Abstract: The present invention relates to S1P analogs that have activity as S1P receptor modulating agents and the use of such compounds to treat diseases associated with inappropriate S1P receptor activity. The compounds have the general structure (I), wherein R1 is C8-C22 alkyl, C8-C22 alkenyl or R12 is O, or R1 and R12 taken together form an optionally substituted aryl or an optionally substituted heteroaryl; R17 is H, alkyl or alkylaryl; R18 is N or CH; R2 and R3 are independently selected from the group consisting of H, NH2, and OH, with the proviso that at least one of R2 and R3 is NH2; R4 is selected from the group consisting of hydroxyl, phosphate, phosphonate methylene phosphonate, &agr;-substituted methylene phosphonate, thiophoasphate and thiophosphonate; and R5 is C8-C22alkenyl.

Abstract: A compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof: wherein R1 represents hydrogen atom, an alkyl group, a substituted alkyl group and the like; R2 and R3 represent hydrogen atom, an alkyl group, a substituted alkyl group, an alkoxyl group and the like; X represents —CH2—, —O—, or —NH—; A represents the following group (II): [in which R7 and R8 represent hydrogen atom, an alkyl group, an acyl group, an alkoxycarbonyl group and the like; R9 and R10 represents hydrogen atom, a halogen atom, hydroxyl group, phenyl group, an alkyl group and the like] and the like; and E represents hydrogen atom and the like, which has inhibitory activity against carboxypeptidase B and is useful for therapeutic and/or preventive treatment of a thrombotic disease.

Abstract: A compound of formula (I): wherein: represents an optionally substituted saturated carbon ring having from 4 to 8 ring members, R1 and R4, which may be identical or different, each represents hydrogen or acyl, R2 and R3, which may be identical or different, each represents hydrogen or alkyl, R5 and R6, which may be identical or different, each represents hydrogen or alkyl, or R5 and R6 together, with the nitrogen atom carrying them, form an optionally substituted nitrogen-containing heterocycle, stereoisomers thereof, and also addition salts thereof with a pharmaceutically acceptable acid. Medicinal products containing the same which are useful for treatment of glucose intolerance or of disorders associated with hyperglycaemia.

Abstract: A compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof: wherein R1 represents hydrogen atom, an alkyl group, a substituted alkyl group and the like; R2 and R3 represent hydrogen atom, an alkyl group, a substituted alkyl group, an alkoxyl group and the like; X represents —CH2—, —O—, or —NH—; A represents the following group (II): [in which R7 and R8 represent hydrogen atom, an alkyl group, an acyl group, an alkoxycarbonyl group and the like; R9 and R10 represents hydrogen atom, a halogen atom, hydroxyl group, phenyl group, an alkyl group and the like] and the like; and E represents hydrogen atom and the like, which has inhibitory activity against carboxypeptidase B and is useful for therapeutic and/or preventive treatment of a thrombotic disease.

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: Aminobutylic acid derivatives of the formula (I) wherein the symbols are as defined in specification; and non-toxic salts thereof. Because of inhibiting matrix metalloproteinase, the compounds of the formula (I) are useful for prevention and/or treatment of diseases, for example, rheumatoid diseases, arthrosteitis, osteoarthritis, unusual bone resorption, osteoporosis, periodontitis, interstitial nephritis, arteriosclerosis, pulmonary emphysema, cirrhosis, cornea injury, cornea ulcer, metastasis, invasion or growth of tumor cells, autoimmune disease, disease caused by vascular emigration or infiltration of leukocytes, arterialization, multiple sclerosis, arota aneurysm, endometriosis, restenosis after PTCA, unstable angina, acute myocardial infarction, transient ischemic attack.

Abstract: The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.

Abstract: Bis-(N,N′-bis-(2-haloethyl)amino)phosphoramidates, pharmaceutical compositions containing them, methods of treatment using them, and processes for their preparation. The compounds possess anti-tumor activities or are capable of being modified to have anti-tumor activities; and this invention relates to the use of the compounds in methods for the treatment of tumors and, especially, for the treatment of cancer.

Abstract: The present invention relates to peptide-like compounds, eg aminocarboxylic acid amide derivatives, and to methods of using same to stimulate cells of the immune system, bone marrow and other organs. The present compounds can be used to enhance vaccination, increase synthesis of and enhance function of blood cell components and enhance anti-neoplastic effects of various agents. The compounds of the invention can be used to produce a variety of further pharmacologic effects.

Abstract: The present invention relates to phosphoric acid derivatives represented by general formula (I), wherein each symbol is as defined in the description and nontoxic salts thereof. Because of having a TNF&agr; production inhibitory effect, the compounds represented by general formula (I) are useful as preventives and/or remedies for rheumatoid arthritis, ulcerative colitis, Crohn's disease, hepatitis, sepsis, hemorrhagic shock, multiple sclerosis, cerebral infarction, diabetes, interstitial pneumonia, uveitis, pain, glomerulonephritis, HIV-associated diseases, cachexia, myocardial infarction, chronic heart failure, oral aphtha, Hansen's disease, infection, etc.

Abstract: Compounds of Formula I are disclosed as inhibitors having activity against the aspartyl proteases, plasmepsin and cathepsin D. The compounds are therefore useful for treatment of diseases such as malaria and Alzheimer's disease. In preferred compounds of Formula I, Y is an dialkoxyphosphonate, or &agr;-hydroxyamide group and Z is an acyl or &agr;-ketocarbamate functionality. Intermediates in the solid phase synthesis of compounds of Formula I, in which compounds are attached to a solid support, are also disclosed.

Abstract: The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds, which comprise a phosphocholine moiety covalently conjugated with one or more therapeutic agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt or a prodrug thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus.

Abstract: The invention concerns (&agr;-aminophosphino) peptide derivative compounds of general formula (I) wherein: R1 and R2 represent each a hydrogen atom or together form an imine with the adjacent nitrogen atom; R3 represents an alkyl group, an alkenyl group, a phenyl group, a benzyl group, all said groups capable of being substituted or not, a hydrogen atom, a cycloalkyl group, a cycloalkylmethyl group or finally a methyl group substituted by an aromatic or saturated heterocyclic group; R4 represents a CH(X)—(O)—C(O)—Y group or a CH2CH2—S—C(O)—W group; R5 represents an alkyl group, an alkenyl group, a phenyl group, a benzyl group, all said groups capable of being substituted or not, a hydrogen atom, a cycloalkyl group, a cycloalkylmethyl group or finally a methyl group substituted by an aromatic or unsaturated heterocyclic group; R6 and R7 can in particular represent a hydrogen atom, an alkyl group, a phenyl group substituted or not; R8 represents an alkyl, alkenyl, phenyl or b

Abstract: Compounds of the formula I 1

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: Osteoblast-specific mitogens and drugs containing such compounds can be used for treating metabolic bone diseases. These compounds include lysophosphatidylic acid derivatives selected from the group consisting of compounds of formula: wherein R1=alkenyl or alkynyl having from 6 to 24 carbon atoms; n=0-12; X=oxygen or NH; the compounds (all-cis-5,8,11,14)-eicosatetraenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-9, cis-12-octadecadienoic acid 2-hydroxy-3-phosphonooxypropyl ester; (all-cis-9,12,15)-octadecatrienoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-9-octadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; and erucic acid 2-hydroxy-3-phosphonooxypropylester being excluded, and the physiologically tolerable salts, esters, optically active forms, and racemates of said compounds, and derivatives of said compounds, salts, esters, optically active forms and racemates which can be metabolized in vivo to yield the corresponding compound of formula (I).

Abstract: Compounds of Formula I ##STR1## are disclosed as inhibitors having activity against the aspartyl proteases, plasmepsin and cathepsin D. The compounds are therefore useful for treatment of diseases such as malaria and Alzheimer's disease. In preferred compounds of Formula I, Y is an dialkoxyphosphonate, or .alpha.-hydroxyamide group and Z is an acyl or .alpha.-ketocarbamate functionality. Intermediates in the solid phase synthesis of compounds of Formula I, in which compounds are attached to a solid support, are also disclosed.

Abstract: The present invention provides compounds that inhibit the association of platelet-derived growth factor and phosphatidylinositol 3-kinase. The present invention also provides pharmaceutical compositions that contain a compound that inhibits the association of platelet-derived growth factor and phosphatidylinosital 3-kinase, and methods of treating cancer, restenosis, arthritis, dermatitis, atherosclerosis, vein graft intimal hyperplasia, neointimal hyperplasia of vascular smooth muscle and psoriasis using compounds that inhibit the association of platelet-derived growth factor and phosphatidylinositol 3-kinase.

Abstract: A phosphite represented by the formula (I): ##STR1## wherein n repesents 1 or 2; A represents alkylene; B represents a direct bond or alkylene; one of Y and Z represents a hydroxyl group, alkoxy or aralkyloxy, and the other one represents a hydrogen atom or alkyl; X represents a group of formula (II): ##STR2## wherein R.sup.1 and R.sup.2 represent a hydrogen atom, an alkyl group, a cycloalkyl group, an alkylcycloalkyl group, an aralkyl group or a phenyl group; R.sup.3 represents a hydrogen atom or an alkyl group; and R.sup.4 represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkylcycloalkyl group, an aralkyl group or a phenyl group, or R.sup.4 may be combined to form a direct bond, a sulfur bond (--S--), or an unsubstituted or substituted methylene group; R.sup.5 and R.sup.6 independently represent a hydrogen atom, an alkyl group, a cycloalkyl group, an alkylcycloalkyl group, an aralkyl group or a phenyl group;R.sup.8 represents a hydrogen atom or an alkyl group; andR.sup.

Abstract: Lipid prodrugs of phosphonoacids and their analogs that have increased antiviral activity over the parent drugs in inhibiting cytomegalovirus and other susceptible viruses.

Abstract: Fluorinated alkene compounds useful for and methods of controlling nematodes, insects, and acarids that prey on agricultural crops. Polar compounds are particularly useful for systemic control of pests.

Abstract: A class of novel phenyl glyoxamides is disclosed together with the use of such compounds for inhibiting sPLA.sub.2 mediated release of fatty acids for treatment of conditions such as septic shock.

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: 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: Process for the enzymatic resolution of 2-amino-4-methylphosphinobutyric acid derivatives.L-PTC (L-phosphinothricin, L-2-amino-4-methylphosphinobutyric acid) is the active herbicidal component of D,L-PTC and can be obtained according to the invention when D,L-PTC derivatives which are N-acylated and esterified on the phosphinic acid group as well as optionally esterified or amidated on the carboxylic group, are treated with a hydrolytically active enzyme in an aqueous or aqueous-organic medium, in which process the L-PTC derivatives are selectively hydrolyzed on the N-acyl group or the modified carboxyl group, the resulting product mixture is resolved, and the desired L-PTC derivative is hydrolyzed to give the L-PTC and isolated by customary methods.

Abstract: An improved process for producing ethylenically unsaturated phosphate ester compounds, especially 2-(methacryloyloxyethyl)-2' (trimethylammoniomethyl) phosphate, (HEMA-PC) comprises a two step reaction in the first of which a phospholane reagent is reacted with a hydroxyl containing ethylenically unsaturated starting material, and in the second of which the intermediate formed in the first step is ring opened by reaction with trimethylamine to produce a zwitterionic product. In the process the two steps of the reaction are carried out in the same solvent with substantially no removal or addition of solvent after the first step. The solvent is preferably acetonitrile. The use of pure reagents avoids the production of undesirable by-products. The product is suitable for polymerising, for instance to provide cross-linked hydrogel copolymers used in ophthalmic applications.

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: 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: 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: 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: This invention is selected novel chiral (essentially pure) alpha-amino phosphonates, process for the preparation which is a catalytic asymmetric hydrogenation of olefins and novel intermediates therefor. The alpha-amino phosphonates are useful as antibiotics and/or as intermediates in the preparation of phosphorus-containing analogs of peptides, i.e., phosphonopeptides or pseudopeptides having known uses, such as in antibiotics, antibiotic enhancers, or enzyme inhibitors.

Abstract: Inks, particularly inks for ink jet printing, contain at least one compound of the formula I ##STR1## as a stabilizer. The symbols R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.3 ' and R.sub.4 ' are as defined in claim 1. The compounds are in part novel and are suitable for use as light stabilizers for organic materials.

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: The composition, synthesis, and applications of tumor associated protease activated prodrugs of phosphoramide mustard, isophosphoramide mustard and analogs with detoxification functionalities are described. These drugs release a cytotoxic phosphoramide mustard analog following activation by tumor associated proteases and esterases. The general structure for these drugs is: ##STR1## Wherein R1 is a beta-X-ethyl-amino group which may optionally bear substituents on the nitrogen or carbon atoms; wherein X is a good leaving group such as a halogen; R2 is a beta-X-ethyl-amino group which may optionally bear substituents on the nitrogen or carbon atoms; or an amino group (NH.sub.2) which may optionally be substituted. Wherein A is a benzyloxy derivative with one or more acyloxy or acylamino groups in para or ortho portions relative to the phosphoester; and wherein the acyloxy or acylamino groups are not (substituted or unsubstituted) p-guanidino-benzoyloxy groups or p-guanidino-benzoylamino groups.

Abstract: The present invention is directed to novel phosphorous-containing inhibitors of cysteine or serine proteases. Methods for the use of the protease inhibitors are also described.

Abstract: New lipopolyamines of general formula (I), their salts, their preparation and their use. ##STR1## n=1 to 5 and m=2 to 6 R represents a radical ##STR2## (R.sub.1 and R.sub.2 : aliphatic radical containing 12 to 22 carbon atoms; R: hydrogen atom or alkyl radical optionally substituted with phenyl), or a radical ##STR3## (X=CH.sub.2, CO; R.sub.3 and R.sub.4 aliphatic radical containing 11 to 21 carbon atoms), their preparation and their use.The lipopolyamines of general formula (I) are especially useful as vectors for the transfection of eukaryotic cells.

Abstract: The compounds disclosed inhibit the prenylation of several proteins. These compounds are potent inhibitors of famesyl-protein transferase and geranylgeranyl-protein transferase. Further contained in this invention are chemotherapeutic compositions containing these prenyl-transferase inhibitors and methods for their production.

Abstract: Compounds of formula (I), in which the groups R are hydrogen or C.sub.1-4 alkyl, n is from 2 to 4, X is alkylene, poly(ethoxy) or an aryl-containing group, Y is a valence bond or a divalent functional or heterocyclic group or a trivalent alkylene group, and Z is a sulphur-containing group which contains a thiol or disulphide group are useful to provide biocompatible treatments of metal surfaces, such as silver and gold surfaces. Processes for the preparation of the compounds, intermediates useful in such processes, articles having a metal surface treated with such compounds and processes of rendering metal surfaces biocompatible which comprise treating the metal surfaces with them.

Abstract: Peptidyl derivatives of diesters of .alpha.-aminoalkylphosphonic acids, particularly those with proline or related structures, their use in inhibiting serine proteases with chymotrypsin-like, trypsin-like, elastase-like, and dipeptidyl peptidase IV specificity and their roles as anti-inflammatory agents, anticoagulants, and anti-tumor agents.

Abstract: Compounds of the formula ##STR1## where X.sub.1 and X.sub.2 are independently O or S, andR.sub.1 is as defined in the descriptionR.sub.2, R.sub.3, and R.sub.4 are each independently straight orbranched chain (C.sub.1-4)alkyl, and pharmaceutically acceptable salts, physiological hydrolysable esters, and pro-drug forms thereof are useful as hypoglycemic agents.

Abstract: Novel .alpha.-aminophosphonates are provided along with processes and intermediates for their preparation. In preferred embodiments, scalemic .alpha.-aminophosphonates are prepared by the stereoselective addition of phosphite salts to chiral imines.

Abstract: A new nitro compound of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are each lower alkyl or lower alkoxy(lower)alkyl, or ##STR2## is cyclized to form ##STR3## X is --O--, --S-- or --NH--, m is an integer 0 or 1, andR.sup.3 is carbamoyl, lower alkylcarbamoyl, lower alkanoyl, di-lower alkylaminosulfonyl, lower alkylsulfonyl, oxamoyl or a group of the formula: --(Y).sub.n --R.sup.4whereinY is --CO--, --SO.sub.2 --, --COCH.sub.2 -- or ##STR4## n is an integer of 0 or 1, and R.sup.4 is heterocyclic group which is optionally substituted with one or more substituents selected from lower alkyl, lower alkoxy, phenyl, carbamoyl, halogen, amino, lower alkylthio, hydroxy, lower alkylsulfonylamino and carbamoylmethyl, and pharmaceutically acceptable salt thereof, which are useful as vasodilators.

Abstract: A novel pseudoceramide which has improved dispersibility in aqueous solutions and which can be produced by an economical manufacturing process. The process for producing new pseudoceramides and cosmetic compositions containing the new pseudoceramides are also disclosed.

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: Phosphorus containing polypeptides as renin inhibitors, useful as antihypertensive agents.

Abstract: Substituted cyclohexane derivatives for the treatment of diseases Esters of cyclohexane derivatives of the formula I ##STR1## in which A--B, R.sup.3, R.sup.4, R.sup.5, Y and Z have the meanings indicated, for use as inhibitors of the glucose-6-phosphatase system of the liver in mammals are described. The compounds are suitable for the production of pharmaceutical preparations.

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: The present invention relates to fluorinated carboxylic acid esters of phosphono- and phosphinocarboxylic acids containing hydroxyl and/or mercapto groups, their use as waterproofing and/or oil-repellency agents, and a method for their preparation.

Abstract: The invention relates to a process for the enantioselective preparation of L-phosphinothricin (L-Ptc) and derivatives of the formula I ##STR1## in which R.sup.1 is H, (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.4)-haloalkyl, (C.sub.3 -C.sub.6)-cycloalkyl or (subst.) phenyl-(C.sub.1 -C.sub.4)-alkyl, R.sup.2 is hydrogen, formyl, [(C.sub.1 -C.sub.6)alkyl]carbonyl, [(C.sub.1 -C.sub.6)alkoxy]carbonyl, (subst.) benzyloxycarbonyl, (C.sub.1 -C.sub.6)-alkylsulfonyl or (subst.) (C.sub.6 -C.sub.10)-arylsulfonyl, and R.sup.3 is OH, NH.sub.2 or (C.sub.1 -C.sub.6)-alkoxy, or their salts with acids or bases.

Abstract: The present invention relates to fluorinated carboxylic acid esters of phosphonocarboxylic acids containing acrylate and/or methacrylate groups, their use as waterproofing or oil-repellency agents, and a method for their preparation.