Abstract: Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

Abstract: The present invention relates to cyclized amide derivatives for treating or preventing neuronal damage associated with neurological diseases. The invention also provides compositions comprising the compounds of the present invention and methods of utilizing those compositions for treating or preventing neuronal damage.

Abstract: This invention relates to novel cyclic malonamides having the formula (I): 1

Abstract: An aminobutyric acid derivative of the formula (I): (wherein all symbols are as defined in the specification) and salt thereof. salt thereof. The compounds of the formula (I) possess an inhibitory activity on matrix metalloproteinase and are useful for prevention and/or treatment of diseases, for example, rheumatoid diseases, arthrosteitis, unusual bone resorption, osteoporosis, periodontitis, interstitial nephritis, arteriosclerosis, pulmonary emphysema, cirrhosis, cornea injury, metastasis of, invasion of or growth of tumor cells, autoimmune disease (e.g. Crohn's disease, Sjogren's syndrome), disease caused by vascular emigration or infiltration of leukocytes, arterialization, multiple sclerosis, aorta aneurysm, endometriosis.

Abstract: The present invention relates to compounds of the formula 1

Abstract: The invention relates to methods and compositions for the prevention, treatment, or management of gastrointestinal disorders or symptoms thereof, employing two or more agents or compounds to provide a triple site action on 5-HT3 receptors, 5-HT4 receptors, and at least one of H2 receptors and proton pumps.

Abstract: The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary artery disease.

Abstract: The present invention relates to compounds of the formula 1

Abstract: The present invention relates to compounds of the formula wherein R1, R2, R3, X, Y and the dashed line are defined as in the specification, to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use. These compounds are useful as psychotherapeutic agents.

Abstract: Compounds of formula (I), wherein R2 is a 5,6,7,8-tetrahydronaphth-1-yl group which may be substituted (the remaining groups defined herein), and pharmaceutical compositions containing the compounds and methods of using the compounds in the treatment of a condition where antagonism of the NK1 and/or NK2 receptors is beneficial.

Abstract: A thrombin receptor antagonist having the formula or a pharmaceutically acceptable salt thereof, useful for inhibiting the aggregation of blood platelets. The compounds can be used in a method of acting upon a thrombin receptor which comprises administering a therapeutically effective but non-toxic amount of such compound to a mammal, preferably a human.

Abstract: Compounds of Formula I are antagonists of VLA-4 and/or &agr;4&bgr;7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of AIDS-related dementia, allergic conjunctivitis, allergic rhinitis, Alzheimer's disease, asthma, atherosclerosis, autologous bone marrow transplantation, certain types of toxic and immune-based nephritis, contact dermal hypersensitivity, inflammatory bowel disease including ulcerative colitis and Crohn's disease, inflammatory lung diseases, inflammatory sequelae of viral infections, meningitis, multiple sclerosis, multiple myeloma, myocarditis, organ transplantation, psoriasis, pulmonary fibrosis, restenosis, retinitis, rheumatoid arthritis, septic arthritis, stroke, tumor metastasis, uveititis, and type I diabetes.

Abstract: This invention discloses that a combination of two drugs, from two different and unrelated categories, provides effective and long-lasting relief from neuropathic pain. Both drugs can be taken orally, in a convenient, painless, non-invasive manner that does not require injections. One drug is an aryl-cyclo-alkanolamine (ACAA) which has antagonist (receptor-blocking) activity at the NMDA subclass of glutamate receptors; such drugs include procyclidine, biperiden, and trihexyphenidyl. The other drug is an &agr;2 adrenergic agonist, exemplified by clonidine. When an ACAA drug which blocks NMDA receptors, such as procyclidine, is administered together with an &agr;2 adrenergic agonist such as clonidine, these drugs mutually potentiate one another's neuropathic pain-relieving action, and provide potent and sustained neuropathic pain relief, even when each agent is administered at a low dosage that is below its threshold for causing adverse side effects.

Abstract: A class of cysteine protease inhibitors which inactivate a cysteine protease by covalently bonding to the protease and releasing a heterocyclic leaving group is presented. The cysteine protease inhibitors of the present invention comprise a first portion which targets a desired cysteine protease and positions the inhibitor near the thiolate anion portion of the active site of the protease, and a second portion which covalently bonds to the cysteine protease and irreversibly deactivates that protease by providing a carbonyl or carbonyl-equivalent which is attacked by the thiolate anion of the active site of the cysteine protease to sequentially cleave a heterocyclic leaving group. The heterocyclic leaving group of the protease inhibitor is of the formula: —O— Het, where Het is a heterocycle having 4-7 atoms in the ring, with at least one of the heterocycle atoms being N, O or S.

Abstract: Novel compounds of general formula I: 1

Abstract: One aspect of the present invention relates to heterocyclic compounds comprising a sulfonamide moiety. A second aspect of the present invention relates to the use of the heterocyclic compounds comprising a sulfonamide moiety to treat diseases, afflictions or maladies caused at least in part by abnormal activity of one or more GPCRs or ligand-gated ion channels. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds comprising a sulfonamide moiety, and the screening of those libraries for biological activity, e.g., in animal models of psychosis.

Abstract: A cyclic amine compound represented by the following general formula (1): wherein, R1, R2 and R3 each independently represent a hydrogen atom or an alkoxy group; W1 and W2 each independently represent N or CH; X represents O, NR4, CONR4 or NR4CO; R4 each independently represents a hydrogen atom, or an alkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl group; and l, m and n each represents a number of 0 or 1, a salt thereof and a hydrate thereof are provided. These compounds have inhibitory effects on both cell adhesion and cell infiltration and are useful as anti-asthmatic agents, anti-allergic agents, anti-rheumatic agents, anti-arteriosclerotic agents, anti-inflammatory agents, anti-Sjogren's syndrome agents or the like.

Abstract: This invention is directed to methods for treating hot flashes as a consequence of declining levels of estrogen or androgen in humans. Specifically, the methods of this invention involve the topical administration of a glycopyrrolate analog of Formula (I) to humans.

Abstract: Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

Abstract: Trisubstituted pyrroles are useful in the control of coccidiosis in poultry.

Abstract: Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

Abstract: The present application describes novel lactams and derivatives thereof of formula I: 1

Abstract: Methods for the prevention, treatment, or management of apnea, apnea disorders, bulimia nervosa, irritable bowel syndrome, urinary incontinence, bradycardia, bradyarrhythnia, syncope, other disorders, or symptoms thereof using (+) norcisapride, or a pharmaceutically acceptable salt thereof, substantially free of its (−) stereoisomer.

Abstract: Compounds of formula I useful for inhibiting the pain enhancing effects of E-type prostaglandins are disclosed wherein A is a ring system in which the —CH(R3)N(R2)B—R1 and —OR4 groups are positioned in a 1,2 relationship to one another on ring carbon atoms. B is a ring system having R1 in a 1,3 or 1,4 relationship with the —CH(R1)N(R2)— linking group. A, B, R1, R2, R3 and R4 are as defined in the specification and may be substituted. Also disclosed are pharmaceutically-acceptable salts, in vivo-hydrolysable esters and amides of compounds of formula I, pharmaceutical compositions containing such compounds, processes for preparing such compounds, and the use of such compounds as therapeutic agents.

Abstract: The invention relates to methods and compositions for the prevention, treatment, or management of gastrointestinal disorders or symptoms thereof, employing two or more agents or compounds to provide a triple site action on 5-HT3 receptors, 5-HT4 receptors, and at least one of H2 receptors and proton pumps.

Abstract: Described is a 4-hydroxy-4-phenylpiperidine derivative represented by the following formula (1): [wherein, R1 and R2 are the same or different and each independently represents a hydrogen atom, a lower alkyl, or the like, R3 represents a hydrogen atom or a group —(CR4R5)n—Y (in which, R4 and R5 each represents a hydrogen atom or a lower alkyl group, Y represents a group —COOR6, —CONR7R8, —OR9 or —OCOR10 (in which R6, R9 and R10 each independently represents a hydrogen atom, a lower alkyl group, or the like, R7 and R8 are the same or different and each independently represents a hydrogen atom, a lower alkyl group, or the like), and n stands for 1 to 6)], or salt thereof. The compound exhibits excellent peripheral analgesic action.

Abstract: The present invention relates to the potentiation of glutamate receptor function using certain heterocyclyl sulphonamide derivatives. It also relates to novel heterocyclyl sulphonamide derivatives, to processes for their preparation and to pharmaceutical compositions containing them.

Abstract: Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-&agr; converting enzyme (TACE), a pro-inflmatory cytokine, catalyzes the formation of TNF-&agr; from membrane bound TNF-&agr; precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states.

Abstract: Compositions and methods for the topical delivery of loperamide hydrochloride are disclosed. Novel solvent mixtures have been found to be beneficial in enhancing the penetration of loperamide hydrochloride through the skin.

Abstract: The invention relates to methods and compositions for the prevention, treatment, or management of gastrointestinal disorders or symptoms thereof, employing two or more agents or compounds to provide a triple site action on 5-HT3 receptors, 5-HT4 receptors, and at least one of H2 receptors and proton pumps.

Abstract: Anti-pruritic compositions and methods of using the compositions for the prevention or treatment of pruritus comprising: wherein: R, R2, R3, R4, R7, Ar1 and Ar2 are as defined in the specification in a pharmaceutically acceptable carrier.

Abstract: This invention is directed to benzenamine derivatives of formula (I): wherein A, W, m, n, R1, R2, R3, R4, R5 and R6 are defined herein. These compounds are useful as anti-coagulants.

Abstract: The invention relates to new imides, to a plurality of processes for their preparation and to their use as fungicides.

Abstract: Compounds of Formula I are antagonists of VLA-4 and/or &agr;4&bgr;7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of AIDS-related dementia, allergic conjunctivitis, allergic rhinitis, Alzheimer's disease, asthma, atherosclerosis, autologous bone marrow transplantation, certain types of toxic and immune-based nephritis, contact dermal hypersensitivity, inflammatory bowel disease including ulcerative colitis and Crohn's disease, inflammatory lung diseases, inflammatory sequelae of viral infections, meningitis, multiple sclerosis, multiple myeloma, myocarditis, organ transplantation, psoriasis, pulmonary fibrosis, restenosis, retinitis, rheumatoid arthritis, septic arthritis, stroke, tumor metastasis, uveititis, and type I diabetes.

Abstract: Compounds of the formula are useful in treating disease conditions mediated by TNF-&agr;, such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.

Abstract: Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-&agr; from membrane bound TNF-&agr; precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states.

Abstract: A compound of the formula 1

Abstract: The present invention relates to urethanes derived from azacycloalkanes and the thio and dithio analogues thereof of general formula wherein m, n, A, X, Y, E and R1 to R8 are defined as in claim 1, the enantiomers, diastereomers and the salts thereof, particularly the physiologically acceptable acid addition salts thereof which have valuable properties, particularly an inhibitory effect on cholesterol biosynthesis, pharmaceutical compositions containing these compounds, their use and processes for preparing them.

Abstract: This invention relates to compounds which are generally muscarinic M2/M3 receptor antagonists and which are represented by Formula I: 1

Abstract: This invention relates to neurotrophic, low molecular weight, small molecule heterocyclic ketone and thioester compounds, compositions containing the same, and the use of such compounds for treating neurological disorders, including physically damaged nerves and neurodegenerative diseases.

Abstract: Imido and amido substituted alkanohydroxamic acids reduce the levels of TNF&agr; and inhibit phosphodiesterase in a mammal. A typical embodiment is 3-(3-cyclopentyloxy-4-methoxyphenyl)-N-hydroxy-3-phthalimidopropionamide.

Abstract: Lactam and cyclic urea derivatives and their pharmaceutically acceptable salts are disclosed. The synthesis of these compounds and their use as alpha 1a adrenergic receptor antagonists is also described. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are typically selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved.

Abstract: Pharmaceutical compositions and related methods are disclosed for treating addiction to an array of agents such as heroin, narcotics, cocaine, amphetamines and/or marijuana. Compositions and methods are also disclosed for treating alcoholism and dependence on nicotine intake, such as smoking. Also disclosed are pharmaceutical compositions and related methods for treating various mental illnesses or conditions, such as for example, schizophrenia and manic depressive psychosis.

Abstract: The invention relates to a compound of the formula 1

Abstract: In view of the situation of the prior art, the present invention specifies the structure of a late-stage product of Mailard reaction in vivo having a close relation with various tissue disorders, and provides a diagnostic reagent for complications associated with diabetes or renal failure, containing the above compound as a main component.

Abstract: Compound of formula (I): wherein: n represents 0 or 1, R1 represents hydrogen, arylalkyl, alkyl, acyl, alkoxycarbonyl, arylalkoxycarbonyl or trifluoroacetyl, R2 represents alkyl, X represents oxygen, chlorine, OR3, SR4 or NOR5, R3 represents hydrogen, alkyl, acyl, alkoxycarbonyl or arylalkoxycarbonyl, R4 represents hydrogen, alkyl or aryl, R5 represents hydrogen or optionally substituted alkyl, represents a single or double bond, Ar represents aryl or heteroaryl, its isomers and addition salts thereof with a pharmaceutically acceptable acid, and medicinal products containing the same which are useful as facilitators of memory and cognition and antalgic agents.

Abstract: This invention relates to novel isoxazolines of formula (I): or a pharmaceutically acceptable salt form thereof. This invention also relates to novel isoxazolines of formula (I) which are useful as antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of thromboembolic disorders.

Abstract: The present invention provides screening methods for identifying compounds which induce tardive dyskinesia (TD) when administered to an animal. In particular, the methods involve assaying for intermediates and end products of reactions associated with candidate compound mediated reduction of reducible substrates. Also provided are high-throughput screening methods for determining whether compounds induce TD when administered to an animal. Further, provided are methods for treating psychoses comprising testing antipsychotic drugs to identify those which will not induce TD when administered to an animal and administering one or more such drugs to a patient in need thereof.

Abstract: Compositions are disclosed utilizing the optically pure (−) isomer of norcisapride. This compound is a potent drug for the treatment of gastro-esophageal reflux disease, emesis, dyspepsia and other conditions while substantially reducing the concomitant liability of adverse effects associated with cisapride. The (−) isomer of norcisapride also avoids the adverse drug interactions associated with racemic cisapride and other therapeutic agents.

Abstract: Sulfonamide derivatives, their physiologically tolerable salts and their prodrugs according to the present invention are vitronectin receptor antagonists and inhibitors of cell adhesion, as well as inhibit bone resorption by osteoclasts. These derivatives, salts and prodrugs are pharmaceutically active compounds useful in the therapy and prophylaxis of diseases which are caused at least partially by an undesired extent of bone resorption, for example of osteoporosis. Processes for the preparation of the sulfonamide derivatives according to the present invention, the use of these derivatives as pharmaceutically active ingredients, and pharmaceutical preparations comprising these derivatives also are disclosed.