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The present invention relates to compounds of Formula I, II or Ill, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: wherein W is a substituted or unsubstituted heterocyclic ring system. The compounds inhibit serine protease activity, particularly the activity of hepatitis c virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis c virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

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In the search for novel antiplatelet agents, convenient and efficient methods for the preparation of 2,5-disubstituted pyridazin-3(2H)-ones are reported that utilise palladium-catalysed cross-coupling reactions. A post-coupling base-promoted isomerisation has been observed during Sonogashira alkynylation of 5-iodopyridazin-3(2H)-ones (3) with 1-phenyl-2-propyn-1-ol. Variable amounts of phthalazinones were isolated as by-products during the Heck alkenylation of 3. The usefulness of the hydroxymethyl fragment as a protecting group during the synthesis of 5-substituted pyridazin-3(2H)-ones has been validated. Graphical Abstract

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Disclosed herein are antibacterial and antimicrobial compositions and methods of use. Also disclosed are screening assays for identification of an agent that specifically inhibits DsbB or bVKOR. Such methods are useful, for example, in identifying antibacterial and antimicrobial agents and compositions.

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The present disclosure is directed to pyridazin-3(2H)-one compounds of formula (I), pharmaceutical compositions thereof and methods for modulating or activating a Parkin ligase The present disclosure is also directed to methods of treating and/or reducing the incidence of diseases or conditions related to the activation of Parkin ligase, R21, R22, R23, R24 and R25 are as defined herein.

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The present application describes compounds according to Formula I, pharmaceutical compositions comprising at least one compound according to Formula I and optionally one or more additional therapeutic agents and methods of treatment using the compounds according to Formula I both alone and in combination with one or more additional therapeutic agents. The compounds have the general Formula I: including all prodrugs, pharmaceutically acceptable salts and stereoisomers, R1, R2, R3, R6, R7, m and n are described herein.

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Ring contraction of 7-substituted 2-phenyl-4H-pyridazino<4,5-e><1,3,4>thiadiazin-8(7H)-ones (5a-d) to 5-substituted 3-phenyl-1H-pyrazolo<3,4-d>pyridazin-4(5H)-ones (7a-d), through base-induced extrusion of sulphur, is described.Similar reactions proceed, not only on the 4-acetyl derivatives (4a-d) in basic media, but on 5a and the 4-methyl derivative (6a) thermally.Probable mechanism of these reactions are discussed.A comparable approach to the ring contraction, photochemical cyclisation of 2-substituted 5-(1-alkyl-2-benzylidenehydrazino)-4-chloro-3(2H)-pyridazinones (9a-e) to the corresponding 1-alkylpyrazolo<3,4-d>-pyridazinone derivatives (8a-e) is also performed.

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The design and synthesis of two closely related series of prostacyclin receptor agonist compounds that showed excellent human IP receptor potency and efficacy is described. Compounds from this series showed in vivo activity after SC dosing in the monocrotaline model of PAH in rat.

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A compound represented by general formula [1] wherein X represents N or the like, Y represents CH or the like; RA represents a cycloalkyl group which may be substituted or the like, R1 represents an alkyl group or the like, R2 represents an alkyl group which may be substituted or the like, R3 represents a hydrogen atom or an alkyl group, or a pharmaceutically acceptable salt thereof has an inhibitory activity on aldosterone synthetase, and is useful as a prophylactic and/or therapeutic agent for various diseases or symptoms associated with aldosterone.

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A novel 3(2H)-pyradazinone derivative of the formula (I) STR1 wherein, R represents an alkyl group having 1 to 4 carbon atoms substituted by a cycloalkyl group having 3 to 8 carbon atoms, an alkyl group having 1 to 4 carbon atoms substituted by a phenyl group which may be substituted or an alkyl group having 1 to 4 carbon atoms substituted by a heterocyclic group, R’ represents a hydrogen atom, a halogen atom, an alkoxy group having 1 to 4 carbon atoms or a hydroxyl group having 1 to 4 carbon atoms, J represents any of various organic radicals. There is also provided a process for preparing said derivatives. These derivatives are useful as active ingredients of insecticidal, acaricidal and/or nematicidal compositions for agricultural and horticultural uses as well as of expellent compositions for pests parasitic on animals.

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IMIDAZO[ 1,2-a]PYRIDINES AND IMIDAZO[ 1,2-b]PYRIDAZINES AS MARK INHIBITORS

The invention encompasses imidazo[ 1,2-a]pyridine and imidazo[ 1,2-b]pyridazine derivatives which selectively inhibit microtubule affinity regulating kinase (MARK) and are therefore useful for the treatment or prevention of Alzheimer’s disease.Pharmaceutical compositions and methods of use are also included.

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