38 results about "HIV-1 protease" patented technology

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 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 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 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.

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.

Novel compounds and compositions for treating patients in need of relief from HIV, AIDS, and AIDS-related diseases are described. Methods for treating HIV, AIDS, and AIDS-related diseases using the compounds described herein are also described.

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.

Various embodiments of the present invention relate to, among other things, compounds and methods of using those compounds to treat an HIV infection. The compounds of the various embodiments of the present invention provide, among other things, therapeutic agents having enhanced penetration capability across the blood-brain barrier, such that they can enter the CNS to treat an HIV-1 infection in the CNS.

The invention relates to the design of inhibitors of the HIV-1-PR homodimer which do not create resistance, by blocking the folding of single monomers with the help of peptides which attach to highly-conserved sites of the monomers.

Various embodiments of the present invention relate to, among other things, compounds and methods of using those compounds to treat an HIV infection. The compounds of the various embodiments of the present invention provide, among other things, therapeutic agents having enhanced penetration capability across the blood-brain barrier, such that they can enter the CNS to treat an HIV-1 infection in the CNS.

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 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.