Abstract: Provided herein are Mcl-1 antagonist compositions and methods of treating g the compositions described herein.

Abstract: Heteroarylpiperidine and -piperazine derivatives of the formula (I) in which the symbols A, X, Y, L1, L2, G, Q, p, R1, R2 and R10 are each as defined in the description, and salts, metal complexes and N-oxides of the compounds of the formula (I), and the use thereof for controlling phytopathogenic harmful fungi and processes for preparing compounds of the formula (I).

Abstract: The present invention relates to a pharmaceutical composition for treating or preventing epilepsy containing a sulfamate derivative compound and/or pharmaceutically acceptable salt thereof as an active ingredient. Furthermore, the present invention relates to a method for treatment or prevention epilepsy comprising administering a sulfamate derivative compound in a pharmaceutically effective amount to a subject in need of treatment or prevention of epilepsy.

Abstract: Malonic ester derivatives of the formula (I) in which the symbols A1, A2, Y, R10, p, X, R2, G, Q, L2 and R1 are each as defined in the description, and salts, metal complexes and N-oxides of the compounds of the formula (I), and the use thereof for controlling phytopathogenic harmful fungi and processes for preparing compounds of the formula (I).

Abstract: Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, stereoisomer or prodrug thereof, wherein R1, R2, R3a, R3b, R4a, R4b, G1, G2, L, m1, m2 and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Abstract: The present invention relates to a novel crystalline form of 2-{3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}-3-chlorophenylmethansulphonate, to processes for its preparation and to its use in agrochemical preparations.

Abstract: The invention refers to a combination comprising a sigma ligand of formula (I) and an opioid or opiate for use in the prevention and/or treatment of pain developed as a consequence of surgery, especially peripheral neuropathic pain, allodynia, causalgia, hyperalgesia, hyperesthesia, hyperpathia, neuralgia, neuritis or neuropathy. The invention also refers to the sigma ligands of formula (I) for use in potentiating the analgesic effect of an opioid or opiate and/or for decreasing the dependency induced thereby when said opioid or opiate is used in the prevention and/or treatment of pain developed as a consequence of surgery.

Abstract: Processes are described for the preparation of tubulysins. The processes are useful for preparing predetermined mixtures of tubulysins, preparing single tubulysins from mixtures of tubulysins, and for converting one tubulysin into a different tubulysin. The tubulysins described herein are useful in treating diseases and disease states that include pathogenic cell populations.

Abstract: The present invention relates to fungicidal N-bicycloalkyl and N-tricycloalkyl pyrazole-4-(thio)carboxamide derivatives of formula (I), wherein T represents O or S; n represents 0 or 1; and B represents where the bond marked by * is attached to the (CZ2Z3)n-N amide moiety, their process of preparation and intermediate compounds for their preparation, their use as fungicides, particularly in the form of fungicidal compositions and methods for the control of phytopathogenic fungi of plants using these compounds or their compositions.

Abstract: This invention relates to compounds (Formula (1)) that are agonists of the muscarinic M1 receptor and which are useful in the treatment of muscarinic M1 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula where R1-R5, X1, X2 and p are as defined herein.

Abstract: The present invention relates to a method for inhibiting the induction of cell death by inhibiting the synthesis or secretion of AGE-albumin in cells of the mononuclear phagocyte system, to an AGE-albumin synthesis inhibitor, and to a pharmaceutical composition comprising the AGE-albumin synthesis inhibitor for preventing or treating degenerative disease and autoimmune disease. The AGE-albumin of the present invention is synthesized and secreted in human microglia or human macrophages in an Alzheimer's model, stroke model, Parkinson's disease model and rheumatoid arthritis model. The AGE-albumin synthesis and secretion are caused by oxidative stress. The expression of RAGE increases in first-order human neurons or cartilage cells to which AGE-albumin is administered, whereupon a MAPK signaling pathway is activated and the expression of Bax increases to induce an increase in calcium in mitochondria, thus finally inducing cell death.

Abstract: This invention relates to novel (Cyano-dimethyl-methyl)-isoxazolesand-[1,3,4]thiadiazoles and their use as CB2 cannabinoid receptor agonists, pharmaceutical compositions containing the same, and their use for the treatment of CB2 receptor mediated disorders or conditions.

Abstract: Pharmaceutically acceptable solubilizing compositions comprising (i) at least one tocopheryl compound having a polyalkylene glycol moiety and (ii) at least one alkylene glycol fatty acid monoester or mixture of alkylene glycol fatty acid mono-and diester are disclosed. The solubilizing compositions are useful in the manufacture of pharmaceutical dosage forms comprising a melt-processed mixture of at least one active ingredient and at least one pharmaceutically acceptable polymer. The solubilizing compositions enhance the bioavailability of the active ingredient following oral intake.

Abstract: The present invention relates to a process for the preparation of (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylene-1-piperidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (Efinaconazole) and intermediates used in such process.

Abstract: The invention relates to active compound combinations, in particular within a composition, which comprises (A) an amidine compound of formula (I) and a further fungicidally (B). Moreover, the invention relates to a method for curatively or preventively controlling the phytopathogenic fungi of plants, to the use of a combination according to the invention for the treatment of seed, to a method for protecting a seed and not at least to the treated seed.

Abstract: An organic carboxylic acid salt of 2-[(3S,4R)-1-{[2-chloro-6-(trifluoromethyl)phenyl]methyl}-3-{[1-(cyclohex-1-en-1-ylmethyl) piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetic acid and a crystal thereof.

Abstract: The present invention relates to fungicidal 1-(heterocyclic carbonyl) piperidines and their thiocarbonyl derivatives, their process of preparation and intermediate compounds for their preparation, their use as fungicides, particularly in the form of fungicidal compositions and methods for the control of phytopathogenic fungi of plants using these compounds or their compositions.

Abstract: The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: Heteroarylpiperidine and -piperazine derivatives of the formula (I) in which the symbols A, X, Y, L1, L2, G, Q, p, R1, R2 and R10 are each as defined in the description, and salts, metal complexes and N-oxides of the compounds of the formula (I), and the use thereof for controlling phytopathogenic harmful fungi and processes for preparing compounds of the formula (I).

Abstract: Successful application of an engineered protein as therapeutics or in other industries would require the protein to have good expression level, good biophysical properties and often desired affinity to its target. The present invention provides a method of screening large numbers of protein candidates (PCs) in all three aspects simultaneously. PCs are fused to a protein anchor, which is captured by the target/antigen. The captured PCs are evaluated for their expression levels, biophysical properties and affinities using conventional methods.

Abstract: Provided are a compound of formula (I), pharmaceutically acceptable salts thereof, preparation methods and applications thereof for inhibiting thrombin, and applications in the treatment and prevention of thrombin-mediated and thrombin-related diseases.

Abstract: Heteroarylpiperidine and -piperazine derivatives of the formula (I) in which the symbols RA1, RA2, X, Y, L1, L2, RB1, RB2, G, Q, p, R1, R2 and R10 are each as defined in the description, and salts, metal complexes and N-oxides of the compounds of the formula (I), and the use thereof for controlling phytopathogenic harmful fungi and processes for preparing compounds of the formula (I).

Abstract: The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: Specifically useful stereoisomers of 1,3-dioxane derivatives are described and their use in the treatment of a disease or condition dependent on PPAR modulation, such as diabetes, cancer, inflammation, neurodegenerative disorders and infections as well as their use in the treatment of a disease related to TP, such as cardiovascular diseases.

Abstract: The invention provides compounds of the formula: in salt or zwitterionic form or a pharmaceutically acceptable salt thereof, wherein R1-6, a, Z and Q are as defined in the specification. These compounds are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes for preparing such compounds and methods of using such compounds to, for example, treat pulmonary disorders such as chronic obstructive pulmonary disease and asthma.

Abstract: Heteroarylpiperidine and -piperazine derivatives of the formula (I) in which the symbols are each as defined in the description, and agrochemically active salts thereof, and use thereof for controlling phytopathogenic harmful fungi, and also processes for preparing compounds of the formula (I).

Abstract: Processes are described for the preparation of tubulysins. The processes are useful for preparing predetermined mixtures of tubulysins, preparing single tubulysins from mixtures of tubulysins, and for converting one tubulysin into a different tubulysin. The tubulysins described herein are useful in treating diseases and disease states that include pathogenic cell populations.

Abstract: Compounds are provided that act as potent antagonists of the CCR1 receptor, and have in vivo anti-inflammatory activity. The compounds are diazole lactam derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR1-mediated disease, and as controls in assays for the identification of competitive CCR1 antagonists.

Abstract: Heteroarylpiperidine and -piperazine derivatives of the formula (I) in which the symbols A, X, Y, L1, L2, G, Q, p, R1, R2 and R10 are each as defined in the description, and salts, metal complexes and N-oxides of the compounds of the formula (I), and the use thereof for controlling phytopathogenic harmful fungi and processes for preparing compounds of the formula (I).

Abstract: The present invention relates to active compound combinations, in particular within a fungicide composition, which comprises (A) a thiazolylisoxazoline of formula (I) and a further fungicidally active compound (B). Moreover, the invention relates to a method for curatively or preventively controlling the phytopathogenic fungi of plants or crops, to the use of a combination according to the invention for the treatment of seed, to a method for protecting a seed and not at least to the treated seed.

Abstract: Compounds are provided that are modulators of the C5a receptor. The compounds are substituted piperidines and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activation of C5a receptors.

Abstract: The present invention is directed to methods of diagnosing and treating a fibrotic condition in a mammalian subject. These methods involve measuring the levels of trimethylation at lysine residue 27 of histone-3 and/or measuring the expression levels of EZH2 or YY-1. Agents useful for treating fibrosis or a fibrotic condition are also disclosed.

Abstract: The compound 1-(2-{4-[3-(3,4-dimethoxyphenyl)-4,4-dimethyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]piperidin-1-yl}-2-oxoethyl)pyrrolidine-2,5-dione is a novel effective inhibitor of the type 4 phosphodiesterase useful in the treatment of psoriasis or atopic dermatitis.

Abstract: The present invention provides compounds of Formula I or a pharmaceutical salt thereof, where the variables for R1, R2, and R3 are as described herein; methods of treating a condition such as hypertriglyceridemia; and processes for preparing the compounds.

Abstract: Disclosed are solid forms of 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazoyl]-2 -thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifuoromethyl)-1H-pyrazol-1-yl]ethanone (Compound 1). Also disclosed are methods for the preparation of solid forms of Compound 1 and for the conversion of one solid form of Compound 1 into another form. Further disclosed are methods for controlling plant diseases caused by fungal plant pathogens comprising applying to a plant or portion thereof, or to a plant seed, a fungicidally effective amount of a solid form of Compound 1. Additionally disclosed are fungicidal compositions comprising a fungicidally effective amount of a solid form of Compound 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid carriers and also compositions comprising a mixture of a solid form of Compound 1 and at least one other fungicide or insecticide.

Abstract: The present invention provides methods for treating onychomycosis. In certain embodiments, the methods comprise comprising applying a pharmaceutically acceptable formulation containing 10% efinaconazole once a day for a treatment period of at least 36 weeks to the treatment area of an onychomycosis patient (a) without debriding the nail or nail-associated tissue initially or during the treatment period and/or (b) without removing the formulation from the treatment area during the treatment period. In certain embodiments, the formulation also comprises, water, cyclomethicone, diisopropyl adipate, alcohol, C12-15 alkyl lactate, butylated hydroxytoluene, citric acid anhydrous, and disodium edetate.

Abstract: Novel 1,2,4-oxadiazole benzoic acid compounds, methods of using and pharmaceutical compositions comprising an 1,2,4-oxadiazole benzoic acid derivative are disclosed. The methods include methods of treating or preventing a disease ameliorated by modulation of premature translation termination or nonsense-mediated mRNA decay, or ameliorating one or more symptoms associated therewith.

Abstract: The disclosure relates to compounds and compositions for bone formation, fracture treatment, bone grafting, bone fusion, cartilage maintenance and repair, and methods related thereto.

Abstract: The invention provides heterocyclic guanidine compounds that inhibit F1F0-ATPase, and methods of using heterocyclic guanidine compounds as therapeutic agents to treat medical disorders, such as an immune disorder, inflammatory condition, or cancer.

Abstract: Aniline compounds are provided which bind to CCR(4) and are useful for the treatment of diseases such as allergic diseases, autoimmune diseases, graft rejection and cancer.

Abstract: Compounds are provided that are modulators of the C5a receptor. The compounds are substituted piperidines and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activation of C5a receptors.

Abstract: A system is described for long-term controlled release delivery of a drug or a therapeutic agent. According to the invention, one or more drugs or therapeutic agents contained in microspheres are mixed with a temperature sensitive hydrogel which is then introduced directly to the desired situs of the drug or therapeutic agent. The temperature sensitive hydrogel may also contain a drug or a therapeutic agent, for example, a pain relieving drug, for a short-term controlled release. The temperature sensitive hydrogel is in liquid state at room temperature, but upon injection, shortly becomes gelatinous. This system is particularly suitable for treatment of diseases, disorders, or conditions, for example, tumors, discogenic back pain, or arthritis, warranting localized administration of a drug or a therapeutic agent. In addition, the specification provides a method for production of a drug- or therapeutic agent-containing microspheres.

Abstract: This invention relates to geranylgeranyl acetone (GGA) derivatives, pharmaceutical compositions comprising GGA derivatives and the use of GGA derivatives.

Abstract: There is provided pharmaceutical compositions for the treatment of pain e.g. short-term pain, which compositions comprise a mixture comprising: (a) microparticles of alfentanil, or a pharmaceutically acceptable salt thereof, which microparticles are presented on the surfaces of larger carrier particles; (b) a water-soluble weak base; and (c) a compound which is a weak acid, which acid is presented in intimate mixture with the microparticles of alfentanil or salt thereof. The composition may further comprise a disintegrant. The acid is preferably citric acid.

Abstract: The invention provides compounds of formula (I): wherein R1-R3, n, and W have any of the values defined in the specification, and salts thereof. The compounds have good solubility and are useful for treating bacterial infections.

Abstract: This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

Abstract: The invention provides a compound of formula I: wherein A1, A2, A3, R1, X, Y, and B have any of the values described herein, as well as salts of such compounds, compositions comprising such compounds, and therapeutic methods that comprise the administration of such compounds. The compounds are inhibitors of monoamine oxidase B (MAO-B) enzyme function and are useful for improving cognitive function and for treating psychiatric disorders in animals.

Abstract: The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a pharmaceutical composition comprising such a compound.

Abstract: The present invention provides for compounds of formula (I): wherein R1-R4 and n are defined herein. The present invention also provides for pharmaceutical compositions and combinations comprising a compound of formula (I) as well as for the use of such compounds as tankyrase inhibitors and in the treatment of Wnt signaling and tankyrase 1 and 2 signaling related disorders which include, but are not limited to, cancer.

Abstract: The compound represented by the formula (I-1): wherein all the symbols have the same meanings as described in the specification, has two cyclic groups, particularly phenoxy groups at specific substitution positions and thus has high human S1P2 antagonistic activity. The compound may therefore be used as a therapeutic agent for S1P2-mediated diseases such as diseases resulting from vascular constriction, fibrosis and respiratory diseases.