Abstract: This invention relates to a novel crystalline diphosphate salt of (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[[2,6-dideoxy-3-C-methyl-3-O-methyl-4-C-[(propylamino)methyl]-?-L-ribo-hexopryanosyl]oxy]-2-ethyl-3,4,10-trihydroxy-3,5,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-?-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one that is useful as an antibacterial and antiprotozoal agent in mammals. This invention also relates to pharmaceutical compositions containing the free base of the diphosphate salt and the methods of treating bacterial and protozoal infections in mammals by administering the free base of the diphosphate to mammals requiring such treatment. The free base of the diphosphate salt of the present invention possesses potent activity against various bacterial and protozoal infections when given by parenteral application to mammals.

Abstract: The present invention relates to novel to P2X7 inhibitors of formula I and to processes for their preparation, intermediates useful in their preparation, pharmaceutical compositions containing them, and their use in therapy. The active compounds of the present invention are potent inhibitors of P2X7 and as such are useful in the treatment of inflammation, osteoarthritis, rheumatoid arthritis, cancer, reperfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.

Abstract: The present invention relates to 5-spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors of the formula wherein said “A” is a 5-7 membered heterocyclic ring as defined in the specification and to pharmaceutical compositions and methods of treating inflammation, cancer and other disorders.

Abstract: Corticotropin-releasing factor (CRF) antagonists having the formulae wherein the dashed lines, A, B, Y, Z, G, R3, R4, R5, R6, R16 and R17 are as defined in the application, and processes for preparing them. These compounds and their pharmaceutically acceptable salts are useful in the treatment disorders including CNS and stress-related disorders.

Abstract: Four antigenic preparations are provided, each of which contains a different protein from Leptospira which can be used immunologically in vaccines for leptospirosis caused by this organism. Also provided in the invention are polynucleotides encoding these four proteins and antibodies which bind the proteins for use in the diagnosis of leptospirosis.

Abstract: The present invention relates to compositions and methods of achieving a therapeutic effect including, the treatment or prevention of Syndrome X in an animal, preferably a mammal including a human subject or a companion animal, using a corticotropin releasing factor (CRF) antagonist alone or together with a glucocorticoid receptor antagonist.

Abstract: The invention relates to a method of preparing compounds of the formula and to pharmaceutically acceptable salts thereof. The compounds of formula 1 are antibacterial agents that may be used to treat various bacterial and protozoa infections. The invention also relates to pharmaceutical compositions containing the compounds of formula 1 and to methods of treating bacterial protozoa infections by administering the compounds of formula 1. The invention also relates to methods of preparing the compounds of formula 1 and to intermediates useful in such preparation.

Abstract: The compounds of the formula wherein R1, R2, R3, R4, R5 and R6 are as defined herein, are useful in the treatment of stress-related and other diseases. These compounds have corticotropin-releasing factor antagonist activity and as such are of use in the treatment of stress and anxiety related, and other disorders.

Abstract: The present invention relates to methods and compositions of growth hormone and/or growth hormone releasing hormone that promote of the release and the elevation of growth hormone when administered to animals. The present invention further relates to methods and compositions of growth hormone and/or growth hormone releasing hormone for treatment of diseases or disorders resulting from growth hormone related deficiencies. The invention also provides methods for producing novel growth hormone releasing hormone variants and their uses thereof.

Abstract: There is provided a compound of formula I, wherein Het1, R1, R2, R3, X and n have meanings given in the description, which are useful in the prophylaxis and in the treatment of diseases mediated by opiate receptors, such as pruritus.

Abstract: The invention relates to adjuvants that contain a lecithin, an oil and an amphiphilic surfactant and that are capable of forming a stable oil-in-water emulsion vaccine so as to minimize local reactions to the vaccine in the injected animal.

Abstract: This invention relates to a series of difluoromethylene aromatic ethers of the formula wherein ring A and X and Y are defined as in the specification, that exhibit activity as glycine transport inhibitors, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, and their use for the enhancement of cognition and the treatment of the positive and negative symptoms of schizophrenia and other psychoses in mammals, including humans.

Abstract: Novel indolyl-2-phenyl bisamidines are described which are DNA methyltransferase inhibiting agents, and pharmaceutical compositions containing them are used as antiproliferative agents for treating a disease, especially a neoplastic disease, characterized by abnormally rapid proliferation of tissue involved in said disease; said indolyl-2-phenyl bisamidines comprising a and a pharmaceutically acceptable salt thereof, wherein: R1 is hydrogen or (C1-C3)alkyl; R3, R4, R5, R8, R9, and R10 are hydrogen or (C1-C3)alkyl, or R3 and R4 may be taken together, or R8 and R9 may be taken together with the nitrogen atoms to which they are attached, to form an imidazolinyl group; R14 is —H; —NHC(═O)(CH2)mR20; —(CH2)mR20; —CH(CH3)R20; —(CH2)m(C6H3)—R17; —(CH2)m(C6H3)—R20; —(CH2)m(heterocyclyl)—R17; —(CH2)m(heterocyclyl)—R20; —CH2CH═CHR20; —(CH2)mC(═O)NH—CHR20R21; or —(CH2)mC(═O)NH—CH2&m

Abstract: The invention provides transgenic, non-human animals and transgenic non-human mammalian cells harboring a transgene encoding a p25 (activator of the protein kinase cdk 5) polypeptide. The two neuropathological lesions associated with Alzheimer's disease (AD) are amyloid plaques and neurofibrillary tangles (NFTs), composed predominantly of amyloid &bgr; peptides and hyperphosphorylated tau, respectvely. While animal models for plaque formation exist, there is no animal model that recapitulates the formation of NFTs. This invention provides transgenic mice that overexpress human p25, an activator of cdk5, resulting in tau that is hyperphosphorylated at AD-relevant epitopes. Deposition of tau is detected in the amygdala, thalamus and cortex. Increased phosphorylated neurofilament, silver-positive neurons and neuronal death are also observed in these regions. We conclude that the overexpression of p25, an activator of cdk5, is sufficient to produce hyperphosphorylation of tau and neuronal death.

Abstract: A process for the purification of 2-methoxy-5-trifluoro-methoxy benzaldehyde oil in which the oil is converted to amine by reaction of a nitroaniline with the oil; the imine is isolated as a solid; and the solid imine is converted back to the 2-methoxy-5-trifluoromethoxy benzaldehyde oil. The nitroaniline is selected from the group consisting of 3-nitroaniline, 3-methyl-2-nitroaniline, 4-methyl-2-nitroaniline, 2 methyl-3-nitroaniline and 4-methyl-3-nitroaniline.

Abstract: The present invention is directed to vaccine compositions that can be used to protect cats against feline immunodeficiency virus. More particularly, the present invention relates to polynucleotide molecules that can be used as vaccine components against feline immunodeficiency virus.

Abstract: The invention relates to crystal forms of 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-ethynyl-phenyl)-1-methyl-1H-quinolin-2-one, 2,3-dihydroxy butanedioate salts having the formula shown below: and to pharmaceutical compositions containing the above compound, methods of treating hyperproliferative diseases, such as cancers, in mammals, especially humans by administering the above compound, and to methods of preparing the crystal forms of the above compound and related compounds.

Abstract: This invention relates to stable pharmaceutical compositions of the NMDA receptor agonist, (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanol], methods of preparing such pharmaceutical compositions and methods of treating stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, CNS degenerative diseases such as Alzheimer's disease, senile dementia of the Alzheimer's type, Huntington's disease, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis, pain, AIDS dementia, psychotic conditions, drug addictions, migraine, hypoglycemia, anxiolytic conditions, urinary incontinence and an ischemic event arising from CNS surgery, open heart surgery or any procedure during which the function of the cardiovascular system is compromised using the pharmaceutical compositions.

Abstract: Compounds that inhibit the peptidyl-prolyl isomerase (rotamase) enzyme activity of the FK-506 binding protein (FKBP) and compositions comprising these compounds are described. The FKBP-inhibiting compounds have a bicyclic [3.3.1], [4.3.1] or polycyclic azaamide nucleus. Pharmaceutical compositions containing such compounds help stimulate the outgrowth of neurites in nerve cells and augmenting nerve regeneration. Methods of treating nerve cells with such compositions are useful to promote repair of neuronal damage caused by disease and physical trauma.

Abstract: The present invention relates to novel quinazolin-4-one derivatives of the formula wherein A is a benzo or thieno fused aromatic ring; B is phenyl, pyridyl or pyrimidyl; X is N or CH; and Y-Z is —CH2NH— or —NHCH2—; and to pharmaceutical compositions containing such compounds, and the use of such compounds to treat neurodegenerative, psychotropic, and drug and alcohol induced central and peripheral nervous system disorders.