-Substituted -amino acids, -substituted -amino acid derivatives, and -substituted -amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The -substituted -amino acid derivatives and -substituted -amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the -substituted -amino acid derivatives and -substituted -amino acid analogs and methods of using the compounds for treating cancer are also disclosed. The -substituted -amino acid derivatives and -substituted -amino acid analogs exhibit selective uptake in tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The -substituted -amino acid derivatives and -substituted -amino acid analogs and (bio)isosteres exhibit cytotoxicity toward several tumor types.

The present disclosure provides macrocyclic compounds inspired by the immunophilin ligand family of natural products FK506 and rapamycin. The generation of a Rapafucin library of macrocycles that contain FK506 and rapamycin binding domains should have great potential as new leads for developing drugs to be used for treating diseases.

The present invention relates to an improved method for preparing acrolein cyanohydrins from hydrocyanic acid and the corresponding acroleins. The method is characterized in that the acrolein cyanohydrins obtained have a very low hydrocyanic acid content or are free of hydrocyanic acid and are therefore particularly well suited as intermediates for the synthesis of glufosinates.

The present invention primarily relates to a process for producing certain phosphorus-containing cyanohydrin esters of formula (I) and the use thereof for producing glufosinate/glufosinate salts. The present invention further relates to a process for producing glufosinate/glufosinate salts.

An aqueous curable composition includes a water-soluble photopolymerization initiator having a structure in which one or more carbonyl groups further directly bond to an aromatic ring of an aromatic acyl group that bonds to a phosphorus atom in an acylphosphine oxide structure, water, and a polymerizable compound. A novel water-soluble photopolymerization initiator is a compound represented by formula 1-1 or formula 2-1.

##STR00001##

The present invention relates to a compound of the following general formula (I): R.sub.1NHCH(R.sub.2)P(O)(OR.sub.3)CH.sub.2C(R.sub.4)(R.sub.5)CONHCH(R.sub.6)COOR.sub.7 (I) or a pharmaceutically acceptable salt of the latter, an isomer or a mixture of isomers in any proportions, especially a mixture of enantiomers, and in particular a racemic mixture, for which R.sub.1 represents a C(O)OC(R.sup.8)(R.sup.9)OC(O)R.sup.10 group; R.sub.2 represents an optionally substituted hydrocarbon-based chain, an aryl or heteroaryl group or a methylene group substituted by a heterocycle; R.sub.3 represents a hydrogen atom or a C(R.sup.12)(R.sup.13)OC(O)R.sup.14 group; R.sub.4 and R.sub.5 form, together with the carbon that bears them, a saturated hydrocarbon-based ring or an optionally substituted piperidine ring or R.sub.4 represents a hydrogen atom and R.sub.5 represents a phenyl or a benzyl that is optionally substituted, a heteroaromatic ring or a methylene group substituted by a heterocycle; R.sub.6 represents an optionally substituted hydrocarbon-based chain or a phenyl or a benzyl that is optionally substituted; and R.sub.7 represents a hydrogen atom or a benzyl, alkyl, heteroaryl, alkylheteroaryl, CHMe-COOR.sup.18, CHR.sup.19OC(O)R.sup.20 and CHR.sup.19OC(O)OR.sup.20 group. The present invention also relates to the use of these compounds as a medicinal product, and in particular for the treatment of pain, more advantageously neuropathic and neuroinflammatory pain, to their method of synthesis and also to the compositions containing them.

Cell binding agent-drug conjugates comprising hydrophilic linkers, and methods of using such linkers and conjugates are provided.

The present invention primarily relates to a process for producing certain phosphorus-containing cyanohydrin esters of formula (I) and the use thereof for producing glufosinate/glufosinate salts. The present invention further relates to a process for producing glufosinate/glufosinate salts.

Compounds represented by the following Formula I:

##STR00001##

wherein:
R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are the same or different and are selected from the group consisting of SIL.sub.1-X, hydrogen, C.sub.1-C.sub.20 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.5-C.sub.8 cycloalkyl, phenyl C.sub.1-C.sub.3 alkyl, and fluorine; X is optional, and if present is C.sub.1-C.sub.12 alkyl; SIL.sub.1 has the general formula:

(R.sup.7SiO.sub.3/2).sub.a(R.sup.7.sub.2SiO.sub.2/2).sub.b(R.sup.7.sub.3SiO.sub.1/2).sub.c wherein: R.sup.7 is selected from the group consisting of C.sub.1-C.sub.20 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.5-C.sub.8 cycloalkyl, alkoxyl, phenyl, and phenyl C.sub.1-C.sub.3 alkyl; a is a positive number, b is 0 or a positive number, c is 0 or a positive number, b/a is from 0 to 100, and c/a is from 0 to 10, wherein at least one of R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 is SIL.sub.1-X; and
R.sup.6 is selected from the group consisting of C.sub.1-C.sub.20 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.5-C.sub.8 cycloalkyl, phenyl, phenyl C.sub.1-C.sub.3 alkyl, trimethylphenol, and fluorine,
a method to produce these compounds, and the use thereof as a photoinitiator.

This invention pertains to the use of fused bicycle heterocyclic adducts of thiohydroxy pyridines or pyrimidines as diacylglycerol O-acyltransferase 1 (DGAT-1) inhibitors to treat hyperlipidiemias and various diseases and disorders associated therewith. Other conditions also be ameliorated or avoided, such as high postprandial triglycerides or diet-related hypertriglyceridemia, cardiovascular risk associated with excessive triglycerides, and insulin resistance/glucose intolerance in overweight patients, those with diabetes or other glucose metabolic disorders such as Syndrome X and/or polycystic ovary disease.