Abstract: Hydroxy substituted fused naphthyl-azoles and fused indeno-azoles are disclosed. Also disclosed are methods for the lowering and controlling of normal or elevated intraocular pressure as well as a method for the treatment of glaucoma using compositions containing one or more of the compounds of the present invention.

Abstract: The novel arylsulfonamide ether compounds, pharmaceutical compositions and uses thereof as inhibitors of interleukin-1? converting enzyme and other cysteine proteases in the ICE family are described. In one embodiment, the compound is described by the generalized structure: and pharmaceutically acceptable salts, esters, amides, and prodrugs thereof. In addition, methods of treating stroke, inflammatory diseases, septic shock, repurfusion injury, Alzheimer's disease, and shigellosis, using a compound of the invention or a pharmaceutical composition thereof, are described.

Abstract: This invention is directed to methods of treating insulin resistance in a mammal which comprise administering an effective amount of a compound of formula I, where the variables are defined in the specification, or the stereoisomeric mixtures, diastereomerically enriched, diastereomerically pure, enantiomerically enriched or enantiomerically pure isomers, or the pharmaceutically acceptable salts and prodrugs thereof to said mammal. The compounds of formula I are growth hormone secretagogues and as such are useful for increasing the level of endogenous growth hormone. In another aspect this invention provides certain intermediates which are useful in the synthesis of the foregoing compounds and certain processes useful for the synthesis of said intermediates and th compounds of formula I. This invention is further directed to methods comprising administering to a human or other animal a combination of a functional somatostatin antagonist such as an alpha-2 adrenergic agonist and a compound of formula I.

Abstract: Substituted indazoles, compositions containing them, method of production and use. The present invention relates in particular to novel specific substituted indazoles exhibiting kinase-inhibiting activity, having therapeutic activity, in particlar in oncology.

Abstract: Process for the protection of a building that has already been built or is going to be built, whereby an effective amount of an insecticidally active compound is spread around or under the said building at discrete locations. The insecticide may be an arylpyrazole.

Abstract: The present invention describes novel compounds of the formula: (Q)d—Ln—Ch, useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The present invention also provides novel compounds useful for imaging atherosclerosis, restenosis, cardiac ischemia, and myocardial reperfusion injury. The present invention also provides novel compounds useful for the treatment of rheumatoid arthritis. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety.

Abstract: Bicyclic heterocyclic substituted phenyl oxazolidinone compounds of the formula: wherein Y is a radical of Formulae II or III: in which the substituents have the meaning indicated in the description. These compounds are useful as antibacterial agents.

Abstract: The present invention relates to novel heterocyclic compounds, to methods for their preparation, to compositions containing them, and to methods and use for clinical treatment of medical conditions which may benefit from immunomodulation, including rheumatoid arthritis, multiple sclerosis, diabetes, asthma, transplantation, systemic lupus erythematosis and psoriasis. More particularly the present invention relates to novel heterocyclic compounds, which are CD80 antagonists capable of inhibiting the interactions between CD80 and CD28.

Abstract: The present invention relates to compound which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula: 1

Abstract: The invention is directed to N-substituted tricyclic 3-AMINOPYRAZOLE derivatives, which are useful as inhibitors of platelet-derived growth factor receptor (PDGF-R) kinase, and methods for the preparation of said derivatives. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as tumors and other cell proliferative disorders.

Abstract: Disclosed are diaryl piperazines and related compounds of the following Formula: wherein the variables are as defined in the specification. These compounds are selective modulators of capsaicin receptors, including human capsaicin receptors, that are, therefore, useful in the treatment of a chronic and acute pain conditions, itch and urinary incontinence. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also provided. Compounds of the invention are also useful as probes for the localization of capsaicin receptors and as standards in assays for capsaicin receptor binding and capsaicin receptor mediated cation conductance. Methods of using the compounds in receptor localization studies are given.

Abstract: Compounds of formula I and II, or pharmaceutically-acceptable salts thereof, are useful as inhibitors of Factor VIIa, Factor IXa, Factor Xa, Factor FXIa, tryptase, and urokinase, wherein ring B is phenyl or pyridyl, L is a linker, and R1-R27, W, Z1, and Z2 are as defined in the specification.

Abstract: Inhibitors of cytokine synthesis in nonimmune, resident ocular surface cells are useful for treating dry eye disorders and other disorders requiring the wetting of the eye.

Abstract: The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

Abstract: There are disclosed &bgr;-sheet mimetics and methods relating to the same for imparting or stabilizing the &bgr;-sheet structure of a peptide, protein or molecule. In one aspect, &bgr;-sheet mimetics are disclosed having utility as protease inhibitors in general and, more specifically, as serine protease inhibitors such as thrombin, elastase and Factor X inhibitors. In one embodiment, the &bgr;-sheet mimetic is a thrombin inhibitor.

Abstract: A method for preventing adverse effects associated with the use of a medical device in a patient by introducing into the patient a device of which at least a portion includes a prophylactic or therapeutic amount of a nitric oxide adduct. The nitric oxide adduct can be present in a matrix coating on a surface of the medical device; can be coated per se on a surface of the medical device; can be directly or indirectly bound to reactive sites on a surface of the medical device; or at least a portion of the medical device can be formed of a material, such as a polymer, which includes the nitric oxide adduct. Also disclosed is a method for preventing adverse effects associated with the use of a medical device in a patient by introducing the device during a medical procedure and before or during said procedure locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.

Abstract: Chemical compounds which are antagonists of Monocyte Chemoattractant Protein-1 (MCP-1) function, pharmaceutical compositions comprising these compounds, methods of treatment employing these compounds and compositions, and processes for preparing these compounds. The compounds are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection.

Abstract: This invention relates to a method of treating human immunodeficiency virus (HIV) infection in a mammal comprising administering to the mammal a therapeutically effective amount of a combination of: (i) at least one cytotoxic agent and (ii) at least one non-nucleoside reverse transcriptase HIV inhibitor (NNRTI). This invention also relates to a method of treating chronic viral infections comprising administering to the mammal a therapeutically effective amount of a combination of: (i) at least one cytotoxic agent and (ii) at least one antiviral agent.

Abstract: Substituted N-(1,4,5,6-tetrahydro-cyclopentapyrazol-3-yl) derivatives, their production, as well as intermediate products for their production, and the use as pharmaceutical agents for treating various diseases are described.

Abstract: The present invention relates to a novel heterocyclic compound, a pharmaceutical composition comprisining said compound, a method and use of said compound for clinical treatment of medical conditions which may benefit from immunomodulation, e.g. rheumatoid arthritis, multiple sclerosis, diabetes, asthma, transplantation, systemic lupus erythematosis and psoriasis. More particularly the present invention relates to novel heterocyclic compounds, which are CD80 antagonists capable of inhibiting the interactions between CD80 and CD28. A method of screening compounds for their ability of inhibiting ligand-induced co-stimulatory receptor internalization pathways in immune competent human cells is described. Said immune competent human cells are incubated at conditions capable of inducing co-stimulatory receptor internalization in the presence of at least one test compound and the suppression of the ligand-induced co-stimulatory receptor internalization determined.

Abstract: There are disclosed &bgr;-sheet mimetics and methods relating to the same for imparting or stabilizing the &bgr;-sheet structure of a peptide, protein or molecule. In one aspect, the &bgr;-sheet mimetics are covalently attached at the end or within the length of the peptide or protein. The &bgr;-sheet mimetics have utility as inhibitors of one or more of proteases, kinases, CAAX, peptides binding to SH2 domains and MHC-I and/or MHC-II presentation of peptides to T cell receptors in warm-blooded animals.

Abstract: This invention is directed to methods of treating insulin resistance in a mammal which comprise administering an effective amount of a compound of formula I, where the variables are defined in the specification, or the stereoisomeric mixtures, diastereomerically enriched, diastereomerically pure, enantiomerically enriched or enantiomerically pure isomers, or the pharmaceutically acceptable salts and prodrugs thereof to said mammal. The compounds of formula I are growth hormone secretagogues and as such are useful for increasing the level of endogenous growth hormone. In another aspect this invention provides certain intermediates which are useful in the synthesis of the foregoing compounds and certain processes useful for the synthesis of said intermediates and the compounds of formula I.

Abstract: The present application describes novel bicyclic lactam derivatives of formula I: 1

Abstract: Pyranoindazoles are disclosed. Also disclosed are methods for the lowering and controlling of normal or elevated intraocular pressure as well as a method for the treatment of glaucoma using compositions containing one or more of the compounds of the present invention.

Abstract: Retinoid compounds which act specifically or selectively on RAR&agr; receptor subtypes in preference over RAR&bgr; and RAR&Ggr; receptor subtypes, posses desirable pharmaceutical properties associated with retinoids, and are particularly suitable for treatment of tumors, such as acute monocytic leukemia, cervical carcinoma, myeloma, ovarian carcinomas and head and neck carcinomas, without having one or more undesirable side effects of retinoids, such as inducement of weight loss, mucocutaneous toxicity, skin irritation and teratogenecity.

Abstract: The present invention is directed to certain novel compounds represented by structural Formula (I):

Abstract: Compounds, compositions and methods are provided which are useful in the treatment of diseases through the modulation of potassium ion flux through voltage-dependent potassium channels. More particularly, the invention provides bisarylamines, compositions and methods that are useful in the treatment of central or peripheral nervous system disorders (e.g., migraine, ataxia, Parkinson's disease, bipolar disorders, trigeminal neuralgia, spasticity, mood disorders, brain tumors, psychotic disorders, myokymia, seizures, epilepsy, hearing and vision loss, Alzheimer's disease, age-related memory loss, learning deficiencies, anxiety and motor neuron diseases) and as neuroprotective agents (e.g., to prevent stroke and the like) by opening potassium channels associated with the onset or recurrence of the indicated conditions.

Abstract: Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds are useful in vitro or in vivo for preventing or treating coagulation disorders.

Abstract: Disclosed are novel 1,4-disubstituted benzo-fused compounds wherein G, X, L, Q, n and Y are defined herein. The compounds are useful in pharmaceutic compositions for treating diseases or pathological conditions involving inflammation such as chronic inflammatory diseases. Also disclosed are processes of making such compounds.

Abstract: The present application describes nitrogen containing heterobicyclics and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.

Abstract: Retinoid compounds which act specifically or selectively on RAR&agr; receptor subtypes in preference over RAR&bgr; and RAR&Ggr; receptor subtypes, possess desirable pharmaceutical properties associated with retinoids, and are particularly suitable for treatment of tumors, such as acute monocytic leukemia, cervical carcinoma, myeloma, ovarian carcinomas and head and neck carcinomas, without having one or more undesirable side effects of retinoids, such as inducement of weight loss, mucocutaneous toxicity, skin irritation and teratogenecity.

Abstract: Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds of formula (I) below: are useful in vitro or in vivo for preventing or treating coagulation disorders.

Abstract: Efficacious remedies for male sterility which are in the form of preparations containing as the active ingredient an adenosine A1 antagonist.

Abstract: The present invention relates to a novel heterocyclic compound, a pharmaceutical composition comprisining said compound, a method and use of said compound for clinical treatment of medical conditions which may benefit from immunomodulation, e.g. rheumatoid arthritis, multiple sclerosis, diabetes, asthma, transplantation, systemic lupus erythematosis and psoriasis. More particularly the present invention relates to novel heterocyclic compounds, which are CD80 antagonists capable of inhibiting the interactions between CD80 and CD28.

Abstract: This application relates to a compound of formula I (or a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug thereof) as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa, as well as a process for its preparation and intermediates therefor.

Abstract: This invention is directed to methods of treating insulin resistance in a mammal which comprise administering an effective amount of a compound of formula I, where the variables are defined in the specification, or the stereoisomeric mixtures, diastereomerically enriched, diastereomerically pure, enantiomerically enriched or enantiomerically pure isomers, or the pharmaceutically acceptable salts and prodrugs thereof to said mammal. The compounds of formula I are growth hormone secretagogues and as such are useful for increasing the level of endogenous growth hormone. In another aspect this invention provides certain intermediates which are useful in the synthesis of the foregoing compounds and certain processes useful for the synthesis of said intermediates and the compounds of formula I.

Abstract: Disclosed are novel aromatic compounds which are useful for treating diseases or pathological conditions involving inflammation such as chronic inflammatory diseases. Also disclosed are pharmaceutical compositions containing and processes of making such compounds.

Abstract: Therapeutically active compositions of matter are described which are useful for treating or preventing diseases and conditions comprising inflammatory diseases including joint inflammation, Crohn's disease, and inflammatory bowel disease; respiratory diseases such as chronic obstructive pulmonary disease (COPD) including asthma, chronic bronchitis, and pulmonary emphysema; infectious diseases including endotoxic shock and toxic shock syndrome; immune diseases including systemic lupus erythematosis and psoriasis; and other diseases including bone resorption diseases and reperfusion injury; wherein said composition of matter comprises a compound which is an inhibitor of phosphodiesterase isozyme 4 (PDE4) and wherein an indazole is one essential component of said compound's overall chemical structure, and wherein said indazole constitutes a bioisosteric replacement of a catechol component or functional derivative thereof in a known compound having the same said therapeutic activity and the same remaining said c

Abstract: The invention relates to antagonists of CX3C chemokine receptor 1 (CX3CR1) function, antagonists of fractalkine function and to therapeutic methods employing the antagonists. The invention also relates to a method for diagnosing rheumatoid arthritis.

Abstract: Disclosed are compounds of the formula 1

Abstract: Disclosed are novel aromatic compounds which are useful for treating diseases or pathological conditions involving inflammation such as chronic inflammatory diseases. Also disclosed are pharmaceutical compositions containing and processes of making such compounds.

Abstract: In accordance with the present invention, there is provided a new class of drugs for therapeutic treatment of such indications as cerebral stroke and other ischemia/reperfusion injury. Thus, in accordance with the present invention, dithiocarbamates are linked to the surface of a non-immunogenic, non-targeting macromolecule other than an antibody (e.g., albumin protein) either by using cross-linking reagents or by nonspecific binding to produce polydithiocarbamate-macromolecule-containing compositions, which represent a new class of drugs for therapeutic treatment of such indications as cerebral stroke and other ischemia/reperfusion injury. In accordance with another aspect of the present invention, combinational therapeutic methods have been developed for the in vivo inactivation or inhibition of formation (either directly or indirectly) of species which induce the expression of inducible nitric oxide synthase, as well as reducing nitric oxide levels produced as a result of .NO synthase expression.

Abstract: This application relates to a compound of formula (I), a pharmaceutically acceptable salt of the compound, or a prodrug thereof, as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa, as well as a process for its preparation and intermediates therefor.

Abstract: Novel compounds that are potent and selective inhibitors of PDE4, as well as methods of making the same, are disclosed. Use of the compounds in the treatment of inflammatory diseases and other diseases involving elevated levels of cytokines, as well as central nervous system (CNS) disorders, also is disclosed.

Abstract: The present invention is to provide a compound of the formula: wherein the ring A is an optionally substituted 5- to 6-membered aromatic heterocyclic ring, the ring B an optionally substituted 5- to 6-membered aromatic homocyclic ring or an optionally substituted 5- to 6-membered aromatic heterocyclic ring, R1 is a hydrogen atom, a hydroxy group or a lower alkyl group, and n is 0 or 1, or a salt thereof, which is effective for the prevention or treatment of ischemic cardiac disease, etc., and which is useful as an agent for preventing or treating ischemic cardiac disease, etc. such as myocardial infarction, arrhythmia, etc.

Abstract: Novel compounds, compositions and methods effective for the prevention and treatment of mast-cell mediated inflammatory disorders are described. The compounds, compositions and methods are effective for the prevention and treatment of inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis, as well as other types of immunomediated inflammatory disorders, such as rheumatoid arthritis, conjunctivitis and inflammatory bowel disease, various dermatological conditions, as well as certain viral conditions. The compounds comprise potent and selective inhibitors of the mast cell protease tryptase. The compositions for treating these conditions include oral, inhalant, topical and parenteral preparations as well as devices comprising such preparations.

Abstract: The present invention is directed to an improved synthesis of clasto-lactacystin-&bgr;-lactone, and analogs thereof, that proceeds in fewer steps and in much greater overall yield than syntheses described in the prior art. The synthetic pathway relies upon a novel stereospecific synthesis of an oxazoline intermediate and a unique stereoselective addition of a formyl amide to the oxazoline. Also described are novel clasto-lactacystin-&bgr;-lactones, and analogs thereof and their use as proteosome inhibitors.

Abstract: There are disclosed &bgr;-sheet mimetics and methods relating to the same for imparting or stabilizing the &bgr;-sheet structure of a peptide, protein or molecule. In one aspect, &bgr;-sheet mimetics are disclosed having utility as protease inhibitors in general and, more specifically, as serine protease inhibitors such as thrombin, elastase and Factor X inhibitors. In one embodiment, the &bgr;-sheet mimetic is a thrombin inhibitor.

Abstract: The present invention relates to 4-haloalkyl-3-heterocyclylpyridines and 4-haloalkyl-5-heterocyclylpyrimidines of the formula (I), to processes for their preparation, to compositions comprising them, and to the use of these compounds for controlling animal pests, in particular insects, spider mites, ectoparasites and helminths. In the formula (I), Q is a 5-membered heterocyclic group which is optionally substituted by halogen or organic radicals, Y is halo-C1-C8-alkyl, X is CH or N and m is 0 or 1.

Abstract: There are provided new 3-hydroxy-4-aryl-5-oxo-pyrazoline derivatives of the formula (I) in which A and B are identical or different and independently of one another in each case represent hydrogen, alkyl, alkenyl, alkynyl, alkoxyalkyl, alkylthioalkyl, cycloalkyl or optionally substituted aryl or A and B together represent the bivalent radical of a saturated or unsaturated, optionally substituted, mono-, bi-, tri- or polycyclic system, X represents alkyl, halogen or alkoxy, Y represents hydrogen, alkyl, halogen, alkoxy or halogenoalkyl, Z represents alkyl, halogen or alkoxy, n represents a number 0, 1, 2 or 3, G represents hydrogen (a) or the groups —CO—R1 (b ), —SO2—R3 (d), or E (g), in which E represents a metal ion equivalent or an ammonium ion, L and M represents oxygen and/or sulphur, and R1, R2, R3, R4, R5, R6 and R7 have the meaning given in the text of the application.