Abstract: Highly efficient process for the preparation of 4-Fluoro-1H-pyrazole or salts thereof by reaction of pyrazole with an electrophilic fluorinating reagent is disclosed.

Abstract: This invention relates to compounds of Formula (I) and enantiomers thereof, and to pharmaceutically acceptable salts of Formula (I) and said enantiomers, wherein R1, R2 and R3 are as defined herein. The invention further relates to pharmaceutical compositions comprising such compounds and salts, and to methods and uses of such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer, in a subject in need thereof.

Abstract: The present invention relates to identification of inhibitors or antagonists of aminoarabinase glycosyltransferase (ArnT) and their use in compositions, methods of treatment or prevention of drug resistant gram negative infections, or inhibiting the growth of gram negative bacterial infections resistant to polymyxin-class antibiotics. In certain aspects, the inhibitors or antagonists can be administered in combination with one or more antibacterial agents.

Abstract: A compound having the structure of below Formula (I), or pharmaceutically acceptable salts thereof, are useful as JAK inhibitors, wherein R1, R2, L1, L2, T and X are as herein described.

Abstract: The present invention relates to substituted pyrazole compounds, methods for their discovery, and their research and therapeutic uses, as well as pharmaceutically acceptable salts, solvates, chelates, non-covalent complexes, prodrugs, mixtures (including both R and S enantiomeric forms and racemic mixtures thereof) and pharmaceutical formulations thereof.

Abstract: The present invention relates to HSF activating compounds, methods for their discovery, and their research and therapeutic uses, as well as pharmaceutically acceptable salts, solvates, chelates, non-covalent complexes, prodrugs, mixtures (including both R and S enantiomeric forms and racemic mixtures thereof), and pharmaceutical Formulations thereof. In particular, the present invention provides compounds capable of facilitating HSF1 homotrimerization, and methods of using such compounds as therapeutic agents to treat a number of conditions associated with irregular HSF1 activity.

Abstract: This invention is directed to compounds, which are PDE10A enzyme inhibitors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. The present invention also provides processes for the preparation of the compounds of formula I. The present invention further provides a method of treating a subject suffering from a neurodegenerative disorder comprising administering to the subject a therapeutically effective amount of a compound of formula I. The present invention also provides a method of treating a subject suffering from a drug addiction comprising administering to the subject a therapeutically effective amount of a compound of formula I. The present invention further provides a method of treating a subject suffering from a psychiatric disorder comprising administering to the subject a therapeutically effective amount of a compound of formula I.

Abstract: Provided is a method whereby a heteroaromatic ring aryl can be very rapidly methylated at a high yield. In an N-alkyl-2-pyrrolidinone, a heteroaromatic ring aryltrialkylstannan is cross-coupled with methyl iodide in the presence of a palladium complex, a phosphine ligand, a cuprous halide, a carbonic acid salt and/or an alkali metal fluoride to thereby rapidly methylate the heteroaromatic ring aryl. (Formula shows a case wherein the heteroaromatic ring aryl is a pyridyl group.

Abstract: The present invention provides novel 1,4-disubstituted phthalazine hedgehog pathway antagonists useful in the treatment of cancer.

Abstract: A process for the manufacture of a cyclic compound of formula (I) which comprises (a) adding an acid halide of formula R1—C (O)—X, to a vinyl ether of formula (II): CH2?CH—OR2, to produce an addition product, and (b) reacting the addition product with a compound of formula (III): Y-A-Z; wherein R1 is a halogenated alkyl group; wherein X is fluorine, chlorine, or bromine; wherein R2 is an alkyl group, an aralkyl group, or an aryl group; wherein Z and Y designate independently carbon or a heteroatom; and wherein A is a linking group between Z and Y comprising 0, 1, 2 or 3 atoms in the cycle.

Abstract: Provided herein are compounds of formula A-L-B, and pharmaceutically acceptable salts and stereoisomers thereof, wherein A is R1 and R2 together with the carbon atoms to which they are attached form a 1,2-phenylene ring optionally substituted with one or more R11; L is —C(R6)2—C(R6)2—; B is a heteroaromatic group defined herein; and -A1-A2- , A3, R11 and R6 are defined herein. Also disclosed are methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. In one embodiment, the compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as CNS disorders and metabolic disorders, including, but not limited to, e.g., neurological disorders, psychosis, schizophrenia, obesity, and diabetes.

Abstract: Certain imidazopyrazines of Formula (I): or pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample.

Abstract: This document discloses molecules having the following formula (“Formula One”): and processes related thereto.

Abstract: The invention relates to lithium-2-methoxy-1,1,2,2-tetrafluoro-ethanesulfonate, to the use thereof as conductive salt in lithium-based energy accumulators, and ionic liquids comprising 2-methoxy-1,1,2,2-tetrafluoro-ethanesulfonate as an anion.

Abstract: Compounds are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9)-mediated diseases, and as controls in assays for the identification of CCR(9) antagonists.

Abstract: Disclosed herein are substituted quinoxaline carboxylic acids of Formula (I): and compositions thereof, which may be useful as inhibitors of PAS Kinase (PASK) activity in a human or animal for the treatment of diseases such as diabetes mellitus.

Abstract: The present invention relates to the use of novel triazolopyridine derivatives of formula I: wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.

Abstract: The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

Abstract: A variety of specific compounds within the scope of formula I which are useful as PI3K inhibitors and can be employed for the treatment of autoimmune diseases, inflammation, cardiovascular diseases, neurodegenerative diseases and tumours, and pharmaceutical compositions and kits containing said specific compounds.

Abstract: The present invention relates to certain pyrazolo[1,5-a]pyrimidine compounds of Formula (I) as inhibitors of mammalian Target Of Rapamycin (mTOR) kinase, which is also known as FRAP, RAFT, RAPT or SEP. The compounds may be used in the treatment of cancer and other disorders where mTOR is deregulated. The present invention further provides pharmaceutical compositions comprising the pyrazolo[1,5-a]pyrimidine compounds.

Abstract: Disclosed herein are compounds and compositions thereof which find use in increasing stability of TTR tetramers reducing its tendency to misfold and form aggregates. Also provided herein are methods for using these compounds and compositions for increasing stability of TTR and thereby decreasing aggregate formation by TTR. Also disclosed herein are methods to screen for candidate compounds that increase stability of TTR. Also disclosed herein are heterobifunctional compounds that include a TTR binding compound connected to a targeting moiety via a linker, for use in disrupting PPIs of a target protein.

Abstract: Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein X, Y, R1, R2, and R3 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with the P2X7 purinergic receptor.

Abstract: The invention relates to compounds the formula (I): and pharmaceutically usable salts, tautomers and stereoisomers thereof, wherein R1, R2 and R3 are defined herein. The compounds of formula (I) and their pharmaceutically usable salts, tautomers and stereoisomers are inhibitors of PDK1 and cell proliferation/cell vitality and can be employed for the treatment of tumors.

Abstract: Provided herein are stabilized radioiodinated and astatinated compounds, and to methods for their preparation.

Abstract: The present invention relates to methods for the treatment of a pathology associated with hyperglycaemia, particularly diabetes, by administering quinoxalinone compounds of formula (I), wherein R1, R2, R3, R4, R5 and R6 are as defined in the claims. The compounds have activity as insulin secretion stimulators. The invention also relates to the preparation and use of these quinoxalinone compounds for modulating insulin secretion in insulin-1 cells by contacting the cells with the compounds.

Abstract: The present invention provides compounds having formula (I): and pharmaceutically acceptable derivatives thereof, wherein R1, R2 and B are as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of any of a number of conditions or diseases in which HGF/SF or the activities thereof, or agonists or antagonists thereof have a therapeutically useful role.

Abstract: The invention relates to compounds of formula (I): as described herein, pharmaceutical preparations comprising such compounds, uses and methods of use for such compounds in the treatment of a disorder or a disease mediated by the activity of MDM2 and/or MDM4, and combinations comprising such compounds.

Abstract: Methods of inhibiting cytochrome P450 2D6 enzymes are provided that can be used for improving the treatment of diseases by preventing degradation of drugs or other molecules by cytochrome P450 2D6. Pharmaceutical compositions are provided that can act as boosters to improve the pharmacokinetics, enhance the bioavailability, and enhance the therapeutic effect of drugs that undergo in vivo degradation by cytochrome P450 2D6 enzymes.

Abstract: The present invention relates to compounds of formula (I) wherein R1, R2, R3, R5, W, X, X1, Y, Y1, Z and Z1 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit PDE10A and can be used in the treatment of CNS disorders such as schizophrenia, Alzheimer's disease, and Parkinson's disease.

Abstract: The present invention relates to novel compounds of Formula (I), wherein X1, X2, Y, Z1, Z2, Z3, M and (A)m are defined as in Formula (I); invention compounds are modulators of metabotropic glutamate receptors—subtype 4 (“mGluR4”) which are useful for the treatment or prevention of central nervous system disorders as well as other disorders modulated by mGluR4 receptors. The invention is also directed to pharmaceutical compositions and the use of such compounds in the manufacture of medicaments, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR4 is involved.

Abstract: The invention provides compounds of the formula (I) having protein kinase B inhibiting activity: Also provided are pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anticancer agents.

Abstract: A number of compounds and use of the compounds in a method for treating or preventing cancer in a subject by administering to the subject a pharmaceutical composition including a compound of formula I or a pharmaceutically acceptable salt thereof are described. The compounds can also be used to inhibit integrin-linked kinase in a cell, which has an effect on the Akt signaling pathway.

Abstract: Compounds of the formula (I) in which the substituents are as defined in claim 1 are suitable for use as microbiocides. Formula (I), wherein X is oxygen or sulfur; A is a 5- or 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur, or a phenyl ring; the heterocyclic ring or the phenyl being substituted by the groups R6, R7 and R8; R6, R7 and R8 are each, independently, hydrogen, halogen, cyano, nitro, C1-4 alky, C1-4 halogenalkyl, C1-4 halogenalkoxy, C1-4 alkoxy(C1-4)alkyl or C1-4halogenalkoxy(C1-4)alkyl, provided that at least one of R6, R7 and R8 is not hydrogen; B is a phenyl, naphthyl or quinolinyl group, which is substituted by one or more substituents R9.

Abstract: The present invention relates to compounds of formula (I) its salts, isomers or prodrugs thereof useful in the treatment of viral infections, in particular respiratory syncytial virus (RSV) infections. The present invention also relates to processes for preparing the compounds and intermediates used in their preparation.

Abstract: A method of modulating one or more of ras-Raf-Mek-Erk signal transduction pathway, PI3K-Akt signal transduction pathway and SAPK signal transduction pathway with 1-ethyl-3-[3-(1-methyl-1H-pyrazol-4-yl)-pyrido[2,3-b]pyrazine-6-yl]thiourea, its geometric isomer, or its tautomer.

Abstract: The invention relates to substituted phenylureas and phenylamides, to processes for the preparation thereof, to pharmaceutical compositions containing these compounds and also to the use of these compounds for preparing pharmaceutical compositions.

Abstract: Invented are novel heterocyclic carboxamide compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.

Abstract: Methods for deterring microglia-mediated neurotoxicity in a human or non-human animal subjects comprising the step of inhibiting or blocking the intermediate-conductance calcium-activated potassium channel KCa3.1 in microglia, such as in subjects how suffer from neurodegenerative diseases (e.g., Alzeheimer's Disease) or ischemic/anoxic/hypoxic conditions. The inhibition or blocking of the KCa1.3 channels may be accomplished by administering a KCa3.1 inhibiting substance, such as 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34).

Abstract: The present invention relates to pesticidal mixtures comprising as active compounds 1) at least one isoaxazoline compound I of the formula (I) wherein R1, R2, R3, R4, R5 and A are defined in the description; and 2) at least one active compound II selected from a group A comprising acteylcholine esterase inhibitors, GABA-gated chloride channel antagonists, sodium channel modulators, nicotinic acteylcholine receptor agonists/antagonists, chloride channel activators, juvenile hormone mimics, compounds affecting the oxidative phosphorylation, inhibitors of the chitin biosynthesis, moulting disruptors, inhibitors of the MET, voltage-dependent sodium channel blockers, inhibitors of the lipid synthesis and other compounds as defined in the description, in synergistically effective amounts.

Abstract: Novel compounds of the general formula (I), the use of these compounds as pharmaceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds are activators of PPAR? and should be useful for treating conditions mediated by the same.

Abstract: A new class of phosphoinositide-dependent kinase-1 (PDK-1) inhibitors of formula I: wherein X is selected from the group consisting of alkyl and haloalkyl; Ar is an aryl radical selected from the group consisting of phenyl, biphenyl, naphthyl, anthryl, phenanthryl, and fluorenyl; and wherein Ar is optionally substituted with one or more radicals selected from the group consisting of halo, C1-C4 alkyl, C1-C4 haloalkyl, azido, C1-C4 azidoalkyl, aryl, alkylaryl, haloaryl, haloalkylaryl, and combinations thereof; and R is selected from the group consisting of nitrile, acetonitrile, ethylnitrile, propylnitrile, carboxamide, amidine, tetrazole, oxime, hydrazone, acetamidine, aminoacetamide, guanidine, and urea. Also provided are methods of using the compounds for the treatment and prevention of cancer in humans.

Abstract: Use of a new class of phosphoinositide-dependent kinase-1 (PDK-1) inhibitors of formula I for inducing apoptosis in unwanted rapidly proliferating cells, for treating, inhibiting, or delaying the onset of cancer, and for preventing restenosis in a subject that has undergone an angioplasty or stent: wherein X is selected from the group consisting of alkyl and haloalkyl; Ar is an aryl radical selected from the group consisting of phenyl, biphenyl, naphthyl, anthryl, phenanthryl, and fluorenyl; and wherein Ar is optionally substituted with one or more radicals selected from the group consisting of halo, C1-C4 alkyl, C1-C4 haloalkyl, azido, C1-C4 azidoalkyl, aryl, akylaryl, haloaryl, haloalkylaryl, and combinations thereof; and R is selected from the group consisting of nitrile, acetonitrile, ethylnitrile, propylnitrile, carboxamide, amidine, tetrazole, oxime, hydrazone, acetamidine, aminoacetamide, guanidine, and urea.

Abstract: The invention relates to compounds of formula (I) wherein the substituens are as defined in the specification, in free form or in the form of a pharmaceutically acceptable salt, solvate, ester, N-oxide thereof; processes for the preparation thereof; to pharmaceuticals containing such compounds, in particular for the use in one or more Protein tyrosine kinase mediated diseases.

Abstract: A process for the manufacture of a cyclic compound of formula (I) which comprises (a) adding an acid halide of formula R1—C (O)—X, to a vinyl ether of formula (II): CH2?CH—OR2, to produce an addition product, and (b) reacting the addition product with a compound of formula (III): Y-A-Z; wherein R1 is a halogenated alkyl group; wherein X is fluorine, chlorine, or bromine; wherein R2 is an alkyl group, an aralkyl group, or an aryl group; wherein Z and Y designate independently carbon or a heteroatom; and wherein A is a linking group between Z and Y comprising 0, 1, 2 or 3 atoms in the cycle.

Abstract: A methodology and pharmaceutical and gene therapies for the treatment and regulation of memory function are provided. The invention identifies specific HDAC, and in particular, HDAC3 and HDAC4 as negative regulators of memory formation and specifically targets one or both HDAC3 and HDAC4 for down-regulation. By specifically targeting HDAC3 and HDAC4 with small molecule inhibitors and gene therapies it is possible to provide a powerful therapeutic approach to facilitate gene expression during memory formation that can lead to the regulation and treatment of memory disorders.

Abstract: 1-ethyl-3-[3-(1-methyl-1H-pyrazol-4-yl)-pyrido[2.3-b]pyrazine-6-yl]thiourea which HAS activity to the modulation of misdirected cellular signal transduction processes such as tyrosine kinases, serine/threonine kinases and/or lipid kinases.

Abstract: The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein A is hydrogen, C1-4alkyl, C3-6cycloalkyl, C1-3alkoxy, C1-3alkoxy C1-4alkyl, C1-2fluoroalkyl, halogen, NR6R7, optionally substituted heteroaryl (Het), or optionally substituted phenyl, and R1, R2, R3, R4, R5, R6 and R7 are as defined in the description. The compounds or salts are thought to modulate P2X7 receptor function and to be capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of the compound or salt in the treatment or prophylaxis of, for example, inflammatory pain, neuropathic pain, visceral pain, rheumatoid arthritis, osteoarthritis or neurodegenerative disorders.

Abstract: The present invention is directed to alkoxy tetrahydro-pyridopyrimidine compounds of formula I, 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 application relates to novel 3-(fluorovinyl)pyrazole derivatives, to processes for their preparation, to their use for treatment and/or prevention of diseases and to their use for the preparation of medicaments for treatment and/or prevention of diseases, in particular for treatment and/or prevention of hyperproliferative and angiogenic diseases and those diseases which arise from metabolic adaptation to hypoxic states. Such treatments can be carried out as monotherapy or also in combination with other medicaments or further therapeutic measures.

Abstract: Certain imidazopyrazines of Formula (I): and pharmaceutical compositions thereof are provided herein. Methods of treating patients responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity of Formula (I) effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample.