德西韦Remdesivir (GS-5734) 是一种核苷类似物,具有抗病毒活性。
IntroductionRemdesivir has been found to show reasonable antiviral activity against more distantly related viruses such as respiratory syncytial virus, Junin virus, Lassa fever virus, and MERS-coronavirus.
Application1瑞德西韦的用途1:最新研究表明瑞德西韦可作为新冠状病毒的先导化合物作为新型冠状病毒新药研发在科研中使用。
Application2瑞德西韦的用途2:之前研究证明瑞德西韦具备治疗埃博拉病毒的功效。
Application3
       瑞德西韦Remdesivir (GS-5734) ,CAS号:1809249-37-3 是一种核苷类似物,具有抗病毒活性,在 HAE 细胞中,对SARS-CoV和MERS-CoV的EC50值为 74 nM,在延迟脑肿瘤细胞中,对鼠肝炎病毒的EC50值为 30 nM,瑞德西韦是最新抗新型冠状病毒的主要成分,目前仍在临床研究过程中。瑞德西韦Remdesivir (GS-5734) is a nucleoside analogue, with effective antiviral activity, withEC50s of 74 nM forSARS-CoVandMERS-CoVin HAE cells, and 30 nM formurine hepatitis virusin delayed brain tumor cells.


      Remdesivir has been found to show reasonable antiviral activity against more distantly related viruses such as respiratory syncytial virus, Junin virus, Lassa fever virus, and MERS-coronavirus. GS-5734 was rapidly pushed through clinical trials due to the 2013–2016 West African Ebola virus epidemic crisis, eventually being used in at least one human patient despite its early development stage at the time. Preliminary results have been promising, and further clinical trials are planned.

瑞德西韦的合成技术路线:
目前根据文献和范德生物自己研发的合成路径,可以总结有一下两条合成途径:

首先合成瑞德西韦该化合物的第一种合成方法:是化合物15在丁基锂的化学作用下与内脂14进行糖苷化学反应(该过程中有一个化合物15的芳香伯胺的原位硅保护且脱保护的反应过程),化合物16接着进行氰基化反应,后再进行脱苄基保护得到化合物4,合成化合物4再与化合物19进行反应得到消旋的最终化合物,但是最终需要对进行SFC拆分得到手性化合物。


图1


瑞德西韦合成路径2:

如下文中图所示,很明显方法1的合成方法需要进行SFC拆分,收率也不高大规模制备的难度比较大。所有就瑞德西韦的第二种合成方法,采用的是手性合成,很好地避免了拆分这一化学过程的发生。第一步化学反应中的糖苷化反应使用碘代物取代一代方法中的溴代物,使用格氏试剂进行卤素交换后,得到产品的产率约为40%,高于第一种的合成方法的产率。氰基化反应和醚的脱苄基反应经过优化以后,最终产物的产率都有大幅度的提升,可以更多的得到化合物4。对化合物4的邻位顺式双羟基进行保护,高产率的可以得到化合物21。化合物21与单一构型的22b进行反应后,再进行脱保护反应可以得到手性的最终化合物。该过程中单一构型的化合物22b显得非常重要。研究发现消旋的化合物22a在异丙醚作为溶剂重结晶的情况下,单一构型化合物22b很容易溶解在溶剂中,这一发现对整个路线的大量生产起到非常重要的作用。

图2



完整的瑞德西韦产品的合成路径:
图2
警示图
危险性 暂无数据
危险性警示 暂无数据
安全声明 暂无数据
安全防护 NA
备注 NA
Bifunctional aryloxyphosphoramidate prodrugs of 2′-C-Me-uridine: synthesis and anti-HCV activity. Mu
Sugar modified pyrimido[4,5-b]indole nucleosides: synthesis and antiviral activity. Juraj Kon, Mich
Reactive cyclic intermediates in the ProTide prodrugs activation: trapping the elusive pentavalent phosphorane.Elika Procházková,Rafael Navrátil, Org.Biomol.Chem.2019 ,17,315

1: Check Hayden E. Experimental drugs poised for use in Ebola outbreak. Nature. 2018 May;557(7706):475-476. doi: 10.1038/d41586-018-05205-x. PubMed PMID: 29789732.



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