Abstract: The present invention relates to substituted pyrazoles, compositions containing such compounds and methods of treatment. The compounds are glucagon receptor antagonists and thus are useful for treating, preventing or delaying the onset of type 2 diabetes mellitus.

Abstract: This invention provides compounds of formula I where X?O or S; Y is O or S; q=1 or 0; and other substituents are defined herein. The invention also provides pharmaceutical compositions comprising compounds of formula I. Such compounds are potassium channel modulators.

Abstract: This invention is concerned with compounds of the formula and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are associated with the modulation of SST receptors subtype 5.

Abstract: Compounds that modulate the estrogen receptor (ER) are disclosed, as well as pharmaceutical compositions containing the same. In a specific embodiment, the compounds are selective for ER-? over ER-?. Methods are disclosed for modulating ER-? in cell and/or tissues expressing the same, including cells and/or tissue that preferentially ER-?. Methods for treating estrogen-related conditions are also disclosed, including conditions such as is breast cancer, testicular cancer, osteoporosis, endometriosis, cardiovascular disease, hypercholesterolemia, prostatic hypertrophy, prostatic carcinomas, obesity, hot flashes, skin effects, mood swings, memory loss, urinary incontinence, hairloss, cataracts, natureal hormonal imbalances, and adverse reproductive effects associated with exposure to environmental chemicals.

Abstract: Quinoline and quinazoline derivatives can be used in the form of pharmaceutical preparations as Neuropeptide Y antagonists for the treatment or prevention of arthritis, cardiovascular diseases, diabetes, renal failure, eating disorders and obesity.

Abstract: Compounds represented by the formula (I), where R1, R2, R3, R4, R5, and Q are as defined herein, exhibit activity against infectious pathogens

Abstract: The invention relates to novel compounds having the general formula: (I) and arc useful as selective ER-? ligands in the treatment or prophylaxis of Alzheimer's disease, anxiety disorders, depressive disorders, osteoporosis cardiovascular disease, rheumatoid arthritis or prostate cancer.

Abstract: A catalytic transfer hydrogenation process is provided. The catalyst employed in the process is a metal hydrocarbyl complex which is coordinated to defined bidentate ligands substituted with at least one group selected from an optionally substituted sulphonated hydrocarbyl group, a sulphonated perhalogenated hydrocarbyl group, or an optionally substituted sulphonated heterocyclyl group. Preferred metals include rhodium, ruthenium and iridium. Preferred bidentate ligands are diamines and aminoalcohols, particularly those comprising chiral centres. The hydrogen donor is advantageously a secondary alcohol or a mixture of triethylamine and formic acid. The process can be employed to transfer hydrogenate ketones and imines, which are preferably prochiral. Catalysts for use in such a process are also provided.

Abstract: The invention relates to novel benzo-fused heterocycles and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as endothelin receptor antagonists.

Abstract: The present invention is directed to novel substituted pyrroline compounds useful as kinase or dual-kinase inhibitors, methods for producing such compounds and methods for treating or ameliorating a kinase or dual-kinase mediated disorder.

Abstract: The present invention relates to new compounds of formula (I) wherein Y, P, R1, R2, R3, n, m are defined as in claim 1, a process for their preparation and new intermediates used therein, pharmaceutical composition containing said therapeutically active compounds and to the use of said active compounds in therapy, especially in the prevention and/or treatment of dementia related disease, Alzheimer's Disease and conditions associated with glycogen synthase kinase-3

Abstract: Heterocyclic amides of formula (1) wherein: is a single or double bond; A is phenylene or heteroarylene; m is 0, 1 or 2; n is 0, 1 or 2; R1 is selected from for example halo, nitro, cyano, hydroxy, carboxy; R2 is hydrogen, hydroxy or carboxy; R3 is selected from for example hydrogen, hydroxy, aryl, heterocyclyl and C1-4alkyl(optionally substituted by 1 or 2 R8 groups); R4 is independently selected from for example hydrogen, halo, nitro, cyano, hydroxy, C1-4alkyl, and C1-4alkanoyl; R8 is selected from for example hydroxy, —COCOOR9, —C(O)N(R9)(R10), —NHC(O)R9, (R9)(R10)N— and —COOR9; R9 and R10 are selected from for example hydrogen, hydroxy, C1-4alkyl (optionally substituted by 1 or 2 R13); R13 is selected from hydroxy, halo, trihalomethyl and C1-4alkoxy; or a pharmaceutically acceptable salt or pro-drug thereof; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity.

Abstract: Provided herein are compounds of the formulae IA–IF. These compounds are tetrahydroisoquinolines of the following structure: wherein R1–R8 for compounds of each of the formulae IA, IB, IC, ID, IE and IF are as described herein. Said compounds are particularly useful in the treatment of various neurological and psychiatric disorders, e.g., ADHD.

Abstract: The present invention pertains to compounds of the formula (1) which are, inter alia, antiproliferative agents, anticancer agents, antimycobacterial agents, antituberculosis agents, and/or thioredoxin/thioredoxin reductase inhibitor: wherein: Q is ?O or ?N—S(?O)2—RQ;RQ is —II or optionally substituted C1-7alkyl, C3-20heterocyclyl, or C5-20aryl; Ar is optionally substituted C5-20aryl; RO is an oxy substituent; the bond marked ? is a single bond or a double bond; the bond marked ? is a single bond or a double bond; R3 and R5 are each independently ring substituents; R2 and R6 are each independently ring substituents; and pharmaceutically acceptable salts, esters, amides, solvates, hydrates, and protected forms thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, for example, in the treatment of proliferative conditions, (e.g., cancer), mycobacterial infections (e.g.

Abstract: The present invention is concerned with novel compounds of formula (I) which are inhibitors of a membrane tripeptidyl peptidase responsible for the inactivation of endogenous neuropeptides such as cholecystokinis (CCKs). The invention further relates to methods for preparing such compounds, pharmaceutical compositions comprising said compounds as well as the use as a medicine of said compounds.

Abstract: The object of the present invention is to provide a compound having a treatment effect based on a chemokine inhibitory activity, which is satisfactory as a pharmaceutical product for oral administration. The present inventors have found that the following benzylpiperidine derivative (the formula (1)) has a chemokine inhibitory activity. Further intensive studies have resulted in successful enhancement of the chemokine inhibitory activity and stability in blood of the present compound, as well as the completion of the present invention. wherein each symbol is as defined in the specification.

Abstract: The present invention discloses compounds and compositions of formula (I): having inhibitory activity on activation of STAT6, wherein X represents quinoline, isoquinoline, quinazoline or imidazopyridine; Y represents phenyl, piperazine, pyridine, thiophene, thiazole, oxathiazole or oxathiadiazole; and variables Z, n, R1, R2, R3 and R4 are as defined in the claims.

Abstract: The present invention relates to an aminophenoxyacetamide derivative of the formula (I): wherein R1 to R4 are, independent from each other, a hydrogen atom or an optionally substituted alkyl group; E1 is —NR4—; and E2 is an oxygen atom or —NR10—; Q is the group —X—Y-Q?, wherein X and Y are connecting bonds or X is an alkylene or alkenylene group and Y is selected from a group comprising C?O, NHC(?), and C(?O)NH, and Q? is a hydrogen atom or a phenyl or pyridyl group which may be substituted; and pharmaceutically acceptable salts thereof. The present invention further relates to compositions comprising compounds of the formula (I) and methods of using said compounds for treating cerebral functional disorders and cerebral organic disorders.

Abstract: The present invention is directed to substituted coumarins and quinolines and analogs thereof, represented by the general Formula I: wherein A, B, X, Y, and Z are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

Abstract: There is provided an aminophenoxyacetic acid derivative of the following formula (I): wherein, R1, R2, R3 and R4 are, independent from each other, alkoxy group, alkyl group or aryl group, etc.; E1 and E2 are oxygen atom, sulfur atom, etc.; n is 0 to 5; X and Y are alkylene group, cycloalkylen group, or alkenylen group; Q is pheny group which may be substituted or benzoyl group, etc, or a pharmaceutically acceptable salt thereof. These compounds have neuroprotective effects by inducing calbindin D28Kd, one of Ca2+-binding proteins.

Abstract: Analogs of saquinavir functionalized at the quinoline portion of the molecule are described. These include pyridyl analogs (replacing the quinoline ring) with a functional handle out of the ring allowing for elaboration with linkers terminated by a functional group such as an activated ester which are useful for attaching the molecule to other entities such as proteins, polysaccharides, and the like. Analogs of saquinavir derivatized out of the quinoline ring are also described.

Abstract: The present invention relates to inhibitors of p38, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

Abstract: Pyridoarylphenyl oxazolidinone compounds of the formula: in which the substituents have the meaning indicated in the description. These compounds are useful as antibacterial agents.

Abstract: A compound of the formula (I): wherein R1 is hydroxy and the like; R2 is optionally substituted lower alkyl and the like; R3 is hydrogen atom and the like; R4 is optionally substituted arylene and the like; R5 is a group represented by the formula: and the like; R6 is optionally substituted aryl and the like, its optically active substance, its prodrug, their pharmaceutically acceptable salt, or solvate thereof and metalloproteinase inhibitors containing them.

Abstract: This invention relates to benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds, all of which may be described by of Formula I The invention is particularly related to such compounds that bind with high selectivity and high affinity to the benzodiazepine site of GABAA receptors. This invention also relates to pharmaceutical compositions comprising such compounds and to the use of such compounds in treatment of certain central nervous system (CNS) diseases. Novel processes for preparing compounds of Formula I are disclosed. This invention also relates to the use of benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds of Formula I in combination with one or more other CNS agents to potentiate the effects of the other CNS agents. Additionally this invention relates to the use such compounds as probes for the localization of GABAA receptors in tissue sections.

Abstract: The invention relates to compounds of the formula I in which R1 to R9 are as defined herein. In one embodiment, these compounds may be used as antihypertensives, for reducing or preventing ischemia-induced damage, as medicaments for surgical intervention for the treatment of ischemias of the nervous system, of stroke and of cerebral edema, of shock, of impaired respiratory drive, for the treatment of snoring, as laxative, as agent against ectoparasites, to prevent the formation of gallstones, as antiatherosclerotics, agents against late complications of diabetes, cancers, fibrotic disorders, endothelial dysfunction, organ hypertrophies and hyperplasias. In one embodiment, the compounds may be inhibitors of the cellular sodium-proton antiporter and influence serum lipoproteins and thus be used for the prophylaxis and for the regression of atherosclerotic lesions.

Abstract: The present invention is directed to substituted coumarins and quinolines and analogs thereof, represented by the general Formula I: wherein A, B, X, Y, and Z are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

Abstract: Quinoline and quinazoline derivatives can be used in the form of pharmaceutical preparations as Neuropeptide Y antagonists for the treatment or prevention of arthritis, cardiovascular diseases, diabetes, renal failure, eating disorders and obesity.

Abstract: Disclosed are novel processes and novel intermediate compounds for preparing aryl-and heteroaryl-substituted urea compounds of the formula(I) wherein Ar1, Ar2, L, Q and X are described herein. The product compounds are useful in pharmaceutic compositions for treating diseases or pathological conditions involving inflammation such as chronic inflammatory diseases.

Abstract: A tetrahydropyridino or piperidino heterocyclic derivative represented by the formula [I]: A-Het ??[I] has a high affinity for CRF receptors and is effective against diseases in which CRF is considered to be involved.

Abstract: The invention provides nicotine receptor agonists of formula I: wherein R1, x, y, and n have any of the values given in the specification, or a pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions comprising such a compound or salt, methods for preparing such a compound or salt, and methods for modulating (e.g. antagonizing or activating) nicotine receptors with such a compound or salt.

Abstract: The invention relates to compounds of formulae: Compounds of the invention have a good affinity to the NMDA receptor and are useful for the treatment of diseases related to this receptor.

Abstract: Compounds of formula (I): and their salts, solvates, hydrates and prodrugs are useful PCP inhibitors, processes for making the same, compositions comprising the same, and methods of treating a PCP-mediated condition or disease using the same.

Abstract: 3,4-Dihydroisoquinoline and isoquinoline compounds of formula I, in which Ar represents a phenyl raidcal of the formulae IIa, IIb or IIc are novel effective PDE7 inhibitors.

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: The present invention provides a novel nitrogen-containing heterocyclic compound useful as a phosphodiesterase-4 inhibitor, and a medicament comprising the same. Further, the present invention provides a nitrogen-containing heterocyclic compound represented by the following formula, its salt or hydrates thereof, and a medicament comprising the same.

Abstract: The invention provides compounds of the formula: 1

Abstract: Substituted tetrahydroisoquinolines and related compounds are provided. Such compounds are ligands that may be used to modulate C5a receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological C5a receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using them to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

Abstract: The present application describes to novel bicyclic hydroxamates derivatives of formula I: or pharmaceutically acceptable salt or prodrug forms thereof, wherein A, B, B1, B2, R1, and C are defined in the present specification, which are useful as inhibitors of matrix metalloproteinases (MMP), TNF-&agr; converting enzyme (TACE), aggrecanase, or a combination thereof.

Abstract: Compounds of the formula I 1

Abstract: The present invention relates to inhibitors of p38, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

Abstract: The present invention is directed to novel substituted pyrroline compounds useful as kinase or dual-kinase inhibitors, methods for producing such compounds and methods for treating or ameliorating a kinase or dual-kinase mediated disorder.

Abstract: The present invention relates to novel benzimidazoles, their preparation and their use as inhibitors of the enzyme poly(ADP-ribose) polymerase or PARP (EC 2.4.2.30) for producing drugs.

Abstract: Compounds that modulate the estrogen receptor (ER) are disclosed, as well as pharmaceutical compositions containing the same. In a specific embodiment, the compounds are selective modulators for ER-&bgr; over ER-&agr;. Methods are disclosed for modulating ER-&bgr; in cell and/or tissues expressing the same, including cells and/or tissue that preferentially express ER-&bgr;. More generally, methods for treating estrogen-related conditions are also disclosed, including conditions such as is breast cancer, testicular cancer, osteoporosis, endometriosis, cardiovascular disease, hypercholesterolemia, prostatic hypertrophy, prostatic carcinomas, obesity, hot flashes, skin effects, mood swings, memory loss, urinary incontinence, hairloss, cataracts, natural hormonal imbalances, and adverse reproductive effects associated with exposure to environmental chemicals.

Abstract: The present invention relates to novel substituted tetrahydroisoquinoline compounds, pharmaceutical compositions containing the compounds, methods of making the compounds, and methods of using the compounds to destroy a target cell, such as a cancer cell, and to treat or prevent a cancerous condition.

Abstract: There are provided compounds represented by the general formula (I): [wherein Ar is indole etc., R1 is hydrogen etc., B is bond, or B—N—R1 forms a ring structure and is piperidine etc., n is 0, 1, etc., A is trimethylene, butylene, etc., Q is piperidine, isoindoline, etc.], or pharmacologically acceptable acid addition salts thereof, and &agr;1B adrenoceptor antagonists composed of these substances. The invented compounds are antagonists having high affinity for &agr;1B adrenoceptor and are useful as pharmaceutical agents for use in prophylaxis/therapy of diseases (e.g., hypertension) in which &agr;1B adrenoceptor is involved or as pharmacological tools for elucidation of physiological activities mediated by &agr;1B adrenoceptor.

Abstract: Disclosed are compounds of the formula: or the pharmaceutically acceptable non-toxic salts thereof wherein the A, B, C, D, X, R1, R2, R3, R4, R5, and R6, are variables defined herein, which compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAa brain receptors, and are therefore useful in the diagnosis and treatment of anxiety, Down Syndrome, sleep, cognitive and seizure disorders, depression, overdose with benzodiazepine drugs, and enhancement of memory and alertness.

Abstract: The invention concerns compounds of formula (I), and their use in therapy, particularly in the modulation of CCR3 activity.

Abstract: Heteroarylpiperidines, pyrrolidines, and piperazines are useful as antipsychotic and analgesic agents. The compounds are especially useful for treating psychoses by administering to a mammal a psychoses-treating effective amount of one of the compounds. The compounds are also useful as analgesics by administering a pain-relieving effective amount of one of the compounds to a mammal.

Abstract: The invention provides compositions electron-deficient nitrogen heterocycle-substituted fluorescein dyes and methods in which the dyes are conjugated to substrates and used as detection labels in molecular biology experiments. The electron-deficient nitrogen heterocycles include pyridine, quinoline, pyrazine, and the like. Substrates include polynucleotides, nucleosides, nucleotides, peptides, proteins, carbohydrates, and ligands.