Abstract: The present invention relates to targeting an intracellular enzyme for release of covalently linked bioactives which results in a synergistic effect between the bioactives. The present invention relates to the use of bioactives that are directly connected covalently or through a covalent molecular linker which have increased therapeutic activity when released as the free bioactives by intracellular enzymes as compared to when the bioactives are administered individually (i.e. not covalently linked). Further, methods are described of administering to patients in need thereof, bioactives as linked bioactives having increased therapeutic activity. Accordingly, this invention also relates to methods of treating patients for certain diseases.

Abstract: Pro-drugs of 1-(2-halo-biphenyl-4-yl)alkanecarboxylic acids are useful for preventing and/or treating neurodegenerative diseases, improving cognitive function and treating cognitive impairment.

Abstract: Anti-agglomerants for gas hydrates, comprising alkoxylated and/or acylated non-quaternary nitrogen-containing compounds, method for inhibiting the agglomeration of gas hydrates in a conduit, and compositions comprising the gas hydrate anti-agglomerant, a corrosion inhibitor and/or a paraffin deposition inhibitor.

Abstract: The present invention relates to a process for the preparation of a compound of the general Formula (I), comprising: a) reacting a compound of the general Formula (II) with a compound of the Formula III R2COOH and a compound of the general Formula IV R3NC under such conditions that compound I is formed, wherein R1 represents a substituted or unsubstituted alkyl, alkenyl, alkynyl, aromatic or non-aromatic, mono-, di- or tricyclic, or heterocyclic structure, and R2 represents a substituted or unsubstituted alkyl, alkenyl, alkynyl, aromatic or non-aromatic, mono-, di- or tricyclic, or heterocyclic structure, and R3 represents a substituted or unsubstituted alkyl, alkenyl, or alkynyl structure. In further aspect the subject invention relates to the use of the the obtained products as intermediates for various peptidomimetics, and preferably as a building block in a convergent synthesis of prolyl dipeptide structures.

Abstract: An inventive substrate is provided which includes a substrate compound of formula A-B1-B2-B3-B4: wherein A is a sugar moiety; B1 is a linker moiety allowing the conjugation of moiety A and the remaining structure of the substrate; B2 is a linker moiety with a free reactive amino group so as to be available for reaction with carboxylic acids or detectable tags; B3 contains a permanently charged element such as a quaternary ammonium group so as to increase sensitivity for mass spectrometry analysis; and B4 of various carbon length conferring specificity amongst individual substrates in detection methods. Also provided is a molecule of the formula B1-B2-B3-B4, with similar structural characteristics to an enzymatic product produced by the action of a target enzyme on an inventive substrate. Further provided are methods for using inventive substrates for detecting enzymatic activity.

Abstract: Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (IOP) may be achieved.

Abstract: The present invention is directed to compounds that are allosteric inhibitors of tumor necrosis factor receptor I, compositions comprising such compounds, and methods of using such compounds and compositions thereof in the treatment of TNF-? mediated conditions.

Abstract: The present invention relates to a process for the preparation of a compound of the general Formula (I), comprising: a) reacting a compound of the general Formula (II) with a compound of the Formula III R2COOH and a compound of the general Formula IV R3NC under such conditions that compound I is formed, wherein R1 represents a substituted or unsubstituted alkyl, alkenyl, alkynyl, aromatic or non-aromatic, mono-, di- or tricyclic, or heterocyclic structure, and R2 represents a substituted or unsubstituted alkyl, alkenyl, alkynyl, aromatic or non-aromatic, mono-, di- or tricyclic, or heterocyclic structure, and R3 represents a substituted or unsubstituted alkyl, alkenyl, or alkynyl structure. In further aspect the subject invention relates to the use of the obtained products as intermediates for various peptidomimetics, and preferably as a building block in a convergent synthesis of prolyl dipeptide structures.

Abstract: This invention relates to the field of biologically active compounds and specifically to closthioamides, pharmaceutical compositions comprising these compounds, and their use as antibiotic, antifungal, and/or cytotoxic agent.

Abstract: Pro-drugs of 1-(2-halo-biphenyl-4-yl)alkanecarboxylic acids are useful for preventing and/or treating neurodegenerative diseases, improving cognitive function and treating cognitive impairment.

Abstract: The invention provides amphiphilic macromolecules that are useful for delivering nucleic acids to cells and that are useful as delivery agents for gene therapy.

Abstract: The disclosed islet isolation method comprises: an injection step of injecting a preservation solution into the pancreatic duct of an excised pancreas; a preservation step of immersing the pancreas into an immersion fluid for preservation; a digestion step of breaking down the pancreas to provide pancreatic tissue; and a purification step of immersing the pancreatic tissue in a purification solution to provide islets. The digestion step consists of: an enzyme injection step of injecting an enzyme solution containing a digestion enzyme into the pancreas; a digestion initiation step of activating the digestion enzyme; a digestion termination step of inactivating the digestion enzyme; and a collection step of collecting the broken-down pancreatic tissue.

Abstract: Disclosed are inhibitors of retroviral growth of formula (I), that are useful in treatment of retroviral infections such as HIV. Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one compound or salt of the invention, a method for inactivating a virus, a method for dissociating a metal ion from a zinc finger-containing protein, and a method for inhibiting the transmission of a virus.

Abstract: The present invention is directed to compounds that are allosteric inhibitors of tumor necrosis factor receptor I, compositions comprising such compounds, and methods of using such compounds and compositions thereof in the treatment of TNF-? mediated conditions.

Abstract: The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

Abstract: The present invention relates to a process for the preparation of a compound of the general Formula (I), comprising: a) reacting a compound of the general Formula (II) with a compound of the Formula III R2COOH and a compound of the general Formula IV R3NC under such conditions that compound I is formed, wherein R1 represents a substituted or unsubstituted alkyl, alkenyl, alkynyl, aromatic or non-aromatic, mono-, di- or tricyclic, or heterocyclic structure, and R2 represents a substituted or unsubstituted alkyl, alkenyl, alkynyl, aromatic or non-aromatic, mono-, di- or tricyclic, or heterocyclic structure, and R3 represents a substituted or unsubstituted alkyl, alkenyl, or alkynyl structure. In further aspect the subject invention relates to the use of the obtained products as intermediates for various peptidomimetics, and preferably as a building block in a convergent synthesis of prolyl dipeptide structures.

Abstract: This invention relates to the field of biologically active compounds and specifically to closthioamides, pharmaceutical compositions comprising these compounds, and their use as antibiotic, antifungal, and/or cytotoxic agent.

Abstract: The present invention is directed to providing epoxycarboxamide compounds, azide compounds and amino alcohol compounds which serve as manufacturing intermediates that can lead to useful ?-ketoamide compounds, and the present invention is also is directed to processes for preparing ?-ketoamide compounds using the intermediates. The epoxycarboxamide compounds, azide compounds and amino alcohol compounds are represented by the following formulae: wherein R1, R2, R3, R4 and R5, as well as subvariables for one or more of R1, R2, R3, R4 and R5 are as defined herein.

Abstract: An oxime ester compound of formula (I) useful as a photopolymerization initiator. A photopolymerization initiator having the oxime ester compound as an active ingredient is activated through efficient absorption of light of long wavelength, e.g., 405 nm or 365 nm, to exhibit high sensitivity. In formula (I), R1 and R2 are each R11, OR11, COR11, SR11, CONR12R13, or CN; R11, R12, and R13 are each hydrogen, a C1-C20 alkyl group, C6-C30 aryl group, a C7-C30 arylalkyl group, or a C2-C20 heterocyclic group; R3 and R4 are each R11, OR11, SR11, COR11, CONR12R13, NR12COR11, OCOR11, COOR11, SCOR11, OCSR11, COSR11, CSOR11, CN, halogen, or a hydroxyl group; a and b is each 0 to 4; X is oxygen, sulfur, selenium, CR31R32, CO, NR33, or PR34; and R31, R32, R33, and R34 each have the same meaning as R1.

Abstract: The present invention relates to an aminimide compound having a structure represented by the following general formula (I) in the molecule thereof, relates to a curable composition using the aminimide compound and relates to a method for curing the composition; in which R0 represents a hydrogen atom, an alkyl group which may have an optional substituent, an aryl group which may have an optional substituent, or a heterocyclic residue which may have an optional substituent. R1, R2 and R3 each independently represent a hydrogen atom, or an optional substituent. However, at least two of R1, R2 and R3 may bond to each other to form a cyclic structure.

Abstract: It is reported herein that certain muscle diseases and conditions, including forms of muscular dystrophy, are characterized by impaired insulin-dependent signaling in the muscle tissue, in essence, a form of insulin resistance. The present disclosure relates to therapeutic agents, compositions and methods for treating a muscle disease or condition characterized by impaired insulin-dependent signaling by targeting components of the defective insulin signaling pathway. The disease or condition may be treated by administering a therapeutic agent that activates the insulin signaling pathway, in particular, therapeutic agents that act post-insulin receptor to modulate intracellular effector molecules. An exemplary modulator is metformin. Metformin may be administered alone or may be co-administered with another therapeutic agent for treating the muscle disease or condition, such as a corticosteroid.

Abstract: High penetration compositions (HPC) of a parent compound, which are capable of crossing biological barriers with high penetration efficiency. The HPCs are capable of being converted to parent drugs or parent drug-related compounds such as metabolites after crossing one or more biological barriers and thus can render treatments for the conditions that the parent drugs or parent drug-related compounds can. Additionally, the HPCs are capable of reaching areas that their parent drugs or parent drug-related compounds may not be able to access or to render a sufficient concentration at the target areas HPCs of NSAIA, for example, have demonstrated indications such as treating hair loss. A HPC can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

Abstract: The invention provides certain bis-acylated hydroxylamine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the invention provides methods of using such compounds or pharmaceutical compositions for treating, preventing, or delaying the onset and/or develop of a disease or condition. In some embodiments, the disease or condition is selected from cardiovascular diseases, ischemia, reperfusion injury, cancerous disease, pulmonary hypertension and conditions responsive to nitroxyl therapy.

Abstract: The present invention relates to azolin-2-ylamino compounds of formula (I), wherein A is a radical of the formulae (A.1) or (A.2), wherein * denotes the binding site and wherein the indices and variables are as defined in the description. The present invention relates as well as to the precursor compounds thereof, which are both useful for combating animal pests selected from insects, arachnids and nematodes. The invention also relates to methods for controlling and/or combating such animal pests by using these compounds, to methods of protecting crops and plant propargation material, and further also to seeds and agricultural and veterinary composition comprising said compounds.

Abstract: Methods and compositions are provided that include degradable gemini surfactants including degradable gemini surfactants. Methods of use include subterranean operations, especially those involving the placement of resin systems, formation of emulsions (e.g., emulsified acids, emulsified fracturing fluids, drilling fluids, etc.), and in the formation of surfactant gelled fluids. Such treatments include, but are not limited to, drilling, stimulation treatments (e.g., fracturing treatments, acidizing treatments), and completion operations (e.g., sand control treatments like gravel packing).

Abstract: Embodiments of the present disclosure provide for prostratin analogs, bryostatin analogs, prodrugs of prostratin and prostratin analogs, methods of making prostratin analogs, and methods of making prodrugs of prostratin and prostratin analogs, methods of use of prostratin analogs, bryostatin analogs, and prodrugs thereof, and the like.

Abstract: A rust inhibitor usable for metal surface coating includes, as an effective component, a compound containing a chelate group, and a long chain alkyl group and/or a cyclic alkyl group, which are bonded by an ester bond or other bonds.

Abstract: The current invention provides novel thiotungstate derivatives, methods of making novel thiotungstate derivatives, pharmaceutical compositions of novel thiotungstate derivatives, methods of using novel thiotungstate derivatives to treat diseases associated with aberrant vascularization, copper metabolism disorders and obesity and methods of using pharmaceutical compositions of thiotungstate derivatives to treat diseases associated with aberrant vascularization, copper metabolism disorders, neurodegenerative disorders, obesity or NF-?B dysregulation.

Abstract: An oxime ester compound of formula (I) useful as a photopolymerization initiator. A photopolymerization initiator having the oxime ester compound as an active ingredient is activated through efficient absorption of light of long wavelength, e.g., 405 nm or 365 nm, to exhibit high sensitivity. In formula (I), R1 and R2 are each R11, OR11, COR11, SR11, CONR12R13, or CN; R11, R12, and R13 are each hydrogen, a C1-C20 alkyl group, C6-C30 aryl group, a C7-C30 arylalkyl group, or a C2-C20 heterocyclic group; R3 and R4 are each R11, OR11, SR11, COR11, CONR12R13, NR12COR11, OCOR11, COOR11, SCOR11, OCSR11, COSR11, CSOR11, CN, halogen, or a hydroxyl group; a and b is each 0 to 4; X is oxygen, sulfur, selenium, CR31R32, CO, NR33, or PR34; and R31, R32, R33, and R34 each have the same meaning as R1.

Abstract: Transition metal complexes include a diazaphosphacycle of formula III and a transition metal. The phosphorus atom of the diazaphosphacycle is bonded to the transition metal and the diazaphosphacycle of formula III has the following structure where the variables have the values set forth herein.

Abstract: The present invention provides novel compositions suitable for use in an intermolecular photodeprotection reaction scheme. Such compositions include a chromophore compound and a second compound having a photocleavable group bonded to a protected functional group. Novel compounds which can used in intramolecular photodeprotection are also provided. These compounds have a chromophore moiety bonded to a photocleavable group, which itself is bonded to a protected group. The compounds and compositions disclosed herein can be used in two-photon and multi-photon excitation.

Abstract: Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially A? amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.

Abstract: The invention relates to substituted amino-thiourea compounds of formula (I), to the enantiomers, diastereomers and salts thereof and to compositions comprising such compounds. The invention also relates to the use of the substituted amino-thiourea compounds, of their salts or of compositions comprising them for combating animal pests. Furthermore the invention relates also to methods of applying such compounds. The substituted amino-thiourea compounds are defined by the following formula (I): wherein A, B, R1, R2, R3, R4, R5.1, R5.2 and R6 are defined as in the description.

Abstract: The present invention relates to the use of a specific group of alkoxylated and/or acylated non-quaternary nitrogen-containing compounds as anti-agglomerants for gas hydrates. The anti-agglomerants are surface-active non-quaternary nitrogen-containing compounds with 1-5 nitrogen atoms, which compounds have at least one hydrophobic group with 6-24 carbon atoms, and where the hydrophobic group is connected to the remainder of the molecule by an amine moiety, an ether moiety or an amide moiety, provided that when the hydrophobic group is connected by means of an amide moiety to the remainder of the molecule, the compounds must contain a total of at least two nitrogen atoms, and optionally contain 1-12 —CH2CH2O— groups and/or 1-6 hydroxyalkyl groups with 3-4 carbon atoms; and which compounds have at least one C2-C3 acyl group and/or at least one hydroxyalkyl group with 3-4 carbon atoms; or a salt thereof.

Abstract: The present invention provides an AP-1 activation inhibitor, NF-kappa B activation inhibitor, inflammatory cytokine production inhibitor, matrix metalloprotease production inhibitor, inflammatory cell adhesion molecule expression inhibitor, anti-inflammatory agent, antirheumatic agent, immunosuppressant, cancer metastasis inhibitor, remedy for arteriosclerosis and antiviral agent which contain the benzene derivative of the following general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.

Abstract: The present invention provides carbohydrate analogs of the formula: wherein X is CH2, O, or NH, and R1-8 are independently H, a short hydrocarbon, a substituted amine, an alcohol, a substituted ether, a substituted amide, a substituted ketone, a substituted carboxylic acid, a short peptide, or a short oligosaccharide, Y is H, a short hydrocarbon, a short peptide, or a short oligosaccharide, and R9 is H, a short hydrocarbon, a substituted amine, an alcohol, a substituted ether, a substituted amide, a substituted ketone, a carboxylic acid, a short peptide, or a short oligosaccharide.

Abstract: This invention provides a class of androgen receptor targeting agents (ARTA). The agents define a new subclass of compounds, which are selective androgen receptor modulators (SARM). Several of the SARM compounds have been found to have an unexpected androgenic and anabolic activity of a nonsteroidal ligand for the androgen receptor. Other SARM compounds have been found to have an unexpected antiandrogenic activity of a nonsteroidal ligand for the androgen receptor.

Abstract: Compounds of formula I in which R1, R2, R3, each X, L, Y, Cy, Lp, D and n have the meanings as set out in the specification, and corresponding compounds in which the unsubstituted or substituted amidine group is replaced with an unsubstituted or substituted aminomethyl group, are useful as serine protease inhibitors.

Abstract: The invention relates to a novel class of aminobenzophenones derivatives, to pharmaceutical preparations comprising said compounds, to dosage units of such preparations, to methods of treating patients comprising administering said compounds, and to the use of said compounds in the manufacture of pharmaceutical preparations.

Abstract: A class of acyl sulfamides comprises compounds that are potent ligands for PPAR gamma and generally have antagonist or partial agonist activity. The compounds may be useful in the treatment, control or prevention of obesity, non-insulin dependent diabetes mellitus (NIDDM), hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, vascular restenosis, inflammation, and other PPAR gamma mediated diseases, disorders and conditions.

Abstract: The invention relates to semicarbazides of the general formula I where R1, R2, R3, R4 and I have the meaning indicated in claim 1. The compounds of the formula I can be employed as pharmaceutical active compounds in human and veterinary medicine, in particular for the control and prevention of thromboembolic disorders such as thrombosis, mycocardial infarct, arteriosclerosis, inflammation, apoplexy, angina pectoris, restenosis after angioplasty and intermittent claudication.

Abstract: This invention relates to novel compounds of Formula (I) to (VII), and compositions thereof, useful in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).

Abstract: The novel compound 3-amidinobenzoyl-D-phenylglycine-3-phenylanilide is useful as a serine protease inhibitor.

Abstract: The present invention is related to new vanilloid analogues containing resiniferatoxin pharmacophores, pharmaceutical compositions that have such analogues, and their uses as vanilloid receptor agonists and potent analgesics. The present invention provides a pharmaceutical composition for preventing, alleviating or treating pain, acute pain, chronic pain, neuropathic pain, post-operative pain, migraine, arthralgia, neutopathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fervescence, stomach-duodenal ulcer, inflammatory bowel disease, inflammatory disease or urgent urinary incontinence.

Abstract: The present invention provides an AP-1 activation inhibitor, NF-kappa B activation inhibitor, inflammatory cytokine production inhibitor, matrix metalloprotease production inhibitor, inflammatory cell adhesion molecule expression inhibitor, anti-inflammatory agent, antirheumatic agent, immunosuppressant, cancer metastasis inhibitor, remedy for arteriosclerosis and antiviral agent which contain the benzene derivative of the following general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.

Abstract: Compounds of Formula I are antagonists of VLA-4 and/or &agr;4&bgr;7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of AIDS-related dementia, allergic conjunctivitis, allergic rhinitis, Alzheimer's disease, asthma, atherosclerosis, autologous bone marrow transplantation, certain types of toxic and immune-based nephritis, contact dermal hypersensitivity, inflammatory bowel disease including ulcerative colitis and Crohn's disease, inflammatory lung diseases, inflammatory sequelae of viral infections, meningitis, multiple sclerosis, multiple myeloma, myocarditis, organ transplantation, psoriasis, pulmonary fibrosis, restenosis, retinitis, rheumatoid arthritis, septic arthritis, stroke, tumor metastasis, uveititis, and type I diabetes.

Abstract: Compounds of formula (i) and of formula (ii) wherein the symbols have the meaning disclosed in the specification, specifically or selectively modulate &agr;2B and/or &agr;2C adrenergic receptors in preference over &agr;2A adrenergic receptors, and as such are useful for alleviating chronic pain and allodynia and have no or only minimal cardivascular and/or sedatory activity.

Abstract: The present invention provides novel aminoadamantane derivatives, methods of making the derivatives, compositions including the novel aminoadamantane derivatives, and methods for the treatment and prevention of neurological diseases using the derivatives and compositions.

Abstract: This invention relates to compounds of formula which inhibit Factor Xa, to pharmaceutical compositions containing the compounds, and to the use of the compounds for the treatment of patients suffering from conditions which can be ameliorated by the administration of an inhibitor of Factor Xa.

Abstract: The invention concerns novel glyoxylic acid derivatives, a process for their preparation and their use as pesticides.