Abstract: There is provided a process for the preparation of 3-cyano-6-alkoxy-7-nitro-4-quinolone intermediates useful for the preparation of protein tyrosine kinase (PTK) inhibitors which are useful in the treatment of cancer of the formula: 1

Abstract: Disclosed are certain alpha amino acid compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract: Compounds of the formula useful for treatment of disorders of the dopaminergic system, such as schizophrenia, schizoaffective disorder, bipolar disorder, Parkinson's disease, L-DOPA induced pychoses and dyskinesias, Tourette's syndrome and hyperprolactinemia and in the treatment of drug addiction such as the addiction to ethanol, nicotine or cocaine and related illnesses.

Abstract: An altered G protein or portion thereof of RSV which retains immunogenicity and which, when incorporated into an immunogenic composition or vaccine and administered to a vertebrate, does not induce enhanced disease (e.g., atypical pulmonary inflammation such as pulmonary eosinophilia) upon subsequent infection with RSV, is disclosed. In a particular embodiment, the altered G protein comprises an alteration in one or more regions selected from the group consisting of the region from amino acid 159 to amino acid 198, the region from amino acid 159 to amino acid 174, the region from amino acid 171 to amino acid 187, the region from amino acid 176 to amino acid 190, and the region from amino acid 184 to amino acid 198 of the RSV G protein. Immunogenic compositions and vaccines comprising the altered RSV G protein, and optionally comprising RSV F protein, are also disclosed.

Abstract: A therapeutic composition for inhibiting the function of a target polynucleotide sequence in a mammalian cell includes an agent that provides to a mammalian cell an at least partially double-stranded RNA molecule comprising a polynucleotide sequence of at least about 200 nucleotides in length, said polynucleotide sequence being substantially homologous to a target polynucleotide sequence. This RNA molecule desirably does not produce a functional protein. The agents useful in the composition can be RNA molecules made by enzymatic synthetic methods or chemical synthetic methods in vitro; or made in recombinant cultures of microorganisms and isolated therefrom, or alternatively, can be capable of generating the desired RNA molecule in vivo after delivery to the mammalian cell.

Abstract: Compounds of Formula (I), 1

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.

Abstract: Compounds of the formula: useful for treatment of disorders such as schizophrenia, schizoaffective disorder, bipolar disorder, Parkinson's disease, L-DOPA induced pychoses and dyskinesias, Tourette's syndrome and hyperprolactinemia and in the treatment of drug addiction such as the addiction to ethanol, nicotine or cocaine and related illnesses.

Abstract: A process is provided for preparing chirally pure S-enantiomers of &agr;-amino acids comprising the steps of: a) preparing an organometallic reagent from an alkyl halide of the formula (R)2CH(CH2)nCH2X; b) adding the organometallic reagent to carbon dioxide to afford a carboxylic acid; c) activating the carboxylic acid with an acid chloride, phosphorus trichloride, acid anhydride, or thionyl chloride in the presence of a tertiary amine base; d) reacting the product of step c) with an alkali metal salt of S-4-benzyl-2-oxazolidinone; e) treating the product of step d) with a strong non-nucleophilic base to form an enolate anion; f) trapping the enolate anion with 2,4,6-triisopropylbenzenesulfonyl azide to afford an oxazolidinone azide; g) hydrolyzing the oxazolidinone azide with an aqueous base to afford an &agr;-azido acid; h) reducing the &agr;-azido acid to the &agr;-amino acid; and i) recrystallizing the &agr;-amino acid to the chirally pure &agr;-amino acid.

Abstract: This invention provides PAI-1 inhibiting compounds of Formula I: wherein: R1, R2, R3, and R4 are eachH, alkyl,, alkanoyl, halo, OH, aryl optionally substituted with R8, perfluoroalkyl, alkoxy, amino, alkylamino, dialkylamino, perfluoroalkoxy; R5 is H, alkyl, perfluoroalkyl, aryl optionally substituted with R8, alkanoyl, aroyl optionally substituted with R8; R6 is H, alkyl, alkylaryl, benzyl optionally substituted with R8, alkanoyl, aroyl optionally substituted with R8; R7 is H, alkyl, alkylaryl, aryl optionally substituted with R8; n is 0-6; A is COOH, or an acid mimic such as tetraazole, SO3H, PO3H2, tetronic acid, etc.; R8 is H, alkyl, cycloalkyl, alkanoyl, halo, OH, perfluoroalkyl, alkoxy, amino, alkylamino, dialkylamino, perfluoroalkoxy; or a pharmaceutically acceptable salt thereof; as well as pharmaceutical compositions and methods of treatment using these compounds.

Abstract: Compounds of the formula: useful for treatment of disorders of the dopaminergic system, such as schizophrenia, schizoaffective disorder, bipolar disorder, Parkinson's disease, L-DOPA induced pychoses and dyskinesias, Tourette's syndrome and hyperprolactinemia and in the treatment of drug addiction such as the addiction to ethanol, nicotine or cocaine and related illnesses.

Abstract: Compounds of the formula useful for treatment of disorders of the dopaminergic system, such as schizophrenia, schizoaffective disorder, bipolar disorder, Parkinson's disease, L-DOPA induced pychoses and dyskinesias, Tourette's syndrome and hyperprolactinemia and in the treatment of drug addiction such as the addiction to ethanol, nicotine or cocaine and related illnesses.

Abstract: Compounds of the formula: 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, bulimia nervosa, vasomotor flushing, cocaine and alcohol addiction, sexual dysfunction and related illnesses.

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

Abstract: Adatanserin is useful for treating neurodegenerative disorders, chronic pain, and other disorders associated with dysfunctional glutamate release. Methods of treating the same comprise administering a therapeutically effective amount of adatanserin or a pharmaceutical salt thereof, to a patient in need of said treatment.

Abstract: Regulatory elements responsible for tissue-specific transcriptional regulation of the human &bgr;3-adrenergic receptor (&bgr;3-AR) were identified. A region localized between −6.50 and −6.30 kb of the proximal promoter contained three sequences that act synergistically to achieve full transcriptional activity. One segment, termed segment A, contains an Sp1 binding site. Another of the sequences, termed segment B, is a binding site for a trans-acting factor present in cells that constitutively express &bgr;3-AR. In a specific embodiment, the trans-acting factor is expressed in neuroblastoma (SK-N-MC) and brown adipose tissue cells, but little or not at all in CV-1, HeLa, or white adipose tissue cells. The third segment, C, is an S1 nuclease-sensitive site having CCTT repeats.

Abstract: Methods for preparing monomeric cytotoxic drug/carrier conjugates with a drug loading significantly higher than in previously reported procedures and with decreased aggregation and low conjugate fraction (LCF) are described. Cytotoxic drug derivative/antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described. Monomeric calicheamicin derivative/anti-CD22 antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described.

Abstract: This invention provides substituted indole compounds of the general formula: and pharmaceutically acceptable salt forms thereof, and methods for using the compounds as inhibitors of the activity of various phospholipase enzymes, particularly phospholipase A2 enzymes, and for the medical treatment, prevention and inhibition of pain and inflammation.

Abstract: This invention provides methods for utilizing a PTPase inhibiting compounds and one or more insulins in methods for use in control and maintenance of type II diabetes in a mammal, for improving the cardiovascular and cerebrovascular risk profiles, reduction of hyperlipidemia, lowering low density lipoprotein blood levels, lowering free fatty acid blood levels and triglyceride levels and inhibition, prevention or reduction of atherosclerosis in a type II diabetic, or the risk factors thereof.

Abstract: The present invention is directed to a pharmaceutical composition and method for the treatment of rhinitis and cold-like symptoms which includes a non-steroidal anti-inflammatory drug (NSAID), a decongestant, and an antihistamine. It has been found that an NSAID enhances the activity of a decongestant and an anti-histamine, thus permitting a reduction in either or both in administration of separate dosage forms. The same enhancement can also occur with an anti-tussitive. Thus, the effective amount of the decongestant or the antihistamine or both is less than about 75% of an amount present in an approved dose of the decongestant or the antihistamine, or both, relative to an amount of the NSAID corresponding to about 100% of the amount present in a normal strength dosage form of the NSAID.