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The invention relates to compounds of formula (I) whichare inhibitors of kinase activity,pharmaceutical formulations containing the compounds andtheir uses in treating andpreventing viral infections anddisorders causedor exacerbatedby the viral infection wherein R1,R2,R3,R4a,R4b,R4c,R5,W,X,Y andZ are definedherein.

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The lack of efficacy of current antibacterials to treat multidrug resistant bacteria poses a life-threatening alarm. In order to develop enhancers of the antibacterial activity, we carried out a medicinal chemistry campaign aiming to develop inhibitors of enzymes that synthesise cysteine and belong to the reductive sulphur assimilation pathway, absent in mammals. Previous studies have provided a novel series of inhibitors for O-acetylsulfhydrylase?a key enzyme involved in cysteine biosynthesis. Despite displaying nanomolar affinity, the most active representative of the series was not able to interfere with bacterial growth, likely due to poor permeability. Therefore, we rationally modified the structure of the hit compound with the aim of promoting their passage through the outer cell membrane porins. The new series was evaluated on the recombinant enzyme from Salmonella enterica serovar Typhimurium, with several compounds able to keep nanomolar binding affinity despite the extent of chemical manipulation.

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Since palladium-catalysts have strong abilities for both hydrogenation of nitro-group and hydrogenolysis of benzylamine, they have a much lower chemoselectivity for the hydrogenation of (N,N-disubstituted aminomethyl)nitrobenzenes. In this article, component stable Pd-Ni bimetallic nanoparticles were prepared by simply heating RANEY-Ni and Na2PdCl4 together in water. They demonstrated novel synergistic effects when they were used as a bimetallic catalyst, by which a highly efficient and chemoselective hydrogenation of (N,N-disubstituted aminomethyl)nitrobenzenes to (N,N-disubstituted aminomethyl)anilines was achieved.

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The present application is directed to compounds of Formula I: compounds comprising these compounds and their uses, for example as medicaments for the treatment of diseases, disorders or conditions mediated or treatable by inhibition of binding between WDR5 protein and its binding partners.

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Structure-activity relationship studies of G9a-like protein (GLP) inhibitors

Given the high homology between the protein lysine methyltransferases G9a-like protein (GLP) and G9a, it has been challenging to develop potent and selective inhibitors for either enzyme. Recently, we reported two quinazoline compounds, MS0124 and MS012, as GLP selective inhibitors. To further investigate the structure?activity relationships (SAR) of the quinazoline scaffold, we designed and synthesized a range of analogs bearing different 2-amino substitutions and evaluated their inhibition potencies against both GLP and G9a. These studies led to the identification of two new GLP selective inhibitors, 13 (MS3748) and 17 (MS3745), with 59- and 65-fold higher potency for GLP over G9a, which were confirmed by isothermal titration calorimetry (ITC). Crystal structures of GLP and G9a in complex with 13 and 17 provide insight into the interactions of the inhibitors with both proteins. In addition, we generated GLP selective inhibitors bearing a quinoline core instead of the quinazoline core.

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HETEROCYCLIC COMPOUND

An object of the present invention is to provide a compound having a superior CH24H inhibitory action, which is useful as an agent for the prophylaxis or treatment of epilepsy, neurodegenerative disease and the like. The present invention relates to a compound represented by the formula: wherein each symbol is as defined in the specification, or a salt thereof.

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Tetrahydropyran – Wikipedia,
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SUBSTITUTED 6-AMINO-NICOTINAMIDES AS KCNQ2/3 MODULATORS

Substituted 6-amino-nicotinamides, pharmaceutical compositions containing these compounds and also use of these compounds in the treatment and/or prophylaxis of pain and further diseases and/or disorders.

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INHIBITOR COMPOUNDS

The present invention relates to compounds of formula (I), wherein R, R, Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1 – also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them

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Direct Use of Unprotected Aliphatic Amines to Generate N-Heterocycles via beta-C-H Malonylation with Iodonium Ylide

An unprecedented method that enables the direct transformation of unprotected secondary aliphatic amines into functionalized N-heterocycles in the absence of transition metals was developed. The activation of these NH-free amines by the iodonium ylide induces a site-selective beta-C-H malonylation process, allowing the construction of three sigma-bonds and one pi-bond in a simple operation.

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NOVEL COMPOUNDS

The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I) and salts thereof. The compounds of the invention are inhibitors of PI3-kinase activity.

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics