52 results about "Phosphoramidate" patented technology

2'-Fluoro-6'-methylene-carbocyclic adenosine (FMCA, 21) and its phosphoramidate prodrug (FMCAP, 31) have demonstrated potential anti-HBV activity against both adefovir- resistant as well as lamivudine-resistant double (rtL180M / rtM204V) mutant hepatitis B virus (HBV). In addition, in vitro, these molecules have reinstated a significant activity against lamivudine / entecavir triple mutants (L180M+S202G+M204V). This invention is directed to compounds, pharmaceuticals and methods of treating HBV infections, especially including infections caused by resistant and multiple resistant HBV. Pursuant to the present invention, a complete structure-activity relationship (SAR) of 2'-fluoro-6'-methylene-carbocyclic derived nucleos(t)ides has been evaluated and that analysis is presented herein. Pursuant to the present invention, the synthesis and antiviral evaluation of purine and pyrimidine-derived nucleosides have been reported against wild-type and various HBV mutants. Guanosine analog (FMCG, 25) demonstrated an EC50 value of 0.217μM and cytosine analog (FMCC, 41) expressed a potent EC50 value of 0.0025 μM compared to entecavir (EC50 = 0.0029) against wild-type HBV. Additionally, FMCC (41) maintains its antiviral potency against various HBV mutants. Furthermore, chiral pure FMCAP Sp (34) isomer demonstrated an EC50 value of 1.3 nM and was more potent against several HBV mutants than entecavir.

The invention provides a modified phosphoramidate intemucleotide linkage, referred to herein as a fiuorosulfonyl phosphoramidate (fsP) internucleotide linkage, wherein the fsP intemucleotide linkage has the structure of formula (I) modified oligonucleotides comprising at least one tsP intemucleotide linkage, and methods of using the modified oligonucleotides comprising at least one fsP internucleotide linkage.

The present invention discloses a high-performance water reducer of organosilicon condensate type and a preparation method thereof. Liquid ammonia and ethylene oxide undergo a ring-opening reaction to obtain an N-hydroxyethylamine compound. The N-hydroxyethylamine compound is condensed with formaldehyde to obtain an N-hydroxyethyl-N-hydroxymethylamine intermediate. The N-hydroxyethyl-N-hydroxymethylamine intermediate undergoes an esterification reaction with phosphorus trichloride to obtain an amino alcohol intermediate containing a phosphate ester group. The amino alcohol intermediate containing a phosphate ester group is polymerized with a dihydrogen-terminated polydimethylsiloxane oligomer to obtain an organosilane-modified oligomer containing amino and phosphate ester groups, and then a high-performance water reducer is obtained through high-temperature dehydration. The phosphate ester group, siloxane group, and amino group connected to the high-performance water reducer of the present invention reduce the liquid-solid interfacial energy and improve the dispersing ability, dispersion stability, and anti-sludge ability of the high-performance water reducer to cement particles. The water reducer of the present invention has a protective effect on the steel bars in reinforced concrete, the preparation process is simple, the product has good uniformity, realizes low cost, green environmental protection, and multifunctionalization, and has good application prospects.

The present invention relates to small molecules having high affinity and specificity to prostrate-specific membrane antigen (PSMA) and methods of using them for therapeutic and diagnostic purposes.

The invention provides a method for efficiently preparing various substituted chiral phosphoramides, which comprises the following steps: in the presence of an organic solvent, alkali, a chiral ligand and a catalyst, reacting a nucleoside compound or alcohol with racemic amino phosphoryl dichloride or alkoxy phosphoryl dichloride to generate chiral phosphoryl chloride; and reacting the chiral phosphoryl chloride with a nucleophilic reagent to obtain the chiral phosphamide. The synthesis method provided by the invention is simple to operate, high in yield and good in diastereoselectivity or enantioselectivity, and the obtained target compound has the characteristics of good functional group compatibility and wide substrate universality. The obtained product is diversified in structure and good in controllability, and has good application potential in the field of medicine synthesis.

The invention discloses a process for removing calcium ions and magnesium ions from nitrate-containing quaternary system brine, and relates to the technical field of brine treatment. The method comprises the following steps: filling a single column with modified composite resin, enabling the nitrate-containing quaternary system brine to pass through the column, and collecting outlet liquid to obtain the calcium ion and magnesium ion removed nitrate-containing quaternary system brine. Wherein the modified composite resin is prepared by the following steps: pretreating phosphoramidate chelate resin with dopamine, compounding the pretreated phosphoramidate chelate resin with nano-crystalline cellulose, a synergist and functionalized carbon quantum dots, cross-linking with a silane coupling agent KH560, and finally soaking with acid and alkali and purifying. The nano cellulose, the synergist, the functionalized carbon quantum dots and the like are introduced, and a specific process method is matched, so that the calcium and magnesium adsorption capacity, the permeation wear impact force resistance, the pollution resistance and the lithium loss resistance of the treatment process are effectively improved. Therefore, the treatment process disclosed by the invention has a wider application prospect.

The invention relates to a high-adhesion anti-stripping primer special for a metal substrate and a preparation method thereof, and belongs to the technical field of paints.The primer comprises silane modified phosphoramidate chelating resin, graphite oxide-Schiff base zirconium-siloxane hybrid filler, a hyperbranched polyamide-siloxane bonding accelerant, an isocyanate curing agent, functional auxiliaries and the like. The silane modified phosphoramidate chelating resin is prepared by carrying out a reaction on bisphenol F epoxy resin and diethylenetriamine, and carrying out a reaction on p-toluenesulfonic acid, diethyl phosphite, KH540 and hydroquinone. The graphite oxide-Schiff base zirconium-siloxane hybrid filler is prepared from the following components: GO-SB, ZrO2-siloxane core-shell particles, zirconium n-propoxide and the like. The hyperbranched polyamide-siloxane bonding accelerator is prepared by the following steps: reacting ethylenediamine with methyl acrylate, then reacting with ethylenediamine, and then modifying with KH540 and perfluoroalkyl phosphate. The problems that a traditional primer is weak in interface bonding force, easy to peel off and insufficient in corrosion resistance are solved.

A pharmaceutically acceptable salt of an acyclic nucleotide phosphoramidate to treat HPV and related conditions including neoplasia, as well as pharmaceutical compositions, morphic forms and dosage forms thereof.

Nucleotides with alpha-imino phosphate groups and bridging sulfurs, and methods of synthesizing and using the same, are provided herein. In some examples, a nucleotide may include a sugar, a nucleobase coupled to the sugar, an alpha-imino phosphate group, and a bridging sulfur coupling the alpha-imino phosphate group to the sugar.

Click-labeled uridine bases, nucleosides, and phosphoramidites are provided, including improved methods of synthesis, oligonucleotides comprising the click-labeled nucleosides, methods of synthesizing spin-labeled oligonucleotides using click-labeled nucleotides, and spin-labeled oligonucleotides comprising click-labeled nucleosides.

The present application relates to a double-stranded DNA molecule comprising a first double-stranded DNA molecule (1) connected to a second double-stranded DNA molecule (2) by at least one covalent bond which is not a phosphodiester, phosphorothioate, phosphoramidate or phosphorodiamidate bond, preferably by a tether, said tether preferably being a double-stranded DNA molecule.

This invention provides a method and equipment for producing lithium carbonate for batteries. The method includes the following steps: S1, crushing and grinding lepidolite ore into fine particles with a particle size of less than 75 μm; S2, placing the ground lepidolite particles into a flotation device to obtain lepidolite concentrate using a flotation process. The lithium carbonate production method provided by this invention incorporates phosphate and carboxylic acid groups into the collector. The phosphate groups in the aminophosphate molecule can form stable chemical bonds or complexes with lithium ions on the surface of lepidolite, enhancing the binding force between the collector and lepidolite, increasing the collection ability of lithium minerals, and improving selectivity. The interaction with the surface of lepidolite is specific, while the interaction with the surface of gangue minerals is weaker, thus better enhancing its selectivity and improving the quality of the lepidolite concentrate, laying the foundation for the subsequent production of higher quality lithium carbonate.

The present invention discloses a nucleoside compound, a pharmaceutical composition, and uses thereof. The nucleoside is linked to a phosphate ester via a phosphorus-oxygen bond, and the nucleoside phosphoramidate compound, as described in Formulas I, Ia, and Ib, and its stereoisomers, salts, hydrates, solvates, or crystals, are described. #imgabs0# The present invention is easy to prepare and has proven efficacy.

The application provides a phosphoramidate morpholino antisense oligonucleotide for antiviral, which comprises a base sequence shown as SEQ ID NO. 1, the antisense oligonucleotide is a phosphoramidate morpholino antisense oligonucleotide, the structural formula of the phosphoramidate morpholino nucleotide monomer in the antisense oligonucleotide is shown in the following formula, Base is a base; R is N, N-dimethylamine or piperazine. The antisense oligonucleotide can be combined with a specific region in the fifth segment of viral RNA of an influenza virus, block the transcription of the viral RNA through steric hindrance, play an antiviral role, and use a PMO structure which is good in nuclease stability, high in antisense efficiency and good in water solubility, and at the same time, by introducing a piperazine group which is positively charged under physiological conditions, the PMO compound can enter the cell across the membrane, and the biological activity of the compound can be effectively enhanced.

Provided is a method for estimating a structure of an oligonucleotide in which a plurality of nucleotides are linked by one or more phosphoramidate bonds or phosphorodiamidate bonds, using a mass spectrometer including an ion source employing a MALDI method, said method comprising: a preparation step for preparing an analysis sample including the oligonucleotide and a matrix; a mass spectrometry step for generating fragment ions by cleaving, in the mass spectrometer, a P-N bond involved in the linkage between the nucleotides in at least one of the phosphoramidate bonds or the phosphorodiamidate bonds of the oligonucleotide contained in the analysis sample, and detecting the fragment ions using the mass spectrometer; and a structure estimation step for estimating at least a portion of the structure of the oligonucleotide by analyzing the result of the mass spectrometry obtained in the mass spectrometry step.

Embodiments for the synthesis of sensitive oligonucleotides as well as insensitive oligonucleotides are provided. Sulfur-based groups are used for the protection of exo-amino groups of nucleobases, phosphate groups and 2′-OH groups, and as cleavable linker for linking oligonucleotides to a support. Oligonucleotide syntheses are achieved under typical conditions using phosphoramidite chemistry with important modifications. To prevent replacing sulfur-based protecting groups by acyl groups via cap-exchange, special capping agents are used. To retain hydrophobic tag to assist RP HPLC purification, special phosphoramidites are used in the last synthetic cycle. With the sulfur-based groups for protection and linking, oligonucleotide deprotection and cleavage are achieved via oxidation followed by beta-elimination under mild conditions. Therefore, besides for insensitive oligonucleotide synthesis, the embodiments of the invention are capable for the synthesis of oligonucleotide analogs containing sensitive functional groups that cannot survive the harsh conditions used in prior art oligonucleotide synthesis technologies.

Provided herein are monosaccharides, e.g., compounds of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for cell labeling for diagnostic and / or therapeutic applications. [Formula 1] TIFF2025541836000133.tif18170

The application discloses low immunogenic collagen and a preparation method and application thereof, and the preparation method comprises the following steps: (1) performing enzymolysis on animal skin; (2) performing salt precipitation treatment on the enzymolysis glue liquid; (3) adding organic amino phosphoric acid or a salt thereof to replace and purify the crude collagen protein prepared through the salt precipitation treatment after redissolving the crude collagen protein, and then performing salt precipitation treatment to obtain purified collagen protein; and (4) redissolving, dialyzing and freeze-drying the purified collagen protein to obtain low immunogenic collagen. Through replacement and removal of DNA impurity molecules on collagen molecular chains by using phosphate in organic amino phosphoric acid or the salt thereof, the amino in the organic amino phosphoric acid or the salt thereof can promote the combination of the phosphate and the collagen under the action of intermolecular hydrogen bonds between the amino and residual carboxyl on the collagen, and the amino and the phosphate play a synergistic effect, so that the removal effect of the DNA impurity in the collagen can be further improved, and the immunogenicity of the collagen is reduced.

The invention provides a synthesis method of aryl phosphate, and solves the problems of harsh reaction conditions, existence of potential safety hazards, high requirements on equipment, tedious process, low yield, high cost and the like which are not beneficial to industrial production in the existing synthesis method. The preparation method comprises the following main preparation steps: S1, reacting chloro phosphate with different types of amines to obtain phosphoramidate; s2, the phosphoramidate and different kinds of benzyne precursors are subjected to an arylation reaction under the fluoride condition, and aryl phosphate is obtained.By means of the one-pot method, the experimental operation process can be simplified, generation of by-product impurities is avoided, the yield is greatly improved through condition screening, and the obvious effect is achieved.

The invention discloses a preparation method of amino phosphorylation synergistically modified nano calcium carbonate, which comprises the following steps: adding 10-20g of nano calcium carbonate into 200mL of absolute ethyl alcohol or deionized water, and treating for 30 minutes by an ultrasonic dispersion instrument to form a uniform dispersion liquid; dissolving 5-15g of a phosphorus source compound in deionized water; taking a nitrogen source compound accounting for 10-20% of the mass of the nano calcium carbonate, slowly adding the nitrogen source compound and the phosphorus source compound solution in the step S2 into the dispersion liquid in the step S1, and stirring while adding; placing the mixed solution in a magnetic stirrer for stirring reaction, and adjusting the pH value of the system to be neutral by using NaOH or HCl after the reaction is finished; washing the product with deionized water for multiple times until the pH value of the solution is close to neutral, and removing unreacted phosphorus source and nitrogen source compounds; and drying the washed product in a vacuum drying oven until the weight is constant, thereby obtaining the phosphoramidated synergistically modified nano calcium carbonate. The P-N modified nano calcium carbonate can be synergistically used with a phosphorus-nitrogen flame retardant, so that the addition amount of the phosphorus-nitrogen flame retardant is reduced, and the cost is reduced.

This invention relates to the field of polymer functional materials and water treatment technology, and discloses a preparation process of a bifunctional chelating resin of a metallo-oxime-aminophosphate group, comprising the following steps: S1. Swelling treatment: Styrene-divinylbenzene (St-DVB) copolymer white spheres are used as the matrix. Aminophosphate groups and metallo-oxime groups are simultaneously grafted onto the resin backbone to form a unique bidentate chelating structure. The aminophosphate groups are highly acid-resistant and can preferentially act on heavy metal complexes in acidic water environments, weakening the coordination bond between the complexing agent and copper ions. The metallo-oxime groups are rich in nitrogen and oxygen coordinating atoms, which can quickly capture dissociated copper ions. The two groups form a chemical synergistic effect, which is not a simple superposition of adsorption performance. X-ray photoelectron spectroscopy characterization proves that the nitrogen and oxygen atoms of both functional groups can participate in the coordination of copper ions to form a stable chelating ring, breaking the thermodynamic equilibrium of strongly complexed heavy metals and avoiding the problem of traditional resins being unable to break the complex.

The invention discloses synthesis of 3 '-amido-5-nucleotide phosphamide and application of the 3'-amido-5-nucleotide phosphamide in oligonucleotide. The phosphamide modified oligonucleotide comprises at least one of nucleotide structural units shown in a formula I, a formula II, a formula III or a formula IV,..., the formula I, the formula II, the formula III,..., the formula IV. Through specific limitation of a nucleotide phosphamide monomer structure, oligonucleotides are prepared by coupling according to a direction from 5 to 3. Compared with a traditional oligonucleotide molecule, the oligonucleotide molecule provided by the invention contains phosphamide modification and has more excellent effects on pharmaceutical parameters such as enzymatic degradation resistance, stability and the like, in addition, the phosphamide modification can improve the binding performance between the modified oligonucleotide molecule and environmental ions, and the stability of the oligonucleotide molecule is improved. A novel chemical modification strategy is provided for research, development and application of oligonucleotide drugs.

Provided herein are monosaccharides, e.g., a compound of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for cell labeling for diagnostic and / or therapeutic applications.

Methods of making and using nucleotide repeat phosphorodiamidate morpholino oligonucleotides (PMO) are provided. Nucleotide repeat PMOs include dinucleotide repeat PMOs, trinucleotide repeat PMOs and tetranucleotide repeat PMOs.

Provided herein are oligonucleotides comprising a phosphoramidite internucleotide bond having the formula: (I) wherein R1 is isopropyl, isobutyl, sec-butyl, C1-6 haloalkyl, C2-6 hydroxyalkyl, C2-8 alkylene-N (RN) 2, C0-2 alkylene-C3-8 cycloalkyl, 4-10 membered heterocycloalkyl having 1-3 ring heteroatoms selected from O, N and S, or 5-10 membered heteroaryl having 1-3 ring heteroatoms selected from O, N and S, with the proviso that the heterocycloalkyl group or the heteroaryl group is attached to sulfur via a carbocyclic atom, and the cycloalkyl group, the heterocycloalkyl group or the heteroaryl group is substituted with 0, 1, 2 or 3 R2 groups; each R2 is independently halo, CN, N (RN) 2, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, oxo, CO2RN, or C (O) C1-3 alkyl; and each RN is independently H or a C1-3 alkyl group. Also provided are formulations comprising the oligonucleotides disclosed herein and methods of treating diseases and disorders using the oligonucleotides disclosed herein and formulations thereof.

The invention discloses a floxuridine phosphamide ester prodrug and application thereof in preparation of a medicine for treating liver cancer, and belongs to the technical field of medicine. The invention designs and synthesizes a series of 5-FdU phosphamide ester derivatives which are subjected to specific esterification modification at 3 '-site. Different aromatic acyl, fatty acyl or amino acid residues are introduced to the 3 '-site, so that the lipophilicity of molecules is further adjusted to enhance liver tissue distribution, and the enrichment and activation process of the medicine in the liver is optimized by utilizing the steric hindrance or metabolic lysis characteristic of the 3'-site. Experiments prove that the series of compounds show excellent anti-hepatoma cell proliferation activity and good pharmacokinetic characteristics, and a new choice is provided for clinical treatment of liver cancer.

Provided herein, in some embodiments, are enzymatic methods for producing an oligonucleotide comprising phosphoramidate-linked nucleotides, and compositions comprising the oligonucleotide thus produced.

Provided herein are monosaccharides, e.g., compounds of Formula (I) and pharmaceutical compositions thereof. Also provided herein are methods of their use in cell labeling for diagnostic and / or therapeutic applications. # imgabs0 #

Provided are: a novel heavy metal treatment agent which improves the treatment performance of a group 6-16 element or a compound thereof in the periodic table, such as wastewater treatment or incineration ash treatment; and a wastewater treatment method and an incineration ash treatment method using the heavy metal treatment agent. This heavy metal treatment agent contains the following component (A) and at least one selected from the group consisting of components (B)-(E). (A) A dithiocarbamate of at least one type of amine compound represented by any of formulae (I) to (III) (wherein each X independently represents a hydrogen atom or a 2-aminoethyl group, at least one of which is a 2-aminoethyl group). (B) a base; (C) at least one substance selected from the group consisting of aminocarboxylic acids, thiols, and phosphoramidates; (D) a dithiocarbamate of a polyethyleneimine; and (E) a sulfur-containing compound. [Chemical Formula 1] # imgabs0 # [Chemical Formula 2] # imgabs1 # [Chemical Formula 3] # imgabs2 #