- Nucleotide derivative and pharmaceutical composition and application thereof
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The invention discloses a nucleotide derivative and a pharmaceutical composition and application thereof, wherein the nucleotide derivative is as shown in a formula (I). The compound can be used for preparing anti-virus infection drugs.
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Paragraph 0165-0170
(2021/08/25)
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- Design, synthesis and evaluation of 2′-acetylene-7-deaza-adenosine phosphoamidate derivatives as anti-EV71 and anti-EV-D68 agents
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A series of phosphoamidate derivatives of nucleoside 2′-acetylene-7-deaza-adenosine (NITD008) were synthesized and evaluated for their in vitro antiviral activities against the enteroviruses EV71 and EV-D68. The phosphoamidate (15f) containing a hexyl est
- Cao, Ruiyuan,Fan, Shiyong,Li, Song,Li, Wei,Li, Xiaoyuan,Li, Yuexiang,Yan, Linjie,Zhang, Hongjie,Zhong, Wu
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supporting information
(2021/09/28)
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- CYCLOBUTYL PURINE DERIVATIVE OR SALT THEREOF
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An object of the present invention is to provide a compound exhibiting an excellent drug efficacy as an anti-adenoviral agent, and an anti-adenoviral agent. The present invention provides a compound represented by General Formula [1] (in the formula, R1 represents a halogen atom, an amino group which may be substituted, a C1-6 alkoxy group which may be substituted, a hydroxyl group which may be protected, or the like; R2 represents a hydrogen atom or an amino protecting group; R3 represents a C1-20 alkoxy group which may be substituted, an aryloxy group which may be substituted, an amino group which may be substituted, or the like; R4 represents a C1-20 alkoxy group which may be substituted, an aryloxy group which may be substituted, an amino group which may be substituted, or the like); or a salt thereof.
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Paragraph 0327-0331
(2021/05/21)
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- 2,4,7-SUBSTITUTED-7-DEAZA-2'-DEOXY-2'-FLUOROARABINOSYL NUCLEOSIDE AND NUCLEOTIDE PRO-DRUGS AND USES THEREOF
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The present disclosure is concerned with 2,4,7-substituted-7-deaza-2'-deoxy-2'- fluoroarabinosyl nucleoside and nucleotide prodrugs that are capable of inhibiting viral infections and methods of treating viral infections such as, for example, human immunodeficiency virus (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), human cytomegalovirus (HCMV), chicken pox, infectious mononucleosis, mumps, measles, rubella, shingles, ebola, viral gastroenteritis, viral hepatitis, viral meningitis, human metapneumovirus, human parainfluenza virus type 1, parainfluenza virus type 2, parainfluenza virus type 3, respiratory syncytial virus, viral pneumonia, Chikungunya virus (CHIKV), Venezuelan equine encephalitis (VEEV), dengue (DENV), influenza, West Nile virus (WNV), zika (ZIKV), 229E, NL63, OC43, HKU1, Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus disease 2019 (SARS-CoV-2), using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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- Preparation method for phosphamide compound used for synthesis chiral drug
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The invention provides a preparation method for a phosphamide compound used for synthesis of a chiral drug. According to the invention, a compound II with high yield and high purity can be prepared byadopting a NaHCO3 aqueous solution with a specific pH value and a specific volume-to-mass ratio as a solvent for pulping and controlling a temperature and a stirring speed during pulping. By adoptionof a reaction system provided by the invention, an organic solvent is not needed; the discharge of a large amount of an organic solvent waste liquid is reduced; and the process is environmentally-friendly, green and pollution-free.
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Paragraph 0032-0034
(2020/05/29)
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- 2'-SUBSTITUTED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR RNA VIRUS TREATMENT
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The use of described compounds or pharmaceutically acceptable salts or compositions thereof for the treatment of a host infected with an RNA virus other than HCV, or other disorder more fully described herein.
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- Method for preparing sofosbuvir key intermediate
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The invention relates to the technical field of medicinal chemistry, and in particular relates to a method for preparing a sofosbuvir key intermediate N-[(S)-(2,3,4,5,6-pentafluorophenyl) phenoxyl phosphoryl-L-alanine isopropyl ester. According to the novel method, on the basis of reaction principles, the influence of an addition sequence of L-alanine isopropyl ester hydrochloride and phenol to the reaction is studied firstly, dichlorophosphate pentafluorophenyl ester is adopted as an initial raw material which is reacted with the L-alanine isopropyl ester hydrochloride to obtain a compound III, and the compound III is further spliced with phenol, and thus a compound I can be prepared. By adopting the method, the problems of rigorous reaction conditions, high reaction equipment requirements and the like can be solved, and according to the method, the reaction condition is mild, the operation is simple and convenient, the product yield is high, the purity is good and the method is applicable to large-scale industrial production.
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Paragraph 0037; 0039; 0041; 0043; 0045; 0046; 0047; 0049
(2017/04/03)
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- Antiviral nucleoside phosphoramidate and pharmaceutical composition and applications thereof
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The invention provides an antiviral nucleoside phosphoramidate and a pharmaceutical composition and applications thereof. The nucleoside phosphoramidate compound is prepared by connecting nucleoside with phosphate through phosphorus-oxygen bonds. The structural formulas of the nucleoside phosphoramidate compound are represented by a, a1, a2, b, b1, and b2. The invention also discloses stereoisomers, pharmaceutically acceptable salts, hydrates, solvates, or crystals of the nucleoside phosphoramidate compound. The anti-hepatitis C activity of the provided novel nucleoside phosphoramidate is obviously better than that of sofosbuvir used in clinic. On the saccharide ring, the fluorine atoms are replaced by chlorine atoms, and the cytotoxicity of measure cell lines is prominently reduced. By systematically modifying and optimizing the basic groups, saccharide rings, and prodrugs, the anti-hepatitis C activity of partial synthesized compounds is 2 to 10 times higher than that of sofosbuvir. At the same time, the key parts of metabolism are optimized, the metabolism stability and chemical stability of synthesized compounds in plasma are better, compared with those of sofosbuvir.
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- A rope non-cloth Wei preparation of intermediate
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The invention discloses a preparation method of a sofosbuvir intermediate, which comprises the following step: in an anhydrous non-protonic solvent, carrying out dynamic kinetic resolution on a compound disclosed as Formula (II) under the action of an organic alkali and/or inorganic alkali to prepare a compound disclosed as Formula (I), wherein the non-protonic solvent is one or more of ester solvent, ketone solvent and ether solvent, the organic alkali and/or inorganic alkali account/accounts for 0.1-10 wt% of the compound disclosed as Formula (II), the temperature of the dynamic kinetic resolution is 10-30 DEG C, and the time of the dynamic kinetic resolution is 5-10 hours. The preparation method has the advantages of high conversion rate, high product purity and low cost, and is environment-friendly.
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Paragraph 0025; 0047-0051
(2017/08/25)
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- Beta-D-2'-DEOXY-2'-alpha-FLUORO-2'-beta-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT
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A compound of the structure: or a pharmaceutically acceptable salt or composition thereof for the treatment of a host infected with or exposed to an HCV virus or other disorders more fully described herein.
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Paragraph 0579; 0580
(2016/09/26)
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- A PROCESS FOR THE PREPARATION OF SOFOSBUVIR INTERMEDIATES and ITS POLYMORPH
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The present invention provides a novel process for preparation N-[(2,3,4,5,6- Pentafluorophenoxy)phenoxyphosphinyl]-L-alanine 1-methylethyl ester (formula 2) and resolving the formula 2 in the presence base to form N-[(S)-(2,3,4,5,6- Pentafluorophenoxy)phenoxyphosphinyl]-L-alanine 1-methylethyl ester (formula 2').
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- NUCLEOSIDE PHOSPHORAMIDATES USEFUL FOR THE TREATMENT OF VIRAL INFECTIONS AND PREPARATION THEREOF
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The present invention relates to an industrially applicable process for the preparation of phosphoramidates useful for the treatment of viral infections, such as sofosbuvir, and to intermediates useful for the preparation thereof. Formula (I):
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- Discovery of 2'-α-C-Methyl-2'-β-C-fluorouridine Phosphoramidate Prodrugs as Inhibitors of Hepatitis C Virus
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2′-α-C-Methyl-2′-β-C-fluorouridine and its phosphoramidate prodrugs were synthesized and evaluated for their inhibitory activity against HCV. The structure?activity relationship analysis of the phosphoramidate moiety found that 17m, 17q, and 17r exhibit potent activities against HCV, with EC50 values of 1.82 ± 0.19, 0.88 ± 0.12, and 2.24 ± 0.22 μM, respectively. The docking study revealed that the recognition of the 2′-β-F by Arg158, 3′-OH by N291, and the Watson?Crick pairing with the template allowed 23 to form the in-line conformation necessary for its incorporation into the viral RNA chain.
- Zeng, Debin,Zhang, Rui,Nie, Quandeng,Cao, Lin,Shang, Luqing,Yin, Zheng
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supporting information
p. 1197 - 1201
(2016/12/18)
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- A ribofuranose method for the preparation of phosphoric acid ester derivative
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Disclosed in the present invention is a method for preparing ribofuranose phosphate derivatives, and the preparation steps thereof comprises: coupling starting materials of isopropyl L-alanine hydrochloride, phenol dichlorophosphate and substituted phenol under the action of alkali; reducing carbonyl into alcoholic hydroxyl by means of treating (2R)-2-deoxy-2-fluoro-2-methyl-D-erythro pentonic acid GAMMA-lactone 3,5-dibenzoate with a strong reducing agent in the solvent of dichloromethane or ethers; reacting the intermediate of formula 2-1 with p-toluene sulfonyl chloride under the action of alkali to obtain p-toluene sulfonate; coupling the intermediate of formula 2-2 with a benzoyl cytosine derivative under the action of a condensation agent; converting cytosine of the intermediate of formula 2-3 into uracil under the action of an organic acid; removing benzoyl acting as protecting group from the intermediate of formula 2-4 under the action of an alkaline reagent; and coupling the intermediate of formula 2-5 with formula 1 under the action of a Grignard reagent to obtain Sofosbuvir.
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Paragraph 0037; 0038
(2016/11/07)
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- 2'-METHYL SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
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The present invention relates to 2'-Methyl Substituted Nucleoside Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R, R1, R2 and R3, are as defined herein. The present invention also relat
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Page/Page column 60
(2014/05/07)
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- 2'-AZIDO SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
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The present invention relates to 2′-Azido Substituted Nucleoside Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein B, X, R1, R2 and R3 are as defined herein. The present invention also relates to compositions comprising at least one 2′-Azido Substituted Nucleoside Derivative, and methods of using the 2′-Azido Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.
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Paragraph 0286; 0287
(2014/08/06)
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- 2',3'-DIDEOXY-2'-α-FLUORO-2'-β-C-METHYLNUCLEOSIDES AND PRODRUGS THEREOF
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The present invention provides 2',3'-dideoxy-2'-fluoro-α-2'-C- methylnucleosides, their prodrugs, and therapeutic use thereof as anti-HCV agents. The present invention also provides processes and intermediates for the preparation of the nucleosides disclosed herein.
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Page/Page column 25; 26
(2013/03/26)
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