Abstract: Administration of a modulator of cell cycle checkpoint activation, which is preferably ?-lapachone, or a pharmaceutically acceptable salt, prodrug, metabolite, analog or derivative thereof, protects normal cells against radiation injury. The invention includes methods of preventing radiation damage. The invention also provides methods for treating conditions such as cancer with radiotherapy, by administering a modulator of cell cycle checkpoint activation to a subject, prior to administration of radiotherapy.

Abstract: The present invention relates to polymer-modified quinone-containing and carbonyl-containing therapeutic agents, including polymer-modified ?-lapachone compounds, and methods of treating cancer by administering the polymer-modified therapeutic agents to a subject. Polymer-modification of therapeutic agents, such as ?-lapachone compounds, provides effective transport of polymer-modified therapeutic agents to tumor cells or tumor tissues by exploiting the EPR effect in tumor tissues.

Abstract: The invention provides lapachone analogs and derivatives as well as methods of use thereof. These compounds can be used in pharmaceutical compositions for the treatment or prevention of cell proliferation disorders. These compounds can also be used in the treatment or prevention of cancer or precancerous conditions.

Abstract: The present invention provides imidazooxazole and imidazothiazole compounds and their synthesis. The compounds of the present invention are capable of inhibiting the activity of RAF kinase, such as B-RAFV600E. The compounds are useful for the treatment of cell proliferative disorders such as cancer.

Abstract: The present invention provides tetrazole compounds, and methods of preparation of these compounds. The present invention also relates to pharmaceutical compositions comprising the tetrazole compounds. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a compound of the present invention.

Abstract: The present invention relates to quinazolinone compounds, and methods of preparation of these compounds. The present invention also relates to pharmaceutical compositions comprising the quinazolinone compounds.

Abstract: The present invention provides imidazooxazole and imidazothiazole compounds and their synthesis. The compounds of the present invention are capable of inhibiting the activity of RAF kinase, such as B-RAFV600E. The compounds are useful for the treatment of cell proliferative disorders such as cancer.

Abstract: Cancers and/or malignancies can be treated by administration of a cell cycle checkpoint activator, which is preferably ?-lapachone, or a derivative or analog thereof, combined with an oncogenic kinase modulator, preferably imatinib. This combination of the cell cycle checkpoint activator with the oncogenic kinase modulator results in an unexpectedly greater than additive (i.e., synergistic) apoptosis in cancer cells. The invention includes methods of treating cancers by administering the combination of the cell cycle checkpoint activator and the oncogenic kinase modulator, pharmaceutical compositions comprising the combination of drugs used in these methods, as well as pharmaceutical kits.

Abstract: The invention relates to a group of novel triazine derivatives which are ligands for human adenosine-A3 receptors, as well as to pharmaceutical compositions containing a pharmacologically active amount of at least one of these compounds as an active ingredient. The invention relates to compounds of the general formula (1) wherein Y represents a group of the general formula (A), (B) or (C) and all other symbols have the meanings as given in the description.

Abstract: Compounds of Formula I, wherein R1—R8 are defined herein are provided, together with pharmaceutically acceptable salts, hydrates, metabolites, and/or prodrugs thereof. Uses of these compounds for inhibiting beta amyloid production and for the prevention and treatment of Alzheimer's Disease and Down's syndrome are also described.

Abstract: Compounds of Formula I, wherein R1–R8 are defined herein are provided, together with pharmaceutically acceptable salts, hydrates, metabolites, and/or prodrugs thereof. Uses of these compounds for inhibiting beta amyloid production and for the prevention and treatment of Alzheimer's Disease and Down's syndrome are described.

Abstract: Beta-lapachone, which is poorly soluble in most pharmaceutically acceptable solvents, has demonstrated significant antineoplastic activity against human cancer lines. The present invention overcomes this significant limitation by teaching novel pharmaceutical compositions comprising a therapeutically effective amount of Beta-lapachone, or a derivative or analog thereof, and a pharmaceutically acceptable solubilizing carrier molecule, which may be at water-solubilizing carrier molecule such as hydroxypropyl-?-cyclodextrin, or an oil-based solubilizing carrier molecule, for enhancing the solubility of Beta-lapachone in aqueous solution. The therapeutically effective amount of Beta-lapachone, or a derivative or analog thereof, may be complexed with the pharmaceutically acceptable solubilizing carrier molecule in aqueous solution. The novel pharmaceutical compositions may be administered with a second anticancer agent or in combination with radiation therapy.

Abstract: A method for obtaining compounds having selected properties for a particular application by forming base modules having at least two structural diversity elements from the reaction of a first compound having at least one structural diversity element and a first reactive group, with a second compound having at least one structural diversity element and a second reactive group, wherein the first and second groups combine by an addition reaction; producing a first array of molecules by varying at least one of the structural diversity elements of the compounds when producing the base modules; and screening the array to determine a first suitable compound for the particular application. The base modules are preferably formed form oxazolone- and aminimide-derived compounds.

Abstract: Beta-lapachone, which is poorly soluble in most pharmaceutically acceptable solvents, has demonstrated significant antineoplastic activity against human cancer lines. The present invention overcomes this significant limitation by teaching novel pharmaceutical compositions comprising a therapeutically effective amount of Beta-lapachone, or a derivative or analog thereof, and a pharmaceutically acceptable solubilizing carrier molecule, which may be at water-solubilizing carrier molecule such as hydroxypropyl-?-cyclodextrin, or an oil-based solubilizing carrier molecule, for enhancing the solubility of Beta-lapachone in aqueous solution. The therapeutically effective amount of Beta-lapachone, or a derivative or analog thereof, may be complexed with the pharmaceutically acceptable solubilizing carrier molecule in aqueous solution. The novel pharmaceutical compositions may be administered with a second anticancer agent or in combination with radiation therapy.

Abstract: A method for constructing an array of synthetic molecular constructs, by forming a plurality of molecular constructs having a scaffold backbone of a chemical molecule comprising a linear, branched or cyclic organic compound having at least atoms of carbon, nitrogen, sulfur, phosphorus, or combinations thereof, and at least one location on the molecule capable of undergoing reaction with other molecules for attachment of at least one structural diversity element; laying out an array possessing a logical ordering of sub-arrays of the molecular constructs; providing each sub-array with molecular constructs having the scaffold backbone and at least one structural diversity element which is different from the others; and relating each sub-array within the array to all other sub arrays by the difference in the structural diversity elements.

Abstract: Compounds of Formula (I), wherein R1, R2, R3, R4, R5, R6, T, W, X, Y and Z are as defined herein are provided, together with pharmaceutically acceptable salt, hydrates and/or prodrugs thereof.

Abstract: Cleavable alkene-containing linkers and supports useful for the solid phase synthesis of chemical compounds, and combinatorial libraries of compounds, are disclosed. Also disclosed are methods of making and using the linkers and supports.

Abstract: Compounds of Formula I, 1

Abstract: Compounds of Formula (I), 1

Abstract: Reactive sites on a substrate molecule, typically a drug, may be identified and the relative rates of their metabolism by the CYP enzymes may be determined. Determining these relative rates is an important factor in determining the absolute rate of metabolism of the individual sites and the substrate molecule as a whole. This information is also a critical factor in determining whether and how the substrate can be redesigned to improve its ADME/PK properties. In this regard, it is particularly important to know how the relative rates compare to the rate of a non-metabolic side reaction (branch pathway) such as water generation and regeneration of the substrate.