155 results about "Oseltamivir" patented technology

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.

Antimicrobial compositions containing two or more antiviral agents coupled to a polymer and methods of making and using the compositions, are described herein. In one embodiment, two or more antiviral agents are covalently coupled to the polymer. Suitable antiviral agents include, but are not limited to, sialic acid, zanamivir, oseltamivir, amantadine, rimantadine, and combinations thereof. The polymer is preferably a water-soluble, biocompatible polymer. Suitable polymers include, but are not limited to, poly(isobutylene-alt-maleic anhydride) (PIBMA), poly(aspartic acid), poly(l-glutamic acid), polylysine, poly(acrylic acid), plyaginic acid, chitosan, carboxymethyl cellulose, carboxymethyl dextran, polyethyleneimine, and blends and copolymers thereof. In another embodiment, the compositions contain a physical mixture of polymer containing one antiviral agent and polymer containing a second antiviral agent. The compositions can be formulated for enteral or parenteral administration. Suitable oral/intranasal dosage forms include, but are not limited to, tablets, capsules, solutions, suspensions, emulsions, syrups, and lozenges. Suitable dosage forms for parenteral administration include, but are not limited to, solutions, suspensions, and emulsions. The compositions described herein are effective at treating a variety of infections, including viral infections such as influenza, while inhibiting or preventing the development of microbial resistance.

The invention relates to the field of medical chemistry, in particular to derivatives of oseltamivir (I). R1, R2, L and X are explained in the specifications. The invention also discloses a method for preparing the derivatives of oseltamivir and the purpose of the derivatives for treating infectious diseases, particularly the infectious diseases caused by influenza viruses. The oseltamivir is shown in the description.

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 a new method for preparing an intermediate (VI) of oseltamivir shown in a formula (I). Starting from a known intermediate (II) reported in a document, chiral acetyl ammonia is built based on a key lossen rearrangement reaction step to obtain a known oseltamivir intermediate structure in the document, so that the use operation of the dangerous sodium azide is avoided, and the high reaction yield is maintained. The method has the advantages that operation is safe and convenient, cheap raw materials are cheap and available. The formula is shown in the specification.

The invention discloses a synthesis method of oseltamivir. The synthesis method of oseltamivir comprises the following steps: starting from a compound 1,3-butadiene-3-amyl ether and compound 3-nitro-ethyl acrylate, carrying out Diels-Alder reaction, then reacting at room temperature in acetonitrile in the presence of a copper catalyst and PhI-NNs to prepare an aziridine compound in a one-pot method, wherein the mole ratio of the 1,3-butadiene-3-amyl ether to 3-nitro-ethyl acrylate to the copper catalyst is 1.1: 1: 0.025-0.1; and finally synthesizing the oseltamivir for preventing bird flu through the aziridine ring opening, nitryl and p-nitrobenzene sulfonyl removal, acetylation and hydrogenation. The method comprises short steps, the used reagent is cheap and easily available, the operation is simple, the total yield is up to 40%, and the method is a simple and efficient synthesis method of oseltamivir.

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 present invention provides methods for producing shikimic acid. In particular the invention provides methods for producing and isolating shikimic acid from a microorganism. Additionally, the invention provides methods for synthesizing compounds such as oseltamivir and 6-fluoroshikimic acid using shikimic acid produced from microorganisms.

The invention discloses a preparation method of an oseltamivir acetyl aziridine intermediate I (shown in a figure 1). The preparation method is characterized in that the oseltamivir acetyl aziridine intermediate I is prepared through six chemical synthesis steps (in figure 2) by taking a shikimic acid epoxy derivative II as a raw material, wherein the yield is 44 to 61 percent. The preparation method comprises the following six chemical synthesis steps: (1) carrying out ring opening in a 3-site of an epoxy compound II, and carrying out 'one-pot' three-step tandem reaction, thus forming 3,4-aziridine compound III; (2) selectively attacking the 3-site by 3-pentanol, and carrying out the ring opening, thus obtaining a compound IV; (3) removing an allyl group in a 4-site, thus obtaining a compound V; (4) carrying out amino acetylization in the 4-site, thus obtaining a compound VI; (5) carrying out hydroxyl methyl sulfonylation in a 5-site, thus obtaining a compound VII; (6) attacking 5-site by a 4-acetamino group, and carrying ring closing, thus obtaining the oseltamivir acetyl aziridine intermediate I.

The present invention provides compositions and methods for inhibiting the replication of influenza virus by administering thiophosphonoformic acid alone or in combination with a neuraminidase inhibitor, for example, oseltamivir.

A process is provided for the synthesis of 4,5-diamino cyclohexene carboxylate ester (1): or a pharmaceutically acceptable salt thereof. R¹-R³ are a silyl-, an aliphatic, alicyclic, aromatic, arylaliphatic, or an arylalicyclic group. R⁴, R¹¹ and R¹² are H, a silyl-group, an aliphatic, alicyclic, aromatic, arylaliphatic, or an arylalicyclic group. 3,4-Dihydropyran compound (9): with R⁵ and R⁶ being suitable protecting groups, is reacted to form aldehyde (4): which is oxidized and converted to N-substituted carbamate (3): with R⁷ being a suitable protecting group. (3) is, via oxazolinidone (13): converted to azido carboxylate ester (2): and then to 4,5-diamino cyclohexene carboxylate ester (1).

The invention discloses a non-biological method for screening effective antivirus components in traditional Chinese medicines. The method comprises the following steps: taking an influenza virus specific drug oseltamivir (OS) as the template molecule, taking acrylamide and 4-vinylpyridine as the functional monomers, carrying out synthesis to obtain non-covalent oseltamivir molecular imprinting polymer (OS-MIP), taking the OS-MIP as the stationary phase to prepare a liquid chromatographic column through a wet method, carrying out affinity screening on effective component groups of traditional Chinese herbals and compounds, identifying the compound components with affinity through mass spectrum, then carrying out in-vitro anti-virus experiments to verify the compound activity, and finally finding the compounds, which have the same antivirus activity as the template molecule, in the traditional Chinese medicines. The method can also be modified to screen and verify other active compounds so as to shorten the screening process of drug entities and promote the research process of replacement drugs, and has a very important meaning and wide application prospect in the field of non-biological drug screening methods.

The invention discloses an analysis method for separating and detecting an oseltamivir phosphate intermediate and impurities thereof, belongs to the field of analytical chemistry, and particularly relates to an analysis method for carrying out gradient elution on the oseltamivir phosphate intermediate by taking pentafluorophenylsilane bonded silica gel as a filler, water-perchloric acid as a mobile phase A and acetonitrile-methanol as a mobile phase B. The method can realize effective separation and detection of the oseltamivir phosphate intermediate and the specific impurities thereof, has the characteristics of high detection sensitivity and accurate and reliable detection result, and provides a reliable reference method for quality research on separation and detection of the oseltamivir phosphate intermediate and the specific impurities thereof.

The invention belongs to the technical field of organic synthesis, aims at solving the problems that an existing synthesis method of oseltamivir is multiple in reaction steps, low in overall yield and high in cost. The invention provides a synthesis method of oseltamivir. The method comprises the following steps of (1) adopting 3-pentyloxy acetaldehyde and nitroolefin as substrates and reacting under catalysis of a catalyst in the presence of lewis acid to obtain an aldehyde intermediate A; (2) reacting the obtained aldehyde intermediate A with 2-diethoxy oxygen-phosphorus acrylic acid ethyl ester under the action of an alkali catalyst to obtain a cyclohexenyl intermediate B; (3) reacting the cyclohexenyl intermediate B with thiocresol to obtain a cyclohexane intermediate C; (4) preparing a compound D from the cyclohexane intermediate C under the action of zinc powder and trimethylchlorosilane; and (5) obtaining a final product oseltamivir from the intermediate D obtained in the step (4) under the action of an ammonia gas and potassium carbonate. The method has the characteristics that the route is short and the catalyst is easy to recover.

The invention provides an improved oseltamivir phosphate medicinal composition, which comprises an effective amount of oseltamivir phosphate for treating or preventing diseases, at least one beta cyclodextrin or cyclodextrin derivative and one or more optional pharmaceutically acceptable excipients. The invention also provides the application of a solid medicinal composition to the preparation of an oral liquid medicament. The invention further provides a liquid medicinal composition which comprises the medicinal composition and a water-containing medium. The medicinal composition has an excellent effect as specified in the specifications.

The invention provides the application of quercetin in the preparation of medicine for preventing or treating diseases caused by influenze virus, adenovirus, staphylococcus aureus and/or streptococcus hemolyticus and the like, and a pharmaceutical composition thereof. The pharmaceutical composition has the activity for resisting the influenze virus being equivalent to oseltamivir.