Abstract: The present invention relates to the use of a bisphosphonate derivative according to general Formula I and/or a pharmaceutically acceptable salt thereof, wherein R1 and/or R2 are independently selected out of a group comprising hydrogen, hydroxyl, halogen, pseudohalogen, formyl, carboxy- and/or carbonyl derivatives, alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, halogenalkyl, aryl, arylene, halogenaryl, heteroaryl, heteroarylene, heterocycloalkylene, heterocycloalkyl, halogenheteroaryl, alkenyl, halogenalkenyl, alkinyl, halogenalkinyl, keto, ketoaryl, halogenketoaryl, ketoheteroaryl, ketoalkyl, halogenketoalkyl, ketoalkenyl, halogenketoalkenyl, phosphoalkyl, phosphonate, phosphate, phosphine, phosphine oxide, phosphoryl, phosphoaryl, suiphonyl, sulphoalkyl, sulphoarenyl, sulphonate, sulphate, sulphone, amine, polyether, silylalkyl, silylalkyloxy, and wherein at appropriate residues one or more non-adjacent CH2-groups may be replaced independently from each other with —O—, —S—, —NH—, —NRo

Abstract: The invention relates to compounds of structural formula (I): or a pharmaceutically acceptable salt, solvate, clathrate, and prodrug thereof, wherein Ra, Rb, and R2 are defined herein. These compounds inhibit tubulin polymerization and/or target vasculature and are useful for treating proliferative disorders, such as cancer.

Abstract: The invention relates to a pesticidal composition comprising as active ingredient a mixture consisting of one compound (A) as defined in the patent claims and at least one compound (B) as defined in the patent claims, to a process for the preparation of and to the use of such a composition, to a method of controlling pests using such a composition and to plant propagation material treated with such a composition.

Abstract: Novel cyclic phosphoramidate prodrugs of drugs of formula I their use in delivery of drugs to the liver, their use in enhancing oral bioavailability, and their method of preparation are described.

Abstract: This invention relates to inhibitors of mitotic kinesins, particularly KSP, and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of various disorders.

Abstract: This invention provides novel ?-lactamase inhibitors of the aryl- and heteroaryl-sulfonamidomethylphosphonate monoester class. The compounds inhibit three classes of ?-lactamases and synergize the antibacterial effects of ?-lactam antibiotics (e.g., imipenem and ceftazimdime) against those micro-organisms normally resistant to the ?-lactam antibiotics as a result of the presence of the ?-lactamases.

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: HIV infection can be detected by measuring phosphorylation levels of the actin-depolymerizing factor (AFD)/cofilin family, and infection can be treated and/or prevented by modulating the HIV co-receptor signaling pathway.

Abstract: A compound of the formula is disclosed as a prodrug of an HIV protease inhibitor. Methods and compositions for inhibiting HIV protease activity and treating HIV infection are also disclosed.

Abstract: This invention provides novel ?-lactamase inhibitors of the aryl- and heteroarylsulfonamidomethylphosphonate monoester class having nitrogen-based cations or quarternary ammonium groups. The compounds inhibit three classes of ?-lactamases and synergize the antibacterial effects of ?-lactam antibiotics (e.g., imipenem and ceftazidime) against those micro-organisms normally resistant to the ?-lactam antibiotics as a result of the presence of the ?-lactamases. Formula (I) or pharmaceutically acceptable salt thereof.

Abstract: Embodiments of the present invention provide novel antibacterials that target penicillin-binding proteins or other important cellular targets. Methods for inhibiting growth (reproduction, etc.) of bacteria using compounds described herein are also provided. Various embodiments exhibit activity against gram positive bacteria, such as certain strains of Entercoccus and Staphylococcus aureus.

Abstract: The invention relates to substituted arylsulphonylaminomethylphosphonic acid derivatives of general formula (I) wherein the groups Ra to Rf, A and Z are defined as mentioned in the specification and claims, which are suitable for preparing a medicament for the treatment of metabolic disorders, particularly type 1 or type 2 diabetes mellitus.

Abstract: The present invention relates to novel classes of compounds of formula I which are caspase and TNF-alpha inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting caspase and TNF-alpha activity and consequently, can be advantageously used as agents against caspase-, interleukin-1-(“IL-1”), apoptosis-, interferon-? inducing factor-(IGIF), interferon-?-(“IFN-?”), or TNF-alpha mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to processes for preparing the compounds of this invention.

Abstract: The invention is directed to Compounds of Formula I: as well as methods of making and using the compounds.

Abstract: Provided herein are phosphothiophene and phosphothiazole compounds, for example, of any of Formulae I, IA, IIA, IIIA, IVA, VA, VIA, VIIA, IB, IIB, IIIB, IVB, VB, VIIB and VIIB disclosed herein, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host infected with HCV.

Abstract: Embodiments of the invention relate to the treatment of neuropathic pain in mammals. Embodiments of the invention include methods for treating neuropathic pain as well as methods for preparing medicaments used in the treatment of mammalian pain. Preferably, methods of the invention comprise the modulation of glycogeno lysis or glycolysis pathways for the treatment of mammalian pain.

Abstract: The invention relates to novel tubulysin conjugates (e.g. of tubulysin A) and the use thereof in the treatment of cancer diseases.

Abstract: A composition and method of treating Alzheimer's disease or a dementia of vascular origin are disclosed. The composition and method utilize an endothelin antagonist as the active agent to treat Alzheimer's disease or a dementia of vascular origin in mammals, including humans.

Abstract: Compounds of Formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, and compounds as shown in Formula (I) wherein C is for example (D), (E), (F); wherein A and B are independently selected from (i) and (ii); R2a to R3b are independently selected from hydrogen and fluorine; R1a and R1b are independently selected from, for example, hydroxy, —NHC(?W)R4, (a) and (b); wherein W is O or S; R4 is, for example, hydrogen, amino, (1-4C)alkyl; HET-1 is, for example, a C-linked 5-membered heteroaryl ring; HET-2 is, for example, an N-linked 5-membered, fully or partially unsaturated heterocyclic ring; are useful as antibacterial agents; and processes for their manufacture and pharmaceutical compositions containing them are described.

Abstract: A compound of the formula is disclosed as a prodrug of an HIV protease inhibitor. Methods and compositions for inhibiting HIV protease activity and treating HIV infection are also disclosed.

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: The invention relates to isoxazole, isothiazole, and triazole compounds that are useful for treating or inhibiting angiogenesis.

Abstract: The invention relates to compounds of the formula I A-B-Z ??I wherein the variables are as defined in the claims. The compounds are pro-drugs of A2A-receptor ligands with improved aqueous solubility, and are useful in the treatment of neurological and psychiatric disorders where an A2A-receptor is implicated.

Abstract: The present invention relates to the use of a protein phosphatase inhibitor selected from an inhibitor of the catalytic subunit of the protein phosphatase 1 (PP1), an inhibitor of GADD34 and an inhibitor of the PP1/GADD34 complex to prepare a pharmaceutical composition to prevent or treat a cancer in a mammal, wherein the pharmaceutical composition is intended for administration in combination with a product used in a treatment of a cancer.

Abstract: The present invention relates to novel compounds (I), their prodrugs, and the pharmaceutically acceptable salts as well as pharmaceutical compositions containing such compounds useful in treating certain metabolic diseases and diseases modulated by the inhibition of the enzyme malonyl-coenzyme A decarboxylase (malonyl-CoA decarboxylase, MCD). In particular, the invention relates to compounds and compositions and the methods for the prophylaxis, management and treatment of cardiovascular diseases, diabetes, acidosis, cancers, and obesity through the inhibition of malonyl-coenzyme A decarboxylase.

Abstract: The invention provides compounds formula I, their preparation, and their use as pharmaceutically active immuno-suppressive agents for the treatment of autoimmune disorders, organ transplant rejection, disorders associated with an activated immune system, as well as other disorders modulated by lymphopenia or SIP receptors.

Abstract: The invention provides compounds formulae I-III, their preparation, and their use as pharmaceutically active immunosuppressive agents for the treatment of autoimmune disorders, organ transplant rejection, disorders associated with an activated immune system, as well as other disorders modulated by lymphopenia or SIP receptors.

Abstract: The invention relates to novel active compound combinations of certain cyclic ketoenols and certain active compounds that together have unexpectedly good insecticidal and acaricidal properties.

Abstract: The invention provides amino-substituted aminothiazole compounds of Formula I and Formula II where A is a group of the formula: and the variables X, Y, R, and R1 to R7 are described herein. These compounds are prodrugs of compounds useful as inhibitors of viral replication. Compositions containing such compounds, and methods of treating viral infections with these compounds, as well as to processes and intermediates useful for preparing such compounds are also provided by the invention.

Abstract: The invention relates to compounds of structural formula (I): or a pharmaceutically acceptable salt, solvate, clathrate, and prodrug thereof, wherein Ra, Rb, and R2 are defined herein. These compounds inhibit tubulin polymerization and/or target vasculature and are useful for treating proliferative disorders, such as cancer.

Abstract: A combination therapy of at least one FBPase inhibitor and at least one other antidiabetic agent is disclosed.

Abstract: Various azetidinone, pyrrolidine, imidazolidine, and oxazolidine derivatives are described, as are pharmaceutical compositions containing these compounds and methods of treatment of diseases using these compounds. Other embodiments are also described.

Abstract: Disclosed herein is a compound having a structure or a pharmaceutically acceptable salt thereof, or a prodrug thereof. Therapeutic methods, compositions, and medicaments related thereto are also disclosed.

Abstract: This invention relates to synergistic combinations of selected microbicides in combination with a second microbicide or formulation ingredient or raw material. The combinations have greater efficacy than would be expected from combinations of the individual components. The combinations include mixtures of (a) 5-Chloro-2-methyl-4-isothiazolin-3-one+2-Methyl-4-isothiazolin-3-one, :(b) Methyl-4-isothiazolin-3-one, or (c) 1,2-Benzisothiazolin-3-one with one or more of a variety of other compounds.

Abstract: Diazonamide A analogs, and the salts, esters and conjugates thereof, having improved aqueous solubility are provided. Also provided are pharmaceutical compositions, and methods for preparing and using such compounds and compositions for the treatment of proliferative diseases.

Abstract: The present invention generally concerns microtubule protrusions in cancer cells, including detached cancer cells, and inhibition of the protrusions. In particular aspects, the inhibition of the protrusions interferes with attachment of the cell to a vessel wall, and in further aspects the cell is killed by forcing it to enter capillaries and be destroyed, for example by shearing. Inhibition by a variety of agents and methods is contemplated.

Abstract: The present invention provides a novel compound having few side effects such as bradycardia and the like and having superior peripheral blood lymphocyte-decreasing effect.

Abstract: Certain substituted benzylamino heterocyclic and heteroaryl derivatives have provided unexpected insecticidal and acaricidal activity. These compounds are represented by formula (1): wherein R, R1, R2, R3, and R4 are fully described herein. In addition, compositions comprising an insecticidally effective amount of at least one compound of formula (1), and optionally, an effective amount of at least one of an additional compound, with at least one insecticidally compatible carrier are also disclosed; along with methods of controlling insects comprising applying said compositions to a locus where insects are present or are expected to be present.

Abstract: A kit for treating a health condition in a mammal, comprises a ERP57 protein and/or compound for inducing a translocation of an ERP57 protein to a cellular membrane in order to provoke an immunogenic apoptosis. The ERP57 protein may include any one or more of: endogenous ERP57, recombinant ERP57, and ERP57 in mimetic form. The endogenous form of ERP57 may include any one of: a plasma membrane ERP57 and an intracellular ERP57.

Abstract: The present invention relates to the compounds of general formula (I) wherein R, R1, R2 are as defined in claim 1. Compounds of formula (I) are particularly useful for preparing 3,3-dimethyl-5-formyl-2,3-dihydrobenzoxepines derivatives.

Abstract: Anthracyclines-treated tumor cells are particularly effective in eliciting an anti-cancer immune response, where the rDNA-damaging agents, such as etoposide and mitomycin C do not induce immunogenic cell death. Anthracyclines induce the rapid, pre-apoptotic translocation of calreticulin (CRT) to the cell surface. Blockade or knock down of CRT suppressed the phagocytosis of anthracyclines-treated tumor cells by dendritic cells and abolished their immunogenicity in mammals, such as mice. The anthracyclines-induced CRT translocation was mimicked by inhibition of the protein phosphatase1/GADD34 complex. Administration of recombinant CRT or inhibitors of protein phosphatase1/GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify CRT as a key feature determining anti-cancer immune responses and delineate a possible strategy for immunogenic chemotherapy.

Abstract: Compounds and compositions are provided for modulating the activity of protein tyrosine phosphatases. In one embodiment, the compounds and compositions are thiazoles and thiadiazoles that inhibit the activity of protein tyrosine phosphatase 1B.

Abstract: The present invention relates to compounds of formula I which are prodrugs of caspase inhibitors and pharmaceutically acceptable salts thereof. This invention further relates to the release of caspase inhibitors from these compounds through selective bond cleavage. This invention further relates to pharmaceutical compositions comprising these compounds, which are particularly well-suited for treatment of caspase-mediated diseases, including inflammatory and degenerative diseases. This invention further relates to methods for preparing compounds of this invention.

Abstract: The present invention relates to compounds of formula I which are prodrugs of caspase inhibitors and pharmaceutically acceptable salts thereof. This invention further relates to the release of caspase inhibitors from these compounds through selective bond cleavage. This invention further relates to pharmaceutical compositions comprising these compounds, which are particularly well-suited for treatment of caspase-mediated diseases, including inflammatory and degenerative diseases. This invention further relates to methods for preparing compounds of this invention.

Abstract: Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R4 is —(CH2)n-Z-(CH2)m—PO(OR7)(OR8), —(CH2)nZ-(CH2)m—PO(OR7)Rg, —(CH2)n-Z-(CH2)m—OPO(OR7)Rg, —(CH2)nZ—(CH2)m—OPO(R9)(R10), or —(CH2)nZ—(CH2)m—PO(R9)(R10); R5 and R6 are independently selected from H, alkyl and halogen; Y is R7(CH2)s or is absent; and X, n, Z, m, R4, R5, R6, R7, and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

Abstract: Fluorescent dyes and probes are key components in multiphoton based fluorescence microscopy imaging of biological samples. In order to address the demand for better performing dyes for two-photon based imaging, a new series of reactive fluorophores tailored for multiphoton imaging has been disclosed. These fluorophores are based upon the fluorene ring system, known to exhibit high fluorescence quantum yields, typically >0.7, and possess high photostability. They have been functionalized with moieties to act, e.g., as efficient amine-reactive fluorescent probes for the covalent attachment onto, e.g., proteins and antibodies. The synthesis and the single-photon spectral characteristics, as well as measured two-photon absorption cross sections of the reactive fluorophores in solution are presented. Spectral characterizations of bovine serum albumin (BSA) conjugated with the new reactive probe is presented.

Abstract: The present invention relates to N-substituted cyclic aza compounds, pharmaceutical compositions comprising such compounds, and methods of their use for effecting neuronal activities.

Abstract: The present invention relates to methods of use of aminodiphosphonate to modulate apolipoprotein E levels and the use of such compounds in therapy, including cardiovascular and neurological disease states.

Abstract: Compounds are provided which have the structure wherein Q is C or N, X1 is C or N, and R1, R2, R2a, R2b, R2c, R3, Y, A, m, n, X2, X3 and X4 are as defined herein, which compounds are useful as antidiabetic, hypolipidemic, and antiobesity agents.

Abstract: The present invention provides compounds that are inducers or inhibitors of apoptosis or apoptosis preceded by cell-cycle arrest. In addition, the present invention provides pharmaceutical compositions and methods for treating mammals with leukemia or other forms of cancer or for treating disease conditions caused by apoptosis of cells.