Abstract: The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders. The methods generally comprise administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that is designed to be substantially active in the gastrointestinal (GI) tract to inhibit NHE-mediated antiport of sodium ions and hydrogen ions therein.

Abstract: The disclosure is directed to improved methods for preparing substituted quinolinylcyclohexylpropanamide compounds.

Abstract: Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): and/or a salt thereof, wherein R1 is —OH or —OP(O)(OH)2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rc are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Abstract: The present invention provides an antipsychotic drug comprising fasudil or a pharmaceutically acceptable salt thereof as an active agent for the treatment of schizophrenia, including schizophrenia caused by dysfunction of ARHGAP10.

Abstract: A stable crystal of a salt of N—[(R)-1-{(S)-2-hydroxy-2-phenylpropylamino}propan-2-yl]isoquinoline-6-sulfonamide may have desirable properties for a pharmaceutical drug substance, and more specifically N—[(R)-1-{(S)-2-hydroxy-2-phenylpropylamino}propan-2-yl]isoquinoline-6-sulfonamide dihydrochloride anhydride. A crystal of the anhydride may have characteristic peaks at 2? angles of 6.8±0.1°, 10.0±0.1°, 12.7±0.1°, 14.6±0.1°, 14.8±0.1°, 16.2±0.1°, 17.4±0.1°, 17.8±0.1°, 19.5±0.1°, 20.0±0.1°, 21.6±0.1°, 24.7±0.1°, 25.5±0.1°, 25.8±0.1°, 29.8±0.1°, 39.5±0.1°, and/or 44.9±0.1° in powder X-ray diffraction spectrum.

Abstract: The present invention relates to the derivatives of compound of formula (I) and pharmaceutically acceptable salts thereof. The present invention further provides the methods of preparation of compound of formula (I) and use thereof as PRMT5 inhibitors. The compounds are useful as medicaments in the treatment of conditions where PRMT5 inhibition is desired, such as cancer, metabolic disorders, inflammation, autoimmune disease and hemoglobinopathies.

Abstract: It relates to a process for the preparation of lifitegrast (I) by: a) reacting benzofuran-6-carboxylic acid (II) with a non-chlorinated carboxyl activating agent; b) reacting the activated compound of formula (II) obtained in step a) with compound (III) or a salt thereof to give lifitegrast or a salt thereof; and c) optionally isolating the obtained lifitegrast. It also relates to a process for the purification of lifitegrast (I) by i) reacting lifitegrast (I) with dicyclohexylamine to give the dicyclohexylamine salt of lifitegrast (Ia); ii) isolating the compound of formula (Ia) from the reaction medium; iii) converting the dicyclohexylamine salt into lifitegrast by the treatment with an acid; and iv) isolating the compound of formula (I) from the reaction medium. It also relates to dicyclohexylamine salt of lifitegrast and to a process for its preparation.

Abstract: Fused bicyclic compounds are inhibitors of GPR91. The compounds, their stereoisomers, tautomers, prodrugs, polymorphs, solvates, pharmaceutically acceptable salts, and pharmaceutical compositions containing them are useful in the treatment, prevention, prophylaxis, management, or adjunct treatment of all medical conditions related to inhibition of GPR91.

Abstract: Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): and/or a salt thereof, wherein R1 is —OH or —OP(O)(OH)2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rc are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Abstract: Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): and/or a salt thereof, wherein R1 is —OH or —OP(O)(OH)2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rc are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Abstract: A compound of general formula (I): wherein the meanings of the variables are explained in the specification, or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof. A pharmaceutical composition can include compounds of the invention, which can be used in a method for inhibiting TLR7/8 receptors.

Abstract: The invention provides certain (phenyl)-(pyrazol)-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one compounds of formula I as D1 positive allosteric modulators (PAMs), and pharmaceutical compositions thereof. The invention further provides methods of using a compound of formula I, or a pharmaceutically acceptable salt thereof, to treat certain symptoms of Parkinson's disease, schizophrenia, ADHD or Alzheimer's disease.

Abstract: Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof. Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the ?-catenin pathway, methods of modulating STAT 1 activity, methods of modulating the TGF?/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.

Abstract: Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof. Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the -catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGF?/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.

Abstract: Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): and/or a salt thereof, wherein R1 is —OH or —OP(O)(OH)2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rc are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Abstract: The present disclosure is generally directed to compositions and methods for treating apicomplexan protozoan related disease, such as toxoplasmosis and cryptosporidiosis.

Abstract: Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols are useful as inhibitors of the phosphodiesterase 4 (PDE4) enzyme and the treatment of certain conditions such as COPD.

Abstract: Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): and/or a salt thereof, wherein R1 is —OH or —OP(O)(OH)2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rc are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Abstract: The present invention provides compounds of formula I: or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds, and methods of using such compounds for treatment of joint damage or joint injury in a mammal, and for inducing differentiation of mesenchymal stem cells into chondrocytes.

Abstract: The present invention relates, inter alia, to metal complexes having improved solubility, to processes for the preparaion of the metal complexes, to devices comprising these metal complexes and to the use of the metal complexes.

Abstract: Novel aryl, heteroaryl, and non-aromatic heterocyle substituted tetrahydroisoquinolines are described in the present invention. These compounds are used in the treatment of various neurological and physiological disorders. Methods of making these compounds are also described in the present invention.

Abstract: There are provided compounds represented by the following general formula (I) or pharmaceutically acceptable salts of thereof, which have a superior monoacylglycerol acyltransferase 2 inhibitory action: wherein Ring A represents a partially saturated heteroaryl group, an aryl group or a heteroaryl group, RB represents a C4-18 alkyl group, a C3-8 cycloalkyl group, a partially saturated aryl group, an aryl group, or the following formula (II): wherein V represents the formula —CR11R12—, —CO—, —CO—O—, or —CO—NH—, W represents a single bond or a C1-3 alkylene group, and Ring B represents a C3-8 cycloalkyl group, a C3-8 cycloalkenyl group, a partially saturated heteroaryl group, a saturated heterocyclyl group, an aryl group, or a heteroaryl group, Y represents a nitrogen atom or the formula N+(RF), RF represents a C1-4 alkyl group, and m and n, which may be the same or different, each represent an integer of 0 or 1.

Abstract: Compounds and compositions comprising compounds that inhibit glutaminase are described herein. Also described herein are methods of using the compounds that inhibit glutaminase in the treatment of cancer.

Abstract: There is provided compounds for treating bone loss diseases and for preventing bone loss. Specifically the present invention relates to compounds, preferable isoquinolene derivatives.

Abstract: Compounds, pyridine N-oxides, and pharmaceutically acceptable salts of formula (I) are useful as inhibitors of the phosphodiesterase 4 (PDE4) enzyme and for preventing and/or treating diseases of the respiratory tract characterized by airway obstruction, such as asthma or COPD.

Abstract: Provided is a method whereby a heteroaromatic ring aryl can be very rapidly methylated at a high yield. In an N-alkyl-2-pyrrolidinone, a heteroaromatic ring aryltrialkylstannan is cross-coupled with methyl iodide in the presence of a palladium complex, a phosphine ligand, a cuprous halide, a carbonic acid salt and/or an alkali metal fluoride to thereby rapidly methylate the heteroaromatic ring aryl. (Formula shows a case wherein the heteroaromatic ring aryl is a pyridyl group.

Abstract: Compounds of Formula (I) along with processes for their preparation that are useful for treating, managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of cannabinoid (CB) receptors. Methods of treating, managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of cannabinoid (CB) receptors of Formula (I).

Abstract: A fullerene derivative represented by the following formula (1): wherein “FLN” represents a fullerene core, R1 represents an optionally substituted C1-C24 alkyl group or an optionally substituted C7-C24 aralkyl group, R2 and R3 independently represent a hydrogen atom or an optionally substituted C1-C24 hydrocarbon group but excluding a case where both of R2 and R3 are hydrogen atoms, and R2 and R3 may combine together to form a ring.

Abstract: The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.

Abstract: The present invention provides a novel isoquinoline-6-sulfonamide derivative that is useful as a medicine. The present invention provides an isoquinoline-6-sulfonamide derivative represented by Formula (1), a salt thereof, or a solvate of the derivative or the salt, wherein R1 and R2 each independently represent a hydrogen atom, or the like; R3 and R4 each independently represent a hydrogen atom, an alkyl group, or the like; R5 represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted cycloalkyl group, an optionally substituted alkanoyl group, or the like; and A represents a linear or branched alkylene group having 2 to 6 carbon atoms.

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

Abstract: Oxazole derivatives are described. The inventive compounds are useful as kinase inhibitors, and may be used in the treatment of cancer, such as prostate cancer, lung cancer, breast cancer, colon cancer, leukemia, CNS cancer, melanoma, ovarian cancer, and renal cancer.

Abstract: Disclosed is a compound of formula (I). Wherein R1, R2Ar and Cy are as defined herein, or a pharmaceutically acceptable salt thereof. Also disclosed are pharmaceutical compositions of the compound of formula (I), methods of making the compounds of formula I, and methods of using the compounds of formula (I) to treat a disorder associated with activation of CCR10.

Abstract: The present invention concerns compounds of general formula (I): Method of preparation and uses thereof.

Abstract: This invention relates to a process of producing compounds, which are useful as bleach boosters, as well as to the compounds, which are obtainable using said process, and to their use.

Abstract: The present invention relates compounds of general formula (I) and stereoisomers and pharmaceutically acceptable salts and prodrugs thereof; wherein R? and R1-R5 are as defined in the claims. The invention also relates to said compounds for use as a medicament and particularly in the treatment of drug addiction and CNS related diseases.

Abstract: The invention provides methods for substituting polyaromatic hydrocarbons or polyheterocyclic compounds with perfluoroalkyl groups. The methods can include heating a polyaromatic hydrocarbon substrate or a polyheterocyclic compound substrate in the presence of a perfluoroalkyl iodide, typically in a closed system, wherein the heating is sufficient to bring both the polyaromatic hydrocarbons or polyheterocyclic compound, and the perfluoroalkyl iodide, into the gas phase, thereby allowing the substrate to react with the perfluoroalkyl iodide in the gas phase to form polyaromatic hydrocarbons or polyheterocyclic compounds having one or more perfluoroalkyl substituents. The methods allow for the creation of versatile libraries of novel perfluoroalkyl-containing derivatives that can serve as important building blocks and active components in biomedical, electronic, and materials applications.

Abstract: Bicycloheteroaryl compounds are disclosed that have a formula represented by the following: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, traumatic injury, and others.

Abstract: The invention relates to 6-substituted isoquinoline and isoquinoline derivatives of the formula (I) useful for the treatment and/or prevention of diseases associated with Rho-kinase and/or Rho-kinase mediated phosphorylation of myosin light chain phosphatase, and compositions containing such compounds.

Abstract: Methods for deterring microglia-mediated neurotoxicity in a human or non-human animal subjects comprising the step of inhibiting or blocking the intermediate-conductance calcium-activated potassium channel Kv1.3 in microglia, such as in subjects how suffer from neurodegenerative diseases (e.g., Alzheimer's Disease) or ischemic/anoxic/hypoxic conditions. The inhibition or blocking of the KCa1.3 channels may be accomplished by administering a substance that inhibits Kv1.3 in microglia. Examples of Kv1.3 inhibiting substances include certain 5-phenoxyalkoxypsoralens, such as (4-Phenoxybutoxy)psoralen (PAP-1) as well as certain 4-phenoxybutoxy-substituted heterocyclic compounds.

Abstract: The invention relates to 6-substituted isoquinoline and isochinolone derivatives of the formula (I) useful for the treatment and/or prevention of diseases associated with Rho-kinase and/or Rho-kinase mediated phosphorylation of myosin light chain phosphatase, and compositions containing such compounds.

Abstract: The compounds of the present invention are represented by the chemical structure found in Formula (I): wherein: the carbon atom designated * is in the R or S configuration; and X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle opt

Abstract: Small molecule compounds are provided for treating lupus as are methods of treating lupus using these compounds.

Abstract: The invention relates to 6-piperidinyl-substituted isoquinoline derivatives of the formula (I) useful for the treatment and/or prevention of diseases associated with Rho-kinase and/or Rho-kinase mediated phosphorylation of myosin light chain phosphatase, and compositions containing such compounds.

Abstract: Methods of treating or suppressing oxidative stress diseases including mitochondrial diseases, impaired energy processing disorders, neurodegenerative diseases and diseases of aging are disclosed, as well as compounds useful in the methods of the invention, such as 2- substituted-p-quinone derivatives as disclosed herein.

Abstract: The invention relates to 6-substituted isoquinoline derivatives of the formula (I) useful for the treatment and/or prevention of diseases associated with Rho-kinase and/or Rho-kinase mediated phosphorylation of myosin light chain phosphatase, and compositions containing such compounds.

Abstract: The present invention is directed to 2,5-disubstituted piperidine amide compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

Abstract: The invention relates to 6-substituted isoquinoline and isoquinolinone derivatives of the formula (I) useful for the treatment and/or prevention of diseases associated with Rho-kinase and/or Rho-kinase mediated phosphorylation of myosin light chain phosphatase, and compositions containing such compounds.

Abstract: Described are GCF-8 inhibitors of the formula (I), and pharmaceutically acceptable salts thereof, wherein n, R1, R2, R5, R6, X and Z are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for inhibiting GDF-8 in a cell and methods for treating a patient suffering from a disease or disorder, wherein the patient would therapeutically benefit from an increase in mass or strength of muscle tissue.

Abstract: The disclosure relates to fumarate salts of 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide, to pharmaceutical compositions thereof, processes for making the same, and methods of use thereof.