Abstract: The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein R1 is hydrogen, optionally substituted C1-6alkyl, aryl; R2 is each independently a halogen, hydroxy, C1-6alkyl, C1-6alkyloxy or nitro; n is 0, 1, 2 or 3; Alk is C1-6alkanediyl; D is an optionally substituted saturated or unsaturated nitrogen containing heterocycle; and aryl is optionally substituted phenyl; having a great therapeutic breadth. It further relates to their use as a medicine, their preparation as well as compositions containing them.

Abstract: Pharmaceutical compounds comprising bridged nicotine analogs of N-octylnicotinium iodide (NONI) having selective antagonist properties at &agr;3&bgr;2-containing nicotinic receptor subtypes, and compositions containing these compounds. The compounds and compositions are used to treat central nervous system pathologies.

Abstract: Compounds containing tetrahydrobenzindole which bind to serotonin receptor and are useful in treatment or prevention of disease induced by abnormality of central peripheral serotonin controlling functions.

Abstract: The present invention relates to novel &bgr;-carboline derivatives of the general formula wherein all the variables are as described within the specification, useful as phosphodiesterase inhibitors. The present invention further relates to use of the described derivatives for the treatment of diseases and conditions related to PDE, for example male erectile dysfunction.

Abstract: Novel triazolo derivatives represented by the following formula and pharmaceutically acceptable salts thereof, as well as chemokine inhibitors containing the same as an effective component. These are useful as therapeutic agents for allergic diseases such as bronchial asthma and atopic dermatitis; therapeutic agents for inflammatory diseases such as chronic rheumatoid arthritis; therapeutic agents for autoimmune diseases such as ulcerative colitis and nephritis; and as anti-AIDS drugs.

Abstract: The present invention relates to indoline derivatives. These compounds are especially useful for the prevention and treatment of disorders of the central nervous system; damage to the central nervous system; cardiovascular disorders; gastrointestinal disorders; diabetes, sleep apnea, and especially for the treatment and prevention of obesity.

Abstract: Cycloalcanoindole and -azaindole derivatives are prepared by reaction of appropriately substituted carboxylic acids with anmines. The cycloahloanindole and -azaindole derivatives are suitable as active compounds for medicaments, preferably antiatherosclerotic medicaments.

Abstract: Non-peptide compounds that act as antagonists of the intestinal hormone glucagons-like peptide 1 (GLP-1) have a 9H-b-carboline central motif. The compounds exhibit advantageous physical, chemical and biological properties and inhibit GLP-1 peptide binding to the GLP-1 receptor and/or prevent activation of the receptor by bound GLP-1. The invention further relates to a method of inhibiting the binding of GLP-1 to the GLP-1 receptor and a method of inhibiting the activation of the GLP-1 receptor. Intermediate compounds useful for making non-peptide GLP-1 receptor antagonists are also described.

Abstract: The invention relates to hydroxamic and carboxylic acid derivatives. Compounds of the formula: are disclosed. These compounds are useful for the treatment of diseases mediated by inhibitors of matrix metalloproteinase, ADAM, ADAM-TS enzymes, and or INF&agr;-mediated diseases including degenerative diseases and certain cancers.

Abstract: Cycloalkano-indole and -azaindole derivatives are prepared by reaction of appropriately substituted carboxylic acids with amines. The cycloalkano-indole and -azaindole derivatives are suitable as active compounds for medicaments, preferably antiatherosclerotic medicaments.

Abstract: Compounds of general structural formula (I) wherein A represents a 5- or 6-membered heteroaryl group containing at least one heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur, and use of the compounds, and salts and solvates thereof, as therapeutic agents, are disclosed.

Abstract: Cysteine protease inhibitors which deactivate the protease by covalently bonding to the cysteine protease and releasing the enolate of a 1,3-dicarbonyl (or its enolic form). The cysteine protease inhibitors of the present invention accordingly 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 &bgr;-dicarbonyl enol ether leaving group.

Abstract: Optically active tetrahydrobenzindole type compounds having affinity for a 5-HT receptor, useful for prevention and treatment of mental diseases. A species compound is (S)-2a-4-(4-(2-methoxyphenyl)piperazinyl)butyl)-2a,3,4,5,-tetrahydro 1 H-benz[cd]indol-2-one.

Abstract: A compound selected from those of formula (I): wherein: represents single or double bond, R1 represents hydrogen, alkyl, —R6-aryl, —R6-cycloalkyl, —R6-heterocycle, —CO2R7—, —COR8, or —CONHR8, wherein R6, R7, and R8 are as defined in the description, R2 represents cyano, mono- or di-alkylaminoalkylaminocarbonyl, —CO2R8, —CONHR8, —NR8R9, —NHCO2R7, or —COR8 wherein R7, R8, and R9 are as defined in the description, R3 and R4 together form (C3-C10)cycloalkyl, R5 represents hydrogen, alkyl, or arylalkyl, Ra, Rb, Rc, Rd, which may be identical or different, represent a group as defined in the description, its isomers, and pharmaceutically-acceptable acid or base addition salts thereof, and medicinal products containing the same which are useful in the treatment of CNS disorders.

Abstract: Therapeutic compounds and methods for inhibiting a glycosaminoglycan (GAG)-associated molecular interaction in a subject, whatever its clinical setting, are described.

Abstract: Disclosed are compounds of the formula: 1

Abstract: A compound of formula and salts and solvates thereof, wherein R0, R1, and R2 are defined in the specification. A compound of the present invention is a potent and selective inhibitor of cGMP-specific PDE and has utility in a variety of therapeutic areas where such inhibition is beneficial.

Abstract: Spiro compounds of the formula (I), where X1, X2, X3, X4 are identical or different and are —S—, —O—, —NR5—, —CR5═N— or —CR5═CH—, with the proviso that at least one of the groups X1-4 is different from —CR5═CH—, are suitable as charge transport materials, in particular for photovoltaic cells, and as electroluminescence materials.

Abstract: Disclosed are compounds of the formula: wherein Ar, R1, R2, R3, W, X, Y, and Z are substituents as defined herein, which compounds are highly selective partial agonists or antagonists at human CRF1 receptors and are useful in the diagnosis and treatment of treating stress related disorders such as post traumatic stress disorder (PTSD) as well as depression, headache and anxiety.

Abstract: This document describes a novel and practically excellent process for the preparation of optically active compounds, such as optically active alcohols or amines which are useful for various applications, for example, as synthetic intermediates of pharmaceuticals, liquid crystal materials, and reagents for optical resolution, wherein a hydrogen transfer type asymmetric reduction is carried out in the presence of both a transition metal complex and an optically active nitrogen compound or a transition metal complex having an optically active nitrogen compounds as an asymmetric ligand, and a hydrogen-donating organic or inorganic compound.

Abstract: A class of novel tricyclics is disclosed together with the use of such compounds for inhibiting sPLA2 mediated release of fatty acids for treatment of conditions such as septic shock.

Abstract: The invention provides a process for the preparation of a compound of general formula (I): wherein Im represents an imidazolyl group of the formula: and R1 represents a hydrogen atom or a group as herein defined including —CO2R5, —COR5, —CONR5R6 or —SO2R5 wherein R5 and R6, which may be the same or different, are as herein defined with the proviso that R5 does not represent a hydrogen atom when R1 represents a group —CO2R5 or —SO2R5; one of the groups represented by R2, R3 and R4 is a hydrogen atom or a C1-6alkyl, C3-7cycloaklyl, C3-6alkenyl, phenyl or phenyl C1-3alkyl group, and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C1-6alkyl group; and n represents 2 or 3; which comprises reacting a compound of formula (II) or a protected derivative thereof, with a compound of formula (III): HOCH2-Im  (III) or a salt thereof in the presence of an acid at an elevat

Abstract: A compound of formula (I) ##STR1## and salts and solvates thereof, in which: R.sup.0 represents hydrogen, halogen or C.sub.1-6 alkyl;R.sup.1 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, haloC.sub.1-6 alkyl, C.sub.3-8 cyloalkyl, C.sub.3-8 cycloalkylC.sub.1-3 alkyl, arylC.sub.1-3 alkyl or heteroarylC.sub.1-3 alkyl;R.sup.2 represents an optionally substituted monocyclic aromatic ring selected from benzene, thiophene, furan and pyridine or an optionally substituted bicyclic ring ##STR2## attached to the rest of the molecule via one of the benzene ring carbon atoms and wherein the fused ring A is a 5- or 6-membered ring which may be saturated or partially or fully unsaturated and comprises carbon atoms and optionally one or two heteroatoms selected from oxygen, sulphur and nitrogen; andR.sup.3 represents hydrogen or C.sub.1-3 alkyl, or R.sup.1 and R.sup.3 together represent a 3- or 4-membered alkyl or alkenyl chain.

Abstract: This invention relates to 4-substituted .beta.-carbolines and .beta.-carboline analogs that inhibit Ca.sup.+2 influx and interleukin-2 (IL-2) production. The 4-substituted .beta.-carbolines and .beta.-carboline analogs of this invention are represented by formula (I): ##STR1## wherein Q, n, R, R', R" and R.sub.1 -R.sub.4 are as defined herein. This invention also relates to methods for producing .beta.-carbolines. Because of their selective immunomodulating properties, the compounds and pharmaceutical compositions of this invention are particularly well suited for preventing and treating immune disorders, including autoimmune disease, inflammatory disease, organ transplant rejection and other disorders associated with IL-2 mediated immune response.

Abstract: The present invention provides novel tetrahydro-beta-carboline compounds having useful central nervous system activity. Further, there is provided 3-ethanamine and 3-ethanamine related compounds which are useful intermediates and have beneficial central nervous system activity. The invention provides formulations and methods for using the novel tetrahydro-beta-carboline and related compounds.

Abstract: This invention concerns the compounds of formula ##STR1## the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Alk is C.sub.1-6 alkanediyl; R.sup.1 is hydrogen, C.sub.1-6 alkyl, aryl or aryl C.sub.1-6 alkyl; R.sup.2, R.sup.3 and R.sup.4 are each independently selected from hydrogen, halo, hydroxy, nitro, cyano, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, trifluoromethyl, C.sub.1-6 alkylthio, mercapto, amino, mono- and di(C.sub.1-6 alkyl)amino, carboxyl, C.sub.1-6 alkyloxycarbonyl or C.sub.1-6 alkylcarbonyl; R.sup.5 is hydrogen, C.sub.1-6 alkyl, phenyl or phenylC.sub.1-6 alkyl; R.sup.6 is hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, C.sub.1-6 alkylthio, or a radical of formula --NR.sup.8 R.sup.9, wherein R.sup.8 and R.sup.9 are each independently selected from hydrogen, C.sub.1-6 alkyl, phenyl or phenylC.sub.1-6 alkyl; R.sup.7 is hydrogen or C.sub.1-6 alkyl; or R.sup.6 and R.sup.7 taken together may form a bivalent radical of formula --R.sup.6 --R.sup.

Abstract: Carboline derivatives of formula (I) ##STR1## are potent and selective inhibitors of cyclic guanosine 3',5'-monophosphate specific phosphodiesterase (cGMP-specific PDE) and have utility in a variety of therapeutic areas where such inhibition is thought to be beneficial, including the treatment of cardiovascular disorders and erectile dysfunction.

Abstract: A compound of formula (I) ##STR1## and salts and solvates thereof, in which: R.sup.0 represents hydrogen, halogen or C.sub.1-6 alkyl;R.sup.1 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, haloC.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkylC.sub.1-3 alkyl, arylC.sub.1-3 alkyl or heteroarylC.sub.1-3 alkyl;R.sup.2 represents an optionally substituted monocyclic aromatic ring selected from benzene, thiophene, furan and pyridine or an optionally substituted bicyclic ring ##STR2## attached to the rest of the molecule via one of the benzene ring carbon atoms and wherein the fused ring A is a 5- or 6-membered ring which may be saturated or partially or fully unsaturated and comprises carbon atoms and optionally one or two heteroatoms selected from oxygen, sulphur and nitrogen; andR.sup.3 represents hydrogen or C.sub.1-3 alkyl, or R.sup.1 and R.sup.3 together represent a 3- or 4-membered alkyl or alkenyl chain.

Abstract: A compound of formula ##STR1## and salts and solvates thereof, wherein R.sup.0, R.sup.1, and R.sup.2 are defined in the specification. A compound of the present invention is a potent and selective inhibitor of cGMP-specific PDE and has utility in a variety of therapeutic areas where such inhibition is beneficial.

Abstract: Tricyclic compounds are described as well as methods for the preparation and pharmaceutical compositions of same, which are useful as inhibitors of matrix metalloproteinases, particularly gelatinase A (72 kD gelatinase) and stromelysin-1 and for the treatment of multiple sclerosis, atherosclerotic plaque rupture, aortic aneurism, heart failure, restenosis, periodontal disease, corneal ulceration, cancer metastasis, tumor angiogenesis, arthritis, or other autoimmune or inflammatory disorders dependent upon tissue invasion by leukocytes.

Abstract: The invention relates to a process and intermediates for the preparation of enantiomerically pure cycloalkanoindolecarboxylic acids and azaindolecarboxylic acids and pyrimido?1,2a!indolecarboxylic acids and their activated derivatives, characterized in that the tolyl acetic acid is first esterified with a chiral alcohol, then diastereoselective substitution at .alpha.-carbon atoms is carried out and this product is halogenated in the tolyl group and then reacted with appropriate cycloalkanoindoles, cycloalkanoazaindoles or pyrimido?1,2a!indoles. It is possible by this method to prepare specifically, in high purity, the enantiomerically pure carboxylic acids which are intermediates for valuable medicaments.

Abstract: Compounds are provided which inhibit microsomal triglyceride transfer protein and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases. The compounds have the structure ##STR1## wherein R.sup.1 to R.sup.6, Q, and X are as defined herein.

Abstract: The present invention provides novel tetrahydro-beta-carboline compounds having useful central nervous system activity. The invention provides formulations and methods for using the novel tetrahydro-beta-carboline and related compounds. Such compounds are particularly useful for the modulation of a 5-HT.sub.2B receptor.

Abstract: 9H-Pyrido?3,4-b!indole compounds have a pronounced leukotriene-B.sub.4 antagonistic action, and thus show a completely different spectrum of activity than known .beta.-carbolines.

Abstract: A compound of formula (I) ##STR1## and salts and solvates thereof, in which: R.sup.0 represents hydrogen, halogen or C.sub.1-6 alkyl;R.sup.1 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, haloC.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkylC.sub.1-3 alkyl, arylC.sub.1-3 alkyl or heteroarylC.sub.1-3 alkyl; R.sup.2 represents an optionally substituted monocyclic aromatic ring selected from benzene, thiophene, furan and pyridine or an optionally substituted bicyclic ring ##STR2## attached to the rest of the molecule via one of the benzene ring carbon atoms and wherein the fused ring A is a 5- or 6-membered ring which may be saturated or partially or fully unsaturated and comprises carbon atoms and optionally one or two heteroatoms selected from oxygen, sulphur and nitrogen; andR.sup.3 represents hydrogen or C.sub.1-3 alkyl, or R.sup.1 and R.sup.3 together represent a 3- or 4-membered alkyl or alkenyl chain.

Abstract: Fibrinogen receptor antagonists having the structureX--Y--Z--A--Band pharmaceutically acceptable salts, wherein X is a 5, 6 or 7 membered aromatic or nonaromatic ring, and Y is a 5 or 6 membered aromatic ring, e.g.

Abstract: We have found that indoles of structural formula (III): ##STR1## can be cost-effectively synthesized in high yield by the palladium-catalyzed coupling/ring closure of a 2-halo- or 2-trifluoromethylsulfonyl-aniline and a cyclic ketone derivative. The process of the present invention is particularly useful to form indoles containing acid-labile substituents such as triazole, acetyl, ketal, cyano, and carbamate, or indoles having a good leaving group in the benzyl position. The advantages of the present process are that it does not require the use of triphenyl phosphine or tetrabutyl ammonium chloride or lithium chloride.

Abstract: Compounds of the formula (I): ##STR1## are prepared by reaction of the phenylacetic acid derivatives substituted by the appropriate heterocycles, optionally in an activated form, with phenylglycinols. The compounds are suitable as active compounds in medicaments, in particular in medicaments having antiatherosclerotic activity.

Abstract: The present invention relates to therapeutically active non competitive antagonists, acting selectively at the metabotropic glutamate receptor. The novel compounds are useful in treating diseases in the central nervous system by modulating synaptic transmission via the metabotropic glutamate receptor.

Abstract: Tetrahydro-beta-carboline compounds having useful central nervous system activity are enclosed.

Abstract: The present invention discloses compounds that are highly isozyme selective protein kinase C beta-1 and beta-2 isozyme inhibitors. Accordingly, the present invention provides a method of selectively inhibiting protein kinase C isozymes beta-1, and beta-2. As isozyme selective inhibitors of beta-1 and beta-2, the compounds are therapeutically useful in treating conditions associated with diabetes mellitus and its complications, as well as other disease states associated with an elevation of the beta-1 and beta-2 isozyme.

Abstract: Compounds of the formula: ##STR1## in which R.sub.1 represents a hydrogen or halogen atom or a methyl or C.sub.1 -C.sub.4 alkoxy group, R'.sub.1 represents a hydrogen or halogen atom, R".sub.1 represents a hydrogen atom or a methoxy group, R.sub.3 represents a C.sub.1 -C.sub.3 alkyl group, R.sub.4 represents a 2,3-dihydro-1H-inden-2-yl, 2,3-dihydro-1H-inden-1-yl or 1,2,3,4-tetrahydronaphthalen-1-yl group, or R.sub.3 and R.sub.4 together form, with the adjacent nitrogen atom, a 1,2,3,4-tetrahydroisoquinol-2-yl, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinol-2-yl, 5,8-dimethoxy-1,2,3,4-tetrahydroisoquinol-2-yl, 1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indol-2-yl, 1,2,3,4-tetrahydro-9H-pyrido[4,3-b]indol-3-yl, 4,5,6,7-tetrahydrothieno[2,3-c]pyrid-6-yl, 2,3-dihydro-1H-isoindol-2-yl or 2,3,4,5-tetra-hydro-1H-3-benzazepin-3-yl, group are useful in the treatment of cerebral disorders.

Abstract: The present invention provides novel tetrahydro-beta-carboline compounds and intermediates having useful central nervous system activity. The invention provides formulations and methods for using the tetrahydro-beta-carboline and related intermediate compounds. Finally, the invention provides an article of manufacture.

Abstract: Trifluoromethylpyrroloindolecarboxylic acid ester derivatives, and optical isomers and pharmaceutically acceptable salts thereof are provided which are represented by the general formula (1): ##STR1## or the general formula (2): ##STR2## The compounds are antineoplastic agents which are selective to cancer cells, effective also to solid cancer, and less toxic.

Abstract: The present invention provides novel tetrahydro-beta-carboline compounds having useful central nervous system activity. Further, there is provided tetrahydro-beta-carboline related compounds which are useful intermediates and have beneficial central nervous system activity. The invention provides formulations and methods for using the novel tetrahydro-beta-carboline and related compounds. Such compounds are particularly useful for the modulation of a 5-HT.sub.2B receptor.

Abstract: Azatoxin and derivatives thereof are illustrative of a new class of antitumor drugs that are topoisomerase II (top 2) inhibitors. The pharmacophore inhibits the catalytic activity of the purified enzyme but does not unwind relaxed or supercoiled DNA. It is nonintercalative and has at least two domains: a quasiplanar polycyclic ring system, which may bind between DNA base pairs, and a pendant substituent thought to interact with the enzyme, with the DNA grooves or with both. In SV40 and c-myc DNA, azatoxin induces numerous double-strand breaks according to a cleavage pattern which differs from those of known top 2 inhibitors. Azatoxin also is a potent inhibitor of tubulin polymerization.

Abstract: Selected acid functional beta-carboline type derivatives effective as thromboxane synthase inhibitors having the formula: ##STR1## where R.sub.1 and R.sub.2 are monovalent radicals, --(L.sub.a)-- is a linking group of 4 to 8 chain atoms, and A is an acidic group.

Abstract: Novel alcohols of the formula ##STR1## wherein R.sup.a is azido or phthalimido, R.sup.4 is alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl, R.sup.7 and R.sup.8 together are a trimethylene or tetramethylene group which is optionally substituted by hydroxy, alkoxycarbonylamino or acylamino or in which one --CH.sub.2 -- group is replaced by --NH--, -N(alkoxycarbonyl)-,-N(acyl)- or --S--or which carries a fused cycloalkane, aromatic or heteroaromatic ring, and R.sup.9 is alkoxycarbonyl, monoalkylcarbamoyl, monoaralkylcarbamoyl, monoarylcarbamoyl or a group of the formula ##STR2## in which R.sup.10 and R.sup.11 each is alkyl, are described along with a process for their manufacture. These alcohols are useful as intermediates, for example in the manufacture of amino acid derivatives having antiviral activity.

Abstract: This invention relates to novel substituted tryptamine and phenalkylamine and related compounds, pharmaceutical compositions thereof and methods of using said compounds.

Abstract: Novel alcohols of the formula ##STR1## wherein R.sup.a is azido or phthalimido, R.sup.4 is alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl, R.sup.7 and R.sup.8 together are a trimethylene or tetramethylene group which is optionally substituted by hydroxy, alkoxycarbonylamino or acylamino or in which one --CH.sub.2 -- group is replaced by --NH--, --N(alkoxycarbonyl)--, --N(acyl)-- or --S-- or which carries a fused cycloalkane, aromatic or heteroaromatic ring, and R.sup.9 is alkoxycarbonyl, monoalkylcarbamoyl, monoaralkylcarbamoyl, monoarylcarbamoyl or a group of the formula ##STR2## in which R.sup.10 and R.sup.11 each is alkyl, are described along with a process for their manufacture. These alcohols are useful as intermediates, for example in the manufacture of amino acid derivatives having antiviral activity.