Abstract: Imidazole prodrugs, pharmaceutically acceptable salts, or isomers thereof, of the invention are disclosed, which are useful as modulators of the activity of liver X receptors (LXR). Pharmaceutical compositions containing the compounds and methods of using the compounds are also disclosed.

Abstract: Administration of a hypoxia activated prodrug in combination with an antiangiogenic agent is useful for treating cancer.

Abstract: The present invention relates to compositions and methods for the treating and empirically investigating conditions associated with neuronal dysfunction (e.g., chronic pain, epileptic neuronal activity). In particular, the present invention provides compositions and methods for using flufenamic acid in the treatment and empirical investigation of conditions associated with neuronal dysfunction (e.g., chronic pain, epileptic neuronal activity).

Abstract: The present invention relates to a pharmaceutical composition comprising a bisphosphonate or a pharmaceutically acceptable salt thereof for preventing or treating diabetes mellitus and a method of preventing or treating diabetes mellitus comprising single or multiple administration of the pharmaceutical composition to a patient in need thereof.

Abstract: The present invention relates to novel active ingredient combinations which consist of fluopyram and other known active ingredients and are very well suited for the control of animal pests, such as insects and/or unwanted acarids and/or nematodes, in foliar and soil application and/or in the treatment of seeds, and are also suitable for increasing yields.

Abstract: In one aspect, the invention relates to compounds having the formula XII: where Ra, Rb, R2, R7, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds described herein are prodrugs of compounds having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising these compounds; methods of using these compounds; and processes and intermediates for preparing these compounds.

Abstract: The invention is directed to a method of administering hydrogen sulfide (H2S) slowly and sustainably to an individual in need thereof comprising administering an effective amount of a compound represented by the following structural formula: or a pharmaceutically acceptable salt thereof.

Abstract: In one aspect, the invention relates to compounds having the formula X: where Ra, Rb, R2, R7, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds described herein are prodrugs of compounds having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising these compounds; methods of using these compounds; and processes and intermediates for preparing these compounds.

Abstract: Preparation and characterization of novel forms of (1-hydroxy-2-imidazol-1-yl-1-phosphono-ethyl) phosphonic acid, suitable for pharmaceutical compositions in drug delivery systems for humans.

Abstract: Oral dosage forms of bisphosphonate compounds, such as zoledronic acid, can be used to treat or alleviate pain or related conditions. Although an oral dosage form with enhanced bioavailability with respect to the bisphosphonate compound can be used, the treatment can also be effective using an oral dosage form that includes a bisphosphonate compound, such as zoledronic acid, wherein the bioavailability of the bisphosphonate is unenhanced, or is substantially unenhanced.

Abstract: Oral dosage forms of bisphosphonate compounds, such as zoledronic acid, can be used to treat or alleviate pain or related conditions. Although an oral dosage form with enhanced bioavailability with respect to the bisphosphonate compound can be used, the treatment can also be effective using an oral dosage form that includes a bisphosphonate compound, such as zoledronic acid, wherein the bioavailability of the bisphosphonate is unenhanced, or is substantially unenhanced.

Abstract: Oral dosage forms of bisphosphonate compounds, such as zoledronic acid, can be used to treat or alleviate pain or related conditions. Although an oral dosage form with enhanced bioavailability with respect to the bisphosphonate compound can be used, the treatment can also be effective using an oral dosage form that includes a bisphosphonate compound, such as zoledronic acid, wherein the bioavailability of the bisphosphonate is unenhanced, or is substantially unenhanced.

Abstract: Oral dosage forms of bisphosphonate compounds, such as zoledronic acid, can be used to treat or alleviate pain or related conditions. Although an oral dosage form with enhanced bioavailability with respect to the bisphosphonate compound can be used, the treatment can also be effective using an oral dosage form that includes a bisphosphonate compound, such as zoledronic acid, wherein the bioavailability of the bisphosphonate is unenhanced, or is substantially unenhanced.

Abstract: The present invention provides novel pyrazolines that are useful as cannabinoid receptor blockers and pharmaceutical compositions thereof and methods of using the same for treating obesity, diabetes, inflammatory disorders, cardiometabolic disorders, hepatic disorders, and/or cancers.

Abstract: Disclosed herein are methods for treating obesity, metabolic syndrome, diabetes, or a combination of these conditions. The methods include selecting a subject with obesity, metabolic syndrome, or diabetes and administering to the subject a therapeutically effective amount of a composition comprising a compound that specifically inhibits hepatic protein kinase C (PKC)-?, thereby treating the obesity, metabolic syndrome, or diabetes in the subject. In some embodiments the compound that specifically inhibits hepatic PKC-? includes a thio-gold compound (such as aurothiomalate, aurothioglucose, and auranofin) or a derivative thereof, or a pharmaceutically acceptable salt thereof. In other embodiments, the compound that specifically inhibits hepatic PKC-? includes 1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl]-[1R-(1?,2?,3?,4?)] (ICAPP) or a derivative thereof, or a pharmaceutically acceptable salt thereof.

Abstract: Hypoxia activated prodrugs, such as, e.g., TH-281, TH-302, and TH-308, are useful for the treatment of various blood cancers, such as acute leukemias, chronic leukemias, MDS, MF, and multiple myeloma.

Abstract: The invention relates to the use of a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor and of a farnesyl-pyrophosphate synthase inhibitor, or of one of their associated physiologically acceptable salts, in the preparation of a composition, particularly a pharmaceutical composition, for use in the treatment of human or animal, pathological or nonpathological situations related to the accumulation and/or the persistence of prenylated proteins in cells, such as during progeria (Hutchinson-Gilford syndrome), restrictive dermopathy or physiological ageing.

Abstract: Compositions containing, and, methods administering, TH302, are useful in treatment of cancer and other hyper-proliferative diseases.

Abstract: This invention relates to biomaterials, said biomaterials for use in methods to control and/or induce bone growth. Particularly, the invention relates to macroporous calcium phosphate biomaterials pre-loaded with certain amounts of osteoclastic activity inhibitors for use in methods to control and/or induce bone growth in primates.

Abstract: Phosphoramidate alkylator prodrugs can be used to treat cancer when administered alone or in combination with one or more anti-neoplastic agents.

Abstract: Cancer can be treated by administration of a hypoxia-activated prodrug, such as TH-302, alone or in combination with other anticancer agents and/or radiation therapy. In combination therapy, the hypoxia-activated prodrug and another anti-cancer agent or radiation therapy may be administered within the same 24-hour period, and administration of the hypoxia-activated prodrug may be completed prior to beginning administration of the other anticancer agent or radiation therapy.

Abstract: The present invention relates to a pyrazole amide derivative, pharmaceutical compositions containing this compound and to its use in therapy.

Abstract: The subject invention pertains to uses of PKC-iota inhibitors for treatment of breast cancer. In one embodiment, the subject invention provides novel uses of 1H-imidazole-4-carboxamide, 5-amino-1-[2,3 -dihydroxy-4-[(phosphonooxy) methyl]cyclopentyl]-,[1R-(1?, 2?, 3?, 4?)] (ICA-1) and related compounds for treatment of breast cancer. The compounds of the subject invention have potent anti-proliferative effects against human breast cancer cells. The compounds of the subject invention also inhibit the phosphorylation of IKK-?/IKK-?, induce chromatin condensation, and/or induce DNA fragmentation in cancer cells.

Abstract: The pesticidal compositions comprising synergistic mixtures of O,O-dimethyl S-phthalimidomethyl phosphorodithioate or suitable salt forms thereof, and at least one benzoylurea based chitin inhibiting compound or suitable salt forms thereof, and especially preferably one or more of (RS)-1-[3-chloro-4-(1,1,2-trifluoro-2-trifluoromethoxyethoxy)phenyl]-3-(2,6-di-fluorobenzoyl)urea (also interchangeably referred to as “novaluron”) or suitable salt forms thereof, and 1-(2-chlorobenzoyl)-3-(4-trifluoromethoxyphenyl)urea (also interchangeably referred to as “triflumuron”) or suitable salt forms thereof, for the control of undesired pests, preferably for the control of Codling moths in fruit. Methods of controlling the incidence of undesired pests, via treatment regimens providing synergistic amounts of each of the foregoing compounds, are also disclosed.

Abstract: The invention provides a novel compound having a structure corresponding to Formula (I): (A)-(B)—(C)-(D)??(I) or a pharmaceutically acceptable salt or prodrug thereof and methods for using them.

Abstract: The present invention relates to novel amine derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of sphingosine-1-phosphate receptors.

Abstract: Methods for treating neurodegeneration, e.g., sensorineural hearing loss, or a demyelinating disease, using bisphosphonates, ERK kinase inhibitors, and osteoprotegerin (OPG) proteins or nucleic acids.

Abstract: The present invention relates to novel 2,5-dioxoimidazolidin-1-yl-3-phenylurea derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor like-1 (FPRL-1) receptor.

Abstract: Bisphosphonamidate prodrugs of therapeutic bisphosphonate compounds and uses thereof to treat diseases are described.

Abstract: The present invention generally relates to compositions and kits comprising a ?2-AR agonist and a modulator of a ?2-AR regulator gene, where the modulator of the ?2-AR regulator gene inhibits the internalization and/or degradation of the ?2-ad-renergic receptor (?2-AR). More specifically, the present invention relates to the use of an agonist of ?2-adrenergic receptor (?2-AR) and an agent which inhibits agonist induced ?2-adrenergic receptor (?2-AR) internalization and/or degradation in method for the treatment of a respiratory disorder in a subject.

Abstract: Embodiments of the invention are directed to methods of treating reperfusion or resuscitation injury in an individual in need of such treatment, comprising the step of administering to the individual who has had, having, or is at immediate risk of having an ischemic event an amount of a composition comprising a protein kinase A (PKA) activator and a ?1-adrenergic receptor antagonist sufficient to reduce reperfusion injury to an ischemic tissue.

Abstract: The present invention relates to amide compounds, processes for their preparation, pharmaceutical compositions containing these compounds and to their use in the treatment of disorders, conditions or disorders such as allergic disorders, inflammatory disorders and disorders of the immune system.

Abstract: Preparation, in-vitro and in vivo characterization of novel forms of (1-hydroxy-2-imidazol-1-yl-1-phosphono-ethyl)phosphonic acid, suitable for pharmaceutical compositions in drug delivery systems for humans.

Abstract: The present invention pertains to use of PKC-iota inhibitors for treatment of glioma. In a specific embodiment, the treatment method comprises administering ICA-1 or a salt thereof to a subject with glioma. In another embodiment, the treatment method comprises contacting glioma cells with an effective amount of ICA-1 or a salt thereof.

Abstract: Novel compounds are disclosed that have a Formula represented by the following: wherein X, R1, R2a, R2b, R2c, R3a R3b, R4a, R4b, R4c, and m1 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cachexia, osteoporosis, sarcopenia, a decline in libido and/or sexual dysfunction.

Abstract: An injectable pharmaceutical composition contained in a receptacle for injection into a human, which comprises a solution of zoledronic acid or the salts thereof, a solvent and a pH regulator.

Abstract: Methods of and kits for determining the pharmacogenetic, pharmacokinetic and cellular basis of bisphosphonate-induced osteonecrosis of the jaw (BONJ) involve associating particular proteins and particular single nucleotide polymorphisms with a risk for developing BONJ after receiving bisphosphonate treatment. Methods and kits for identifying the genetic basis for a patient's predisposition to BONJ, and methods of identifying patients who are prone to develop BONJ following bisphosphonate administration provide for the development of a tool for physicians to prescribe treatment protocols for BONJ patients based on the patients' genomes (“personal/tailored medicine”). A haplotype tagging SNP approach was used to analyze candidate genes involved in bone absorption and destruction and to examine the influence of genetic variants on the susceptibility of BONJ. Bone biomarkers of BONJ were examined using molecular cell techniques.

Abstract: Preparation and in vitro and in vivo characterization of novel forms of active pharmaceutical ingredients, suitable for pharmaceutical compositions in drug delivery systems for humans.

Abstract: Compositions for pharmaceutical use are described, comprising bisphosphonates and vitamin D in high concentration, destined to the intramuscular and subcutaneous intermittent administration for treatment of bone and skeletal system diseases, particularly osteoporosis, and sensitive cancers. These formulations are characterized by the use of a lipid and phospholipid emulsion at high concentration, having optimal carrier and solvent power for both the pharmacologically active components.

Abstract: A method of intravenously administering a bisphosphonate to a patient in need of bisphosphonate treatment comprising intravenously administering 4 mg of 2-(imidazol-1yl)-1-hydroxyethane-1,1-diphosphonic acid (zoledronic acid) or a pharmaceutically acceptable salt thereof over a period of 15 minutes to a patient in need of said treatment.

Abstract: A method of detecting prostate tumorigenesis in a subject, the method including the steps of (a) obtaining a sample from the prostate of the human subject, (b) detecting quantitatively or semi-quantitatively in the sample a level of expression for PKC-? and (c) comparing the expression level in (b) to a level of expression in a normal control, wherein overexpression of PKC-?, with respect to the control, indicates the presence of prostate cancer in the subject. The present invention is based upon the discovery that PKC-? levels are elevated during prostate tumorigenesis. Furthermore, the proliferation rate of the tumor correlates with the level of PKC-?. The invention also provides methods of treating prostate cancer by administering to the subject a compound that inhibits the expression of PKC-?. The compound can be a small interfering RNA (siRNA) molecule.

Abstract: A method of treating a warm-blooded animal, especially a human, having a proliferative disease or acute or chronic transplant rejection comprising administering to the animal a combination which comprises (a) N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine and (b) a chemotherapeutic agent selected from antineoplastic agents, especially as defined herein, and agents effective in treating acute or chronic transplant rejection; a combination comprising (a) and (b) as defined above and optionally at least one pharmaceutically acceptable carrier for simultaneous, separate or sequential use, in particular for the delay of progression or treatment of a proliferative disease, especially a solid tumor disease.

Abstract: The present invention relates to compounds of general formula (I) as tublin polymerization inhibitors and methods for preparing such compounds.

Abstract: Disclosed herein are methods for treating obesity, metabolic syndrome, diabetes, or a combination of these conditions. The methods include selecting a subject with obesity, metabolic syndrome, or diabetes and administering to the subject a therapeutically effective amount of a composition comprising a compound that specifically inhibits hepatic protein kinase C (PKC)-?, thereby treating the obesity, metabolic syndrome, or diabetes in the subject. In some embodiments the compound that specifically inhibits hepatic PKC-? includes a thio-gold compound (such as aurothiomalate, aurothioglucose, and auranofin) or a derivative thereof, or a pharmaceutically acceptable salt thereof. In other embodiments, the compound that specifically inhibits hepatic PKC-? includes 1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl]-[1R-(1?,2?,3?,4?)] (ICAPP) or a derivative thereof, or a pharmaceutically acceptable salt thereof.

Abstract: Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.

Abstract: The present invention provides for methods and compositions for treating and/or preventing cardiac dysfunction by administering to subject a therapeutically effective amount of a bisphosphonate, functional analogue or a pharmaceutically effective salt thereof.

Abstract: The present invention relates to a series of substituted 3-aminopropane phosphinic acid derivatives of formula I: wherein R, R1, P1, P2 and P3 are as defined herein. The compounds of this invention are useful in treating a variety of diseases including but not limited to depression, anxiety, certain psychiatric symptoms, cognitive impairment and schizophrenia.

Abstract: The present disclosure relates to salts and compositions of isophosphoramide mustard and isophosphoramide mustard analogs. In one embodiment the salts can be represented by the formula wherein A+ represents an ammonium species selected from the protonated (conjugate acid) or quaternary forms of aliphatic amines and aromatic amines, including basic amino acids, heterocyclic amines, substituted and unsubstituted pyridines, guanidines and amidines; and X and Y independently represent leaving groups. Also disclosed herein are methods for making such compounds and formulating pharmaceutical compositions thereof. Methods for administering the disclosed compounds to subjects, particularly to treat hyperproliferative disorders, also are disclosed.

Abstract: Novel solution complexes of zoledronic acid are described which give rise to improved properties of zoledronic acid. The invention includes aqueous solution and molecular complexes of zoledronic acid with and optical isomers of asparagine, histidine, arginine and proline as well as pharmaceutical complexes containing them and methods of treatment using them.

Abstract: Novel compounds are disclosed that have a Formula represented by the following: wherein X, R1, R2a, R2b, R2c, R3aR3b, R4a, R4b, R4c, and m1 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cachexia, osteoporosis, sarcopenia, a decline in libido and/or sexual dysfunction.