87 results about "Anti influenza drug" patented technology

The present invention provides a pyrone derivative and a pyridone derivative, which are novel intermediates for synthesizing an anti-influenza drug, a method of producing the same, and a method of using the same.

The invention discloses a method for synthesizing a novel anti-influenza drug baloxavir marboxil. The method comprises the following steps: directly docking a thiosalicylic acid compound 1 and a 1-(halogenated methyl)-2,3-difluorobenzene compound 2 serving as initial raw materials so as to obtain a compound 3; performing PPA ring closure to obtain a 7,8-difluorodibenzo[b,e]thiozepine-11(6H)-one compound 4, and obtaining a key chiral thiazem intermediate compound 5 under catalysis of a chiral enzyme; directly condensating the compound 5 and a key chiral fragment compound 6 by virtue of a Mitsubobu reaction so as to obtain a compound 7; finally performing dealkylation protection, and condensating with ((methoxycarbonyl)oxo)4-methyl-toluenesulfonate, so as to obtain the final product compound9, namely the baloxavir marboxil. According to the synthetic route, the process operation magnification difficulty of the route is reduced, the production of by-products is reduced, the product purity is improved, and the cost of the route is reduced.

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 present invention provides a pyrone derivative and a pyridone derivative, which are novel intermediates for synthesizing an anti-influenza drug, a method of producing the same, and a method of using the same.

The invention relates to polypeptide, protein or peptide-like medicine from influenza virus hemagglutinin, and a method of the polypeptide, belongs to the technical field of biological medicines, and in particular relates to eight influenza virus hemagglutinin fragment peptides which can block influenza virus infection and have the serial numbers SEQ ID NO.1 to SEQ ID NO.8. The fragment peptides can inhibit and block infection of different species and influenza viruses of different subtypes to a host, including multiple influenza virus strains such as highly pathogenic avian influenza virus, seasonal human influenza virus and the like. The invention provides the peptide sequence (including amino acid sequences of peptides and polynucleotide sequences of encoded peptides), derivative peptides (including amino acid sequences of peptides and polynucleotide sequences of encoded peptides), peptide compositions and independent or united applications of peptides in preventing or treating influenza virus, such as medicine combination of peptides provided by the invention and other anti-influenza medicines.

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 present invention aims to express influenza virus RNA polymerase on a large scale, to crystallize the influenza virus RNA polymerase, and to provide a method for screening a substance capable of serving as an active ingredient in anti-influenza drugs which target a protein highly conserved among influenza virus species.The present invention provides a complex comprising a polypeptide consisting of an amino acid sequence at positions 239-716 of the RNA polymerase PA subunit in influenza A / Puerto Rico / 8 / 1934 H1N1 and a polypeptide consisting of an amino acid sequence at positions 1-81 of the RNA polymerase PB1 subunit in influenza A / Puerto Rico / 8 / 1934 H1N1, as well as a method for screening a substance capable of serving as an active ingredient in anti-influenza drugs, which comprises the step of selecting a substance which inhibits the interaction between α-subunit and β-subunit 1, each constituting influenza virus RNA polymerase, in the presence of a candidate substance.

The invention discloses an application of a BST-2 protein in preparing medicaments for treating diseases caused by influenza A virus. The BST-2 protein can inhibit IAV viral infection and prevent budding and releasing of the IAV virus from host cell surfaces through inhibiting expression of IAV virus M2 protein and interacting with the M2 protein. According to the invention, the BST-2 protein will become a new target for anti-influenza drugs, paves the way for research and development of the anti-influenza drugs in the future, and may even provide a potential therapeutic approach for treatment of the influenza.

Novel dual-targeted, bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents are disclosed. Exemplary drugs according to the invention include caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1), ZA-7-CA-amide (7) and ZA-7-Nap (43) for simultaneous inhibition of influenza virus neuraminidase and suppression of proinflammatory cytokines. Synthetic methods for preparation of these enhanced anti-influenza conjugate drugs are provided. The synthetic bifunctional ZA conjugates act synergistically towards protection of mice lethally infected by H1N1 or H5N1 influenza viruses. The efficacy of ZA-7-CA, ZA-7-CA-amide and ZA-7-Nap conjugates is much greater than the combination therapy of ZA with anti-inflammatory agents.

The invention provides an anti-virus or / and anti-tumor drug and a preparation method thereof and an application of fenugreek biflavone glycosides for preparing anti-virus or / and anti-tumor drugs. The invention provides the application of the chemical component fenugreek biflavone glycosides in fenugreek seeds as drugs for the first time, and uses the fenugreek biflavone glycosides for preparing anti-virus drugs and anti-tumor drugs for the first time. In vivo and in vitro experiment research shows that fenugreek biflavone glycoside tablets or fenugreek biflavone glycoside capsules of the invention have obvious effect on resisting influenza viruses, and the anti-influenza drug effect of the fenugreek biflavone glycoside tablets or fenugreek biflavone glycoside capsules of the invention is superior to the anti-influenza drug effect of the existing Western medicine ribavirin tablets. The anti-HBV effect of the fenugreek biflavone glycoside tablets or fenugreek biflavone glycoside capsules is superior to the anti-HBV effect of kurarinone capsules, and the anti-HIV effect of the fenugreek biflavone glycoside tablets or fenugreek biflavone glycoside capsules is superior to the anti-HIV effect of zidovudine tablets. The fenugreek biflavone glycoside tablets or fenugreek biflavone glycoside capsules have obvious effect on resisting proliferation of liver cancer, gastric cancer, intestinal cancer, lung cancer and cervical cancer cells, and the anti-tumor effect of the fenugreek biflavone glycoside tablets or fenugreek biflavone glycoside capsules is superior to the anti-tumor effect of the existing chemical component preparation hydroxycamptothecine injection.

The invention discloses a preparation method of indole-3-acetonitrile-6-O-beta-D-pyran glucoside and an application thereof in preparing anti-influenza drugs. The invention also relates to an anti-influenza drug containing the indole-3-acetonitrile-6-O-beta-D-pyran glucoside. The application of the indole-3-acetonitrile-6-O-beta-D-pyran glucoside in the anti-influenza drugs is provided by the invention, so that a safe and effective natural drug with small toxic and side effects is provided for treatment of clinic influenza viral diseases.

The present invention provides a pyrone derivative and a pyridone derivative, which are novel intermediates for synthesizing an anti-influenza drug, a method of producing the same, and a method of using the same.

The invention belongs to the field of synthetic pharmacy and relates to an application of polysaccharide sulfate as the preparation of anti-influenza virus drugs. The invention discloses an application of porphyra haitanensis polysaccharide sulfate with the molecular weight range of 1000-100000 and the degree of substitution of monosaccharide sulfate of 0.5-3.0 in the preparation of the anti-influenza virus drugs, prepares practical drug formulation with the average molecular weight range of 1000-100000 and the degree of substitution of the monosaccharide sulfate of 0.5-3.0 and determines that the polysaccharide sulfate has the use of synergistic anti-A and B-type influenza virus independently or after composing a compound with amantadine, ribavirin and other prior anti-influenza virus drugs.

The invention discloses siRNA and a recombinant vector by aiming at caveolin 2 and surfactant protein D; a construction method of a recombinant vector containing a transcription factor A and paraoxonase 3 transcription box, a corresponded cell model and a method for screening medicines. The invention has the advantages that the provided siRNA can reduce mRNA or protein expression of mammal cells after transfection by more than 60%; and the siRNA and the recombinant vector can be used for treating influenza by gene or performing nucleic acid immunization by aiming at influenza virus. The provided cell model can be used for virus research, and especially relates to swine influenza virus pathogenesis researches, and can be used for establishing a model for screening antiviral drugs, especially an anti-influenza medicine cell model.

The invention discloses an influenza luciferase reporter virus-based animal model building method and application. In the method, a mouse is mainly infected with Gaussia luciferase gene-carrying recombinant influenza virus, and the infection degree of the mouse is evaluated by detecting the expression level of luciferase in a lung tissue of the mouse. The invention further discloses an influenza luciferase reporter virus technology-based method for screening and evaluating an anti-influenza drug. According to the method, anti-influenza drugs with prevention / treatment effects are screened by mainly detecting the influence of antiviral treatment on the expression level of the luciferase in the lung tissue of the mouse. Detection of positive drugs ribavirin and oseltamivir phosphate shows that the method disclosed by the invention has a wide application value in the aspect of screening, researching, developing and evaluating the novel anti-influenza drug.

A medicament characterized in that (A) a compound represented by the formula (I):its pharmaceutically acceptable salt, or a solvate thereof,whereinP is hydrogen or a group to form a prodrug;A1 is CR1AR1B, S or O;A2 is CR2AR2B, S or O;A3 is CR3AR3B, S or O;A4 is each independently CR4AR4B, S or O;the number of hetero atoms among atoms constituting the ring which consists of A1, A2, A3, A4, nitrogen atom adjacent to A1 and carbon atom adjacent to A4 is 1 or 2;R1A and R1B are each independently hydrogen, halogen, alkyl or the like;R2A and R2B are each independently hydrogen, halogen, alkyl, or the like;R3A and R3B are each independently hydrogen, halogen, alkyl, or the like;R4A are each independently hydrogen, halogen, alkyl, or the like;R4B are each independently hydrogen, halogen, alkyl, or the like;R3A and R3B may be taken together with an adjacent carbon atom to form non-aromatic carbocycle or non-aromatic heterocycle;n is any integer of 1 to 2; andR1 isor the like,is combined with (B) compound(s) having an anti-influenza activity, its pharmaceutically acceptable salt or a solvate thereof and / or an antibody having anti-influenza activity, is useful for treating or preventing influenza.

The invention provides a use of 1,2,3,4,6-penta-O-galloyl-b-D-glucose in the preparation of anti-flu drugs, foods or cosmetics. The 1,2,3,4,6-penta-O-galloyl-b-D-glucose not only has very strong anti-viral activity, but also has activity of inactivating virus, and the activity concentration is out of the range of cytotoxicity, so that the 1,2,3,4,6-penta-O-galloyl-b-D-glucose can directly inactivate the virus, inactivate the contacted virus, lead the virus to lose infection ability or play a therapeutic role to cells infected by the virus, be used for developing drugs, be applied in the food field, such as beverages and the like or the cosmetics field, and be also widely applied in health care products which can prevent and treat the virus.

The invention discloses a method for preparing a key intermediate of an anti-influenza drug peramivir and belongs to the technical field of drug synthesis. The method includes taking a combination of cobalt and iron in a specific ratio as an additive and sodium borohydride as a reducing agent and reacting in an alcohol solvent. The method has the advantages of mild reaction conditions, simplicity and convenience in operation, low cost, high yield and high chiral purity.

The invention belongs to the field of medical chemistry antivirus, 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 application of the novel pyridone derivative or the stereoisomer, the pharmaceutically acceptable salt, the solvate or the crystal thereof in preparation of drugs for prevention or treatment of influenza A type or / and influenza B type and other viral infection diseases, particularly application as a PA subunit cap dependent endonuclease inhibitor in prevention or treatment of influenza A type or / and influenza B type viral infection diseases. The compound disclosed by the invention has remarkable activity of inhibiting influenza incision enzyme and influenza DNA, canbe used 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 shortens the time ofinfluenza infection and reduces the mortality, and has excellent clinical application prospects.

The invention relates to a replication-defective drug-resistant influenza virus and a nucleic acid segment recombination rate detection method thereof. According to the genome sequence of drug-resistant influenza virus strains, 12 drug-resistant influenza virus strains are obtained through a molecular cloning technology, and the drug resistance rate of the drug-resistant influenza virus strains to anti-influenza drugs is evaluated. Seven drug-resistant replication-defective influenza virus strains (DRRIV) are constructed; visual labeled influenza viruses for detecting the recombination rate of each segment of the influenza virus are also constructed. NA28TAG / H274Y with the best effect is screened out. A small molecular NA inhibitor (NAIs) is used in a combined mode, so that the neutralizing effect of the NA28TAG / H274Y on the wild type influenza virus is further enhanced. A mouse model shows that the NA28TAG / H274Y and oseltamivir have a combined synergistic effect on the drug-resistant influenza virus.

The invention discloses tetravalent zanamivir, its preparation method and its application. A structural formula of tetravalent zanamivir is shown as a formula I, wherein m in the formula is a number between 3 and 12. The invention also provides the application of tetravalent zanamivir in the formula I in preparation of medicines for resisting influenza, and the application concretely appears as 1) or 2): 1) the anti-influenza medicines can inhibit enzymatic activity of neuraminidase; and 2)the anti-influenza medicines can inhibit the growth of the cells infected by influenza. The provided tetravalent zanamivir can used for treating various viral influenza. Compared with the current zanamivir, tetravalent zanamivir has anti-influenza virus activity with higher efficiency, and has inhibition effect with high efficiency to the drug-resistant strains of influenza virus; and the provided tetravalent zanamivir can be prepared to oral medicines.

The invention belongs to the field of pharmaceutical preparations and particularly relates to a pharmaceutical composition and novel use of a preparation of the pharmaceutical composition in preparation of an anti-influenza drug. The composition has an inhibiting effect on influenza virus A I-induced pneumonia and can be used for remarkably reducing the death rate of living bodies infected by the influenza virus A I. The death protective effects of a medial-dose group and a high-dose group of the composition are stronger than that of a low-dose group. The composition has a good inhibiting effect to parainfluenza virus 3, influenza virus A I, respiratory syncytial virus, rhinovirus 14 and the like. The composition has a remarkable curative effect in resisting influenza, which is verified by virtue of a pharmacodynamic research method, so that the pharmaceutical composition has a scientific basis in the clinical application in resisting influenza.

An application of the polyose sulfate (marinofloridpolyose sulfate, alpha-D-(1-6)-glucosan sulfate, or porphyran sulfate) in preparing the medicines for preventing and treating viral influenza A or B is disclosed.

The invention discloses an application of tiliroside in preparation of an anti-influenza drug. Prevention and treatment effects on influenza viruses are achieved by inhibiting neuraminidase activity.The invention provides a novel neuraminidase inhibitor, namely tiliroside, from a natural product duchesnea indica extract. The tiliroside can inhibit neuraminidase of influenza virus oseltamivir sensitive strains and drug-resistant strains, makes up for defects in the prior art, and is expected to be popularized and used as a novel neuraminidase inhibitor anti-influenza drug.

The invention discloses a compound shown as a general formula (I) with an anti-influenza effect, an active pharmaceutical ingredient of a pharmaceutically acceptable salt of the compound, and a preparation method of the compound. The compound shown as the general formula (I) can directly inhibit activity of endonuclease for a PA_N target, can kill influenza virus fundamentally, and is used for preparing anti-influenza drugs.

The invention provides recombination sequence information of a key host factor ANP32A / B necessary for replication of an influenza virus in a host. More specifically, the invention relates to a 129-130motif and a 149 site of host factor ANP32A / B protein, which are key active sites for their promotion of influenza virus replication and are potential targeting sites for anti-influenza drugs.

The invention belongs to the field of medicines, and particularly relates to a 2-substituted-5-hexahydropyridazinone-4-carboxylic acid amine derivative, a compound thereof, and pharmaceutically acceptable salts and solvates thereof, comprising hydrates, polycrystals, prodrugs, eutectic crystals, tautomers and stereoisomers. More specifically, the compound provided by the invention can be used as an anti-influenza drug with a CEN inhibition effect.