Abstract: The present invention provides 2,4-pyrimidinediamine compounds that inhibit the IgE and/or IgG receptor signaling cascades that lead to the release of chemical mediators, intermediates and methods of synthesizing the compounds and methods of using the compounds in a variety of contexts, including in the treatment and prevention of diseases characterized by, caused by or associated with the release of chemical mediators via degranulation and other processes effected by activation of the IgE and/or IgG receptor signaling cascades.

Abstract: The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain biarylamine compounds (referred to herein as BAA compounds), and especially certain pyrazin-2-yl-pyridin-2-yl-amine and pyrazine-2-yl-pyrimidin-4-yl-amine compounds, which, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.

Abstract: Provided herein are compounds, pharmaceutical compositions and combination therapies for inhibition of hepatitis C.

Abstract: The present disclosure relates to pyrazine compounds of formula I: wherein L, n, R1, and R2 are as described in the specification. These compounds are useful as inhibitors of ATR protein kinase. The disclosure also relates to pharmaceutically acceptable compositions comprising the compounds of the disclosure; methods of treating of various diseases, disorders, and conditions using the compounds of the disclosure; processes for preparing the compounds of the disclosure; intermediates for the preparation of the compounds of the disclosure; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.

Abstract: Multifunctional compounds are provided, comprising two or more functional moieties selected from: (i) a moiety that imparts an iron chelator function; (ii) a moiety that imparts a neuroprotective function; (iii) a moiety that imparts combined antiapoptotic, neuroprotective and/or neurorestorative functions; (iv) a moiety that imparts brain MAO inhibition, preferably with little or no MAO inhibition in liver and small intestine; (v) a moiety that imparts cholinesterase inhibitory function; and (vi) a moiety that imparts an N-methyl-D-aspartic acid receptor (NMDAR) inhibition, and pharmaceutically acceptable salts and optical isomers thereof. The multifunctional compounds are useful in the treatment or prevention of diseases, disorders or conditions that can be prevented and/or treated by iron chelation therapy, and/or neuroprotection and/or neurorestoration, and/or apoptosis inhibition and/or MAO inhibition and/or cholinesterase inhibition and/or NMADR inhibition.

Abstract: The present invention relates to oligooxopiperazines and their use. Methods for preparing oligooxopiperazines are also disclosed.

Abstract: Provided is a compound useful as an inhibitor against the kinase activity of EML4-ALK fusion protein. As a result of intensive and extensive studies on compounds having inhibitory activity against the kinase activity of EML4-ALK fusion protein, the present inventors found that the diamino heterocyclic carboxamide compounds of the present invention had inhibitory activity against the kinase activity of EML4-ALK fusion protein. By this finding, the present invention was completed. The compounds of the present invention can be used as a pharmaceutical composition for preventing and/or treating cancer, such as lung cancer, non-small cell lung cancer, and small cell lung cancer.

Abstract: The use of CCR5 antagonists of the formula or a pharmaceutically acceptable salt thereof, wherein R is optionally substituted phenyl, pyridyl, thiophenyl or naphthyl; R1 is hydrogen or alkyl; R2 is substituted phenyl, substituted heteroaryl, naphthyl fluorenyl, diphenylmethyl or optionally substituted phenyl- or heteroaryl-alkyl; R3 is hydrogen, alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, or optionally substituted phenyl, phenylalkyl, naphthyl, naphthylalkyl, heteroaryl or heteroarylalkyl; R4, R5 and R7 are hydrogen or alkyl; R6 is hydrogen, alkyl or alkenyl; for the treatment of HIV, solid organ transplant rejection, graft v.

Abstract: The present invention relates to pyrazine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula II: wherein the variables are as defined herein.

Abstract: The present invention relates to pyrazine and pyridine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula V: wherein the variables are as defined herein.

Abstract: Provided herein are Heteroaryl Compounds having the following structure: wherein R1-R4 are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, neurodegenerative diseases, diabetes, obesity, neurological disorders, age-related diseases, or cardiovascular conditions, comprising administering an effective amount of a Heteroaryl Compound to a patient in need thereof.

Abstract: Disclosed are substituted pyridine compounds as well as pharmaceutical compositions and methods of use. One embodiment is a compound having the structure wherein E, J, T, the ring system denoted by “B”, T, R3, R4, w and x are as described herein. In certain embodiments, a compound disclosed herein activates the AMPK pathway, and can be used to treat metabolism-related disorders and conditions.

Abstract: Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.

Abstract: The present invention is directed in part towards methods of modulating the function of calcium channels with dihydropyrimidine, dihydropyrimidone, dihydropyrimidinethione, and dihydropyridine compounds. In addition, the invention describes methods of preventing and treating protein kinase-related abnormal conditions in organisms with a compound identified by the invention. Furthermore, the invention pertains to T-channel agonists that have a slow onset of activity and long duration of activity.

Abstract: The present invention relates to a compound or a pharmacologically acceptable salt thereof having superior glucokinase activating activity, and is a compound represented by general formula (I), or pharmacologically acceptable salt thereof: [wherein, A represents, for example, an oxygen atom or sulfur atom, R1 represents, for example, a C1-C6 alkyl group, a C1-C6 alkoxy group or a C1-C6 halogenated alkyl group, A and R1 together with the carbon atom bonded thereto form a heterocyclic group that may be substituted with 1 to 3 group(s) independently selected from Substituent Group ?, R2 represents a phenyl group that may be substituted with 1 to 5 group(s) independently selected from Substituent Group ? or a heterocyclic group that may be substituted with 1 to 3 group(s) independently selected from Substituent Group ?, R3 represents a hydroxy group or a C1-C6 alkoxy group, and Substituent Group ? consists of, for example, a halogen atom, a C1-C6 alkyl group, a C1-C6 alkyl group substituted with 1 or 2 hyd

Abstract: The present invention relates to soluble guanylate cyclase (sGC) and to phosphodiesterases (PDEs) and the pharmacology of sGC stimulators, sGC activators and PDE inhibitors. More particularly, the invention relates to the use of sGC stimulators and sGC activators in combination with PDE5 inhibitors for preparation of medicaments for the treatment of male erectile dysfunction (MED) in particular for the MED treatment of difficult to treat patients and patients not or not fully responding to PDE5 inhibitors.

Abstract: This invention comprises the novel compounds of formula (I) wherein n, m, t, R1, R2, R3, R4, L, Q, X, Y, Z and have defined meanings, having histone deacetylase inhibiting enzymatic activity; their preparation, compositions containing them and their use as a medicine.

Abstract: Compounds of Formula (I) or pharmaceutically acceptable salts or N-oxides thereof: (relative chemistry shown) pharmaceutical compositions comprising them, their use in therapy especially against tuberculosis, and methods of preparing them are described.

Abstract: The present application relates to new compounds of formula (I), to pharmaceutical compositions comprising the compounds, to processes for their preparation, and to the use of the compounds as leptin receptor modulator mimetics in the preparation of medicaments against conditions associated with weight gain, type 2 diabetes and dyslipidemias.

Abstract: The present invention relates to a process for the preparation of compounds which are therapeutically active in the central nervous system. In one aspect, the invention relates to a process for the preparation of compounds of the general formula (I): wherein HA is a pharmaceutically acceptable acid and R1-R4 are each independently selected from the group consisting of hydrogen, halogen, C1-C6-alkyl, C1-C6-alkoxy, and di-C1-C6-alkylamino-C2-C6-alkoxy. The invention also relates to the use of said compound to manufacture a medicament for the treatment of a serotonin-related disorder.

Abstract: Compounds of formula (I) have antibacterial activity: wherein: m is 0 or 1; Q is hydrogen or cyclopropyl; Alk is an optionally substituted, divalent C1-C6 alkylene, alkenylene or alkynylene radical which may contain an ether (—O—), thioether (—S—) or amino (—NR)— link, wherein R is hydrogen, —CN or C1-C3 alkyl; X is —C(?O)NR6—, —S(O)NR6—, —C(?O)O— or —S(?O)O— wherein R6 is hydrogen, optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -Cyc, or —(C1-C3 alkyl)-Cyc wherein Cyc is optionally substituted monocyclic carbocyclic or heterocyclic having 3-7 ring atoms; Z is N; R2 and R3 are as defined in the description.

Abstract: Compound corresponding to the general formula (I): in which A=N or CR2; R2?H, F, OH, CN, CF3, C1-6-alkyl, C1-6-alkoxy; n=2 or 3 and m=2 when A=N; n=1, 2 or 3 and m=1 or 2 when A=CR2; B=covalent bond or C1-8-alkylene; R1=optionally substituted heteroaryl; R3?CHR4CONHR5; R4?H or C1-6-alkyl; R5?H, C1-6-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-C6-alkylene; in the form of a base, an acid-addition salt, a hydrate or a solvate. Therapeutic uses thereof.

Abstract: Compounds of formula (I), are aurora kinase inhibitors: wherein X is —N—, —CH2-N—, —CH2-CH—, or —CH—; R1 is a radical of formula (IA) wherein Z is —CH2-, —NH—, -0-, —S(O)— —S—, —S(O)2 or a divalent monocyclic carbocyclic or heterocyclic radical having 3-7 ring atoms; Alk is an optionally substituted divalent C1-C6 alkylene radical; A is hydrogen or an optionally substituted monocyclic carbocyclic or heterocyclic ring having 5-7 ring atoms; r, s and t are independently 0 or 1, provided that when A is hydrogen then at least one of r and s is 1; R2 is halogen, —CN, —CF3, —OCH3, or cyclopropyl; and R3 is a radical of formula (IB) wherein Q is hydrogen or an optionally substituted phenyl or monocyclic heterocyclic ring with 5 or 6 ring atoms; Z&It;1> is —S—, —S(O)—, —S(O)2-, —O—, —SO2NH—, —NHSO2-, NHC(?O)NH, —NH(C?S)NH—, Or —N(R4)— wherein R4 is hydrogen, C1-C3 alkyl, cycloalkyl, or benzyl; and Alk&It;1> and Alk&It;2> are, independently, optionally substituted divalent C1-C3 alkyle

Abstract: This invention is directed to compounds and salts that are generally useful as anthelmintic agents or as intermediates in processes for making anthelmintic agents. This invention also is directed to processes for making the compounds and salts, pharmaceutical compositions and kits comprising the compounds and salts, uses of the compounds and salts to make medicaments, and treatments comprising the administration of the compounds and salts to animals in need of the treatments.

Abstract: The invention is concerned with novel nitrogen-containing heteroaryl compounds of formula (I) wherein A1, A2, R1, R2, R3, R4, R5 and R6 are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds inhibit PDE10A and can be used as therapeutics.

Abstract: Aryl- and heteroaryl-nitrogen heterocyclic compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, Huntington's Disease, bipolar disorder, obsessive-compulsive disorder, and the like.

Abstract: A compound of formula (I) wherein R1 is selected from H, F, Cl, Br, CF3, C1-C6 alkoxy and OH; R2 is selected from H and C1-C6 alkyl; n is 1-12; m is O or 1; Y is selected from CH2, NR3, (NR3R4)+X, O and S; R3 and R4 are independently selected from H and C1-C4 alkyl; and X? is selected from phannaceutically acceptable anions. A method of preparing the compound, its use as a pharmaceutical, and a method of treatment.

Abstract: Heterocyclic compounds of structural formula (I), or a pharmaceutically acceptable salt thereof, wherein W is a R1— substituted heteroaryl, R1 is an heteroaryl ring substituted with an ester or carboxylic acid containing radical, X-T is N—CR5R6, C?CR5 or CR13—CR5R6, Y is a bond or —C(O)—, a and b represent an integer selected from 1 to 4, and Ar is an optionally substituted phenyl or naphtyl, are inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD) The heterocyclic compounds are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, atherosclerosis, obesity, diabetes, neurological disease, Metabolic Syndrome, insulin resistance, cancer, liver steatosis, and non-alcoholic steatohepatitis.

Abstract: A heterocyclic compound or a salt thereof represented by the formula (1): where R2 represents a hydrogen atom or a lower alkyl group; A represents a lower alkylene group or lower alkenylene group; and R1 represents an aromatic group or a heterocyclic group. The compound of the present invention has a wide treatment spectrum for mental disorders including central nervous system disorders, no side effects and high safety.

Abstract: The invention relates to tropane urea derivatives of general formula (I) and to the application thereof as modulators of the activity of 11?-hydroxysteroid dehydrogenose type 1 (11?HSD1).

Abstract: The present invention provides compound of Formula (I): or a stereoisomer, tautomer, salt or solvate thereof, wherein the variables are defined herein. The compounds of formula (I) are inhibitors of Bcl-2 family antiapoptotic proteins, compositions containing the compounds and methods of treating diseases using the compounds.

Abstract: The present disclosure is generally directed to antiviral compounds, and more specifically directed to compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such compounds, and methods for inhibiting the function of the NS5A protein.

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

Abstract: The present invention relates to a compound represented by general formula [1] satisfying the following (I) or (II), or a pharmaceutical acceptable salt of the compound. (I) X is CH or N; R1 is a halogen atom,; and R2 is H, a halogen atom, CN, [2], [3], [8], [9], an —O-alkyl, an —O-(saturated ring), etc. [2]: —C(RC)(RD)(RE) (RC to RE each are H, an alkyl, etc.) [3]: —N(RF)(RG) (RF and RG each are H, OH, amino, a (hetero)aryl, etc.) [8]: —C(?O)RL (RL is an alkyl, OH, an alkoxy, amino, etc.) [9]: a (substituted)phenyl; (II) X is >C—C(—O)R3 (R3 is a (substituted)amino, an alkoxy, OH, etc.); R1 is a halogen atom; R2 is H; R3 is H or OH; and R3 and R4 each are H or an alkyl.

Abstract: The instant invention provides for compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity by administering the compound to a patient in need of treatment of cancer.

Abstract: The present invention encompasses compounds of general Formula (1) wherein R1 to R4 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a medicament having the above-mentioned properties.

Abstract: The present invention provides a new group of protein kinase inhibitors, pyrropyrimidine and pyrazolopyrimidine derivatives, and pharmaceutically acceptable salts and prodrugs thereof that are useful for treating cell proliferative disease and disorder such as cancer, autoimmune diseases, infection, cardiovascular disease and neurodegenerative disease and disorder. The present invention provides methods for synthesizing and administering the protein kinase inhibitor compounds. The present invention also provides pharmaceutical formulations comprising at least one of the protein kinase inhibitor compounds together with a pharmaceutically acceptable carrier, diluent or excipient therefor. The invention also provides useful intermediates generated during the syntheses of the pyrropyrimidine and pyrazolopyrimidine derivatives.

Abstract: The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain biarylamine compounds (referred to herein as BAA compounds), and especially certain pyrazin-2-yl-pyridin-2-yl-amine and pyrazine-2-yl-pyrimidin-4-yl-amine compounds of formula (I), which, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc.

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

Abstract: Axl kinase inhibitory compounds are disclosed, as well as compositions and methods of using the same in the treatment of cancer and other conditions mediated by and/or associated with Axl kinase.

Abstract: Compounds of general formula (I), (II), (III) and (V) are described for use in modulating microtubule polymerisation and in the treatment of associated disease states. Use of compounds (I), (III) and (V) in the treatment of kinase-associated disease states is also described. Further described are novel compounds of formula (II), (III) and (V).

Abstract: The present invention provides compounds according to general formula (I) which are proposed for the treatment of respiratory complaints, particularly asthma and COPD.

Abstract: The invention relates to 4-aminocarbonyl-pyrimidine derivatives and their use as P2Y12 receptor antagonists in the treatment and/or prevention and/or treatment of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.

Abstract: Compounds of formula (I) have antibacterial activity: wherein: m is 0 or 1; Q is hydrogen or cyclopropyl; Alk is an optionally substituted, divalent C1-C6 alkylene, alkenylene or alkynylene radical which may contain an ether (—O—), thioether (—S—) or amino (—NR)— link, wherein R is hydrogen, —CN or C1-C3 alkyl; X is —C(?O)NR6—, —S(O)NR6—, —C(?O)O— or —S(?O)O— wherein R6 is hydrogen, optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -Cyc, or —(C1-C3 alkyl)-Cyc wherein Cyc is optionally substituted monocyclic carbocyclic or heterocyclic having 3-7 ring atoms; Z is N or CH, or CF; R2 and R3 are as defined in the description.

Abstract: Provided are a novel low-molecular-weight compound that suppresses production of induction type MMPs, particularly MMP-9, rather than production of hemostatic type MMP-2, as well as a prophylactic/therapeutic drug for autoimmune diseases or osteoarthritis. An amide derivative represented by the following formula (I) wherein each symbol is as defined in the specification, a pharmacologically acceptable salt thereof, or a hydrate or solvate thereof.

Abstract: The present invention relates to novel compounds that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.

Abstract: A compound, particularly an antimalarial compound, according to formula I: or a pharmaceutically acceptable salt thereof, wherein: X is an electron-withdrawing group; A is an optionally substituted alkanediyl or an optionally substituted cycloalkanediyl that includes 2 to 5 carbon atoms; and R1 and R2 are each individually H, tert-butyl, isopropyl, or optionally substituted cycloalkyl.

Abstract: The disclosure concerns heterobicyclic compounds of general formula (I) and acid addition salts, hydrates and solvates thereof, as well as enantiomers, diastereoisomers and mixtures thereof. Methods for preparing the compounds, pharmaceutical compositions, and methods of treatment also are disclosed.

Abstract: The present invention provides compounds of Formula I, including tautomers, resolved enantiomers, diastereomers, solvates, metabolites, salts and pharmaceutically acceptable prodrugs thereof. Also provided are methods of using the compounds of this invention as AKT protein kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.

Abstract: A compound of Formula I in free or salt or solvate form, where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 have the meanings as indicated in the specification, is useful for treating diseases which respond to the blockade of the epithelial sodium channel. Pharmaceutical compositions that contain the compounds and processes for preparing the compounds are also described.