107 results about "Phosphoramidate" patented technology

The present invention is the use of a small group of purine nucleotide phosphoramidate disclosed herein or a pharmaceutically acceptable salt thereof in an effective amount for the treatment or prevention of the novel 2019 coronavirus disease (COVID-19) in a host, for example a human, in need thereof.

The invention provides a preparation method of a high-expansion phosphoramidated natural polysaccharide flame retardant. The preparation method comprises the following preparation steps: S1, carrying out amination treatment on a phosphoramidated reagent to obtain a precursor solution; and S2, adding the natural polysaccharide into the precursor solution, and carrying out phosphoramidation reaction to obtain the high-expansion phosphoramidated natural polysaccharide flame retardant. According to the invention, the natural biomass is used as the raw material, and the water is used as the solvent, so that the prepared flame retardant has the advantages of high expansion rate, low environmental hazard, high matrix compatibility and excellent flame retardance. Moreover, on one hand, the flame retardant prepared by the invention has higher expansion rate and fire endurance, and on the other hand, the heat released by the flame retardant during combustion can be reduced and inhibited, so that the harm to the environment is reduced, and the practical effect of the flame retardant prepared by the invention during use is further ensured.

The invention discloses a humic acid type amino-phosphoric acid functionalized hydrogel adsorption material and a preparation method and application thereof.According to hydrogel, natural product macromolecular carbohydrates serve as raw materials, functional groups of phosphate groups and Schiff base structures are introduced through etherification modification, and the adsorption material of a three-dimensional network structure is formed; compared with the prior art, the metal ion adsorbent has high specificity and affinity to metal ions, the long-term stable adsorption effect on pollutant molecules is remarkably improved, and the pollutant molecules can be effectively removed through multiple interactions such as hydrogen bonds, conjugation, electrostatic attraction and coordinate bonds; montmorillonite and potassium humate are introduced, so that the conjugation and chelation coordination between active binding sites of the three-dimensional network structure and pollutants are further enhanced, the efficiency of the adsorption material is improved, and a foundation is laid for wide application of the adsorption material in the field of environmental governance.

The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the AASS gene, as well as methods of inhibiting expression of AASS, and methods of treating subjects that would benefit from reduction in expression of AASS, such as subjects having an AASS-associated disease, disorder, or condition, using such dsRNA compositions.

The invention belongs to the technical field of medicinal chemistry, and particularly discloses a novel tubulin and metalloproteinase double-target inhibitor as well as a preparation method and application of the novel tubulin and metalloproteinase double-target inhibitor. A novel tubulin and metalloproteinase double-target inhibitor is obtained as a compound with a targeting function. A verification result shows that the synthesized target compound shows good anti-proliferative activity on tested cancer cells, 15j has the optimal anti-tumor activity, the IC50 value range of the target compound is 0.154-0.296 mu M, and the tumor inhibition rate of the target compound on human lung cancer transplantation tumors is 74.7% (20 mg / kg). Besides, the anti-proliferative activity of the 15j to cis-platinum drug-resistant cells A549 / CDDP is 136.70 times that of the cis-platinum, the anti-proliferative activity of the 15j to adriamycin drug-resistant cells MCF-7 / DOX is 71.14 times that of the adriamycin, and the toxicity of the 15j to human normal cells (LO2 and MCF-10A) is lower than that of positive drugs such as the cis-platinum, the adriamycin and the paclitaxel. Therefore, the compound has the potential purpose of targeted treatment of lung cancer.

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.

According to the decalcification-free trace DNA extraction method for the old bone sample, an independent decalcification step is not adopted, a specific metal chelating agent and a phosphoramidate derivative are introduced into a bone incubation solution, the specific metal chelating agent has high chelating capacity on calcium and magnesium ions, and the specific metal chelating agent and a complex product thereof are high in water solubility and not prone to being separated out; the phosphoramidate derivative is easy to remove and does not affect the DNA adsorption efficiency of the magnetic beads and subsequent PCR amplification, the phosphoramidate derivative preferentially acts with a phosphate group fixed site on the surface of the soil, adsorption of the soil to the DNA is greatly reduced, an incubation product can be obtained to the maximum extent, then soil impurities are removed through centrifugation, and it is ensured that no adverse effect is generated on subsequent DNA adsorption of the magnetic beads. According to the method, trace DNA can be effectively extracted and purified from old bone detection materials, independent decalcification pretreatment is not needed, sample loss is avoided, and the extracted DNA can be used for forensic medicine identification.

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 provides a method for preparing a suspension-type structured flame-retardant polyether polyol and its use, belonging to the field of polymer synthesis. The method includes: at 0-10 °C, introducing a mixture of phosphite, carbon tetrachloride and anhydrous tetrahydrofuran, dropping a mixture of N-allylmethylamine, triethylamine and anhydrous tetrahydrofuran, raising the temperature to 15-30 °C, and reacting for 6-12 h to obtain allylmethylaminophosphate; at 110-130 °C, a small molecule alcohol compound, propylene oxide and allyl glycidyl ether react to obtain a polyether polyol with double bonds in the side chain; mixing allylmethylaminophosphate, an initiator, a chain transfer agent and isopropanol, and introducing them into the polyether polyol with double bonds in the side chain for reaction to obtain the flame-retardant polyether polyol. This suspension-type structured flame-retardant polyether polyol has the characteristics of a relatively high content of flame-retardant elements, high tensile strength, high tear strength and low Shore hardness, and can be widely used in the preparation of flame-retardant polyurethane products.

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.

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

The present invention relates to a method of extracting at least one liquid organic product from an aqueous medium into an extraction medium, the method comprising: a) contacting the extraction medium with the aqueous medium to form a resultant mixture; and b) allowing the extraction medium and aqueous medium to settle forming almost no droplets in the resultant mixture during the extraction, wherein the extraction medium comprises at least one trialkyl-phosphine-oxide and at least one alkane.

The invention relates to an aminophospholipid lipid molecule compound, a compound as shown in a chemical formula (I), or pharmaceutically acceptable salt, prodrug and # imgabs0 # thereof. The invention also discloses a preparation method of the compound and application of the compound as a delivery treatment component in preparation of drugs.

The present invention relates to a method of producing octanoic acid and / or salts thereof, the method comprising: a) contacting a carbon substrate comprising ethanol or a mixture of ethanol and acetate to the aqueous medium comprising Clostridium kluyveri; b) holding the aqueous medium for a suitable period of time until the Clostridium kluyveri produces a significant amount of octanoic acid and / or salts thereof; c) separating the octanoic acid and / or salts thereof from the aqueous medium using an extraction medium; and d) repeating step (c) continuously as the octanoic acid and / or salts thereof is being formed wherein the extraction medium comprises: - at least one trialkyl-phosphine-oxide, and at least one alkane.

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.

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

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.

The present invention provides NUC-7738 (3 '-deoxyadenosine-5'-O-[phenyl (benzyloxy-L-alanine)] phosphate), a phosphoramidate derivative of 3 '-deoxyadenosine for use in the treatment of proliferative diseases, such as cancer, by reducing the amount of extracellular PD-L1 protein (e.g., soluble PD-L1 or exosome PD L1) and / or increasing the amount of OX40-L. The invention also relates to the use of NUC-7738 in combination with an immune tumor agent, such as an immune checkpoint inhibitor.

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.

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

The present invention relates to chemical compounds, the compounds for use in a method of treatment, particularly in a method of prophylaxis or treatment for cancer, a process for preparation of the compounds and pharmaceutical compositions comprising the compounds. The compounds may, in particular, be useful in the treatment of leukaemia, lymphoma and / or solid tumours in Homo sapiens. The compounds are derivatives of cordycepin (3′-deoxyadenosine).

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.