78 results about "Acyclic nucleoside" patented technology

There are provided, inter alia, acyclic nucleoside phosphonate compounds having reduced toxicity and enhanced antiviral activity, and pharmaceutically accepted salts and solvates thereof. There are also provided methods of using the disclosed compounds for inhibiting viral RNA-dependent RNA polymerase, inhibiting viral reverse transcriptase, inhibiting replication of virus, including hepatitis C virus or a human retrovirus, and treating a subject infected with a virus, including hepatitis C virus or a human retrovirus.

The present disclosure relates, inter alia, to compositions and methods for treating viral diseases and cancer. There are disclosed lipophilic antiviral and anticancer acyclic nucleoside phosphonate diesters, preparation thereof, and methods of using the compounds to treat viral diseases and cancer.

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.

A conjugate compound comprising an acyclic nucleoside phosphonate covalently coupled to a lipid for the therapeutic and / or prophylactic treatment of viral infection in an immunodeficient subject is described, along with compositions and methods of using the same. A preferred conugate compound is CMX001, having formula (I) or a pharmaceutically acceptable salt 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 group is a compound shown in a formula (I) or a formula (II) or its isomer or medicinal salt, which can be used as the prodrug of various nucleoside analogues such as acyclic nucleoside, carbocyclic nucleoside, and furan ring nucleoside, biological activity of the nucleoside compound can be enhanced, so that the derivative can be used for treating virus infection and cancer.

Methods and novel intermediates for the preparation of and the treatment with acyclic nucleoside derivatives of the formula:where one of R1 and R2 is an amino acid acyl group and the other of R1 and R2 is a -C(O)C3-C21 saturated or monounsaturated, optionally substituted alkyl andR3 is OH or H.

The present invention relates to an acyclic nucleoside phosphonate derivative which is useful as an antiviral agent (particularly, against hepatitis B virus), pharmaceutically acceptable salts, stereoisomers, and a process for the preparation thereof.

The present invention provides new (R)-PMPA or (R)-PMPDAP precursor medicine as shown in the expression.

The invention relates to a preparation method and a purpose of a novel nucleoside phosphoramidic acid / phosphonate prodrug simultaneously formed by alkoxide benzyl alcohol and D or L-amino-acid ester. The novel nucleoside phosphoramidic acid / phosphonate prodrug containing alkoxide benzyl is a compound shown by the formula (I) or an isomer or a medicinal salt of the compound. The compound can be used as prodrug of various nucleoside analogs such as acyclic nucleoside, carbocyclic nucleoside and furan ring nucleoside; the bioactivity of the nucleoside compounds are enhanced, so that the application of the compound in the fields of virus infection and cancer treatment is optimized. The formula is shown in the description.

Disclosed herein, inter alia, are acyclic nucleotide analogs and methods of using an acyclic nucleotide analog for treating and / or ameliorating a papillomavirus infection.

Compounds of the Formula Iwhere one of R1 and R2 is -C(O)CH(CH(CH3)2)NH2 or -C(O)CH(CH(CH3)CH2CH3)NH2;the other of R1 and R2 is -C(=O)C3-C21 saturated or monounsaturated, optionally substituted alkyl; andR3 is OH or H;and pharmaceutically acceptable salts thereof have utility as enhanced bioavailability antivirals against herpes and retroviral infections.

There are provided, inter alia, acyclic nucleoside phosphonate compounds having reduced toxicity and enhanced antiviral activity, and pharmaceutically accepted salts and solvates thereof. There are also provided methods of using the disclosed compounds for inhibiting viral RNA-dependent RNA polymerase, inhibiting viral reverse transcriptase, inhibiting replication of virus, including hepatitis C virus or a human retrovirus, and treating a subject infected with a virus, including hepatitis C virus or a human retrovirus.

Disclosed is a non-cyclic nucleotide phosphonic acid represented by formula (I) and its ester derivative, its non-toxic pharmaceutically acceptable salts, or their hydrates or solvates, wherein R1 represents C1-C6 alkyl, X represents NH or S, R2 represents hydrogen, C1-C3 alkyl or halogen substituted alkoxy, C1-C3 alkyl or halogen substituted alkyl, halogen, R3 represents H, C1-C3 alkyl, C1-C3 hydroxyl substituted alkyl or C1-C3 alkyl substituted by more than one halogen atoms, R4 and R5 represent H, C1-C22 alkyl, phenyl, acylorxy or alkyl substituted by more than one halogen atoms. Z represents C or N.

The invention discloses acyclic nucleoside compounds with an HIV-1 / HBV viral replication inhibition activity, preparation methods thereof, and antiviral applications thereof. The invention also discloses a general formula I of the compounds. R1 is hydrogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C5-6 aryl, or C5-12 aralkyl. R2 is a side chain of any natural or pharmaceutically acceptable amino acid. When the side chain contains carboxyl, the carboxyl is esterified optionally by using alkyl or aryl. The invention also discloses preparation methods of the compounds represented by the structural general formula I and a structural general formula II, and medicine compositions comprising the compounds. As a result of experiments, the compounds provided by the invention have the activity of inhibiting HIV-1 / HBV viral replication. One of the compounds has activity higher by more than 385 times that of a current AIDS-treating medicine tenofovir disoproxil fumarate (TDF), and higher fat-solubility than TDF. The compounds can be used in developments of medicines used for treating AIDS or hepatitis B.

The invention provides acyclic nucleoside phosphonate derivatives and their pharmaceutically acceptable salts represented by the formula disclosed in the specification, wherein R1 and R2 represent C1-C3 alkoxy and halogen (un)substituted alkoxy, C1-C3 alkyl and halogen (un)substituted alkyl, halogen, R3 represents hydrogen, C1-C3 alkyl and halogen (un)substituted alkoxy, C1-C3 alkyl and halogen (un)substituted alkyl, halogen, R1, R2, R3 are identical or different, R4 represents H or C1-C3 alkyl, R5 represents H, CH2CF3, OCH2-OOR6, OCOOR6, R6=straight chain or branched chain C1-6 alkyl.

This invention provides trifluoroacetate derivatives of (R)-PMPA or (R)-PMPDAP represented by formula I and their non-toxic biological pharmaceutical acceptable salts, wherein R1 is H or NH2, R2 is H or COO-R3, and R3 is C1-C10 alkyl or phenyl substituted C1-C3 alkyl. This invention also provides drug combinations with acyclic nucleoside phosphonates as shown in formula I and their non-toxic pharmaceutical acceptable salts as active ingredients, and their applications in antiviral drugs, especially in anti-HBV and anti-HIV drugs.

A conjugate compound comprising an acyclic nucleoside phosphonate covalently coupled to a lipid for the therapeutic and / or prophylactic treatment of viral infection in an immunodeficient subject is described, along with compositions and methods of using the same. A preferred conjugate compound is CMX001, having formula (I) or a pharmaceutically acceptable salt thereof.

The present invention discloses a sulfur-containing acyclic nucleoside phosphonate analog and a preparation method, which belongs to the technical fields of medicines and chemistry. The structural formula of the compound of the present invention is shown on the right, wherein, B is one of adenine, guanine, cytimidine, uracil and thymine and the substituted base, X is one of hydrogen, hydroxyl, fluorin, methoxyl and azido, and the carbon atom shown as * is a chiral carbon, which has two types of chiral enantiomers, the R-configuration and the S-configuration. The compound of the present invention can apply the market-purchased three carbon chiral material and can be prepared by a fundamental chain containing a three carbon alkyl side chain, which is obtained by a reaction between the material and a base, protection by an active group, the introduction of sulfur atoms, the linkage of a phosphonic acid-containing side chain and the removal of the protective group. The synthesis method of the present invention has the advantages of easy acquirement of materials, mild reaction conditions and convenient operation.

The present disclosure relates, inter alia, to compositions and methods for treating viral diseases and cancer. There are disclosed lipophilic antiviral and anticancer acyclic nucleoside phosphonate diesters, preparation thereof, and methods of using the compounds to treat viral diseases and cancer.

The invention discloses a novel benzyl amido phosphate structure shown as a formula (I). The novel benzyl amido phosphate ester structure can be taken as a prodrug of various nucleoside compounds (including acyclic nucleoside, carbocycle nucleoside, furan ring nucleoside and the like) for enhancing the bioactivity of the nucleoside compounds, so that the novel benzyl amido phosphate ester structure is applied to treatment of virus infection and cancers.

The invention provides a preparation method of an acyclic nucleoside antiviral drug phosphoric acid monoester compound. Acyclic nucleoside antiviral drugs like Adefovir or Viread are used as raw materials to react with liposoluble long-chain alkyloxy-ethanol / propyl alcohol to obtain the object compound. The invention overcomes insufficiencies of a prior art, can increase quality of Adefovir or Viread as well as reduce production cost, and is convenient for operation and easy for industrialized production.

The invention relates to the field of pharmaceutical chemistry, specifically, the invention relates to a type of purine compounds with structure shown in structural formula (I) and its pharmaceutically-acceptable inorganic or organic salt crystal hydrate and solvate capable of treating hepatitis B, and its preparation method and use, and composition containing the compound. The inventive purine compounds have strong antiviral activity, and are especially suitable for treating hepatitis B.

The present invention is directed to branched chain nucleoside phosphonate ester compounds and methods of synthesis thereof. The present invention is also directed to pharmaceutical compositions comprising branched chain nucleoside phosphonate ester compounds and methods of treating and / or preventing double stranded DNA viral infection and / or viral infection associated disease or disorder.

Methods and novel intermediates for the preparation of acyclic nucleoside derivatives of the formula: where one of R1 and R2 is an amino acid acyl group and the other of R1 and R2 is a —C(O)C3-C21 saturated or monounsaturated, optionally substituted alkyl and R3 is OH or H; or a pharmaceutically acceptable salt thereof.

The invention belongs to the technical field of chemical synthetic drugs, and particularly relates to acyclic nucleotide analogs as well as a preparation method and an application of the acyclic nucleotide analogs in antiviral drugs. The technical problem to be solved by the invention is to provide a new class of acyclic nucleotide analogs which has the structure shown as the formula I. The acyclic nucleotide analogs provided by the invention has an antiviral pesticide effect, and provides a new choice for the development of antiviral drugs.

The invention provides a new acyclic nucleoside phosphonate compound as well as a composition, a preparation method and application thereof, in particular an acyclic nucleoside phosphonate compound presented in a general formula (1), an inorganic salt or an organic salt pharmaceutically accepted and a composition containing the compound of the general formula (1). The invention also provides the preparation method of the compound and the application of the compound of the general formula (1) to the treatment of virus infective diseases, in particular virus infective diseases caused by an HBV virus or an HIV virus.

The invention discloses acyclic nucleoside phosphonate compounds or pharmaceutically acceptable salts thereof shown in the formula (I), a preparation method, application, intermediate compounds thereof, and a medicinal composition containing the same. The acyclic nucleoside pyrimidine phosphonate compounds per se have no cytotoxicity, high activity of tumor and virus resistance and high selectivity; and the preparation method has low cost and high product yield.

The present invention provides a novel R-PMPA predrug as shown in formula I and various medical salts thereof. Meanwhile, the present invention also relates to a medical composition using the compounds as active ingredients and an application of the medical composition as an antiviral drug, particularly a drug for treating and preventing hepatitis B and AIDS viruses.

Induction of telomere shortening, G2 arrest and apoptosis in telomerase positive cancer cells using acyclic nucleoside analogs has been disclosed. In addition, methods for impairment or prevention of tumorigenic telomerase positive cells from having a chance to grow into a tumor and methods for promoting tumor regression (decrease in size of an established tumor) using acyclic nucleoside analogs has been disclosed.