205 results about "Polymerase inhibitor" patented technology

4-Amino-1-((2R,3S,4S,5R)-5-azido-3,4-dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one (I:R1=R2=R3=R4=H) and prodrugs thereof are hepatitis C(HCV) polymerase inhibitors. Also disclosed are compositions and methods for inhibiting HCV and treating HCV-mediated diseases, processes for making the compounds and synthetic intermediates employed in the process.

Compounds having the formula I wherein A, m and R1 are herein defined are Hepatitis C virus polymerase inhibitors. Also disclosed are compositions and methods for treating diseases mediated by HCV and for inhibiting hepatitis replication. Also disclosed are processes for making the compounds and synthetic intermediates used in the process

High throughput lyophilized polymerase devices and methods for their use in the production of nucleic acids using template dependent polymerase reactions are provided. The subject devices are typically made up of a multi-well substrate that includes in a least one well a lyophilized nucleic acid polymerase composition. The subject nucleic acid polymerase compositions include at least one polymerase and a carbohydrate stabilizing composition that is made up of at least one low molecular weight sugar and a starch. In many embodiments, the compositions also include buffer components and nucleotides, as well as a temperature dependent polymerase inhibitor, e.g., a polymerase specific antibody. Also provided are kits that include the subject devices.

An isomer, enantiomer, diastereoisomer, or tautomer of a compound, represented by formula I: wherein: A is O, S, NR1, or CR1, wherein R1 is defined herein; — represents either a single or a double bond; R2 is selected from: H, halogen, R21, OR21, SR21, COOR21, SO2N(R22)2, N(R22)2, CON(R22)2, NR22C(O)R22 or NR22C(O)NR22 wherein R21 and each R22 is defined herein; B is NR3 or CR3, with the proviso that one of A or B is either CR1 or CR3, wherein R3 is defined herein; K is N or CR4, wherein R4 is defined herein; L is N or CR5 wherein R5 has the same definition as R4 defined above; M is N or CR7, wherein R7 has the same definition as R4 defined above; Y1 is O or S; Z is N(R6a)R6 or OR6, wherein R6a is H or alkyl or NR61R62 wherein R61 and R62 are defined herein; a salt or a derivative thereof, as an inhibitor of HCV NS5B polymerase.

Disclosed are medicaments, pharmaceutical compositions, pharmaceutical kits, and methods based on combinations of at least one HCV protease inhibitor and at least one HCV polymerase inhibitor but not HCV-796; for concurrent or consecutive administration in treating or ameliorating one or more symptoms of HCV, or disorders associated with HCV in a subject in need thereof.

The invention provides methods for amplification of RNA. The methods are particularly suitable for specifically amplifying RNA in the presence of DNA. The methods involve producing a marked first primer extension product from a target RNA in the presence of a DNA-dependent DNA polymerase inhibitor, which prevents replication of DNA by the reverse transcriptase enzyme. The marked nucleic acid products are subsequently selectively amplified in the presence on non-marked nucleic acids. The methods are useful for production and analysis of polynucleotide sequences complementary to an RNA sequence. The methods are useful for preparation of nucleic acid libraries and substrates for analysis of gene expression of cells in biological samples. The invention also provides compositions and kits for practicing the amplification methods, as well as methods which use the amplification products.

This invention generally relates to use of 8-fluoro-2{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one represented by formula 1 as a chemosensitizer that enhances the efficacy of cytotoxic drugs or radiotherapy. This invention provides pharmaceutical combinations of 8-fluoro-2{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one, or a pharmaceutically acceptable salt thereof and at least one additional therapeutic agent, kits containing such combinations and methods of using such combinations to treat subjects suffering from diseases such as cancer.

The present invention provides nucleoside aryl phosphoramidates of structural formula (I) which are precursors to inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors to inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as precursors to inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors to inhibitors of HCV replication, and / or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside aryl phosphoramidates alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and / or treating RNA-dependent RNA viral infection with the nucleoside aryl phosphoramidates of the present invention.

The present invention relates to a tetracyclic fused heterocyclic compound represented by the following formula [I]wherein each symbol is as defined in the specification, or a pharmaceutically acceptable a salt thereof, and a hepatitis C virus (HCV) polymerase inhibitor and a therapeutic agent for hepatitis C containing this compound. The compound of the present invention shows an anti-HCV activity based on the HCV polymerase inhibitory activity, and useful as an agent for the prophylaxis or treatment of hepatitis C.

Compounds having the formula I wherein R1 is as herein defined are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for inhibiting hepatitis replication, and processes for making the compounds of formula I

The invention provides compounds of the formula:which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.

An enantiomer, diastereoisomer or tautomer of a compound, represented by formula I: wherein A, B, R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are as defined herein, or a salt or ester thereof, as an inhibitor of HCV NS5B polymerase.

The present invention provides nucleoside aryl phosphoramidates of structural formula (I) which are precursors to inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors to inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as precursors to inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors to inhibitors of HCV replication, and / or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside aryl phosphoramidates alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and / or treating RNA-dependent RNA viral infection with the nucleoside aryl phosphoramidates of the present invention. (I)

Compounds having the formula are hepatitis C (HCV) polymerase inhibitors. Also disclosed are a composition and method for inhibiting hepatitis C (HCV) polymerase, processes for making the compounds, and synthetic intermediates employed in the processes.

The present invention provides thionucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and / or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such thionucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and / or treating RNA-dependent RNA viral infection with the thionucleoside compounds of the present invention.

The present invention provides mutants of DNA polymerases having an increased rate of incorporation of nucleotides into nucleic acids undergoing polymerization and having an enhanced resistance to inhibitors of DNA polymerase activity. The mutant polymerases are well suited for fast PCR applications, for PCR amplification of targets in samples that contain inhibitors of wild-type polymerases, and for fast PCR amplification of samples containing DNA polymerase inhibitors. In exemplary embodiments, the mutants are mutants of Taq DNA polymerase.

A method for identifying compounds binding to HCV polymerase comprising the steps of: contacting said HCV polymerase or an analog thereof with a probe formula I:wherein A is O, S, N, NR1, or CR1, wherein R1 is defined herein;----- represents either a single or a double bond;R2 is selected from: H, halogen, R21, OR21, SR21, COOR21, SO2N(R22)2, N(R22)2, CON(R22)2, NR22C(O)R22 or NR22C(O)NR22 wherein R21 and each R22 is defined herein;B is NR3 or CR3, wherein R3 is defined herein;with the proviso that, when A is not N, then one of A or B is either CR1 or CR3,K is N or CR4, wherein R4 is defined herein;L is N or CR5, wherein R5 has the same definition as R4 defined above;M is N or CR7, wherein R7 has the same definition as R4 defined above;R5 is C(Y1)Z wherein Y1 is O or S; andZ is N(R6a)R6 or OR6, wherein R6a is H or alkyl or NR61R62 wherein R61 and R62 are defined herein; and R6 is H, alkyl, cycloalkyl, alkenyl, Het, alkyl-aryl, alkyl-Het; or R6 iswherein R7 and R8 and Q are as defined herein;Y2 is O or S;R9 is H, (C1-6 alkyl), (C3-7)cycloalkyl or (C1-6)alkyl-(C3-7)cycloalkyl, aryl, Het, (C1-6)alkyl-aryl or (C1-6)alkyl-Het, all of which optionally substituted with R90; or R9 is covalently bonded to either of R7 or R8 to form a 5- or 6-membered heterocycle; or a salt thereof; where the probe comprises a detectable label attached to any suitable position, whereby said probe binds to an HCV polymerase or an analog thereof and is capable of being displaced by an inhibitor thereof.

The present invention provides nucleoside cyclic phosphoramidates of structural formula (I) which are precursors to inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors to inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as pre-cursors to inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors to inhibitors of HCV replication, and / or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside cyclic phosphoramidates alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and / or treating RNA-dependent RNA viral infection with the nucleoside cyclic phosphoramidates of the present invention.

Novel hepatitis C virus (“HCV”) inhibitor combinations comprising an HCV protease inhibitor and HCV polymerase inhibitor, and optionally one or more biologically active agents, as well as uses of these combinations as HCV inhibitors and for treating hepatitis C and related disorders are disclosed.

Disclosed are DNA polymerases having increased reverse transcriptase efficiency, mismatch tolerance, extension rate and / or tolerance of RT and polymerase inhibitors relative to a corresponding, unmodified polymerase. The polymerases are useful in a variety of disclosed primer extension methods. Also disclosed are related compositions, including recombinant nucleic acids, vectors, and host cells, which are useful, e.g., for production of the DNA polymerases.

The efficacy of reverse transcriptase and DNA polymerase inhibitors (nucleoside analogs) in a mammalian host is enhanced by administering an effective amount of PNP inhibitor of prodrug of PNP inhibitor and / or an effective amounts of 2′-de-oxyguanosine and / or prodrugs thereof.