38 results about "HIV-1 protease" patented technology

The invention relates to a combination of treatments, more particularly a combination treatment for HIV-1 infection. The present invention is directed to the use of bryostatin-1 and their natural and synthetic derivatives for AIDS therapy, in particular to the use of bryostatins in combination with other active drugs such as Histone Deacetylases (HDACs) inhibitors and anti-retrovirals, for the treatment of HIV-1 latency. According to the present invention, we provide a combination therapy for the treatment of HIV-1 latency which employs bryostatin-1 (and analogues) and one of the following HDAC inhibitors; valproic acid, butyrate derivatives, hydroxamic acids and benzamides. While HDACi can be used in continuous dosing protocol, bryostatins can be used following a cyclical dosing protocol. Bryostatins can be formulated in pharmaceutical acceptable carriers including nanoparticles, phospholipids nanosomes and / or biodegradable polymer nanospheres. This combination therapy needs to be used in patients treated with antiretroviral therapy (HIV-1 protease inhibitors, HIV-1 reverse transcriptase inhibitors, HIV-1 integrase inhibitors, CCR5 co-receptor inhibitors and fusion inhibitors).

A mammalian protein, like the human serum transferrin (HST), is modified with an inserted peptide sequence flanked at both ends by cleavage sites. The peptide insert contains a motif known to induce apoptosis in cells and the cleavage sites are specific for the viral protease of HIV-1. The delivery of such recombinant transferrin into an HIV-1 infected cell results in the release of the peptide which then induces apoptosis. The peptide is inserted into surface exposed loops of the N-terminal lobe of the HST containing the RGD motif flanked by two modified p17 / p24 HIV-1 protease cleavage sites. When delivered to the infected cell the cleavage of the loop inserted sequences by the HIV-1 protease results in the release of the central RGD-containing peptide sequences. Peptides containing the RGD motif (arginine, glycine, aspartic acid) have been shown to induce cell apoptosis even in small concentrations.

Inhibitors of HIV-1 protease and compositions containing them are described. Use of the inhibitors and compositions containing them to treat HIV, AIDS, and AIDS-related diseases is described.

The present invention discloses a novel combination therapy for HIV-1 treatment relying on a combination of at least one CCR5 antagonist, at least one HIV-1 protease inhibitor and at least one pharmacokinetic enhancer of said at least one CCR5 antagonist and / or at least one HIV-1 protease inhibitor. The combination is intended for use in oral treatment of a disorder selected from the group consisting of HIV-1 infection, retroviral infections genetically related to HIV and AIDS, in a treatment-naïve patient infected with CCR5 tropic HIV-1 virus.

The invention belongs to the technical field of medicine and relates to a tertiary amine derivative as shown as the general formula I, and pharmaceutically acceptable salt or a prodrug of the tertiary amine derivative. Results of experimental studies show that the tertiary amine derivative has higher capacity of inhibiting the activity of HIV-1 (human immunodeficiency virus-1) protease and is expected to be developed into an effective drug for resisting Aids.

The present invention provides a therapeutic compound of formula (I) and their pharmaceutically acceptable salts for the prevention and treatment of lipodystrophy caused because of HIV infection or combination therapy of HIV-1 protease inhibitors (PIs) and / or reverse transcriptase inhibitors (nRTIs) by neutralizing lipohypertrophy, lipoatrophy and metabolic abnormalities in HIV patient.

The invention provides an application of stilbene glucosides in preparing drugs for treating and preventing AIDS. Structural formulas of the stilbene glucosides are show as a general formula (I), wherein R1, R2, R3, R4, R5 or R6 independently represent hydrogen, hydroxyl, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 acyloxy, halogen, nitryl, trifluoromethyl or a cyano group, and pre-conditions are that at least one of R1, R2 and R3 is the hydroxyl, at least one of R4, R5 and R6 is the hydroxyl, and at least one hydroxyl of R1, R2, R3, R4, R5 and R6 is connected with sugar. In the compounds represented by the general formula (I), an inhibitory activity (IC50) for the HIV-1 protease of 2,3,5,4-tetera-hydroxystilbene-2-O-beta-D-glucoside of the stilbene glucosides for reaches 126 [mu]M.

The present invention provides an oligopeptide compound with an amino acid sequence of Tyr-Leu-Val-Leu-His (SEQ ID NO:1) and HIV-1 protease inhibitory activity. The oligopeptide compound provided by the invention can be produced from chemical synthesis, or recombination, or microorganism (particularly actinomycetes) extraction. The invention also provides an extract obtained from microorganism (particularly actinomycetes) and having HIV-1 protease inhibitory activity and a preparation method thereof. The extract contains the oligopeptide compound provided by the invention. The invention also provides microorganisms (particularly actinomycetes, such as Actinomyces CGMCC 4766) for obtaining the oligopeptide compound or extract provided by the invention. The oligopeptide compound or extract provided by the invention can be used for prevention and treatment of HIV infection related diseases, such as AIDS.

The invention provides a nucleic acid base compound or a medically acceptable salt thereof. The compound or the medically acceptable salt thereof has the obvious inhibitory HIV protease and / or reversetranscriptase activity; toxicity studies show that the compound has the good druggability, it is indicated that the compound has a good application prospect by serving as an anti-AIDs drug. Accordingto experimental data, the compound has inhibitory activity on HIV-1 protease and HIV-1 reverse transcriptase, and low cytotoxicity exits. The nucleic acid base compound or the medically acceptable salt thereof is expected to become a double-target inhibitor inhibiting the HIV protease and the reverse transcriptase simultaneously.

The invention provides an amide derivative or a pharmaceutically acceptable salt thereof with the structure as shown in formula I. A compound or the pharmaceutically acceptable salt thereof has significant activity in inhibiting HIV protease and reverse transcriptase; toxicity study shows that the compound or the pharmaceutically acceptable salt thereof has better druggability, and the compound has better application prospect in using as anti-Aids drugs. According to experimental data, the compound has inhibiting activity both on HIV-1 protease and HIV-1 reverse transcriptase and has lower cytotoxicity. The compound or the pharmaceutically acceptable salt thereof is expected to be a double-target inhibitor which can inhibit the HIV protease and the reverse transcriptase.

The invention provides a method for screening an HIV protease inhibitor based on combination of a fluorogenic substrate and crystal soak. The method comprises the steps of measuring inhibitory activity of a series of compounds that are separated and purified from natural products to the HIV-1 protease; and finally separating and purifying the series of compounds into a single component, wherein the single component is a small molecular inhibitor of the natural products. With the above method, the extract of the Berberis nummularia Bge is found to have effective inhibitory activity for the HIV-1 protease; small molecules with relatively strong combination capacity for the HIV-1 protease are found via the crystal soak method; then the inhibitory activity of the small molecules to the HIV-1 protease is determined via enzyme activity assay; and finally a small molecular inhibitor capable of effectively inhibiting the activity of the HIV-1 protease is provided. Besides, a method for screening anti-HIV materials by the combination of the small molecular substance and an HIV protease compound is provided, novel sites that the HIV protease can interact to the inhibitor are provided, and a method for screening the anti-HIV active materials by using the sites is provided.

Compounds of the formula I:whereinR1, R2, X and N are as defined in the specification;E is N, CH;A′ and A″ are terminal groups as defined in the specification.The compounds have utility as HIV-1 protease inhibitors.

The invention provides an application of a traditional Chinese medicine Cassia fistula L. fruit in preparing medicines used for treating AIDS, and especially in preparing medicines used for inhibiting HIV-1 protease. A Cassia fistula L. fruit ethyl acetate extract provided by the invention has an HIV-1 protease activity inhibition rate of 83.4%. IC50 of HIV-1 protease inhibition activity of piceatannol separated from Cassia fistula L. fruit is 59mum.

The invention provides a purpose of a Chinese medicine lychee seed in preparing of drugs for treating aids, and particularly provides a purpose in preparing of drugs for restraining HIV-1 protease. The IC 50 value of extractives for inhibitory activity of the Chinese medicine lychee seed to the HIV-1 protease is 10.34 microgram per milliliter.

A mammalian protein, like the human serum transferrin (HST), is modified with an inserted peptide sequence flanked at both ends by cleavage sites. The peptide insert contains a motif known to induce apoptosis in cells and the cleavage sites are specific for the viral protease of HIV-1. The delivery of such recombinant transferrin into an HIV-1 infected cell results in the release of the peptide which then induces apoptosis. The peptide is inserted into surface exposed loops of the N-terminal lobe of the HST containing the RGD motif flanked by two modified p17 / p24 HIV-1 protease cleavage sites. When delivered to the infected cell the cleavage of the loop inserted sequences by the HIV-1 protease results in the release of the central RGD-containing peptide sequences. Peptides containing the RGD motif (arginine, glycine, aspartic acid) have been shown to induce cell apoptosis even in small concentrations.

Described are novel protease inhibitors and methods for using said protease inhibitors in the treatment of human immunodeficiency virus (HIV) infection.

Inhibitors of HIV-1 protease and compositions containing them are described. Use of the inhibitors and compositions containing them to treat HIV, AIDS, and AIDS-related diseases is described.

The invention relates to a new synthetic method of an HIV-1 protease inhibitor, Atazanavir, which adopts a convergent-typed synthetic strategy, introduces a construction unit, methoxycarbonyl-tert-lencyl, as an N atom protecting group in the whole early synthetic stage, and takes the diastereomeric selective reduction of aminoketone as the key and final reaction step of the new process. The method comprises the steps that: the compound of formula V, namely, N-1-[N-(methoxycarbonyl)-L-tert-leucine]-N-2-[4-(2-pyridyl)-phenmethyl]hydrazine, and the compound of formula VI, namely, (S)-1-((S)-4-chlorine-3-carbonyl-1-phenyl butane-2-yl-2-amino)-3, 3-dimethyl-1-carbonyl butane-2-yl-methyl carbamate, are treated with nucleophilic substitution reaction to generate the compound of formula VII, namely, 1-[4-(2-pyridyl)phenyl]-5(S)-2, 5-bis{[N-(methoxycarbonyl)-L-tert-leucineyl] amino}-4-carbonyl-6-phenyl-2-azahexane; and the compound of formula VII is treated with reduction reaction to generate the Atazanavir. The invention has the advantages of less process route steps, easily-controlled reaction conditions, simple and convenient operation, low-price and easily-obtained raw material, high product yield, low cost and being suitable for large-scale production.

The invention provides a lignin compound and functions thereof. The structural formula of the lignin compound is as shown in a general formula (I), wherein R1 is from an alkyl group of C1-C4 or an alkyl acyl group of the C1-C4, and R2 is from hydrogen or the alkyl group of the C1-C4 or the alkyl acyl group of the C1-C4. The lignin compound can effectively inhibit activity of human immunodeficiency virus-1 (HIV-1) protease, and inhibitory activity IC 50 of a compound 5-allyl-5'-(1-ethyoxyl-2-hydroxy-propyl group)-biphenyl-2,2'-diphenol on the HIV-1 protease is 200uM.

The invention provides a nucleic acid base compound or a medically acceptable salt thereof. The compound or the medically acceptable salt thereof has the obvious inhibitory HIV protease and / or reversetranscriptase activity; toxicity studies show that the compound has the good druggability, it is indicated that the compound has a good application prospect by serving as an anti-AIDs drug. Accordingto experimental data, the compound has inhibitory activity on HIV-1 protease and HIV-1 reverse transcriptase, and low cytotoxicity exits. The nucleic acid base compound or the medically acceptable salt thereof is expected to become a double-target inhibitor inhibiting the HIV protease and the reverse transcriptase simultaneously.

The invention relates to novel application of NCI compounds, specifically to novel application of the NCI compounds with accession numbers of NSC111887 and NSC121217 in inhibition of the activity of HIV type 1 protease. According to the invention, through integration of conventional anti-HIV-1 protease drug and inhibitor data, computational simulation and an in-vitro compound screening method, molecules of the compounds with the accession numbers of NSC111887 and NSC121217 are found out for the first time, and the compound molecules have the structural characteristics of tripeptide derivatives, certain inhibition capability on the activity of HIV-1 protease and 50% inhibiting concentrations of 62 mu M and 162 mu M, respectively.

The present invention relates to a mutant HIV-1 (Human immunodeficiency virus-1) protease capable of effectively enhancing cell-mediated immune responses to DNA vaccination, and use of a nucleic acid encoding the same as a vaccine adjuvant. The mutant HIV-1 protease according to the present invention has inactivated or attenuated proteolytic activity, while retaining chaperone-like activity. When the mutant HIV-1 protease is used together with a DNA vaccine against the HIV-1 envelope protein or the HPV antigen (E6 or E7), cell-mediated immune responses can be effectively enhanced for the prevention or treatment of AIDS or cervical cancer.

The present invention relates to a yeast screening assay for the identification of suppressors of a protease, such as the HIV-I protease and / or HIV-2 protease, for example. Upon overexpression of HIV-I protease in Schizosaccharomyces pombe, for example, the cell dies, but in the presence of a candidate inhibitor with protease suppressor activity, the cell lives, thereby providing an assay for the identification of one or more suppressors. In additional aspects, there is an in vivo protease activity screen, used alternatively or additionally to a viability screen, such as for cleavage of a HIV-I protease-specific site. In further aspects, the suppressor is employed for the treatment of an individual infected with HIV virus or with AIDS.