Abstract: Compounds are provided for use with glucokinase that comprise the formula: wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.

Abstract: The present invention relates generally to pharmacological methods for the prevention of amelioration of sleep-related breathing disorders via administration of agents or combinations of agents that possess serotonin-related pharmacological activity.

Abstract: The invention relates to new methods for the treatment of oncological and fibrotic disease comprising the combined administration of a cell signalling and/or angiogenesis inhibitor in conjunction with an Aurora kinase inhibitor.

Abstract: The present invention relates to compounds and pharmaceutically acceptable salts of Formula (I): wherein X, R1, R2, R3, R4, R5, R6, R7, and R8 are as defined above. The invention further relates to pharmaceutical compositions comprising the compounds and pharmaceutically acceptable salts and to methods of treating diabetes mellitus and its complications (including in particular diabetic retinopathy, nephropathy or neuropathy), cancer, ischemia, inflammation, central nervous system disorders, cardiovascular disease, Alzheimer's disease and dermatological disease pression, viral diseases, inflammatory disorders, or diseases in which the liver is a target organ.

Abstract: The present invention relates to compounds useful as inhibitors of Aurora protein kinases. The invention also provides pharmaceutically acceptable compositions comprising those compounds and methods of using the compounds and compositions in the treatment of various disease, conditions, and disorders. The invention also provides processes for preparing compounds of the invention.

Abstract: There is provided compounds of formula (I): wherein R1, R2 and R3 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K) is desired and/or required, and particularly in the treatment of cancer.

Abstract: The invention relates to compounds of formula (I), wherein n is 1 or 2, Ar is a C-bound 1,2,4-triazol radical which carries a radical R1 on the remaining carbon atom and a radical R1a on one of the nitrogen atoms; R1 is hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C4 alkoxymethyl, fluorinated C1-C6 alkyl, fluorinated C3-C6 cycloalkyl, fluorinated C1-C4 alkoxymethyl, or optionally substituted phenyl or 5- or 6-membered heteroaryl; R1a is hydrogen or C1-C4 alkyl; and R2 is C1-C6 alkyl, C3-C6 cycloalkyl, fluorinated C1-C6 alkyl or fluorinated C3-C6 cycloalkyl; and to the physiologically tolerated acid addition salts of there compounds.

Abstract: Disclosed are new compounds of formula (1) exhibiting excellent activity for glucokinase, pharmaceutical compositions having the same as an active ingredient, and a method of using the same as an active ingredient for lowering blood glucose level: in which the substituents are as defined herein.

Abstract: Certain heterocyclic amide compounds are described. The compounds may be used in pharmaceutical compositions and methods for treating disease states, disorders, and conditions mediated by TRPA1 activity, such as pain, arthritis, itch, cough, asthma, or inflammatory bowel disease.

Abstract: Bone targeted compounds and methods are provided. Compounds can include a Bone Targeting Portion (RT), having an affinity for bone; a Bone Active Portion (RA) for interacting with and affecting bone; and a Linking Portion (RL) connecting the Bone Targeting Portion and the Bone Active Portion.

Abstract: THE INVENTION RELATES TO compounds, proteins and methods of treatment therewith. Aspects of embodiments of the invention further relates to compounds and methods of treatment for bone, bone marrow, and bone tissue.

Abstract: Provided herein are methods of and compositions for, treating, preventing and managing various neurological disorders. The methods comprise administering a transnorsertraline in combination with a serotonin receptor IA agonist, antagonist or modulator.

Abstract: The invention relates to (among other things) oligomer-PTK inhibitor conjugates and related compounds. A compound of the invention, when administered by any of a number of administration routes, exhibits advantages over PTK inhibitor compounds lacking a water soluble, non peptidic oligomer.

Abstract: The present invention relates to substituted pyrrolyl-pyrimidines which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular MPS1. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such these compounds or the pharmaceutical compositions containing them.

Abstract: THE INVENTION RELATES TO compositions, compounds, proteins and methods of treatment therewith. Aspects of embodiments also relate to a method of treating a patient by delivering to the tissues of said patient or administering to said patient a therapeutically effective amount of one or more compounds. Aspects of embodiments also relate to a method of detecting the presence of bone disease by machine-assaying detectable serotonin. Aspects of embodiments also relate to methods of treating disease in subjects.

Abstract: The invention relates to novel oxindole derivatives of general formula (I), in which the substituents A, B, R1, R2 and R3 are defined as cited in claim 1, to medicaments containing said derivatives and to the use of the latter for the prophylaxis and/or treatment of vasopressin-dependent and/or oxytocin-dependent diseases.

Abstract: Novel compounds selected from 2-(3-aminoaryl)amino-4-aryl-thiazoles of formula (I) that selectively modulate, regulate, and/or inhibit signal transductions mediated by certain native and/or mutant tyrosine kinases implicated in a variety of human and animal diseases such as cell proliferative metabolic, allergic and degenerative disorders. More particularly, these compounds are potent and selective c-kit inhibitors.

Abstract: 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 kinase activity, in particular PI3-kinase activity.

Abstract: The present invention relates to compositions and methods for treating inflammation-associated tissue damage, and particularly transfusion-associated, disorders, by inhibiting or reducing E-selectin mediated signal transduction pathways, such as E-selectin mediated activation of ?M?2.

Abstract: The present invention relates to a method of treating cancer in a mammal by administration of 4-quinazolinamines and at least one additional anti-neoplastic compound. In particular, the method relates to a methods of treating cancers by administration of N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine and salts and solvates thereof in combination with at least one additional anti-neoplastic compound.

Abstract: The present application relates to novel substituted dihydropyrazolone derivatives, processes for their preparation, their use for treatment and/or prophylaxis of diseases and their use for the preparation of medicaments for treatment and/or prophylaxis of diseases, in particular cardiovascular and haematological diseases and kidney diseases, and for promoting wound healing.

Abstract: Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful. Also disclosed are methods of making the compounds.

Abstract: The disclosure relates to methods for identifying a tumor as an E2F-responsive gene over-expressing (ERGO) tumor, methods of determining the likelihood that an ERGO tumor patient will survive to a future date, methods of treating an ERGO tumor in a patient, and methods of selecting patients diagnosed as ERGO tumor prostate cancer patients for aggressive clinical treatment. The methods of the disclosure are applicable to ERGO tumors present in different human organs and tissues such as breast, lung, thyroid, ovary, and prostate.

Abstract: The present invention relates to 6-(3-aza-bicyclo[3.1.0]hex-3-yl)-2-phenyl-pyrimidine derivatives and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.

Abstract: A compound represented by the formula (I): or a pharmaceutically acceptable salt thereof, wherein: R1 represents a branched lower alkyl group having from 3 to 9 carbon atoms or the like; R2 represents a 6-membered heteroaryl group having 1 or 2 nitrogen atoms or the like; R3 represents a hydrogen atom, an alkanoylamino group or the like; R4 represents a hydrogen atom, a lower alkyl group or the like; X1 represents an oxygen atom or a sulfur atom; X2 represents an oxygen atom or a single bond; and m indicates an integer of from 0 to 4. This compound has a metabotropic glutamate receptor 1 inhibitory effect, and therefore is useful for the treatment of a brain disorder such as convulsion, acute pain, inflammatory pain, chronic pain, cerebral infraction or transient cerebral ischemic attack, a mental dysfunction such as schizophrenia, and a disease such as anxiety and drug addition.

Abstract: The invention relates to compounds of the formula I: wherein n is 1 or 2, Ar is a C-bound 1,2,4-triazol radical which carries a radical R1 on the remaining carbon atom and a radical R1a on one of the nitrogen atoms; R1 is hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C4 alkoxymethyl, fluorinated C1-C6 alkyl, fluorinated C3-C6 cycloalkyl, fluorinated C1-C4 alkoxymethyl, or optionially substituted phenyl or 5- or 6-membered heteroaryl; R1a is hydrogen or C1-C4 alkyl; and R2 is C1-C6 alkyl, C3-C6 cycloalkyl, fluorinated C1-C6 alkyl or fluorinated C3-C6 cycloalkyl; and to the physiologically tolerated acid addition salts of these compounds.

Abstract: The present application describes deuterium-enriched dasatinib, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.

Abstract: The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including CF Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Abstract: The present invention provides thiazole sulfonamide and oxazole sulfonamide compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.

Abstract: Provided are substituted pyrazole compounds which are useful as protein kinase inhibitors, compositions comprising the compounds, and methods of use thereof. The protein kinase inhibitors are particularly for inhibition of Aurora A (Aurora-2) protein kinase and are useful in the treatment of diseases associated with protein kinases, especially diseases associated with Aurora-2, such as cancer.

Abstract: This invention relates to the identification and treatment of aggressive lung cancer tumors in patients. More particularly, it provides a method of identifying patients with non-small cell lung carcinoma (NSCLC) who have an aggressive node-negative (N0) tumor and a likelihood of a poor overall survival. The method comprises the step of determining if one or more of certain identified proteins are activated in tumor cells obtained from the patient's tumor, wherein the activation of one or more of the proteins indicates that the patient has an aggressive N0 tumor and is likely to have a poor overall-survival. The invention also provides a method for selecting a treatment for an NSCLC patient with an N0 tumor and a method for treating such patients. It further provides a kit for identifying an NSCLC patient with an aggressive N0 tumor and a likelihood of a poor overall survival and a pharmaceutical composition for treating such patients.

Abstract: The present application discloses the use of the anti-malarial drug lumefantrine and related compounds in the treatment of cancer.

Abstract: Heterocyclic compounds of structural formula (I), or a pharmaceutically acceptable salt thereof, wherein W is a R1— substituted heteroaryl, R1 is an heteroaryl ring substituted with an ester or carboxylic acid containing radical, X-T is N—CR5R6, C?CR5 or CR13—CR5R6, Y is a bond or —C(O)—, a and b represent an integer selected from 1 to 4, and Ar is an optionally substituted phenyl or naphtyl, are inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD) The heterocyclic compounds are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, atherosclerosis, obesity, diabetes, neurological disease, Metabolic Syndrome, insulin resistance, cancer, liver steatosis, and non-alcoholic steatohepatitis.

Abstract: Compounds of formula I or pharmaceutically acceptable salts thereof, wherein R5 is a group of formula (a) or (b): and wherein m, n, p, q, X, Y, R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as defined herein. The compounds and compositions disclosed herein are useful to modulate the activity of JNK and treat diseases associated with JNK activity.

Abstract: In general, the present invention relates to compounds capable of inhibiting p38 in vivo or in vitro, and methods for treating conditions associated with p38 activity or cytokine activity.

Abstract: Described are compounds which inhibit, regulate and/or modulate kinase signal transduction, for example of Met kinase. The compounds are of the formulae A1 to A148 and B1 described herein, including 2-oxobenzoxazol-3-ylmethyl]phenyl}carbamate and 2-oxooxazolo[4,5-b]pyridin-3-ylmethyl)phenyl]carbamate compounds, and pharmaceutically usable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios. Also described are compositions containing these compounds. Also described are methods for the treatment of diseases in which the inhibition, regulation and/or modulation of kinase signal transduction plays a role by administering these compounds.

Abstract: The present invention relates to a method for enhancing the activity of kinase inhibitors in target cells, and more specifically for enhancing the activity of tyrosine kinase inhibitors (TKIs), said method comprising contacting a cell with a kinase inhibitor and a photosensitizing agent and irradiating said cell with light of a wavelength effective to activate the photosensitizing agent, and to the use of this method for enhancing the effects of kinase inhibitors or kinase inhibitor-based drugs in particular to achieve cell death, for example, in cancer treatment and other diseases or conditions in which kinase inhibitors, such as TKIs, have a beneficial effect.

Abstract: The present invention provides methods for treating fragile X syndrome and/or other neurodevelopmental disorders by administering small molecule p21-activated kinase (PAK) inhibitors to a patient suffering from, susceptible to, and/or exhibiting one or more symptoms of FXS and/or other neurodevelopmental disorders. The present invention provides specific small molecule PAK inhibitors and pharmaceutical compositions comprising small molecule PAK inhibitors.

Abstract: Compounds that inhibit protein kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed.

Abstract: The present application relates to novel substituted dihydropyrazolone derivatives, processes for their preparation, their use for treatment and/or prophylaxis of diseases and their use for the preparation of medicaments for treatment and/or prophylaxis of diseases, in particular cardiovascular and haematological diseases and kidney diseases, and for promoting wound healing.

Abstract: The present application includes methods for using IL-8 as a biomarker for, e.g., tumor size, for example, during course of treatment with an anti-cancer agent such as an ERK inhibitor.

Abstract: The present invention encompasses compounds of general formula (1) wherein A, B, X, R1 to R3 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use for preparing a medicament having the above-mentioned properties.

Abstract: Oral dosage forms for basic amine drugs, the dosage forms having a gastro-retentive component and a non gastro-retentive component. These dosage forms are capable of providing both IR and SR release rates for these drugs. In addition, they provide for release of the drug in the stomach and/or intestine of a mammal to which such dosage forms are administered. Such dosage forms include tablets and capsules. Such dosage forms provide improved bioavailability of otherwise poorly bioavailable basic amine drugs.

Abstract: Compositions which act synergistically to inhibit the growth of cancer cells and methods of use thereof are disclosed.

Abstract: Compositions and methods are provided for using tyrosine kinase inhibitors to treat pathogenic infection. In particular, methods for using Abl-family tyrosine kinase inhibitors to treat pathogenic infection are provided. Infections to be treated according to the present invention include, particularly, those caused by microbial pathogens such as bacteria and viruses.

Abstract: The present invention provides a new group of protein kinase inhibitors, pyrropyrimidine and pyrazolopyrimidine derivatives, and pharmaceutically acceptable salts and prodrugs thereof that are useful for treating cell proliferative disease and disorder such as cancer, autoimmune diseases, infection, cardiovascular disease and neurodegenerative disease and disorder. The present invention provides methods for synthesizing and administering the protein kinase inhibitor compounds. The present invention also provides pharmaceutical formulations comprising at least one of the protein kinase inhibitor compounds together with a pharmaceutically acceptable carrier, diluent or excipient therefor. The invention also provides useful intermediates generated during the syntheses of the pyrropyrimidine and pyrazolopyrimidine derivatives.

Abstract: The present invention provides substituted pyrazolo-heterocycles having the general structure of formula I The structures of rings A and B and substituents Ra, Rb and Rc are described in the specification. Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis, treatment and inhibition of cannabinoid receptor-associated diseases and conditions, such as pain, inflammation and pruritis.

Abstract: This invention is directed to a compound of Formula (I): and forms thereof, wherein A, B, E, G, X and L2 are as defined herein and their use as urotensin II receptor antagonists.

Abstract: Compounds of the formula (I), their derivatives, analogs, tautomeric forms, regioisomers, stereoisomers, polymorphs, solvates, intermediates, pharmaceutically acceptable salts, pharmaceutical compositions, N-oxides, metabolites and prodrugs thereof. These compounds are phosphodiesterase type 4 (PDE4) inhibitors. They are useful in the treatment of a variety of allergic or inflammatory diseases including asthma, COPD, chronic bronchitis, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, vernal conjunctivitis, psoriasis, rheumatoid arthritis, ulcerative colitis, Crohn's disease, uveitis, NASH and lupus.

Abstract: Compounds of the formula I, in which R1, R2, R3, R3?, R4, R4?, E, E?, E? and E?? have the meanings indicated in Claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumours.