- Method for preparing antiviral drug tenofovir alafenamide fumarate
-
The invention discloses a method for preparing an antiviral drug tenofovir alafenamide fumarate, which comprises the following steps of: (1) reacting adenine with (R)-propylene carbonate to generate a compound I; (2) treating the compound I with magnesium tert-butoxide, and then adding phosphonate S to react to obtain a compound II; (3) the compound III is obtained by hydrolyzing the compound II in hydrobromic acid; (4) reacting the compound III with thionyl chloride to obtain phosphonyl chloride, and directly reacting the phosphonyl chloride with L-alanine isopropyl ester without purification to generate a compound IV; and (5) obtaining a final product, wherein the preparation of the propionyl phenol fumarate tenofovir is completed by salifying the compound IV and fumaric acid. The method has the advantages of few synthetic route steps, mild reaction conditions and principle saving, and can improve the yield of the final product.
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-
- Industrial synthesis method of propofovir disoproxil fumarate
-
The invention provides a preparation process of propofovir disoproxil fumarate, which is short in production period, simple to operate and suitable for industrial production, and the high-purity propofovir disoproxil fumarate is prepared by taking the propofovir disoproxil fumarate as a starting material through special phosphorus chiral atom synthesis, purification and separation. The purity of the prepared propofovir disoproxil fumarate is greater than 99.90%, the diastereoisomer is less than 0.15%, the content of other single impurities is less than 0.10%, and the method has high commercialscale production value.
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Paragraph 0047-0060
(2021/01/29)
-
- Chemical resolution method of tenofovir alafenamide
-
The invention provides a chemical resolution method of tenofovir alafenamide. The method comprises the following steps: by using tenofovir alafenamide racemate and D-malic acid as raw materials and acetonitrile and water as reaction solvents, reacting at 70-90 DEG C for 3-10 hours under the protection of nitrogen, separating out solids at normal temperature, and continuing cooling to grow crystalsto obtain D-malate; and carrying out weak base hydrolysis, extraction and low-temperature seed crystal induced crystallization on the D-malate to obtain the tenofovir alafenamide crystal. According to the resolution method, tenofovir alafenamide reacts with D-malic acid to form a salt, resolution is completed, and hydrolysis, extraction and seed crystal induced crystallization are performed on the D-malate to obtain a tenofovir alafenamide crystal; and the method is mild in condition in the reaction process, simple in process, convenient to operate, high in universality and suitable for large-scale production. The obtained target product is high in yield and purity and stable in performance, the medicine effect of the medicine prepared from the target product can be effectively guaranteed, and the treatment effect is improved.
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Paragraph 0029; 0032-0037; 0039-0043
(2021/03/11)
-
- Preparation method of intermediate GS103 of tenofovir prodrug
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The invention relates to a preparation method of an intermediate GS103 of a tenofovir prodrug. A product obtained by the method is good in purity and high in yield.
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Paragraph 0008; 0009
(2021/02/13)
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- Preparation methods of tenofovir alafenamide fumarate isomer impurities
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The invention discloses preparation methods of tenofovir alafenamide fumarate isomer impurities, which comprise preparation methods of four isomer impurities, specifically, preparation methods of 9-{(R)-2-[((R)-{[(R)-1-(isopropoxycarbonyl) ethyl] amino}-phenoxy phosphoryl) methoxy] propyl} adenine, 9-{(R)-2-[((R)-{[(S)-1-(isopropoxycarbonyl) ethyl] amino}-phenoxy phosphoryl) methoxy] propyl} adenine, 9-{(R)-2-[((S)-{[(R)-1-(isopropoxycarbonyl) ethyl] amino}-phenoxy phosphoryl) methoxy] propyl} adenine and 9-{(S)-2-[((R)-{[(R)-1-(isopropoxycarbonyl) ethyl] amino}-phenoxy phosphoryl) methoxy] propyl} adenine. The preparation methods of tenofovir alafenamide fumarate isomer impurities have the beneficial effects that the methods are simple and easy to implement, raw materials are easy to obtain, conditions are mild, cost is low, production is facilitated, and meanwhile the obtained isomer impurity has important significance in preparing high-purity tenofovir alafenamide fumarate.
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Paragraph 0107; 0111-0114
(2020/07/13)
-
- Tenofovir alafenamide diastereoisomer, preparation method and application of diastereoisomer
-
The invention relates to a tenofovir alafenamide diastereomer as shown in a formula I. The invention also relates to a preparation method of the tenofovir alafenamide diastereoisomer as shown in the formula I, and application of the tenofovir alafenamide diastereomer in detection of purity of the tenofovir alafenamide and salt thereof, detection of content of optical isomers in the tenofovir alafenamide and salt thereof, and quality control in production or preparation of the tenofovir alafenamide and salt thereof. The tenofovir alafenamide diastereomer disclosed by the invention has importantsignificance for quality monitoring and standard research in industrial production of tenofovir alafenamide.
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Paragraph 0049; 0052-0053
(2020/09/16)
-
- NRTI THERAPIES
-
Polymer-of-prodrug (POP) materials enable new nucleoside reverse transcriptase inhibitor (NRTI) therapy strategies. The materials are prodrugs of NRTIs in the form of polymers. Suitable materials include products which are polymeric NRTI delivery systems comprising polymeric materials which are capable of degradation after administration to release NRTIs or NRTI prodrugs which themselves are capable of metabolism to the parent NRTIs. The NRTIs may optionally be selected from tenofovir (TFV), emtricitabine (FTC), lamivudine (3TC) and MK-8591 (EFdA). The invention facilitates long-acting (LA) regimens. Constructs of the materials may be in the form of injectable compositions or implants.
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Page/Page column 71-72
(2020/07/14)
-
- Preparation method of tenofovir alafenamide
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The invention relates to a preparation method of tenofovir alafenamide represented by a formula IV. The preparation method comprises the following steps: 1) performing a halogenation reaction on a compound I and a halogenation reagent to obtain a halogenated compound II, wherein the halogenated compound II is a raceme; 2) performing solvent-mediated asymmetric transformation on the halogenated compound II obtained in the step 1) in an organic solvent B, and removing the solvent after the complete reaction to obtain a compound III, wherein the asymmetric conversion reaction is carried out at atemperature lower than the reflux temperature of the organic solvent B, a ratio S/R of the two diastereoisomers in the compound III is greater than or equal to 90%, and the organic solvent B is one ora combination comprising one or a plurality of materials selected from toluene, dimethylbenzene, ethylbenzene and chlorobenzene; and (3) carrying out an amidation reaction on the compound III obtained in the step (2) and L-alanine isopropyl ester or a salt thereof to prepare the tenofovir alafenamide represented by the formula IV. The preparation method disclosed by the invention can be used forenhancing the reaction controllability and shortening the reaction time, and is suitable for industrial production of TAF.
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Paragraph 0050; 0053; 0054; 0064-0067
(2020/05/01)
-
- Method for synthesis of tenofovir alafenamide by oxidation process
-
The invention discloses a preparation method of tenofovir alafenamide (TAF). The method includes: taking (R)-2-(6-amino-9H-purine-9-yl)isopropoxymethyl N'-[(S)-1-isopropoxyformyl]ethyl phenoxy phosphoramidite (2) is used as the raw material, carrying out amidation reaction, oxidation reaction and hydrolysis reaction, and then performing splitting to obtain tenofovir alafenamide (TAF, 1). The method provided by the invention has the advantages of green and environmental protection, no pollution, environmental friendliness, easily available raw materials, wide sources, low cost, simplicity and suitability for industrial production. The preparation method solves the problems of high preparation cost and difficult industrial production in the prior art.
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Paragraph 0015; 0020
(2020/01/12)
-
- Preparation method of tenofovir alafenamide (TAF) synthesized through three-step method
-
The invention discloses a preparation method of tenofovir alafenamide (TAF). The preparation method comprises the steps that phenoxy N-(1-isopropoxyformyl)ethyl phosphoramidite (2) is taken as a raw material, and after the raw material is subjected to a nucleophilic addition reaction, a sulfonylation reaction and a nucleophilic substitution reaction, splitting is conducted to obtain the TAF. The preparation method has the advantages that environmental protection is realized, pollution is avoided, environmental friendliness is realized, the raw material is easy to obtain, wide in source and lowin cost, and the method is simple and suitable for industrial production, and the problems of high preparation cost and difficult industrial production in the prior art are solved through the preparation method.
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- Preparation method for synthesizing tenofovir alafenamide in two steps
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The invention discloses a preparation method of tenofovir alafenamide (TAF). The method comprises the following steps: with (R)-2-(6-amino-9H-purin-9-yl)isopropoxymethyl di(N,N-dialkyl)phosphamide (2)as a raw material, carrying out a nucleophilic substitution reaction twice to obtain the tenofovir alafenamide (TAF). The preparation method has the advantages of greenness, environmental protection,no pollution, environmental friendliness, easily-available raw materials, a wide source, low costs, a simple method and suitability for industrial production, and solves the problems that preparationcosts are high, and industrial production is difficult to realize in the prior art.
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Paragraph 0016-0018
(2020/01/03)
-
- THE ANTIVIRAL AGENT COMPRISING A NOVEL CRYSTALLINE FORM AND THE MANUFACTURING METHOD THEREOF
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The present invention relates to an antiviral agent used as a pharmaceutical composition for treating or preventing HIV-1 infection and chronic hepatitis B as a free base in a novel crystalline form of tenofovir alafenamide having the same water solubility as acid additional salt, excellent adhesion and uniformity which are easy to be formulated, and low elastic forces while overcoming a decomposition problem cause by moisture absorption of tenofovir alafenamide hemifumarate on the market.COPYRIGHT KIPO 2020
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Paragraph 0055-0062
(2019/11/27)
-
- Efficient synthesis technology of tenofovir alafenamide
-
The invention discloses an efficient synthesis technology of tenofovir alafenamide. The efficient synthesis technology comprises the steps that A, tenofovir reacts with triphenyl phosphite under an alkali catalysis condition to prepare tenofovir monophenyl ester, wherein the initial reaction temperature is 50-70 DEG C, the reaction temperature rises according to the gradient of 5-10 DEG C/h, and the total reaction duration is 6-10 h; B, the tenofovir monpohenyl ester is subjected to acylating chlorination to prepare tenofovir phenyl ester phosphoryl chloride; C, the tenofovir phenyl ester phosphoryl chloride is isomerized, then the isomerized tenofovir phenyl ester phosphoryl chloride reacts with an L-alanine isopropyl ester compound to prepare a target compound, wherein methylbenzene andother non-polar solvents are adopted for an isomerization solvent. The prepared tenofovir alafenamide has high purity and high yield, the technology operation is simple, the cost is low, complicated technology operation and purification means like using chiral resolution agents are omitted, and the efficient synthesis technology is very suitable for industrial production.
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Paragraph 0040; 0049-0056
(2019/10/01)
-
- Tenofovir alafenamide hemifumarate preparation method
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The invention belongs to the technical field of medicines and particularly relates to a tenofovir alafenamide hemifumarate preparation method. The method includes steps: subjecting tenofovir II and triphenyl phosphite to reaction to generate an intermedia
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Paragraph 0059-0063; 0083-0086
(2019/10/17)
-
- Novel antiviral nucleoside reverse transcriptase inhibitor
-
The invention relates to a novel antiviral nucleoside reverse transcriptase inhibitor compound, a pharmaceutical composition comprising the same and preparation and application thereof. Particularly,the invention discloses a condensed pyrimidine compound
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- A method for preparing for fuwei ira phenol amine intermediate
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The invention discloses a key intermediate for the fuwei ira phenol amine PMPA single phenyl ester preparation method. It is will be PMPA, triphenyl phosphate and organic alkali mixing, in the absence of solvent the heating reaction preparation PMPA singl
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- Simple synthesizing process for tenofovir alafenamide fumarate
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The invention discloses a simple synthesizing process for tenofovir alafenamide fumarate. According to the simple synthesizing process for the tenofovir alafenamide fumarate, a target product, namely,tenofovir alafenamide fumarate, is synthesized by taking tenofovir as a raw material through four steps of esterifying by using triphenyl phosphite, amidating by using L-alanine isopropyl ester hydrochloride, regulating pH by using phenol and DBU for resolving, and salifying by using fumaric acid. The process is simple and low in reaction temperature, and is more suitable for industrialization.
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- Preparation method of tenofovir alafenamide hemifumarate
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The invention discloses a preparation method of tenofovir alafenamide hemifumarate. The preparation method comprises the following steps of: reacting tenofovir with triphenyl phosphite under the condition of alkali catalysis to prepare tenofovir phenol ester; preparing tenofovir alafenamide through acylating chlorination and a reaction with L-alanine isopropyl ester; preparing tenofovir alafenamide hemifumarate by a special salt-forming process with fumaric acid. The tenofovir alafenamide hemifumarate prepared by the process is accurate in control of a salt type ratio, and simple in process operation, and avoids complex process operation and purification means such as chiral resolution, the total purity can reach 99% or more, and indexes of related substances are qualified.
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Paragraph 0010; 0040-0046; 0047
(2018/03/25)
-
- Efficient synthesis and resolution of tenofovir alafenamide
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Background: Tenofovir alafenamide (TAF) is an oral antiviral prodrug of tenofovir (TFV), we have developed a facial and efficient method for the synthesis and chiral resolution of TAF. Method: The practical synthetic route of a mixed two diastereomers at phosphorous could start from (R)-9-[2-(Phosphonomethoxy)propyl]adenine (PMPA), the esterification reaction between PMPA and phenol occurred under the catalysis of dicyclohexylcarbodiimide (DCC) in 1-methyl-2-pyrrolidinone (NMP) at the temperature of 100o C to afforded 1. Phosphonochloridate was synthesized from 1 by chloride acetylation with thionyl chloride, and then react with an excess of L-Alanine isopropyl ester hydrochloride to give the diastereomer mixture of 9-[(R)-2-[[(R,S)-[[(S)-1-(isopropoxycarbonyl)ethyl] amino]-phenoxyphosphinyl]methoxy]propyl]adenine (2). The antipodes of 2 were separated in a satis-factory yield and diastereomeric excess (99% de) by resolution via formation diastereoisomer salt or inclusion complex to afford the more potent diastereomer (3). Tenofovir Alafenamide hemifumarate could be afforded by 3 and fumaric acid in a 1:0.5 ratio. Results: The diastereomeric excess of 3 could reach to 99% de. Conclusion: In a word, we have developed an efficient and chromatography-free route for the prepara-tion of TAF. In consideration of the expensive equipment and higher operation cost of SMBC, we chose a traditional resolution route to obtain chiral phosphorus.
- Gan, Yongjun,Ran, Kerui,Xie, Hongmeng,Yang, Bin
-
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- Preparation method of fumaric acid tenofovir alafenamide
-
The invention provides a preparation method of fumaric acid tenofovir alafenamide. By esterification reaction, halogenating reaction, condensation reaction, refining and salt forming reaction, the fumaric acid tenofovir alafenamide which is high in yield, easy to purify and suitable for industrial mass production is obtained.
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Paragraph 0069; 0073; 0074
(2018/09/11)
-
- A method for preparing tenofovir alafenamide
-
A method for preparing tenofovir alafenamide is disclosed. The method includes subjecting (R)-9-(2-phosphonylmethoxypropyl)-adenine (TAF-01) and L-alanine isopropyl ester hydrochloride (TAF-02) to a condensation reaction to obtain TAF-03, and the reacting the TAF-03 with triphenyl phosphite to obtain the tenofovir alafenamide (TAF-04) having high chiral purity, with the chiral purity being greaterthan 99%. Raw materials of the process are easily available, generation of three wastes is little, and the method is environmentally friendly and mild in reaction condition and is particularly beneficial to industrial production of the bulk pharmaceutical chemical.
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Paragraph 0007; 0015; 0017; 0019
(2018/10/27)
-
- Nucleoside phosphoramidate type compound with HBV/HIV resistance activity and salt and application of nucleoside phosphoramidate type compound
-
The invention relates to a nucleoside phosphoramidate type compound with HBV/HIV resistance activity, an isomer of the nucleoside phosphoramidate type compound, pharmaceutically-acceptable salt of the nucleoside phosphoramidate type compound, a solvate or crystal of the nucleoside phosphoramidate type compound, a medicine composition of the nucleoside phosphoramidate type compound, and application of the nucleoside phosphoramidate type compound. According to related novel non-cyclic nucleoside phosphoramidate, on the phosphoramidate part, amino acid is D-amino-acid. D-amino-acid ester is introduced in the prodrug, and a new non-cyclic nucleotide amide compound which has higher chemical stability, higher lipid solubility and higher virus inhibition activity is expected to be obtained. By means of the creative design, the virus resistance activity of medicine is improved, solubility and pharmacokinetics characteristics of the medicine are improved, the concentration ratio in tissue cells and plasma is increased, and therefore the curative effect, safety and tolerance of the medicine can be improved, and very good clinical application prospects are achieved.
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Paragraph 0031; 0032; 0033; 0034; 0035; 0036
(2017/08/28)
-
- Preparation method and application for high-purity tenofovir alafenamide fumarate intermediate
-
The invention discloses a preparation method and an application for a high-purity tenofovir alafenamide fumarate intermediate. The preparation method for the tenofovir alafenamide fumarate intermediate namely tenofovir alafenamide II provided by the invention comprises the following steps: subjecting crude tenofovir alafenamide fumarate intermediate namely tenofovir alafenamide II to recrystallization in a mixed solvent of a nitrile solvent and water or a mixed solvent of the nitrile solvent and an aromatic hydrocarbon solvent so as to obtain the high-purity tenofovir alafenamide fumarate intermediate namely tenofovir alafenamide II. The high-purity tenofovir alafenamide II has an optical purity larger than 99.50% and a chemical purity larger than 99.60%; and the crude tenofovir alafenamide fumarate intermediate namely tenofovir alafenamide II has the optical purity in a range of 60.00% to 99.00% and the chemical purity in a range of 60.00% to 99.00%. The preparation method provided by the invention has the advantages of simple and safe operation, high yield, high product purity, low production cost, and applicability to industrial production.
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- Preparation method of tenofovir alafenamide
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The invention discloses a preparation method of tenofovir alafenamide. The preparation method comprises the following specific steps: carrying out heating reaction on PMPA and a chlorination agent to obtain PMPA-2Cl; enabling the PMPA-2Cl to react with phenol and L-alanine isopropyl ester in sequence through a one pot method to obtain TAF-RS; purifying the TAF-RS to obtain the tenofovir alafenamide, wherein the chlorination agent is one of sulfoxide chloride, phosphorus chloride, phosphorus pentachloride and oxalyl chloride; the one pot method is to enable the PMPA-2Cl to react with the phenol first in an organic solvent under a condition of -30 to -20 DEG C under existence of organic alkali, and then add the L-alanine isopropyl ester for reaction. According to the synthesis process provided by the invention, the complicated operation process is avoided, the reaction steps are simplified; furthermore, as the raw materials are readily available, the reactions are mild, and the cost is relatively low, the preparation method is suitable for industrial production.
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Paragraph 0030
(2017/08/29)
-
- Industrialized continuous production method of hemifumarate tenofovir alafenamide
-
The invention discloses an industrialized continuous production method of tenofovir alafenamide and hemifumarate. The method comprises the following steps: firstly, in the presence of an acid-binding agent, reacting tenofovir with triphenyl phosphate to obtain a TAF-I M shown as a formula II; secondly, continuously preparing a TAF-II M by using the TAF-I M; thirdly, carrying out a salt forming reaction on the TAF-II M to obtain the hemifumarate tenofovir alafenamide. According to the industrialized continuous production method disclosed by the invention, a key compound tenofovir alafenamide is obtained by continuous production; the hemifumarate tenofovir alafenamide is obtained by accurately feeding fumaric acid and the tenofovir alafenamide; and in addition, a diastereoisomer of the tenofovir alafenamide is inhibited by using high catalytic enantioselectivity of a proline catalyst, and industrial production of optically-pure tenofovir alafenamide of which the purity is greater than 99.9 percent is realized by primary crystallization. The industrial production method disclosed by the invention has the advantages of simplicity, safety and low production cost; and besides, a high-purity product is obtained.
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Paragraph 0057; 0059; 0069; 0072; 0073; 0074;0083-0087
(2018/01/19)
-
- Tenofovir alafenamide hemifumarate novel crystal form
-
The invention discloses a tenofovir alafenamide hemifumarate, ((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxyl)methyl(phenoxyl) phosphono)-L-alanine isopropyl hemifumarate, novel crystal form (crystal form B), drug preparations containing the tenofovir alafenamide hemifumarate novel crystal, and treatment applications and preparation methods of the tenofovir alafenamide hemifumarate novel crystal. The tenofovir alafenamide hemifumarate novel crystal is stable at high temperature high moisture conditions; large-scale preparation is convenient to realize; and application prospect is promising.
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Paragraph 0028; 0030
(2018/03/24)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF TENOFOVIR ALAFENAMIDE OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
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The present invention generally relates to an improved process for the preparation of tenofovir alafenamide or pharmaceutically acceptable salts thereof and preparation thereof. The present invention also relates to crystalline forms of monophenyl PMPA, an important intermediate of tenofovir alafenamide, and their preparation.
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Page/Page column 34
(2018/04/12)
-
- Method of preparing nucleoside analogs and intermediates thereof which has advantages of high reaction yield, high product purity, convenient post-treatment, and suitable for industrial mass production
-
The present invention relates to a method of preparing nucleoside analogs and intermediates thereof, which is the method of preparing the compound as shown by formula (I) and intermediates thereof. The disclosed method has advantages of high reaction yield, high product purity, convenient post-treatment, and suitable for industrial mass production, wherein the compound (III) is the key intermediate to produce the high purity compound (I), and the definitions of the substitution groups in the compound (III) are the same as those in the specification.
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- COMBINATION THERAPY COMPRISING TENOFOVIR ALAFENAMIDE HEMIFUMARATE AND COBICISTAT FOR USE IN THE TREATMENT OF VIRAL INFECTIONS
-
The use of the hemifumarate form of {9-[(R)-2-[[(S)-[[(S)-1-(isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]propyl]adenine} (tenofovir alafenamide hemifumarate) in combination with cobicistat is disclosed. In addition, the combination of tenofovir alafenamide hemifumarate, cobicistat, emtricitabine, and elvitegravir, and the combination of tenofovir alafenamide hemifumarate, cobicistat, emtricitabine, and darunavir, are disclosed.
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-
- A PREPARATION METHOD OF DIASTEREOMERICALLY PURE TENOFOVIR ALAFENAMIDE OR ITS SALTS
-
The invention relates to an efficient preparation method of diastereomerically pure Tenofovir Alafenamide (TA) of structure la with the absolute configuration (S) at the phosphorus atom - Sp-diastereoisomer. Tenofovir Alafenamide Fumarate of formula 2 (TAF) is a reverse transcriptase inhibitor, which is currently in the clinical study stage as a prodrug of Tenofovir 3 for the treatment of HIV infection and hepatitis B. Compared to the hitherto used prodrug, Tenofovir disoproxil fumarate of formula 4, TAF exhibits greater antiviral activity and better distribution in the lymphatic system.
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Page/Page column 10; 11
(2017/10/13)
-
- Preparation method of amino phosphate ester derivatives and preparation method of intermediates and intermediates characterized in that at 0 DEG C -100 DEG C and in a solvent, the compound represented by the general formula (II) is subjected to an amino deprotection reaction in the presence of an alkaline reagent, an acidic reagent or a hydrogenolysis catalyst
-
The present invention relates to a process for the preparation of an amino phosphate ester derivative having antiviral activity as shown in the general formula (I) and a process for the preparation of intermediates and intermediates thereof, characterized in that at 0 DEG C -100 DEG C and in a solvent, the compound represented by the general formula (II) is subjected to an amino deprotection reaction in the presence of an alkaline reagent, an acidic reagent or a hydrogenolysis catalyst; the solvent used in the reaction is selected one or two from the group consisting of alcohol solvents, aromatic hydrocarbon solvents, ether solvents, halogenated alkane solvents, ester solvents, ketone solvents, lipid solvents, amide solvents, sulfoxide solvents and water; the acidic reagent is selected from organic acids or inorganic acids; the alkaline reagent is selected one or two from the group consisting of alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates, alkaline earth metal carbonates and organic amines.
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Page/Page column 30; 34; 35
(2017/10/14)
-
- Acyclic nucleoside phosphamide D-amino-acid ester derivative, preparation method of derivative salt and application of derivative to antiviral effect
-
The invention belongs to the field of medical chemical antiviral effects, and relates to an acyclic nucleoside phosphamide D-amino-acid ester derivative, a preparation method of derivative salt and an application of the derivative to the antiviral effects. The invention further provides a compound comprising the derivative, a stereoisomer of the derivative, pharmaceutically acceptable salt, a hydrate, a solvate or crystal and drug combination and an application of the compound or combination to treatment and/or prevention of Aids and hepatitis B virus infection. The in vivo activity of the compound is remarkably superior to that of a pro-drug of acyclic nucleoside phosphamide L-amino-acid ester, and the compound has obvious clinical application values.
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-
-
- D-amino-acid ester-containing nucleoside amino phosphonate derivative and medical purpose thereof
-
The invention relates to a novel nucleoside phosphate/phosphonate prodrug containing non-naturalD-amino acid ester, a preparation method and a medical purpose thereof. The novel nucleoside phosphate/phosphonate prodrug containing a substituted benzyl grou
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Paragraph 0130; 0131; 0132; 0133; 0137; 0138; 0139-0145
(2017/06/10)
-
- PHOSPHORIC ACID/PHOSPHONIC ACID DERIVATIVES AND MEDICINAL USES THEREOF
-
The present invention relates to phosphoric acid/phosphonic acid derivatives shown by formula (I), wherein, R1 or R2 represents the following structures: (Q1), or (Q2), or (Q3). Q1 represents ester derivatives of L-amino acid, wherein R3 is alkyl with 1-6 carbon atoms or cycloalkyl, R4 is H or alkyl with 1-6 carbon atoms; Q2 represents hydroxyl substituted benzodioxane derivatives; Q3 represents hydroxyl substituted benzodioxolane derivatives; R1 or R2 is the same or different, but at least one of them is Q2 or Q3; D represents residues of pharmacologically active molecules containing a phosphate/phosphonate group, i.e. formula (II) represents pharmacologically active molecules containing a phosphate/phosphonate group; and when R1 and R2 are different, the configuration of the P atom connected to R1 and R2 is of R or S type.
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Paragraph 0042
(2016/05/19)
-
- A RECYCLING PROCESS FOR PREPARING TENOFOVIR ALAFENAMIDE DIASTEREOMERS
-
The present invention relates to an efficient and economical process to recycle the undesired diastereomer of Tenofovir alafenamide to desired diastereomer by racemization of the undesired diastereomer followed by separation of the desired diastereomer from the racemic mixture.
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-
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF TENOFOVIR ALAFENAMIDE OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
-
The present invention provides an improved process for the preparation of Tenofovir alafenamide or pharmaceutically acceptable salts thereof in high yield and purity. Also provided is a process for the separation of diastereomers of Tenofovir alafenamide by simulated moving bed chromatography or preparative high performance liquid chromatography.
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-
- AN EFFICIENT PROCESS FOR SEPARATION OF DIASTEREOMERS OF 9-[(R)-2-[[(R,S)-[[(S)-1-(ISOPROPOXYCARBONYL)ETHYL]AMINO]-PHENOXYPHOSPHINYL] METHOXY]PROPYL]ADENINE
-
The present invention relates to an efficient process for the separation of diastereomers of 9-[(R)-2-[[(R,S)-[[(S)-1-(Isopropoxycarbonyl)ethyl]amino]-phenoxyphosphinyl]methoxy]propyl]adenine and to a process for preparing 9-[(R)-2-[[(R)-[[(S)-1-(Isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]propyl]adenine and 9-[(R)-2-[[(S)-[[(S)-1-(Isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]propyl] adenine.
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Page/Page column 13; 14
(2015/01/06)
-
- Methods for preparing anti-viral nucleotide analogs
-
Methods for isolating 9-{(R)-2-[((S)-{[(S)-1-(isopropoxycarbonyl)ethyl]amino}phenoxyphosphinyl)methoxy]propyl}adenine (compound 16): a method for preparing, in high diastereomeric purity, intermediate compounds 13 and 15: and a method for preparing intermediate compound 12: 9-{(R)-2-[((S)-{[(S)-1-(isopropoxycarbonyl)ethyl]amino}phenoxyphosphinyl)methoxy]propyl}adenine has anti-viral properties.
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-
- Practical synthesis, separation, and stereochemical assignment of the PMPA pro-drug GS-7340
-
The practical synthesis of a mixed phenoxy-amidate derivative of PMPA with high oral bioavailability and favorable pharmacokinetics is described. The non-stereoselective synthetic route produces a 1:1 mixture of two diastereomers at phosphorous. Simulated moving bed chromatography using Chiralpak AS enabled kilo-scale isolation of the more potent diastereomer (GS-7340). The GS-7340 phosphorous chiral center was found to be (S) by X-ray crystallography.
- Chapman,Kernan,Prisbe,Rohloff,Sparacino,Terhorst,Yu
-
p. 621 - 628
(2007/10/03)
-