Abstract: Compounds of the formula I are suitable for the production of pharmaceuticals for the prophylaxis and therapy of disorders in the course of which an increased activity of matrix-degrading enzymes is involved.

Abstract: The invention provides compounds, compositions and methods relating to novel arylsulfonanilide derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infrections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.

Abstract: Vitronectin receptor antagonists, their preparation and their use The present invention relates to compounds of the formula I A—B—D—E—F—G   (I) in which A, B, D, E, F and G have the meanings given in the patent claims, to their preparation and to their use as medicaments. The compounds of the invention are used as vitronectin receptor antagonists and as inhibitors of bone resorption.

Abstract: A low volatile organic compound co-solvent system is disclosed for preparing emulsion concentrates of low melting organophosphorous insecticides wherein the bioefficacy of the insecticide active is significantly enhanced. The co-solvent system comprises a water-soluble ethoxylated fatty acid/rosin acid-nonionic surfactant composition.

Abstract: Claimed are newly synthesized phosphorus containing cytisine derivatives of the general formula wherein n is 0 or 1; X is O or S; R=CH3; C2H5; C3H7; 1-C3H7; C4H9; at n=1: X=O R=CH3 R1=1—C3H7; C6H5; CH3—O—C6H4—; with a proviso that n is 1, X is O. It is shown that some of the synthesized compounds exhibit substantial hepatoprotective and antienzyme activity.

Abstract: The subject invention pertains to a process for preparing a compound having a formula (4) or (5), in either optically-enriched or racemic form, wherein R1, R2, R3 and R4 are independently selected from hydrogen, alkyl, aryl, alkaryl, aralkyl and acyl groups. In one embodiment, the process of the invention comprises mixing with a plant extract obtained from crushed daffodil bulbs or crushed snowdrop bulbs an oxidative cyclisation precursor of the compound.

Abstract: The invention encompasses the novel class of compounds represented by formula I which are inhibitors of the PTP-1B enzyme. The invention also encompasses pharmaceutical compositions and methods of treating or preventing PTP-1B mediated diseases.

Abstract: New halogenobezimidazoles of the formula ##STR1## in which A, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and X have the meanings given in the description,and their acid addition salts and metal salt complexes,a process for their preparation and their use as microbicides in crop protection and in the protection of materials.New intermediates of the formulae ##STR2## which R.sup.12 -R.sup.7 and X have the meanings given in the description,and processes for the preparation of these substances.

Abstract: Phosphate derivatives are disclosed of quinazolinone compounds having structural formula (I) or a pharmaceutically acceptable salt thereof, wherein X' represent hydroxyl, alkyl, alkoxy, or O--Z where Z is a phosphate or phosphate derivative; Y' represents hydrogen, alkyl or an optionally substituted aryl group or optionally substituted aralkyl group; and R' is hydrogen, alkyl, or CH.sub.2 --O--Z where Z is again a phosphate or phosphate derivative; subject to the proviso that if neither X' nor R' contains Z, Y' is an aryl or aralkyl group having an O--Z substituent therein with Z once again being a phosphate or phosphate derivative as hereinabove defined. These compounds are useful as prodrugs for providing active PARP inhibiting substances for medical use in conjunction with a cytotoxic drug or radiotherapy in order to increase the effectiveness of the latter, especially in connection with antitumor treatment.

Abstract: There is provided an emulsifier composition comprising (a) a blend consisting essentially of a polyoxyethylene (EO)/polyoxypropylene (PO) block copolymer which contains 10-40% EO, and where the molecular weight of the PO hydrophobe is about 500-6000; anionic surfactants; and a solvent; (b) a blend consisting essentially of a polyoxyethylene (EO)/polyoxypropylene (PO) block copolymer which contains 50-80% EO, and where the molecular weight of the PO hydrophobe is about 500-6000; anionic surfactants; and a solvent; and (c) a butyl ether of an EO/PO block copolymer.

Abstract: Novel benzimidazole compounds of the following structure and their use as fructose-1,6-bisphosphatase inhibitors is described ##STR1##

Abstract: Estratriene derivatives of the following formula have a powerful inhibitory effect on estrone sulfatase and are hence useful for the prophylaxis or treatment of diseases caused by estrogens, such as breast cancer, uterine cancer, ovarian cancer, endometriosis, adenomyosis uteri and mastopathy. ##STR1## wherein one of A and B represents C.dbd.O or CH.sub.2 and the other represents O or NH; and R represents --SO.sub.2 NR.sup.1 R.sup.2 or --PO(OM).sub.2 in which R.sup.1 and R.sup.2 each independently represent a hydrogen atom or a lower alkyl group and M represents a hydrogen atom or an alkali metal; provided that, when one of A and B represents NH, the other represents C.dbd.O.

Abstract: The disclosure relates to quinoxaline derivatives of Formula I ##STR1## wherein R.sup.1, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 are as defined in the disclosure, as well as their production and use in medicinal agents.

Abstract: The present invention relates to phosphonic acid derivatives that inhibit N-Acetylated .alpha.-Linked Acidic Dipeptidase (NAALADase) enzyme activity, pharmaceutical compositions comprising such derivatives, and methods of using such derivatives to inhibit NAALADase activity, to treat a glutamate abnormality and to treat a prostate disease in an animal.

Abstract: Phosphonate-nucleotide ester compounds of the formula (I) have excellent antiviral activity and antineoplastic activity. Further, they can be orally administered. ##STR1## wherein ring A represents ##STR2## wherein R.sup.1 and R.sup.2 independently represent hydrogen, halogen, hydroxyl, mercapto, C.sub.6 -C.sub.10 arylthio or amino; R.sup.3 represents C.sub.1 -C.sub.4 alkyl or ethyl having one or more substituents selected from the group consisting of fluorine, C.sub.1 -C.sub.4 alkoxy, phenoxy, C.sub.7 -C.sub.10 phenylalkoxy and C.sub.2 -C.sub.5 acyloxy; R.sup.4 represents ethyl having one or more substituents selected from the group consisting of fluorine, C.sub.1 -C.sub.4 alkoxy, phenoxy, C.sub.7 -C.sub.10 phenylalkoxy and C.sub.2 -C.sub.5 acyloxy; X, Y and Z independently represent methyne or nitrogen atom; or a pharmaceutically acceptable salt thereof.

Abstract: New halogenobenzimidazoles of the formula in whichA, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and X have the meanings given in the description,and their acid addition salts and metal salt complexes,a process for their preparation and their use as microbicides in crop protection and in the protection of materials.New intermediates of the formula ##STR1## in which R.sup.12 -R.sup.17 and X have the meanings given in the description,and processes for the preparation of these substances.

Abstract: The present invention relates to a method of treating a glutamate abnormality and a method of effecting a neuronal activity in an animal using a NAALADase inhibitor, and a pharmaceutical composition comprising an effective amount of a NAALADase inhibitor for treating a glutamate abnormality and effecting a neuronal activity in an animal.

Abstract: This invention relates generally to medical treatment methods. Specifically, the invention relates to methodology for the correction of defective chloride transport by activation of chloride channels of the lung and other epithelia using genetic or chemical modification. These methods relate to the treatment of epithelia with compounds which cause activation of the channel as measured by increased probability (Po) of opening of the channel at physiologically relevant holding potentials. These methods also relate to the treatment of epithelia with gene therapy to introduce chloride channels genes with site mutations which cause activation of the channel as measured by increased probability (Po) of opening of the channel at physiologically relevant holding potentials. These treatments will reduce life-threatening complications frequently found in diseases such as cystic fibrosis. These methods of activation of chloride channels also comprise treatment of chloride channels with amidation reactions.

Abstract: Selective blockade of DA and 5-HT uptake sites with 3-aryltropane derivatives.

Abstract: The present invention includes compositions and methods of treatment for glutamate abnormalities and associated nervous tissue insult in a animal by inhibition of NAALADase enzyme. Compositions include glutamate-derived hydroxyphosphinyl derivative compounds, acidic peptide analogs, phosphinic acid derivatives and mixtures thereof that inhibit NAALADase enzyme activity and their use for treating glutamate abnormalities such as created by global and focal ischemia.

Abstract: Compounds having the following formulae I and II, and pharmaceutically acceptable salts thereof, including dual inhibitors of ACE and NEP and selective ACE inhibitors: ##STR1## and wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.5a, R.sup.5b, R.sup.6, R.sup.7, R.sup.11, q and r are defined herein.

Abstract: Heterocyclic derivatives of the formula (I) ##STR1## wherein each symbol is as defined in the specification, pharmaceutically acceptable salts thereof and method of producing them. Pharmaceutical compositions containing the heterocyclic derivative or a pharmaceutically acceptable salt thereof, particularly, ACAT inhibitors and lipoperoxidation inhibitors. The heterocyclic derivatives and pharmaceutically acceptable salts thereof of the present invention show superior ACAT inhibitory activity and lipoperoxidation inhibitory activity, and are useful as ACAT inhibitors and hyperlipemia inhibitors. To be specific, they are useful for the prevention and treatment of arteriosclerotic lesions of arteriosclerosis, hyperlipemia and diabetes, as well as ischemic diseases of brain, heart and the like.

Abstract: The present invention is drawn to water soluble derivatives aliphatic acid aromatic secondary and tertiary amine containing drugs. The present invention is further drawn to methods of making water soluble derivatives of aliphatic and aromatic secondary and tertiary amine containing drugs.

Abstract: A phosphonic diester derivative represented by the following formula (1): ##STR1## wherein R.sup.1 represents a cycloalkyl group; a phenyl group which may have 1 to 3 substituents selected from the group consisting of a lower alkoxy group, a lower alkyl group, a halogen atom, a halogen-substituted lower alkyl group, a lower alkanoyl group, a nitro group, a benzoyl group, a cyano group, an N-lower alkylcarbamoyl group, an N-phenyl-lower alkylcarbamoyl group, an N-(halogen-substituted phenyl)carbamoyl group and an N,N-di-lower alkylcarbamoyl group; a 1,3,4-thiadiazol-2-yl group having a halogen-substituted lower alkyl group as a substituent; a thiazolyl group; a pyridyl group which may be substituted by a halogen atom; a benzothiazol-2-yl group having 1 to 2 lower alkoxy groups on the phenyl ring; or a 4,5-dihydrothieno[3,2-e]benzothiazol-2-yl group; R.sup.2 represents a hydrogen atom or a phenyl lower alkyl group; R.sup.3 and R.sup.

Abstract: Tricyclic diazepines of the formula: ##STR1## wherein A, B, D, E, F, Y and Z are defined in the specification which compounds have vasopressin and oxytocin antagonist activity.

Abstract: Mammalian hair growth is reduced by inhibiting the activity of a matrix metalloproteinase in the skin.

Abstract: A novel estrogen derivative represented by the formula: ##STR1## is useful for treating or preventing diseases caused by estrogen deficiency.

Abstract: Phosphoramidates and phosphinic amides and related compounds are provided. Also provided are methods that use the compounds for modulating the activity of the endothelin family of peptides are provided. In particular, compounds having formula: ##STR1## in which A, B, R.sup.1 and R.sup.2 are as described are provided. Also provided are methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these compounds or prodrugs thereof. Methods for elucidating the physiological and pathophysiological roles of endothelin, as well as isolating endothelin receptors are also provided.

Abstract: A method is described to prevent neural cell injury by use of a compound from a class of phosphonometyl-imidazo?1,2-a!pyrimidine-2-carboxylic acid compounds. The treatment includes administration of a compound of this class alone or in a composition in an amount effective as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites. Compounds of most interest are those of the formula: ##STR1## wherein Y.sub.m is --CH.sub.2 -- or --CH.sub.2 --CH.sub.2 --; where m is one; wherein X is one or more groups attachable at one or more of the 5-, 6- and 7-ring positions of the imidazo?1,2-a!pyrimidine ring system; wherein each X and T is independently selected from hydrido, halo, alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, alkenyl, alkynyl, phenyl, benzyl, hydroxy, hydroxyalkyl, alkoxy, phenoxy, alkoxyalkyl, benzyloxy, cyano, alkanoyl, alkylthio, arylthio and amino; wherein each of R.sup.1, R.sup.2 and R.sup.

Abstract: Novel galanthamine derivatives of general fonnulae (Ia) and (Ib), a method for preparing same, pharmaceutical compositions containing said derivatives, and their use, in particular as cholinesterase inhibitors, are disclosed.

Abstract: A composition for preventing and treating milk fever in freshening cows, and a method of administering the composition. The basic composition is a mixture of water, calcium chloride, propylene glycol, B vitamins and minerals. The calcium content is lower than conventional calcium treatments used for this purpose. The propylene glycol gives the cow an energy boost and sweetens the taste so the cow does not object to it as it does to conventional gels and liquids. The B vitamins stimulate the cow's appetite. The minerals replace minerals lost in the milk and also help the cow absorb calcium. The composition of the present invention is in a liquid form and is preferably administered using a 200-300 cc drench gun. The end of the dispensing tube of the drench gun is placed between the teeth and cheek of the cow near the receptors that stimulate the esophageal groove reflex.

Abstract: Novel products of formula (I): ##STR1## preparation thereof and pharmaceutical compositions containing said products are disclosed. In formula (I), R is a group of formula --(CH.sub.2).sub.m --X.sub.1 --(CH.sub.2).sub.n --Z, where X.sub.1 is a simple bond or O or S, n is 0 or 1 and n is 0, 1 or 2, the CH.sub.2 groups being optionally substituted by carboxy, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, amino, alkylamino or dialkylamino, and Z is carboxy, COOR.sub.4, where R.sub.4 is alkyl, or CON(R.sub.5)(R.sub.6), where R.sub.5 hydrogen or alkyl and R.sub.6 is hydrogen or optionally substituted alkyl, or else R.sub.5 is hydrogen or alkyl and R.sub.6 is hydroxy, optionally substituted alkoxy or amino, or PO(OR.sub.7).sub.2, where R.sub.7 is hydrogen or alkyl; or a group --NH--CO--T where T is hydrogen or optionally substituted alkyl; or else a group (a); R.sub.1 and R.sub.2 are hydrogen or halogen or optionally substituted alkyloxy or alkyl, or else R.sub.1 and R.sub.

Abstract: Novel substituted benzimidazoles of the formula ##STR1## in which Q, R, X and Z have the meanings given in the description,a process for the preparation of the novel substances and their use for combating pests.

Abstract: Disclosed herein are compositions containing NO donors, inhibitors of iNOS induction, and endopeptidase inhibitors, and methods for their use for combating injury induced by ischemia and reperfusion following ischemic episodes.

Abstract: Tricyclic diazepines of the formula: ##STR1## wherein A, B, D, E, F, Y and Z are defined in the specification which compounds have vasopressin and oxytocin antagonist activity.

Abstract: Novel chemotherapeutic agents having utility in treating infectious diseases such as periodontal disease, certain urinary tract infections, and infectious urinary tract stones, are obtained by combining chemically a diphosphonate compound with a therapeutic agent effective against the foregoing diseases.

Abstract: Tricyclic diazepines of the formula: ##STR1## wherein A, B, D, E, F, Y and Z are defined in the specification which compounds have vasopressin and oxytocin antagonist activity.

Abstract: Tricyclic compound of the general Formula I: ##STR1## as defined herein which exhibit antagonist activity at V.sub.1 and/or V.sub.2 receptors and exhibit in vivo vasopressin antagonist activity, methods for using such compounds in treating diseases characterized by excess renal reabsorption of water, and process for preparing such compounds.

Abstract: The principal activity of the amides of ethanol-.beta.-aminophosphoric acid with active moieties having anti-inflammatory and analgesic activity (FANS) remains substantially unchanged but they have considerably lower toxicity particularly in terms of damage to the stomach.The method for their preparation is also described.

Abstract: Tricyclic diazepines of the formula: ##STR1## wherein A, B, D, E, F, Y and Z are defined in the specification which compounds have vasopressin and oxytocin antagonist activity.

Abstract: Tricyclic compounds of the general Formula I: ##STR1## as defined herein which exhibit antagonist activity at V.sub.1 and/or V.sub.2 receptors and exhibit in vivo vasopressin antagonist activity, methods for using such compounds in treating diseases characterized by excess renal reabsorption of water, and processes for preparing such compounds.

Abstract: A phosphonate nucleotide compound having antiviral activity and is useful for an orally available and highly safe antiviral agent, which is represented by the following formula (I): ##STR1## wherein R.sup.1 represents hydrogen, a C.sub.1 -C.sub.6 alkoxy, a halogen-substituted C.sub.1 -C.sub.4 alkoxy, halogen, amino, or nitro; R.sup.2 and R.sup.3 independently represent hydrogen, a C.sub.1 -C.sub.22 alkyl, an acyloxymethy, an acylthioethyl, or a halogen-substituted ethyl; R.sup.4 represents hydrogen, a C.sub.1 -C.sub.4 alkyl, a C.sub.1 -C.sub.4 hydroxyalkyl, or a halogen-substituted C.sub.1 -C.sub.4 alkyl; and X represents carbon or nitrogen.

Abstract: Compounds of the invention have the formula ##STR1## The compounds have fibrinogen receptor antagonist activity.

Abstract: The invention provides a phosphonic diester derivative of the formula: ##STR1## wherein R.sup.1 -R.sup.7 are substituent groups, as defined in the specification.The derivatives according to the invention are useful as therapeutic or preventive compositions for hyperlipidemia, hypertension, and diabetes.

Abstract: Tricyclic compounds of the general Formula I: ##STR1## as defined herein which exhibit antagonist activity at V.sub.1 and/or V.sub.2 receptors and exhibit in vivo vasopressin antagonist activity, methods for using such compounds in treating diseases characterized by excess renal reabsorption of water, and processes for preparing such compounds.

Abstract: The present invention provides novel compounds represented by the general formula I: ##STR1## wherein R.sub.1 is a straight or branched lower alkyl, a cycloalkyl-lower alkyl, an aryl-lower alkyl, a cycloalkyl, an aryl an aryl-cycloalkyl, lower alkoxy, an aryloxy, or a heteroaryl;R.sub.2 is hydrogen, a straight or branched lower alkyl, a cycloalkyl, or a cycloalkyl-lower alkyl;R.sub.3 and R.sub.3 ' are each the same or different and each is hydrogen atom, a straight or branched lower alkyl, a cycloalkyl, an aryl-lower alkyl, an aryl, or a heteroaryl; orR.sub.3 and R.sub.3 ' together form a ring structure;R.sub.3 " is hydrogen, lower alkyl or an aryl; orR.sub.2 and R.sub.3 " together form a lower alkylene group --(CH.sub.2).sub.n -- wherein n is an integer of 1, 2 or 3; orR.sub.2 and R.sub.3 " together form a group represented by the formula: --(CH.sub.2).sub.p --Ar-- or --Ar--(CH.sub.2).sub.p --, respectively, wherein p is zero or an integer of 1 or 2, and Ar is an arylene or heteroarylene;C(.dbd.X) is C(.dbd.

Abstract: Compounds of formula (I): ##STR1## as single stereoisomers or mixtures thereof and their pharmaceutically acceptable salts inhibit matrix metalloproteases, such as interstitial collagenases, and are useful in the treatment of mammals having disease states alleviated by the inhibition of such matrix metalloproteases, for example arthritic diseases or bone resorption diseases, such as osteoporosis.

Abstract: The present invention relates to compositions comprising pharnaceutically-acceptable carriers and a phosphonocarboxylate, or a pharmaceutically-acceptable salt thereof, having a structure according to formula (I): ##STR1##

Abstract: A phosphonic acid derivative compound represented by formula ?I ! or a pharmaceutically acceptable salt thereof: ##STR1## wherein R.sub.1, R.sub.2 and R.sub.3 each represent hydrocarbon groups which may be substituted, except cases in which (1) R.sub.2 is unsubstituted methyl, ( 2 ) R.sub.3 is an unsubstituted hydrocarbon group having 1 to 3 carbon atoms, and (3) R.sub.1 is benzyloxycarbonylaminomethyl, R.sub.2 is isobutyl and R.sub.3 is isobutyl or phenylmethyl, which has endothelin-converting enzyme inhibiting activity and is useful as pharmaceutical drugs such as therapeutic agents for hypertension, cardiac or cerebral circulatory diseases and renal diseases.This is a Reissue of a Patent which was the subject of a Reexamination Certificate No. B1 5,330,978, dated Jun. 18, 1996, Request No. 90/00400, Oct. 18, 1995.