Abstract: New heterocyclic compounds that may be used to modulate a histamine receptor in an individual are described. Pyrido[4,3-b]indoles are described, as are pharmaceutical compositions comprising the compounds and methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

Abstract: The present invention provides 4-Aza-2,3-didehydropodophyllotoxin compound of general formula A (4a-4z and 4aa-4ae) as useful potential antitumour agents against human cancer cell lines. The present invention further provides a process for the synthesis of 4-Aza-2,3-didehydropodophyllotoxin compounds (4a-4z and 4aa-4ae).

Abstract: The invention provides tris(hydroxymethyl)aminomethane salts of a small-molecule GLP1R agonist. The invention further provides solid compositions comprising tris(hydroxymethyl)aminomethane salts of a small-molecule GLP1R agonist. The invention further provides uses of tris(hydroxymethyl)aminomethane salts of a small-molecule GLP1R agonist, e.g., for treating type 1 diabetes, type 2 diabetes, or obesity.

Abstract: The present invention features tryptoline derivatives and related compounds having kinase inhibitory activity. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions, such as cancers, inflammatory disorders, or autoimmune disorders.

Abstract: The present invention is concerned with the use of Protease-Activated Receptor-1 (PAR1) inhibitors for preventing or treating a Paramyxoviridae infection in a subject. Described herein are methods, compounds and pharmaceutical compositions useful in addressing such infections, and more particularly infections from human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV).

Abstract: The disclosure relates particularly to certain carboxamide, sulfonamide and amine compounds and pharmaceutical compositions thereof, and to methods of treating and ameliorating disorders and conditions related to the adiponectin pathway, sphingolipid metabolism, oxidative stress, mitochondrial dysfunction, free radical damage and metabolic inefficiency, among others. In certain embodiments, the compounds have the structures (I-1), (2-I) and (3-I) (The chemical formulas should be inserted here) in which the variables are as described herein.

Abstract: Disclosed are 1,4-dihydro-naphthyridine derivatives and pharmaceutical composition and uses thereof. The 1,4-dihydro-naphthyridine derivatives are a compound capable of inhibiting acetylcholinesterase activity and preventing extracellular calcium from flowing into a cell via a calcium channel, i.e., having a dual-activity, which are of potential importance as a pharmaceutical and can be used to prepare the drugs for treating cardiovascular diseases, cerebrovascular diseases and dementia.

Abstract: This disclosure is directed to pyrido[4,3-b]indoles having rigid moieties. The compounds in one embodiment are pyrido[4,3-b]indoles having an unsaturated hydrocarbon moiety. The compounds in another embodiment are pyrido[4,3-b]indoles having a cycloalkyl, cycloalkenyl or heterocyclyl moiety. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

Abstract: The invention concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1 to R5 have any of the meanings defined hereinbefore in the description: processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.

Abstract: The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.

Abstract: The present invention provides compounds of Formula (Ia): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: The invention relates to FSH receptor antagonist according to general formula (I) or a pharmaceutically acceptable salt thereof and to a pharmaceutical composition containing the same. The compounds can be used for the treatment and prevention of endometriosis, for the treatment and prevention of pre-menopausal and peri-menopausal hormone-dependent breast cancer, for contraception, and for the treatment of uterine fibroids and other menstrual-related disorders.

Abstract: As disclosed herein, co-administration of pimavanserin with an agent that ameliorates one or more cholinergic abnormalities can have a synergistic effect on the efficacy of the agent. Disclosed herein are compositions which include pimavanserin in combination with an agent that ameliorates one or more cholinergic abnormalities. Also disclosed herein are methods for ameliorating or treating a disease condition characterized by one or more cholinergic abnormalities that can include administering pimavanserin in combination with an agent that ameliorates one or more cholinergic abnormalities.

Abstract: This invention relates to novel 2,3-dihydroimidazo[1,2-c]quinazoline compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for phosphotidylinositol-3-kinase (PI3K) inhibition and treating diseases associated with phosphotidylinositol-3-kinase (PI3K) activity, in particular treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients.

Abstract: The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with Toll-Like Receptors, including TLR7 and TLR8. In one aspect, the compounds are useful as adjuvants for enhancing the effectiveness of a vaccine (formula I) wherein: X3 is N; X4 is N Or CR3; X5 is —CR4?CR5.

Abstract: Disclosed are carboxamide, sulfonamide and amine compounds, as well as pharmaceutical compositions and methods of use. One embodiment is a compound having the structure in which R1, R2, R4, D, E, J, T, p, q and x are as described herein. In certain embodiments, a compound disclosed herein activates the AMPK pathway, and can be used to treat metabolism-related disorders and conditions.

Abstract: This technology relates generally to compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death. Various compounds are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.

Abstract: A compound of formula (I) useful for the treatment or prevention of hepatitis C viral infection, (Formula (I)) wherein: X1 and X2 are each independently CRB or N; RB is H, (C1-6)alkyl, (C1-6)haloalkyl, halo.

Abstract: Provided are compounds and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and their use for treating viral infections mediated by a member of the retrovirus family of viruses such as the Human Immunodeficiency Virus (HIV).

Abstract: The present invention relates to small molecule modulators of mTORC1 and mTORC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e.g., benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORC1, mTORC2, and PI3K-related proteins. Novel methods of providing soluble mTORC1 and mTORC2 complexes are discussed, as well as methods of using the soluble complexes in a high-throughput manner to screen for inhibitory compounds.

Abstract: Provided herein are compounds capable of activating GPR139. Also provided are methods of increasing and decreasing the activity of GPR139. Methods of using the identified compounds to modulate GPR139 activity or conditions that may be affected by GPR139 activity are also disclosed.

Abstract: The disclosure relates to diseases in the peripheral nervous system, particularly hereditary neuropathies, such as Charcot-Marie-Tooth (CMT) disease. It is shown that this disease is associated with decreased acetylated tubulin levels, which can be overcome by inhibition of histone deacetylases (HDACs). Using HDAC inhibitors, it is shown herein that the symptoms of the CMT phenotype can be overcome both in vitro and in vivo. Also provided herein are two different mouse models of CMT disease.

Abstract: The invention provides for novel benzonaphthyridine derivatives and compositions comprising novel benzonaphthyridine derivatives. In some embodiments, the compounds are phosphodiesterase inhibitors. The invention further provides for methods for inhibition of phosphodiesterase comprising contacting phosphodiesterase with novel benzonaphthyridine derivatives or compositions comprising novel benzonaphthyridine derivatives. The invention further provides for methods for treatment of neurodegenerative diseases, increasing memory or long term potentiation with novel benzonaphthyridine derivatives or compositions comprising novel benzonaphthyridine derivatives. In some embodiments, the phosphodiesterase is PDE5.

Abstract: The present invention relates to new medicament combinations which contain in addition to one or more PDE4-inhibitors (1) at least one EP4 receptor antagonist (2), as well as the use thereof for the treatment of preferably respiratory complaints such as particularly COPD, chronic sinusitis and asthma. The invention relates in particular to those medicament combinations which contain at least one EP4 receptor antagonist (2), in addition to one or more, preferably one, PDE4 inhibitor of general formula 1 wherein X is SO or SO2, but preferably SO, and wherein R3 denotes an optionally substituted, mono- or bicyclic, unsaturated, partly saturated or saturated heterocyclic group or an optionally substituted, mono- or bicyclic heteroaryl and wherein R1 and R2 have the meanings given in claim 1, the preparation thereof and the use thereof for the treatment of respiratory complaints.

Abstract: Disclosed are uses of carboxamide, sulfonamide and amine compounds for the treatment and amelioration of disorders and conditions related to oxidative stress, mitochondrial dysfunction, free radical damage and metabolic inefficiency, among others. Also described are methods for increasing exercise endurance, exercise efficiency and aerobic workload using the compounds described herein.

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 treating, preventing, inhibiting, ameliorating, or eradicating the pathology and/or symptomology of a disease caused by a Plasmodium parasite, such as malaria.

Abstract: A pharmaceutical composition comprising an mTOR/PI3K inhibitor, and an Hsp90 inhibitor according to the following formulae (I) and (Ia) or tautomers, or pharmaceutically acceptable salts thereof, wherein the variables in the structural formulae are defined herein. Also provided are methods for treating a proliferative disorder in a subject in need thereof, using pharmaceutical compositions described herein.

Abstract: The present invention provides compounds of formula (I) wherein R1, R2, A, X, D1, D2 and Y3 are as defined in the claims. The invention further provides intermediates used in the preparation of these compounds, to compositions which comprise these compounds and to their use in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.

Abstract: This document relates to inhibitors of G protein coupled receptor 6 kinase (GRK6) polypeptides as well as methods and materials for using such inhibitors to treat hematological malignancies, inflammation diseases, and autoimmune disorders.

Abstract: The present invention relates to a method of treating attention deficit hyperactivity disorder in a subject. This method includes selecting a subject with attention deficit hyperactivity disorder and administering to the selected subject a sodium/hydrogen exchanger inhibitor under conditions effective to treat the subject for attention deficit hyperactivity disorder. Methods of identifying compounds suitable to treat attention deficit hyperactivity disorder are also disclosed.

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 adrenergic receptor ?2B antagonists. The compounds may also bind to and antagonize adrenergic receptor ?2B. The compounds may find use in therapy, e.g., to (i) reduce blood pressure and/or (ii) promote renal blood flow and/or (iii) decrease or inhibit sodium reabsorption. The compounds may also be used to treat diseases or conditions that are, or are expected to be, responsive to a decrease in blood pressure. Use of the compounds to treat cardiovascular and renal disorders is particularly described.

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 adrenergic receptor ?2B antagonists. The compounds may also bind to and antagonize adrenergic receptor ?1B—The compounds may find use in therapy, e.g., to (i) reduce blood pressure and/or (ii) promote renal blood flow and/or (iii) decrease or inhibit sodium reabsorption. The compounds may also be used to treat diseases or conditions that are, or are expected to be, responsive to a decrease in blood pressure. Use of the compounds to treat cardiovascular and renal disorders is particularly described.

Abstract: In one aspect, the invention provides compounds of Formula I, and salts, hydrates and isomers thereof. In another aspect, the invention provides a method of promoting bone formation in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of Formula I, Formula II, or Formula III. The present invention also provides orthopedic and periodontal devices, as well as methods for the treatment of renal disease and cancer, using a compound of Formula I, Formula II, or Formula III.

Abstract: The present invention relates to new biphenyl-3-carboxylic acid modulators of beta-3-adrenoceptor activity, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The present invention provides substituted tricyclic heteroaryl compounds, including, for example, pyridoindoles, pyrimidinoindoles and triazinoindoles that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases such as immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.

Abstract: The present invention relates to tricyclic heterocycles which are inhibitors of BET proteins such as BRD2, BRD3, BRD4, and BRD-t and are useful in the treatment of diseases such as cancer.

Abstract: Inhibitors of BET bromodomains and compositions containing the same are disclosed. Methods of using the BET bromodomain inhibitors in the treatment of diseases and conditions wherein inhibition of BET bromodomain provides a benefit, like cancers, also are disclosed.

Abstract: The invention relates to a process for obtaining compounds derived from tetrahydro-?-carboline, specifically tadalafil and intermediate products from the synthesis, comprising the reaction between piperonal and an alkyl ester of D-tryptophan as a salt, and in the absence of any other component, followed by haloacetylation and a final cyclization with methylamine.

Abstract: The present invention relates to novel heterocyclic compounds which specifically inhibit bacterial FabI and can be used for the treatment of Staphylococcal infections.

Abstract: Provided are certain compounds and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and their use for treating viral infections.

Abstract: The present invention provides for a pharmaceutical composition that includes tetrabenazine and a release-retarding agent; and a method of treating a hyperkinetic movement disorder (e.g., Huntington's disease, chorea associated with Huntington's disease, hemiballismus, senile chorea, tic disorders, tardive dyskinesia, myoclonus, dystonia and/or Tourette's syndrome). The method includes administering an effective amount of the pharmaceutical composition, for a period of time effective to treat the hyperkinetic movement disorder.

Abstract: Compositions and methods that are useful for the treatment of herpesvirus infection (including herpes simplex virii) are disclosed. Methods for identifying compounds useful for the treatment of herpesvirus infection are also disclosed.

Abstract: Novel 5-HT3 receptor modulators are disclosed. These compounds are used in the treatment of various disorders, including chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, and irritable bowel syndrome. Methods of making these compounds are also described in the present invention.

Abstract: In one aspect, the invention relates to novel substituted 2-alkyl-1-oxo-N-phenyl-3-heteroaryl-1,2,3,4-tetrahydroisoquinoline-4-carboxamides; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating and/or preventing malaria. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: Various methods for treating a patient with neoplasia are disclosed, in particular, methods using topoisomerase Ila-preferential poisons, methods using a combination of a topoisomerase Illi-preferential inhibitor and a topoisomerase II poison, and methods using a combination of a topoisomerase II poison and a proteasome inhibitor are disclosed. Novel topoisomerase Ila-preferential poisons are disclosed, particularly, several novel 13-carboline derivatives are identified. Methods for identifying the novel topoisomerase Ila-preferential poisons and methods for identifying the novel topoisomerase EP-preferential inhibitors are also provided herein.

Abstract: Polycyclic aryl and polycyclic heteroaryl substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases or conditions associated with Axl catalytic activity are also disclosed.

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 are compounds of the formula (I): or a stereoisomer, tautomer, salt, hydrate or prodrug thereof that modulate tyrosine kinase activity, compositions comprising the compounds and methods of their use.

Abstract: Novel compounds of formulae (I) to (VII), which more particularly include sulfonylurea derivatives, sulfonylthiourea derivatives, sulfonylguanidine derivatives, sulfonylcyanoguanidine derivatives, thioacylsulfonamide derivatives, and acylfulfonamide derivatives which are effective platelet ADF receptor inhibitors. These derivatives may be used in various pharmaceutical compositions, and are particularly effective for the prevention and/or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also relates to a method for preventing or treating thrombosis in a mammal comprising the step of administering a therapeutically effective amount of a compound of formulae (I) to (VIII), or a pharmaceutically acceptable salt thereof.

Abstract: The present invention provides compounds of Formula (Ia): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.