Abstract: The present invention provides, inter alia, compounds of Formula (I) and pharmaceutically acceptable salts thereof, to processes for the preparation of, intermediates used in the preparation of and compositions containing such compounds and the uses of such compounds as a method for the treatment of a disease or condition selected from the group consisting of central nervous system disorders, cognitive disorders, schizophrenia, dementia and other disorders in a mammal. The present invention further provides compounds of Formula (Id) and pharmaceutically acceptable salts thereof as CYP3A4 selective inhibitors.

Abstract: Provided are compositions and methods for treating a condition or disorder mediated by fascin activity in a subject in need thereof which method comprises administering to the subject a therapeutically effective amount of at least one compound of any one of Formula I-a to I-n, II, II-a, II-b or III or a pharmaceutically acceptable salt thereof.

Abstract: Described herein are irreversible Btk inhibitor compounds, and methods for using such irreversible inhibitors in the treatment of diseases and disorders characterized by the presence or development of solid tumors.

Abstract: The present disclosure provides compounds such as pyrazolpyrimidine compounds, and pharmaceutically acceptable salts thereof, that are tyrosine kinase inhibitors, in particular BLK, BMX, EGFR, HER2, HER4, ITK, TEC, BTK, and TXK and are therefore useful for the treatment of diseases treatable by inhibition of tyrosine kinases such as cancer and inflammatory diseases such as arthritis, and the like. Also provided are pharmaceutical compositions containing such compounds and pharmaceutically acceptable salts thereof and processes for preparing such compounds and pharmaceutically acceptable salts thereof.

Abstract: The invention relates to novel 1,6-disubstituted pyrazolopyrimidinones, wherein i.) the nitrogen atom of the pyrazolo-group that is next to the pyrimidino-group is attached to a non-aromatic, organic heterocycle having at least one ring hetero atom selected from O, N and S and ii.) to the C-atom between the two nitrogen atoms of the pyrimidinone-ring a second substituent is bound via an optionally substituted methylene-bridge. According to one aspect of the invention the new compounds are for the manufacture of medicaments, in particular medicaments for the treatment of conditions concerning deficits in perception, concentration, learning or memory. The new compounds are also for the manufacture of medicaments for the treatment of Alzheimer's disease.

Abstract: Genetic markers of schizophrenia (SCZ) are presented herein, as are methods for using same for assessing risk of developing SCZ and diagnosing SCZ. Methods for choosing a therapeutic regimen and predicting and/or determining efficacy of a therapeutic regimen based on these genetic markers are also encompassed herein.

Abstract: Disclosed herein are compounds, including compounds having the structure of Formula (A), (B), (C), and (D), as described in further detail herein, that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract: Concentrated methotrexate solutions are described which are suitable for the use of an active substance in the production of a parenterally administered medicament for the treatment of inflammatory autoimmune diseases. The methotrexate is added to a pharmaceutically acceptable solvent at a concentration of more than 30 mg/ml. The invention also relates to a ready-made syringe and a carpule containing such a pharmaceutical solution formulation, as well as a pen injector comprising such a carpule and/or a ready-made syringe.

Abstract: Compounds of formula (I) and salts thereof: wherein R1 is n-C1-6alkyl or C1-2alkoxyC1-2alkyl-, R2 is halo, OH or C1-3alkyl, m is an integer having a value of 4, 5, 6 or 7, n is an integer having a value of 0, 1, 2 or 3, and p is an integer having a value of 0, 1 or 2, are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions, for example allergic rhinitis and asthma, infectious diseases and cancer, and may also be useful as vaccine adjuvants.

Abstract: Described herein are irreversible kinase inhibitor compounds, methods for synthesizing such irreversible inhibitors, and methods for using such irreversible inhibitors in the treatment of diseases. Further described herein are methods, assays and systems for determining an appropriate irreversible inhibitor of a protein, including a kinase.

Abstract: Disclosed herein are compounds, including compounds having the structure of Formula (A), (B), (C), and (D), as described in further detail herein, that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract: The present invention generally relates to the transdermal delivery of various compounds. In some aspects, transdermal delivery may be facilitated by the use of a hostile biophysical environment. One set of embodiments provides a composition for topical delivery comprising a phosphodiesterase type 5 inhibitor and/or a salt thereof, and optionally, a hostile biophysical environment and/or a nitric oxide donor. In some cases, the composition may be stabilized using a combination of a stabilization polymer (such as xanthan gum, KELTROL® BT and/or KELTROL® RD), propylene glycol, and a polysorbate surfactant such as Polysorbate 20, which combination unexpectedly provides temperature stability to the composition, e.g., at elevated temperatures such as at least 40° C. (at least about 104° F.), as compared to compositions lacking one or more of these.

Abstract: The present invention concerns a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, where R1-R3 and Y are defined in the description, and its use in the treatment of disorders in which pi3 kinase is implicated.

Abstract: The present invention provides compounds of Formula (I), pharmaceutical compositions thereof, and method of using the same in the treatment or prevention of diseases mediated by the activation of ?3-adrenoceptor.

Abstract: The present invention encompasses compounds of general formula (1) wherein the groups R1 to R4, X1, X2, X3, L1 and L2 are defined as in claim 1, which are suitable for the treatment of diseases characterized by excessive or anomalous cell proliferation, and the use thereof in such a treatment.

Abstract: The present invention provides a compound of formula I: or a pharmaceutically acceptable salt or mixtures thereof. These compounds are inhibitors of protein kinases, particularly inhibitors of GSK mammalian protein kinase, and more particularly inhibitors of GSK-3 mammalian protein kinase. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of utilizing those compounds and compositions in the treatment of various protein kinase mediated disorders.

Abstract: The invention relates to novel substituted pyrazolopyrimidines. Chemically, the compounds are characterized by general Formula (I): with R1 being phenyl or pyridyl, any of which is substituted with 1 to 4, preferably 1 to 3 substituents X; X independently of each other being selected from C2-C6-alky1 or Ci-C6-alkoxy, where C2-C6-alkyl and C1-C6-alkoxy are at least dihalogenated up to perhalogenated. preferably with 2 to 6 halogen substituents, and the halogen atoms being selected from the group of fluoro, chloro and bromo, preferably fluoro; R2 being phenyl or heteroaryl, where phenyl is substituted by 1 to 3 radicals and heteroaryl is optionally substituted by 1 to 3 radicals in each case independently of one another selected from the group of C1-C6-alkyl, C1-C6-alkoxy, hydroxycarbonyl, cyano, trifluoromethyl, amino, nitro, hydroxy, C1-C6-alkylamino, halogen, C6-C10-arylcarbonylamino, C1-C6-alkylcarbonylamino, C1-C6-alkylaminocarbonyl. C1-C6-alkoxycarbonyl, C6-C10-arylaminocarbonyl, heteroarylaminocarbonyl.

Abstract: Provided herein are methods for treating or preventing pulmonary fibrosis in subjects suffering from diffuse parenchymal lung diseases using selective active-site mTOR inhibitors.

Abstract: The present invention relates to cGMP protein kinase (PKG) and regulatory domains and methods of use thereof. The structural determination of PKG domains is also described. cGMP independent PKG activators and uses thereof are also described.

Abstract: The present invention provides novel compounds that are antagonists of PI3 kinase, PI3 kinase and tyrosine kinase, PI3 kinase and mTOR, or PI33 kinase, mTOR and tyrosine kinase.

Abstract: Compounds of Formula I: and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on one or more protein kinases, including a Zeta-chain-associated protein kinase 70 (ZAP-70), and any mutations thereof. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with increased expression of ZAP-70 cancer, B-cell chronic lymphocytic leukemia, aggressive B-cell chronic lymphocytic leukemia, an allergy-related disease or an allergic inflammation.

Abstract: The invention relates to novel 6-cyclylmethyl- and 6-alkylmethyl-substituted pyrazolopyrimidines, process for their preparation and their use for producing medicaments for improving perception, concentration, learning and/or memory. The pyrazolopyrimidine compounds are within the formula (I) as described herein.

Abstract: The present invention provides PI3K protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of kinase mediated diseases or disorders with them.

Abstract: The present invention provides chemical entities or compounds and pharmaceutical compositions thereof that are capable of modulating certain protein kinases such as mTor, tyrosine kinases, and/or lipid kinases such as PI3 kinase. Also provided in the present invention are methods of using these compositions to modulate activities of one or more of these kinases, especially for therapeutic applications.

Abstract: The present disclosure is directed to novel compounds of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variables are as defined herein. The compounds of Formula (I) are useful as kinase inhibitors and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases and proliferative disorders and conditions, for example, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Crohn's disease, psoriasis and asthma.

Abstract: A method of treating a movement abnormality associated with the pathology of a neurological movement disorder, such as Parkinson's disease or Restless Leg(s) Syndrome by administering a therapeutically effective amount of a PDE7 inhibitory agent. An aspect of the invention provides for the administration of a PDE& inhibitory agent in conjunction with a dopamine agonist or precursor, such as levodopa. In another aspect of the invention, the PDE7 inhibitory agent may be selective for PDE7 relative to other molecular targets (i) known to be involved with the pathology of Parkinson's disease or (ii) at which other drug(s) that are therapeutically effective to treat Parkinson's disease act.

Abstract: Methods for reducing blood clotting in a subject are provided, including methods to reduce the risk of and/or treat blot clotting pathologies. Also provided are compositions useful to reduce the risk or treat blood clotting pathologies.

Abstract: Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with p110? activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lympho

Abstract: The present invention relates to stable crystalline (6S)—N(5)-formyl-5,6,7,8-tetrahydrofolic acid, commonly referred to as levofolinic acid, in essentially pure 6S diastereomeric form, and to a process for its preparation.

Abstract: Disclosed are compounds of Formula 1, and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating immunological disorders, cardiovascular disease, cancer, and other diseases, disorders or conditions associated with PI3K?.

Abstract: The present invention relates to a method of ameliorating the drawbacks of anti-platelet drug named clopidogrel. The method of the present invention comprises administration of an (S)oxo-clopidogrel or its derivative of the Formula IIA in its free or pharmaceutically acceptable salt form for alleviating the symptoms of thrombosis or embolism by inhibiting blood platelet aggregation. Compositions for use in such methods are also provided.

Abstract: Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

Abstract: The present invention relates to selective inhibitors of PI3K delta protein kinases, methods of preparing them, pharmaceutical compositions containing them and methods of treatment and/or prevention of kinase mediated diseases or disorders with them.

Abstract: Use of allopurinol or a pharmaceutically acceptable salt thereof for the treatment or prevention of palmar plantar erythrodysesthesia induced by chemotherapy. The allopurinol or its salt is administered topically to the affected areas, palms and soles, preferably in the form of a cream.

Abstract: Use of allopurinol or a pharmaceutically acceptable salt thereof for the treatment or prevention of Hand Foot Skin Reaction (HFSR) induced by Multitargeted Kinase Inhibitor (MKI) therapy. The allopurinol or its salt is administered topically to the affected areas, palms and soles, preferably in the form of a cream.

Abstract: The invention described herein relates to novel fused pyrimidinediones derivatives of formula (I) which are TRPA (Transient Receptor Potential subfamily A) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPA1 (Transient Receptor Potential subfamily A, member 1). This invention also provides processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPA1.

Abstract: The invention relates to novel 1,6-disubstituted pyrazolopyrimidinones, Formula (I) with is a mono-, bi- or tri-cyclic heterocyclyl group, the ring members of which are carbon atoms and at least 1, preferably 1, 2 or 3, heteroatom(s), which are selected from the group of nitrogen, oxygen and sulphur, which is in the form of —S(O)r— with r being 0, 1 or 2, and—said heterocyclyl group is or comprises 1 non-aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member and—said heterocyclyl group is bound to the scaffold by said 1 non-aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member. According to one aspect of the invention the new compounds are for the manufacture of medicaments, in particular medicaments for the treatment of conditions concerning deficits in perception, concentration, learning or memory.

Abstract: In one aspect, the present invention provides for a compound of Formula I in which in Formula I, the variables X1, X2a, X2b, X2c, R1, B, L, E, A and the subscript n are as defined herein. In another aspect, the present invention provides for pharmaceutical compositions comprising compounds of Formula I as well as methods for using compounds of Formula I for the treatment of diseases and conditions (e.g., cancer, thrombocythemia, etc) characterized by the expression or over-expression of Bcl-2 anti-apoptotic proteins, e.g., of anti-apoptotic Bcl-xL proteins.

Abstract: Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

Abstract: The present invention comprises a new class of compounds capable of modulating the activity of Raf kinase and, accordingly, useful for treatment of Raf kinase mediated diseases, including melanomas, tumors and other cancer-related conditions. The compounds have a general Formula I wherein each of A1, A2, A3, A4, A5, A6, A7, A8, A9, bond B, X, rings Z1 and Z2, R1 and R3 are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of Raf kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.

Abstract: The invention provides PDE9-inhibiting compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, A, and n are as defined herein. Pharmaceutical compositions containing the compounds of Formula I, and uses thereof in treating neurodegenerative and cognitive disorders, such as Alzheimer's disease and schizophrenia, are also provided.

Abstract: Provided herein are methods, kits, and pharmaceutical compositions that include a PI3 kinase inhibitor for treating lupus, a fibrotic condition, or inflammatory myopathies and other conditions (e.g., skin conditions).

Abstract: The present invention provides compounds useful as inhibitors of Tec family kinases, compositions thereof, and methods of using the same.

Abstract: There are provided compounds of the formula or a pharmaceutically acceptable salt thereof, wherein Q, R1 and R2 are as defined herein. The compounds of formula I are useful in the treatment of cancer.

Abstract: Described herein is the Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, including crystalline forms, solvates and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions that include the Btk inhibitor, as well as methods of using the Btk inhibitor, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract: A conjugated compound of formula Q-Z—R4 wherein Q is a TLR7 and/or TLR8 agonist and Z—R4 is a lipid covalently linked to an amino acid or peptide coupled to a polyamine group, and a process for the manufacture of the conjugated compound, as well as a complex formed between the conjugated compound and a polyanionic molecule and a pharmaceutical composition containing the conjugated compound or complex. Also described is the use of the conjugated compound or complex in the treatment of infection, cancer or immune disorders or for use in vaccines.

Abstract: The present invention relates to (1- or 2- and/or 5 and/or 7-substituted)-(3-oxy)-(4H, 4-imino, 4-thioxo or 4-oxo)-pyrazolo[3,4-d]pyrimidin-6-ones, e.g., a compound of formula II as described below, processes for their production, their use as pharmaceuticals and pharmaceutical compositions comprising them. Of particular interest are novel compounds useful as inhibitors of phosphodiesterase 1 (PDE1), e.g., in the treatment of diseases involving disorders of the dopamine D1 receptor intracellular pathway, such as Parkinson's disease, depression, narcolepsy, damage to cognitive function, e.g., in schizophrenia, or disorders that may be ameliorated through enhanced progesterone-signaling pathway, e.g., female sexual dysfunction.

Abstract: One embodiment relates to a method of treating pulmonary hypertension based upon co-administering to a subject in need thereof a pharmaceutically effective amount of an oral therapeutic agent for treating pulmonary hypertension and a pharmaceutically effective amount of an inhaled therapeutic agent for treating pulmonary hypertension. The benefit of the co-administration of these agents is to eliminate or reduce one or more side effects associated with mono-therapy of either agent, as well as one or more side effects associated with other administration routes such as subcutaneous or intravenous administration.

Abstract: The present invention relates to compounds defined by formula (I) wherein the groups R1 and R2 are defined as in claim 1, possessing valuable pharmacological activity. Particularly the compounds are inhibitors of 11 ?-hydroxysteroid dehydrogenase (HSD) 1 and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this enzyme, such as metabolic diseases, in particular diabetes type 2, obesity, and dyslipidemia.

Abstract: The invention provides ?-helix mimetic structures and a chemical library relating thereto. The compounds, pharmaceutical compositions comprising the compounds, and methods of the invention using the compounds, relate to the treatment of diseases including fibrosis, such as pulmonary fibrosis.