33 results about "Hiv 1 integrase" patented technology

Pharmacophore models to be used in drug design and discovery are provided. An in silico protocol and in vitro assays are presented. Compounds and their pharmaceutically acceptable salts with HIV-1 integrase inhibitory and anti-HIV activity and use thereof in the treatment of HIV/AIDS and related infections either alone or in combination with all the known antiretroviral therapeutics are described.

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).

The invention relates to a 5-chlorol-2-hydroxyl-3-(4-substituted-1H-1,2,3-triazole) benzoic acid compound expressed in the formula (I) as well as a preparation method and application thereof. The definition of R is shown as the specification. In the preparation method, 5-chlorolsalicylic acid used as a raw material is nitrified and reduced, is subjected to azidation and reacts with end alkyne to obtain the corresponding 5-chlorol-2-hydroxyl-3-(4-substituted-1H-1,2,3-triazole) benzoic acid compound. The compound has the inhibiting function on HIV-1 integrase, and the IC50 of part of the compound reaches 1.6 mircograms/mL, therefore, the compound is a stronger HIV-1 integrase inhibiting agent and is expected to be developed into a new HIV virus resistant medicament.

Peptides comprising an Rpt1 domain of an INI1/hSNF5 which inhibit HIV-1 production in a human cell, and vectors encoding those peptides are provided. Also provided are methods of inhibiting HIV-1 production in a cell, or spread of the HIV-1 to another cell, by treating the cells with the above peptides or vectors. Other methods of inhibiting HIV-1 production in a cell, or spread of the HIV-1 to another cell, by inhibiting production of INI1/hSNF5 are provided. Additionally, methods of determining whether a test compound inhibits HIV-1 virion production in a mammalian cell, or spread of the HIV-1 to another cell, are provided. Those methods comprise determining whether the test compound inhibits the production of INI1/hSNF5 or disrupts the interaction of HIV-1 integrase with INI1/hSNF5.

The invention relates to an HIV-1 integrase expression bacterial strain and an integrase inhibitor in-vitro screening model. In the model, HIV-1 integrase soluble expression plasmid and expression plasmid with integrase LTR sequence are firstly established based on gene engineering technology, and established recombinant plasmid pET28a-IN is transferred into commercial colibacillus BL21 to obtainthe integrase expression bacterial strain; and then the integrase expression bacterial strain is cultured in large-scale, finally integrase is separated and purified, works on the substrate plasmid and is added into samples to measure the activity. The detection model overcomes the defects such as high cost, high background and more influence factors in the existing ELISA detection method; the detection model can carry out primary screening on various natural or chemically synthetic integrase inhibitors in-vitro largely and quickly; and the detection model is an HIV-1 integrase in-vitro screening model with the advantages of quick operation, flexibility, fewer interference factors and low cost.

The present invention provides one kind of integrase inhibiting peptide, which is selected from seven kinds of organic polypeptide compounds, a, b, c, d, e, f and g, with molecular weight of 974.3, 770.8, 822.9, 830.9, 849.0, 789.8 and 788.8 separately, is water soluble, and has amino acids connected through peptide bond and capacity of inhibiting the activity of HIV-1 integrase. The organic polypeptide compound of the present invention can inhibit the activity of HIV-1 integrase, and block the proliferation and life period of virus DNA in host cell, and may be applied in preparing medicine for treating AIDS. The present invention may be also used in the further research of integrase structure, action mechanism and AIDS-treating medicine.

Isolated peptides comprising sequences derived from the protein integrase of HIV-1, as well as their analogs, mixtures, conjugates with permeability enhancing moieties, and pharmaceutical compositions are disclosed. The peptides and compositions are capable of selectively killing HIV-1 infected cells and are used in treatment of HIV infection and AIDS.

The present invention discloses non-catechol compounds, such as thiazolothiazepines, and analogs and derivatives thereof, which are anti-integrase inhibitors. The compounds, which are useful as treatments for HIV disease, include compounds (I), (II), (III), or pharmaceutically acceptable salts thereof wherein A is thiazole, benzene, naphthalene, pyridine, pyrimidine, pyrazine, or quinoline; R is one or more of H, halogen, lower alkyl, lower alkoxy, NO₂, lower ester or carboxylic acid; X—Y is CH₂—S, S—CH₂, CH₂—O, CH₂—S(O). S(O)—CH₂, CH₂—CH₂, CH₂—CH₂—CH₂, or CH₂—CH₂—CH₂—CH₂; R₄ is H or hydroxy; R₅ is H, phenyl, or alkylamine; W is S or O; and R₆ is H, substituted or unsubstituted alkyl or amine; and Z is S, O, CH₂, CH₂CH₂, or C═O.

The present invention discloses a construction method of an HIV-1 integrase mutant library. The method comprises the following elements: (1) manufacturing gaps on random sites of a target gene by using transposition of transposon and restriction enzyme on both ends of the transposon, inserting mutation insertion boxes, using the restriction enzyme sites on the box to achieve replacement of three bases on the gene through digestion self-connection, and translating the target gene into protein to cause mutation o one or two consecutive amino acids on the target protein; and (2), using site-directed mutagenesis PCR to realize mutation of three bases, for the replacement of the original target gene and on the inserted mutation insertion boxes, from codons encoding cysteine into codons encoding other 19 amino acids, thereby increasing the diversity of the final mutant library.

The present invention discloses symmetric and asymmetric m-hydroxybenzoic acid dimer compounds with constitutional formula (I), and as well as a method of the preparation of and the function of such products. Basic framework m-hydroxybenzoic acid and as well as hydroxybenzoic acid replaced by the same or different hydroxyl groups are condensed into m-hydroxybenzoic acid dimer compound with a parent nucleus symmetric structure and with the replacement of the same or different number of hydroxyl groups, the pharmacological test proves that the product has the activities of anti-human papillomavirus, herpes virus and resist HIV-1 integrase inhibitors; the product is capable to resist the virus that can integrally enter the chromosome of human cell, inhibit the breeding of the virus that integrally enter into the chromosome, prevent the relapse of virus infection; in addition, the product has antitumor activity.

The invention discloses a drug for treating acquired immunodeficiency syndrome (AIDS) and a preparation method thereof. The chemical structure of the drug is a formula (I), when the concentration is 5 micrograms per milliliter, the inhibition rate of a compound HIV-integrase shown in the formula (I) is from 45% to 95%, and the inhibition rate of Ib is up to 94.8% and exceeds that of a listed drug Elvitegravir. The inhibition rate of Ia is relatively low and less than 50%. The compound shown in the formula (I) can be taken as a HIV-integrase inhibitor and used for treating the acquired immunodeficiency syndrome (AIDS).

The disclosure generally relates to compounds of formulas (I) and (II)7 including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV-1 integrase, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

The invention provides an HIV-1 integrase inhibitor phospholipid complex, a preparation method and applications thereof, wherein a mass ratio of the HIV-1 integrase inhibitor to the phospholipid is 1:1-20. According to the present invention, the complex formed by HIV-A5 and phospholipid can effectively improve the hydrophilicity and the lipophilicity of drugs, the phospholipid has good biologicalaffinity, the in vivo absorption capacity is improved, and the bioavailability is improved.

The invention provides an HIV-1 (human immunodeficiency virus-1) integrase inhibitor tablet and a preparation method thereof. The preparation method includes the steps: mixing an HIV-1 integrase inhibitor HIV-A5 with pharmaceutically acceptable auxiliary materials; pressing the materials to prepare the HIV-1 integrase inhibitor tablet. The method is simple in preparation process, mechanical in production, high in automation degree, large in output and low in cost, and the prepared HIV-1 integrase inhibitor tablet is high in dissolubility, short in disintegration time, stable in quality and convenient to carry, transport and store and is a solid preparation.

The invention relates to a novel 2, 4-disubstituted amino-6-substituted-(1, 3, 5) triazine or a 1, 3-pyrimidine derivative, the preparation method, a drug combination and the pharmacological usage; the structure general formula is shown as the formula (I), wherein, the definitions of R1, R2, R3, R4, R5, R6, A, B, X, Y and Z are described in an instruction. The compounds and a HIV-1 integrase have high binding activity and can effectively inhibit the binding of the integrase with a substrate in a substrate competition test. Therefore, the compounds are stronger HIV-1 integrase inhibitors, which are expected to be developed into new anti-HIV drugs.

A method of inhibiting drug-resistant HIV-1 integrase in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or ester thereof, having a structure of: wherein X is N, C(OH), or CH; Y is H or OH; each of Z1-Z5 is independently H or halogen; R4 is H, OH, NH2, NHR8, NR8R9 or R8; R5, R6, and R7 is each independently H, halogen, OR8, R8, NHR8, NR8R9, CO2R8, CONR8R9, SO2NR8R9, or R5 and R6 together with the carbon atoms to which R5 and R6 are attached form an optionally-substituted carbocycle or optionally-substituted heterocycle; and R8 and R9 is each independently H, optionally-substituted alkyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted cycloalkylene, optionally-substituted heterocycle, optionally-substituted amide, optionally-substituted ester, or R8 and R9 together with the nitrogen to which R8 and R9 are attached form an optionally-substituted heterocycle.

The present invention discloses one kind of compound, citiofuran. The compound, citiofuran has very high combination activity, KD=16.4 microM, with HIV-1 integrase, and effective inhibition of the combination of the integrase to the substrate, IC50=120 microM, in substrate competition test. Therefore, the compound exhibits very high medicine preparing value.

The invention provides an HIV-1 integrase inhibitor solution agent, a preparation process and applications thereof, wherein the HIV-1 integrase inhibitor HIV-A5 solution agent comprises: HIV-A5, wherein the mass concentration (g/ml) of the HIV-A5 in the solution agent is 0.3-5%; a solvent, wherein the solvent comprises at least one selected from 10-50% of ethanol, 5-15% of propylene glycol and 1-10% of glycerol and at least one selected from 1-10% of Tween 80 and 10-35% of Poloxamer 188; and optionally a coloring agent and a flavoring agent, wherein the mass concentrations (g/ml) of the coloring agent and the flavoring agent in the solution agent respectively are 0.01-0.09% and 0.01-0.1%. According to the present invention, the preparation process is simple; the drug is uniformly dispersedin the form of small molecules in the solvent, and is quickly absorbed by the body after the drug enters the body so as to quickly enter the tissue, the in vivo absorption capacity is improved, the bioavailability is high, the drug can be taken orally, and the medication is convenient.

The invention provides a preparation method of a fungal extract for inhibiting human immunodeficiency virus (HIV-1). The dependent bacterial strain is hypoxylon fungi Q-s-4(hypoxylon sp.). The fungi Q-s-4 is fermented and cultured in liquid to prepare extract of fermentation products. The method can be applied to the mass industrial culture of fungi Q-s-4 and industrial production of extract of fermentation products by taking fermentation products as the raw materials. The extract prepared by the method has a prominent activity on inhibiting HIV-1 integrase, an antibacterial activity, and an important value on research and development of novel drugs for curing AIDS and bacterial infections.