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ANTIBACTERIAL QUINOLINE DERIVATIVES

The present invention relates to novel substituted quinoline derivatives according to the general Formula (Ia) or Formula (Ib): including any stereochemically isomeric form thereof, a pharmaceutically acceptable salt thereof, a N-oxide form thereof or a solvate thereof. The claimed compounds are useful for the treatment of a bacterial infection. Also claimed is a composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of the claimed compounds, the use of the claimed compounds or compositions for the manufacture of a medicament for the treatment of a bacterial infection and a process for preparing the claimed compounds.

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ACYCLIC CYANOETHYLPYRAZOLO PYRIDONES AS JANUS KINASE INHIBITORS

The instant invention provides compounds of formula I which are JAK inhibitors, and as such are useful for the treatment of JAK-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer

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Synthesis and antileishmanial activity of 6-methoxy-4-methyl-N-[6-(substituted-1-piperazinyl)hexyl]-8-quinolinami nes and related compounds

The 8-quinolinamine, 4-[6-[(6-methoxy-4-methyl-8-quinolinyl)amino]hexyl]-1-piperazineethanol (1b), has been shown to be highly effective against Leishmania donovani infections in hamsters. In an effort to obtain a more potent, less toxic 8-quinolinamine, a series of analogues (2) was prepared that examined particularly the structural requirements of the terminal of the terminal piperazine moiety. Of the substituted piperazines and alternative heterocycles prepared, as well as those quinoline analogues with ring insertion of a methyl group in the 2-position or an aryloxy substituent in the 5-position, an increase in potency was achieved only with the 2-hydroxypropyl analogue (2f).

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ISOXAZOLO-PYRIDAZINE DERIVATIVES

The invention relates to isoxazolo-pyridazine compounds, in particular those of formula I as described above and to a pharmaceutically acceptable salts thereof, having affinity and selectivity for the GABA A alpha5 receptor binding site, their manufacture, pharmaceutical compositions containing them and their use as cognitive enhancers or for the treatment of cognitive disorders like Alzheimer”s disease.

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PYRROLOPYRIDINEAMINO DERIVATIVES AS MPS1 INHIBITORS

The present invention relates to the use of certain pyrrolopyridineamino derivatives (hereinafter referred to as “PPA derivatives”), particularly 1H-pyrrolo[3,2-c]pyridine-6-amino derivatives, to inhibit the spindle checkpoint function of Monospindle 1 (Mpsl also known as TTK) kinases either directly or indirectly via interaction with the Mps kinase itself. In particular, the present invention relates to PPA derivatives for use 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 the PPA derivatives, and pharmaceutical compositions comprising them. Formula (1)

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beta-N-Biaryl ether sulfonamide hydroxamates as potent gelatinase inhibitors: Part 2. Optimization of alpha-amino substituents

The introduction and the optimization of an alpha-amino substituent based on a series of alpha-hydroxy-beta-N-biaryl ether sulfonamide hydroxamates is described. The modification leads to a new series of MMP-2/MMP-9 inhibitors with enhanced inhibitory activities and improved ADME properties. An efficacy study on reducing the ischemia-induced brain edema in the rat transient middle cerebral artery occlusion (tMCAo) model is also demonstrated.

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Pyrimidines substituted by nitrogen-containing heterocyclic rings as intermediates

1,2,4-Triazolo[4,3-c]pyrimidines substituted at the 5 or 7 position through a nitrogen atom which is part of a heterocyclic ring have been found to have potent bronchodilator activity and to be useful synthetic intermediates in the preparation of 1,2,4-triazolo[1,5-c]pyrimidines. Methods for inducing bronchodilation, pharmaceutical compositions, and synthetic processes and intermediates are also described.

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INHIBITORS OF JANUS KINASES

The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2). The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 and TYK2 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer

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3-ARYL AND HETEROARYL SUBSTITUTED 5-TRIFLUOROMETHYL OXADIAZOLES AS HISTONE DEACETYLASE 6 (HDAC6) INHIBITORS

The present invention is directed to substituted 5-trifluoromethyl oxadiazole compounds of generic formula (I) or a pharmaceutically acceptable salt thereof. In particular, the invention is directed to a class of aryl and heteroaryl substituted 5-trifluoromethyl oxadiazole compounds of formula I which may be useful as HDAC6 inhibitors for treating cellular proliferative diseases, including cancer, neurodegenerative diseases, such as schizophrenia and stroke, as well as other diseases.

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NOVEL BREATHING CONTROL MODULATING COMPOUNDS, AND METHODS OF USING SAME

The present invention includes pyrimido[5,4-d]pyrimidines that are useful in the prevention and/or treatment of breathing control diseases or disorders in a subject in need thereof. The present invention also includes a method of preventing and/or treating a respiratory disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the invention. The present invention further includes a method of preventing destabilization or stabilizing breathing rhythm in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the invention.

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