Abstract: Processes for preparing substituted oxindole-2-ones, and specifically the following, are described, wherein R1-R4, R6, and n are defined herein. The processes include reacting a first alkali metal hydroxide, a tetraalkyl ammonium salt, a benzonitrile, and R6X or XCH2(CH2)nX?, wherein R6 is C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, or substituted heterocyclic, X and X? are, independently, leaving groups, and n is 1 to 5; (ii) reacting the product of step (i) with a second alkali metal hydroxide at a temperature of at least about 60° C.; (iii) reacting the product of step (ii) with an alkali alkoxide at a temperature of at least about 140° C. to form an oxindol-2-one; (iv) brominating the oxindol-2-one; and (v) coupling the brominated oxindol-2-one with a coupling reagent.

Abstract: The present invention provides a compound of formula I, pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof.

Abstract: The present invention relates generally to substituted sulfonamide indoles such as substituted sulfonamide indoles, and methods of using them.

Abstract: This invention provides compounds of formula 1, having the structure wherein R1, R2, R3, R4, and R5 are described within the specification.

Abstract: A method is disclosed for preparing hydrazides from hydrazine and an acyl chloride which comprises the steps of (a) preparing a stirred substantially uniform slurry comprising hydrazine and an inert solvent at low temperature; and (b) adding an acyl chloride continuously to said slurry. The method avoids or limits production of undesired bis-hydrazide by-products. The method is used to prepare 3-methyl-3-mercaptobutanoic acid hydrazide, a molecule used to link calicheamicin to a monoclonal antibody.

Abstract: The present invention provides a compound of formula I wherein one of A and B is hydrogen and the other an optionally substituted fused bicyclic heteroaryl group; and X is O, pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof.

Abstract: Novel polymorph Form II and III, solvate Forms I, II, III, and IV, and the hydrate of 5-(4?-fluoro-2?-oxo-1?,2?-dihydrospiro[cyclopropane-1,3?-indol]-5?-yl)-1-methyl-1H-pyrrole-2-carbonitrile are provided, as are methods for preparing the same. Pharmaceutical compositions and kits containing these novel polymorphs, solvates, and hydrate, and combinations thereof are further provided, as are methods of contraception; treating or preventing fibroids, uterine leiomyomata, endometriosis, dysfunctional bleeding, polycystic ovary syndrome, hormone-dependent carcinomas; treating symptoms of premenstrual syndrome and premenstrual dysphoric disorder; providing hormone replacement therapy; stimulating food intake; synchronizing estrus; or treating symptoms of premenstrual syndrome using one or more of these polymorphs, solvates, or hydrate.

Abstract: The present invention relates to methods of treating ADAMTS-5-associated diseases and particularly osteoarthritis comprising administering an agent capable of modulating ADMATS-5 activity to a subject afflicted with the disease. The agent is preferably a biaryl sulfonamide compound. The invention is based, in part, on the discovery that transgenic animals that do not express functional ADAMTS-5 show a reduction in the degree of osteoarthritis after the induction of osteoarthritis as compared to WT animals. Furthermore, the ADAMTS-5 transgenic animals have reduced aggrecanase activity in articular tissue as compared to WT animals. These animals are good models for ADAMTS-5-associated diseases, and for screening of drugs useful in the treatment and/or prevention of these diseases. There are no other animal models in which the deletion of the activity of a single gene is capable of abrogating the course of osteoarthritis.

Abstract: The present invention is directed to methods/systems for measuring the pH of a cell culture medium in a small-scale system utilizing a pH-sensitive dye. The present invention is also directed to methods for predicting the performance of cells in a large-scale culture system.

Abstract: Mutant cholera holotoxins having single or double amino acid substitutions or insertions have reduced toxicity compared to the wild-type cholera holotoxin. The mutant cholera holotoxins are useful as adjuvants in antigenic compositions to enhance the immune response in a vertebrate host to a selected antigen from a pathogenic bacterium, virus, fungus, or parasite, a cancer cell, a tumor cell, an allergen, or a self-molecule.

Abstract: The present invention relates generally to substituted acetic acid derivatives and methods of using them.

Abstract: The present invention relates to the field of anti-inflammatory substances, and more particularly to novel compounds that act as antagonists of the mammalian adhesion proteins known as selectins. In some embodiments, methods for treating selectin mediated disorders are provided which include administration of compound of Formula I: wherein the constituent variables are defined herein.

Abstract: A system and method for high throughput patch clamp measurements to study the effect of various chemicals on ion transfer channels is provided. One or more patch clamp configurations is established, each comprising a cell sealed to a pipette. The pipettes are affixed to a pipette fixture. The pipette fixture and a plate comprising one or more wells are relatively moved so that each cell is inside a well. Electrical properties of the cells are measured.

Abstract: The present invention relates to the field of anti-inflammatory substances, and more particularly to novel compounds that act as antagonists of the mammalian adhesion proteins known as selectins. In some embodiments, methods for treating selectin mediated disorders are provided which include administration of compound of Formula I: wherein the constituent variables are defined herein.

Abstract: A compound of the formulae (I) or (II): wherein: Y is a moiety selected from NR or —(CH2)n; wherein R is hydrogen or (C1-C6) lower alkyl, and n is 1; represents: (1) a phenyl ring optionally substituted with one or two substituents selected, independently, from the group comprising hydrogen, (C1-C6) lower alkyl, halogen, cyano, CF3, hydroxy, (C1-C6) lower alkoxy, (C1-C6) lower alkoxy carbonyl, carboxy, —CONH2, —CONH[(C1-C6) lower alkyl], —CON[(C1-C6) lower alkyl]2; or (2) a 6-membered aromatic (unsaturated) heterocyclic ring having one nitrogen atom, optionally substituted by (C1-C6) lower alkyl, halogen or (C1-C6) lower alkoxy; represents: (1) a phenyl ring optionally substituted with one or two substituents selected, independently, from the group comprising hydrogen, (C1-C6) lower alkyl, halogen, cyano, CF3, hydroxy, (C1-C6) lower alkoxy, or (C1-C6) lower alkoxy carbonyl, carboxy, —CONH2, —CONH[(C1-C6) lower alkyl], —CON[(C1-C6) lower alkyl]2; or (2) a 5-membered aromatic (unsaturated

Abstract: This invention provides a method of treating solid tumors which comprises administering an effective amount of a combination of (1) a bioresponse modifier and (2) a chemotherapeutic agent. This invention also provides a method of potentiating the effects of a chemotherapeutic regimen in a mammal in need of treatment with such regimen which comprises administering a bioresponse modifier in addition to a chemotherapeutic regimen.

Abstract: The present invention relates to a stable, antiparasitic, non-aqueous pour-on parasiticidal composition which comprises an effective amount of amitraz, optionally a macrocyclic lactone, a stabilizer and a carrier system having no active hydroxyl group.

Abstract: The present invention provides a compound of formula I and the use thereof for the treatment of a central nervous system disorder related to or affected by the 5-HT6 receptor.

Abstract: Compounds of the structure: are provided. Also provided are methods of using these compounds as progesterone receptor modulators. Also described are methods of producing these compounds from a Verticillium species.

Abstract: The present invention provides a 2-amino-5-heteroaryl-5-phenylimidazolone compound of formula I The present invention also provides methods for the use thereof to inhibit ?-secretase (BACE) and treat ?-amyloid deposits and neurofibrillary tangles