Abstract: The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase L1 (UCHL1). The invention further relates to the use of DUB inhibitors in the treatment of cancer and other indications. Compounds of the invention include compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 to R8 are as defined herein.

Abstract: The present invention relates to an FGFR4 inhibitor having a structure represented by formula (I), preparation method therefor, and applications thereof. A series of compounds represented by formula (I) in the present invention have very-strong inhibition effect on the activity of FGFR4 kinase, have very-high selectivity, can be widely used in the preparation of drugs for treating cancers, specially a liver cancer, a stomach cancer, a prostate cancer, a skin cancer, an ovarian cancer, a lung cancer, a breast cancer or a colon cancer, and can be developed into a new-generation FGFR4 inhibitor drug.

Abstract: The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase L1 (UCHL1). The invention further relates to the use of DUB inhibitors in the treatment of cancer and other indications. Compounds of the invention include compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 to R8 are as defined herein.

Abstract: The present invention relates to a medicament for treating neuropsychiatric diseases, comprising a compound of Formula (1): or a pharmaceutically acceptable salt thereof, as an active ingredient.

Abstract: Disclosed herein are compounds of formula I and salts thereof. Also disclosed are compositions comprising compounds of formula I and methods using compounds of formula I.

Abstract: The present disclosure provides compounds represented by Formula I: and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R1a, R1b, R2a, R2b, R3, R4, R5, R6, and R7 are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I for use to treat a condition or disorder responsive to inhibition of ALK such as cancer.

Abstract: A method of promoting hair growth of a subject includes administering to follicle cells of the subject a therapeutically effective amount of a TLR2 agonist that promotes TLR2 activation and hair growth of the subject.

Abstract: The present disclosure relates to the use of 2-((4S)-6-(4-chlorophenyl)-1-methyl-4H-benzo[c]isoxazolo[4,5-e]azepin-4-yl)acetamide, and pharmaceutically acceptable salts thereof, for treating myelofibrosis.

Abstract: The disclosure relates to inhibitors of USP28 and/or USP25 useful in the treatment of cancers, inflammation, autoimmune diseases, and infectious diseases, having the Formula: where R1, R2, R3, R4, R5, R5?, R6, R7, X, m, and n are described herein.

Abstract: This invention concerns a dosage form comprising a therapeutically effective amount of A19-144 or A2-73 and a therapeutically effective amount of at least one AED. This invention further encompasses a method of treating a subject in need of such treatment comprising administering a therapeutically effective amount of A19-144 or A2-73 in conjunction with an therapeutically effective amount of an AED.

Abstract: The present invention is related to a method of treating idiopathic pulmonary fibrosis comprising administering to a subject in need thereof an effective amount of a composition containing a compound that binds FK506 binding protein 4.

Abstract: Glucosepane is a structurally complex protein post-translational modification (PTM) believed to exist in all living organisms. Glucosepane possesses a unique chemical structure that incorporates a surprising, never-before-prepared non-aromatic tautomer of imidazole, rendering it a challenging target for chemical synthesis. In this application, the inventors report the first total synthesis of glucosepane and related compounds according to the chemical structure: Methods of synthesis, compounds obtained therefrom, pharmaceutical compositions and methods of treatment provide embodiments of the present invention.

Abstract: The present invention provides a method for predicting whether a human patient 65 years of age or older is at increased risk for developing heart failure, comprising obtaining the results of an assay that measures levels of NT-proBNP and/or cardiac troponin T in a specimen from the patient wherein an increased NT-proBNP and/or cardiac troponin T level compared to levels in a control indicate an increased risk for developing heart failure.

Abstract: There is provided a 5,6-dihydro-4H-benzo[b]thieno-[2,3-d]azepine derivative which is useful in the treatment of respiratory syncytial virus (RSV) infection and for the prevention of disease associated with RSV infection. (Formula (I)).

Abstract: This invention relates to compounds and methods for the treatment of cancer. In particular, the invention provides compounds that inhibit Aurora kinase, pharmaceutical compositions comprising the compounds, and methods of using the compounds for the treatment of cancer.

Abstract: The present invention is directed to a composition for treating alopecia containing minoxidil, cyclosporine A and a compound that binds FK506 binding protein 4 suitable for administration to humans. The present invention is further directed to treating alopecia in humans by administering a composition of the invention.

Abstract: A combination of a muscarinic cholinergic receptor agonist, a non-anticholinergic antiemetic agent and a non-selective, peripheral anticholinergic agent for the treatment of hypocholinergic disorders of the central nervous system.

Abstract: The present invention is directed to a composition for treating alopecia containing minoxidil, cyclosporine A and a compound that binds FK506 binding protein 4 suitable for administration to humans. The present invention is further directed to treating alopecia in humans by administering a composition of the invention.

Abstract: Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.

Abstract: The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted heterocyclic derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of lysine specific demethylase-1. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

Abstract: Novel FXR agonists are disclosed, embodiments of a method of making the same, and of a composition comprising them are disclosed herein. Also disclosed are embodiments of a method of treating or preventing a metabolic disorder in a subject, comprising administering to a subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and treating or preventing a metabolic disorder in the subject. Additionally disclosed are embodiments of a method of treating or preventing inflammation in an intestinal region of a subject, comprising administering to the subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and thereby treating or preventing inflammation in the intestinal region of the subject.

Abstract: The present invention is directed to a compound of formula (I): or a crystalline form thereof, or a solvate thereof; to a solid pharmaceutical composition comprising a pharmaceutically effective amount of the compound of formula (I), or a crystalline form thereof, or a solvate thereof, and at least one pharmaceutically acceptable carrier or diluent, and to the use of a compound of formula (I), or a crystalline form thereof, or a solvate thereof, for treating a patient suffering from, or subject to, a disease, disorder, or condition mediated by Aurora kinase, and methods related thereto.

Abstract: Disclosed are compounds of Formula G1: where “RG3”. “Rd1” to “Rd4”, “n”, “m”, “p”, “W”, “X”, “Y”, and “Z” are defined herein, which compounds are antagonists of A2A receptor. Disclosed herein also are uses of the compounds described herein as antagonists of the A2A receptor in the potential treatment or prevention of neurological disorders and diseases in which A2A receptors are involved. Disclosed herein also are pharmaceutical compositions comprising these compounds and uses of these pharmaceutical compositions.

Abstract: NSC antagonists are disclosed as useful in the treatment of dementia, in delaying the onset of dementia, and in the prevention of dementia. Dementia so treated may be, for example, Alzheimer's Disease (AD). NSC antagonists for treating dementia such as AD may be administered alone, a) in combination with other drugs used for treating dementia, b) in combination with drugs that stabilize or increase blood plasma glucose levels, or with both a) and b). Pharmaceutical compositions, dosage forms, and methods for using the same are disclosed, which include NSC antagonists, NSC antagonists combined with dementia drugs, NSC antagonists combined with glucose-level stabilizing or enhancing drugs, or combinations of these. Dosage forms may be designed to provide stable plasma levels for extended periods of time.

Abstract: The present invention provides compounds of Formula (I) (Formula (I)) including pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Abstract: The present invention relates to compounds and methods for the treatment of cancer. In particular, the invention provides potent inhibitors of Aurora A kinase, pharmaceutical compositions comprising the compounds, and methods of using the compounds for the treatment of cancer.

Abstract: The present disclosure relates to a crystalline form of 2-((4S)-6-(4-chlorophenyl)-1-methyl-4H-benzo[c]isoxazolo[4,5-e]azepin-4-yl)acetamide, which is useful as an inhibitor of bromodomain-containing proteins. The present disclosure also provides pharmaceutically acceptable compositions comprising the crystalline form and methods of using said compositions in the treatment of various disorders.

Abstract: Compositions and methods for treating preeclampsia in a subject in need thereof are disclosed.

Abstract: The present invention is directed to novel compounds of Formula (I), pharmaceutically acceptable salts or solvates thereof, and their use.

Abstract: The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. 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 compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted heterocyclic derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of lysine specific demethylase-1. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

Abstract: Pharmaceutical compositions and methods for inhibiting cell growth, modulating function of PCNA, treating prostate cancer, and enhancing PCNA trimer formation are disclosed. The methods include administering an effective amount of a compound of Formula (I): (a representative image), or an effective amount of a specific compound of Formula (II): (a representative image).

Abstract: The present application relates to aryl- and heteroaryl-fused decahydropyrroloazepine, octahydrooxepinopyrrole, octahydropyrrolothiazepine dioxide, decahydrocyclohepta[c]pyrrole, and octahydrocyclohepta[c]pyrrole derivatives of formula (I) wherein R1, R2, R3, R4, R5, A, Y1, Y2, and Y3 are as defined in the specification. The present application also relates to compositions comprising such compounds, processes for making such compounds, and methods of treating disease conditions using such compounds and compositions, and methods for identifying such compounds.

Abstract: In part, the present invention is directed to antibacterial compounds and salts thereof.

Abstract: This invention relates to compounds and methods for the treatment of cancer. In particular, the invention provides compounds that inhibit Aurora kinase, pharmaceutical compositions comprising the compounds, and methods of using the compounds for the treatment of cancer.

Abstract: The present invention is directed to immune adjuvants containing IAP inhibitors, including Smac mimetics. The invention further provides pharmaceutical compositions and vaccines containing an IAP inhibitor and an antigen. Methods of enhancing an immune response by administration of an IAP inhibitor, methods of treating or preventing cancer, methods of treating or preventing infections, methods of treating autoimmune disorders, and methods of potentiating cytokine or antibody production are also provided.

Abstract: Certain tetrahydro-pyrimidoazepine compounds are described, which are useful as TRPV1 modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by TRPV1. Thus, the compounds may be administered to treat, e.g., pain, itch, cough, asthma, or inflammatory bowel disease.

Abstract: A gel useful in reducing bacterial colonization in or around the area of a wound can be provided from at least one PEG and an aqueous composition having a pH of from 2 to 4, a total solute concentration of from 1.8 to 4.0 Osm/L, and from 0.9 to 1.7 g/L of at least one cationic surfactant. The aqueous composition can include a buffer system that includes an organic acid and a salt of an organic acid. The resulting gel is effective even when free of materials having antimicrobial properties other than those provided by the aqueous composition such as sporicides, antifungals and antibiotics.

Abstract: Disclosed are methods for the treatment of proliferative disorders. Disclosed in particular, are methods for treatment of proliferative disorders such as cancer, by administering an mTORC1/2 inhibitor in combination with a selective inhibitor of Aurora A kinase. Preferred MTORC1/2 inhibitors include MLN0128 and the preferred Aurora A kinase inhibitor of the combination is MLN8237.

Abstract: The invention provides a chemical entity of Formula (I), wherein R1, R2, R3, R4, R5 and X have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies; detection and imaging techniques; radioactive treatments; modulating and treating disorders mediated by GlyT1 activity; treating neurological disorders, CNS disorders, dementia, neurodegenerative diseases, and trauma-dependent losses of function; treating stroke, including cognitive and motor deficits during stroke rehabilitation; facilitating neuroprotection and neurorecovery; enhancing the efficiency of cognitive and motor training, including animal skill training; and treating other disorders, including pain and alcohol-dependence.

Abstract: This invention pertains to a method for the treatment of non-small cell lung cancer in a subject who is a smoker, comprising administering to the subject an effective amount of 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (veliparib or ABT-888), or a pharmaceutically acceptable salt thereof, in combination with carboplatin and paclitaxel.

Abstract: Compounds that are fatty acid synthesis modulators are provided. The compounds may be used to treat disorders characterized by disregulation of the fatty acid synthase function by modulating the function and/or the fatty acid synthase pathway. Methods are provided for treating such disorders including viral infections, such as hepatitis C infection, cancer and metabolic disorders.

Abstract: The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. 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: Provided is a compound which is useful as an agent for treating or preventing 5-HT2C receptor-related diseases, particularly incontinence such as stress urinary incontinence, urge urinary incontinence, mixed urinary incontinence, and the like, sexual dysfunction such as erectile dysfunction syndrome and the like, obesity, and the like. The present inventors have investigated compounds having a 5-HT2C receptor agonist activity and have found that the benzazepine compounds of the present invention have an excellent 5-HT2C receptor agonist activity, thereby completing the present invention. That is, the benzazepine compounds of the present invention have a 5-HT2C receptor agonist activity and can be used as an agent for treating or preventing 5-HT2C receptor-related diseases, particularly incontinence such as stress urinary incontinence, urge urinary incontinence, mixed urinary incontinence, and the like, sexual dysfunction such as erectile dysfunction syndrome and the like, obesity, and the like.

Abstract: A method of synthesizing cycloalkanyl[b]indoles, as well as related cycloalkanyl[b]benzofurans and cycloalkanyl[b]benzothiophenes is provided. The method is a single, multicomponent reaction that combines (1) an indole, benzofuran, or benzothiopene, (2) an aldehyde, ketone, or ketal, and (3) a diene in the presence of an acid, in particular a Ga(III) or In(III) salt. Compositions and methods of using these compounds to stimulate secretion and/or production of glucagon-like peptide-1 or inhibit the activity of Calcitonin Gene-Related Peptide receptor are also provided.

Abstract: The present invention provides a compound having a superior serotonin 5-HT2C receptor activating action. The present invention relates to a compound represented by the formula (1) wherein ring A is an aromatic carbocycle optionally having substituent(s) or an aromatic heterocycle optionally having substituent(s), X is —N(R1)—, —O— or the like, when ring A is an aromatic carbocycle optionally having substituent(s), then R1 is a hydrogen atom, an alkyl group optionally having substituent(s), or the like, and when ring A is an aromatic heterocycle optionally having substituent(s), then R1 is a hydrogen atom, an alkyl group optionally having substituent(s), a cycloalkyl group optionally having substituent(s), or the like, is a single bond or a double bond, and n is an integer of 0, 1 or 2, or a salt thereof.

Abstract: Hydrogenated pyrido[4,3-b]indoles, pyrido[3,4-b]indoles and azepino[4,5-b]indoles are described. The compounds may bind to and are antagonists of the adrenergic receptor ?2A. The compounds may also bind to and are an antagonist of the adrenergic receptor ?2B; or the compounds are not antagonists of the adrenergic receptor ?2B and the compounds are administered in conjunction with a second agent that reduces, or is expected to reduce, blood pressure in an individual. The compounds may find use in therapy, e.g., to regulate blood glucose level, increase insulin secretion and treat diseases or conditions that are, or are expected to be, responsive to an increase in insulin production. Use of the compounds to treat type 2 diabetes is particularly described.

Abstract: Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.

Abstract: The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. 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: Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.