Abstract: Preparation of O,O-dimethyl phosphoramidothioate and O,O-dimethyl phosphoroamidothioate. A process of making O,O-dimethyl phosphoroamidothioate is described including reacting sulfur with PCl3 to form PSCl3, reacting the PSCl3 formed with methanol to form O-methyl phosphorodichloridothioate, and reacting the O-methyl phosphorodichloridothioate formed with methyl lye to form O,O-dimethyl phosphorochloridothioate in solution in CH2Cl2, and reacting the O,O-dimethyl phosphorochloridothioate formed with sodium hydroxide and ammonium hydroxide to form O,O-dimethyl phosphoroamidothioate in solution in CH2Cl2. Reacting the O,O-dimethyl phosphoroamidothioate formed with catalytic dimethyl sulfate to form methamidophos, and reacting the methamidophos formed with acetic anhydride to form N-(methoxy-methylsulfanylphosphoryl) acetamide is also described. Throughout the process, the O,O-dimethyl phosphorochloridothioate and the O,O-dimethyl phosphoroamidothioate formed are maintained in solution in CH2Cl2 at all times.

Abstract: The present invention relates to the use of osmolytes for treating allergic or viral respiratory diseases, e.g. allergic rhinitis (hay fever) as well as rhinovirus and/or adenovirus infections. The invention also relates to a medicament preparation containing one or more compounds from the group of osmolytes. The group of osmolytes used in the invention comprises various low-molecular substances, more specifically ectoine, 4,5,6,7-tetrahydro-2-methyl-1H-[1,3]-diazepine-4-S-carboxylic acid (homoectoine), hydroxyectoine, di-myo-inositol-phosphate (DIP), to cyclic 2,3-diphosphoglycerate (cDPG), 1,1-diglycerol phosphate (DGP), ?-mannosylglycerate (firoin), ?-mannosylglyceramide (firoin-A), dimannosyl-diinositol phosphate (DMIP), glucosylglycerol, taurine, betaine, citrulline, and/or a derivative, e.g. an acid, salt, or ester of said compounds.

Abstract: Compounds of the formulae, (I), wherein each variable is as defined herein are provided which are useful in (i) diagnostic methods for detecting and/or identifying cells presenting PSMA; (2) compositions comprising a compound of the invention together with a pharmaceutically acceptable carrier, excipient, and/or diluent; (3) methods for inhibiting or treating prostrate cancer; and (4) methods for blocking or destabilizing neovasculature of a tumor.

Abstract: The present disclosure relates to pantothenate derivatives for the treatment of neurologic disorders (such as pantothenate kinase-associated neurodegeneration), pharmaceutical compositions containing such compounds, and their use in treatment of neurologic disorders.

Abstract: Provided herein are methods for treating multiple myeloma by administering canfosfamide or a pharmaceutically acceptable salt thereof as a monotherapy, and also by administering canfosfamide or a pharmaceutically acceptable salt thereof as part of novel combination therapies further comprising one or more of bortezomib, lenalidomide, vorinostat, carfilzomib, pomalidomide, and elotuzumab.

Abstract: A process for and intermediates in the preparation of canfosfamide and its salts. Some of the intermediates have anticancer activity.

Abstract: The present invention provides methods for preparing TLR-4 receptor agonist E6020: and stereoisomers thereof, which compounds are useful as an immunological adjuvants when co-administered with antigens such as vaccines for bacterial and viral diseases. Also provided are synthetic intermediates useful for implementing the inventive methods.

Abstract: This invention relates to the synthesis for a precursor of E6020, compound 26, via a ?-keto amide alcohol intermediate, compound 22. The synthesis reacts compound 22 with compound 25 and the resultant intermediate is oxidized to produce compound 26, the precursor to E6020. Compounds 22 and 25, and their crystalline forms, represent separate embodiments of the invention. The invention also relates to compounds of formulas (3) and (4) and processes for their preparation. The ?-keto amide alcohol intermediate compound 22 is a compound of formula (3). Compound 25 is a compound of formula (4).

Abstract: The present invention relates to a suspension stabilizer for dispersing inorganic nanoparticles into aqueous medium. More particularly, the present invention is directed to a biocompatible suspension stabilizer which comprises phosphoryl domain having an affinity to the surface of an inorganic nanoparticle and poly(ethylene glycol) having an affinity to the aqueous medium, and which is prepared by reacting a biocompatible poly(ethylene glycol)-derivatized polymer with phosphine oxide having a leaving group.

Abstract: The present invention provides methods for preparing TLR-4 receptor agonist E6020: and stereoisomers thereof, which compounds are useful as an immunological adjuvants when co-administered with antigens such as vaccines for bacterial and viral diseases. Also provided are synthetic intermediates useful for implementing the inventive methods.

Abstract: This invention relates to the synthesis for a precursor of E6020, compound 26, via a ?-keto amide alcohol intermediate, compound 22. The synthesis reacts compound 22 with compound 25 and the resultant intermediate is oxidized to produce compound 26, the precursor to E6020. Compounds 22 and 25, and their crystalline forms, represent separate embodiments of the invention. The invention also relates to compounds of formulas (3) and (4) and processes for their preparation. The ?-keto amide alcohol intermediate compound 22 is a compound of formula (3). Compound 25 is a compound of formula (4).

Abstract: A compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof: 1

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 a process for the preparation of phosphinic acid esters, which comprises a) reacting elemental yellow phosphorus with alkylating agents in the presence of a base to give a mixture which comprises, as principal constituents, the (metal) salts of alkylphosphonous, phosphorous and hypophosphorous acids, b) esterifying the principal constituents of the mixture from a) to give an ester mixture, c) isolating the ester of the alkylphosphonous acid from the ester mixture, d) adding the resultant ester of the alkylphosphonous acid onto an olefin containing a functional group. The invention likewise relates to the use of the phosphinic acid esters prepared by this process, inter alia as flame retardants and precursors for further syntheses.

Abstract: An organic phosphorous compound represented by the following formula (I): ##STR1## wherein R.sup.1, R.sup.2, R.sup.5 and R.sup.6 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; R.sup.4 represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkylcycloalkyl group, an aralkyl group or a phenyl group, or the two R.sup.4 may be combined with each other to form a direct bond, a sulfur bond (--S--), or aN optionally substituted methylene group; R.sup.7 and R.sup.8 represent a hydrogen atom or an alkyl group, or R.sup.7 and R.sup.

Abstract: A 2-N-amidoethyl protected nucleoside analog phosphoramidite of formula (1): ##STR1## is useful in the synthesis of a wide variety of oligonucleotide analogs. Coupling yields with phosphoramidite (1) in solution or solid phase oligonucleotide analog synthesis are high and the 2-N-amidoethyl protecting group can be removed easily under standard conditions.

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 invention relates to phosphoric acid derivatives of the formula (I) ##STR1## in which R represents optionally substituted alkyl;R.sup.1 represents optionally substituted alkyl;R.sup.2 represents optionally substituted alkyl or optionally substituted alkenyl;R.sup.3 represents optionally substituted C.sub.4 -C.sub.6 -alkyl;X represents oxygen or sulphur, andY and Z represent identical or different radicals from the series comprising hydrogen, halogen, alkyl and alkoxy,which can be used as pesticides.

Abstract: An insecticidal, acaricidal or nematocidal composition which comprises an organophosphorus compound represented by formula (I): ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 each represents C.sub.1 to C.sub.4 alkyl; A represents H, C.sub.1 to C.sub.4 alkyl, C.sub.1 to C.sub.4 alkylthio or N(R.sup.4)R.sup.5 ; Z represents C(CN)R.sup.4 or N-R.sup.7 and an inert carrier show excellent effect for controlling harmful insects, mites and nematodes, do not give off a bad or irritating odor and exhibit very low toxicity to warm-blooded animals. R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are defined in the specification.

Abstract: Compounds of the general formula: ##STR1## are useful as surfactants in the preparation of fluorocarbon emulsions, which can be used as oxygen-carrying blood substitutes, and for many other therapeutic and diagnostic applications. They are further useful in liposomal formulations which are themselves therapeutic agents or provide a vehicle for such agents.

Abstract: Oxamides useful as dye intermediates have the formula ##STR1## where R.sup.1 and R.sup.2 are independently of each other hydrogen, C.sub.1 -C.sub.4 -alkyl or phenyl,X is hydroxyl, nitro or a radical of the formula --NR.sup.3 R.sup.4, where R.sup.3 is hydrogen or C.sub.1 -C.sub.4 -alkanoyl and R.sup.4 is hydrogen, C.sub.1 -C.sub.4 -alkyl or phenyl,Z is C.sub.2 -C.sub.8 -alkylene, substituted or unsubstituted phenylene or substituted or unsubstituted naphthylene, or X--Z and R.sup.1 are, together with the nitrogen atom joining them together, the radical of the formula ##STR2## where R.sup.3 is as defined above,L is a bridge member andY is vinyl or a radical of the formula --C.sub.2 H.sub.4 --A, where A is hydroxyl or a group which is detachable under alkaline reaction conditions.

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.

Abstract: The composition, methods of synthesis, and applications of a new class of tumor selective antineoplastic drugs is described. These novel antineoplastic agents are of the general structure: A-C-B. The agents are designed with two key functionalities: a trigger which toxifies the drug; (A) and a deactivator which detoxifies the drug (B) The trigger is selected such that it is activated by an enzyme which is present in elevated levels in the tumor. The deactivator is selected such that it is actuated by an enzyme ubiquitous to all tissues. The fate of the drug in a given cell is then determined by the ratio of the enzymatic activity that triggers toxication to the enzymatic activity which detoxifies the drug. The partitioning of the drug between toxic metabolite and nontoxic metabolite defines the resulting specificity of cytotoxic effect.

Abstract: Compounds having the formula ##STR1## in which: R is C.sub.1 -C.sub.8 alkyl; or phenyl optionally substituted by 1 or 2 groups selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 haloalkoxy, nitro or halo;R.sub.1 is C.sub.1 -C.sub.4 alkyl or phenyl;R.sub.2 is C.sub.1 -C.sub.4 alkyl;R.sub.3 is C.sub.2 -C.sub.4 alkyl or allyl; andX is oxygen, sulfur or NR.sub.4 where R.sub.4 is hydrogen or C.sub.3 -C.sub.4 alkyl;provided that(i) if R.sub.1 is methyl, R is phenyl or substituted phenyl and(ii) if R.sub.3 is isopropyl, X is NR.sub.4, and R.sub.1 is alkyl; and their agriculturally acceptable salts are herbicides.

Abstract: Novel phosphorus containing compounds are described, as well as methods for the preparation and pharmaceutical composition of same, which are useful in preventing the intestinal absorption of cholesterol and thus are useful in the treatment of hypercholesterolemia and atherosclerosis.

Abstract: Ester and amide derivatives of N-(((alkoxy-(alkylthio)phosphinyl)amino)carbonyl)amino)alkanecarboxylic acids of the formula: ##STR1## (wherein R.sup.2 represents an alkyl group containing a carboxylic acid ester or amide moiety) were prepared by the reaction of O,S-dialkyl phosphoroisocyanatidothioates and ester and amide derivatives of naturally occurring and synthetic aminoacids and were found to be effective plant systemic and contact insecticides. Ethyl N-(((methoxy(methylthio)phosphinyl)amino)-carbonyl)methioninate, for example, were prepared from O,S-dimethyl phosphoroisocyanatidothioate and ethyl methioninate and found to control aster leafhoppers when applied to rice plants.

Abstract: As new compounds, substituted aryloxyphenoxy benzamides having the formula ##STR1## in which X is CH or nitrogen; Y is chlorine, bromine, fluorine, iodine, methyl, cyano or hydrogen; Z is hydrogen, chlorine, bromine, fluorine, iodine, CH.sub.n, F.sub.3-n where n is an integer from 0 to 3; R is nitrogen dioxide, hydrogen or halogen; R' is hydrogen, CH.sub.3, lower alkyl, having 1-10 carbon atoms, SCCl.sub.3, ##STR2## or --PO.sub.3 R.sup.3.sub.2 wherein R.sup.3 is hydrogen, alkyl having 1-10 carbon atoms, aryl, or an equivalent of base such as a salt; R" is cyano, --C.tbd.CH, ##STR3## wherein R.sup.4 is hydrogen, alkyl having 1-10 carbon atoms, aryl or an equivalent of base such as a salt; and m is 0, 1, 2 or 3.

Abstract: Monoethylenically unsaturated compounds whose polymers are useful as polymeric photoinitiators are of formula Ar.sup.1 COC(R.sup.1)(R.sup.2)R.sup.3 where R.sup.1 is (C.sub.1 -C.sub.10 alkyl or alkoxy, R.sup.2 is C.sub.1 -C.sub.10 alkyl, --X--O--R.sup.4 -OCOC(R.sup.5).dbd.CH.sub.2 (II) --X--NH--R.sup.6 --OCOC(R.sup.5).dbd.CH.sub.2 (III), or --CH.sub.2 [OCH.sub.2 CH(OH)CH.sub.2 ].sub.a OCOC(R.sup.5).dbd.CH.sub.2 (IIIA) or R.sup.1 and R.sup.2, together with the attached carbon, denote C.sub.4 -C.sub.8 cycloalkyl, R.sup.3 is a C.sub.6 -C.sub.20 aromatic group, OH tert. amino,--OCOC(R.sup.5).dbd.CH.sub.2 (VI) or --OCH.sub.2 CH(OH)CH.sub.2 OCOC(R.sup.5).dbd.CH.sub.2 (VIA), R.sup.4 is C.sub.1 14 C.sub.4 alkylene, which may be substituted by --OH or by C.sub.2 -C.sub.20 acyloxy, R.sup.5 is H or C.sub.1 -C.sub.4 alkyl, R.sup.6 is C.sub.1 to C.sub.4 alkylene, X is a group of formula R.sup.7 CO-- or ##STR1## where R.sup.7 is C.sub.1 -C.sub.4 alkylene, R.sup.8 is C.sub.1 to C.sub.4 alkyl, and is 0 or 1, Ar.sup.1 is a C.

Abstract: Compounds of the formula ##STR1## wherein Y is O or NH and X is ##STR2## will inhibit the action of neutral endopeptidase. As a result, such compounds produce diuresis, natriuresis, and lower blood pressure as well as being useful in the treatment of congestive heart failure, relieving pain, and diarrhea when administered to a mammalian host.

Abstract: Oligonucleotide functionalizing reagents are disclosed which are useful in introducing sulfhydryl, amino and additional hydroxyl groups into oligonucleotides. The reagents are substantially linear in structure, at one end provided with a phosphoramidite moiety, at an opposing end provided with a sulfhydryl, amino or hydroxyl moiety, the two ends linked through a hydrophilic spacer chain. Methods of using and synthesizing the novel reagents are disclosed as well.

Abstract: Certain N-acyl phosphonamidothioates and dithioates are useful as insecticides, acaricides and nematocides.

Abstract: The present invention relates to novel compounds of the formula (I) ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and stand for alkyl having 1 to 4 carbon atoms optionally substituted by one or more halogen atoms, alkenyl having 2 to 6 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, phenyl or lower alkoxy-alkyl group,R.sub.3 stands for alkyl having 1 to 6 carbon atoms or alkenyl having 2 to 6 carbont atoms,R.sub.4 and R.sub.5 are the same or different and represent hydrogen, alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, phenyl, benzyl, phenyl substituted by one or more alkyl having 1 to 3 carbon atoms and/or by one or more halogen atoms, lower alkoxy-alkyl, a group of the formula --(CH.sub.2).sub.n --R.sub.6, wherein n is an integer between 0 to 3 and R.sub.

Abstract: Compounds of the formula ##STR1## wherein the symbols have assigned meanings, and their use as insecticides and/or miticides.

Abstract: Compounds of the formula ##STR1## wherein the symbols have assigned meanings, and their use for controlling insects and mites.

Abstract: A biologically active compound can be solubilized by reaction in different sequences to form a derivative carrying the active moiety, a linking group such as an optionally substituted diisocyanate radical, a polyether moiety such as a polyoxyethylene radical, and a terminal group such as a butyl radical, e.g. ##STR1## n=1 to 400. The active materials can be agricultural chemicals, pharmaceuticals, and the like.

Abstract: Phosphonyl hydroxyacyl amino acids of the formula ##STR1## wherein X is a substituted or unsubstituted imino or amino acid or ester. These compounds possess angiotensin converting enzyme activity and are thus useful as hypotensive agents.

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.