Abstract: The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins that are degraded and/or otherwise inhibited by bifunctional compounds of the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand that binds to the ubiquitin ligase and on the other end a moiety that binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds of the present invention, consistent with the degradation/inhibition of targeted polypeptides.

Abstract: The present invention features a method for determining the prognosis for survival of a cancer patient. Methods for measuring the level of NOL3 expression in a cancer cell-containing sample from a patient, and comparing the level of NOL3 expression in the sample to a reference level of NOL3 expression are also included. A higher level of NOL3 relative to the reference level correlates with decreased survival of the patient, and an equivalent or lower level of NOL3 relative to the reference level correlates with increased survival of the patient.

Abstract: Methods and pharmaceutical compositions for reducing number of gout flares experienced by a patient are disclosed. The methods can comprise administering to a patient with hyperuricemia an effective amount of a xanthine oxidase inhibitor in a modified release dosage form once daily or in an immediate release dosage form two or more times daily to prevent at least one gout flare or reduce the number of gout flares experienced by the patient.

Abstract: Compounds are provided having an excellent hypoglycemic effect and ? cell- or pancreas-protecting effects, or pharmaceutically acceptable salts thereof, and a pharmaceutical composition having an excellent therapeutic effect and/or prophylactic effect on type 1 diabetes, type 2 diabetes, and the like, which cause hyperglycemia due to abnormal glucose metabolism. A compound represented by general formula (I), or a pharmaceutically acceptable salt thereof, is disclosed.

Abstract: The invention relates to a novel compound of formula (I) or a stereoisomer, or a racemate or a mixture or a pharmaceutically acceptable salt thereof: wherein: R is phenyl or a 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms selected from S, N and O, such rings may be optionally substituted with n groups Q; Q is selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN, SO2CH3 or a group —O[(CR1R2]pQ1; or Q may be a group Q2; Q1 is phenyl, which may be optionally substituted with n substituents selected from a group consisting of: C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN, or a group Q2; or corresponds to 2,2-difluoro-benzo[d][1,3]dioxol-4-yl; Q2 is a 5- or 6-membered heteroaryl containing at least one nitrogen atom, which may optionally substituted with n substituents selected from a group consisting of: Cl C1-C4 alkyl, halogen, halo C1-C4 alkyl, C1-C4 alkoxy, CN; P is a 6-membered heteroaryl or a 8-1 1 membered bicyclic heteroaryl group, which

Abstract: The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.

Abstract: The present invention discloses compositions and a method of improving the pharmacokinetics of pharmaceutical agents (or pharmaceutically acceptable salts, esters, and prodrugs thereof) which are metabolized by cytochrome P450 monoxygenase comprising coadministering ritonavir or a pharmaceutically acceptable salt, ester, and prodrug thereof.

Abstract: The present invention relates to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, corresponding pharmaceutical compositions, compound preparation and treatment methods directed to bacterial infections and inhibition of bacterial peptide deformylase (PDF) activity.

Abstract: Disclosed are compounds having the formula: wherein X1, X2, X3, R1, R2, R3, R4, Y, A, Z, L and n are as defined herein, and methods of making and using the same.

Abstract: The invention relates to novel compounds of Formula I: wherein A, Y, R1, R2 and the subscript b each has the meaning as described herein and compounds of Formula I, and stereoisomers, geometric isomers, tautomers, solvates, metabolites, isotopes, pharmaceutically acceptable salts, or prodrugs thereof. Compounds of Formula I and pharmaceutical compositions thereof are useful in the treatment of disease and disorders in which undesired or over-activation of NF-kB signaling is observed.

Abstract: Provided herein are novel compounds, pharmaceutical compositions for use, inter alia, in methods of reducing Wnt-mediated effects and treating cancer.

Abstract: The present invention relates to compounds of formula (I): wherein Q, G1, G2, and G3, are defined herein. Pharmaceutical compositions and methods for treating DGAT-1 related diseases or conditions are also disclosed.

Abstract: The present invention relates to novel derivatives of oxazolidinone, a method thereof and pharmaceutical compositions comprising the derivatives for use in an antibiotic. The oxazolidinone derivatives of the present invention show inhibitory activity against a broad spectrum of bacteria and lower toxicity. The prodrugs, prepared by reacting the compound having hydroxyl group with amino acid or phosphate, have an excellent efficiency on solubility thereof against water. Further, the derivatives of the present invention may exert potent antibacterial activity versus various human and animal pathogens, including Gram-positive bacteria such as Staphylococi, Enterococci and Streptococi, anaerobic microorganisms such as Bacteroides and Clostridia, and acid-resistant microorganisms such as Mycobacterium tuberculosis and Mycobacterium avium. Accordingly, the compositions comprising the oxazolidinone are used in an antibiotic.

Abstract: The present invention relates to methods of reducing blood pressure in a subject by administering a plasma kallikrein inhibitor.

Abstract: The present disclosure relates to compounds effective as human protein tyrosine phosphatase beta (HPTP-?) inhibitors thereby regulating angiogenesis. The present disclosure further relates to compositions comprising said human protein tyrosine phosphatase beta (HPTP-?) inhibitors, and to methods for regulating angiogenesis.

Abstract: An object of the present invention is to provide a compound having a modulating activity at an S1P receptor which is useful for preventing and treating autoimmune diseases, allergic diseases, and the like. According to the present invention, a compound represented by formula (I) or a pharmaceutically acceptable salt thereof is provided.

Abstract: The present invention provides isoindolinone and pyrrolopyridinone derivatives, as well as their compositions and methods of use, that inhibit the activity of the serine/threonine kinase, Akt, and are useful in the treatment of diseases related to the activity of Akt including, for example, cancer and other diseases.

Abstract: Epothilone compounds represented by formula (I), their preparation methods and their use for preparing medicines are disclosed. The epothilone compounds are prepared by bioconversion and chemosynthesis or chemical modifications using epothilones or their derivatives as starting materials. Said epothilone compounds can be used to treat proliferative diseases.

Abstract: Disclosed herein are cannabinoid receptor ligands of formula (I) wherein L1, A1, R1g, z, R2, R3, and R4 are as defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also presented.

Abstract: Provision of an agent for promoting proliferation of meibomian gland epithelial cells or corneal epithelial cells, and a therapeutic agent for ocular diseases such as meibomian gland dysfunction, dry eye and the like. A preparation containing [3-[2-[4-isopropyl-2-(4-trifluoromethyl)phenyl-5-thiazolyl]ethyl]-5-methyl-1,2-benzisoxazol-6-yl]oxyacetic acid, [4-[3-[2-(4-trifluoromethyl)phenyl-4-isopropyl-5-thiazolyl]propionyl]-2-methylphenoxy]acetic acid or [4-[3-[2-(2-hydroxy-4-chlorophenyl)-5-isopropyl-4-oxazolyl]propionyl]-2-methylphenoxy]acetic acid, or a pharmacologically acceptable salt thereof as an active ingredient is used as an agent for promoting proliferation of meibomian gland epithelial cells or corneal epithelial cells, as well as a therapeutic agent for ocular diseases such as meibomian gland dysfunction, dry eye and the like.

Abstract: 3-aza-bicyclo[3.1.0]hexane-6-carboxylic acid amide derivatives which are agonists of somatostatin receptor subtype 4 (SSTR4), useful for preventing or treating medical disorders related to SSTR4.

Abstract: Disclosed are compounds and methods of using compounds of the invention for treating a subject with a proliferative disorder, such as cancer, and methods for treating disorders responsive to Hsp70 induction and/or natural killer induction. Also, disclosed are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier.

Abstract: Macular degeneration, closed head injury, stroke, irritable bowel disease, and reperfusion injury are all associated with biological injury due to reactive oxygen species, probably due to focal iron overload in many instances. The present invention provides methods and pharmaceutical compositions for treating these diseases and conditions using desferrithiocin analogs of Formula (I). In certain embodiments, the analogs include a polyether moiety at the 4?-position of the phenyl ring of the compound.

Abstract: A new class of haloalkyl heteroaryl benzamides is described. These compounds show strong activity against hepatitis viruses.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). 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.

Abstract: The present invention relates to compounds of formula (IA) wherein QA is QA1 or QA2 P is P1, heterocycyl or heterocyclyl substituted by one to five Z; and wherein A1, A2, A3, A4, G1, Z, R1, R2, R3 and R4 are as defined in claim 1; or a salt or N-oxide thereof. Furthermore, the present invention relates to processes and intermediates for preparing compounds of formula (IA), to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising the compounds of formula (IA) and to methods of using the compounds of formula (IA) to control insect, acarine, nematode and mollusc pests.

Abstract: Tubulysins are a series of naturally occurring cytotoxic agents that are of interest as anticancer therapeutic agents. Processes and intermediates useful for preparing naturally occurring and non-naturally occurring tubulysins and analogs and derivatives thereof are described.

Abstract: The invention relates to a mixture comprising clothianidin, metofluthrin, and piperonyl butoxide which provides superior insect knockdown and mortality rates, and is especially effective against bed bugs. This mixture of actives may be formulated with adjuvants, such as solvents, anti-caking agents, stabilizers, defoamers, slip agents, humectants, dispersants, wetting agents, thickening agents, emulsifiers, and/or preservatives which increase the activity of the mixture. Mixtures of the present invention have long lasting residual control.

Abstract: This application relates to chemical compounds which may act as inhibitors of; or which may otherwise modulate the activity of, a bromodomain-containing protein, including bromodomain-containing protein 4 (BRD4), and to compositions and formulations containing such compounds, and methods of using and making such compounds. Compounds include compounds of Formula (I) wherein R1a, R1b, R2, R2b, R3, R4a, R4b, and R5 are described herein.

Abstract: The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

Abstract: Disclosed are methods for preventing metastasis of cancer cells. The disclosed compounds can be used to prevent the spread of tumor or other types of cancer cells.

Abstract: Methods and compositions are provided for preventing or reversing loss of the therapeutic effect of a drug, where the loss is associated with the repeated administration of the drug to a patient. The method includes administering to the patient a dopamine receptor agonist or partial agonist or a drug that increases the extracellular level of dopamine by enhancing release of dopamine, decreasing the removal of dopamine from the extracellular space, enhancing the synthesis of dopamine within the brain, or decreasing metabolic degradation of dopamine; and also administering to the patient an opioid receptor antagonist in an ultra-low dose amount, wherein the ultra-low dose amount is effective to prevent or reverse loss of therapeutic effects associated with the repeated administration of the drug to the patient. The methods are useful for various treatments, including treating Parkinson's Disease, Restless Leg Syndrome, depression, schizophrenia, psychostimulant drug abuse, or attention deficit disorder.

Abstract: The present invention relates to novel compounds of formula I wherein W, n, X and W? are defined in the description; invention compounds are modulators of metabotropic glutamate receptors—subtype 5 (“mGluR5”) which are useful for the treatment of central nervous system disorders as well as other disorders modulated by mGluR5 receptors.

Abstract: The invention relates to active compound combinations, in particular a fungicidal and/or insecticidal composition, comprising Isotianil (3,4-dichloro-N-(2-cyanophenyl)-5-isothiazolecarboxamide) and at least one further insecticide of the anthranilamide group and optionally one further insecticide of the neonicotinoids. Moreover, the invention relates to a method for curatively or preventively controlling the phytopathogenic fungi and/or microorganisms and/or pests of plants or crops, to the use of a combination according to the invention for the treatment of seed, to a method for protecting a seed and not at least to the treated seed.

Abstract: The present specification discloses honeybee repellents exhibiting repellent properties similar to 2-heptanone, compositions comprising such repellents, uses to repel a honeybee from a mammal, location, plant, structure treated of such repellents, and methods of treating a mammal, location, plant, structure by applying such repellents.

Abstract: The present invention relates to methods of treating subjects suffering from pre-hypertension or hypertension by administering to a subject in need of treatment thereof a therapeutically effective amount of at least one xanthine oxidoreductase inhibiting compound or salt thereof.

Abstract: The present invention aims to provide a novel compound having a TRPA1 antagonist activity, and a medicament containing the compound. Moreover, the present invention aims to provide a TRPA1 antagonist and a medicament useful for the prophylaxis or treatment of diseases involving TRPA1. A medicament containing a compound represented by the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a pharmaceutically acceptable salt thereof, and the like.

Abstract: The present specification discloses honeybee repellents exhibiting repellent properties similar to 2-heptanone, compositions comprising such repellents, uses to repel a honeybee from a mammal, location, plant, structure treated of such repellents, and methods of treating a mammal, location, plant, structure by applying such repellents.

Abstract: The invention relates to new compounds of the formula I to their use as medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.

Abstract: The present disclosure provides substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes, of Formula I D-M-D??(Formula I) useful as antiviral agents. In certain embodiments disclosed herein M is a group —P-A-P— where A is Certain substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes disclosed herein are potent and/or selective inhibitors of viral replication, particularly Hepatitis C virus replication. Pharmaceutical compositions/and combinations containing one or more substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes and a pharmaceutically acceptable carrier are also provided by this disclosure. Methods for treating viral infections, including Hepatitis C viral infections are provided by the disclosure.

Abstract: Compositions and methods are disclosed which are useful of the treatment and prevention of proliferative disorders.

Abstract: Disclosed herein is a compound of the formula Therapeutic methods, compositions, and medicaments, related thereto are also disclosed.

Abstract: Macular degeneration, closed head injury, stroke, irritable bowel disease, and reperfusion injury are all associated with biological injury due to reactive oxygen species, probably due to focal iron overload in many instances. The present invention provides methods and pharmaceutical compositions for treating these diseases and conditions using desferrithiocin analogs of Formula (I). In certain embodiments, the analogs include a polyether moiety at the 3?-position of the phenyl ring of the compound. Formula (I).

Abstract: Immune-modulators of formula (I) below are prepared: A pharmaceutical composition contains the immune-modulators. The pharmaceutical composition is used as a drug, especially as an immune-modulating drug. The compound can be used in treatment of immune disorders and for immune suppression. Thus, for example, the compound can be used in treating hypo-immunity, rejection after organ transplantation and auto-immune disease.

Abstract: A process for formulating certain epothilones and analogs thereof for parenteral administration is provided wherein the pH of the formulation for administration can be controlled to enhance the stability and thus, potency of the epothilone, or analog thereof.

Abstract: The present invention relates to azole compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

Abstract: Novel compounds and compositions for treating patients in need of relief from HIV, AIDS and AIDS-related diseases are described. Methods for treating HIV, AIDS, and AIDS-related diseases using the compounds described herein are also described.

Abstract: Provided are: an agent for suppressing an undesirable effect of an opioid-type analgesic (opioid), which comprises a compound having adenosine A2A receptor antagonistic activity or a pharmaceutically acceptable salt thereof as an active ingredient; the agent for suppressing an undesirable effect of an opioid-type analgesic (opioid), wherein the undesirable effect of the opioid-type analgesic (opioid) is analgesic tolerance or constipation; the agent for suppressing an undesirable effect of an opioid-type analgesic (opioid), wherein the undesirable effect of the opioid-type analgesic (opioid) is analgesic tolerance; and the like.

Abstract: The present application relates to thiazolylidene containing compounds of formula (I) wherein R1, R2, R3, R4, L2 and A are as defined in the specification. Compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

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