Abstract: The present invention relates to compositions and methods for inhibiting and reversing nonenzymatic cross-linking (protein aging). Accordingly, compositions are disclosed which comprise an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins, and which additionally reverse pre-formed crosslinks in the advanced glycosylation endproducts by cleaving alpha-dicarbonyl-based protein crosslinks present in the advanced glycosylation endproducts. Certain agents useful are thiazolium salts. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated. A immunoassay for detection of the reversal of the nonenzymatic crosslinking is also disclosed.

Abstract: The invention relates to heteroaromatic carboxamides of formula (I), 1

Abstract: The present invention relates to new phenylserine derivatives as integrin antagonists with a broad spectrum of action having, inter alia, antiosteoporotic, antirestenotic, anticarcinogenic and antiatherosclerotic activity. The present invention moreover relates to the preparation of these compounds and their use for the production of medicaments, and also medicaments comprising them.

Abstract: 3-(Substituted phenyl)-5-(substituted heterocyclyl)-1,2,4-triazole compounds are useful as insecticides and acaricides. New synthetic procedures and intermediates for preparing the compounds, pesticide compositions containing the compounds, and methods of controlling insects and mites using the compounds are also provided.

Abstract: The invention provides fungicidal compounds of formula I and salts thereof: 1

Abstract: Tetrazolyl-phenyl acetamides are active as glucokinase activators, and are able to increase insulin secretion, which makes them useful for treating type II diabetes.

Abstract: The present invention relates to prodrug compounds of inhibitors of dipeptidyl peptidase IV (DP IV), which prodrug compounds have the general formula A-B-C, wherein

Abstract: This invention is directed to novel indole and benzothiazole compounds which are selective for cloned human alpha 2 receptors. This invention is also related to uses of these compounds for any indication where use of an alpha 2 agonist may be appropriate. Specifically, this includes use as analgesic, sedative and anaesthetic agents. In addition, this invention includes using such compounds for lowering intraocular pressure, presbyopia, treating migraine, hypertension, alcohol withdrawal, drug addiction, rheumatoid arthritis, ischemic pain, spasticity, diarrhea, nasal decongestion, urinary incontinence as well as for use as cognition enhancers and ocular vasoconstriction agents. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.

Abstract: A compound of formula I 1

Abstract: Compounds of the formula 1

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: Tetrazolyl-phenyl acetamides are active as glucokinase activators, and are able to increase insulin secretion, which makes them useful for treating type II diabetes.

Abstract: This invention relates to 2-arylimino heterocycles, including 2-arylimino-1,3-thiazolidines, 2-arylimino-2,3,4,5-tetrahydro-1,3-thiazines, 2-arylimino-1,3-thiazolidin-4-ones, 2-arylimino-1,3-thiazolidin-5-ones, and 2-arylimino-1,3-oxazolidines, and their use in modulating progesterone receptor mediated processes, and pharmaceutical compositions for use in such therapies.

Abstract: Amide derivatives represented by general formula (I) or salts thereof wherein each symbol has the following meaning: ring B: an optionally substituted heteroaryl optionally fused with a benzene ring; X: a bond, lower alkylene or lower alkenylene optionally substituted by hydroxy or lower alkyl, carbonyl, or a group represented by —NH— (when X is lower alkylene optionally substituted by lower alkyl which may be bonded to the hydrogen atom bonded to a constituent carbon atom of ring B to form lower alkylene to thereby form a ring); A: a lower alkylene or a group represented by -(lower alkylene)—O—; R1a and R1b: the same or different and each hydrogen or lower alkyl; R2: hydrogen or halogeno; and Z: nitrogen or a group represented by ═CH—.

Abstract: The subject of the invention is the compounds of formula: in which R1, R2, R3, R4, R5 and R6 are as defined in Claim 1. The compounds have a high affinity for CRF receptors.

Abstract: Hydantoin compounds which are active as glucokinase activators to increase insulin secretion which makes them useful for treating type II diabetes.

Abstract: Compounds represented by the general formula (1): (where R1 and R2 are typically a hydrogen atom; R3 and R4 are typically a hydrogen atom or a lower alkyl group; R5 is typically a hydrogen atom; X1, X2, X3 and X4 are typically a hydrogen atom or a lower alkoxy group; A is typically an optionally substituted pyridine ring; m and n are each 0 or 1) have an NOS inhibiting activity and are useful as therapeutics of cerebrovascular diseases and other pharmaceuticals.

Abstract: A compound of formula (I) wherein X is a —CONHOH group and the R groups are defined in the claims. The compounds are inhibitors of matrix metalloproteinases involved in tissue degradation and inhibitors of the release of tumour necrosis factor from cells.

Abstract: The present invention provides compounds of the formula where R1-R5 are each, independently, a hydrogen atom or a normal or branched C1-C6-alkyl group; A is a methionyl, phenylalanyl or phenylglycyl residue; n is 0 or 1; R6 is a hydrogen atom; and R7 is a carbocylic group, an aromatic group, a C1-C4-alkyl group, a pyridylalkyl group or a heterocyclic group. In another embodiment, R6 is benzyl or —C(O)OR8, where R8 is a C1-C6-alkyl group, and R7 is a heteroaromatic group, such as a 2-thiazolyl group.

Abstract: The present invention relates to the use of aminothiazole derivatives of Formula I of as inhibitors of PAI-1, and to novel classes of aminothiazole derivatives, their synthesis and their use as inhibitors of PAI-1.

Abstract: A compound of formula I in which: ring A is one of the five alternative multi-cyclic rings as shown wherein a dotted line adjacent to a bond indicates that a single bond or a double bond may be present at that position; X is nitrogen, oxygen or sulfur; R is hydrogen, lower straight or branched chain alkyl of 1 to 6 carbon atoms, or lower straight or branched chain alkenyl of 2 to 6 carbon atoms, a cycloaliphatic ring of 3 to 6 carbon atoms, phenyl optionally mono- or di-substituted with hydroxy, halogen, alkyl of 1 to 3 carbon atoms or alkoxy of 1 to 2 carbon atoms, or methylenedioxyphenyl; or a stereoisomer, or a pharmaceutically acceptable salt thereof. These compounds have &agr;2 receptor blocking activity and hence find use in the treatment or palliation of elevated intraocular pressure, non insulin-dependent diabetes, male impotence and obesity.

Abstract: Urocanic acid derivatives useful as antiallergic agents represented by the following formula (I) or a pharmacologically acceptable salt thereof: wherein R2 denotes hydrogen or lower alkyl, R3 denotes nitro, amino, cyano or COOR2, wherein R2 in said COOR2 is as defined above, and Q denotes carbon or nitrogen.

Abstract: A series of activated iodo-benzamide derivatives are described as antineoplastic and antiviral drug compounds. The compounds generally possess a chelating group, a thiol trapping group and an activating group. The presumptive mechanism of action in preventing cancer cell and virus replication is through inhibition of the binding of transcription factors to zinc finger binding domains. The compounds are effective in inhibiting growth of a variety of human and animal tumor and leukemia cell lines at low concentrations.

Abstract: This invention is directed to indole and benzothiazole compounds which are selective for cloned human alpha 2 receptors. This invention is also related to uses of these compounds for any indication where use of an alpha 2 agonist may be appropriate. Specifically, this includes use as analgesic, sedative and anaesthetic agents. In addition, this invention includes using such compounds for lowering intraocular pressure, presbyopia, treating migraine, hypertension, alcohol withdrawal, drug addiction, rheumatoid arthritis, ischemic pain, spasticity, diarrhea, nasal decongestion, urinary incontinence as well as for use as cognition enhancers and ocular vasoconstriction agents. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.

Abstract: The dihalopropene compounds of the general formula [I] have excellent insecticidal/acaricidal activity, so that they are satisfactorily effective for the control of noxious insects, mites and ticks.

Abstract: This invention is directed to novel oxamyl dipeptide ICE/ced-3 family inhibitor compounds. The invention is also directed to pharmaceutical compositions containing these compounds, as well as to the use of such compositions in the treatment of patients suffering inflammatory, autoimmune and neurodegenerative diseases, for the prevention of ischemic injury, and for the preservation of organs that are to undergo a transplantation procedure.

Abstract: Compounds of Formula I including pharmaceutically acceptable salts thereof in the form of individual enantiomers, racemates, or other mixtures of enantiomers, in which Ar is phenyl, naphthyl or benzo[b]thiophenyl, each of which may be optionally substituted; R1 and R2, which may be the same or different, independently are a) H, b) an alkyl group containing 1 to 6 carbon atoms, c) an alkenyl group containing 3 to 6 carbon atoms, d) a cycloalkyl group containing 3 to 7 carbon atoms, e) a cycloalkylmethyl group in which the ring contains 3 to 7 carbon atoms, f) an aryl or heteroaryl group optionally substituted g) an arylalkyl or heteroarylalkyl group each optionally substituted; or R1 and R2 form an alkylene chain optionally substituted by one or more alkyl groups each containing 1 to 3 carbon atoms, such that, together with the atoms to which they are attached, they form a 5 or 6 membered ring; R3 is a) H, b) an aryl or heteroaryl group each optionally substituted c) an optionally

Abstract: The present invention is concerned with compounds of formula ##STR1## the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein R.sup.1 is hydrogen, hydroxy, C.sub.1-6 alkyl or aryl; R.sup.2 is hydrogen; optionally substituted C.sub.1-12 alkyl; C.sub.3-7 cycloalkyl; C.sub.2-8 alkenyl, optionally substituted pyrrolidinyl or aryl; R.sup.3 is hydrogen, optionally substituted C.sub.1-6 alkyl or aryl; Het is an optionally substituted unsaturated heterocycle selected from imidazolyl, triazolyl, tetrazolyl and pyridinyl; ##STR2## is an optionally substituted unsaturated mono- or bicyclic heterocycle; and aryl is optionally substituted phenyl. The present invention also relates to processes for their preparation and compositions comprising said new compounds, as well as their use as a medicine.

Abstract: There are described compounds of formula I*, ##STR1## wherein R.sub.1 is lower alkoxycarbonyl,R.sub.2 is secondary or tertiary lower alkyl or lower alkylthio-lower alkyl,R.sub.3 is phenyl that is unsubstituted or substituted by one or more lower alkoxy radicals, or C.sub.4 -C.sub.8 cycloalkyl,R.sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl (--SO--) and sulfonyl (--SO.sub.2 --) and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl,R.sub.5, independently of R.sub.2, has one of the meanings mentioned for R.sub.2, andR.sub.6, independently of R.sub.1, is lower alkoxycarbonyl,or salts thereof, provided that at least one salt-forming group is present.The compounds are inhibitors of retroviral aspartate protease and can be used, for example, in the treatment of AIDS.

Abstract: A compound of general formula (I), wherein X is a group of formula (II) or (III), R.sub.2, R.sub.1, R.sub.21, R.sub.3, R.sub.4, and R.sub.5 being as defined in the specification are matrix metalloproteinase inhibitors.

Abstract: One pot synthesis of 1,2,4-triazoles uses thioimidate intermediate and 1,2-dichloroethane solvent.

Abstract: Compounds of Formula 1 and of Formula 2 ##STR1## where the symbols have the meaning defined in the specification, have retinoid-like biological activity.

Abstract: The present invention relates to a novel 2-hydroxy-naphthalene-3,6-dicarboxylic acid derivative. The compound is useful as a raw material for dyes, pigments, photosensitive materials and the like.

Abstract: The present invention relates to thiazole containing compounds capable of inhibiting protein tyrosine phosphatase activity. The invention further relates to the use of such compounds to modulate or regulate signal transduction by inhibiting protein tyrosine phosphatase activity. Finally, the invention relates to the use of such compounds to treat various disease states including diabetes mellitus.

Abstract: This invention relates to methods for inhibiting herpes replication and for treating herpes infection in a mammal by inhibiting the herpes helicase-primase enzyme complex. This invention also relates to thiazolyphenyl derivatives that inhibit the herpes helicase-primase and to pharmaceutical compositions comprising the thiazolylphenyl derivatives, to methods of using and methods of producing the thiazolylphenyl derivatives.

Abstract: The present invention concerns novel compounds represented by the Formula: ##STR1## wherein: A is R.sup.1.sub.q (R.sup.3 R.sup.60 N).sub.m (Z)(NR.sup.2).sub.n ; m and q are each 0 or 1, with the proviso that when q is 1, m is 0 and when q is 0, m is 1; Z is C.dbd.O or SO.sub.2 ; n is 1 with the proviso that, when Z is C.dbd.O, m is 1; X is --NH--, --CH.sub.2 --, or --OCH.sub.2 --; Y is [2-imidazoline, 2-oxazolin] 2-thiazoline, [or 4-imidazole] R.sup.1 is H, lower alkyl, or phenyl, with the proviso that, when R.sup.1 is H, m is 1; R.sup.2, R.sup.3, R.sup.60 are each independently H, lower alkyl, or phenyl; R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are each independently hydrogen, lower alkyl, --CF.sub.3, lower alkoxy, halogen, phenyl, lower alkeny, hydroxyl, lower alkylsulfonamido, or lower cycloalkyl, wherein R.sup.2 and R.sup.

Abstract: N-(5-isoxazolyl)benzenesulfonamides and N-(3-isoxazolyl) benzene-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(5-isoxazolyl)-biphenylsulfonamides and N-(3-isoxazolyl)biphenylsulfonamides and methods for inhibiting the binding of an endothelin peptide to an endothelin receptor or increasing the activity of endothelin peptides by contacting the receptor with a sulfonamide are provided. N-isoxzolyl-4-biphenylsulfonamides are particularly preferred. These compounds exhibit activity as endothelin receptor B antagonists. Methods for treating endothelin-mediated disorders, particularly inflammatory diseases, such as asthma, by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

Abstract: Disclosed are compounds of formula (I) selected from the following ##STR1## wherein Y is ##STR2## and wherein A, B, C, D, R, k, m, n, o, p, s, t and u are as defined in the specification. These compounds are useful in treating diseases in the central nervous system related to malfunctioning of the nicotinic cholinergic system.

Abstract: The present invention relates to compositions and methods for inhibiting and reversing nonenzymatic cross-linking (protein aging). Accordingly, compositions are disclosed which comprise an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins, and which additionally reverse pre-formed crosslinks in the advanced glycosylation endproducts by cleaving alpha-dicarbonyl-based protein crosslinks present in the advanced glycosylation endproducts. Certain agents useful are thiazolium salts. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated. A novel immunoassay for detection of the reversal of the nonenzymatic crosslinking is also disclosed.

Abstract: A retroviral protease inhibiting compound of the formula: ##STR1## is disclosed.

Abstract: 1-Aryl-3-iminopyrazoles of the formula: ##STR1## wherein R.sub.31, R.sub.32, R.sub.33, R.sub.4, R.sub.5, R.sub.12, R.sub.13, R.sub.14, R.sub.15 and Z are as defined in the specification, are useful as pesticides or as intermediates to other pesticides. Compositions comprising the compounds of formula (I) and methods for their use, particularly in agriculture or for animal protection, as pesticides, especially for controlling arthropods, are described.

Abstract: Compounds of formula I ##STR1## and pharmaceutically acceptable salts thereof in which A is methylene or O; B is methylene or O; g is 0,1,2,3 or 4; R.sub.1 is an optional substituent; U is an alkylene chain optionally substituted by one or more alkyl; Q represents a divalent group containing nitrogen atoms; and T represents CO.HET, have utility in the treatment of central nervous system disorders, for example depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, Parkinson's disease, obesity, hypertension, Tourette's syndrome, sexual dysfunction, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, obsessive-compulsive behavior, panic attacks, social phobias, eating disorders and anorexia, cardiovascular and cerebrovascular disorders, non-insulin dependent diabetes mellitus, hyperglycaemia, constipation, arrhythmia, disorders of the neuroendocrine system, stress, prostatic hypertrophy, and spasticity.

Abstract: The present invention provides a compound of formula: ##STR1## wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6a and R.sup.6b are defined herein or a pharmaceutically acceptable salt thereof, a process for its preparation, intermediates and its use as a tachykinin antagonist.

Abstract: This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as vitronectin receptor antagonists. The vitronectin receptor antagonist compounds of the present invention are .alpha.v.beta.3 antagonists, .alpha.v.beta.5 antagonists or dual .alpha.v.beta.3/.alpha.v.beta.5 antagonists useful for inhibiting bone resorption, treating and preventing osteoporosis, and inhibiting restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation and tumor growth.

Abstract: This invention relates to novel 3-substituted-2-oxindole derivatives of the formula ##STR1## and the pharmaceutically-acceptable salts thereof which are inhibitors of prostaglandin H.sub.2 synthase, 5-lipoxygenase and interleukin-1 biosynthesis. The compounds of the invention are useful as inhibitors of prostaglandin H.sub.2 synthase and interleukin-1 biosynthesis, per se, and as analgesic, antiinflammatory and antiarthritic agents in the treatment of chronic inflammatory diseases. This invention also relates to pharmaceutical compositions comprising said 3-substituted-2-oxindole derivatives; to methods of inhibiting prostaglandin H.sub.2 synthase and biosynthesis of interleukin-1; and to treating chronic inflammatory diseases in a mammal with said compounds. Further, this invention relates to certain novel carboxylic acids useful as intermediates in the preparation of the 3-substituted-2-oxindole derivatives of this invention and to a process for the preparation of the 3-substituted-2-oxindole derivatives.

Abstract: This invention relates to thrombin inhibiting compounds having the Formula IX--Y--NH--(CH.sub.2).sub.r --G Iwhere X, Y, r and G have the values defined in the description, as well as pharmaceutical formulations containing those compounds and methods of their use as thrombin inhibitors, coagulation inhibitors, and thromboembolic disorder agents.

Abstract: A compound, as well as its stereoisomers and addition salts, possssing antagonist activity with respect to corticotropin releasing hormone (CRF) has the formula: ##STR1## in which R.sub.1, and R.sub.21 which are identical or different, are independently selected from a halogen atom; a (C.sub.1 -C.sub.5)hydroxyalkyl radical; a (C.sub.1 -C.sub.5)alkyl; a (C.sub.7 -C.sub.10)aralkyl; a (C.sub.1 -C.sub.5)alkoxy; a trifluoromethyl; a nitro; a nitrile; an --SR group in which R is selected from hydrogen, a (C.sub.1 -C.sub.5)alkyl radical and a (C.sub.7 -C.sub.10)aralkyl radical; an --S--CO--R group in which R is selected from a (C.sub.1 -C.sub.5)alkyl radical and an aralkyl radical in which the aryl part is (C.sub.6 -C.sub.8) and the alkyl part is (C.sub.1 -C.sub.4); a --COOR' group in which R' is selected from hydrogen and a (C.sub.1 -C.sub.

Abstract: The present invention includes novel (7R)-7-(acylamino)-3-(arylthio)-3-cephem-4-carboxylic acids or their pharmacologically acceptable salts which exhibit antibiotic activity against a wide spectrum of organisms including organisms which are resistant to .beta.-lactam antibiotics and are useful as antibacterial agents. The invention also relates to novel intermediates useful for making the novel compounde of the present invention and to novel methods for producing the novel compounds and intermediate compounds.

Abstract: The present invention relates to compositions and methods for inhibiting and reversing nonenzymatic cross-linking (protein aging). Accordingly, compositions are disclosed which comprise an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins, and which additionally reverse pre-formed crosslinks in the advanced glycosylation endproducts by cleaving alpha-dicarbonyl-based protein crosslinks present in the advanced glycosylation endproducts. Certain agents useful are thiazolium salts. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated. A novel immunoassay for detection of the reversal of the nonenzymatic crosslinking is also disclosed.