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HEPATITIS C VIRUS INHIBITORS

The present disclosure is generally directed to antiviral compounds, and more specifically directed to compounds which inhibit the function of the NS3 protease (also referred to herein as “serine protease”) encoded by Hepatitis C virus (HCV), compositions comprising such compounds, and methods for inhibiting the function of the NS3 protease. ”

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Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Inhibitors of Hepatitis C Virus

Macrocyclic peptides are disclosed having the general formula: wherein R3, R3?, R4, R6, R?, X, Q and W are described. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

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PIPERAZINE-PIPERIDINE ANTAGONISTS AND AGONISTS OF THE 5-HT1A RECEPTOR

The present invention relates to novel piperazine-piperidine compounds. The compounds are useful as 5-HT1A binding agents, particularly as 5-HT1A receptor antagonists and agonists. These compounds are useful in treating central nervous system disorders, such as cognition disorders, anxiety disorders, depression and sexual dysfunction.

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Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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SMALL MOLECULE OXIDIZERS OF PDI AND THEIR USE

The present invention provides a method for treating or ameliorating the effects of a neurodegenerative disorder in a subject in need thereof comprising administering to the subject an effective amount of a compound selected from the group consisting of combinations thereof, or an N-oxide, crystalline form, hydrate, or pharmaceutically acceptable salt thereof. The present invention also provides a method for treating or ameliorating the effects of a condition associated with increased protein disulfide isomerase (PDI) activity and a method of modulating PDI activity in a cell. The present invention also provides compounds, salts, compositions and kits useful for the provided methods.

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Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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HEPATITIS C VIRUS INHIBITORS

Hepatitis C virus inhibitors are disclosed having the general formula:(I) wherein R1, R2, R3, R’, B, Y and X are described in the description. Compositions comprising the compounds and methods for using the compounds toinhibit HCV are also disclosed.

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Benzisoxazole – Wikipedia,
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FUSED HETEROCYCLIC SUCCINIMIDE COMPOUNDS AND ANALOGS THEREOF, MODULATORS OF NUCLEAR HORMONE RECEPTOR FUNCTION

Fused cyclic compounds, methods of using such compounds in the treatment of nuclear hormone receptor-associated conditions such as cancer and immune disorders, and pharmaceutical compositions containing such compounds.

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Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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BENZISOXAZOLES

The present invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein m represents an integer from 1 to 3; X represents amino, hydroxy, -oxo or -Z-R1; Y is absent when X represents -Z-R1 and -(C=O)-R6 when X represents oxo; Z represents carbonyl, -oxy-carbonyl- or -NR 5-carbonyl-; R1 represents C1-4alkyl, Ar1, Ar1-C1-4a1ky1-, -NR3R4 or -Het1; R2 represents hydrogen, halo, nitro, hydroxycarbonyl-, C1-4alkyloxy or C1-4alkyl; R3 and R4 are each independently selected from hydrogen, Ar3 or C1-4alkyl; R5 represents hydrogen, C1-4alkylcarbonyl- or Ar4-carbonyl-; R6 represents a substituent selected from the group consisting of C1.4alkyl, Ar5, Ar6-C1-4alkyl- or NR7R8; R7 and R8 are each independently selected from hydrogen, Het4 or C1-4alkyl; Het1 represents a heterocycle selected from oxazolyl, isoxazolyl, imidazolyl or pyrazolyl wherein said heterocycle is optionally substituted with one, two or three substituents selected from the group consisting of amino, C1-4alkyl, hydroxy-C1-4alkyl, phenyl, phenyl-C1-4alkyl- and phenyl substituted with one or more halo substituents; Het4 represents a heterocycle selected from oxazolyl or isoxazolyl, wherein said heterocycle is optionally substituted with one or more substituents selected from the group consisting of amino, C1-4alkyl, hydroxy-C1-4alkyl-, phenyl, phenyl-Cl-4alkyl and phenyl substituted with one or more halo substituents; and Ar1, Ar2, Ar3, Ar4, Ar5 or Ar6 each independently represents phenyl optionally substituted one or where possible two or more substituents selected from halo, nitro, C1-4alkyl, hydroxy or C1-4alkyloxy-.

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Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Validating and enabling phosphoglycerate dehydrogenase (PHGDH) as a target for fragment-based drug discovery in PHGDH-amplified breast cancer

3-Phosphoglycerate dehydrogenase (PHGDH) has recently been identified as an attractive target in cancer therapy as it links upregulated glycolytic flux to increased biomass production in cancer cells. PHGDH catalyses the first step in the serine synthesis pathway and thus diverts glycolytic flux into serine synthesis. We have used siRNA-mediated suppression of PHGDH expression to show that PHGDH is a potential therapeutic target in PHGDH-amplified breast cancer. Knockdown caused reduced proliferation in the PHGDH-amplified cell line MDA-MB-468, whereas breast cancer cells with low PHGDH expression or with elevated PHGDH expression in the absence of genomic amplification were not affected. As a first step towards design of a chemical probe for PHGDH, we report a fragment-based drug discovery approach for the identification of PHGDH inhibitors. We designed a truncated PHGDH construct that gave crystals which diffracted to high resolution, and could be used for fragment soaking. 15 fragments stabilising PHGDH were identified using a thermal shift assay and validated by X-ray crystallography and ITC competition experiments to exhibit 1.5-26.2 mM affinity for PHGDH. A structure-guided fragment growing approach was applied to the PHGDH binders from the initial screen, yielding greater understanding of the binding site and suggesting routes to achieve higher affinity NAD-competitive inhibitors.

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Benzisoxazole – Wikipedia,
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Processes and intermediate compounds for the preparation of 2-(N,N-disubstituted) amino-4-(perfluoroalkyl)-1, 3- oxazin-6-one and 6-(perfluoroalkyl) uracil compounds

An improved process and intermediate compounds for the preparation of 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds having the structural formula I and an improved process for the preparation of 6-(perfluoroalkyl)uracil compounds having the structural formula V

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Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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1,2-BENZISOSELENAZOL-3(2H)-ONE AND 1,2-BENZISOTHIAZOL-3(2H)-ONE DERIVATIVES AS BETA-LACTAM ANTIBIOTIC ADJUVANTS

Provided herein are compositions and methods useful in the treatment of beta-lactam antibiotic resistant bacteria.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics