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, 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 R1, R2, R3 and R4 have the meanings given in claim 1, at least one EP4 receptor antagonist (2), the preparation thereof and the use thereof for the treatment of respiratory complaints.

Abstract: The present invention is related to 2-amino-4-arylthiazole derivatives as 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). Also provided herein are 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 substituted benzothiazoles, benzoxazoles—and their counterparts having pyridine and pyrimidine rings replacing the benzene ring—that are PDE4 inhibitors useful for treating stroke, myocardial infarct, and cardiovascular inflammatory conditions, to pharmaceutical compositions comprising these compounds, and to methods for the treatment of stroke, myocardial infarct, and cardiovascular inflammatory conditions in a mammal. The compounds have general formula I: in which A and B are carbocycles or heterocycles.

Abstract: The present invention relates to compounds of formula IA-i useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

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: The present intervention generally relates to compositions comprising a PDE11 inhibitor for increasing cortisol levels in a subject, or for increasing the production of cortisol from adenocortical cells in a subject. Aspects of the invention relate to the use of a PDE11 inhibitor in a method of treatment of low cortisol levels and/or adrenal insufficiency in a subject, or a method of treating a disease or disorders associated with adrenal insufficiency. Aspects of the invention relate to PDE11 inhibitors belonging to compounds of formula (I)-(VI), and their use alone or in combination with long-term corticosteroid treatment to elevate cortisol levels in a subject, and/or to treat adrenal insufficiency.

Abstract: Disclosed are new thienyl[3,2-d]pyrimidin-4-one compounds shown as the general formula (I), preparation method, pharmaceutical compositions and pharmacological use thereof. The compounds are strong DPPIV (dipeptide peptidase IV) inhibitors and can treat type II diabetes through well inhibiting DPPIV indirectly increasing the content of GLP-1 in vivo and inducing a series of physiological actions in vivo. Therefore, the compounds could be developed as new promising drugs for treating diabetes.

Abstract: The invention relates to amino alcohol-substituted arylthienopyrimidinones having a formula I and their derivatives, and their physiologically tolerated salts and physiologically functional derivatives, their preparation, medicaments comprising at least one amino alcohol-substituted arylthienopyrimidinone of the invention or its derivative, and the use of the amino alcohol-substituted arylthienopyrimidinones of the invention and their derivatives as MCH antagonists.

Abstract: The present invention relates to novel thienopyrimidine compounds of general formula pharmaceutical compositions comprising these compounds and their therapeutic use for the prophylaxis and/or treatment of diseases which can be influenced by the inhibition of the kinase activity of Mnk1 and/or Mnk2 (Mnk2a or Mnk2b) and/or variants thereof.

Abstract: The invention relates to oxazolopyrimidine compounds of formula (I), where A, R1, R2, R3, R4, X and Y are defined as stated in the claims. The compounds of formula I are suitable, for example, for wound healing.

Abstract: Heterocyclic carboxylic acid derivatives comprising a 2,5-substituted oxazolopyrimidine ring as Edg-1 receptor agonists The present invention relates to oxazolopyrimidine compounds of the formula I, in which A, R1, R2, R3, X and Y are defined as indicated in the claims. The compounds of the formula I modulate the activity of the Edg-1 receptor and in particular are agonists of this receptor, and are useful for the treatment of diseases such as atherosclerosis, heart failure or peripheral arterial occlusive disease, for example. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.

Abstract: The present invention relates to oxazolopyrimidine compounds of the formula I, in which A, R1, R2, R3 and X are defined as indicated in the claims. The compounds of the formula I modulate the activity of the Edg-1 receptor and in particular are agonists of this receptor, and are useful for the treatment of diseases such as atherosclerosis, heart failure or peripheral arterial occlusive disease, for example. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.

Abstract: Compounds are disclosed for the treatment, management and prevention of diseases and disorders affecting the bone. Particular compounds are potent inhibitors of Notum Pectinacetylesterase, and are of the formula: wherein E, G, Y, Z, R1, R2, and R3 are defined herein.

Abstract: The present invention relates generally to thienopyrimidine and thienopyridine class compounds and methods of use thereof. In particular embodiments, the present invention provides compositions comprising thienopyrimidine class compounds and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins (e.g., for the treatment of leukemia, solid cancers and other diseases dependent on activity of MLL1 and MLL2 or menin).

Abstract: The present invention relates to novel 3-substituted (7-imino-2-thioxo-3,7-dihydro-2H-thiazolo[4,5-d]pyrimidin-6-yl of formula 1 wherein R is selected from a group consisting of hydrogen, alkyl having carbon no up to 10, allyl, cycloalkyl, aromatic, substituted aromatics (halogen, OH, COOH, OCH3, alkyl, etc), pyridyl, piperidine, piprazine, morphine. R1 is selected from a group consisting of NH2, NHR, N(R)2 (wherein R could be aliphatic or olefinic group up to 10 carbon), hetrocycles such as furan, thiophene, pyrole, prydyl, piprazine, morphine and R2 is O and S separately. Particularly the present invention relates to (7-Imino-3-substituted-2-thioxo-3,7-dihydro-2H-thiazolo[4,5-d]pyrimidin-6-yl)-urea (15-21) and Furan-2-carboxylic acid (7-imino-3-substituted-2-thioxo-3,7-dihydro-2H-thiazolo[4,5-d]pyrimidin-6-yl)-amide.

Abstract: The invention relates to azacyclyl-substituted arylthienopyrimidinones and their derivatives, of the Formula (I); and their physiologically tolerated salts and physiologically functional derivatives, their preparation, medicaments comprising at least one azacyclyl-substituted arylthienopyrimidinone according to Formula (I) or its derivative, and the use of the azacyclyl-substituted arylthienopyrimidinones according to Formula (I) and their derivatives as MCH antagonists.

Abstract: The invention provides a crystal of 2-(3,4-dichlorobenzyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylic acid (which has the chemical structure shown below) and a mixed crystal comprising such a crystal. The invention also provides methods of producing such crystals, pharmaceutical compositions comprising such crystals, and methods of modulating phosphodiesterase-9 activity and treating disorders such as overactive bladder syndrome by administration of an effective amount of the crystals.

Abstract: Provided is a compound useful for the prophylaxis or treatment of cancer. The present invention relates to a compound represented by formula (I): wherein each symbol in the formula is as defined in the specification, or a salt thereof or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer.

Abstract: The invention relates to molecules ANT-ligands having a substituted nitrogeneous heterocycle A wherein A is a substituted pyrazinone of formula I wherein R1 is —(CH2)n—CO—OH; —(CH2)n—CO—OR; —(CH2)n—CO—NHR; —(CH2)n—CO—N(R,R?); —(CH2)n—OH; —(CH2)n—OR; —(CH2)n—OAr; —(CH2)n—C(R,R?)—(CH2)n—OH, R and R?, in the above radicals, being identical or different and representing H or a C1-C12 alkyl or cycloalkyl radical; and Ar is a phenyl or Het., Het.

Abstract: Bicyclic aryl substituted triazoles or 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 activity are also disclosed.

Abstract: A method of treating diabetes mellitus or a microvascular or macrovascular complication of diabetes mellitus in a patient in need thereof, the method comprising administering to the patient a compound of formula 1 wherein R1, R2, R3, and R4 are as defined in claim 1.

Abstract: Provided is a compound useful for the prophylaxis or treatment of cancer. The present invention relates to a compound represented by formula (I): wherein each symbol in the formula is as defined in the specification, or a salt thereof or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer.

Abstract: The present invention relates to N-(hetero)aryl-pyrrolidine derivatives of Formula I: which are JAK inhibitors, such as selective JAK1 inhibitors, useful in the treatment of JAK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.

Abstract: The present invention provides a compound represented by the formula: wherein R1 is a C1-4 alkyl; R2 is (1) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1?) a halogen, (2?) a hydroxy group, (3?) a C1-4 alkyl and (4?) a C1-4 alkoxy, (2) a phenyl which may have a substituent selected from the group consisting of (1?) a halogen, (2?) a C1-4 alkoxy-C1-4 alkyl, (3?) a mono-C1-4 alkyl-carbamoyl-C1-4 alkyl, (4?) a C1-4 alkoxy and (5?) a mono-C1-4 alkylcarbamoyl-C1-4 alkoxy, or the like; R3 is a C1-4 alkyl; R4 is a C1-4 alkoxy, or the like; n is an integer of 1 to 4; or a salt thereof, as a thienopyrimidine compound having gonadotropin-releasing hormone antagonistic activity.

Abstract: N3-Heteroaryl substituted triazoles and N5-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 activity are also disclosed.

Abstract: Chemical entities that modulate PI3 kinase activity, and chemical entities, pharmaceutical compositions, and methods of treatments of diseases and conditions associated with P13 kinase activity are described herein.

Abstract: The present invention relates to thienopyrimidine compounds which are potassium channel inhibitors. Pharmaceutical compositions comprising the compounds and their use in the treatment of arrhythmia are also described.

Abstract: The present invention relates to 3-Heterocyclic Substituted Indole Derivatives, compositions comprising at least one 3-Heterocyclic Substituted Indole Derivative, and methods of using the 3-Heterocyclic Substituted Indole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient.

Abstract: The present invention relates to provision of a novel compound that has an activity of promoting insulin secretion from pancreatic ? cells and thus is useful as a prophylaxis and/or therapeutic agent for diseases caused by hyperglycemia such as diabetes mellitus, and the compound represented by the following formula (1): wherein one of A and B represents a nitrogen atom and the other represents a nitrogen atom or CR10, X represents an oxygen atom, a sulfur atom or —(CH2)n-N(R12)—, Y represents an oxygen atom, a sulfur atom or —N(R13)—, and R1 to R9 each represent a hydrogen atom or another substituent, or a salt thereof, or a solvate of the compound or the salt.

Abstract: The present invention relates to N-containing heterocyclic compounds that are inhibitors of protein kinases including JAK kinases. In particular, the compounds are selective for JAK1, JAK2, JAK3 or TYK2 kinases and combinations thereof such as JAK1 and JAK2. The kinase inhibitors can be used in the treatment of kinase associated diseases such as immunological and inflammatory diseases including organ transplants; hyperproliferative diseases including cancer and myeloproliferative diseases; viral diseases; metabolic diseases; and vascular diseases.

Abstract: 2-Phenoxy pyrimidinone analogues are provided, of the Formula: wherein variables are as described herein. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using such compounds to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

Abstract: Provided are compounds of Formula I, stereoisomers, tautomers, solvates, prodrugs and pharmaceutically acceptable salts thereof, wherein A, X, R1, R2, R4 and R5 are defined herein, a pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, methods of using the compound or composition in therapy, and methods of manufacturing a compound of Formula I.

Abstract: The invention relates to treatment and/or prevention of nerve injury. In one embodiment, the present invention provides a method of preserving the neuromuscular junction (NMJ) in an individual by administering a therapeutically effective dosage of a composition comprising an inhibitor of Wnt3a, and an inhibitor of MMP3 to the individual. In another embodiment, the present invention provides a method of stabilizing NMJ after nerve injury by inhibiting the WNT and beta-catenin signaling pathway and preserving agrin.

Abstract: The present invention provides methods and compositions comprising compounds useful for stimulating neurogenesis. The methods and compositions comprising compounds are also useful for inhibiting neuronal degeneration. Thus, the present invention can be used in the treatment of diseases and conditions characterized by neuronal loss and reduced neurogenesis including Alzheimer's disease, stroke, traumatic brain injury, traumatic nerve injury, and depression. This invention is useful for research products including single agents or mixtures of agents to promote, proliferate, differentiate, or maintain neurons from stem or progenitor cells.

Abstract: Piperidinodihydrothienopyrimidines of formula 1 wherein X is SO or SO2 (preferably SO), and R1, R2, R3, and R4 may have the meanings given in the disclosure and claims, pharmacologically acceptable salts thereof, and pharmaceutical compositions containing these compounds. These piperidinodihydrothienopyrimidines are suitable for the treatment of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin, or eyes, diseases of the peripheral or central nervous system, or cancers.

Abstract: The present invention relates to novel thienopyrimidine compounds of general formula pharmaceutical compositions comprising these compounds and their therapeutic use for the prophylaxis and/or treatment of diseases which can be influenced by the inhibition of the kinase activity of Mnk1 and/or Mnk2 (Mnk2a or Mnk2b) and/or variants thereof.

Abstract: The invention relates to oxazolopyrimidine compounds of formula (I), where A, R1, R2, R3, R4 and X are defined as stated in the claims. The compounds of formula I are suitable, for example, for wound healing.

Abstract: The invention provides a crystal of 2-(3,4-dichlorobenzyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylic acid (which has the chemical structure shown below) and a mixed crystal comprising such a crystal. The invention also provides methods of producing such crystals, pharmaceutical compositions comprising such crystals, and methods of modulating phosphodiesterase-9 activity and treating disorders such as overactive bladder syndrome by administration of an effective amount of the crystals.

Abstract: Bridged bicyclic aryl or 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 activity are also disclosed.

Abstract: The present application relates to novel bicyclic azaheterocycles, to processes for preparation thereof, to the use thereof, alone or in combinations, for treatment and/or prophylaxis of diseases and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially for treatment and/or prophylaxis of cardiovascular disorders.

Abstract: The present invention relates to cycloalkyloxycarboxylic acid derivatives of the formula I in which A, R1, R2a, R2b, R2c, R3 and X are as defined in the claims. The compounds of the formula I are suitable, for example, for wound healing.

Abstract: The present invention relates to oxazolopyrimidine compounds of the formula I in which A, R1, R2 and R3 are defined as indicated in the claims. The compounds of the formula I modulate the activity of the Edg-1 receptor and in particular are agonists of this receptor, and are useful for the treatment of diseases such as atherosclerosis, heart failure or peripheral arterial occlusive disease, for example. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.

Abstract: The present invention provides a compound represented by the formula: wherein R1 is a C1-4 alkyl; R2 is (1) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1?) a halogen, (2?) a hydroxy group, (3?) a C1-4 alkyl and (4?) a C1-4 alkoxy, (2) a phenyl which may have a substituent selected from the group consisting of (1?) a halogen, (2?) a C1-4 alkoxy-C1-4 alkyl, (3?) a mono-C1-4 alkyl-carbamoyl-C1-4 alkyl, (4?) a C1-4 alkoxy and (5?) a mono-C1-4 alkylcarbamoyl-C1-4 alkoxy, or the like; R3 is a C1-4 alkyl; R4 is a C1-4 alkoxy, or the like; n is an integer of 1 to 4; or a salt thereof, as a thienopyrimidine compound having gonadotropin-releasing hormone antagonistic activity.

Abstract: Phosphorylation of histones was observed at certain tyrosine residues which have not been associated with epigenetic modification. These sites include H2B Tyr37, H4 Tyr88 and Tyr51 and H3 Tyr99. Kinases responsible for the phosphorylation as well as downstream genes regulated by such phosphorylation were also identified. Antibodies that are specific to such phosphorylated histones have been generated, which are useful for detecting the phosphorylation and related events. With such findings, the present disclosure provides compositions and methods for disease diagnosis, prognosis and therapy selection, in particular for cancer, obesity and diabetes.

Abstract: Drug candidates for inhibition of HIV-1 replication can target Src family kinases (SFK), such as Hck, that interact with Nef protein of the virus. Compounds characterized by such inhibitory activity were identified via an assay for kinase activity of an SFK in a Nef:SFK complex. Illustrative of inhibitors identified using the kinase assay are various 2,3-diaminoquinaxolines and furo[2,3-d]pyrimidines. The inventive inhibitors were found to arrest HIV-1 viral replication in vitro.

Abstract: The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein R1, R2, R3, A, B, and n are defined in the description. The present invention relates also to compositions containing compounds of formula (I) which are useful for inhibiting kinases such as wee-1 and methods of treating diseases such as cancer.

Abstract: The compounds of formula (1) in which A, X, R1, R2, R3 and R7 have the meanings as given in the description, are novel effective inhibitors of type 4 and type 5 phosphodiesterase.

Abstract: Provided herein are substituted bicyclic compounds, e.g., compounds of Formula IV, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are useful for inhibiting phosphatidyl inositol-3 kinase (PI3 kinase), e.g., for the treatment of various diseases and conditions associated with PI3 kinase activity, including but not limited to, cancer, inflammatory disease, immune disease, and respiratory disease.

Abstract: Certain TRPV1-modulating imidazolo-, oxazolo-, and thiazolopyrimdine compounds are described. The compounds may be used in pharmaceutical compositions and methods for treating disease states, disorders, and conditions mediated by TRPV1 activity, such as pain, arthritis, itch, cough, asthma, or inflammatory bowel disease.

Abstract: The present patent application relates to a pharmaceutical composition comprising a transient receptor potential ankyrin-1 receptor (“TRPA1”) antagonist and a beta-2 adrenergic receptor agonist (“beta-2 agonist”).