Abstract: Methods and compositions for treating cholangiocarcinoma.

Abstract: Disclosed herein are quinoline-based compounds and method for inhibiting CDK8 or CDK19 for the intervention in diseases, disorders, and conditions. The quinoline-based composition comprise substituents at quinoline ring positions 4 and 6, wherein the substituent at position 4 is selected from a substituted or unsubstituted arylalkylamine or a substituted or unsubstituted arylhetrocyclylamine. Pharmaceutical compositions comprising the substituted quinoline compositions, methods of inhibiting CDK8 or CDK19, and methods of treating CDK8/19-associated diseases, disorders, or conditions are also disclosed.

Abstract: Methods and compositions for treating cholangiocarcinoma.

Abstract: The present invention relates to inhibitors of ROCK1 and ROCK2 and methods of modulating the pharmacokinetic and/or pharmacodynamic properties of such compounds. Also provided are methods of inhibiting ROCK1 and or ROCK2 that are useful for the treatment of disease.

Abstract: The present invention relates to compounds of Formula (I), or an agronomically acceptable salt of said compounds wherein A1a, A1b, R1, R2, R3 and R4 and R5 are as defined herein. The invention further relates to herbicidal compositions which comprise a compound of Formula (I), and to their use for controlling weeds, in particular in crops of useful plants.

Abstract: The present invention features a compound having the formula A-X-B, where A is peptide vector capable of enhancing transport of the compound across the blood-brain barrier or into particular cell types, X is a linker, and B is a peptide therapeutic selected from the group consisting of neurotensin, a neurotensin analog, or a neurotensin receptor agonist. The compounds of the invention can be used to treat any disease in which increased neurotensin activity is useful and can be used to induce hypothermia or analgesia.

Abstract: The invention relates to inhibitors of ROCK1 and/or ROCK2. Also provided are methods of treating diseases and disorders involving inhibiting ROCK1 and/or ROCK2.

Abstract: Provided are fused tricyclic compounds effective to inhibit the function of the NS5A protein of formula (I), wherein X, X?, Y, Y?, A, A?, Q1, Q2, R1-R4, X4, R5a, f and W are defined as in the description. Also provided herein are pharmaceutical compositions thereof, and uses in the manufacture of a medicament for treating HCV infection or a HCV disorder thereof.

Abstract: Methods for stopping or slowing bleeding from a wound are provided; these methods include the step of administering a composition comprising a polyphosphate (polyP) to blood from the wound at the site of the wound. Also provided are methods for slowing fibrinolysis and for blocking the action of Tissue Factor Pathway Inhibitor (TFPI) with the use of polyP.

Abstract: The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, A1, A2, A3, m, n and p are as described herein, compositions including the compounds and methods of using the compounds.

Abstract: The present invention relates to inhibitors of ROCK1 and ROCK2 and methods of modulating the pharmacokinetic and/or pharmacodynamic properties of such compounds. Also provided are methods of inhibiting ROCK1 and or ROCK2 that are useful for the treatment of disease.

Abstract: The present invention relates to compounds of general formula wherein R1 hydrogen, lower alkyl, halogen or lower alkyl substituted by halogen; R2 is hydrogen or halogen; X1 is N or CH; X2 is N or CH; with the proviso that only one of X1 or X2 is N; X3 is C(R) or N; and R is hydrogen, lower alkyl, halogen, lower alkyl substituted by halogen, lower alkoxy or SO2-lower alkyl; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof.

Abstract: Provided herein is an optically active pyrazolylaminoquinazoline, and pharmaceutical compositions thereof. Also provided herein is a method for treating, preventing, or ameliorating one or more symptoms of a JAK-mediated condition, disorder, or disease. Further provided herein is a method for treating, preventing, or ameliorating one or more symptoms of a proliferative disease, inflammatory disease, or renal disease.

Abstract: Disclosed are 1-(arylmethyl)quinazoline-2,4(1H,3H)-diones thereof, represented by the Formula (I) wherein Ar, R1-R6 are defined herein. Compounds having Formula (I) are PARP inhibitors. Therefore, compounds of the invention may be used to treat clinical conditions that are responsive to the inhibition of PARP activity.

Abstract: Proteases such as memapsin-1 are import enzymes, playing roles in a variety of diseases including diabetes. The inventors have developed inhibitors of memapsin 1 and methods of use therefore in the treatment of disease.

Abstract: Provided herein is an optically active pyrazolylaminoquinazoline, and pharmaceutical compositions thereof. Also provided herein is a method for treating, preventing, or ameliorating one or more symptoms of a JAK-mediated condition, disorder, or disease. Further provided herein is a method for treating, preventing, or ameliorating one or more symptoms of a proliferative disease, inflammatory disease, or renal disease.

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

Abstract: Described herein are polymeric nanoparticles that include a therapeutic agent which is 2-(3-((7-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide (also known as AZD1152 hqpa) or a pharmaceutically acceptable salt thereof, and methods of making and using such therapeutic nanoparticles.

Abstract: A compound in combination with a pharmaceutically acceptable carrier, the compound having a formula: wherein: R1 is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl, and lower alkoxy; R2 is a member of the group consisting of hydroxy, acetoxy, and lower alkoxy; and R3 is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl; and n is either 1 or 2; and pharmaceutically acceptable salts thereof; for use in treatment of or prevention of skeletal muscle fibrosis and/or for inducing skeletal muscle regeneration.

Abstract: Quinazoline derivatives of formula (I): wherein A is 5-membered heteroaryl containing a nitrogen atom and one or two further nitrogen atoms; compositions containing them, processes for their preparation and their use in therapy.

Abstract: The disclosure relates to quinazoline derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidases (Nox enzymes) and/or myeloperoxidase.

Abstract: In one aspect, the invention relates to substituted 4-(1H-pyrazol-4-yl)benzyl analogs compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChR M1); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor 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: Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including those mediated by inhibition of fatty acid synthase (FASN) enzyme, such as, cancer, obesity or related discorders, and liver related disorders. Such compounds are represented by formula (I) as follows: wherein L1, a, b, m, n, R1, R2, R3, R4, and R5 are defined herein.

Abstract: The invention relates to the preparation and use of new aminopyrimidine derivatives as drug candidates in free form or in pharmaceutically acceptable salt form and formulations thereof for the modulation of a disorder or disease which is mediated by the activity of the PI3K enzymes. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of disorders or diseases, such as disorders of immunity and inflammation in which PI3K enzymes play a role in leukocyte function, and hyperproliferative disorders associated with PI3K activity, including but not limited to leukemias and solid tumors, in mammals, especially humans.

Abstract: Compounds having the formula (I) wherein R1, R2, R3 and Ar as defined herein are inhibitors of ERK kinase. Also disclosed are compositions and methods for treating hyperproliferative disorders.

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

Abstract: Provided herein is an optically active pyrozolylaminoquinazaline, and pharmaceutical compositions thereof. Also provided herein is a method for treating, preventing, or ameliorating one or more symptoms of a JAK-mediated condition, disorder, or disease. Further provided herein is a method for treating, preventing, or ameliorating one or more symptoms of a proliferative disease, inflammatory disease, or renal disease.

Abstract: The present invention relates to new antifungal compositions and their use in the treatment of agricultural products.

Abstract: The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

Abstract: Solid forms comprising pyrazolylaminoquinazoline, compositions comprising the solid forms, methods of making the solid forms and methods of their use for the treatment of various diseases and/or disorders are disclosed.

Abstract: Quinazolinone compounds of formula (I) are described, which are useful as prolyl hydroxylase inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by prolyl hydroxylase activity. Thus, the compounds may be administered to treat, e.g., anemia, vascular disorders, metabolic disorders, and wound healing.

Abstract: A triazole bridged flavonoid dimer compound library was efficiently constructed via the cycloaddition reaction of a series of flavonoid-containing azides (Az 1-15) and alkynes (Ac 1-17). These triazole bridged flavonoid dimers and their precursor alkyne- and azide-containing flavonoids were screened for their ability to modulate multidrug resistance (MDR) in P-gp-overexpressed cell line (LCC6MDR), MRP1-overexpressed cell line (2008/MRP1) and BCRP-overexpressed cell line (HEK293/R2 and MCF7-MX100). Generally, they displayed very promising MDR reversal activity against P-gp-, MRP1- and BCRP-mediated drug resistance. Moreover, they showed different levels of selectivity for various transporters. Overall, they can be divided into mono-selective, dual-selective and multi-selective modulators for the P-gp, MRP1 and BCRP transporters.

Abstract: The present invention provides a combination comprising (a) a compound of formula (I) and (b) one or more antineoplastic agents selected from the group consisting of an antimetabolite agent, analkylating or alkylating-like agent, an intercalating agent, a topoisomerase I or II inhibitor, an antimitotic agent, a kinase inhibitor, a proteasome inhibitor and an antibody inhibiting a growth factor or its receptor, wherein active ingredients of the combination are present in each case in free form or in the form of a pharmaceutically acceptable salt or any hydrate or solvate thereof, useful in the treatment of tumors.

Abstract: The invention provides compounds of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.

Abstract: This invention relates to novel sulfoximine substituted quinazoline derivatives of formula I wherein Ar, R1 and R2 are as defined in the description and claims, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.

Abstract: Inhibitors of HCV replication of formula (I) including stereochemically isomeric forms, salts, and solvates thereof, wherein R and R? have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HCV inhibitors, in HCV therapy.

Abstract: The present invention relates to inhibitors of ROCK1 and ROCK2 and methods of modulating the pharmacokinetic and/or pharmacodynamic properties of such compounds. Also provided are methods of inhibiting ROCK1 and or ROCK2 that are useful for the treatment of disease.

Abstract: A novel bicyclic compound having an HSP90 inhibitory effect and a carcinostatic effect. A pharmaceutical agent based on the HSP90 inhibitory effect and useful in the prevention and/or treatment of a disease involving HSP90, particularly cancer. The compound has a general formula (I) or is a salt thereof wherein at least one of X1, X2, X3, and X4 represents N or N-oxide and the rest thereof are each independently C—R2; any one or two of Y1, Y2, Y3, and Y4 represent C—R4 and the rest thereof are each independently CH or N; R1 represents an optionally substituted monocyclic or bicyclic unsaturated heterocyclic group having 1 to 4 heteroatoms selected from N, S, and O; R2 represents a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms etc.; R3 represents a hydrogen atom, —CO—R5 etc.

Abstract: Inhibitors of HCV replication of formula I, including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein R and R? have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HCV inhibitors, in HCV therapy.

Abstract: The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C 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 HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: Oxazole derivatives are described. The inventive compounds are useful as kinase inhibitors, and may be used in the treatment of cancer, such as prostate cancer, lung cancer, breast cancer, colon cancer, leukemia, CNS cancer, melanoma, ovarian cancer, and renal cancer.

Abstract: The present invention relates to known and novel compounds of formula (I) as herein described and pharmaceutical compositions thereof. The compounds of formula (I) have inhibitory effect on the Wnt pathway and are therefore useful in the preparation of a medicament, in particular for the treatment of cancer.

Abstract: Aminoquinazolinyl compounds of formula (I) are described, which are useful as prolyl hydroxylase inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by prolyl hydroxylase activity. Thus, the compounds may be administered to treat, e.g., anemia, vascular disorders, metabolic disorders, and wound healing.

Abstract: Embodiments of the present disclosure relate to methods and compositions for treating a subject with ovarian cancer. Some embodiments include treating a subject with a particular combination of chemotherapeutic agents.

Abstract: This invention is in the fields of cancer therapy. More particularly it concerns compounds which are useful agents for inhibiting cell proliferative disorders, especially those disorders characterized by over activity and/or inappropriate activity of a EGFR, including EGFR-related cancers, and methods for treating these disorders.

Abstract: The present invention is directed to methods and compositions for suppressing lymphangiogenesis, angiogenesis and/or tumor growth. The methods comprise contacting the tumor with a compound that (i) stabilizes a protein kinase in the inactive state and (ii) is not an ATP competitive inhibitor of the protein kinase in the active state.

Abstract: PROBLEM There are provided a composition for controlling plant diseases and a method for controlling plant diseases having excellent control effect for plant diseases. SOLUTION A composition for controlling plant diseases comprising, as active ingredients, a compound represented by formula (1), wherein X1 represents a methyl group, a difluoromethyl group or an ethyl group; X2 represents a methoxy group or a methylamino group; and X3 represents a phenyl group, a 2-methylphenyl group or a 2,5-dimethylphenyl group, and at least one azole compound selected from the group consisting of bromuconazole, cyproconazole, difenoconazole, fenbuconazole, fluquinconazole, hexaconazole, imibenconazole, ipconazole, myclobutanil, prothioconazole, simeconazole, tetraconazole, triticonazole and metconazole.

Abstract: Disclosed are inhibitors of human galactokinase of formula (1) that are useful in treating or preventing a galactokinase mediated disease or disorder, e.g., galactosemia. Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one inhibitor of the invention, and a method of treating or preventing such disease or disorder in a mammal.

Abstract: The present invention relates to sulphone-substituted quinazoline derivatives of the formula (I), processes for their preparation and their use as a medicament for the treatment of various diseases.