Abstract: The present invention relates to certain 3-[4-(substituted heterocyclyl)-pyrrol-2-ylmethylidene]-2-indolinone derivatives that inhibit kinases, in particular VEGFR and/or PDGFR kinases. Pharmaceutical compositions comprising these compounds, methods of treating diseases mediated by kinases utilizing pharmaceutical compositions comprising these compounds, and methods of preparing them are also disclosed.

Abstract: This invention is directed to novel (N-substituted) indole ICE/ced-3-inhibitor compounds. The invention is also directed to pharmaceutical compositions of such indole compounds, plus the use of such compositions in the treatment of patients suffering inflammatory, autoimmune and neurodegenerative diseases, for the prevention of ischemic injury.

Abstract: The present invention relates to certain 3-(4,5,6,7-tetrahydroindol-2-yl-methylidene)-2-indolinone derivatives that inhibit kinases, in particular Src kinase. Pharmaceutical compositions comprising these compounds, methods of treating diseases mediated by kinases utilizing pharmaceutical compositions comprising these compounds, and methods of preparing them are also disclosed.

Abstract: This invention concerns compounds for inhibiting intracellular signal transduction, especially intracellular signal transduction mediate by one or more molecular interactions involving a phosphotyrosine-containing protein. This invention also relates to pharmaceutic compositions containing the compounds and prophylactic and therapeutic methods involving pharmaceutical and veterinary administration of the compounds. The compounds are of formula (1) as defined herein.

Abstract: The invention features linker molecules that have at one terminus a amino-protecting group and at the other terminus a phosphorous activating group, typically phosphoramidite. The linker molecules can be used, for example, to produce amino-modified linkers that space an oligonucleotide from a solid support. The invention also features an amino-protected nucleotide that includes an activated phosphorous group such as a phosphoramidite for the production of a 5′ amino-modified oligonucleotide. The invention further provides a phthalimido-modified support that can be used to synthesize a polynucleotide that includes an amino group at the 3′ terminus.

Abstract: The object of the present invention are diketopyrrolopyrroles of the general formula (I) wherein, independently of one another, Q1 and Q2 represent an optionally substituted, aromatic, isocyclic or heterocyclic group with 5 to 14 atoms in the ring, the heterocyclic group containing at least one oxygen, nitrogen or sulfur atom, and the R1 and R2 groups, independently of one another represent hydrogen or a Y—B+A− group, with the proviso that at least one of the R1 and R2 groups is not hydrogen; B+ is an aromatic, aliphatic, alicyclic, aromatic heterocyclic or non-aromatic heterocyclic, quaternary ammonium group or a quaternary phosphonium group; Y is an optionally substituted linear or branched C1 to C6 alkylene group and A− is an anion; a method for their synthesis as well as agents, containing compounds of formula (I), for dyeing keratin fibers.

Abstract: The invention provides derivatives of 5-arylsulfonyl indole and 5-arylsulfonyl indoline compounds which may be in the form of pharmaceutical acceptable salts or compositions that are useful in treating central nervous system diseases such as anxiety and depression. The invention also includes intermediates and processes to make the compounds, isotopically-labeled forms of the compounds and the use of the isotopically labeled forms of the compounds to perform nuclear magnetic resonance imaging and positron emission tomography.

Abstract: The present invention is directed to prodrugs of certain 3-(pyrrol-2-yl-methylidene)-2-indolinone derivatives that modulate the activity of protein kinases (“PKs”). Pharmaceutical compositions comprising these compounds, methods of treating diseases related to abnormal PK activity utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.

Abstract: The present invention provides analogues of duocarmycins that are potent cytotoxins. Also provided are peptidyl and disulfide linkers that are cleaved in vivo. The linkers are of use in forming prodrugs and conjugates of the cytotoxins of the invention as well as other diagnostic and therapeutic moieties. The invention provides prodrugs and conjugates of the duocarmycin analogues with the linker arms of the invention.

Abstract: This invention provides PAI-1 inhibiting compounds of Formula I: 1

Abstract: Chromogenic 3-Indoxyl choline phosphate compounds of formula (I): 1

Abstract: Sulfanyl-indirubin derivatives, their production and their intermediate products for production, as well as their use as medications for treating cancer, such as solid tumors and leukemia; auto-immune diseases, such as psoriasis, alopecia and multiple sclerosis, chemotherapy agent-induced alopecia and mucositis; cardiovascular diseases, such as stenoses, arterioscleroses and restenoses; infectious diseases, such as, e.g., those caused by unicellular parasites, such as trypanosoma, toxoplasma or plasmodium, or those caused by fungi; nephrological diseases, such as, e.g., glomerulonephritis; chronic neurodegenerative diseases, such as Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, AIDS dementia and Alzheimer's disease; acute neurodegenerative diseases, such as ischemias of the brain and neurotraumas; viral infections, such as, e.g., cytomegalic infections, herpes, hepatitis, B and C, and HIV diseases, are described.

Abstract: Chemically reactive carbocyanine dyes incorporating an indolium ring moiety that is substituted at the 3-position by a reactive group or by a conjugated substance, and their uses, are described. Conjugation through this position results in spectral properties that are uniformly superior to those of conjugates of spectrally similar dyes wherein attachment is at a different position. The invention includes derivative compounds having one or more benzo nitrogens.

Abstract: Compounds of formula (I), their salts and prodrugs thereof, where the substituents are as defined herein are disclosed as opiate binding agents useful in the treatment of opiate-mediated conditions. Also described are processes for making such substances.

Abstract: A process for preparing 1H-indole-3-glyoxamides useful for inhibiting SPLA2 and novel intermediates useful in the preparation of such compounds.

Abstract: The present invention is directed to prodrugs of certain 3-(pyrrol-2-yl-methylidene)-2-indolinone derivatives that modulate the activity of protein kinases (“PKs”). Pharmaceutical compositions comprising these compounds, methods of treating diseases related to abnormal PK activity utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.

Abstract: Disclosed are multibinding compounds which inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-COA reductase), the rate limiting enzyme in cholesterol biosynthesis. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is a moiety capable of binding to HMG-CoA reductase and the distance between ligands is at least 10 Å. The multibinding compounds of this invention are useful in the treatment and prevention of hypercholesterolemia, hyperlipidemia, atherosclerosis and the like.

Abstract: This invention is directed to novel (N-substituted) indole ICE/ced-3-inhibitor compounds. The invention is also directed to pharmaceutical compositions of such indole compounds, plus the use of such compositions in the treatment of patients suffering inflammatory. autoimmune and neurodegenerative diseases, for the prevention of ischemic injury.

Abstract: Objects of the present invention are compounds of a peptido-mimetic character having the capacity of acting as inhibitors of metalloproteinases produced by venom of snake, and of other metalloproteinases of human origin which have been put in relation with various pathologies in man, including tumoral growth and metastatization, aterosclerosis, multiple sclerosis, Alzheimer's disease, osteoporosis, hypertension, rheumatoid arthritis and other inflammatory diseases. Object of the present invention is also the procedure for the production of diethylester of (1)-phosphotryptophan, as an initial product necessary to synthesize all compounds mentioned above.

Abstract: Disclosed are novel substituted pyrroles having the formula These compounds and their pharmaceutically acceptable salts are suitable for administration to patients as continuous infusion solution and are useful in the treatment and/or control of cell proliferative disorders, in particular cancer. Also disclosed are pharmaceutical compositions containing the foregoing compounds and methods for the treatment and/or control of cancer.

Abstract: Chiral diphosphines constituted by an aromatic pentatomic biheterocyclic system, suitable to act as chiral ligands, complexes between said diphosophines and transition metals, and their utilization as chiral catalysts in stereocontrolled reactions, such as diastereo- and enantioselective reduction reactions. Process for the preparation of said chiral diphosophines and process for the preparation of said complexes and for their utilization as chiral catalysts in stereocontrolled reaction.

Abstract: Substituted triols are prepared by reducing appropriately substituted carboxylic esters. The substituted triols can be used as active substances in medicaments.

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: Novel products of formula (I), their preparation, the pharmaceutical compositions which contain them and their use in the preparation of medicaments. ##STR1## In the formula (I), the following substituents are among the preferred: Ar represents a substituted or condensed phenyl radical or a polycyclic or heterocyclic aromatic radical, R represents a radical of general formula --(CH.sub.2).sub.m --X.sub.1 --(CH.sub.2).sub.n --Z in which X.sub.1 =single bond, O, S; m=0, 1; n=0, 1, 2; it being possible for the CH.sub.2 radicals to be substituted; Z represents carboxyl, COOR.sub.6 (R.sub.6 =alkyl), CON(R.sub.7)(R.sub.8) (R.sub.7 =hydrogen or alkyl and R.sub.8 =hydrogen, hydroxyl, arylsulphonyl, heterocyclyl, optionally substituted amino, optionally substituted alkyloxy or optionally substituted alkyl), PO(OR.sub.9).sub.2 (R.sub.9 =hydrogen or alkyl), an --NH--CO--T (T=hydrogen or optionally substituted alkyl) radical, or else--a ##STR2## radical, R.sub.1 and R.sub.

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: The present invention relates to asymmetric syntheses and intermediates for preparing enantiomer-enriched hydroxyphosphinyl derivatives.

Abstract: The present disclosure relates to dipeptidase inhibitors, and more particularly, to novel methods of using phosphonate derivatives, hydroxyphosphinyl derivatives, and phosphoramidate derivatives to inhibit N-Acetylated .alpha.-Linked Acidic Dipeptidase (NAALADase) enzyme activity, and to treat prostate diseases, especially using the compounds of the present invention for the inhibition of the growth of prostate cancer cells.

Abstract: The invention relates to novel bis-benzimidazole compounds which have the ability to bind to the minor groove of DNA and to alkylate DNA, to methods of preparing the compounds, and the use of the compounds in the treatement of neoplastic disease.

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

Abstract: Novel pro-drugs to new and unnatural dipeptoids of .alpha.-substituted Trp-Phe derivatives useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, or as antipsychotics are disclosed. Further, the dipeptoids are antianxiety agents and antiulcer agents. They are agents useful for preventing the response to the withdrawal from chronic treatment or with use of nicotine, diazepam, alcohol, cocaine, caffeine, or opioids. The pro-drugs are also useful in treating and/or preventing panic attacks. Also disclosed are pharmaceutical compositions and methods of treatment using the pro-drugs as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the subject pro-drug compounds in diagnostic compositions.

Abstract: The invention relates to pyrrolidine monomeric units and to oligomers which are joined via phosphate linkages, including phosphorothioate, phosphodiester and phosphoramidate linkages.

Abstract: Therapeutically active, heteroaryl-substituted deoxy glycero-phosphoethanolamines are disclosed having the general Formula I: ##STR1## wherein one of X, Y or Z is a fatty ether substituent, one is a heteroaryl ring substituent with 1-4 nitrogens as the only heteroatoms, one of which is bonded to a carbon of the glyceryl backbone, and one is a phosphoethanolamine substituent substituted at the nitrogen, provided that each of X, Y and Z is a different substituent, and the pharmaceutical compositions comprising the therapeutically active compounds and methods of using the therapetically active compounds to treat cancerous tumors, psoriasis and inflammation are also disclosed.

Abstract: Novel intermediates having an indolenine nucleus which are useful in the synthesis of fluorescent sulfoindocyanine dyes are described. Dyes synthesized using such intermediates do not contain a reactive group that will covalently attach to a target molecule at an amine- or hydroxy-containing site. Rather, these intermediates are linked to an enzyme substrate or a member of a specific binding pair. Also included are tyramide-comaining sulfonidocyanine dyes.

Abstract: Novel phosphinic acid-containing peptidyl compounds of formula I are found to be useful inhibitors of matrix metalloendoproteinase-mediated diseases including osteoarthritis, rheumatoid arthritis, septic arthritis, tumor invasion in certain cancers, periodontal disease, corneal ulceration, proteinuria, dystrophobic epidermolysis bullosa, and coronary thrombosis associated with atherosclerotic plaque rupture. These inhibitors may also be useful in preventing the pathological sequelae following a traumatic injury that could lead to permanent disability. These compounds may also have utility as a means for birth control by preventing ovulation or implantation.

Abstract: A compound of formula (I): ##STR1## in which: R.sub.1, R.sub.2, which may be identical or different, represent hydrogen or halogen, or alkyl, alkoxy, nitro or trihalomethyl,X represents CO, SO.sub.2 or CH.sub.2,A.sub.1 represents any one of the groups as defined in the description,A.sub.2 represents --(CH.sub.2).sub.n or --CH.dbd.CH--,R.sub.3, R.sub.4, which may be identical or different, represent hydrogen or alkyl,its isomers as well as its addition salts with a pharmaceutically acceptable base and medicinal product containing the same are useful as angiogenesis inhibitors.

Abstract: Compounds of the tautomeric formula Ia, Ib or Ic, ##STR1## where R is a radical of the formula ##STR2## are effective compounds for the treatment and prophylaxis of degenerative bone disorders. They are used as pharmaceuticals.

Abstract: This invention provides novel bicyclic compounds which are useful as excitatory amino acid receptor antagonists and in the treatment of neurological disorders. This invention also provides intermediates useful in the synthesis of excitatory amino acid antagonists.

Abstract: The invention relates to new 1H-3-aryl-pyrrolidine-2,4-dione derivatives of the formula (I) ##STR1## in which A, B, X, Y and G have the meanings given in the description, to a plurality of processes for their preparation, and to their use as pesticides.

Abstract: Dipeptide compounds and analogs thereof having a phosphonomethyl moiety are disclosed. These compounds inhibit Endothelin Converting Enzyme and are thus useful in treating conditions responsive to inhibition of production of Endothelin.

Abstract: Compound of formula (I): ##STR1## in which: R.sub.1 represents a hydroxyl, alkoxy or amino (unsubstituted or substituted) group,R.sub.2 represents an unsubstituted or substituted alkyl group,X.sub.1 represents --NH--,X.sub.2 represents --O--,R.sub.3 represents a hydrogen atom or an alkyl or phenyl group,R.sub.4 represents an alkyl group which is always substituted with one or more hydroxyl, benzyloxy, benzyloxycarbonylamino, amino, mono- or dialkylamino, acetoxy or 2,2-dimethyl-1,3-dioxolan-4-yl groups, such groups being identical or different,R.sub.5 represents a 3-indolylmethyl, naphthylmethyl, alkyl, phenyl or benzyl group, its isomers as well as its addition salts with a pharmaceutically acceptable acid or base, and medicinal products containing the same are useful as endothelin convertase inhibitor.

Abstract: An optically active manganese complex of the formula I.sub.a, I.sub.b, I.sub.c and I.sub.d ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently represent hydrogen atom, C.sub.1 -.sub.4 alkyl group, phenyl group which may be substituted by a halogen atom, C.sub.1 -.sub.4 alkyl group, C.sub.1 -.sub.4 alkoxyl group, cyano group or nitro group; and any two of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 together form a C.sub.4 -.sub.8 ring, X.sup.- represents a counter anion which may form a salt, Y represents hydrogen atom, halogen atom, C.sub.1 -.sub.4 alkyl group, C.sub.1 -.sub.4 alkoxyl group, nitro group or cyano group, R represents hydrogen atom, C.sub.1 -.sub.4 alkyl group, phenyl group which may be substituted by halogen atom, C.sub.1 -.sub.4 alkyl group or C.sub.1 -.sub.4 alkoxyl group, or substituted silyl group and a process for producing epoxy compounds using the complex as a catalyst.

Abstract: A class of novel 1H-indole-3-acetic acid hydrazides is disclosed together with the use of such indole compounds for inhibiting sPLA.sub.2 mediated release of fatty acids (e.g., arachidonic acid) for treatment of conditions such as septic shock.

Abstract: The invention encompasses the novel compound of Formula I as well as a method of treating cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula I. ##STR1## The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.

Abstract: The pharmaceutically active bicyclic heterocyclic amines (XXX) ##STR1## where W.sub.1 is --N.dbd. or --CH.dbd.; W.sub.3 is --N.dbd. or --CH.dbd.; W.sub.5 is --N.dbd. or --CR.sub.5 -- with the proviso that W.sub.5 is --CR.sub.5 -- when both W.sub.1 and W.sub.3 are --N.dbd. which are useful as pharmaceuticals in treating mild and/or moderate to severe head injury, subarachnoid hemorrhage and subsequent ischemic stroke, asthma and reduction of mucous formation/secretion in the lung and other diseases and injuries.

Abstract: Phosphinic acid derivatives of the structural formula ##STR1## or a pharmaceutically acceptable salt thereof, wherein R is H, alkyl or alkanoyloxymethylene;R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are H, alkyl, alkenyl, alkenylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxyalkyl, carboxyalkyl, thioalkyl, alkoxythioalkyl, aminoalkyl, alkylaminoalkyl, cycloalkyl-substituted alkyl or heterocycloalkyl; or R.sub.1 and R.sub.2 form a cycloalkyl ring of 3-8 members and R.sub.3 and R.sub.4 are as defined; or R.sub.3 and R.sub.4 form a cycloalkyl ring of 3-7 members and R.sub.1 and R.sub.2 are as defined; or R.sub.1 and R.sub.2 together, and R.sub.3 and R.sub.4 together, each form a cycloalkyl ring;R.sub.5 is --OR.sub.9 or --NHR.sub.9, wherein R.sub.9 is hydrogen or alkyl;n is 0 or 1;A.sub.1 is p-aminobenzoyl or p-aminobenzenesulfonyl, or A.sub.1 and R.sub.5 together form a radical of an .alpha.-aminoacyl derivative; andR.sub.6 is phenylmethoxycarbonyl, arylcarbonyl, heteroarylcarbonyl or --A.sub.2 --R.sub.

Abstract: Amine phosphate having a terminal imide cycle resulting from the reaction, under formation conditions for an amine salt, of at least one phosphate complying with the general formula (I): ##STR1## in which n is equal to 1 or 2, R.sup.1 is a divalent hydrocarbon group having 1 to 32 carbon atoms, R.sup.6 stands for a hydrogen atom or a hydrocarbon group normally having 1 to 200 carbon atoms, with at least one amine. Preparation process in accordance with standard methods and use of these compounds as additives in fuels for engines, if appropriate in formulations containing a second constituent consisting of at least one product chosen from among the germination additives of paraffins, whereby said formulations can also contain at least one paraffin crystal growth inhibiting product.

Abstract: Hypotensive activity is exhibited by new phosphonate substituted amino or imino acids of the formula ##STR1## isomeric mixtures thereof and pharmaceutically acceptable salts thereof, wherein:X is an imino or amino acid of the formula ##STR2##

Abstract: An optically active manganese complex of the formula I or I': ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 independently represent hydrogen atom, C.sub.1 -C.sub.4 alkyl group, phenyl group which may be substituted by a halogen atom, C.sub.1 -C.sub.4 alkyl group, C.sub.1 -C.sub.4 alkoxyl group, cyano group or nitro group; and any two of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 together form the C.sub.4 -C.sub.8 ring, X.sup.- represents a counter anion which may form a salt, Y represents hydrogen atom, halogen atom, C.sub.1 -C.sub.4 alkyl group, C.sub.1 -C.sub.4 alkoxyl group, nitro group or cyano group, R represents hydrogen atom, C.sub.1 -C.sub.4 alkyl group, phenyl group which may be substituted by halogen atom, C.sub.1 -C.sub.4 alkyl group or C.sub.1 -C.sub.4 alkoxyl group, or substituted silyl group and a process for producing epoxy compounds using the complex as a catalyst.

Abstract: Quinolone carboxylic acids 7 -substituted by azabicyclo groups have antibacterial activity.

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.