206 results about "Neuraminidase inhibitor" patented technology

Compounds I-III wherein U is CH, O, or S; Z is mono- or di-substituted carbon; R is (CH2)nCO2H, (CH2)nSO3H, (CH2)nPO3H2, (CH2)nNO2, CH(SCH3)3, esters; R1 is H, hydroxyalkyl, aminoalkyl, alkoxyalkyl; RR1 is O; n is 0-4; R2, R3 is H, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkyl; R4 is (CH2)nOH, (CH2)nNH2, substituted alkyl were prepd. as neuraminidase inhibitors. Thus, (1R,3R,4R,1'S)-(-)-(1'-acetylamino-2 '-ethyl)butyl-4-(aminoimino)methylaminocyclopentan-1-carboxylic acid was prepd. and tested in vitro as neuraminidase inhibitor (IC50<1.mu.M).

The present invention is related to pharmaceutical formulations and methods of treating a subject afflicted with the influenza virus, the method includes administering to the respiratory tract of the patient particles that include more than about 5% to about 50% weight percent (wt %) of a neuraminidase inhibitor. The particles are delivered to the patient's pulmonary system, including the upper airways, central airways and deep lung.

Compositions for treating flu comprise an M2 inhibitor, and optionally a neuraminidase inhibitor, wherein at least one of said M2 inhibitor or said neuraminidase inhibitor is provided in an extended release dosage form.

The invention relates to a multimeric compound or a pharmaceutically acceptable salt or derivative thereof which comprises three or more neuraminidase-binding groups attached to a spacer or linking group, in which the neuraminidase-binding group is a compound which binds to the active site of influenza virus neuraminidase, but is not cleaved by the neuraminidase. The invention also relates to processes for the preparation of the multimeric compound defined above, pharmaceutical compositions containing them or methods for the treatment and / or prophylaxis of a viral infection involving them.

The present invention relates to targets for Human microRNAs in Avian Influenza Virus (H5N1) Genome and provides specific miRNA targets against H5N1 virus. Existing therapies for Avian flu are of limited use primarily due to genetic re-assortment of the viral genome, generating novel proteins, and thus escaping immune response. In animal models, baculovirus-derived recombinant H5 vaccines were immunogenic and protective, but results in humans were disappointing even when using high doses. Currently, two classes of drugs are available with antiviral activity against influenza viruses: inhibitors of the M2 ion channel, amantadine and rimantadine, and inhibitors of neuraminidase, oseltamivir, and zanamivir. There is paucity of information regarding effectiveness of these drugs in H5N1 infection. These drugs are also well known to have side effects like neurotoxicity. Thus there exists a need to develop alternate therapy for targeting the Avian flu virus (H5N1). The present invention addresses this need in the field.

The invention relates to application of N-{5-(1,2,4-triazole-1-yl) thiazole-2-yl} fatty acid amide in preparing an influenza virus neuraminidase inhibitor. The N-{5-(1,2,4-triazole-1-yl) thiazole-2-yl} fatty acid amide has the chemical structural formula shown as I, wherein in the formula I, R is selected from C1 to C2 alkyls, C3 to C4 straight chains or branched alkyls; R1 is selected from C1 to C2 alkyls, C3 to C11 straight chains or branched alkyls, C12 to C17 straight chains or branched alkyls, vinyls, allyls or C4 to C17 alkyls containing dual keys or three keys.

The present invention provides a dual release solid dosage form containing a first composition that releases a neuraminidase inhibitor, such as oseltamivir, zanamivir, or peramivir, in a controlled manner and a second composition that releases an H1 antagonist in a rapid and / or immediate manner. A wide range of H1 antagonist antihistamines, especially fexofenadine and loratadine, can be used in this device. Particular embodiments of the invention provide osmotic devices having predetermined release profiles. The device is useful for the treatment of respiratory congestion and other viral infection associated symptoms.

The invention relates to 3-[[2-(benzylamino) thiazole-5-yl]-methyl] quinolone-2(1H)-ketone as shown in chemical structural formulas I and II or a salt thereof. In the chemical structural formulas, R, X<1> and X<2> are selected from hydrogen, deuterium, C1-C2 alkyl, C3-C4 linear-chain alkyl or branched-chain alkyl; X<3> is selected from hydroxyl, methoxyl and ethyoxyl; is selected from hydrogen, deuterium, C1-C2 alkyl, fluorine, fluorine or bromine; X4 and X6 are selected from hydrogen, deuterium, C1-C2 alkyl, fluorine, fluorine, bromine or nitryl; X5 and X7 are selected from hydrogen, deuterium and C1-C2 alkyl. The invention also provides an application of the 3-[[2-(benzylamino) thiazole-5-yl]-methyl] quinolone-2(1H)-ketone in preparation of an influenza virus neuraminidase inhibitor.

The invention provides a compound expressed by a general formula I, or its pharmaceutically acceptable salt, and an analyzed enantiomer and a purified diastereomer, wherein R<1>is H or C1-12 alkyl groups; R<2> is H, -C(O)R<1a>, -C(O)OR<1a> or -S(O)2R<1b>, wherein R<1a> is H or C1-6 alkyl groups, R<1b> is selected from H or C1-6 alkyl groups halogenated hydrocarbon, phenyl or aryl group; R<3> is selected from C1-4 alkyl groups substituted amino, halogen, hydroxyl, sulfydryl, guanidyl, nitryl or cyano group; and R<4> is -(CH2)nCO2H, -(CH2)nP(O)(OH)2, -(CH2)nCO2R<1a> and -(CH2)nP(O)(OR<1a>)2, wherein R<1a> is H or C1-6 alkyl groups, n is an integer between 0 and 4, or a salt of the above groups. The invention also provides a preparation method of the cyclohexene compound expressed by the general formula I, and an application of the cyclohexene compound taken as an influenza virus neuraminidase inhibitor for preparing the medicines to prevent or treat the influenza diseases.

The invention discloses a preparation method and medical application of 4-tert-butyl-6-phenyl-2-amino-6H-1,3-thiazine salt. The preparation method of the 4-tert-butyl-6-phenyl-2-amino-6H-1,3-thiazine salt comprises the steps of: stirring 0.010 mol of 1-phenyl-4,4-dimethyl pentene-3-ketone, 0.012 mol of thiourea and 0.011 mol of acid in an organic solvent at a temperature of between 30 and 80 DEG C, performing TLC detection on reaction process, completing reaction, filtering, washing and drying the obtained product and obtaining the 4-tert-butyl-6-phenyl-2-amino-6H-1,3-thiazine salt (I). The 4-tert-butyl-6-phenyl-2-amino-6H-1,3-thiazine salt (I) can be medically used for preparing influenza virus neuraminidase inhibitors. In a formula, HX is hydrochloric acid, phosphoric acid, hydrobromic acid, sulphuric acid, trifluoroacetic acid or methanesulfonic acid, and Y is Cl, Br, CH3, Et, CF3, OCH3 or OEt.

The invention belongs to the antiviral field of medical chemistry and relates to a novel pyridine derivative shown in a formula (I), a stereisomer, pharmaceutical salt, a solvent compound or a crystalof the pyridine derivative and an application of the pyridine derivative and the stereisomer, pharmaceutical salt, the solvent compound or the crystal in preparing drugs for preventing or treating viral infection diseases such as influenza A and / or influenza B, particularly in preparing a cap dependent endonuclease inhibitor in preventing or treating influenza A and / or influenza B viral infectiondiseases. The compound has remarkable activity for inhibiting influenza endonuclease and influenza DNA, can be independently used or can be combined with a neuraminidase inhibitor, nucleoside medicines, a PB2 inhibitor, a PB1 inhibitor, an M2 inhibitor or other anti-influenza drugs, the influenza infection time is notably shortened, the death rate is remarkably reduced, and the pyridine derivative has very good clinical application prospects.

The invention relates to an oseltamivir derivative as well as a preparation method and application thereof. The compound has the structure shown in a formula I. The invention provides an efficient influenza virus neuraminidase inhibitor with high selectivity, which is used for preparing drugs for preventing or curing flu, particularly the diseases caused by N1 influenza virus. The invention also relates to a drug composition comprising the compound shown in the formula I.

The invention discloses an oseltamivir derivative, a preparation method and an application thereof. The derivative has a structure shown as formula I. The invention also discloses the preparation method for the oseltamivir derivative, the application thereof as an avian influenza virus neuraminidase inhibitor and the application of a composition containing one or more compounds in preparing anti-influenza virus drugs.

The invention provides use of a compound shown as formula Ia or a prodrug thereof in preparation of drugs for the prevention and / or treatment of Tamiflu resistant influenza viruses strain infection, a Tamiflu resistant influenza viruses strain is preferably H1N1 Swine-origin influenza A virus H274Y. The invention also provides a method for the treatment, prevention or delay of virus infection caused by the Tamiflu resistant influenza viruses strain, and the method comprises administering of a therapeutically effective amount of the compound or the prodrug thereof to patients needing the treatment.

The invention relates to an extraction method of hyperin and application thereof in medicament preparation. The extraction method of the hyperin comprises the following steps: placing Turpinia formosana leaves or Hypericum perforatum in 30%-90% ethanol of 5-15 times, carrying out reflux extraction for 1-3 times, and filtering, wherein the reflux extraction of each time is carried out for 1-3 hours; merging the filtrates, recovering the ethanol, eluting the aqueous solution with a macroporous adsorption resin column, collecting eluted parts, carrying out depressurized concentration, and drying to obtain mixed total glycoside of the hyperin; and carrying silicagel column chromatography and Sephadex LH-20 column chromatography separation, merging hyperin fractions, and crystallizing to obtain the pure hyperin product. The hyperin can be used as a neuraminidase inhibitor for preventing and treating flu, and can be prepared into pharmaceutically acceptable dosage forms.

The invention relates to a rhoifolin and a prepared medicament application thereof. The method for extracting the rhoifolin comprises the following steps of: taking turpinia formosana leaves or exocarpium citrl grandis, adding 5-15 times of 30-90 percent ethanol for carrying out refluxing extraction for 1-3 times and filtering, wherein each refluxing extraction is carried out for 1-3 hours; combining filter liquid and recycling ethanol; eluting an aqueous solution by a macroporous resin column, collecting an eluted part, depressurizing for concentrating and drying to obtain the mixed total glycoside of the rhoifolin; and separating, combining rhoifolin fractions and crystallizing to obtain pure rhoifolin. The rhoifolin can be used as a neuraminidase inhibitor for preventing and treating influenza and made into a pharmaceutically acceptable formulation.

The invention discloses use of 4-alkyl-6-aryl-5-acetyl-1,3-thiazine represented by a chemical structural formula I and 4-alkyl-6-aryl-5-acetyl-2-amino-1,3-thiazine salts, or 4-alkyl-6-aryl-5-acetyl-2-amido-1,3-thiazine represented by a chemical structural formula II and 4-alkyl-6-aryl-5-acetyl-2-amido-1,3-thiazine salts for preparing a neuraminidase inhibitor of influenza viruses.

A composition is described having improved oral permeability of polar agents such as neuraminidase inhibitors. The composition includes one or more polar agents and one or more permeability enhancers such that the composition increases the amount of the polar agent capable of being transported across a Caco-2 cell membrane by at least 150% relative to the amount capable of being transported across the Caco-2 Cell membrane in the absence of the permeability enhancer. Oral dosage forms including the composition, and methods of treating or preventing influenza infection are also provided.

The invention discloses 4-alkyl-6-aryl-2-acylamino-1,3-thiazine-5-formic ether having the following chemical structural formula shown in the specification. The preparation method of the 4-alkyl-6-aryl-2-acylamino-1,3-thiazine-5-formic ether (I) comprises the following steps of: adding 2-benzal-2-acyl acetate and thiourea in organic solvent, stirring at 55-80 DEG C under acid catalysis, filtering and washing after reacting completely, and drying to obtain 4-alkyl-6-aryl-2-amino-1,3-thiazine-5-formic ether salt; neutralizing the 4-alkyl-6-aryl-2-amino-1,3-thiazine-5-formic ether salt with alkali to obtain 4-alkyl-6-aryl-2-amino-1,3-thiazine-5-formic ether; and acylating the 4-alkyl-6-aryl-2-amino-1,3-thiazine-5-formic ether to obtain the 4-alkyl-6-aryl-2-acylamino-1,3-thiazine-5-formic ether (I). The invention also discloses an application of the 4-alkyl-6-aryl-2-acylamino-1,3-thiazine-5-formic ether in preparing the drug of neuraminidase inhibitor.

The invention relates to a novel sialic acid derivant represented by the following general formula, a preparation method thereof, a drug composite comprising the same and an application of the novel sialic acid derivant in preparing neuraminidase inhibitor and drug capable of treating and preventing relevant diseases of influenza viruses. The compound and the neuraminidase have high binding activity, and cells can be effectively prevented from being infected by viruses in a biotic experiment test. Therefore, the compound is the strong neuraminidase inhibitor and is possible to develop into a new anti-influenza virus drug.

The invention provides a compound shown as formula Ia, its pharmaceutically acceptable salts, solvates, polymorphs, enantiomer or racemic mixtures. The compound is used as a neuraminidase inhibitor prodrug, and can improve the half-life in the body of a neuraminidase inhibitor. The invention also provides a preparation method of the compound, a pharmaceutical composition containing the compound, and use of the pharmaceutical composition and the compound in preparation of neuraminidase inhibitor drugs and treatment of related diseases.

The invention relates to N-[4-phenyl-5-(1,2,4-triazole-1-yl)thiazole-2-yl]amide shown in a chemical structural formula I (please see the formula in the specification), wherein X<1> and X<3> are selected from chlorine, bromine, fluorine and iodine, X<4> is selected from hydrogen, deuterium, methyl, ethyl, chlorine, bromine, fluorine and iodine, X<2> and X<5> are selected from hydrogen, deuterium, methyl and ethyl, R is selected from hydrogen and methyl, n is selected from 0,1,2 and 3, and Y is selected from hydrogen, C1-C2 alkyl, C3-C11 straight-chain alkyl or branch-chain alkyl, C1-C2 halogenation alkyl or dihalogenation alkyl, C3-C5 halogenation straight-chain alkyl or halogenation branch-chain alkyl and phenyl. The application of the N-[4-phenyl-5-(1,2,4-triazole-1-yl)thiazole-2-yl]amide in preparation of anti-cancer drugs or neuraminidase inhibitors for Hela cells is achieved.

The invention provides a dihydroxybenzoylhydrazone neuraminidase inhibitor and preparation and application thereof. The neuraminidase inhibitor is characterized by adopting a structural formula as shown in the description. The neuraminidase inhibitor has excellent anti-H1N1 influenza virus activity, adopts a structure completely different from that of previous neuraminidase, has a good effect of inhibiting A / WSN / 33H1N1 virus strain, is less in toxicity and has high druggability.

The invention provides a benzoyl hydrazone neuraminidase inhibitor. The inhibitor is characterized in that the structure of the inhibitor is shown in the formula I. The inhibitor has the advantage that according to the structural formula, the synthesized compound has good neuraminidase inhibiting activity.

The invention relates to 2-(thiazol-2-yl)imino-5-(benzylidene)thiazolidin-4-one shown as formulas I, II, III or IV or a mixture thereof, wherein R1 is selected from hydrogen, C1-C2 alkyl or C3-C4 straight-chain or branched chain alkyl, R2 is selected from hydrogen, C1-C2 alkyl or C3-C4 straight-chain or branched chain alkyl, X1-X5 are selected from hydrogen, C1-C2 alkyl, C3-C4 straight-chain or branched chain alkyl, nitro, amino or NHCOR, and R is selected from hydrogen, C1-C2 alkyl or C3-C4 straight-chain or branched chain alkyl. Applications of the 2-(thiazol-2-yl)imino-5-benzal thiazoline-4-one or the mixture thereof in preparation of neuraminidase inhibitors are also disclosed.

The present disclosure belongs to the field of medicinal chemistry, and relates to a novel pyridone derivative represented by Formula (I) or a stereoisomer, a pharmaceutically acceptable salt, a solvate or a crystal thereof, and use thereof in the preparation of a drug for preventing or treating diseases such as influenza type A viral infection and / or influenza type B viral infection, particularly use thereof as a PA subunit cap-dependent endonuclease inhibitor for preventing or treating diseases such as influenza type A viral infection and / or influenza type B viral infection. The compounds of the present disclosure have significant activity in inhibiting influenza endonuclease and influenza DNA, can be used either alone or in combination with a neuraminidase inhibitor, a nucleoside drug, a PB2 inhibitor, a PB1 inhibitor, an M2 inhibitor or other anti-influenza drugs, significantly shorten the time of influenza infection and reduces mortality, and have excellent clinical application prospects.

The invention provides a 2D-HPLC-AS / UF and ESI-TOF / MS method for screening and characterizing medium-trace neuraminidase inhibitors in honeysuckle flower. By adoption of the method, 44 neuraminidase inhibitory active compounds are found from a honeysuckle flower extract and are primarily identified by comparison with standards and references. The method has the advantages of high efficiency, low energy consumption and high pertinence, and provides the method and technical support for rapid screening and identification of medium-trace neuraminidase inhibitors in complex natural medicine materials.

Methods and compositions for detection of drug resistant pathogens and treatment against infections thereof are provided. Methods for detection of oseltamivir-resistant influenza viruses by competitive binding assays utilizing non-oseltamivir influenza virus neuraminidase inhibitors and oseltamivir carboxylate are provided. Influenza virus neuraminidase inhibitors coupled to sensors and useful for employment in the methods of the invention are disclosed. Novel phosphonate compounds active as neuraminidase inhibitors against wild-type and oseltamivir-resistant influenza strains of H1N1, H5N1 and H3N2 viruses are disclosed. An enantioselective synthetic route to preparation of these phosphonate compounds via sialic acid is provided.

The invention relates to an acute turpinia leaf general flavone ethanol reflux extract, which is prepared from acute turpinia leaves through ethanol reflux extraction, wherein an extraction method comprises the following steps: taking acute turpinia leaves; adding 30 to 90 percent of ethanol accounting for 5 to 15 times of the volume for carrying out reflux extraction for 1 to 3 times, wherein each time of reflux extraction lasts for 1 to 3 hours; carrying out filtration; merging filter liquid; recovering the ethanol from the filter liquid; using nonpolar macroporous absorbent resin for absorbing water solution; using the ethanol lower than 20 percent for elution to remove impurities; then, using 25 to 90 percent of ethanol for elution; collecting elution liquid; recovering the ethanol; and carrying out concentration and drying to obtain the acute turpinia leaf general flavone ethanol reflux extract. The general flavone content is higher than 50 percent, and the flavone type major chemical ingredients are one kind or several kinds of materials in nuezhenoside, rhoifolin, hyperin, meletin, cyanidenon, apiolin and glucoside or aglycon thereof. The extract can be used as a neuraminidase inhibitor to be used for preventing and treating flu, and can be made into pharmaceutically acceptable preparations.