Abstract: Provided herein are amino isoquinolinyl amide and sulfonamide compounds that affect the function of kinases and other proteins in a cell and that are useful as therapeutic agents. In particular, these compounds are useful in the treatment of eye diseases such as glaucoma and retinal diseases, as anti-inflammatory agents, for the treatment of cardiovascular diseases, and for diseases characterized by abnormal growth, such as cancers.

Abstract: Compounds having formula I, or pharmaceutically acceptable salts, hydrates or N-oxides thereof are provided and are useful for binding to CXCR7, and treating diseases that are dependent, at least in part, on CXCR7 activity. Accordingly, the present invention provides in further aspects, compositions containing one or more of the above-noted compounds in admixture with a pharmaceutically acceptable excipient.

Abstract: The present invention is directed to novel compounds of Formula (I), or a pharmaceutically acceptable salt, solvate or hydrate thereof. Pharmaceutical compositions comprising a compound of Formula (I), or a pharmaceutically acceptable salt, solvate or hydrate thereof, are also described. The invention is also directed to use of the compounds of Formula (I) for treating a condition in a mammal associated with AhR imbalance, such as an inflammatory disease or disorder.

Abstract: The present disclosure provides, inter alia, compounds with MASP-2 inhibitory activity, compositions of such compounds, and methods of making and using such compounds.

Abstract: A TLR9 inhibitor includes 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 TLR9 activity in vitro or in vivo. The method can be performed by administering the compound to a subject to inhibit TLR9 activity, which can be used to treat a disease or disorder associated with TLR9.

Abstract: The present disclosure provides pharmaceutical combinations of orally administered irinotecan and a P-gp inhibitor. The pharmaceutical combinations are suitable for the treatment of cancer in a subject and for reducing or preventing toxicity, hypersensitivity-type infusion reactions, and other negative outcomes resulting from or associated with intravenously administered irinotecan (e.g., Camptosar®) therapy in a subject suffering from cancer.

Abstract: 6-(2-(2H-tetrazol-5-yl)ethyl)-6-fluorodecahydroisoquinoline-3-carboxylic acid and 6-(2-(2H-tetrazol-5-yl)ethyl)-6-fluorodecahydroisoquinoline-3-carboxylic acid hydrocarbyl ester derivatives of formula are disclosed, as are pharmaceutical compositions and methods for the treatment of pain, epilepsy, convulsions, and seizures employing those compositions.

Abstract: The present invention is directed to novel compounds of Formula (I), or a pharmaceutically acceptable salt, solvate or hydrate thereof. Pharmaceutical compositions comprising a compound of Formula (I), or a pharmaceutically acceptable salt, solvate or hydrate thereof, are also described. The invention is also directed to use of the compounds of Formula (I) for treating a condition in a mammal associated with AhR imbalance, such as an inflammatory disease or disorder.

Abstract: A series of 8-phenyl-isoquinoline derivatives (I) exhibit high binding affinity to 5-HT7 receptor (5-HT7R) and demonstrate potent antinociceptive activity in two animal models for Irritable Bowel Syndrome (IBS) by intraperitoneal injection (i.p.) or by oral administration (p.o.). These 5-HT7 receptor antagonists are a new class of therapeutic agents for the treatment of IBS.

Abstract: The invention relates to a process for the preparation of Lifitegrast of formula (I), which comprises: a) condensation of the compound of formula (II) with the compound of formula (III) to give the compound of formula (IV) wherein R1, R2 and R3 are independently selected from straight or branched C1-C6 alkyl groups; b) chlorination of compound (IV) in the presence of a chlorinating agent (IV), (V), c) condensation of compound (V) with amino acid (VI) to give compound (I), c) condensation of compound (V) with amino acid (VI) to give compound (I), d) optional purification of the crude Lifitegrast in mixtures of polar aprotic solvents and water.

Abstract: Provided herein are amino isoquinolinyl amide and sulfonamide compounds that affect the function of kinases and other proteins in a cell and that are useful as therapeutic agents. In particular, these compounds are useful in the treatment of eye diseases such as glaucoma and retinal diseases, as anti-inflammatory agents, for the treatment of cardiovascular diseases, and for diseases characterized by abnormal growth, such as cancers.

Abstract: During development, OPCs migrate extensively throughout the spinal cord, but their migration is restricted at transition zones (TZ). At these specialized locations, unique glial cells in both zebrafish and mice are at least partially responsible for preventing peripheral OPC migration, but the mechanisms of this regulation are not understood. In order to elucidate the signals that mediate OPC segregation at motor exit point (MEP) TZs, we performed an unbiased small molecule screen. Using chemical screening and in vivo imaging, we discovered that inhibition of A2a adenosine receptors (AR) causes ectopic OPC migration out of the spinal cord. In our studies, we provide in vivo evidence that endogenous neuromodulation by adenosine regulates OPC migration along motor axons, specifically at the MEP TZ. This work opens exciting possibilities for understanding how OPCs reach their final destinations during development and identifies mechanisms that could promote their migration in disease.

Abstract: The present invention relates to a process for the preparation of (S)-Netarsudil or its pharmaceutically acceptable salts using novel intermediates. The present invention further provides novel salts, novel intermediates and novel polymorphic forms of the (S)-Netarsudil salts and process for the preparation of the same.

Abstract: Potent opioid receptor antagonists of formula (I) and their use as pharmacotherapies for treating depression, anxiety, schizophrenia, eating disorders, and addiction to cocaine, methamphetamine, nicotine, alcohol, and opiates are disclosed. More specifically, the disclosure provides potent and selective kappa opioid receptor antagonist compounds, pharmaceutical compositions of those compounds and uses of those compounds to ameliorate or treat addictions, eating disorders, etc.

Abstract: The present invention is directed to novel compounds of Formula (I), or a pharmaceutically acceptable salt, solvate or hydrate thereof. Pharmaceutical compositions comprising a compound of Formula (I), or a pharmaceutically acceptable salt, solvate or hydrate thereof, are also described. The invention is also directed to use of the compounds of Formula (I) for treating a condition in a mammal associated with AhR imbalance, such as an inflammatory disease or disorder.

Abstract: The present invention relates to a novel process for the preparation of lifitegrast of Formula I. The present invention further provides a novel process for the purification of lifitegrast of Formula I.

Abstract: Compositions and methods for repelling arthropods. The compositions include a carrier and an arthropod repelling compound, which can be a compound discovered by a novel and complex cheminformatic process to demonstrate repellency behavior across a broad spectrum of arthropods. The compound can be a thiane compound, a pyrrolidone compound, a cyclohexadiene compound, a cyclohexenone compound, a cyclohexene compound, a furanone compound, a pyran compound, a tetrahydropyran compound, a thiazolidine compound, a thiazoline compound, a dihydrothiophene compound, a dithiolane compound, a dithiane compound, an epoxide compound, an oxathiane compound, a cyclopentene compound, a cyclohexane compound, a quinoline compound, an oxazoline compound, a tetrahydropyridine compound, and an imidazolidinone compound, or a combination thereof.

Abstract: Disclosed are a class of isoquinoline compounds acting as RHO protein kinase inhibitors, and the use thereof in the preparation of a drug for treating diseases associated with RHO protein kinase. Particularly disclosed are compounds as shown in formula (I) and pharmaceutically acceptable salts thereof.

Abstract: The present disclosure provides solid state forms of a selective potassium channel modulator and pharmaceutical compositions comprising the solid state crystalline forms and pharmaceutically acceptable excipients, and methods for preparing and using the solid state forms and the pharmaceutical compositions thereof.

Abstract: Compounds having formula I, or pharmaceutically acceptable salts, hydrates or N-oxides thereof are provided and are useful for binding to CXCR7, and treating diseases that are dependent, at least in part, on CXCR7 activity. Accordingly, the present invention provides in further aspects, compositions containing one or more of the above-noted compounds in admixture with a pharmaceutically acceptable excipient.

Abstract: The invention provides various methods comprising the administration of a CYP2D6 bioactive drug covalently bound to a water-soluble oligomer. Metabolism of CYP2D6 bioactive drug conjugates is diverted from CYP2D6 to alternative pathways, and the conjugates may therefore be utilized to alleviate the problems associated with interpopulation variation resulting from the genetic polymorphism in the CYP2D6 gene.

Abstract: Novel crystalline polymorphic forms, Forms A, B, C, D, and E of a compound of Formula I, which has been found to be a potent inhibitor of LFA-1, are disclosed. Methods of preparation and uses thereof in the treatment of LFA-1 mediated diseases are also disclosed in this invention.

Abstract: A method for inhibiting TLR9 includes contacting the TLR9 with 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 TLR9 activity in vitro or in vivo. The method can be performed by administering the compound to a subject to inhibit TLR9 activity, which can be used to treat a disease or disorder associated with TLR9.

Abstract: A method for inhibiting TLR7 and/or TLR8 receptors includes contacting the receptor with 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 receptors and/or TLR8 receptors. The method can be performed by administering the compound to a subject to inhibit TLR7, TLR8, or TLR7/8 activity, which can be used to treat a disease or disorder associated with the receptors.

Abstract: The invention provides novel compounds having the general formula (I) wherein R1, R2, R9, Y, W, m, n, p and q are as defined herein, compositions including the compounds and methods of using the compounds.

Abstract: Described herein are compositions and methods for the treatment of ocular surface disorders including meibomian gland dysfunction, blepharitis, dry eye disease and other inflammatory and/or infectious disease of the anterior surface of the eye. Said compositions and methods comprise keratolytic conjugates which demonstrate keratolytic activity, and anti-inflammatory or other desirable activities. Topical administration of said compositions to the eyelid margin or surrounding areas provides therapeutic benefit to patients suffering from ocular surface disorders.

Abstract: Disclosed herein are methods and compositions for treating learning and memory deficits associated with Noonan Syndrome.

Abstract: Described are methods of treating or preventing a disease in a subject treatable by modulating cell mechanics.

Abstract: The invention provides novel compounds having the general formula (I) wherein R1, R2, R9, Y, W, m, n, p and q are as defined herein, compositions including the compounds and methods of using the compounds.

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

Abstract: A compound of formula (I) or a pharmaceutically acceptable salt thereof is provided. In formula (I), Ar is indazole, 5-isoquinoline, 6-isoquinoline, or their N-oxide. X is —C(?Z)—, wherein Z is N—CN, NH, NR4, NCOR4, NCONR4R5, NCO-aryl, S, or O. Y and J are independently H, alkyl, aryl, aminoalkyl, —NH2, —CN, —OH, —O-alkyl, —O-aryl, —COOH, —COOR4, —CONHR4, —CONHCH2-aryl, —CONR4CH2-aryl, —NHCOR4, halogen, halogened alkyl, -alkyl-OR4, -alkyl-ONO2, alkyl-ONO2, —OCOOR4, —O(C?O)-aryl, —CHR4OH, —CH2OH, —CH2O(C?O)-aryl, —CH2O(C?O)—R4, —CHR4O(C?O)-aryl, —CHR4O(C?O)—R4, unsaturated carboxylic ester, substituted alkynyl, —NHSO2R4, —SO2R4, —SO2NHR4, or —SO2NR4R5, or Y and J bond together to form a carbocylic or aromatic ring, wherein R4 and R5 are independently H, substituted C1-C6 alkyl, substituted aryl, cycloalkyl, alkylaryl, -alkyl-NR6R7, —S(O)0-2-(alkyl-NR6R7).

Abstract: Inhibitors of HBV replication of Formula (I) including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein B, R1, R2 and R4 have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HBV inhibitors, in HBV therapy.

Abstract: Described herein is a previously unknown function of XBP1 in triple-negative breast cancer (TNBC). It is shown that XBP1 is preferentially spliced and activated in TNBC, and that deletion of XBP1 significantly blocks triple negative breast tumor growth. Strikingly, XBP1 is required for the self-renewal of breast tumor initiating cells (TICs). Genome-wide mapping of the XBP1 transcriptional regulatory network identified a fundamental role for XBP1 in regulating the response to hypoxia via the transcription factor hypoxia-inducible factor 1? (HIF1?). Importantly, activation of this pathway appears to carry prognostic implications, as expression of the XBP1-dependent signature is associated with shorter survival times in human TNBC.

Abstract: Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (IOP) may be achieved.

Abstract: A compound of the general formula (A) or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, prodrug, codrug, cocrystal, tautomer, racemate, stereoisomer or mixture thereof, in which: X is independently NO2 or H; and Y is selected from H, amino, amide, ester, carboxy and its esters and amides, alkyl, alkenyl, alkynyl, cycloalkyl, alkaryl, aryl, heterocyclic or heteroaryl groups, all of which can be substituted with heteroatoms and/or side groups, and wherein any chains can be straight or branched is disclosed.

Abstract: Chemical compounds are useful in the treatment of a subject afflicted by a thyroid disease. The compounds exhibit activity as thyroid-stimulating hormone receptor (TSHR) antagonists and can be used in the treatment of hyperthyroidism, Graves' disease, Graves' Ophthalmopathy and thyroid cancer.

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: Small molecule compounds derived from ?-sulfophenylacetic amide (SPAA) are provided as novel sulfonic acid based pTyr mimetics. These compounds effectively inhibit a variety of protein tyrosine phosphatases (PTPs), such as mPTPA, mPTPB, LMWPTP, and Laforin. Use of these compounds as pharmaceutical agents for treating diseases associated with abnormal protein tyrosine phosphatase activity is also provided.

Abstract: Derivatives of 1,2,3,4-tetrahydroisoquinoline (THIQ) having the general formula A-(CH2)n—B are provided, wherein A is THIQ or a substituted derivative thereof and B is an aryl, cycloalkylaryl, or cycloalkyl group, wherein A and B are linked to each other by an alkyl or substituted alkyl chain. The compounds are useful as selective ligands (agonists or antagonists) of central nervous system receptors, and in particular of the seratonin receptors. The compounds or their salts can be formulated into pharmaceutical in need thereof by any route of administration suitable for a desired treatment protocol and especially for the treatment of psychiatric disorders.

Abstract: Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, azadecaline derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formula I: These compounds are useful for the treatment of HIV and AIDS.

Abstract: The disclosure relates to chemokine receptor modulators and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising compounds disclosed herein or pharmaceutically acceptable salts or prodrugs thereof. In certain embodiments, the compositions disclosed herein are used for managing chemokine related conditions, typically prevention or treatment of viral infections such as HIV or for managing cancer.

Abstract: Provided herein are stable lisinopril oral liquid formulations. Also provided herein are methods of using lisinopril oral liquid formulations for the treatment of certain diseases including hypertension, heart failure and acute myocardial infarction.

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.

Abstract: The present invention relates to a piperidine derivative and the preparation method and a pharmaceutical use thereof. In particular, the present invention relates to the piperidine derivative as shown by general formula (I) and the preparation method thereof and a pharmaceutical composition containing the same, and the use thereof as an estrogen receptor modulator in the treatment of estrogen receptor mediated or dependent diseases or conditions, the diseases preferably being breast cancer. In the abstract, the definition of each substituent of the general formula (I) is the same as that in the description.

Abstract: The present invention provides a method for determining the oxygen status of a cancer of an individual. The method comprise determining the transcriptional expression level of ADM (SEQ ID No:1), and/or at least one gene selected from ANKRD37 (SEQ ID NO.: 3), P4HA2 (SEQ ID NO.: 12), NDRG1 (SEQ ID NO: 10), SLC2A1 (SEQ ID NO:15), P4HA1 (SEQ ID NO.: 11), LOX (SEQ ID NO.: 9), C3orf28 (SEQ ID NO.: 6), BNIP3L (SEQ ID NO.: 5), BNIP3 (SEQ ID NO.:4), EGLN3 (SEQ ID NO.: 7), PDK1 (SEQ ID NO.: 13), PFKFB3 (SEQ ID NO.: 14), KCTD11 (SEQ ID NO.: 8), and/or ALDOA (SEQ ID NO.: 2), in a cancer sample. The transcriptional level is then correlated to the transcriptional level to at least one reference gene, and oxygen status 10 is then evaluated by comparing the correlated transcription level with a predetermined reference sample comprising cancer cells characterized by a high oxygen level.

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.

Abstract: The present invention relates to novel compounds and their use as fragrance materials.

Abstract: Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (IOP) may be achieved.

Abstract: In DN-DISC1 mice, a mouse model for major mental illnesses, the model that expresses pathological phenotypes relevant to schizophrenia, mood disorders, and addiction simultaneously, the inventors of the present invention found pronounced levels of oxidative stress in the prefrontal cortex, but not in the striatum. These mice also displayed greater amounts of GAPDH-Siah1 binding, a protein-protein interaction that is activated under exposure to oxidative stress. The present inventors investigated the role of oxidative stress in other organ systems. As detailed herein, the inventors found that GAPDH-Siah1 binding was increased in mouse models of cardiac failure. It was also found, that certain novel analogs of deprenyl, significantly inhibited GAPDH-Siah1 binding in cardiac tissue.

Abstract: A method of classifying a subject having idiopathic scoliosis (IS) or at risk of developing IS comprising: determining the cellular response to Gi stimulation in a cell sample from the subject in the presence of OPN; determining the cellular response to Gi stimulation in a cell sample from the subject in the absence of OPN; and comparing the cellular response obtained in the presence of OPN with the cellular response obtained in the absence of OPN, whereby the comparing step enables the classification of the subject into one IS functional group. Also provided is the use of the foregoing method to classify borderline subjects and kits for applying the methods.