The present invention is directed to new 5-ALA derivatives, particles and formulation thereof, related methods of preparation and methods of use thereof. In particular, the invention relates to compounds of the invention, particles and formulation thereof useful in the treatment of a cancer and/or the diagnosis of a cancer cell such as in photodynamic therapy or photodynamic diagnosis.

Compounds having the following formula (E): Formula E or a pharmaceutically acceptable salt thereof, wherein R, R, R, X and n are as defined herein are provided. Methods comprising use of such compounds for the treatment of neurologic disorders, such as pantothenate kinase-associated neurodegeneration, and pharmaceutical compositions containing such compounds, and their use in treatment of neurologic disorders are also provided. ##STR00001##

The instant invention relates to a method of phosphorodiamidite production that comprises: (E1) preparing a purified solution of a dialkylamine in a polar solvent as follows: the dialkylamine dissolved in a polar solvent is contacted with a quantity of phosphorus trihalide that is sufficient to react with the alcohol impurities contained in the dialkylamine but sufficiently low to leave a major part of the dialkylamine unreacted, whereby a mixture is obtained that contains the dialkylamine in the polar solvent and reaction products of the impurities with the phosphorous trihalide; the unreacted dialkylamine and polar solvent present in the mixture obtained in step (E1.1.) are extracted from the solution S by their difference of volatility, typically by distillation, whereby the purified solution of the dialkylamine in the polar solvent is obtained; (E2) the purified solution of dialkylamine in a polar solvent as obtained in step (E1) is reacted with a phosphorus trihalide, whereby an intermediate compound is formed; (E3) the intermediate compound obtained in step (E2) is reacted with a hydroxyalkyl compound in the presence of a non-polar co-solvent.

[Problem] To provide a fluorine-containing phosphate ester-amide which has high flame retardancy such as exhibiting flame retardant effects at a small quantity of addition, and sufficient hydrolysis resistance. [Solution] A fluorine-containing phosphate ester-amide represented by general formula (1). (In the formula, R1 and R2 are the same or different and represent a branched or linear alkyl group having 1 to 20 carbon atoms in which at least one carbon bonded to a nitrogen atom is a secondary or tertiary carbon, wherein R1 and R2 may have a substituent group selected from the group consisting of an alkoxy group, a hydroxy group, an amino group, a methyl amino group, an ethyl amino group, a dimethyl amino group, diethyl amino group and a fluorine atom. In addition, R1 and R2 may be bonded together to form a five- to eight-membered cyclic structure. X and Y are the same or different and represent a hydrogen atom or a fluorine atom, and n and m represent an integer of 1 to 6.) ##STR00001##

Novel non-nucleoside solid supports and phosphoramidite building blocks for preparation of synthetic oligonucleotides containing at least one non-nucleosidic moiety conjugated to a ligand of practical interest and synthetic processes for making the same are disclosed. Furthermore, oligomeric compounds are prepared using said solid supports and phosphoramidite building blocks, preferably followed by removal of protecting groups to provide oligonucleotides conjugated to ligands of interest.

Compositions of dendrimers conjugated with one or more glutamine antagonist(s) that inhibit glutamine metabolism, preferably in activated microglia, and methods of use thereof for treating, alleviating, and/or preventing one or more neurological, oncological, and/or immune disorders associated with pathogenic or dysregulated glutamine-dependent pathways and/or glutamate transmission, have been developed. Dendrimers conjugated with one or more glutamine antagonists effectively inhibit the activity of glutaminase without any systemic toxicity. Dendrimers conjugated with one or more glutamine antagonists accumulate in activated microglia associated with the injured or diseased cells and tissues.

The invention includes processes for the synthesis of amphetamine, dexamphetamine, methamphetamine, derivatives of these, including their salts, and novel precursors and intermediates obtained thereby, by synthesizing aziridine phosphoramidate compounds in specified solvents at specified temperatures, and then converting to a novel aryl or aryl-alkyl phosphoramidate precursors using an organometallic compound such as a copper salt, where the novel aryl or aryl-alkyl phosphoramidate precursor is then easily converted to the target compounds using known reactions,

Phosphate-based linkers with tunable stability for intracellular delivery of drug conjugates are described. The phosphate-based linkers comprise a monophosphate, diphosphate, triphosphate, or tetraphosphate group (phosphate group) and a linker arm comprising a tuning element and optionally a spacer. A payload is covalently linked to the phosphate group at the distal end of the linker arm and the functional group at the proximal end of the linker arm is covalently linked to a cell-specific targeting ligand such as an antibody. These phosphate-based linkers have a differentiated and tunable stability in blood vs. an intracellular environment (e.g. lysosomal compartment).

The invention includes processes for the synthesis of amphetamine, dexamphetamine, methamphetamine, derivatives of these, including their salts, and novel precursors and intermediates obtained thereby, by synthesizing aziridine phosphoramidate compounds in specified solvents at specified temperatures, and then converting to a novel aryl or aryl-alkyl phosphoramidate precursors using an organometallic compound such as a copper salt, where the novel aryl or aryl-alkyl phosphoramidate precursor is then easily converted to the target compounds using known reactions.

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.