Abstract: The present invention is directed to 3-(ethoxydifluoromethyl)-6-(5-fluoro-6-(2,2,2-trofluoroethoxy)pyridine-3-yl)-[1,2,4]triazolo[4,3-?]pyridine, or a pharmaceutically acceptable salt thereof, or a composition thereof, which is useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein.

Abstract: The present invention is directed to 3-(ethoxydifluoromethyl)-6-(5-fluoro-6-(2,2,2-trofluoroethoxy)pyridine-3-yl)-[1,2,4]triazolo[4,3-a]pyridine, or a pharmaceutically acceptable salt thereof, or a composition thereof, which is useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein.

Abstract: The present invention relates to compounds that inhibit Polycomb Repressive Complex 2 (PRC2) activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of treating cancer using the compounds and pharmaceutical compositions of the present invention.

Abstract: The present invention discloses substituted pyrrolo[1,2-c]pyrimidines, such as the compound which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The present invention aims to provide a heterocyclic compound having an AMPA receptor potentiator effect, which is expected to be useful as an agent for the prophylaxis or treatment of depression, Alzheimer's disease, schizophrenia, attention deficit hyperactivity disorder (ADHD) and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as described in the specification, or a salt thereof.

Abstract: This invention concerns pharmaceutical compositions for administration via intramuscular or subcutaneous injection, comprising micro- or nanoparticles of the NNRTI compound TMC278, suspended in an aqueous pharmaceutically acceptable carrier, and the use of such pharmaceutical compositions in the treatment and prophylaxis of HIV infection.

Abstract: The present invention relates to a class of tricyclic compounds and an application thereof as a sphingosine 1-phosphate type 1 (S1P1) receptor agonist. The invention specifically relates to a compound represented by formula (II), and a tautomer and pharmaceutically acceptable salt of same.

Abstract: The present invention relates to compounds that inhibit Polycomb Repressive Complex 2 (PRC2) activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of treating cancer using the compounds of Formula (I) and pharmaceutical compositions of the present invention.

Abstract: The present invention relates to a compound represented by the Chemical Formula 1 defined in the present specification, or a pharmaceutically acceptable salt thereof. The compound according to the present invention can be usefully used for the prevention or treatment of diseases which are associated with kinase inhibitory actions.

Abstract: The present invention relates to fused heterocyclic derivatives, processes for their preparation and their use in medicine. Specifically, the present invention relates to a novel derivative represented by the formula (I?), or its pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the derivative or its pharmaceutically acceptable salt thereof, and the method for preparing the derivative and its pharmaceutically acceptable salt thereof. The present invention also relates to the use of the derivative and its pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the derivative and its pharmaceutically acceptable salt thereof in the preparation of medicines, in particularly as IDO inhibitor medicines, for treating and/or preventing cancers. Wherein each substituent of the formula (I?) is the same as defined in the specification.

Abstract: The present invention relates to pharmaceutical agents administered to a subject either in combination or in series for the treatment of a Respiratory Syncytial Virus (RSV) infection, wherein treatment comprises administering a compound effective to inhibit the function of the RSV and an additional compound or combinations of compounds having anti-RSV activity.

Abstract: Provided is an amino pyrazolopyrimidine compound as represented by the following structural formula used as a neurotrophic factor tyrosine kinase receptor inhibitor. The compound can inhibit the activity of Trk kinase and can treat diseases mediated by a Trk tyrosine kinase receptor in mammals.

Abstract: Imidazopyridine derivatives according to formula I are described wherein X is selected from CH, N, S, and O, Y is selected from S, CO, and O, R1 and optional R2 are independently selected from H, OH, substituted or unsubstituted C1-C6 alkyl, and substituted or unsubstituted C4-C6 cycloalkyl or cycloheteroalkyl, R3 is selected from H, OH, substituted or unsubstituted C1-C6 alkyl, and optional Z is selected from OH, NH2, NH(CO)R4, NH(SO2)R4, guanidine, alkylguanidine, and fluoroguanidine, R4 is polyethylene glycol or substituted or unsubstituted C1-C6 alkyl, and pharmaceutically acceptable salt thereof. The imidazopyridine derivatives can be used for treatment of cancer in a subject.

Abstract: A process for preparing one or more carbazoles comprising (a) contacting one or more compounds represented by formula (1) below with diboron reagents in the presence of PdCl2(dppf) to form one or more 2,2?-dichlorobiaryl represented by formula (2) below; and (b) contacting the one or more 2,2?-dichlorobiaryls with one or more H2N—Y compounds, in the presence of one or more palladium containing catalytic components; thereby forming one or more carbazoles represented by formula (3) below is provided.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, thereof: which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The present invention relates to an improved process for the preparation of carboxamide structured androgen receptor (AR) antagonists such as N—((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (1A) and key intermediates thereof such as 2-chloro-4-(1H-pyrazol-3-yl)benzonitrile (V). AR antagonists are useful in the treatment of cancer, particularly prostate cancer and other diseases where AR antagonism is desired.

Abstract: Systems and methods for evaluating multiple candidate electrostimulation vectors for use in therapeutic cardiac stimulation are disclosed. The system can include a programmable electrostimulator circuit for delivering electrostimulation to one or more sites of a heart according to multiple candidate electrostimulation vectors. One or more physiologic sensors can detect resulting physiologic responses to the electrostimulation. A processor circuit can generate categories of indicators including therapy efficacy indicators, battery longevity indicators, or complication indicators using the sensed physiologic responses. The candidate electrostimulation vectors can be ranked according to the categories of indicators in specified orders.

Abstract: Compounds of formula I, wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, can be used as insecticides and can be prepared in a manner known per se.

Abstract: A series of substituted imidazo[1,2-a]pyrimidine derivatives of formula (I), being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.

Abstract: Imidazopyridine derivatives according to formula I are described wherein X is selected from CH, N, S, and O, Y is selected from S, CO, and O, R1 and optional R2 are independently selected from H, OH, substituted or unsubstituted C1-C6 alkyl, and substituted or unsubstituted C4-C6 cycloalkyl or cycloheteroalkyl, R3 is selected from H, OH, substituted or unsubstituted C1-C6 alkyl, and optional Z is selected from OH, NH2, NH(CO)R4, NH(SO2)R4, guanidine, alkylguanidine, and fluoroguanidine, R4 is polyethylene glycol or substituted or unsubstituted C1-C6 alkyl, and pharmaceutically acceptable salt thereof. The imidazopyridine derivatives can be used for treatment of cancer in a subject.

Abstract: The invention provides substituted imidazo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted imidazo[1,5-a]pyrimidinyl carboxamide compounds described herein include substituted 2-heterocyclyl-4-alkyl-imidazo[1,5-a]pyrimidine-8-carboxamide compounds and variants thereof.

Abstract: Pyrimidone compounds defined herein exhibit human neutrophil elastase inhibitory properties and are useful for treating diseases and condition in which HNE is implicated.

Abstract: It has been desired to develop a pharmaceutical composition, which is used in agents for preventing and/or treating various diseases related to PDE10 (e.g. mental disorder and neurodegenerative disorder). The present invention provides: compounds having PDE10 inhibitory effect, in particular, compounds having a 4-heteroarylpyrazole-5-carboxylic acid amide structure represented by the following formula (I), or their pharmaceutically acceptable salts, or their solvates; pharmaceutical compositions comprising, as active ingredients, the compounds, or their pharmaceutically acceptable salts, or their solvates; and medical use of the compounds, or their pharmaceutically acceptable salts, or their solvates.

Abstract: Antiviral compositions and methods are contemplated that are especially effective in the treatment and prevention of influenza A viruses. Also presented are cellular assays to identify small molecule compounds having antiviral properties, particularly as it relates to detection of influenza A RNA-dependent RNA polymerase activity in a mammalian cell independent of other influenza A components. Preferred assays allow for identification of viral replication inhibitors that do not disrupt normal cellular activity.

Abstract: The present invention relates to methods for synthesizing energetic compounds and intermediates thereof. Specifically, the present invention relates to methods for synthesizing adamantanes and intermediates that are useful in such synthesis. Synthesized intermediates are useful in the synthesis of bicyclic and tricyclic substituted adamantanes. Examples of various intermediates are: acyclic 2-nitromalonaldehyde intermediates, 2,6,9-tri-substituted-4,8-dinitro-2,6,9-triazabicyclo[3.3.1]nona-3,7-dienes and 2,6-dinitro-4,8,9,10-tetra-aza-4,8,9,10-tetra-substituted adamantanes. Intermediates synthesized according to the methods of the present invention are useful toward the synthesis of tetraaza-adamantanes, which can serve as precursors to potentially superior new high-energy-density compounds (HEDCs).

Abstract: Disclosed is an antidepressant, neuroprotectant, amyloid ? deposition inhibitor, or age retardant composition containing a heterocyclic compound having the general formula (I):

Abstract: The present invention relates to novel substituted imidazo[1,2-a]pyrimidine compounds of formula (I), their pharmaceutically acceptable salts, and their isomers, stereoisomers, conformers, tautomers, polymorphs, hydrates and solvates. The present invention also encompasses pharmaceutically acceptable compositions of said compounds and process for preparing novel compounds. The invention further” relates to the use of the above-mentioned compounds for the preparation of medicament for use as pharmaceuticals. (Formula I).

Abstract: Compounds of formula (I): are useful as inhibitors of human neutrophil elastase.

Abstract: Disclosed are compounds of Formula 1, N-oxides, and salts thereof, wherein Z is O or S; A1, A2, A3 and A4 are independently N or CR1, provided that only one of A1, A2, A3 and A4 is N; and R1, R2, R3 and Q are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling a parasitic nematode comprising contacting the parasitic nematode or its environment with a biologically effective amount of a compound or a composition of the invention.

Abstract: The present invention provides, for example, the following compound: wherein ring A is a substituted or unsubstituted carbocycle or a substituted or unsubstituted heterocycle, X1—X2?X3 is CR5—CR6?CR7, N—CR6?CR7, CR5—N?CR7 or CR5—CR6?N, R1 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or the like, R2a and R2b are each independently hydrogen, substituted or unsubstituted alkyl or the like, R4a, R4b, R5, R6 and R7 are each independently hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl or the like, its pharmaceutically acceptable salt or a solvate thereof having an effect of inhibiting amyloid ? production, especially a BACE1 inhibitory activity, and useful as a medicament for treating diseases induced by production, secretion or deposition of amyloid ? proteins.

Abstract: The present application relates to novel substituted annellated pyrimidines, methods for production thereof, use thereof alone or in combinations for treating and/or preventing diseases and use thereof for the production of medicinal products for treating and/or preventing diseases, in particular for treating and/or preventing cardiovascular diseases.

Abstract: The present invention relates to certain amido-benzyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

Abstract: The present invention provides novel heteroaryl compounds having a pyrimidine-containing core that is linked to a 4-trifluoromethoxyphenyl group via an amine linker. Such compounds are useful for the treatment of cancers.

Abstract: Disclosed are 2,3-dihydroimiazo[1,2-c]pyrimidin-5(IH)-one compounds that inhibit Lp-PLA2,processes for their preparation, compositions containing them and their use in the treatment of diseases associated with the activity of Lp-PLA2, for example atherosclerosis, Alzheimer's disease.

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 invention relates to compounds of Formula (0): wherein Q, A1-A8, R4 and R5 and each has the meaning as described herein. Compounds of Formula (0) and pharmaceutical compositions thereof are useful in the treatment of diseases and disorders in which undesired or over-activation of NF-kB signaling is observed.

Abstract: The present invention provides new oxime derivatives of the general formula (I), pharmaceutical compositions containing them and their use for the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. This invention further provides new oxime derivatives of the general formula (I) consisting of modulators of nervous system receptors sensitive to glutamate, which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders. In particular embodiments, the new oxime derivatives of the invention are modulators of metabotropic glutamate receptors (mGluRs). The invention further provides positive allosteric modulators of mGluRs and more specifically positive alSosteric modulators of mGluR4.

Abstract: Compounds of Formula I: and stereoisomers and pharmaceutically acceptable salts and solvates thereof in which R1, R2, R3, R4, R5, R6, R7, X1 and X2 have the meanings given in the specification, are inhibitors of one or more JAK kinases and are useful in the treatment of autoimmune diseases, inflammatory diseases, rejection of transplanted organs, tissues and cells, as well as hematologic disorders and malignancies and their co-morbidities.

Abstract: Compounds of formula (I) or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer, wherein ring B and the pyrimidine to which it is fused, R4, R5, R6, R7, m and n have the meanings as given in the description and the claims, which are effective inhibitors of the Pi3K/Akt pathway, processes for their production and their use as pharmaceuticals.

Abstract: The present invention relates to compounds represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof. Definitions for the variables are provided herein.

Abstract: The present invention provides novel heteroaryl compounds of formula (I) having a pyrimidine-containing core that is linked to a 4-trifluoromethoxyphenyl group via an amine linker. Such compounds are useful for the treatment of cancers.

Abstract: Compounds of formula (I) or (II) wherein Rx, Rz, R9, R10, R14, R14?, R15, R15?, A and B are as defined in the claims and pharmaceutically acceptable salts and esters thereof, are disclosed. The compounds possess utility as tissue-selective androgen receptor modulators (SARM) and are useful as medicaments in the treatment of prostate cancer and other AR dependent conditions and diseases where AR antagonism is desired.

Abstract: The present invention relates to compounds of formula I: in which R1, R2, R3 and R4 are as defined in the Summary of the Invention. Compounds of formula I are capable of disrupting the BCL-2 interations with proteins containing a BH3 domain. Disrupting this interaction can restore the anti-apoptotic function of BCL-2 in cancer cells and tumor tissue expressing BCL-2. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancerous diseases.

Abstract: The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein A, R1, R2, R3 and m, are defined in the description. The present invention relates also to methods of making said compounds, and compositions containing said compounds which are useful for inhibiting kinases such as Glycogen Synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus Kinases (JAK), Cdc7, AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.

Abstract: The present invention is directed to aryloxymethyl cyclopropane derivatives which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

Abstract: The present invention provides a constant release copolymer composition adapted for use in a controlled release formulation for a bioactive agent, such as a formulation adapted for implantation within a patient's body tissues as a depot to release the agent over a period of time, wherein the copolymer provides a substantially constant rate of release of the bioactive agent over the time period for which the depot persists in the body tissues. The copolymer includes a PLG copolymer and a PLG oligomer of about 5-10 kDa average molecular weight, which can lack free carboxylic acid groups. When the PLG copolymer is a low burst copolymer, the constant release copolymer composition is a low burst, constant release copolymer composition adapted for implantation in the body tissues of a mammal, wherein a substantially constant rate of release of the bioactive agent is achieved.

Abstract: Provided herein are kinase inhibiting compounds and methods of using the same.

Abstract: In one aspect, the invention relates to imidazopyrimidin-5(6H)-one analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The disclosure relates to methods, compositions, and kits for treatment of parasite-mediated disease. In one embodiment, the disclosure relates to compounds, compositions, methods and kits for the treatment of malaria. In still another embodiment, the disclosure relates to a method for treating malaria comprising the use of a Syk kinase inhibitor.

Abstract: The present invention 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 W1, W2, W3, R1, Q, X1, X2 and X3 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.