Abstract: Methods of using di, tri, and tetracyclic acylhydrazide derivatives and analogs, as well as pharmaceutical compositions containing the same, for the treatment or prophylaxis of viral infections and diseases associated therewith, particularly those viral infections and associated diseases caused by the orthopoxvirus.

Abstract: Composition and methods of treating pain and reducing or reversing tolerance to opiate analgesics are disclosed. The composition and method utilize an opiate analgesic and an endothelin antagonist as active agents to treat pain in mammals, including humans.

Abstract: This invention concerns novel substituted unsaturated tetracyclic tetrahydrofuran derivatives with binding affinities towards serotonine receptors, in particular 5-HT2A and 5-HT2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in claim 1.

Abstract: A method of using photodynamic therapy to perform selective targeted therapy of biological tissue. The method includes intravenously injecting a porphyrin-based photosensitizing drug followed by irradiating the tissue with light while the drug is being injected. The duration of the irradiation and other parameters are controlled so that the selected biological tissue is treated and non-selected tissue is not damaged. By controlling the flow rate of the injection and other parameters, so that irradiation of the effected tissue overlaps with injection of drug, the target tissue is effectively treated without damage to non-target tissue.

Abstract: Methods of using di, tri, and tetracyclic acylhydrazide derivatives and analogs, as well as pharmaceutical compositions containing the same, for the treatment or prophylaxis of viral infections and diseases associated therewith, particularly those viral infections and associated diseases caused by the orthopoxvirus.

Abstract: An intrauterine device and more specifically an intracervical device (ICD) for the local release of drugs in the loco-regional treatment of tumours of the uterine cervix comprises an elongated stem (2) to be positioned in the cervical canal (15), this stem consisting of an inner hollow core (3) and a coating (4) containing a gradual-release drug, the stem being attached to: a first element (5) for blocking the stem (2) inside the uterine cavity (12), and located at the cranial or upper end; a second blocking element (7, 71) positioned inside the vagina (11), against the ectocervix (16), located at the caudal or lower end of the stem (2).

Abstract: The present invention provides a polymeric scaffold containing an antibacterial photoactive drug and optionally comprising seeded cells such as stem cells. The invention also includes methods of using the scaffold for tissue regeneration, prevention or reduction of infection whilst tissue regeneration occurs, methods for improving graft or implant survival, promoting scaffold integration and tissue repair and wound healing.

Abstract: Provided are a photosensitizer-metal nanoparticle charge complex and a composition for photodynamic therapy or diagnosis containing the same. The complex includes a metal nanoparticle, a photosensitizer charged with a first charge, and a linker bound to the metal nanoparticle and charged with a second charge having an opposite polarity to the first charge. During circulation in blood, the photosensitizer-metal nanoparticle charge complex is maintained in a complex type, and thus duration of a side effect of photosensitivity can be reduced. In a tumor tissue, the complex is specifically accumulated, but in a normal tissue, it is difficult for the complex to penetrate. Thus, the complex can selectively destroy the tumor tissue. Moreover, selective fluorescence in the tumor tissue can provide further improvement in accuracy of diagnosing a tumor using the complex.

Abstract: Disclosed herein are compounds represented by a formula: R1—Ar1—X—Ar2—Ar3-Het, wherein R1, Ar1, X, Ar2, Ar3, and Het are described herein. Compositions and light-emitting devices related thereto are also disclosed.

Abstract: A nano-capsule construct for imaging and therapeutic uses and method for production are provided. One nano-probe embodiment based on genome-depleted plant brome mosaic virus (BMV) whose interior is doped with indocyanine green (ICG), an FDA-approved near infrared fluorescent dye, is used to illustrate the invention. The material encapsulated in viral shell components may be coated with functionalized coatings such as branched, dendritic polymer coatings to improve longevity and distribution in the body as well as antibody conjugation for increased target specificity. The constructs can also be coated with ferromagnetic iron oxide nanoparticles, enabling the ICG-containing capsules to be used as nano-probes with the capability of being detected in both optical and magnetic resonance imaging. The capsules may be produced by purifying a plant or animal viruses and disassembling the viruses to provide virus shell components.

Abstract: Compounds of the general structural formula (I) and (II) and use of the compounds and salts and hydrates thereof, as therapeutic agents are disclosed. Treatable diseases and conditions include cancers, inflammatory diseases and conditions, and immunodeficiency diseases.

Abstract: Provided herein are multimodal barrier materials useful for preventing adhesions in a subject, which may include a collagen, a collagen deposition inhibitor and/or a chitosan.

Abstract: Porphyrazines capable of localizing in a tumor of a mammal are disclosed. The porphyrazines are used in methods of imaging a tumor and in methods of treating tumors, either alone or in combination with a chemotherapeutic agent and/or radiation.

Abstract: Disclosed are fused heterocyclic compounds of Formula (I) or pharmaceutically-acceptable salts or stereoisomers thereof. Also disclosed are methods of using such compounds in the treatment of at least one androgen receptor-associated condition, such as, for example, cancer, and pharmaceutical compositions comprising such compounds.

Abstract: In one aspect, the invention relates to a method for identifying a drug candidate with activity as a neuroprotective agent. The method includes determining whether a compound reduces ATF4 activity; and identifying the compound that reduces ATF4 activity as a drug candidate.

Abstract: The present invention describes linking a therapeutic agent to a compound which is known to be naturally concentrated in a tissue affected by, or that is causing, a disease, to create a prodrug for treatment of the disease. Embodiments of the present invention include a new class of carotenoid-linked drugs to treat such blinding retinal disease such as age-related macular degeneration, retinoblastoma, and diabetic macular edema. For example, the present invention comprises a method for the treatment of a disorder of the eye comprising linking a therapeutic agent to a xanthophyll carotenoid to create a prodrug, and administering a therapeutically effective amount of the prodrug to an individual in need of treatment. Provided are prodrugs for treatment of retinoblastoma, cystoid macular edema (CME), exudative age-related macular degeneration (AMD), diabetic retinopathy, diabetic macular edema, or inflammatory disorders.

Abstract: Compositions, which are stable in storage, and a method of production of pharmaceutical based nanoparticulate formulations for clinical use in photodynamic therapy comprising a hydrophobic photosensitizer, poly(lactic-co-glycolic) acid and stabilizing agents are provided. These nanoparticulate pharmaceutical formulations provide therapeutically effective amounts of photosensitizer for parenteral administration. In particular, tetrapyrrole derivatives can be used as photosensitizers, whose efficacy and safety are enhanced by such nanoparticulate formulations. It also teaches the method of preparing PLGA-based nanoparticles under sterile conditions. In one of the preferred embodiments of the present invention PLGA-based nanoparticles have a mean particle size less than 500 nm and the photosensitizer is temoporfin, 5,10,15,20-tetrakis(3-hydroxyphenyl)-chlorin (mTHPC).

Abstract: Compositions and methods for treating, preventing, or ameliorating one or more symptoms, disorders, or conditions associated with particular c-Jun N-terminal kinase(s) (JNKs) activity are provided. Compositions contain small molecules such as pyrazoloanthrones.

Abstract: The present application provides compositions and methods using bioorthogonal inverse electron demand Diels-Alder cycloaddition reaction for rapid and specific covalent delivery of a “payload” to a ligand bound to a biological target.

Abstract: Organic chelating ligands, organic chelating ligand precursors, and metal chelates are disclosed. Methods for synthesizing the same are also described, including methods for preparing optically-enriched or optically-pure compositions of the same.

Abstract: Methods for increasing the generation of IL-17-producing T cells (TH17) in vivo and in vitro, and enriched populations of TH17 cells for the treatment of diseases benefiting from an induced or enhanced immune response, e.g., infection and cancer.

Abstract: The invention relates to pyrrolo[2,3-a]carbazole derivatives, to a method for preparing the same, and to the use thereof as PIM kinase inhibitors. The invention can particularly be used in the pharmaceutical field.

Abstract: The invention provides the use of a compound of formula (I), or metallated derivative thereof, for killing, inhibiting or preventing the growth of a microbial biofilm: wherein X1, X2, X3, X4, Y1, Y2, Y3, Y4 and Z have meanings given in the description. The biofilm may be on a living or inert support. Preferably, the microorganisms are selected from the group consisting of bacteria and fungi.

Abstract: The present invention provides pharmaceutical photosensitizer-loaded nanoparticle formulations and their methods of preparation for photodynamic therapy, comprising a hydrophobic or hydrophilic photosensitizer, nanoparticulate calcium phosphate and in certain cases auxiliary reagents such as stabilizers. The calcium phosphate-based nanoparticle formulations of the present invention provide excellent storage stability and therapeutically effective amounts of photosensitizer for intravenous or topical administration. In a preferred embodiment, tetrapyrrole derivatives such as porphyrins, chlorins and bacteriochlorins, are the preferred hydrophobic photosensitizers to be formulated in calcium phosphate nanoparticle formulations for photodynamic tumor therapy. Additionally, 5,10,15,20-tetrakis(4-phosphonooxyphenyl)porphine (pTPPP) is a preferred hydrophilic photosensitizer for photodynamic tumor therapy.

Abstract: Methods of using di, tri, and tetracyclic acylhydrazide derivatives and analogs, as well as pharmaceutical compositions containing the same, for the treatment or prophylaxis of viral infections and diseases associated therewith, particularly those viral infections and associated diseases cased by the orthopoxvirus.

Abstract: A formulation or preparation for treating and preventing arterial and venous thrombi is provided. This preparation includes a non-metal containing photodynamic dye and a fat soluble vitamin. A method of administration for treatment and prophylaxis of arterial and venous thrombi is also provided. This method includes steps of: combining a non-metal containing photodynamic dye and a fat soluble vitamin; combining the non-metal containing photodynamic dye and fat soluble vitamin with a sodium solution; and administering the combination of non-metal containing photodynamic dye, fat soluble vitamin, and sodium solution as an intravenous drip.

Abstract: The disclosed subject matter includes methods of preparation, properties, pharmaceutical compositions and methods of therapy of sulfonated chlorins and bacterioclorins designed for the photodynamic therapy (PDT) of hyperproliferative tissues such as tumors, hyperproliferative blood vessels and other disorders or abnormalities that are responsive to PDT. In particular, the economical large-scale synthesis of stable chlorins and bacteriochlorins is described. Their properties were tailored to meet those of ideal photosensitizers for PDT. In another embodiment, pharmaceutical compositions and methods of therapy for systemic administration are provided. In a further embodiment, pharmaceutical compositions and methods of therapy for topical administration are also provided. Further provided is a method of labeling a target tissue and providing an image of that tissue by fluorescence of magnetic resonance imaging.

Abstract: The present invention relates to acenaphtho heterocyclic compounds, cyclodextrin inclusion compounds and complexes thereof, and their uses in manufacturing the inhibitors of BH3 analogue, Bcl-2 family proteins. The acenaphtho heterocyclic compounds are obtained by introducing oxo-, thio-, carbonyl, ester or acyl in the 3-, 4- and 6-position of 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile, or further substituting 9-cyano with carboxyl, ester or amide. The compounds can simulate BH3-only protein, competitively binding and antagonizing Bcl-2, Bel-XL and Mcl-1 proteins in vitro or intracellular, to induce cell apoptosis. The cyclodextrin inclusion compounds and complexes can improve the effects. Therefore, they all can be used in the manufactures of anticancer compounds.

Abstract: A bioluminescence imaging-based high-throughput assay for inhibitors of ABCG2 is described. Compositions of inhibitors of ABCG2 and methods of using ABCG2 inhibitors are also described.

Abstract: The invention relates to the selection and treatment of subjects afflicted with occult choroidal neovascular lesions, including subjects with age-related macular degeneration, by use of photo dynamic therapy (PDT).

Abstract: This invention provides for dimeric1-arylpyrazole compounds, of formulas (I), (II), and (III): or salts thereof, and the use of these compounds against ectoparasites such as insects, arthropods and acarina. The resulting compounds may be used in veterinary formulations such as, for example, spot-on and pour-on formulations, which may be used for treatment, controlling and preventing of parasitic infections in warm-blooded animals and birds.

Abstract: Methods of treating disorders such as neurofibromatosis-1 are provided, including methods in which catalytic antioxidants such as metalloporphyrins are administered. Methods of regulating longevity, and methods and systems for screening for modulators of aging or longevity, are also provided. In addition, related transgenic animals are described.

Abstract: The invention relates to new compounds for cancer therapy or diagnosis and more specifically to the use of a non-toxic B subunit of Shiga toxin mutant as a vector for diagnostic products or drugs in over-expressing Gb3 receptor cells, such compounds having the following formula: STxB-Z(n)-Cys-Y(m)-T wherein STxB is the Shiga Toxin B subunit or a functional equivalent thereof, Z(n) whrein n is 0 or 1 and when n is 1, Z is an amino-acid residue devoidof sulfydryl group, or is a polypeptide, Cys is the amino-acid residue for Cysteine, T is a molecule linked by a covalent bound to the S part of Cys, selected in a group comprising: agents for in vivo diagnosis, cytotoxic agents, prodrugs, or enzymes for the conversion of a prodrug to a drug, Y(m) wherein m is 0 or 1 and when m is 1, Y is a linker between T and Cys, said linker being either cleavable or not cleavable for the release of T after the internalization of the hybrid compound into said cells.

Abstract: The present invention is directed to a dendritic polyamidoamine phthalocyanine derivative which is useful as, for example, a fluorescent material or a photodynamic therapeutic drug for cancer. The derivative is represented by the following formula (1): (wherein each member of one to eight of R1 to R8 is a polyamidoamine dendron represented by the following formula (a): (wherein p is a number from 1 to 4; R9 represents —NH(CH2)tNH2 or OR10 (wherein R10 represents an alkyl group); and each of l, m, q, and t is a number from 1 to 8), and each member of the remainder represents a hydrogen atom; M represents a metal atom having a valency of two or more; and a ring marked with (N) is a benzene ring, a pyridine ring, or a pyrazine ring).

Abstract: This invention is directed to tricyclic spiro-oxindole derivatives of formula (I), wherein j, k, m, n, w, q, Y, Q, X, R1, R2 and R3 are as defined herein, as a stereoisomer, enantiomer, tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof, which are useful for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain. Pharmaceutical compositions comprising the compounds and methods of preparing and using the compounds are also disclosed.

Abstract: Disclosed herein is the identification of human DNA polymerase ? (pol ?) as the polymerase that mediates repair of DNA containing interstrand cros slinks (ICLs). The mechanism of action of a number of chemotherapeutic and antimicrobial agents is the induction of ICLs. Thus, provided herein is a method of enhancing the efficacy of a chemotherapeutic or antimicrobial agent in a subject, including selecting a subject in need of treatment with an ICL-inducing agent and administering to the subject an ICL-inducing agent and a therapeutically effective amount of an inhibitor of pol ?. Subjects in need of treatment with an ICL-inducing agent, include, for example, subjects diagnosed with a hyperproliferative disease, an autoimmune disease or an infectious disease. Also provided is a composition for treating a hyperproliferative disease, an autoimmune disease or an infectious disease, comprising an ICL-inducing agent and an amount of an inhibitor of pol ? sufficient to enhance the efficacy of the ICL-inducing agent.

Abstract: The invention relates to novel betulinic acid derivatives of formula (I), wherein R is C(?CH2)CH3 or CH(CH3)2; R2 together with the adjacent carbonyl group forms a carboxylic acid, carboxylic acid ester or amide or substituted amide; R3 or R4 are hydrogen or aryl with the proviso that both are not independently hydrogen or alkyl or R3 and R4 are combined together to form an aryl ring optionally substituted with a group X, wherein X is selected from halogen, alkyl, cyano, nitro, alkoxy, amino or substituted amine; Y is N or O; and R1 is zero when Y is O, and R1 is hydrogen, alkyl or aryl alkyl when Y is N, useful for inhibition of tumor cancer cells.

Abstract: This invention concerns novel substituted unsaturated tetracyclic tetrahydrofuran derivatives with binding affinities towards serotonine receptors, in particular 5-HT2A and 5-HT2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substitutents are defined as in Claim 1.

Abstract: A compound that is a conjugate of an antagonist to an integrin expressed by a tumor cell and at least one of a tumor avid tetrapyrollic photosensitizer, a fluorescent dye, and a radioisotope labeled moiety wherein the radioisotope is 11C, 18F, 64Cu, 124I, 99Tc, 111In or GdIII and its method of use for diagnosing, imaging and/or treating hyperproliferative tissue such as tumors. Preferably the photosensitizer is a tumor avid tetrapyrollic photosensitizer, e.g. a porphyrin, chlorin or bacteriochlorin, e.g. pheophorbides and pyropheophorbides. Such conjugates have extreme tumor avidity and can be used to inhibit or completely destroy the tumor by light absoption. The integrin is usually ?v?3, ?5?1, ?v?5, ?4?1, or ?2?1. Preferably, the antagonist is an RGD peptide or another antagonist that may be synthetic such as a 4-{2-(3,4,5,6-tetra-hydropyrimidin-2-ylamino)ethyloxy}-benzoyl]amino-2-(S)-amino-ethyl-sulfonylamino group.

Abstract: The present disclosure relates to nanoparticle-containing implantable and preferably biodegradable medical products and their use for the thermotherapeutic after-treatment after surgical removal of tumors and cancerous ulcers.

Abstract: Cytosine deaminase inhibitors and methods for identifying inhibitors of the anti-retroviral activity of APOBEC3G are described.

Abstract: A condensation compound of a fluorinated cyclopentane ring and an aromatic ring, which is useful, for example, for electronic materials, and a process for producing the same are provided. For instance, according to Scheme 1 below, a compound (68) containing a condensed structure formed of a hexafluorocyclopentane ring and an aromatic ring is synthesized. The aromatic ring is not limited to a thiophene ring but can be any ring and any substituent can be used. Thus a compound containing a condensed ring structure formed of a hexafluorocyclopentane ring and an aromatic ring, particularly, for instance, a thiophene ring, which was impossible to produce conventionally, can be produced easily with high yield. The compound of the present invention is particularly suitable to be applied to, for example, electronic materials or semiconductors.

Abstract: Biologically active compounds are provided that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PDT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, ophthalmological or urological disorders as well as providing methods to obtain them in pharmaceutical quality. One embodiment consists of a method to synthesize a porphyrin with a defined arrangement of meso-substituents and then converting this porphyrin system to a chlorin system by dihydroxylation or reduction, and if more than one isomer is formed separate them by chromatography either on normal or reversed phase silica. In another embodiment the substituents on the porphyrin are selected to direct the reduction or dihydroxylation to the chlorin so that a certain isomer is selectively formed.

Abstract: Provided are methods and compositions for treating ocular conditions characterized by the presence of unwanted choroidal neovasculature, for example, neovascular age-related macular degeneration. The selectivity and sensitivity of, for example, a photodynamic therapy (PDT)-based approach can be enhanced by combining the PDT with an anti-FasL factor, for example, an anti-FasL neutralizing antibody.

Abstract: A class of macrocyclic compounds of formula (I), wherein R7, A, Ar, B, D, F, M, Q1, Q2, W, X, Y and Z are defined herein, that are useful as inhibitors of viral proteases, particularly the hepatitis C virus (HCV) NS3 protease, are provided. Also provided are processes for the synthesis and use of such macrocyclic compounds for treating or preventing HCV infection.

Abstract: Novel compounds that are potent inhibitors of hepatitis C virus protease are provided. Pharmaceutical compositions containing one or more of these inhibitors, methods of preparing the inhibitors and methods of using the inhibitors to treat hepatitis C and related disorders also are provided.

Abstract: The invention provides a method of sustained delivery of a tertiary amine-containing parent drug comprising administering to a patient an effective amount of a prodrug compound of the invention wherein upon administration to the patient, release of the parent drug from the prodrug is sustained release. Prodrug compounds suitable for use in the methods of the invention are labile quaternary ammonium salts of tertiary amine-containing parent drugs (or tertiary imine-containing parent drugs) that are derivatized through aldehyde-linked prodrug moieties that reduce the solubility of the prodrug compound at a reference pH as compared to the parent drug. The physical, chemical and solubility properties of these derivatives can be further modulated by the choice of counterion X?. In one embodiment, the present invention provides a prodrug compound of Formula I: where R1-R5 are defined in the written description of the invention.

Abstract: The present invention generally relates to a series of compounds, to pharmaceutical compositions containing the compounds, and to use of the compounds and compositions as therapeutic agents. More specifically, compounds of the present invention are hexahydroazepinoindole and octahydroazepinoindole compounds. These compounds are serotonin receptor (5-HT) ligands and are useful for treating diseases, disorders, and conditions wherein modulation of the activity of serotonin receptors (5-HT) is desired (e.g. anxiety, depression and obesity).

Abstract: The present invention generally relates to a series of compounds, to pharmaceutical compositions containing the compounds, and to use of the compounds and compositions as therapeutic agents. More specifically, compounds of the present invention are tricyclic indeno-pyrrole compounds. These compounds are serotonin receptor (5-HT) ligands and are useful for treating diseases, disorders, and conditions wherein modulation of the activity of serotonin receptors (5-HT) is desired (e.g. anxiety, depression and obesity).

Abstract: The present invention relates to a tetracyclic fused heterocyclic compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable a salt thereof, and a hepatitis C virus (HCV) polymerase inhibitor and a therapeutic agent for hepatitis C containing this compound. The compound of the present invention shows an anti-HCV activity based on the HCV polymerase inhibitory activity, and useful as an agent for the prophylaxis or treatment of hepatitis C.