Abstract: Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt, solvate or ester thereof, wherein U, W, X, L, Y, M, Z, c, d, e, f, g, h, s, t, R1, R2, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17 and R18 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Abstract: The present invention relates to nonaqueous preparation for percutaneous absorption prepared by laminating an adhesive layer comprising a nonsteroidal anti-inflammatory analgesic in an alkali metal salt form, and an inorganic acid which is strongly acidic compared with the nonsteroidal anti-inflammatory analgesic in a free form, together with a nonaqueous base, on a support. According to the present invention, drug-releasing characteristics and skin penetration in a nonaqueous preparation for percutaneous absorption can be improved because the addition of an inorganic acid in a nonaqueous base containing a drug in an alkali metal salt form leads to an improvement in the solubility of the drug in the base, and a good partitioning of the drug to skin surface. In addition, as the inorganic acid has no alcoholic hydroxy group in the structure, the inorganic acid does not react with the drug, therefore it causes no lowering in the stability of the drug by esterification.

Abstract: Nicotine receptor agonists or analogs or derivatives thereof for treating inflammatory pulmonary diseases, and pharmaceutical compositions including nicotine receptor agonists or analogs or derivatives thereof. Compounds of formula wherein R1, R2, Xa and Ya are as defined herein are also provided.

Abstract: The present invention relates to triazolopyridine compounds of general formula (I) which are Monopolar Spindle 1 kinase (Mps-1 or TTK) inhibitors: Formula (I), in which R1, R2, R3, R4, and R5 are as given in the description and in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis proliferative of diseases, as well as to intermediate compounds useful in the preparation of said compounds.

Abstract: The present invention relates to a method for treating recurrent tumor metastases following liver resection that includes administration of an effective amount of an agonist of A2A adenosine receptors (ARs).

Abstract: The present invention relates to novel substituted 3-(arylsulfonyl)pyrazolo[1,5-a]pyrimidines of general formula 1 pharmaceutically acceptable salts and/or hydrates, to novel serotonin 5-HT6 receptor antagonists, to novel drug substances, pharmaceutical compositions, medicaments and methods for their preparation and use for treatment and prophylaxis of pathological states and diseases of CNS, pathogenesis of which is associated with disturbance of serotonin 5-HT6 receptor activation. In compounds of general formula 1 Ar represents optionally substituted aryl or heterocyclyl; R1, R2 and R3 independently of each other represent hydrogen, C1-C3 alkyl or phenyl; R4 represents hydrogen, optionally substituted C1-C5 alkyl, substituted hydroxyl group or substituted sulfanyl group.

Abstract: Fatty acid inhibitors, pharmaceutical compositions including fatty acid inhibitors, methods for using fatty acid inhibitors to treat a variety of diseases, and methods for preparing fatty acid inhibitors are provided herein.

Abstract: The invention provides a novel class of 2,7-naphthyridin derivatives; pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly Syk, ZAP70, KDR, FMS, FLT3, c-Kit, RET, TrkA, TrkB, TrkC-GR-1R, Alk, c-FMS, or combinations thereof.

Abstract: Compounds of Formula (I) inhibit the PARP enzyme and are useful for treating a disease or a disorder associated with PARP. Also disclosed are pharmaceutical compositions comprising compounds of Formula (I), methods of treatment comprising compounds of Formula (I), and methods of inhibiting the PARP enzyme comprising compounds of Formula (I).

Abstract: The present invention relates to stable salts of creatine imino sugar amides and an inorganic or organic acid endowed with enhanced nutritional and/or therapeutical efficacy in respect to their individual effects and to solid compositions containing such salts, particularly suited to oral and parenteral administration. Methods of preparation and use of these compositions are also provided.

Abstract: In various embodiments, the present invention provides methods of treating and/or preventing cardiovascular-related disease and, in particular, a method of blood lipid therapy comprising administering to a subject in need thereof a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.

Abstract: Thalidomide analogs that modulate tumor necrosis factor alpha (TNF-?) activity and angiogenesis are disclosed. In particularly disclosed embodiments, the thalidomide analogs are isosteric sulfur-containing analogs. Also disclosed are methods of treating a subject with the analogs.

Abstract: The invention relates to active compound combinations, in particular a fungicidal and/or insecticidal composition, comprising Isotianil (3,4-dichloro-N-(2-cyanophenyl)-5-isothiazolecarboxamide) and at least one further insecticide of the anthranilamide group and optionally one further insecticide of the neonicotinoids. Moreover, the invention relates to a method for curatively or preventively controlling the phytopathogenic fungi and/or microorganisms and/or pests 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: A composition for stimulating NKT cells to produce anti-cancer and anti-viral cytokines without causing anergy of NKT cells includes a glycolipid antigen and a nanoparticle conjugated with the glycolipid antigen. The glycolipid antigen and the nanoparticle are not antigenic in mouse and human being. The composition can further include covalent or non-covalent connection between the glycolipid antigen and the nanoparticle. The glycolipid antigen is alpha-galactosylceramide or an analog of that. The nanoparticle can be a polymer. A production method of the composition includes preparing a nanoparticle and a glycolipid antigen and loading the glycolipid antigen to the nanoparticle. The glycolipid antigen can be coated onto the surface of the nanoparticle or encapsulated within the nanoparticle. A method of stimulating NKT cells to produce anti-cancer and anti-viral cytokines without causing anergy of NKT cells is also provided.

Abstract: Pharmaceutical preparations, compositions, systems, and devices including medical devices and diagnostic or therapeutic agents, and methods to treat disease by modification of local tissue environment to modulate the therapeutic index of locally or systemically delivered therapeutic or diagnostic agents. Improved ability to reduce sympathetic nerve activity in the adventitia and perivascular tissues around arteries and veins in the body. Modulation of the local tissue environment around an artery to enable more effective denervation with or without a therapeutic agent. Modulation may include adjustment of the pH of the tissue.

Abstract: A method for treating hair loss in mammals uses compositions containing prostaglandin F analogs. The compositions can be applied topically to the skin. The compositions can arrest hair loss, reverse hair loss, and promote hair growth.

Abstract: Compositions are provided which contain immobilized flavorants for flavor delivery. In particular, smoking compositions are provided which contain flavorant ester salts of polycarboxylic acids.

Abstract: Disclosed herein are compounds useful in inhibiting the action of AB-type bacterial toxins such as cholera, traveler's diarrhea, enterohemorrhagic diarrhea caused by E. coli O157:H7 and pertussis or whooping cough. Also included in the invention is the use of these compounds in treatment of diseases associated with those toxins.

Abstract: The present invention provides a variety of radicals, which are useful as polarizing compounds. Exemplary radicals are represented by compounds of Structural Formulae (I), (II), (III) and (IV) as described herein.

Abstract: This invention provides polydentate selective high affinity ligands (SHALs) that can be used in a variety of applications in a manner analogous to the use of antibodies. SHALs typically comprise a multiplicity of ligands that each binds different regions on the target molecule. The ligands are joined directly or through a linker thereby forming a polydentate moiety that typically binds the target molecule with high selectivity and avidity.

Abstract: Combinations of PI3K inhibitor compounds having Formula I and chemotherapeutic agents, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for treating hematopoietic malignancies. Methods of using such combinations 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: Ingenol angelate is a potent anticancer agent, and can be stabilized by dissolving it in an aprotic solvent in the presence of an acidic buffer.

Abstract: Conjugates of 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropanes with a variety of conjugating members are used in the formation of dinuclear metal complexes which bind to phosphate esters. By virtue of their conjugated forms, the complexes are incorporated into chromatographic media, affinity binding reagents, and dyes, which make the complexes useful in a wide range of assays, separations, and purifications. In addition, dinuclear metal complexes of 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropanes that are not so conjugated are used in the detection of phosphate esters of biological species by either MALDI-TOF mass spectrometry or by dye displacement.

Abstract: Biodegradable polymers incorporating biomolecules and methods of their use are provided. Certain aspects provide biomolecules crosslinked with diglycidyl esters. The disclosed compositions have numerous applications including cellular regeneration, wound healing, and cellular differentiation.

Abstract: The present invention relates to macrocyclic small molecule inhibitors of the Sonic Hedgehog signaling pathway, syntheses thereof, and intermediates thereto. Such small molecule modulators of the Sonic Hedgehog signaling pathway are useful in the treatment of proliferative diseases (e.g., basal cell carcinoma, Gorlin syndrome, medulloblastoma, or pancreatic cancer), pulmonary diseases (e.g., interstitial pnuemonitis or interstitial pulmonary fibrosis), and developmental disorders (e.g., phocomelia or cyclopia). Novel non-natural macrocycles are provided that inhibit Sonic Hedgehog induced-protein transcription.

Abstract: Treatment of lymphangioleiomyomatosis with the MEK1/2 inhibitor CI-1040 delayed the development of primary tumors and blocked the estrogen-induced lung metastases in treated animals. Such treatment also reduced the number of circulating ELT3 cells and decreased their lung colonization after intravenous injection.

Abstract: The invention provides active agents, such as paclitaxel, rapamycin, or 17-DMAG, encapsulated by safe poly(ethylene glycol)-block-poly(lactic acid) (“PEG-b-PLA”) micelles. The compositions provide effective solubilization of drug combinations, such as paclitaxel, rapamycin, and 17-DMAG, as well as others described herein. A significant advantage of PEG-b-PLA as a carrier is that it is less toxic than Cremophor® EL or DMSO, which are used in currently known compositions. Additionally, PEG-b-PLA micelles are easier to handle than DMSO and they do not possess a foul odor, which is a problem with formulations currently in clinical trials. Accordingly, the invention provides stable and biocompatible drug formulations that improve bioavailability without causing toxicity. It was also found that larger doses of individual drugs in micelle formulations can be administered compared to non-micelle formulations.

Abstract: Polyal-Drug conjugates comprising a variable rate-releasing linker are described along with methods of making such conjugates. Uses for such Polyal-Drug conjugates is also described.

Abstract: Water-soluble compositions comprising a lipophilic compound and a solubilizing agent of the general formula: {X—OOC—[(CH2)n—COO]m}p—Y??(I) wherein: X is a residue of a hydrophobic moiety, Y is a residue of a hydrophilic moiety, p is 1 or 2, m is 0 or 1, and n is an integer greater than or equal to 0 are disclosed. The lipophilic compound is preferably selected from the group consisting of water-insoluble ubiquinones, ubiquinols, vitamins, provitamins, polyene macrolide antibiotics, and mixtures thereof. The hydrophobic moiety is preferably a sterol or a tocopherol and the hydrophilic moiety is preferably a polyalkylene glycol. In some embodiments, the sterol is cholesterol or sitosterol, the tocopherol is ?-(+)-tocopherol, the polyalkylene glycol is a polyethylene glycol or its methyl monoether having an average molecular weight between 400 and 1000, p is equal to 1 or 2, m is equal to 0 or 1 and n is an integer between 2 and 18.

Abstract: Modified release pharmaceutical compositions (controlled release, sustained release, and/or extended release) of the R-(+) enantiomer of pramipexole (RPPX) and methods of using such compositions for the treatment of neurodegenerative diseases, or those related to mitochondrial dysfunction or increased oxidative stress are disclosed.

Abstract: In various embodiments, the present invention provides methods of treating and/or preventing cardiovascular-related disease and, in particular, a method of blood lipid therapy comprising administering to a subject in need thereof a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.

Abstract: The present invention provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, esters, prodrugs, tautomers, or isomers of said compounds), having the general structure: wherein L, R1, R2, R3, R4, R5, and R6 are selected independently of each other and as defined herein. The present invention also provides compounds (and salts, solvates, esters, prodrugs, tautomers, and isomers) of Formulas II, III, IV, V, and VI, as defined herein. Also provided are pharmaceutical compositions, methods of preparing, and methods of using such compounds in the treatment and prophylaxis of a wide range of immune, autoimmune, and inflammatory diseases and conditions.

Abstract: Provided herein is a method for chemically programmed vaccination. Methods include inducing a covalent-binding polyclonal antibody response in a subject and programming the polyclonal response with a targeting compound.

Abstract: The invention provides compounds of formula I: wherein A, B, D, E, R1, R2, R3, R4, R5, X, and - - - have any values defined herein, as well as salts thereof. The compounds have activity as G-quadruplex DNA stabilizers and as anti-proliferative agents.

Abstract: Pharmaceutical compositions of (R)-pramipexole and methods and kits of using such compositions for the treatment of neurodegenerative diseases, or those related to mitochondrial dysfunction or increased oxidative stress are disclosed.

Abstract: The present invention relates to an opioid controlled release oral dosage form comprising at least one opioid for the manufacture of a medicament to treat patients with Chronic Obstructive Pulmonary Disease (COPD).

Abstract: In various embodiments, the present invention provides methods of treating and/or preventing cardiovascular-related disease and, in particular, a method of blood lipid therapy comprising administering to a subject in need thereof a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.

Abstract: The present invention provides a therapeutic combination comprising (a) a compound of formula (I) as set forth in the specification and (b) one or more antineoplastic agents selected from the group consisting of alkylating or alkylating-like agents, antimetabolite agents and topoisomerase I inhibitors, wherein the active ingredients are present in each case in free form or in the form of a pharmaceutically acceptable salt or any hydrate thereof.

Abstract: The invention features a class of 2-nitroimidazole compounds with a secondary basic nitrogen atom and a linker bearing one or more therapeutic agents, cytotoxic agents, detectable labels, or chelating groups. In particular, the invention provides 2-nitroimidazole compounds containing a cluster of boron atoms for use in boron neutron capture therapy (BNCT). The 2-nitroimidazole compounds can be used to treat hypoxic conditions, including, e.g., cancer, inflammation, and ischemia. The weakly basic 2-nitroimidazole compounds target to hypoxic tissue and provide increased tissue concentration overall.

Abstract: Inhibition of CXCR4 can inhibit tumor growth and metastasis during certain therapeutic windows. Disclosed are novel methods for treating and preventing cancer in a subject related to administration of CXCR4 inhibitors during a therapeutic window following treatment with another anti-tumor therapy.

Abstract: Compounds and pharmaceutical compositions are provided that inhibit the activity of poly ADP-ribose synthetase (PARP). Such compounds are useful in the treatment of various diseases, conditions and injuries such as stroke, myocardial infarction, ischemia-perfusion injury in various organs, traumatic brain injury, atherosclerosis, inflammatory diseases and cancer.

Abstract: This invention relates to the use of a cyclic compound of formula (I) wherein A, B independently in each occurrence is alkane-i,j-diyl having k carbon atoms, i and independently j being less than or equal k and k being selected from 1 to 10, wherein said alkane-i,j-diyl (i) may comprise one or more double bonds; (ii) is optionally substituted; and/or (iii) comprises a cycle, wherein the total number of cycles being cyclic sugars in said compound is selected from 0 to 4 and is less than p·(n+m); X,Y independently in each occurrence is a biocompatible functional group comprising at least one oxygen atom or two sulphur atoms; n, m independently of each other are selected from 0 to 20; p is selected from 1 to 10; n+m is equal or greater than 1; and p·(n+m) is selected from 3 to 30; wherein said compound is capable of forming a complex with a protonated primary and/or protonated secondary amino group and/or a protonated guanidinium group for the manufacture of a pharmaceutical or diagnostic composition.

Abstract: An oral dosage form comprises cromolyn sodium (sodium or disodium cromoglycate), and an acylated amino acid delivery agent.

Abstract: Treatment with N-(2-phenylethyl)succinamic acid or its salts protects against inhibition of growth by a neonicotinoid compound applied as a seed treatment or applied directly on or near the root zone of the seedling.

Abstract: This invention provides a combination of antagonists of the hedgehog signaling pathway with a BCR-ABL inhibitor. The combination of the present invention may be used for treating cancers known to be associated with protein tyrosine kinases such as, for example, Src, BCR-ABL and c-kit.

Abstract: Contemplated pharmaceutical compositions comprise a benzodiazepine anti-convulsive compound for intranasal administration in a single phase, multi-component solvent system with water content of at least 15 vol % and a benzodiazepine concentration of at least 30 mg/ml. It is noted that contrary to common expectation, the concentration of the anti-convulsive compound was increased by increasing water content in the multi-component solvent. Moreover, the anti-convulsive compound remained chemically stable and substantially completely dissolved over large periods of time. Thus, stable and highly concentrated spray formulations for intranasal administration could be prepared having sufficiently high concentrations of the anti-convulsive compounds that now allow single spray administration to achieve clinically relevant dosages.

Abstract: According to some embodiments, the present invention provides compositions and methods for making and using multifunctional polymerized liposomes finding relevant application in medical sciences, particularly in bioimaging, diagnostics, drug delivery, and drug formulation. The compositions and methods involve lipids that are both polymerizable and have a “clickable” group that provides the ability to functionalize via a click reaction with various functional moieties useful for the above-listed applications.

Abstract: Compounds of the general formula (I), wherein the substituents are as defined in claim 1, are useful as fungicides.

Abstract: The present invention identifies a compound which binds to the PAH1 domain of mSin3B that specifically binds to neural restrictive silencer factor NRSF, and uses the compound as a prophylactic and/or a therapeutic for diseases associated with abnormal expression of neural restrictive silencer factor NRSF/REST or abnormal expression of genes targeted by NRSF/REST, such as Huntington's disease, medulloblastoma and neuropathic pain. The present invention provides a pharmaceutical composition comprising a substance capable of binding to the PAH1 domain of mSin3B, e.g.

Abstract: The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.