Abstract: In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.

Abstract: A method of increasing the bioavailability of balsalazide by administration of an oral dosage form with food is provided, as well as an article of manufacture comprising an oral dosage form of balsalazide in a suitable container and associated with printed labeling which describes the increased bioavailability of the medication in the container when taken with food.

Abstract: Compounds are provided that act as potent antagonists of the CCR1 receptor, and which have been further confirmed in animal testing for inflammation, one of the hallmark disease states for CCR1. The compounds are generally aryl piperazine derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR1-mediated diseases, and as controls in assays for the identification of competitive CCR1 antagonists.

Abstract: Disclosed herein are methods of treating lentigo maligna, superficial spreading malignant melanoma, acral lentiginous malignant melanoma or nodular malignant melanoma with bis(thio-hydrazide amides) represented by a formula selected from structural formulas (i)-(ix) or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising these bis(thio-hydrazide amides) and compositions comprising these bis(thiohydrazide)amides and one or more anti-cancer agent.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a compound. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal patched pathway or agonizing smoothened or hedgehog activity.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel ecdysone receptor/chimeric retinoid X receptor-based inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large-scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: Disclosed are compounds of the Formula I and pharmaceutically acceptable salts and prodrugs thereof, wherein W, R1, R2, R7, R8, R9 and R10 are as defined in the specification. Such compounds are MEK inhibitors and useful in the treatment of hyperproliferative diseases, such as cancer and inflammation, in mammals. Also disclosed is a method of using such compounds in the treatment of hyperproliferative diseases in mammals, and pharmaceutical compositions containing such compounds.

Abstract: The present invention provides novel compounds that demonstrate protective effects on target cells from HIV infection in a manner as to bind to a chemokine receptor, and which affect the binding of a natural ligand or chemokine to a receptor, such as CXCR4 of a target cell.

Abstract: Pyrimidinedione derivatives of the general formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts and pharmaceutically acceptable compositions containing them are useful for the treatment of inflammation and immunological diseases.

Abstract: Efflux pump inhibitors are co-administered with antimicrobial agents for the treatment of ophthalmic or otic infections. The agents may be co-administered directly to the site of infection (e.g., the eye or ear).

Abstract: The present invention includes compositions and methods for the treatment and prevention of conditions associated with Respiratory Syncytial Virus (RSV) infection. RSV-associated conditions include acute infections in mammals, typically bronchiolitis and pneumonia, and post-infectious chronic respiratory conditions. In particular, the present invention describes new therapeutic and preventative uses for 3,3?-diindolylmethane (DIM), or a DIM-related indole, alone or in combination with an inhibitor of a membrane bound Epidermal Growth Factor Receptor (EGFR) inhibitors, to treat conditions associated with exposure to RSV.

Abstract: The present invention is related to a novel method for splitting nucleic acids at specific points on a complementary nucleic acid segment using a dinuclear copper-based compound of Formula I. Additionally, the present invention is related to a novel treatment of cancer, tumors, and cancer cells using a dinuclear copper-based compound of Formula I or a naked ligand of formula II: (Formula I and II).

Abstract: It is described the use of thymosin alpha in combination with dacarbazine and optionally with Interferon alpha, for preparing a medicament for the treatment of malignant melanoma on stage IV characterized by distant unresectable metastases.

Abstract: A compound of Formula I are provided: wherein R is: R1 is a substituted or unsubstituted alkyl group; W1-4 are independently selected from hydrogen, substituted or unsubstituted alkyl groups, substituted or unsubstituted haloalkyl groups, substituted or unsubstituted alkanoyl groups, substituted or unsubstituted aroyl groups, or substituted or unsubstituted haloalkanoyl groups; X1-5 are independently selected from H, NO2, N3, and NH2;Y is absent or is a substituted or unsubstituted C1-alkyl group, other than carbonyl; Z is selected from a bond or NH, provided that when Z is a bond, Y is absent, and provided that when Z is NH, Y is a substituted or unsubstituted C1-alkyl group, other than carbonyl. Also provided are D-arabinitol compounds, methods for preparing such compounds and compositions of such compounds, and methods of using such compounds.

Abstract: This invention concerns N-(ortho phenylaminoaryl), N?-alkyl sulfamides which are inhibitors of MEK and are useful in the treatment of cancer and other hyperproliferative diseases.

Abstract: The present invention relates to novel heterocyclic compounds of the general formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts and compositions, metabolites and prodrugs thereof. The present invention more particularly provides novel hetereocycles of the general formula (I).

Abstract: The present invention provides agents that decrease carbonyl stress comprising biguanides, such as metoformin. Through oral administration and such, the carbonyl stress-decreasing agents of the present invention are useful as drugs directly acting against carbonyl stress in vivo.

Abstract: Group A streptogramin derivatives of general formula (I) in which: R1 represents a halogen atom or an azido or thiocyanato radical, R2 represents a hydrogen atom or a methyl or ethyl radical, R3 represents a hydrogen atom, or the residue of an aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic or heterocyclylaliphatic ester which may be substituted, and the bond --- represents a single bond (stereochemistry 27R) or a double bond, as well as its salts when they exist

Abstract: Methods for modulating macrophage proliferation in an individual afflicted with or at risk for a macrophage-associated disease are provided. The methods employ a polyamine analog, or salt or protected derivative thereof. Macrophage proliferation has been implicated in a number of serious disorders, including AIDS (HIV)-associated dementia, AIDS-associated non-Hodgkin's lymphoma, and Alzheimer's disease. The invention also provides methods for aiding diagnosis and monitoring therapy of a macrophage-associated non-HIV associated dementia, especially Alzheimer's disease. The invention also provides methods of delaying development of macrophage-associated non-HIV associated dementias, including Alzheimer's disease, which entail administration of an agent which modulates macrophage proliferation.

Abstract: The invention provides methods and compositions for azide tagging of biomolecules. In one embodiment of the invention, proteins are tagged by metabolic incorporation of prenylated azido-analog substrates. Examples of such analogs are azido farnesyl diphosphate and azido farnesyl alcohol. The azido moiety in the resulting modified proteins provides an affinity tag, which can be chemoselectively captured by an azide-specific conjugation reaction, such as the Staudinger reaction, using a phosphine capture reagent. When the capture agent is biotinylated, the resulting conjugates can be detected and affinity-purified by streptavidin-linked- HRP and streptavidin-conjugated agarose beads, respectively. The invention allows detection and isolation of proteins with high yield, high specificity, and low contamination without harsh treatment of proteins.

Abstract: This invention provides methods for screening a modulating agent which when combined with antitumor therapeutic agent increases apoptosis in tumor cells. This invention also provides methods for screening antitumor therapeutic agents suitable for combination therapy with a protein kinase C inhibitors capable of potentiating apoptosis in tumor cells. This invention further provides different combination therapies comprising the specific protein kinase C inhibitors and the antitumor therapeutic agents.

Abstract: Disclosed is both a method and composition for controlling deleterious organisms, such as insects, nematodes and weeds by applying a compound comprised of a liquid medium comprising azide and amine. The azide can be selected from the group consisting of sodium azide and potassium azide or a combination of the two. The composition provides an effective pesticide, without causing significant harm to the environment. The composition may be applied to soil to control a population of a deleterious organism.

Abstract: The present invention discloses novel photoactive compounds that may be crosslinked to target substrates. Methods for the preparation and use of the compounds, as well as compositions comprising them, are also disclosed.

Abstract: Disclosed is both a method and composition for controlling deleterious organisms, such as insects, nematodes and weeds while maintaining beneficial soil organisms, by applying a compound comprised of a liquid medium and comprising an azide and an amino acid polymer. The azide can be selected from the group consisting of sodium azide and potassium azide or a combination of the two. The composition provides an effective pesticide, without causing significant harm to the environment. The composition may be applied to soil to control a population of a deleterious organism.

Abstract: Novel formulations containing a fluorinated chloramphenicol or thiamphenicol derivative antibiotic such as florfenicol, and methods for using such formulations in the treatment and prevention of infectious diseases of bovines and swine, including bovine respiratory disease.

Abstract: This invention relates to substituted isoquinoline derivatives and their use as anticonvulsants.

Abstract: The present invention is drawn to methods of characterization of the properties and functions of SV2 proteins. The invention further includes methods of identifying compounds or agents which modulate the activity of SV2 proteins. Included in these methods is the identification of compounds or agents which modulate the binding of levetiracetam to SV2 proteins, including SV2A. Additionally, the present invention provides biotinylated ligands as a tool to screen chemical libraries and characterize the SV2 proteins. Further, the present invention provides a method of solubilizing and purifying functionally active membrane associated proteins, such as SV2.

Abstract: Novel formulations combining an antiparasitic compounds, such as an avermectin, with a fluorinated chloramphenicol or thiamphenicol derivative antibiotic such as Florfenicol are disclosed. Methods for using such formulations in the treatment and prevention of infectious diseases of bovines and swine, including bovine respiratory disease and parasitic infections are also disclosed.

Abstract: The present invention provides aqueous Ifosfamide compositions and a process for their preparation, in which the compositions have a reduced toxicity over and above the concomitant use of the uroprotective agent, Mesna. Aqueous Ifosfamide compositions can be prepared at concentrations as high has 1,1000 mg/ml.

Abstract: The present invention provides substituted azetidinone compounds, formulations and processes for preparing the same which can be useful for treating vascular conditions such as atherosclerosis or hypercholesterolemia, diabetes, obesity, stroke, demyelination and lowering plasma levels of sterols and/or stanols in a subject.

Abstract: The present invention discloses novel aromatic azide derivatives and their bioconjugates for phototherapy of tumors and other lesions. The organic azides of the present invention are designed to absorb low-energy ultraviolet, visible, or near-infrared (NIR) region of the electromagnetic spectrum. The phototherapeutic effect is caused by direct interaction of nitrene, the reactive intermediate produced upon photoexcitation of the aromatic azide, with the tissue of interest. The compounds of the present invention are administered to a patient, allowed to accumulate at the site of the tumor or other lesion, and are exposed to light in order to perform a phototherapeutic procedure.

Abstract: The present invention provides substituted azetidinone compounds, formulations and processes for preparing the same which can be useful for treating vascular conditions such as atherosclerosis or hypercholesterolemia, diabetes, obesity, stroke, demyelination and lowering plasma levels of sterols and/or stanols in a subject.

Abstract: Novel formulations combining a non-steroidal anti-inflammatory drug (NSAID) such as flunixin, with a fluorinated chloramphenicol or thiamphenicol derivative antibiotic such as florfenicol are disclosed. Methods for using such formulations in the treatment and prevention of infectious diseases of bovines and swine, including bovine respiratory disease and swine respiratory disease, are also disclosed.

Abstract: Compounds which are active against viruses have the following Formulas: wherein B is a purine or pyrimidine heterocyclic ring and is preferably selected from the group consisting of 6-aminopurine (adenine), 2,6-diaminopurine, 2-amino-6-azidopurine, 2-amino-6-cyclopropylaminopurine, 6-hydroxypurine (hypoxanthine), 2-amino-6-halo substituted purines, 2-amino-6-alkoxy substituted purines, 2-amino-6-hydroxypurine (guanine), 3-deazapurines, 7-deaza-purines, 8-azapurines, cytosine, 5-halo substituted cytosines, 5-alkyl substituted cytosines, thymine, uracil and 6-azapyrimidines; X is O; and, R1 and R2 are alkyl or aryl groups. The compounds of the present invention also include the R- and S-enantiomers of the above compounds. The R1X and/or R2X can also be amino acid residues with X as NH.

Abstract: The invention encompasses novel compounds of Formula I, which are nitric oxide-releasing prodrugs of diaryl-2-(5H) furanones useful in the treatment of cyclooxygenase-2 mediated diseases.

Abstract: The invention relates to compounds of the formulas 1 and 2 and to prodrugs thereof, pharmaceutically acceptable salts or solvates of said compounds or said prodrugs, wherein X, R1 and R11 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formulas 1 and 2 and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formulas 1 and 2.

Abstract: The present invention relates to a novel class of androgen receptor targeting agents (ARTA), which contain a haloacetamide or azide moiety and are alkylating agents.

Abstract: Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of indole-3-carbinol metabolites wherein the structures and substituents of the compounds are selected to enhance the compounds' overall efficacy, particularly with respect to therapeutic activity, oral bioavailability, long-term safety, patient tolerability, and therapeutic window. The compounds are useful not only in treatment of cancer but also in prevention of cancer.

Abstract: 11,12-Oxidoarachidonic acid derivatives and methods of their use for treating dry eye are disclosed.

Abstract: Certain fatty acids and related compounds useful in the control nematodes that infest plants or the situs of plants are described. Nematodes that parasitize animals can also be controlled using the methods and compounds of this invention.

Abstract: Tricyclic compounds according to the structure below, protected intermediates thereof, and methods for inhibition of HIV-integrase are disclosed.

Abstract: One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including G-protein-coupled receptors (GPCRs). A third aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian kinases.

Abstract: The present invention is directed to methods of using pro-NAD agents capable of enhancing the dermal and epidermal skin cell NAD content. These pro-NAD agents may be administered topically, orally, or parenterally to enhance DNA repair and other protective responses to DNA damage. The invention further relates to pharmaceutical compositions comprising pro-NAD agents that effectively elevate intracellular NAD content. Finally, the invention relates to the method of using the pro-NAD agents to treat disorders such as sunburn and other skin deterioration that results from DNA damage in skin cells.

Abstract: Methods of treating select mammalian disorders using a leukotriene antagonist are described.

Abstract: The present invention relates generally to the enantiomers of para-hydroxy-milnacipran or congeners thereof. Biological assays revealed that racemic para-hydroxy-milnacipran is approximately equipotent in inhibiting serotonin and norepinephrine uptake (IC50=28.6 nM for norepinephrine, IC50=21.7 nM for serotonin). Interestingly, (+)-para-hydroxy-milnacipran is a more potent inhibitor of norepinephrine uptake than serotonin uptake (IC50=10.3 nM for norepinephrine, IC50=22 nM for serotonin). In contrast, (−)-para-hydroxy-milnacipran is a more potent inhibitor of serotonin uptake compared to norepinephrin uptake (IC50=88.5 nM for norepinephrine, IC50=40.3 nM for serotonin). The invention also relates to salts and prodrug forms of the aforementioned compounds. In certain embodiments, the compounds of the present invention and a pharmaceutically acceptable excipient are combined to prepare a formulation for administration to a patient.

Abstract: This invention provides compounds of Formula (Ia)-(If) 1

Abstract: Methods and novel intermediates for the preparation of and the treatment with acyclic nucleoside derivatives of the formula: 1

Abstract: This invention relates to the novel use of amide squaramides in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).

Abstract: The present invention is generally drawn to novel isolated therapeutic agents, termed resolving, generated from the interaction between a dietary omega-3 polyunsaturated fatty acid (PUFA) such as eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), cyclooxygenase-II (COX-2) and an analgesic, such as aspirin (ASA). Surprisingly, careful isolation of compounds generated from the combination of components in an appropriate environment provide di- and tri-hydroxy EPA or DHA compounds having unique structural and physiological properties. The present invention therefore provides for many new useful therapeutic di- or tri-hydroxy derivatives of EPA or DHA (resolvins) that diminish, prevent, or eliminate inflammation or PMN migration, for example. The present invention also provides methods of use, methods of preparation, and packaged pharmaceuticals for use as medicaments for the compounds disclosed throughout the specification.

Abstract: Reagents and methods are provided for crosslinking and immobilizing biomolecules, drugs and synthetic polymers. The reagents possess (i) a thiol or amino reactive group; and (ii) a hydrazino or oxyamino moiety. Conjugates and immobilized biomolecules are also provided.