229 results about "Entecavir" patented technology

The invention discloses a synthesis method of entecavir, which sequentially comprises the preparations of Ente-0, Ente-1, Ente-2, Ente-3, Ente-4, Ente-5 and Ente-6; and a process for producing product from Ente-6. The synthesis method of entecavir has easily obtained materials, simple process, low production cost and easy operation.

This invention discloses a method for synthesizing entecavir as an anti-hepatitis B drug. The method is characterized by: diphenyl methylchlorosilane is utilized as a protective agent is step 1, and cyclohexyl methanol is utilized as an esterifying agent in step 4. The method has such advantages as low cost, high drug purity and high yield, and is suitable for industrialization.

The invention aims to provide an entecavir compound prepared in a novel method. The reaction procedures in the preparation method of the entecavir compound are simplified. Moreover, isopropyl is adopted as a protection agent. Since the steric hindrance can function as multiple types of directional substitution, the invention reduces the introduction of heterogeneous impurities. The reaction in multiple procedures needs no strict operating conditions. Therefore, the invention lays a foundation for industrial production.

The invention relates to a method for preparing an antiviral medicinal entecavir intermediate compound with a formula I. An oxidation system formed by TEMPO and iodine under an alkali condition is adopted to oxidize a compound with a formula III to obtain a compound with a formula II, and methylenation is carried out on the formula II by a methylenation system formed by titanium tetrachloride, magnesium, methylene chloride and tetrahydrofuran to obtain the compound with the formula I. The invention has easy acquirement of raw materials and simple and convenient method and is suitable for industrialized production.

The invention relates to a synthesis method of nucleoside analogs, particularly to a synthesis method of an anti-virus-activity compound Entecavir. The invention also relates to intermediates for preparing Entecavir and a method for preparing the intermediates.

The invention discloses a novel synthesis process of entecavir monohydrate. In the method, monomer cyclopentadiene serves as a starting raw material, the entecavir hydrate is prepared by thirteen steps, i.e. salification, silanization, condensation, reduction, resolution, esterification, reduction, desilanization, hydroxyl protection, epoxidation, condensation, allylation, deprotection. According to the invention, raw material is available and is low in price, synthesis operation is simple, reaction conditions are mild and are easy to control, reaction selectivity is good, and yield is high, thus the process is applicable to industrial production.

The invention relates to a method for preparing a medicament for treating hepatitis B, i.e. entecavir I. The method uses [1S(1alpha, 2alpha, 3beta, 5alpha)]-3-benzoyloxy-2-benzyl methoxymethyl-6-oxabicyclo[3.1.0]hexane II and 2,6-diaminopurine III as the raw materials, and prepares the entecavir by carrying out ring-opening condensation, carrying out trityl amino protection, oxidization and methylenenation, then using acetyl to protect 2-amino and 6-amino to carry out diazotization hydrolysis, and finally carrying out de-protection. The invention has high reaction yield, high optical purity of the product and simple and convenient operation, and is suitable for the industrial production.

The invention relates to a parenteral preparation containing active entecavir and a preparation method thereof. The invention is characterized in that the parenteral preparation comprises the active entecavir, xylitol, water-soluble filler, pH regulator, water for injection and osmo-regulator, wherein the active entecavir is 0.001 percent to 30 percent by weight, and the balance is pharmaceutic adjuvant or water. The parenteral preparation has the advantages of good stability and high bioavailability, thus solving the defects of the oral administration of entecavir in treating the acute exacerbation of viruses. The parenteral preparation is particularly suitable for treatment on the acute exacerbation of hepatitis of a diabetic.

The invention belongs to the field of chemical synthesis, and relates to a preparation method of entecavir, in particular to a new preparation method of an intermediate compound related in the entecavir as a hydrate and a synthetic method. The method of the invention overcomes the defects of low yield, large pollution and the like existing in the prior art, and provides the method for preparing the entecavir in a formula (I), which has high yield, little environment pollution and convenient purification.

The invention relates to a synthesis method of nucleoside analogues, in particular to a synthesis method of a compound Entecavir with antiviral activity. The invention also relates to intermediates used for preparing Entecavir and methods for preparing the intermediates.

The invention discloses a method for preparing a compound shown as the formula (I), which is characterized by comprising the following steps of: (1) carrying out hydroxyl protection on a compound shown as the formula (II) by using a first hydroxyl protecting group, and then, reacting with hydride to generate a compound shown as the formula (III); (2) carrying out hydroxyl protection on the compound shown as the formula (III) by using a second hydroxyl protecting group, and then, removing the first hydroxyl protecting group to obtain a compound shown as the formula (IV); (3) enabling the compound shown as the formula (IV) to carry out non-corresponding selective epoxidation reaction to generate a compound shown as the formula (V); (4) reacting the compound shown as the formula (V) with thecompound shown as the formula (VI) in a polar aprotic solvent to obtain a compound shown as the formula (VII); and (5) carrying out condensation, desilylation and oxidization on the compound shown asthe formula (VII) to generate the compound shown as the formula (I). In the general formulas of the compounds in each step, R1 is selected from naphthyl or any substituted naphthyl; R2 is selected from alkyl or benzyl of C1-C4; P is selected from hydroxyl protecting groups, such as 2-methoxyl propyl or p-methoxyl benzyl and the like; P' is a hydroxyl protecting group capable of resisting and removing P, such as benzyl; and X is selected from Cl, Br, I or benzyloxyl.

The invention provides an improved method for preparing an antiviral medicine, i.e., entecavir. The method comprises the following steps of: taking a compound in a formula II shown as the specification as a raw material and carrying out further reaction under the action of a boron chloride dichloromethane solution, methyl alcohol and water to obtain entecavir. A formula II is shown as the specification; R in the formula II and I is used for representing 4-methoxyl triphenylmethyl or triphenylmethyl, and the Bn is used for representing benzyl. The method has the advantages of simpleness and convenience for operation, good repeatability, high yield, suitability for industrial production and higher application value.

The invention relates to a synthesis method of a nucleoside analogue, in particular to a synthesis method of compound entecavir with antiviral activity. The invention also relates to midbodies for preparing the entecavir and a method for preparing the midbodies.

The invention discloses a method for preparing an intermediate (I) of an Entecavir antiviral agent, which comprises the following steps: (1) reacting a compound of a formula (II) with magnesium under a condition of a proper solvent to generate a compound of a formula (III); and performing the Grignard reaction of the compound of the formula (III) and a compound of a formula (IV). In the formulae, X and Y are identical or different and may be F, Cl and Br atoms. The method has the advantages of simple reaction conditions, cheap and readily available raw materials, simple and safe process, low cost and easy industrial production.

The invention relates to the field of biological medicine, and in particular relates to liver targeted medicine. The medicine is chemical micromolecular medicine connecting galactosamine. The chemicalmicromolecular medicine is medicine for treating liver diseases or liver-related diseases. The chemical micromolecular medicine is prepared from but not limited to thyroxine T3, sorafenib, taxol, regorafenib, lamivudine, entecavir, telbivudine, statins, fibrates, niacin, bile acid sequestrants, other hepatitis virus DNA (RNA) polymerase inhibition compounds and the like. The galactosamine is tervalent acetylgalactosamine. The connection is the direct connection of the galactosamine and the chemical micromolecular medicine or the connection through linking fragments; the linking fragments comprise but not limited to carbon chains, disulfide bonds, pyrophosphate diester, cysteic acid, polypeptide and thioether or valine-citrulline. The medicine provided by the invention has the advantages that the liver targeted performance is improved; the medicine curative effect is enhanced; the toxic and side reactions on other non-targeted tissues are few.

The invention relates to an Entecavir dispersible tablet for treating hepatitis B and process for its preparation by using Entecavir as raw material, charging auxiliary materials of specific species and proportions, and preparing tablet through the conventional techniques in the pharmaceutical industry.

The invention relates to an Entecavir dispersible tablet and the preparation method; wherein, the Entecavir dispersible tablet comprises Entecavir, binder, filler, disintegrating agent, and lubricant; the uniformity of dosage units (A+1.8S) is not larger than 10.0. The preparation method for the dispersible tablet in the invention has the advantages of simple process, and suitability for large-scale industrial production.

The invention discloses a method for synthesizing Entecavir and belongs to the technical field of medicine synthesis methods. According to the method, Entecavir is synthesized through taking 1,3-propanediol as a starting raw material, carrying out oxidation so as to form an aldehyde, then, producing an unsaturated ester, and then, carrying out reactions such as reduction, asymmetric epoxidation, ring opening, silane protecting group removing, hydroxyl protection, deprotection, oxidation, ring closing, oxidation, reduction, condensation and deprotection. According to the method, the used raw material is cheap and readily available, and the reaction conditions are mild and are easy in control, so that the industrial production is facilitated.

The present invention discloses an anti-hepatitis B medicine enticavi dispersing tablet preparation and its preparation method. Said preparation adopts proper binding agent and prescription, and the invented enticavi dispersing tablet has high bioavailabity and blood concentration and good disintegration solution effect.

The invention belongs to the field of drug intermediates and provides a five-membered ring chiral intermediate (1R, 2S, 3S, 5R)-3-(1-phenylcyclo silicon)-6-oxa-bicyclo [3.1.0] hexane-1, 2-dimethyl carbinol for synthesis of entecavir and a synthesis of the five-membered ring chiral intermediate. A chiral five-membered carboatomic ring is obtained by reacting 1-phenyl-1-chlorocyclosilane with alkali metal salt of cyclopentadiene and introducing cyclosilane into a molecule to serve as a construction protecting group and by the aid of a chemical resolution method. Introduction of the cyclosilane enhances molecule rigidity to enable a solid product to be crystallized and purified more easily, and the synthesis method is simpler in reaction operation, cheap in raw materials, available to raw materials and suitable for industrial production.

The invention relates to a synthesis intermediate of Entecavir and a preparation method thereof. Specifically, the invention relates to a synthesis intermediate shown as formula II for preparation of Entecavir, a preparation method of the intermediate, and a method for preparing Entecavir from the intermediate shown in formula II, wherein R and R' are as defined in the specification.

The invention relates to a hepatitis B virus multi-drug resistant gene locus typing detection method and a kit thereof, wherein the detection method comprises the following steps that: DNA extraction is performed, wherein PCR amplification is applied to the abstracted DNA, the used PCR primers are two pairs of positive primers and negative primers; the PCR primers contain all correlative drug resistant locuses; amplified products of PCR are subjected to LDR amplification; the used probes are probes for correlation locus, which comprise a fluorescence labeling probe and a detection probe; a sequencing machine analyzes LDR products to judge the genotype of drug resistant locus; the multi-drug resistant gene locus is a drug resistant locus of lamivudine, ADV and ETV. The hepatitis B virus multi-drug resistant gene locus typing detection kit has reliable stable result, simple and quick operation; the kit can detect the drug resistant condition of various hepatitis B viruses, and supply clinical individuation medicine application instruction to hepatitis B virus patients. The kit can reduce the ineffectivity of drugs and administration times of the patients, thereby alleviating pains and economic burden of the patients.

The invention discloses a making technique of entikawei monohydrate as antiviral drug, which comprises the following steps: reacting cyclopentadiene monomer and sodium hydride protected by inert gas to make sodium cyclopentadiene; oxidizing through tert-butyl hydroperoxide; reacting with benzyl halogen under alkaline to obtain compound 3 to react with 6-benzyloxy guanine acted by alkaline to obtain compound 4; reacting with amino protective group to prepare compound 5; oxidizing through DMP tert-butanol oxidizing system to obtain ketone compound 6 to generate methylene compound 7 acted by Zn / TiCl4 / CH2Br2; stripping protective product under acid condition to produce compound 8; recrystallizing to obtain the product.

This invention discloses a method for preparing entecavir acid-addition salts, entecavir magnesium salt and entecavir barium salt. The entecavir acid-addition salts are prepared from entecavir and inorganic or organic acids, and are preferential entecavir hydrochloride, entecavir bromate, entecavir sulfate, entecavir phosphate, entecavir sulfonate, and entecavir benzenesulfonate. The entecavir slats are stable, and have higher water solubility than entecavir itself, thus are more suitable to manufacture anti-HBV drugs.

The present invention relates to one kind of new compound, entecavir amido ursodesoxycholate, its preparation process, medicine composition with the compound as active component and the application of the compound in preventing and treating hepatitis B.

The invention belongs to the field of medicine synthesis, and provides a method for synthesising entecavir by taking (1R,2S,3S,5R)-3-(1-phenyl cyclo-silicon)-6-oxa-bicyclo[3.1.0] hexane-1,2-dimethyl carbinol as a raw material. The synthesis method comprises the following steps of: combining the raw material with purine compounds at first, then building a chiral five-membered exocyclic double bond via deoxidization reaction, and finally removing a protecting group to obtain entecavir. Via the cyclosilane structure of the raw material, the rigidity of molecules is enhanced, so that the product obtained via the method is easier to crystallize and purify; and the tar generated during the reaction is less, and the yield is high. Therefore, the synthesis method is good in industrialization prospect.

The invention provides entecavir fatty acid derivatives and pharmaceutical composition thereof and further relates to preparation methods of the entecavir fatty acid derivatives. The entecavir fatty acid derivatives had higher bioavailability and smaller toxic and side effects, and the pharmaceutical composition of the entecavir fatty acid derivatives is safer and more efficient when used for treating hepatitis B virus infection.

The present invention pertains to the pharmaceutical field and relates to an antiviral compound drug, in particular to an entecavir drug composition and the anti-HBV usage. The present invention is composed of entecavir, (1s-(1 Alpha, 3 Alpha, 4 Beta))-2-amino-1, 9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]-6H-purine-6-ketone, monocase compound which is extracted from one or more traditional Chinese medicines and the pharmaceutical excipients. The results of the in vitro and the duck hepatitis B animal model tests show that the present invention has obvious anti-HBV efficacy; at the same time, the present invention also has good hepatoprotective effect. The entecavir drug composition becomes the more safe and effective drug for treating hepatitis B and thus having very broad application prospect and far-reaching social benefits.

The invention discloses a soluble Endicarwei acid additional salt or tautomer or drug solvate and utility, which resists hepatitis B virus.