Abstract: Compounds of the formula I or II: wherein X, m, Ar, R1 and R2 are as defined herein. The subject compounds are useful for treatment of IRAK-mediated conditions.

Abstract: The present invention relates to a method for controlling invertebrate pests which method comprises treating the pests, their food supply, their habitat or their breeding ground or a plant, seed, soil, area, material or environment in which the pests are growing or may grow, or the materials, plants, seeds, soils, surfaces or spaces to be protected from pest attack or infestation with a pesticidally effective amount of a pyrazole compound of formulae I or II or a salt or an N-oxide thereof, wherein A is a pyrazole radical of the formulae A1 or A2, wherein # denotes the binding; D is a 5- or 6-membered heterocyclic radical fused to the pyrazole moiety; Rp1, Rp2 and Rpx are H, halogen, CN, NO2, C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, etc.

Abstract: The present disclosure provides technologies relating to lysosomal activation. The disclosure provides several strategies for increasing level and/or activity of lysosomal enzyme, and furthermore demonstrates the surprising applicability of such strategies in the treatment and/or prophylaxis of certain proteinopathies. Among other things, the present invention provides methods and compositions for the treatment and/or prophylaxis of proteinopathies other than lysosomal storage diseases through lysosomal activation. In particular, the present disclosure provides methods and compositions for the treatment and/or prophylaxis of neurodegenerative proteinopathies, and in particular those associated with accumulation of ?-synuclein. The present disclosure specifically provides methods and compositions for the treatment and/or prophylaxis of Parkinson's disease.

Abstract: Provided herein are novel substituted bicyclic aza-heterocycle sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Abstract: This invention relates to pyrazolopyridyl compounds of the structural formula: or their pharmaceutically acceptable salts, wherein the variable are defined herein. The inventive compounds selectively inhibit aldosterone synthase. This invention also provides for pharmaceutical compositions comprising the compounds of Formula I or their salts as well as potentially to methods for the treatment, amelioration or prevention of conditions that could be treated by inhibiting aldosterone synthase.

Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: or a pharmaceutically acceptable salt, wherein the variables are as defined herein.

Abstract: The present invention relates to compounds useful as inhibitors of one or more histone demethylses. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

Abstract: The present invention relates generally to amide containing heterobicyclic compounds having the following formulas: wherein R1, R2, D, and Q are as defined in the specification. More particularly, the present invention provides a new class of amide containing heterobicyclic compounds, that exhibit an increased potency in relation to currently known MMP-13 and MMP-3 inhibitors.

Abstract: Methods for regulating cancer cell growth and survival, inhibiting cancer cell growth, promoting cancer cell death, and/or treating a cancer make use of antagonists of a type I BMP receptor. In some embodiments the cancer is a lung cancer and the cancer cell is a lung cancer cell.

Abstract: Heterocyclylpyri(mi)dinylpyrazole of the formula (I) in which R1 to R5, X1, U, Q, W, Y, n, a, b have the meanings given in the description, and agrochemically active salts, to their use and to methods and compositions for controlling phytopathogenic harmful fungi in and/or on plants or in and/or on seed of plants and for reducing mycotoxins in plants and parts of the plants, to processes for preparing such compounds and compositions and treated seed and also to their use for controlling phytopathogenic harmful fungi in agriculture, horticulture, forestry, in animal husbandry, in the protection of materials, in the domestic and hygiene field and for the reduction of mycotoxins in plants and parts of the plants

Abstract: The present invention relates to novel substituted 2-amino-3-(arylsulfonyl)pyrazolo[1,5-a]pyrimidines of general formula 1, to serotonin 5-HT6 receptor antagonists, to novel drug substances and pharmaceutical compositions, to medicaments, methods for preparation thereof, and to methods for prophylaxis and treatment of various CNS diseases, pathogenesis of which is associated with disturbance of monoaminergic signaling pathways, more specifically over- or hypo-activation of serotonin 5-HT6 receptors.

Abstract: Substituted pyrazolopyrimidines and dihydropyrazolopyrimidines and related compounds, their methods of manufacture, compositions containing these compounds, and methods of use of these compounds in treating lysosomal storage disorders such as Gaucher disease are described herein. The compounds are of general Formula (I) in which variables R1-R7 and X are described in the application.

Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: or a pharmaceutically acceptable salt, wherein the variables are as defined herein. Moreover, The compounds of this invention have formula I-A: or a pharmaceutically acceptable salt, wherein the variables are as defined herein.

Abstract: The invention provides certain 2-pyridyl carboxamide-containing compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein A and B are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions mediated by Spleen Tyrosine Kinase (Syk) kinase.

Abstract: The invention provides a pyrazolopyrimidine derivative of formula (I), wherein, for example, R1 represents —NR1aR1b (wherein R1a and R1b are the same or different and each is a hydrogen atom or aralkyl), R2 represents formula (Ya) [wherein k and m each represents an integer of 0-2, n represents an integer of 0-4, L represents a single bond, R5 represents halogen, R6 represents aryl, X represents —CR8 (wherein R8 represents a hydrogen atom), and R7 represents a hydrogen], R3 represents —SO2R13a [wherein R13a represents lower alkoxy, —NR13dC(?O)R13e (wherein R13d represents a hydrogen atom, and R13e represents lower alkyl)], and R4 represents a hydrogen atom, or a pharmaceutically acceptable salt thereof. The invention also provides a medicament containing the pyrazolopyrimidine derivative, as well as a method of using the pyrazolopyrimidine derivative to prevent and/or treat skin diseases.

Abstract: The present invention provides heteroaromatic derivatives and pharmaceutical acceptable salts and formulations thereof useful in modulating the protein kinase activity, especially phosphatidylinositol 3-kinases (PI3 kinases) and mTOR, and in modulating inter- and/or intra-cellular signaling activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

Abstract: Various tetrahydropyrazolo[1,5-a]pyrimidine compounds, compositions, methods of making, and methods for the prevention and treatment of HCV infections and associated diseases are disclosed. The invention further relates to biomarkers for identification of HCV strains which are resistant to the tetrahydropyrazolo[1,5-a]pyrimidine compounds.

Abstract: The invention relates to novel pyrazolopyrimidinones according to formula (I): wherein X, D, Ra, Rb, Rc, Rd, Re, m and n are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds and methods of using these compounds in the treatment of various diseases concerning deficits in perception, concentration, learning or memory.

Abstract: The present invention is directed to pyrimidine compounds which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

Abstract: The invention provides a chemokine receptor activity modulator containing a pyrazolopyrimidine derivative represented by the formula (I) wherein R1, R2, R3, and R4 are as described herein.

Abstract: Compounds active on c-kit protein kinases or mutant c-kit protein kinases having any mutations are described, as well as methods of making and using such compounds to treat diseases and conditions associated with aberrant activity of the c-kit protein kinases and/or mutant c-kit protein kinases.

Abstract: The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

Abstract: Compounds of Formula (I) and salts thereof in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification, are inhibitors of Trk kinases and are useful in the treatment of diseases which can be treated with a Trk kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

Abstract: This invention relates to amidopyrazole compounds that are inhibitors of Interleukin receptor-associated kinases, in particular IRAK-4, and are useful in the treatment of cellular proliferative diseases, for example, cancer, hyperplasia, restenosis, cardiac hypertrophy, immune disorders and inflammation.

Abstract: Provided herein are methods for treating pain, cancer, inflammation, neurodegenerative disease or Typanosoma cruzi infection in a mammal, which comprises administering to said mammal in need thereof a therapeutically effective amount of a compound of Formula I: in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification.

Abstract: The present invention provides, among other things, compounds represented by the general Formula I: and pharmaceutically acceptable salts thereof, wherein X, Y, R1A, R1B, R2, and R3 are as defined in classes and subclasses herein and compositions (e.g., pharmaceutical compositions) comprising such compounds, which compounds are useful as inhibitors of hepatitis C virus polymerase, and thus are useful, for example, as medicaments for the treatment of HCV infection.

Abstract: PI3K? selective compounds having the structure

Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: or a pharmaceutically acceptable salt, wherein the variables are as defined herein. Moreover, The compounds of this invention have formula I-A: or a pharmaceutically acceptable salt, wherein the variables are as defined herein.

Abstract: The present invention relates to pyrazolo pyrimidine derivatives, to methods of preparing these, to combinations and pharmaceutical composition comprising these, and to their use in the treatment of diseases and disorders which may for example involve autoimmune diseases, angiogenesis, pain, and/or inflammatory diseases.

Abstract: There is provided a calcium receptor modulator comprising a compound of the formula (I): wherein ring A is an optionally substituted 5- to 7-membered ring; ring B is an optionally substituted 5- to 7-membered heterocyclic ring; X1 is CR1, CR1R2, N or NR13; X2 is N or NR3; Y is C, CR4 or N, Z is CR5, CR5R6, N or NR7; Ar is an optionally substituted cyclic group; R is H, an optionally substituted hydrocarbon group, etc.; and is a single bond or a double bond; R1, R2, R3, R4, R5, R6, R7 and R13 are independently H, an optionally substituted hydrocarbon group; or a salt thereof or a prodrug thereof. Compounds of the formula (II) and (III): wherein ring A is an optionally substituted 5- to 7-membered ring; Q is C, CR5 or N; R8, R9, R10, R11 and R12 are independently, H, an optionally substituted hydrocarbon group, etc., or a salt thereof are also provided. Also specify X1, R3, R1, Y and X3 in formula (II) and (III) as before.

Abstract: The invention provides compounds of Formula I or Formula II: or a pharmaceutically acceptable salt or ester, thereof, as described herein. The compounds and compositions thereof are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

Abstract: Fungicidal mixtures comprising, as active components, 1) azolopyrimidinylamines of the formula I, in which the substituents are as defined in the description and 2) at least one active compound II selected from the following groups: azoles, strobilurins, carboxamides, heterocylic compounds, carbamates and other active compounds selected from the group consisting of guanidines, antibiotics, sulfur-containing heterocyclyl compounds, organophosphorus compounds, organochlorine compounds, inorganic active compounds, growth retardants and cyflufenamid, cymoxanil, dimethirimol, ethirimol, furalaxyl, metrafenone and spiroxamine; in a synergistically effective amount. Methods for controlling harmful fungi using mixtures of the compound I with active compounds II and the use of the compound I with active compounds II for preparing such mixtures, and also compositions comprising these mixtures.

Abstract: The invention relates to doxepin, pharmaceutically acceptable salts and prodrugs of doxepin; compositions containing the same, and the use of any of the aforementioned for the treatment of sleep disorders.

Abstract: Antiviral compositions and methods are contemplated that are especially effective in the treatment and prevention of influenza A viruses. Also presented are cellular assays to identify small molecule compounds having antiviral properties, particularly as it relates to detection of influenza A RNA-dependent RNA polymerase activity in a mammalian cell independent of other influenza A components. Preferred assays allow for identification of viral replication inhibitors that do not disrupt normal cellular activity.

Abstract: The invention provides compounds that inhibit protein kinase CK2 activity (CK2 activity), and compositions containing such compounds.

Abstract: In alternative embodiments, the invention provides compositions that inhibit the polypeptide SSH-2, or SlingSHot-2, a phosphatase enzyme that regulates actin filaments, and methods for making and using them, including methods comprising administering compositions of the invention to regulate or modify actin filament polymerization by inhibiting SSH-2, where in one embodiment compositions of the invention slow or inhibit F-actin depolymerization and severing. In alternative embodiments, compositions and methods of the invention are used to slow or inhibit cell motility and/or internal remodeling. In alternative embodiments, compositions and methods of the invention are used to slow or inhibit, or reverse, or ameliorate the progression of a cancer or a metastasis or other uncontrolled or unregulated cell growth, and/or Alzheimer's disease.

Abstract: Fungicidal mixtures comprising, as active components, 1) azolopyrimidinylamines of the formula I, ?in which the substituents are as defined in the description and 2) at least one active compound II selected from the following groups: azoles, strobilurins, carboxamides, heterocylic compounds, carbamates and other active compounds selected from the group consisting of guanidines, antibiotics, sulfur-containing heterocyclyl compounds, organophosphorus compounds, organochlorine compounds, inorganic active compounds, growth retardants and cyflufenamid, cymoxanil, dimethirimol, ethirimol, furalaxyl, metrafenone and spiroxamine; in a synergistically effective amount. Methods for controlling harmful fungi using mixtures of the compound I with active compounds II and the use of the compound I with active compounds II for preparing such mixtures, and also compositions comprising these mixtures.

Abstract: This invention is directed to the treatment of pain by inhibiting adaptor associated kinase 1 (AAK1). Numerous AAK1 inhibitors are disclosed.

Abstract: In its many embodiments, the present invention provides a method of inhibiting one or more cyclin dependent kinases in a patient comprising administering to said patient a therapeutically effective amount of at least one pyrazolo[1,5-a]pyrimidine compound or a pharmaceutical composition comprising such compound, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

Abstract: The invention provides compounds of Formula I or Formula II: or a pharmaceutically acceptable salt or ester, thereof, as described herein. The compounds and compositions thereof are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

Abstract: The present invention relates to compounds of formula IVA, formula IVB, or formula IVC, useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating diseases using such CFTR modulators.

Abstract: The present invention relates to ethynyl compounds of formula wherein X, Y, Z, and R4 are as defined herein or to a pharmaceutically acceptable salt or acid addition salt, to a racemic mixture, or to its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof. Compounds of formula I are positive allosteric modulators (PAM) of the metabotropic glutamate receptor subtype 5 (mGluR5) and they are therefore useful for the treatment of diseases related to this receptor.

Abstract: The invention discloses methods and compositions for treating or preventing Parkinson's disease by administering a compound of Formula (I): or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the variables are defined as herein.

Abstract: Disclosed herein is a compound of Formula I: wherein X, R1, R2, and R3 are as defend herein, or a pharmaceutically acceptable salt thereof to allow the drug to penetrate the cell membrane; or a prodrug, or the compound is labeled with a detectable label or an affinity tag thereof. Also disclosed is a pharmaceutical composition, a method of treating a disorder mediated by melanocortin-4 receptors, and a method of treating obesity using the compounds described.

Abstract: The present invention relates to a compound having the general formula (Di), (Dii), or (Diii), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.

Abstract: A compound of Formula (I) or a pharmaceutically acceptable salt thereof: wherein: R1 represents a group selected from: i) phenyl optionally substituted with one or two substituents independently selected from Me, OMe, CF3, F, Cl and NMe2; furanyl, thiophenyl, pyrrolyl, pyridyl, cyclohexyl or naphthyl, each of which is optionally substituted with one or two substituents independently selected from Me, OMe, CF3, F, Cl and NMe2; and iii) benzo[1,3]dioxo5-yl or 2,3-dihydrobenzo[1,4]dioxin-6-yl; R2 represents CF3, C1-4alkyl, or CHF2; when R1 represents optionally substituted furanyl, thiophenyl, pyrrolyl, pyridyl or naphthyl, R3 represents Et; when R1 represents optionally substituted cyclohexyl, R3 represents Et or Me; otherwise R3 represents Et, Me, Br or OMe, compositions containing them, their use in therapy, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided, together with certain novel compounds.

Abstract: The present invention relates to novel heterocyclically fused diaryldihydropyrimidine derivatives, to processes for their preparation, to their use alone or in combination for the treatment and/or prevention of diseases and also to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of disorders of the lung and the cardiovascular system.

Abstract: Methods of treating a head and neck cancer are disclosed.

Abstract: The invention provides JAK kinase inhibitors of Formula Ia, enantiomers, diasteriomers or pharmaceutically acceptable salts thereof, wherein R1, R2, R7 and Z are defined herein, a pharmaceutical composition that includes a compound of Formula Ia and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a JAK kinase activity in a patient.

Abstract: The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.