Abstract: Muscarinic Acetylcholine Receptor Antagonists and methods of using them are provided.

Abstract: The present invention relates to 1-aza-bicycloalkyl derivatives of formula I, wherein X is CH2 or a single bond; Y is a group of formula and wherein R has the meanings as defined in the specification, which compounds are alpha 7 nicotinic acetylcholine receptor (nAChR) agonists; to processes for their production, their use as pharmaceuticals and to pharmaceutical compositions comprising them.

Abstract: Carbamates of formula (I) or pharmaceutically acceptable salts thereof, including quaternary ammonium salts of formula (II) are disclosed; as well as processes for their preparation, pharmaceutical compositions comprising them and their use in therapy as antagonists of M3 muscarinic receptors.

Abstract: The present invention relates to a method for substantially preventing a reduction in feed intake in an animal which occurs when said animal is administered an antibiotic, the method comprising administering to an animal in need of prevention of a reduction in feed intake, increasing doses of a composition comprising one or more antibiotics. The present invention also relates to a method for treating laminitis and fermentative acidosis in an animal in need of said treatment, the method comprising administering increasing doses of a composition comprising one or more antibiotics. The present invention further relates to a method for treating equine grass sickness and pulpy kidney in an animal in need of said treatment, the method comprising administering increasing doses of a composition comprising one or more antibiotics.

Abstract: The present invention relates to (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide, novel salt forms thereof, methods for its preparation, novel intermediates, and methods for treating a wide variety of conditions and disorders, including those associated with dysfunction of the central and autonomic nervous systems.

Abstract: Compounds of Formula (I); in salt or zwitterionic form wherein R1, R2, R3 and R4 have the meanings as indicated in the specification, are useful for treating conditions that are mediated by the muscarinic M3 receptor, especially inflammatory or obstructive airways diseases. Pharmaceutical compositions that contain the compounds and a process for preparing the compounds are also described.

Abstract: The present invention is directed to compounds of formula I compositions comprising them and their use.

Abstract: Compounds of formula I: wherein A, D, Ar1, E and Ar2 are as defined in the specification, processes for preparing them, pharmaceutical compositions containing them and their use in therapy, especially in the treatment or prophylaxis of psychotic and intellectual impairment disorders.

Abstract: The field of the invention relates to stable dosage forms comprising spiro or dispiro 1,2,4-trioxolane antimalarials, or their pharmaceutically acceptable salts, prodrugs and analogues, and processes for their preparation. The water content of the dosage form is not more than 6.5% w/w.

Abstract: New quinuclidine amide derivatives having the chemical structure of general formula (I) and pharmaceutically acceptable salts thereof including quaternary salts of formula (II) are disclosed; as well as processes for their preparation, pharmaceutical compositions 10 comprising them and their use in therapy as antagonists of M3 muscarinic receptors.

Abstract: Muscarinic Acetylcholine Receptor Antagonists and methods of using them are provided.

Abstract: [Problem] To provide a compound which may be used for the prevention and/or treatment of diseases in which 5-HT2B receptor and 5-HT7 receptor are concerned, particularly for the treatment of irritable bowel syndrome (IBS). [Means for Resolution] It was found that a pyrrole derivative characterized by the possession of a guanidinocarbonyl group or amido group as a substituent group at the 3-position, or a pharmaceutically acceptable salt thereof, has a strong antagonism for both of the 5-HT2B receptor and 5-HT7 receptor. In addition, the compound of the present invention having the antagonistic activity for both of the receptors showed a good pharmacological action in comparison with the case in which an antagonist selective for either one of the receptors was used alone. Based on the above, the compound of the present invention is useful for the prevention and/or treatment of diseases in which 5-HT2B receptor and 5-HT7 receptor are concerned, particularly for the treatment of irritable bowel syndrome (IBS).

Abstract: Novel compounds are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR 119 G protein-coupled receptor modulator therapy. These novel compounds have the structure Formula I or Formula IA.

Abstract: The present invention relates to heterocyclic compounds of the formula (I) or a pharmaceutically acceptable salt, a solvate or hydrate thereof wherein the heterocycle comprises two double bonds which may be present at several positions, and which are represented by the dashed lines (---); the heterocycle contains two heteroatoms, W is N or NH; Y is CH, O or NH, wherein if Y is O, X1 is CH and X2 is C-Z-R2 or C—R3, wherein Z is NH, O, or S; and if Y is CH or NH, one of X1 and X2 is CH or N, wherein if X1 is CH or N, X2 is C-Z-R2 or C—R3, and if X2 is CH or N, X1 is C-Z-R2 or C—R3, wherein Z is NH or S; R1 is chosen from structures (a), (b) and (c): R2 is chosen from (C1-C10)alkyl, (C2-C10)alkenyl and (C2-C10)alkynyl, optionally independently substituted with one or more substituents chosen from halogen, hydroxy, cyano, oxo, (C1-C6)alkoxy, (C1-C6)alkylthio, (C1-C6)alkenyloxy, (C1-C6)alkenylthio, (C1-C4)alkoxy(C1-C4)alkoxy, (C5-C7)cycloalkyl, a 5-membered unsaturated heterocycle (optionally s

Abstract: The present invention relates to methods for intradermally delivering one or more biologically active agents such as vaccines and therapeutic agents into the dermis layer of the skin of a subject to obtain systemic delivery or an immune response using a microneedle drug delivery device containing the agent to be delivered. The methods employ a microneedle device with a row of hollow microneedles. The microneedles penetrate the skin of the subject and assume an anchored state in which the microneedles are anchored in the skin and project laterally from the device. A pivotal motion is then performed with the device so that the skin in which the microneedles are engaged is lifted above the initial plane of the surface of the skin while the biologically active agent is delivered. The methods of the invention elicit increased humoral and/or cellular response as compared to conventional vaccine delivery routes, facilitating dose sparing.

Abstract: A method of forming analogs of CDD-0304, i.e., tetra(ethyleneglycol) (4-methoxy-1,2,5-thiadiazol-3-yl)[3-(1-methyl-1,2,4,5-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl]ether hydrochloride includes one or more of the following steps: a) replacing the tetrahydropyridine moiety with one of the following heterocyclic rings, including quinuclidine, [2.2.1]-exo-azabicy-cloheptane, [2.2.1]-endo-azabicycloheptane and terahydropyrimidine; b) varying the length of the linking group by replacing the tetra(ethylene) glycol moiety with one of: ethylene glycol, di(ethylene) glycol, penta(ethylene) glycol, or diether diol; and/or, c) replacing the 1,2,5-thiadiazole moiety with an ester isostere. Also, a method for an asymmetric analog CCD-0304 includes replacing at least one moiety with an ester isostere and at least a second moiety with an ammonium isostere. Also, such analogs compounds and their uses are disclosed.

Abstract: Provided are muscarinic receptor antagonists, which can be useful in treating various diseases of the respiratory, urinary or gastrointestinal system mediated through muscarinic receptors. Also provided are processes for preparing compounds described herein, pharmaceutical compositions comprising compounds described herein, and methods for treating diseases mediated through muscarinic receptors.

Abstract: Carbamates of formula (I) or pharmaceutically acceptable salts thereof, including quaternary ammonium salts of formula (II) are disclosed; as well as processes for their preparation, pharmaceutical compositions comprising them and their use in therapy as antagonists of M3 muscarinic receptors.

Abstract: This invention relates to novel quinuclidine derivatives and their use as pharmaceuticals. 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 is directed to methods of enhancing insulin release, GLP-1 release, and insulin sensitivity, methods of increasing insulin gene expression, methods of decreasing gastric secretion and emptying and glucagons secretion, and methods of inhibiting food intake, and methods of treating diabetes mellitus, insulin resistance syndrome, hyperglycemia, and obesity comprising administering to a subject an effective amount of a TRPM5 inhibitor.

Abstract: The invention relates to the use of sabcomeline or a pharmaceutically acceptable salt thereof in monotherapy for the treatment of bipolar disorder or mania or and to adjunctive and simultaneous combination therapies for the treatment of bipolar disorder or mania in which sabcomeline or a pharmaceutically acceptable salt thereof and at least one other mood stabilizing or antimanic agent are administered adjunctively or simultaneously. The invention provides methods of treatment of bipolar disorder or mania utilizing such monotherapy and such adjunctive or simultaneous therapeutic combination therapies, therapeutic combinations for use therein and pharmaceutical compositions comprising them.

Abstract: The invention describes compositions and kits comprising at least qrie organic nitric oxide enhancing salt of an angiotensin converting enzyme inhibitor, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; Q) treating osteoporosis; (k) treating nephropathy; (l) treating peripheral vascular diseases; (m) treating portal hypertension; (n) treating ophthalmic disorders; (o) treating metabolic syndrome; and (p) treating hyperlipidemia.

Abstract: This invention provides compounds of the formula: useful in the inhibition or modulation of serine palmitoyl transferase and their use in methods of treatment or amelioration of type 2 diabetes, type 1 diabetes, insulin resistance, the effects of obesity, metabolic syndrome (sometimes referred to as Syndrome X), impaired glucose tolerance, Cushing's disease, cardiovascular disease, prothrombotic conditions, myocardial infarction, hypertension, congestive heart failure, cardiomyopathy, atherosclerosis, dyslipidemia, sepsis, liver damage, retinal degenerative disorders, cachexia, emphysema, hepatitis C infections, HIV infections and inflammatory disorders and useful in methods for raising HDL plasma levels in a mammal. The compounds of this invention can also be used to prevent damage or loss of pancreatic islet beta cells (such as in the case of pancreatic beta cell apoptosis, including those related to insulin-dependent diabetes mellitus).

Abstract: Muscarinic Acetylcholine Receptor Antagonists and methods of using them are provided.

Abstract: Carbamate of general formula (I), wherein R1, R2, and R3 are H, OH, NO2, SH, CN, F, Cl, Br, I, COOH, CONH2, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkoxyl optionally substituted with one or several F, and (C1-C4)-alkyl optionally substituted with one or several F or OH; R4 is cycloalkyl, phenyl, heteroaryl or a bicyclic ring system; R5 is cycloalkyl, (C5-C10)-alkyl, a substituted (C1-C10)-alkyl; and X? is a physiologically acceptable anion. Carbamate (I) is selective M3 receptor antagonists versus M2 receptor and may be used for the treatment of urinary incontinence (particularly, the one caused by overactive bladder), irritable bowel syndrome, and respiratory disorders (particularly, chronic obstructive pulmonary disease, chronic bronchitis, asthma, emphysema, and rhinitis), as well as in ophthalmic interventions.

Abstract: A method is provided for using ?2? subunit calcium channel modulators or other compounds that interact with the ?2? calcium channel subunit in combination with one or more compounds with smooth muscle modulatory effects to treat and/or alleviate the symptoms associated with painful and non-painful lower urinary tract disorders in normal and spinal cord injured patients. According to the present invention, ?2? subunit calcium channel modulators include GABA analogs (e.g. gabapentin and pregabalin), fused bicyclic or tricyclic amino acid analogs of gabapentin, and amino acid compounds. Compounds with smooth muscle modulatory effects include antimuscarinics, ?3 adrenergic agonists, spasmolytics, neurokinin receptor antagonists, bradykinin receptor antagonists, and nitric oxide donors.

Abstract: The present invention relates to compounds of formula (I) wherein n represents 0, 1, 2, 3, 4 or 5 R represents independent from each other hydroxyl, cyano, nitro, halogen, alkyl, alkoxy alkylcarbonyl, alkoxycarbonyl, alkylamine, dialkylamine, alkylcarbonylamine, alkylcarbamate Y represents one of the following groups: in free base or acid addition salt form, to processes for their production, their use as pharmaceuticals and to pharmaceutical compositions comprising them.

Abstract: The invention provides novel quinolinone-carboxamide 5-HT4 receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT4 receptor activity, and processes and intermediates useful for preparing such compounds.

Abstract: Compounds of formulae I, II and III: are disclosed as 5-HT3 inhibitors. The compounds are useful in treating CINV, IBS-D and other diseases and conditions.

Abstract: Carbamates of formula (I) or pharmaceutically acceptable salts thereof, including quaternary ammonium salts of formula (II) are disclosed; as well as processes for their preparation, pharmaceutical compositions comprising them and their use in therapy as antagonists of M3 muscarinic receptors.

Abstract: The invention relates to the quinuclidine compounds of formula I having quaternary ammonium group, its preparation, and the pharmaceutical composition comprising an effective amount of the compound of formula I. The compound and the composition are used to prevent and treat the diseases by blocking acetylcholine receptor. Wherein: R1 is selected from C1-12 saturated straight-chain alkyl and cycloalkyl; R2 is selected from C1-12 saturated straight-chain alkyl or straight-chain alkyl; X is selected from halogen ion, organic and inorganic acid radical.

Abstract: The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, which are useful for the inhibition of the uptake of one or more physiologically active monoamines (serotonin, norepinephrine, and dopamine).

Abstract: The present invention provides an improved synthetic strategy for the preparation of solifenacin and pharmaceutically acceptable salts thereof.

Abstract: Disclosed is the use of compounds of formula (I) wherein X, Y and Z are as defined in the description of the invention, for the preparation of an antitumor medicament, optionally in combination with different biologically active substances.

Abstract: This invention provides compounds and pharmaceutical compositions thereof for treating human type 1 and type 2 diabetes, particularly insulin-resistant diabetes.

Abstract: The present invention relates to 3-substituted-2-(arylalkyl)-1-azabicycloalkanes, methods of preparing the compounds and methods of treatment using the compounds. The azabicycloalkanes generally are azabicycloheptanes, azabicyclooctanes, or azabicyclononanes. The aryl group in the arylalkyl moiety is a 5- or 6-membered ring heteroaromatic, preferably 3-pyridinyl and 5-pyrimidinyl moieties, and the alkyl group is typically a C1-4 alkyl. The substituent at the 3-position of the 1-azabicycloalkane is a carbonyl group-containing moiety, such as an amide, carbamate, urea, thioamide, thiocarbamate, thiourea or similar functionality. The compounds exhibit activity at nicotinic acetylcholine receptors (nAChRs), particularly the ?7 nAChR subtype, and are useful towards modulating neurotransmission and the release of ligands involved in neurotransmission.

Abstract: A compound according to formula (I) wherein: © is a phenyl ring, a C4 to C9 heteroaromatic compound containing one or more heteroatoms, or a naphthalenyl, 5,6,7,8-tetrahydronaphthalenyl or biphenyl group; R1, R2 and R3 each independently represent a hydrogen or halogen atom, or a hydroxy group, or a phenyl, —OR4, —SR4, —NR4R5, —NHCOR4, —CONR4R5, —CN, —NO2, —COOR4 or —CF3 group, or a straight or branched lower alkyl group which may optionally be substituted, for example, with a hydroxy or alcoxy group, wherein R4 and R5 each independently represent a hydrogen atom, straight or branched lower alkyl group, or together form an alicyclic ring; or R1 and R2 together form an aromatic, alicyclic or heterocyclic ring; n is an integer from 0 to 4; A represents a —CH2—, —CH?CR6, —CR6?CH—, —CR6R7—, —CO—, —O—, —S—, —S(O)—, SO2 or —NR6— group, wherein R6 and R7 each independently represent a hydrogen atom, straight or branched lower alkyl group, or R6 and R7 together form an alicyclic ring; m is an integer from 0 to 8

Abstract: Compounds of formulae I and II: are disclosed as 5-HT3 inhibitors. Those compounds are useful in treating CINV, IBS-D and other diseases and conditions.

Abstract: The invention relates to N-biarylamides useful for the prophylaxis and/or treatment of impairments of perception, concentration, learning and/or memory, and to processes for preparing them, and pharmaceutical compositions containing them.

Abstract: Compounds of formula (I) wherein the different substituents and/or radicals have the values defined in the claims. The invention also relates to a process for the preparation of said compounds, to pharmaceutical compositions comprising them, as well as to combinations of said compounds with other compounds which are active in the treatment of respiratory, urological or gastrointestinal disorders or diseases. Finally the invention also relates to the use of the compounds of formula (I) for the treatment of respiratory, urological or gastrointestinal disorders or diseases.

Abstract: The invention provides compounds of the formula (I) or a salt, tautomer, solvate or N-oxides thereof; wherein: R1 is selected from (a) 2,6-dichlorophenyl; (b) 2,6-difluorophenyl; (c) a 2,3,6-trisubstituted phenyl group wherein the substituents are fluorine, chlorine, methyl or methoxy; and (d) a group R0 wherein R0 is a 3-12 membered carbocyclic or heterocyclic group; or optionally substituted C1-8 hydrocarbyl; R2a and R2b are each hydrogen or methyl; and R3 is as defined in the claims. The compounds have activity as inhibitors of Cyclin Dependent Kinases (CDK) and Glycogen Synthase Kinases (GSK) kinases and are useful in the treatment or prophylaxis of disease states or conditions mediated by the kinases.

Abstract: The invention provides a therapeutic method for preventing or treating a pathological condition or symptom in a mammal, such as a human, wherein the infectivity of a pathogen such as a retrovirus toward mammalian cells is implicated and inhibition of its infectivity is desired comprising administering to a mammal in need of such therapy, an effective amount of a benzoylquinuclidine derivative that inhibits pathogenic infectivity, including pharmaceutically acceptable salts

Abstract: The present invention relates to 1-aza-bicycloalkyl derivatives of formula (I) wherein the substituents are as defined in the specification, to processes for their production, their use as pharmaceuticals in the prevention and treatment of psychotic and neurodegenerative disorders. The claimed compounds act as nicotinic acelylcholine receptors (NACHR) ligands.

Abstract: Azacyclic ethynyl derivatives, which 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: Compounds of formula I: wherein A and R1 are as defined in the specification, processes for preparing them, pharmaceutical compositions containing them and their use in therapy, especially in the treatment or prophylaxis of psychotic and intellectual impairment disorders.

Abstract: Substituted piperidines of formulae (I) and (II) with the substituent definitions as explained in the specification. The compounds are suitable in particular as renin inhibitors and are highly potent.

Abstract: A method for the treatment or prophylaxis of an infection in a mammal, said infection caused by an anti-microbial resistant bacteria, comprising, administering, to the mammal a pleuromutilin derivative is disclosed.

Abstract: The invention provides a combination of a cytotoxic compound or signalling inhibitor and a compound having the formula (0): or salts or tautomers or N-oxides or solvates thereof; wherein X is a group R1-A-NR4- or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C?O, NRg(C?O) or 0(C?O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2; R2 is hydrogen; halogen; C1-4alkoxy (e.g.

Abstract: A series of N-substituted 9-azabicyclo[3.3.1]nonan-3?-yl phenylcarbamate analogs are disclosed, as well as methods of their preparation. Their affinities for sigma (?1 and ?2) receptors are described. Two new compounds, N-(9-(4-aminobutyl)-9-azabicyclo[3.3.1]nonan-3?-yl)-N?-(2-methoxy-5-methylphenyl)carbamate and N-(9-(6-aminohexyl)-9-azabicyclo[3.3.1]nonan-3?-yl)-N?-(2-methoxy-5-methylphenyl)carbamate, are shown to have a high affinity and selectivity for ?2 versus ?1 receptors. Among the disclosed compounds are biotinylated and fluorescent analogs. These compounds can serve as probes to the ?2 receptor. In addition, some disclosed compounds can induce apoptotic cell death by both caspase-dependent and caspase-independent mechanisms, and are effective for treatment of tumors. The compounds can be used as chemotherapeutics or chemosensitizers in the treatment of a wide variety of solid tumors.

Abstract: The present invention relates to the use of at least one inhibitor of at least one ABC-transporter capable of transporting hyaluronan across a lipid bilayer, such as verapamil or valspodar, for the preparation of a pharmaceutical composition for the treatment of a disease which is associated with an excess transport of hyaluronan across a lipid bilayer, e.g. arthritis. Furthermore, the present invention relates to a method for screening a compound which is suitable for the treatment of a disease which is associated with an excess transport of hyaluronan across a lipid bilayer, e.g. arthritis. The present invention also relates to a method for screening a compound which reduces the transport of hyaluronan mediated by (an) ABC-transporter(s). Furthermore, the present invention relates to a method for identifying a subject at risk for a disease which is associated with an excess transport of hyaluronan across a lipid bilayer, e.g.