Abstract: This invention provides compounds of Formula I, having the structure: that are useful in treating diseases or disorders mediated by TNF-?. The invention further provides methods for use of the compounds for treating such a disease or disorder or for alleviating symptoms thereof.

Abstract: This invention relates to substituted indoline derivative compounds which are antagonists of the progesterone receptor, their preparation and pharmaceutical utility, particularly including contraception and treatment of benign or malignant neoplastic diseases, having the general structure: wherein R1 and R2 may be single substituents or fused to form spirocyclic rings.

Abstract: Compounds of the Formula I: are useful for the treatment of depression (including but not limited to major depressive disorder, childhood depression and dysthymia), anxiety, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder (also known as pre-menstrual syndrome), attention deficit disorder (with and without hyperactivity), obsessive compulsive disorder, social anxiety disorder, generalized anxiety disorder, obesity, eating disorders such as anorexia nervosa and bulimia nervosa, vasomotor flushing, cocaine and alcohol addiction, sexual dysfunction and related illnesses.

Abstract: This invention provides estrogen receptor modulators having the structure: wherein R1 to R7, R9 and R10 X, Y, and Z are as defined in the specification; or a pharmaceutically acceptable salt thereof.

Abstract: The present invention provides a compound of formula I and the use thereof for the therapeutic treatment of a CNS disorder relating to or affected by the 5-HT6 receptor.

Abstract: An improved system for large scale production of proteins and/or polypeptides in cell culture, particularly in media characterized by one or more of: i) a cumulative amino acid concentration greater than about 70 mM; ii) a molar cumulative glutamine to cumulative asparagine ratio of less than about 2; iii) a molar cumulative glutamine to cumulative total amino acid ratio of less than about 0.2; iv) a molar cumulative inorganic ion to cumulative total amino acid ratio between about 0.4 to 1; or v) a combined cumulative glutamine and cumulative asparagine concentration between about 16 and 36 mM, is provided. The use of such a system allows high levels of protein production and lessens accumulation of certain undesirable factors such as ammonium and/or lactate. Additionally, culture methods including a temperature shift, typically including a decrease in temperature when the culture has reached about 20-80% of it maximal cell density, are provided.

Abstract: The present invention provides probe arrays and methods of using the same for concurrent and discriminable detection of multiple strains of different species. In one aspect, the probe arrays of the present invention are nucleic acid arrays comprising (1) a first group of probes, each of which is specific to a different respective strain of a first species; and (2) a second group of probes, each of which is specific to a different respective strain of a second species. In many embodiments, the nucleic acid arrays of the present invention further include a third group of probes, each of which is specific to a different strain of a third species. In one example, a nucleic acid array of the present invention includes probes for sequences selected from SEQ ID NOs: 1 to 18,598, and can discriminably detect different strains of Streptococcus pyogenes, Streptococcus agalactiae and Staphylococcus epidermidis.

Abstract: This invention relates to new antibiotics designated AA-896-A1, AA-896-A2, AA-896-A3, AA-896-A4, AA-896-A5, AA-896-A6, AA-896-Bl, AA-896-B2, AA-896-B3, AA-896-B4, AA-896-B5, AA-896-B6, AA-896-B7, AA-896-C1, AA-896-C2, AA-896-C3, AA-896-C4, AA-896-C5, AA-896-D1, AA-896-D2, AA-896-D3 and AA-896-D4 derived from the microorganism Streptomyces spp. LL-AA896 which are useful an anti-bacterial agents.

Abstract: Substituted 3-carbonyl-1H-indol-1-yl acetic acid derivatives of formula I are provided: wherein: R1, R2, R3, R4 and R5 are as defined herein which are useful as inhibitors of plasminogen activator inhibitor-1 (PAI-1) for treating conditions resulting from fibrinolytic disorders, such as deep vein thrombosis and coronary heart disease, and pulmonary fibrosis.

Abstract: The invention relates to new antibiotics designated Cyan-416A, Cyan 416B, Cyan-416C, Cyan-416D and Cyan-416E to their production by fermentation of Acremonium sp. NRRL 30631 to methods for recovery and concentration from the crude solutions, and to a process for purification and to semisynthetic ethers of Cyan-416B.

Abstract: Novel aggrecanase proteins and the nucleotide sequences encoding them as well as processes for producing them are disclosed. Methods of identifying and developing inhibitors of the aggrecanase enzymes and antibodies to the enzymes for treatment of conditions characterized by the degradation of aggrecan are also disclosed.

Abstract: The invention is a process for the preparation of compounds of the Formula I: where R1, R2, R3, R4 and R5 are defined in the specification, which are intermediates useful for the preparation of tubulin inhibitors which are useful in the treatment of cancer.

Abstract: The invention provides isolated nucleic acids molecules, designated PCIP nucleic acid molecules, which encode proteins that bind potassium channels and modulate potassium channel mediated activities. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PCIP nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PCIP gene has been introduced or disrupted. The invention still further provides isolated PCIP proteins, fusion proteins, antigenic peptides and anti-PCIP antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

Abstract: The invention provides methods for determining effective immunotherapeutic agents which may be used for the treatment of cognitive disorders.

Abstract: This invention provides pharmaceutically active enantiomers of the venlafaxine metabolite O-Desmethyl venlafaxine, R(?)-4-[2-(Dimethylamino-1-(1-hydroxycyclo-hexyl)ethyl)phenol or R(?)1 -[2-(dimethylamino)-1-(4-hydroxyphenyl)ethyl]cyclo-hexanol, and S(+)-1-[2-(Dimethylamino)-1-(4-hydroxyphenyl)ethyl]cyclohexanol or S(+)-4-[2-(Dimethylamino)-1-(1-hydroxycyclohexyl)ethyl]phenol, or one or more pharmaceutically acceptable salts or salt hydrates thereof, as well as pharmaceutical compositions utilizing these enantiomers and methods of using the enantiomers to treat, inhibit or control central nervous system disorders.

Abstract: The present invention provides processes and intermediates for the preparation of aminoethoxybenzyl alcohols of Formula I useful in the production of pharmaceutically useful compounds.

Abstract: This invention provides estrogen receptor modulators having the structure: wherein R1 to R7 are as defined in the specification; or a pharmaceutically acceptable salt thereof.

Abstract: Compounds of Formula I or a pharmaceutically acceptable salt thereof are provided: where R1 through R7 are defined herein. The compounds of Formula I are 5HT2c agonists or partial agonists, and are useful for treating a variety of disorders.

Abstract: This invention provides compounds of the formula: wherein: X is a chemical bond, —CH2— or —C(O)—; R1 is alkyl, cycloalkyl, —CH2-cycloalkyl, pyridinyl, —CH2-pyridinyl, phenyl or benzyl; R2 is H, alkyl, cycloalkyl, —CH2-cycloalkyl, or perfluoroalkyl; R3 is H, halo, alkyl, perfluoroalkyl, alkoxy, cycloalkyl, —CH2-cycloalkyl, —NH2, or —NO2; R4 is optionally substituted phenyl, benzyl, benzyloxy, pyridinyl, or —CH2-pyridinyl, or the salt or ester forms thereof, as well as methods for using the compounds as inhibitors of plasminogen activator inhibitor-1 (PAI-1) and as therapeutic compositions for treating conditions resulting from fibrinolytic disorders such as deep vein thrombosis and coronary heart disease, and pulmonary fibrosis.

Abstract: The present invention provides a compound of formula I and the use thereof for the therapeutic treatment of disorders relating to or affected by the 5-HT6 receptor.