Abstract: The present invention provides: an uracil derivative represented by general formula (I) or a physiologically acceptable salt thereof (in the formula, R1 represents a hydrogen atom, a C1-10 alkyl group, a C2-6 alkene group or a 3- to 6-membered saturated or 4- to 6-membered unsaturated aliphatic ring group which may contain 1 to 2 hetero atoms independently selected from the group consisting of N, O and S; R2 represents a hydrogen atom, a halogen atom, a cyano group, —NRcRd, —N?CHN(CH3)2, or an C1-3 alkyl group; Ar1 and Ar2 independently represent a 5- to 6-membered aromatic ring group which may contain 1 to 3 hetero atoms independently selected from the group consisting of N, O and S; and L represents a 6-membered aromatic ring group which may contain 1 to 4 nitrogen atoms, a pyrazole group, a triazole group, or an imidazole group); and a therapeutic agent or prophylactic agent for various inflammatory diseases associated with elastase, comprises the compound or the like as an active ingredient.

Abstract: A solid pharmaceutical dosage form providing improved oral bioavailability is disclosed for inhibitors of HIV protease. In particular, the dosage form comprises a solid dispersion of at least one HIV protease inhibitor and at least one pharmaceutically acceptable water-soluble polymer and at least one pharmaceutically acceptable surfactant, said pharmaceutically acceptable water-soluble polymer having a Tg of at least about 5° C. Preferably, the pharmaceutically acceptable surfactant has an HLB value of from about 4 to about 10.

Abstract: Provided herein are compounds having anti-proliferative effect. Also provided are compounds that can modulate the activity of multi-domain proteins comprising a dimerization arm and interdomain tether, such as EGFR, where an untethered, extended conformation is the active state and a tethered conformation is the inactive state, resulting in an autoinhibited configuration. Also provided are methods and pharmacophores for identifying such compounds. Other aspects provide methods or therapeutic treatment for proliferative diseases, disorders, or conditions, such as those associated with EGFR.

Abstract: Disclosed are methods for treating Vascular Leak Syndrome. Further disclosed are methods for treating vascular leakage due to inflammatory diseases, inter alia, sepsis, lupus, inflammatory bowel disease. Yet further disclosed are methods for treating renal cell carcinoma and melanoma. Still further disclosed are methods for reducing metastasis of malignant cells and/or preventing the proliferation of carcinoma cells via spreading due to vascular leakage.

Abstract: Compounds of Formula I are useful for inhibition of CHK1 and/or CHK2. Methods of using compounds of Formula I and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

Abstract: The present invention is directed to certain oxazole derivatives which are useful as inhibitors of Fatty Acid Amide Hydrolase (FAAH). The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzeimer Disease, and Parkinson's Disease.

Abstract: The invention relates to treatment and/or prevention of nerve injury. In one embodiment, the present invention provides a method of preserving the neuromuscular junction (NMJ) in an individual by administering a therapeutically effective dosage of a composition comprising an inhibitor of Wnt3a, and an inhibitor of MMP3 to the individual. In another embodiment, the present invention provides a method of stabilizing NMJ after nerve injury by inhibiting the WNT and beta-catenin signaling pathway and preserving agrin.

Abstract: In alternative embodiments the invention provides compositions, e.g., pharmaceutical compositions and preparations, formulations, kits and other products of manufacture, e.g., exemplary drug combinations packaged together or separately in blister packs, lidded blisters or blister cards, or wrapped in paper, plastic or cellophane wrappers (e.g., a shrink wrap), comprising a combination regimen of at least two active ingredients designed to diminish systemic inflammation by targeting (inhibiting) two different, but convergent, signaling pathways, i.e., the sympathetic nervous system and the lipid-derived autacoid system; and methods for making and using these compositions. In alternative embodiments, the compositions of the invention (e.g., the combination of drugs) are used to ameliorate, diminish, treat, block or prevent an inflammatory response secondary to an infection, e.g., a viral infection and/or a reactivation.

Abstract: The present invention relates to the field of pharmaceutical chemistry, and in particular, to a novel class of azole compounds represented by general formula (I), (II) or (III) and a preparation method thereof, a pharmaceutical composition with the compounds as active components, and a use of the azole compounds and the pharmaceutical composition in the preparation of a medicament for treatment of diseases associated with Lp-PLA2 enzyme activities, wherein each substituent is as defined in the specification.

Abstract: Compounds of Formula I are useful as antagonists of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

Abstract: The invention relates to certain compounds or pharmaceutically acceptable salts, solvates, clathrates, or prodrugs thereof, that are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.

Abstract: The present invention provides a method of treating an Hsp70 dependent cancer, including: providing at least one Hsp70 dependent cancer cell; contacting the at least one cell with a sub-effective concentration of a dihydropyrimidinone compound; and contacting the at least one cell with a sub-effective concentration of a proteasome inhibitor, wherein the sub-effective concentration of the dihydropyrimidinone compound and the sub-effective concentration of the proteasome inhibitor have a synergistic effect upon the at least one cell.

Abstract: The present invention relates to pyrroloquinolinyl-pyrrolidine-2,5-dione compounds in combination with chemotherapeutic agents. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a pyrroloquinolinyl-pyrrole-2,5-dione compound or pyrroloquinolinyl-pyrrolidine-2,5-dione compound of the present invention and also administering a effective amount of a chemotherapeutic agent.

Abstract: The present invention relates to compounds of Formula (I), wherein X1, X2, X3, X4, R1, R2, R3, and Q are as defined herein, useful as N-type calcium channel blockers.

Abstract: The present invention relates to compounds and pharmaceutically acceptable salts thereof and formulations comprising the compounds or a pharmaceutically acceptable salts thereof that are useful in modulating lyn kinase activity. In particular, the compounds or a pharmaceutically acceptable salts thereof are useful for treating or preventing a disease or disorder including cardiovascular disease, dyslipidemia, dyslipoproteinemia, a disorder of glucose metabolism, metabolic syndrome (i.e., Syndrome X), a peroxisome proliferator activated receptor-associated disorder, septicemia, a thrombotic disorder, type II diabetes, obesity, pancreatitis, hypertension, renal disease, inflammation, or impotence.

Abstract: One aspect of the disclosure relates to derivatives of aryl and heterocyclic ureido aryl and heterocyclic carboxamido isobutyric acids, dichlorophenyl urea, curcumin, and 1,3-diazetidine-2,4-dione, and pharmaceutical compositions thereof. The derivatives disclosed herein can modulate development of adipocytes and various cancer cells, including resistant cancer cells and cancer stem cells. Another aspect of the disclosure relates to the use of the derivatives and pharmaceutical compositions disclosed herein in treatment of obesity and various cancers.

Abstract: The present invention provides compounds of Formula (Ia): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: Disclosed are compounds represented by Formula (I): or pharmaceutically acceptable salts, enantiomers or diastereomers thereof. Also disclosed are pharmaceutical compositions comprising the compounds of Formula (I) or pharmaceutically acceptable salts, enantiomers or diastereomers thereof and methods of inhibiting 11 ?-HSD1 activity comprising the step of administering to a mammal in need of such treatment an effective amount of a compound of Formula (I) or pharmaceutically acceptable salt, enantiomer or diastereomer thereof. Values for the variables of Formula (I) are defined herein.

Abstract: Chemical compounds derived by in silico molecular modelling, having a well defined structure suitable for the blocking of the phosphorylation event, through the specific interaction of the chemical with the Casein Kinase 2 enzyme substrate phosphorylation domain or it's neighbourhood. This invention comprises also the pharmaceutical compositions containing such compounds, and their use in the preparation of medicines or agents for the treatment of diseases or conditions related with neoplasic processes.

Abstract: This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.

Abstract: The present invention provides compounds of Formula (I), pharmaceutical compositions thereof, and methods of using the same in the treatment or prevention of diseases mediated by the activation of b3-adrenoceptor.

Abstract: In accordance with the present invention, there are provided methods for the treatment of mitochondrial disorders. Invention methods include the administration of a pyrimidine-based nucleoside such as triacetyluridine, or the like. Also provided are methods of reducing or eliminating symptoms associated with mitochondrial disorders. Mitochondrial disorders particularly appropriate for treatment include those attributable to a deficiency of one or more pyrimidines.

Abstract: The present invention is directed to compounds of formula I and 1a: which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.

Abstract: The invention provides small molecule inhibitors of EYA2 phosphatase activity and EYA2 binding to Six1. These inhibitors are proposed for use in methods of treating cancer in a subject, such as those involving Six1 and/or EYA2 disregulation. In some embodiments, the invention further provides for the administration of a second cancer therapy to the subject.

Abstract: The present invention includes novel methods of treating a disease or disorder characterized by hyperactivity of Vps34, and compound as Vps34 inhibitors; particularly compounds of Formula I: or a pharmaceutically acceptable salt thereof, as well as methods of treating a disease, disorder, or syndrome associated with Vps34 inhibition, particularly hyperproliferative diseases. The present invention also includes pharmaceutical compositions including compounds of formula I and pharmaceutically acceptable salts thereof.

Abstract: The present invention is directed to novel dihydropyrimidin-2(1H)-one compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same.

Abstract: This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.

Abstract: Derivatized coumarin-based pharmaceutical compositions and methods to use them are provided. The compositions are characterized in that they inhibit the activity of tumor-related CAIX and CAXII to a greater degree than they inhibit the activity of CAI and CAII. The compositions can be used to suppress tumor growth and/or suppress tumor metastases in a mammal.

Abstract: Certain imidazopyridines (I) 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: There is provided compositions and methods for the treatment of respiratory conditions such as pulmonary hypertension and sickle-cell disease in a patient in need thereof. The composition and method are for treating a patient in need thereof by inhalation of a composition containing amino acid ester compounds comprising at least one nitric oxide releasing group and pharmaceutical salts thereof.

Abstract: Disclosed are nucleopeptide compounds that include a nucleobase, and an amino acid. Certain compounds further comprise a glycoside. The compounds may self-assemble to form supramolecular hydrogels. Also, the compounds may be used as a platform to examine specific biological functions (e.g., binding to DNA and RNA) of a dynamic supramolecular system that is able to interact with both proteins and nucleic acids. Other uses include: methods of growing cells and methods of delivering a substance to a cell.

Abstract: Compounds having the formula (I) wherein R1, R2, R3 and X are as defined herein are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.

Abstract: There is provided a compound which is (a) a pyrimidine sulfonamide of formula (I) or (b) a pharmaceutically acceptable salt thereof, crystalline forms of the compound, processes for obtaining the compound, pharmaceutical intermediates used in the manufacture of the compound, and pharmaceutical compositions containing the compound. The compound is useful in the treatment of a disease/condition in which modulation of chemokine receptor activity is beneficial.

Abstract: The present invention relates to pharmaceutical compositions comprising a compound and a pharmaceutically acceptable carrier. The present invention is also directed to a method of treating cancer in a subject. Also disclosed are methods of inhibiting SCF-Skp2 activity and a method of identifying inhibitors of SCF-Skp2 activity.

Abstract: The present invention relates to drug discovery methods, particularly methods for assaying compounds for activity as Aurora kinase inhibitors. This invention also relates to a pharmacophore describing compounds that are able to promote a conformational change in the protein AuroraB and whose binding constant for the two-step process is given as Ki*. Finally, this invention also relates to compounds having the features of the pharmacophore.

Abstract: Compounds, methods, and compositions for the treatment of infections in or exposure to humans and other host animals of Flaviviridae viruses, including HCV, that includes the administration of an effective amount of a spiro[2.4]heptane as described herein or a pharmaceutically acceptable salt or prodrug thereof, optionally in a pharmaceutically acceptable carrier, are provided. The spiro[2.4]heptane compounds either possess antiviral activity, or are metabolized to a compound that exhibits such activity.

Abstract: Compounds, methods, and compositions for the treatment of infections in or exposure to humans and other host animals of Flaviviridae viruses, including HCV, that includes the administration of an effective amount of a spiro[2.4]heptane as described herein or a pharmaceutically acceptable salt or prodrug thereof, optionally in a pharmaceutically acceptable carrier, are provided. The spiro[2.4]heptane compounds either possess antiviral activity, or are metabolized to a compound that exhibits such activity.

Abstract: Disclosed herein are pharmaceutically acceptable rapid dissolve vaginal tablet compositions comprising one or more active pharmaceutical ingredients suitable for therapy via topical action or systemic absorption, and methods of making and using such compositions.

Abstract: A composition and method for the treatment of the side-effects associated with the administration of cancer chemotherapeutic agents involves the oral ingestion of a slow release capsule containing adenine. In some embodiments, the slow release capsule also contains orotate. The systemic administration of a proton pump inhibitor decreases systemic absorption of orotate, and the systemic administration of allopurinol decreases the formation of 2,8-dihydroxy adenine from adenine. In an alternative embodiment, cationic liposomes contain purine/pyrimidine precursors. The cationic liposomes bind to the cells lining the mucosa of the intestinal tract and then the contents of the cationic liposome are then taken up in the interior of the cells to prevent the metabolism of the cancer treatment drug 5-FU into a toxic species. A method for prevention of oral stomatitis and a method for treatment of dysplastic tissue are also disclosed.

Abstract: The invention provides a compound of formula (Ia), and pharmaceutically acceptable salts thereof. The invention also provides use of the compounds or salts as modulators of Kv3.1 and/or Kv3.2, and in the treatment of diseases or disorders where a modulator of Kv3.1 and/or Kv3.2 is required, such as depression and mood disorders, hearing disorders, schizophrenia, substance abuse disorders, sleep disorders or epilepsy.

Abstract: The present invention describes nanoprodrugs of non-steroidal anti-inflammatory drug (NSAIDs) and nanoprodrugs of ?-lipoic acid-containing and NSAIDs. These nanoprodrugs have antioxidant properties and stimuli-responsiveness, which can be used to treat various disease conditions.

Abstract: Described are drug delivery systems incorporating electrospun fibers that comprise and deliver physicochemically diverse drug compounds. Such fibers provide significant advantages in drug agent release, such as adaptability for solid dosage delivery to mucosal tissues. This is in addition to allowing for controlled drug release. Systems and methods for large-scale electrospinning productivity are described, including novel microarchitectures allowing for variable pharmacokinetics in drug release.

Abstract: The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof and N-oxides of the foregoing; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, salts or N-oxides, and their uses for treating D1-mediated (or D1-associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, impulsivity, compulsive gambling, overeating, autism spectrum disorder, MCI, age-related cognitive decline, dementia, RLS, Parkinson's disease, Huntington's chorea, anxiety, depression, MDD, TRD, and bipolar disorder.

Abstract: Compounds that modulate mitochondrial reactive oxygen species (ROS) production are provided. The compounds may modulate ROS production at defined sites without also altering energy production. Methods of using and identifying such compounds are also provided.

Abstract: The invention provides certain cycloalkyl-fused tetrahydroquinolines of the Formula (I), and their pharmaceutically acceptable salts and esters, wherein R1, R2, R7, R8a, E, Y, Z, n, u, and t are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions associated with uncontrolled or inappropriate stimulation of CRTH2 function.

Abstract: Compounds active on protein kinases are described, as well as methods of making and using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.

Abstract: This application provides compositions and methods useful in the treatment of certain cancers. In part, this application is based on the recognition that certain molecules that target abasic lesions or AP sites in DNA improve, augment, or potentiate the chemotherapeutic efficacy of certain anticancer agents.

Abstract: A herbicide combination comprising a) at least one herbicide (A) selected from the group consisting of glyphosate (A1) and its agrochemically compatible salts, and glufosinate (A2) and its agrochemically compatible salts, and b) a herbicide (B) which is a hydrate of the compound 2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1-(2H)-pyrimidinyl]-4-fluoro-N-[[methyl-(1-methylethyl)amino]sulfonyl]benzamide, and the use thereof for controlling harmful plants.

Abstract: The present invention relates to spirocarbamate compounds of Formula (I) in which R1, (R2)Y, R3, R4, X and A have the meanings given in the specification. The invention further provides pharmaceutical compositions containing the compounds or pharmaceutically acceptable salts thereof and relates to their use of these compounds as TRPV4 antagonists in treating or preventing conditions associated with TRPV4 imbalance.

Abstract: The invention is based on the surprising finding that treatment with a chemotherapeutic agent such as 5-fluorouracil (5-FU) and an autophagy inducer effectively inhibit the continued growth of, and prevent the recovery following drug withdrawal, of cancer cells. In vivo, drug resistance from a failure to adequately engage in apoptotic programmed cell death leads to a recurrence of cancer and tumours can remain dormant for periods of time before re-emerging as drug resistant metastases. It has been hypothesised that autophagy (Type II cell death) may help cancer cells survive in response to growth limiting conditions, such as nutrient depletion, hypoxia, absence of growth factor, or presence of cytotoxic drug. LiCl is a known autophagy inducer and accelerates cell survival to autophagic programmed cell death.