233 results about "Integrases" patented technology

The invention encompasses a series bicyclic pyrimidinone compounds of Formula I which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

The present invention describes a comprehensive system for gene discovery using retrovirus that have been engineered to exhibit increased accessibility to genomic DNA, or to mutate and identify the chromosomal target sequences of DNA binding proteins. The strategy employs the combination of retroviral integrase/DNA binding protein fusion constructs and gene-trapping methodologies. This novel technology provides the ability to establish proviral integration at any location within the genome. In addition, it allows for the generation of a collection of eukaryotic cells in which each cell contains a mutation in a target gene or sequence for a known DNA binding protein which also allow for rapid in vivo functional analysis. Sequence information obtained for genes identified using the described methods identify a collection of eukaryotic genes related by, or directly or indirectly regulated by, a given DNA binding protein.

The invention encompasses series bicyclic pyrimidinone compounds of Formula I which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

The invention encompasses a series bicyclic pyrimidinone compounds of Formula I which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

The invention encompasses a series bicyclic pyrimidinone compounds of Formula I which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

An anti-HIV agent containing, as an active ingredient, a 4-oxoquinoline compound represented by the following formula [I]

wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof. The compound of the present invention has HIV integrase inhibitory action and is useful as an anti-HIV agent for the prophylaxis or therapy of AIDS. Moreover, by a combined use with other anti-HIV agents such as protease inhibitors, reverse transcriptase inhibitors and the like, the compound can become a more effective anti-HIV agent. Since the compound has high inhibitory activity specific for integrases, it can provide a safe pharmaceutical agent with a fewer side effects for human.

The disclosure generally relates to the novel compounds of formula I, including their salts, which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

The invention encompasses a series cyclic bicyclic heterocyclic compounds of Formula I which are inhibitors of HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

A compound of the formula (I):wherein X is hydroxy, protected hydroxy or optionally substituted amino; Y is -COORA wherein RA is hydrogen or ester residue, -CONRBRC wherein RB and RC each is independently hydrogen or amide residue, optionally substituted aryl or optionally substituted heteroaryl; and A1 is optionally substituted heteroaryl; provided that a compound wherein Y and/or A1 is optionally substituted indol-3-yl is excluded, a tautomer, a prodrug, a pharmaceutically acceptable salt or a hydrate thereof has an inhibitory activity against an integrase.

The subject invention provides a unidirectional site-specific integration system for integrating a nucleic acid into the genome of a target cell. The provided system includes a site-specific integrating expression cassette (INTEC) vector, consisting of (a) a polynucleotide of interest operably linked to a promoter, (b) a single recombination site, and (c) a hybrid recombination site. In using the subject systems for site-specific integration, the INTEC vector and integrase are introduced into the target cell and the cell is maintained under conditions sufficient to provide for site-specific integration of the nucleic acid into the target cell genome via a recombination event mediated by the site-specific recombinase. Also provided are kits that include the subject systems. The subjects systems, methods and kits find use in a variety of different applications, several representative ones of which are described in detail as well.

The present invention provides a compound useful as a synthetic intermediate for an anti-HIV agent having an integrase inhibitory activity, a production method thereof, and a production method of an anti-HIV agent using the synthetic intermediate. Specifically, the present invention provides, for example, compounds represented by the formulas (6), (7-1), (7-2) and (8):

wherein R is a fluorine atom or a methoxy group, R¹ is a C₁-C₄ alkyl group, R² is a hydroxyl-protecting group, and X² is a halogen atom, a production method thereof, and a production method of an anti-HIV agent using the synthetic intermediate.

The present invention relates to a combination therapy for treating an HIV infection or inhibiting integrase comprising (S)-6-(3-Chloro-2-fluorobenzyl)-1-(1-hydroxymethyl-2-methylpropyl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (“Compound A”) or a pharmaceutically acceptable solvate or salt thereof in combination with at least one other anti-HIV agent. In some embodiments of the present invention, the other anti-HIV agents are chosen from reverse transcriptase inhibitors and protease inhibitors. In certain embodiments of the present invention, the other anti-HIV agents are chosen from AZT, 3TC, PMPA, efavirenz, indinavir, nelfinavir, a combination of AZT/3TC, and a combination of PMPA/3TC. Since Compound A has a high inhibitory activity specific for integrases, when used in combinations with other anti-HIV agents it can provide a combination therapy with fewer side effects for humans.

The invention encompasses a series cyclic bicyclic pyrimidinone compounds of Formula I which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

The present invention is transgenic chickens obtained from long-term cultures of avian PGCs and techniques to produce and transgenic birds derived from prolonged PGC cultures. In some embodiments, these PGCs can be transfected with genetic constructs to modify the DNA of the PGC, specifically to introduce a transgene encoding an exogenous protein. When combined with a host avian embryo by known procedures, those modified PGCs are transmitted through the germline to yield transgenic offspring. This invention includes compositions comprising long-term cultures of PGCs and offspring derived from them that are genetically modified. The genetic modifications introduced into PGCs to achieve the gene inactivation may also include, but are not restricted to, random integrations of transgenes into the genome, transgenes inserted into the promoter region of genes, transgenes inserted into repetitive elements in the genome, site specific changes to the genome that are introduced using integrase, site specific changes to the genome introduced by homologous recombination, and conditional mutations introduced into the genome by excising DNA that is flanked by lox sites or other sequences that are substrates for site specific recombination.

Compounds of formula I:

wherein R₁, R₂, R₄, R₁₀, R₁₁, and Q are as defined herein, and their pharmaceutically acceptable salts, are useful in the prevention or treatment of HIV infections.

A method of detecting an enzyme-mediated DNA cleavage reaction in a fluorometric assay is provided. The method can be used to detect DNA cleavage caused by restriction endonucleases, retroviral integrase enzymes, DNases, RNases, or enzymes utilized in other strand separating processes in molecular biology.

The subject invention provides a unidirectional site-specific integration system for integrating a nucleic acid into the genome of a target cell. The provided systems include a (1) a mutant, unidirectional site specific integrase, which can be provided by an integrase vector encoding the mutant integrase and (2) a targeting vector that includes: (a) a nucleic acid to be integrated; and (b) a vector attachment site, where the targeting vector attachment site serves as a substrate for the mutant, unidirectional site-specific integrase. In using the subject systems for site-specific integration, the targeting vector and integrase are introduced into the target cell and the cell is maintained under conditions sufficient to provide for site-specific integration of the nucleic acid into the target cell genome via a recombination event mediated by the site-specific integrase. Also provided are kits that include the subject systems. The subjects systems, methods and kits find use in a variety of different applications, several representative ones of which are described in detail as well.