Abstract: Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, wherein Q1 is a phenyl ring, naphthalenyl ring system, a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each as described with optional substituents as defined in the disclosure; Q2 is a phenyl ring, a naphthalenyl ring system, a 5- to 6-membered saturated, partially unsaturated or fully unsaturated heterocyclic ring, or an 8- to 10-membered heteroaromatic bicyclic ring system, each as described with optional substituents as defined in the disclosure; X is O, S(O)m, NR4, CR15R16, C(?O) or C(?S); and R1, R1a, R2, R4, R15, R16 and m are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention.

Abstract: A method for treating an inflammatory disease or an immune disorder includes administering to a subject in need of such treatment an antagonist against ENO1. The antagonist binds ENO1 and inhibits ENO1 plasminogen receptor activity. The antagonist may be an anti-human ENO1 antibody, or an scFv, Fab, or F(ab)2 fragment thereof, that specifically binds to human ENO1 (GenBank: AAH50642.1) for the treatment of an inflammatory disease or an immune disorder, which may be multiple sclerosis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, systemic Lupus erythematosus, chronic obstructive pulmonary disease (COPD), asthma, allergy, psoriasis, type 1 diabetes mellitus, artherosclerosis or osteoporosis.

Abstract: The present invention relates to compounds of the formula I, wherein A, Y, Z, R3 to R6, R20 to R22 and R50 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. Specifically, they are inhibitors of the endothelial differentiation gene receptor 2 (Edg-2, EDG2), which is activated by lysophosphatidic acid (LPA) and is also termed as LPA1 receptor, and are useful for the treatment of diseases such as atherosclerosis, myocardial infarction and heart failure, for example. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use and pharmaceutical compositions comprising them.

Abstract: This disclosure relates to novel compounds containing an H2S releasing moiety and a nitric oxide (NO) releasing moiety covalently linked with a core (e.g., a salicylic acid moiety) and the use of such compounds in treating inflammatory diseases, including cancers. Therapeutic potency of these compounds is significantly higher than NSAIDs containing a H2S-releasing moiety alone (HS-NSAIDs) and NSAID containing a NO-releasing moiety alone (NO-NSAIDs). The compounds, in addition, exhibit reduced side effect, e.g., reduced stomach ulcers, upon administration.

Abstract: This application discloses pharmaceutical compositions (e.g., oral, parenteral or topical ophthalmic formulations) for treating Fuchs endothelial corneal dystrophy (FECD) with one or more Nrf2 activators and/or mitochondrially targeted antioxidants. The compositions may be topically administered to the eye and are effective in the treatment of FECD. The invention further provides methods of treating FECD by in a subject in need of such treatment by topical application of one or more Nrf2 activators and/or mitochondrially of the invention.

Abstract: Described herein are methods for modulation of the activity of the carotid body that afford therapeutic benefit for sleep-related breathing disorders and related conditions.

Abstract: The present invention is directed at methods for preventing or minimizing the intensity of the serotonin syndrome in humans and lower animals which comprises administering proserotonergic agents and serotonin surge protectors. The present invention is also directed to pharmaceutical compositions comprising proserotonergic agents and serotonin surge protectors useful for carrying out the method of the present invention.

Abstract: Compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are pharmaceutical compositions comprising the compounds, and methods of using the compounds in the treatment of cancer.

Abstract: Methods for the treatment or prevention of diseases which are caused by the degradation of histone deacetylase 2 (HDAC2) in cells are described. The diseases which may be treated by the methods of the invention include chronic obstructive pulmonary disease (COPD) and asthma. The invention provides methods for treating or preventing of diseases caused by the degradation of HDAC2 by providing to the subject in need of treatment or prevention a molecular compound capable of preventing the degradation of HDAC2. Such molecular compounds include protein kinase CK2 inhibitors, ubiquitination inhibitors, ubiquitin-proteosome inhibitors, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activators and MAPK phosphatase 1 activators. Methods are also provided for the treatment and prevention of diseases caused by the degredation of HDAC2 by interfering with the expression of protein kinase CK2 or by increasing expression of Nrf2.

Abstract: This invention provides a method for treating or preventing malaria in a subject. The method includes administering to the subject an effective amount of a substituted tetracycline compound, such that malaria is treated or prevented. In one aspect, the invention relates to pharmaceutical compositions which include an effective amount of a tetracycline compound to treat malaria in a subject and a pharmaceutically acceptable carrier. The substituted tetracycline compounds of the invention can be used to in combination with one or more anti-malarial compounds or can be used to treat or prevent malaria which is resistant to one or more other anti-malarial compounds.

Abstract: Fluorene-based molecules and their derivatives are described in compositions for the treatment of intestinal fluid loss.

Abstract: The present invention provides new derivatives of 4- or 5-aminosalicylic acid, and a pharmaceutical composition containing these derivatives of 4- or 5-aminosalicylic acid as active ingredients, useful for the treatment of intestinal diseases such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and for the prevention/treatment of colon cancer. More particularly, these derivatives comprise a hydrogen sulfide releasing moiety linked via an azo, an ester, an anhydride, a thioester or an amide linkage to a molecule of 4- or 5-aminosalicylic acid. Furthermore, the present invention provides a process for preparing these compounds and their use for treating IBD and IBS and the prevention/treatment of colon cancer.

Abstract: 7-substituted fused ring tetracycline compounds, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7-substituted fused ring tetracycline compounds are described.

Abstract: Astrocytes possess important roles in maintaining normal brain function and providing trophic support to the neurons. They also suffer a range of toxic insults, being a chief target of prooxidants such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA), 4-hydroxy-2-nonenal (HNE), and acrolein. Recently, we have observed that the cellular antioxidants and phase 2 enzymes can be upregulated by 3H-1,2-dithiole-3-thione (D3T), a nutraceutical found in cruciferous vegetables, against many prooxidants in human neuroblastoma cell lines (SH-SY5Y). However, the regulation of the above cellular factors by D3T in astrocytes and their role in ameliorating the neurotoxic effects of the above neurotoxins have not been investigated.

Abstract: A powder composition, includes: (A) an oil-soluble antioxidant substance powder; (B) a water-soluble antioxidant substance powder; and (C) thioctic acid.

Abstract: The present invention relates to derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) having improved anti-inflammatory properties useful in the treatment of inflammation, pain and fever. More particularly, NSAIDs are derivatized with a hydrogen sulfide (H2S) releasing moiety to produce novel anti-inflammatory compounds having reduced side effects.

Abstract: The present invention relates to new prostaglandin derivatives having improved pharmacological activity and enhanced tolerability. They can be employed for the treatment of glaucoma and ocular hypertension.

Abstract: The present invention relates to derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) having improved anti-inflammatory properties useful in the treatment of inflammation, pain and fever. More particularly, NSAIDs are derivatized with a hydrogen sulfide (H2S) releasing moiety to produce novel anti-inflammatory compounds having reduced side effects.

Abstract: Cosmetic and therapeutic, in particular dermatological bioprecursors have the formula [A]n—PP—[B]m wherein PP is a polyphenol radical in which each hydroxyl function is protected by a group A or a group B, A is a saturated or unsaturated, substituted or unsubstituted alkyl radical having 1 to 20 carbon atoms which is bonded to the polyphenol, n is an integer not less than 1, and B is a precursor of a biologically active molecule, which is also bonded to the polyphenol, and m is an integer also not less than 1.

Abstract: The present invention provides methods and compositions for the prophylaxis of blood cell disorders such as neutropenia, thrombocytopenia, lymphocytopenia, and anaemia. The invention provides methods wherein compositions comprising at least one cytokinin compound are administered either therapeutically or prophylactically. The invention further has utility in methods of DNA repair.

Abstract: The present invention provides new derivatives of 4- or 5-aminosalicylic acid, and a pharmaceutical composition containing these derivatives of 4- or 5-aminosalicylic acid as active ingredients, useful for the treatment of intestinal diseases such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and for the prevention/treatment of colon cancer. More particularly, these derivatives comprise a hydrogen sulfide releasing moiety linked via an azo, an ester, an anhydride, a thioester or an amide linkage to a molecule of 4- or 5-aminosalicylic acid. Furthermore, the present invention provides a process for preparing these compounds and their use for treating IBD and IBS and the prevention/treatment of colon cancer.

Abstract: Compounds of general formula: wherein R?, R, x and z have the meaning reported in the specification, are useful for treating inflammatory diseases including metabolic syndrome, diabetes, obesity, dyslipidemia, and insulin resistance.

Abstract: Novel methods for inhibiting angiogenesis and treating diseases associated with angiogenesis are described. The methods may comprise administering to a patient an effective amount of a 1,2-dithiol-3-thione derivative or metabolite thereof. Preferred compounds for use in the methods include 5-(2-pyrazinyl)-4methyl-1,2-dithiol-3-thione (Oltipraz) and its metabolites.

Abstract: A 1,2,4-triazole derivative of formula 1 or a non-toxic salt thereof, a preparation method thereof, and a pharmaceutical composition containing the derivative or the salt as an active ingredient are provided.

Abstract: Compounds of the structure I: are useful for treating bacterial growth, wherein E is selected from the group consisting of B, P, and S, T1 and T2 are each independently selected from the group consisting of O, NR, and CH2, where R=H or C1-C8 alkyl, or C1-C8 oxoalkyl, and L is selected from the group consisting of ethylene, propylene, and four to six-membered alicyclic and aromatic rings, provided that structure I does not include AI-2-borate. The compounds may be used to treat bacterial infections in human beings and to regulate biofilm formation. Pharmaceutical compositions comprising one or more such compounds are useful for treating bacterial infections in human beings.

Abstract: Novel diphenylethylene compounds and derivatives thereof containing thiazolidinedione or oxazolidinedione moieties are provided which are effective in lowering blood glucose level, serum insulin, triglyceride and free fatty acid levels in animal models of Type II diabetes. In contrast to previously reported thiazolidinedione compounds, known to lower leptin levels, the present compounds increase leptin levels and have no known liver toxicity. The compounds are disclosed as useful for a variety of treatments including the treatment of inflammation, inflammatory and immunological diseases, insulin resistance, hyperlipidemia, coronary artery disease, cancer and multiple sclerosis.

Abstract: Novel methods for inhibiting angiogenesis and treating diseases associated with angiogenesis are described. The methods may comprise administering to a patient an effective amount of a 1,2-dithiol-3-thione derivative or metabolite thereof. Preferred compounds for use in the methods include 5-(2-pyrazinyl)-4methyl-1,2-dithiol-3-thione (Oltipraz) and its metabolites.

Abstract: Novel diphenylethylene compounds and derivatives thereof containing thiazolidinedione or oxazolidinedione moieties are provided which are effective in lowering blood glucose level, serum insulin, triglyceride and free fatty acid levels in animal models of Type II diabetes. In contrast to previously reported thiazolidinedione compounds, known to lower leptin levels, the present compounds increase leptin levels and have no known liver toxicity. The compounds are disclosed as useful for a variety of treatments including the treatment of inflammation, inflammatory and immunological diseases, insulin resistance, hyperlipidemia, coronary artery disease, cancer and multiple sclerosis.

Abstract: A compound of the formula (I): wherein A is alkylene optionally having an unsaturated bond; R is —C(?O)—R1; R1 is hydroxy or the like; m is 0 or 1; p is 0 or 1; X1 and X3 are each independently optionally substituted aryl or optionally substituted heteroaryl or the like; X2 is a bond, —CH2—, —S—, —SO2—, —CH2—O—, —O—CH2—, —CH2—S—, —S—CH2—, or the like; X4 is —CH2—, —CH2—CH2—, —C(?O)—, or the like, having a dual antagonistic activity against both a thromboxane A2 receptor and a prostaglandin D2 receptor is found.

Abstract: Compounds of the structure I: are useful for treating bacterial growth, wherein E is selected from the group consisting of B, P, and S, T1 and T2 are each independently selected from the group consisting of O, NR, and CH2, where R?H or C1–C8 alkyl, or C1–C8 oxoalkyl, and L is selected from the group consisting of ethylene, propylene, and four to six-membered alicyclic and aromatic rings, provided that structure I does not include AI-2-borate. The compounds may be used to treat bacterial infections in human beings and to regulate biofilm formation. Pharmaceutical compositions comprising one or more such compounds are useful for treating bacterial infections in human beings.

Abstract: Compositions and methods for using these compositions to produce high yields of thionated compounds are provided.

Abstract: The production of a purified extracellular bacterial signal called autoinducer-2 is regulated by changes in environmental conditions associated with a shift from a free-living existence to a colonizing or pathogenic existence in a host organism. Autoinducer-2 stimulates LuxQ luminescence genes, and is believed also to stimulate a variety of pathogenesis related genes in the bacterial species that produce it. A new class of bacterial genes is involved in the biosynthesis of autoinducer-2.

Abstract: Described herein are compounds related to lactacystin and lactacystin ?-lactone, pharmaceutical compositions containing the compounds, and methods of use.

Abstract: The present invention relates to inhibiting the production of TSST-1 using absorbent products and non-absorbent products comprising an additive, as well as methods for inhibiting such production. The absorbent and non-absorbent products or articles include an effective amount of an inhibitory compound, such as thiolactomycin or thiomalonate to substantially inhibit the production of TSST-1 or exoprotein by Gram positive bacteria.

Abstract: 7-substituted fused ring tetracycline compounds, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7-substituted fused ring tetracycline compounds are described.

Abstract: Methods are provided for inhibiting stenosis following vascular trauma or disease in a mammalian host, comprising administering to the host a therapeutically effective dosage of a therapeutic conjugate containing a vascular smooth muscle binding protein that associates in a specific manner with a cell surface of the vascular smooth muscle cell, coupled to a therapeutic agent dosage form that inhibits a cellular activity of the muscle cell. Methods are also provided for the direct and/or targeted delivery of therapeutic agents to vascular smooth muscle cells that cause a dilation and fixation of the vascular lumen by inhibiting smooth muscle cell contraction, thereby constituting a biological stent.

Abstract: P51084 The present invention relates to sulfonamides, pharmaceutical compositions containing them, and their use as antagonists of urotensin II.

Abstract: The invention provides autoinducer-2 analogs that regulate the activity of autoinducer-2 and methods of using such analogs for regulating bacterial growth and pathogenesis.

Abstract: The present invention is directed to isolated nucleic acid molecules that encode LIM mineralization protein, or LMP. The invention further provides vectors comprising nucleotide sequences that encode LMP, as well as host cells comprising those vectors. Moreover, the present invention relates to methods of inducing bone formation by transfecting osteogenic precursor cells with an isolated nucleic acid molecule comprising a nucleotide sequence encoding LIM mineralization protein. The transfection may occur ex vivo or in vivo by direct injection of virus or naked plasmid DNA. In a particular embodiment, the invention provides a method of fusing a spine by transfecting osteogenic precursor cells with an isolated nucleic acid molecule having a nucleotide sequence encoding LIM mineralization protein, admixing the transfected osteogenic precursor cells with a matrix and contacting the matrix with the spine.

Abstract: The present invention relates to pharmaceutically acceptable compounds, including certain substituted indolinyl and derivatives thereof, 1,2,3,4-tetrahydroquinolinyl and derivatives thereof, 1,2,3,4-tetrahydroisoquinolinyl, benz[cd]indolinyl and 5,6-dihydrophenanthridinyl compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are particularly useful for the treatment or prophylaxis of neurological injury and neurodegenerative disorders.

Abstract: The present invention provides new methods for the treatment of viral hepatitis C involving the administration of vitamin E and other compounds with antioxidant properties. Treatment with high doses of vitamin E is effective in treating chronic hepatitis C in patients refractory to interferon. In addition, new methods are described for the treatment of hepatic fibrosis and hepatic conditions manifesting hepatic fibrosis involving the administration of butylated hydroxytoluene and a metabolite of pentoxifylline, 1-[3-carboxypropyl]-3,7-dimethylxanthine. Furthermore, new methods are described for the treatment and prevention of hepatic disorders involving the use of 2,6-di-tert-butylphenol derivatives.

Abstract: Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

Abstract: Compounds related to lactacystin and lactacystin &bgr;-lactone, pharmaceutical compositions containing the compounds, and methods of use.

Abstract: The present invention is directed to a biocompatible tissue reactive composition comprising a functionalized polymer having tissue reactive substituents that are capable of forming covalent bonds with tissue associated functional groups.

Abstract: Methods are provided for inhibiting stenosis following vascular trauma or disease in a mammalian host, comprising administering to the host a therapeutically effective dosage of a therapeutic conjugate containing a vascular smooth muscle binding protein that associates in a specific manner with a cell surface of the vascular smooth muscle cell, coupled to a therapeutic agent dosage form that inhibits a cellular activity of the muscle cell. Methods are also provided for the direct and/or targeted delivery of therapeutic agents to vascular smooth muscle cells that cause a dilation and fixation of the vascular lumen by inhibiting smooth muscle cell contraction, thereby constituting a biological stent. Also discussed are mechanisms for in vivo vascular smooth muscle cell proliferation modulation, agents that impact those mechanisms and protocols for the use of those agents.

Abstract: A method for treating HIV infection in human beings comprising the step of measuring viremia, and if viremia is less than 50,000-100,00 copies per milliliter, administering a combination of compounds selected from the group consisting of hydroxyurea, and one or more reverse transcriptase inhibitors.

Abstract: Compounds related to lactacystin and lactacystin &bgr;-lactone, pharmaceutical compositions containing the compounds, and methods of use.

Abstract: Cysteine protease inhibitors which deactivate the protease by covalently bonding to the cysteine protease and releasing the enolate of a 1,3-dicarbonyl (or its enolic form). The cysteine protease inhibitors of the present invention accordingly comprise a first portion which targets a desired cysteine protease and positions the inhibitor near the thiolate anion portion of the active site of the protease, and a second portion which covalently bonds to the cysteine protease and irreversibly deactivates that protease by providing a carbonyl or carbonyl-equivalent which is attacked by the thiolate anion of the active site of the cysteine protease to sequentially cleave a .beta.-dicarbonyl enol ether leaving group.

Abstract: The present invention is directed to pharmaceutical compositions including a saturated 1,2-dithiaheterocyclic compound having antiviral activity. The present invention also provides a kit containing the pharmaceutical composition and methods of treating or preventing viral disease using the composition, as well as methods for inactivating retrovirus in a body fluid.

Abstract: A method for inhibiting replication of reverse transcriptase dependent virus in plant or animal cells, comprising the step of administering to said cells a combination of compounds selected from the group consisting of hydroxyurea, a nucleoside analog, and a protease inhibitor.