- METHODS OF PREPARING 1'-CYANO NUCLEOSIDES
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The present disclosure generally describes methods of preparing l'-cyano nucleosides, such as a compound of Formula (I). For example, the compound of Formula (I) can be prepared from a compound of Formula (Il-a) in a flow reactor.
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- Synthesis and evaluation of a collection of purine-like C-nucleosides as antikinetoplastid agents
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The kinetoplastid parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are the causative agents of neglected tropical diseases with a serious burden in several parts of the world. These parasites are incapable of synthesizing purines de nov
- Bouton, Jakob,Maes, Louis,Karalic, Izet,Caljon, Guy,Van Calenbergh, Serge
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supporting information
(2021/01/06)
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- Novel compound and application thereof
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The invention relates to a novel compound and application thereof, and also relates to an application of the compound in preparation of antiviral drugs and the like. In particular, AIDS virus is present. Application of hepatitis B virus, paramyxovirus and
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- Synthesis method of antiviral drug ridexivir and intermediate thereof
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The invention discloses a synthesis method of an antiviral drug retegravir, which comprises the following steps: carrying out addition reaction on a compound 1 and a compound 2 to obtain a compound 3,carrying out cyanation reaction under the action of Lewis acid to obtain a compound 4, carrying out copper-catalyzed ammonolysis reaction to obtain a compound 5, carrying out palladium-catalyzed hydrogenation debenzylation to obtain a compound 6, and finally, reacting with a compound 7 to obtain a retegravir product. According to the method, the compound 1 is directly used as a raw material, no extra active hydrogen exists, and the reaction yield is high,the method has the advantages of simple operation, no amino interference, high cyanation reaction yield, clean and efficient palladium-carbon alkylation debenzylation reaction, convenient palladium-carbon recovery, and less three wastes. In addition, the leaving group of the compound 7 is improved to improve the activity of the compound 7, and the unprotected docking reaction of 6 and 7 is optimized by adding a proper auxiliary agent, so that the selectivity and the reaction yield can be greatly improved. The route is simple to operate, high in total yield, high in product purity and suitable for large-scale production.
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- Method for preparing retegravir by using micro-channel reactor
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The invention discloses a method for synthesizing retegravir by using a micro-channel reactor, which realizes continuous flow synthesis of retegravir by using a scale effect of a micro-flow field technology and using a novel micro-channel reactor to repla
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- Synthesis method of key intermediate of ridecevir
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The invention provides a novel method for preparing a key intermediate of ridecevir as shown in a formula (VII). Benzyl fully-protected lactone as shown in a formula (I) is used as a starting material and is subjected to ring opening to obtain a compound as shown in a formula (II). The hydroxyl of the compound (II) is protected by a proper protecting group to obtain the compound shown in the formula (III). The compound (III) and the compound (IV) are subjected to coupling, protecting group removal and cyclization to obtain an intermediate shown as a formula (V) by a one-pot method. The intermediate (V) is subjected to two-step conversion to obtain the key intermediate (VII) of the ridecevir. According to the method provided by the invention, the compound (I) which can be bought in the market is used as the starting material, and the key intermediate compound (VII) for preparing the ridecevir is obtained at high yield through five-step reaction, so that the cost is greatly reduced, and the method is suitable for industrial mass production.
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- Preparation process of ridecevir mother nucleus intermediate
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The invention discloses a preparation process of a ridecevir mother nucleus intermediate (3aR,4R,6S,6aS)-6-(4-aminopyrrole[2,1-f][1,2,4]triazine-7-yl)-2,2-dimethyltetrahydrofuran[3,4-d][1,3]dioxo-4-yl)methanol. The preparation method comprises the following steps: carrying out a coupling reaction on a pyrrole triazine halide II serving as a raw material and a halide III under the promotion of a metal reagent MX to obtain a coupling product IV with high stereoselectivity; and carrying out a free radical reaction on the IV and a cyaniding reagent in the presence of an oxidizing agent, and carrying out a boron trichloride debenzylation reaction on the obtained intermediate to obtain the ridecevir mother nucleus intermediate I with high stereoselectivity. The method has the main beneficial effects that the process route is relatively short, the reaction condition is mild, tedious procedures such as strong acidity and column chromatography separation and purification are avoided from the source, the reaction yield is high, the stereoselectivity is good, the method is easy to industrialize, and the method has relatively high implementation value and social and economic benefits.
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Paragraph 0025-0026; 0028; 0030; 0039-0040; 0042
(2021/10/27)
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- N-protected heterocyclic compound, preparation method thereof and method for preparing C-nucleoside derivative by using N-protected heterocyclic compound
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The invention provides an N-protected heterocyclic compound, a preparation method thereof and a method for preparing a C-nucleoside derivative by using the N-protected heterocyclic compound. Specifically, the invention provides a method for preparing the C-nucleoside derivative by using a heterocyclic compound protected by N-carbobenzoxy or N-tert-butyloxycarboryl. According to the method, halogenation is not needed, temporary amino protection is not needed, protons of the heterocyclic compound are removed by directly using an organic lithium or organic magnesium compound, and addition with ribose lactone is carried out. According to the method, the synthesis route of the C-nucleoside derivative is shortened, and the yield of the reaction of the heterocyclic compound and the ribose lactone is remarkably improved under the condition that no halogen atom is used as a substituent group.
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Paragraph 0442; 0443; 0444
(2021/08/14)
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- Potency and pharmacokinetics of GS-441524 derivatives against SARS-CoV-2
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The nucleoside metabolite of remdesivir, GS-441524 displays potent anti-SARS-CoV-2 efficacy, and is being evaluated in clinical as an oral antiviral therapeutic for COVID-19. However, this nucleoside has a poor oral bioavailability in non-human primates, which may affect its therapeutic efficacy. Herein, we reported a variety of GS-441524 analogs with modifications on the base or the sugar moiety, as well as some prodrug forms, including five isobutyryl esters, two L-valine esters, and one carbamate. Among the new nucleosides, only the 7-fluoro analog 3c had moderate anti-SARS-CoV-2 activity, and its phosphoramidate prodrug 7 exhibited reduced activity in Vero E6 cells. As for the prodrugs, the 3′-isobutyryl ester 5a, the 5′-isobutyryl ester 5c, and the tri-isobutyryl ester 5g hydrobromide showed excellent oral bioavailabilities (F = 71.6%, 86.6% and 98.7%, respectively) in mice, which provided good insight into the pharmacokinetic optimization of GS-441524.
- Wei, Daibao,Hu, Tianwen,Zhang, Yumin,Zheng, Wei,Xue, Haitao,Shen, Jingshan,Xie, Yuanchao,Aisa, Haji A.
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- Method for synthesizing nucleoside analogue by using continuous flow reactor
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The invention discloses a method for synthesizing a nucleoside analogue by using a continuous flow reactor. The method comprises the following steps that: a dichloromethane solution of (2R, 3R, 4R, 5R)-2-(4-aminopyrrolo[1, 2-f][1, 2, 4]triazin-7-yl)-3, 4-dibenzyloxy-5-((benzyloxy)methyl)tetrahydrofuran-2-nitrile used as a raw material solution and a dichloromethane solution of boron trichloride used as an auxiliary material solution of a debenzylation reaction respectively enter a mixer through respective pump systems, then flow through a main reaction pipeline, and then enter an aqueous alkali solution for quenching, and filtering and pulping are carried out so as to obtain a target product (2R, 3R, 4S, 5R)-2-(4-aminopyrrolo[1, 2-f][1, 2, 4] triazin-7-yl)-3, 4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-nitrile. The method disclosed by the invention is simple to operate, efficient, high in product yield, high in purity and suitable for large-scale production.
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Paragraph 0040-0048
(2021/05/05)
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- Preparation method of nucleoside analogue
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The invention belongs to the technical field of chemical synthesis, and specifically relates to a new preparation method of (2R,3R,4S,5R)-2-(4-aminopyrrolo[1,2-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carbonitrile. The metho
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- Pyrrolotriazine compound, composition and application thereof
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The invention relates to a pyrrolotriazine compound, a composition and an application thereof, the pyrrolotriazine compound has a structure as shown in a formula (I), and the definitions of R1-R11 areas defined in claim 1. The pyrrolotriazine compound has an excellent antiviral effect, and particularly can be used for preparing drugs for treating feline coronavirus infection-resistant diseases, such as feline infectious peritonitis.
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Paragraph 0097; 0105-0107; 0118; 0126-0130
(2020/02/14)
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- METHODS FOR TREATING ARENAVIRIDAE AND CORONAVIRIDAE VIRUS INFECTIONS
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Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I: wherein the 1′ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.
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Paragraph 0521
(2017/04/04)
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- METHODS FOR TREATING FILOVIRIDAE VIRUS INFECTIONS
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Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae vims infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula (IV): The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.
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Paragraph 0184
(2016/05/19)
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- METHODS AND COMPOUNDS FOR TREATING PARAMYXOVIRIDAE VIRUS INFECTIONS
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Provided are methods for treating Paramyxoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula (I): wherein the 1 ? position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Human parainfluenza and Human respiratory syncytial virus infections
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- Synthesis and antiviral activity of a series of 1′-substituted 4-aza-7,9-dideazaadenosine C-nucleosides
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A series of 1′-substituted analogs of 4-aza-7,9-dideazaadenosine C-nucleoside were prepared and evaluated for the potential as antiviral agents. These compounds showed a broad range of inhibitory activity against various RNA viruses. In particular, the whole cell potency against HCV when R = CN was attributed to inhibition of HCV NS5B polymerase and intracellular concentration of the corresponding nucleoside triphosphate.
- Cho, Aesop,Saunders, Oliver L.,Butler, Thomas,Zhang, Lijun,Xu, Jie,Vela, Jennifer E.,Feng, Joy Y.,Ray, Adrian S.,Kim, Choung U.
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scheme or table
p. 2705 - 2707
(2012/05/20)
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