Abstract: Disclosed are intermediates and methods of synthesizing Compound 1.

Abstract: The invention relates to pyrridinobenzodiazepines (PDDs) comprising three fused 6-7-6-membered rings linked to aromatic groups, and pharmaceutically acceptable salts thereof, which are useful as medicaments, in particular as anti-proliferative agents. PDDs may be represented by formula (I) and pharmaceutically acceptable salts thereof.

Abstract: This invention relates to novel, deuterated forms of VX-661 and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating cystic fibrosis.

Abstract: The present invention is based, in part, on our studies of molecular pathways that include the deubiquitinase CYLD. Accordingly, the present invention features, inter alia, nucleic acid constructs that express CYLD or a biologically active variant thereof (e.g., a variant including the catalytic domain), nucleic acids that inhibit the expression of a negative regulator of CYLD (e.g., PDE4B or LNK2), nucleic acids that modulate the expression of downstream CYLD targets (e.g., Akt, by inhibiting or promoting the expression of the downstream target), compositions including one or more of these types of constructs (e.g., pharmaceutical compositions), kits including one or more of the compositions described herein and instructions for use, screening methods to identify therapeutic agents {e.g., anti-inflammatory agents) that upregulate CYLD, downregulate a negative regulatory of CYLD, or modulate (e.g., inhibit) a downstream CYLD target (e.g.

Abstract: The invention provides a composition which comprises (a) a PDE3/PDE4 inhibitor which is 9,10-Dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof and (b) a muscarinic receptor antagonist.

Abstract: Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

Abstract: Provided herein are spirocyclic aminoquinolones of formula I and compositions containing the compounds. The compounds and compositions provided herein are useful in the prevention, amelioration or treatment of GSK-3 inhibitors mediated diseases.

Abstract: Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Abstract: Provided herein are compounds and methods of synthesis thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as pain, neurological disorders, psychiatric disorders, and neuromuscular disorders. Compounds provided herein modulate the activity of opioid receptor (e.g., ?-opioid receptor) in the central nervous system or the periphery. Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.

Abstract: The present invention provides 4H,6H-5-oxa-2,3,10b-triaza-benzo[e]azulenes, which act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.

Abstract: This invention relates to novel indolyl-oxadiazolyl-diazabicyclononane derivatives and their use in the manufacture of pharmaceutical compositions. The compounds of the invention are found to be cholinergic ligands at the nicotinic acetylcholine receptors and modulators of the monoamine receptors and transporters. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

Abstract: The present invention provides a compound of formula I or a pharmaceutically acceptable salt thereof; and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Abstract: This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

Abstract: Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Abstract: This invention generally relates to a method for promoting growth and increasing feed utilization efficiency in animals, and, more specifically, to combinations comprising zilpaterol (and salts thereof) and melengestrol acetate. Included within this invention are treatment methods comprising the administration of such combinations to animals, compositions comprising such combinations, uses of such combinations to prepare medicaments, and kits for using such combinations.

Abstract: Multimodal particulate formulations of medicaments and methods for their use, e.g. by nasal or pulmonary administration for the treatment of various medical conditions, are provided.

Abstract: The present invention relates to dihydropteridinones, their use as modulators of ?-secretase and to pharmaceutical compositions containing said compounds. In particular, the present invention relates to compounds which interfere with ?-secretase and/or its substrate and therefore modulate the formation of A? peptides.

Abstract: Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

Abstract: The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I: wherein Y, Z, n, R1 and R3 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.

Abstract: Bridged bicyclic sulphamides of formula (I) are disclosed for treatment of cancer.

Abstract: Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Abstract: Compounds of formula 1: are disclosed, wherein V is CH2; W is S(O)m; m is the integer 0, 1 or 2; U is O, C(O), CR13R14 or NR15; where R13 is H, alkyl; R14 is H, OH, OR13 or OCOR13; R15 is H, alkyl, cycloalkyl, alkenyl, C(O)R13, C(O)OR13 or alkylaminocarbonyl; R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein. These compounds are inhibitors of tumor necrosis factor-alpha (TNF-?) and are useful as medicaments for the treatment and prevention of disorders caused by increased TNF-? activity, in particular inflammations.

Abstract: A compound of formula (I), wherein R, R1, R2, ring A, which ring contains one or two nitrogen atoms, and ring B are as defined in the Specification, pharmaceutical compositions containing these compounds, and uses for these compounds and compositions, in particular, in transplantation.

Abstract: Derivatives of pyrrolo[2,1-b]benzothiazepines with formula (I) where A is CH—CH2C?CH; R is hydrogen, halogen, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkyl, C5-C6 cycloalkyl; R1 is 1-peperazinyl, 1-homopiperazinyl and 1-piperidinyl; R2 is hydrogen, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkyl, CHO, CH?NOH,CH2OH. The formula (I) compounds are endowed with characteristic atypical anti-psychotic activity, and are therefore useful as medicaments, in particular for the treatment and prevention of schizophrenia, paranoid states, manic-depressive states, disorders of the affective sphere, social regression, personality regression, and hallucinations. Said compounds also present advantageous pharmacokinetic properties.

Abstract: The present invention is directed to compounds of Formula I: I (where A1, A2, B1, B2, B3, B4, D1, D2, J, K, T, U, V, W, X, Y, Z, R4, R5a, R5b, R5c, m and n are defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

Abstract: The present application relates to novel tricyclic benzazepine derivatives, processes for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for producing medicaments for the treatment and/or prophylaxis of diseases, preferably for the treatment and/or prevention of cardiovascular disorders, especially of dyslipidaemias, arteriosclerosis, restenosis and ischaemias.

Abstract: The present invention relates to tricyclic compounds each represented by the following formula (I): (wherein, R1, R2, R2?, R3, R4, X, Y and Z have the same meanings as defined in the specification); and a drug containing the compound. Since the compounds according to the present invention exhibit an excellent squalene synthetase inhibitory effect and cholesterol synthesis inhibitory effect so that they are useful as a drug such as preventive and/or remedy for diseases in mammals including humans such as hyperlipemia, e.g., hypercholesterolemia, hypertriglyceridemia, and low HDL cholesterolemia and/or arteriosclerosis.

Abstract: Novel triazole derivatives are inhibitors of TGF-beta receptor I kinase, and can be employed, inter alia, for the treatment of tumours.

Abstract: The invention encompasses a series of pyrimidinone compounds which inhibit HIV integrase and thereby prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses intermediates useful for making the pyrimidone compounds. Additionally, pharmaceutical compositions and methods for treating those infected with HIV are encompassed.

Abstract: Novel compounds according to general formula 1, wherein G1 is NR5R6 or a fused polycyclic group that are specific OT receptor agonists and/or V1a receptor antagonists. Pharmaceutical compositions comprising such compounds are useful in the treatment of, inter alia, primary dysmenorrhoea.

Abstract: The present invention provides dihydrodiaryloxazepine derivative represented by the following formula [1], analogs thereof and pharmaceutical compositions containing them.

Abstract: The invention encompasses a series of pyrimidinone compounds which inhibit HIV integrase and thereby prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses intermediates useful for making the pyrimidone compounds.

Abstract: This invention concerns the compounds of formula or a prodrug, a N-oxide, an addition salt, a quaternary amine or a stereochemically isomeric form thereof wherein R1, R2, —A—B—, L, and n have the meaning given in the description. The invention relates to preparations and compositions of the present compounds and their use as medicines.

Abstract: A compound of formula (I), or a pharmaceutically acceptable derivative thereof, wherein A, B, V, W, X, Y, and Z are as defined herein; pharmaceutical compositions thereof; and uses thereof.

Abstract: This invention concerns the compounds of formula or a prodrug, a N-oxide, an addition salt, a quaternary amine or a stereochemically isomeric form thereof wherein R1, R2, -A-B—, L, and n have the meaning given in the description. The invention relates to preparations and compositions of the present compounds and their use as medicines.

Abstract: The invention relates to the use of compound of Formula I in treating patients for inflammatory or neuropathic pain as well as various symptoms of multiple sclerosis

Abstract: Compounds of formula (I): 1

Abstract: The present invention relates to pyrrolobenzoxazepines, pyrrolobenzthiazepines and related compounds having the ability to induce apoptosis, to pharmaceutical compositions comprising these compounds and to their use as anti-tumour agents.

Abstract: The invention provides compounds or salts thereof of the general formula (I): wherein each of R1 and R2 independently represents a C1-6 alkyl or C2-7 acyl group; X represents OCH2 or a group CR3R4; wherein each of R3 or R4 independently represents a hydrogen atom or a C1-3 alkyl group; R5 represents a hydrogen atom or a C1-3 alkyl, C2-3 alkenyl or C2-3 alkynyl group; R6 represents a hydrogen atom or a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, amino, C1-6 alkylamino, di(C1-6) alkylamino or C2-7 acylamino group; each of R7 and R8 independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkylthio, C1-6 alkoxy, C3-6 cycloalkyl; and R9 represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkylthio, C1-6 alkoxy or C3-6 cycloalkyl group. The compounds or salts thereof are useful for treatment of respiratory disorders such as asthma.

Abstract: Compounds of general formula (I) wherein each of R1 and R2 independently represents a C1-6 alkyl or C2-7 acyl group; R5 represents a hydrogen atom or a C1-3 alkyl, C2-3 alkenyl or C2-3 alkynyl group; R6 represents a hydrogen atom or a C1-6 alkyl C2-6 alkenyl, C2-6 alkynyl, amino, C1-6 alkylamino, di(C1-6) alkylamino or C2-7 acylamino group; each of R7 and R8 independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkythio, C3-6 alkoxy, C3-6 cycloalkyl; and R9 represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-7 acyl, C1-6 alkythio.

Abstract: The present invention relates to benzoxazepine derivative having the general formula I, wherein X represents CO or SO2; R1, R2, R3 and R4 are independently selected from H, (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy(C1-4)alkyl, halogen, nitro, cyano, NR8R9, NR8COR10, and CONR8R9, R5, R6 and R7 are independently H or (C1-4)alkyl; R8 and R9 are independently H or (C1-4)alkyl; or R8 and R9 form together with the nitrogen atom to which they are bound a 5- or 6-membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O, S or NR11; R10 is (C1-4)alkyl; R11 is (C1-4)alkyl; A represents the residue of a 4-7 membered saturated heterocyclic ring, optionally containing an oxygen atom, the ring being optionally substituted with 1-3 substituents selected from (C1-4)alkyl, (C1-4)alkyloxy, hydroxy, halogen and oxo; or a pharmaceutically acceptable salt thereof.

Abstract: The invention relates to the use of compound of Formula I in treating patients for inflammatory or neuropathic pain as well as various symptoms of multiple sclerosis.

Abstract: A pharmaceutical composition comprising a salt, preferably a crystalline salt, of an organic acid of low water solubility and a compound of formula (I) is provided. The salts are useful in treating Parkinson's disease. Also provided are methods of treatment using the salts and methods of making crystalline forms of the salts.

Abstract: Novel fused indazoles and indoles are disclosed. Also disclosed are methods for the lowering and controlling of normal or elevated intraocular pressure as well as a method for the treatment of glaucoma using compositions containing one or more of the compounds of the present invention.

Abstract: Compounds with formula (I) are described where the groups are as defined here below, as well as processes for their preparation, pharmaceutical compositions containing them and their use for the preparation of medicaments with antipsychotic activity.

Abstract: The invention provides compounds or salts thereof of the general formula (I): 1

Abstract: This invention concerns the compounds of formula 1

Abstract: The invention provides compounds or salts thereof of the general formula (I): 1

Abstract: The invention provides methods and compositions for promoting neural cell growth and/or regeneration. The general methods involve contacting with an activator of a cyclic nucleotide dependent protein kinase a neural cell subject to growth repulsion mediated by a neural cell growth repulsion factor. The activator may comprise a direct or an indirect activator of the protein kinase; the repulsion factor typically comprises one or more natural, endogenous proteins mediating localized repulsion or inhibition of neural cell growth; and the target cells are generally vertebrate neurons, typically injured mammalian neurons. The subject compositions include mixtures comprising a neural cell, an activator of a cyclic nucleotide dependent protein kinase and a neural cell growth repulsion factor.

Abstract: The present invention is a method of treating sexual disturbances in humans and inducing mating in non-human mammals using the compounds of formula (A) 1