76 results about "Nucleoside Analogs" patented technology

Provided are compounds of Formula I:nucleosides, nucleoside phosphates and prodrugs thereof, wherein R6 is CN, ethenyl, 2-haloethen-1-yl, or (C2-C8)-alkyn-1-yl. The compounds, compositions, and methods provided are useful for the treatment of Flaviviridae virus infections.

The present invention relates to an antiviral application of nucleoside analogs. Specifically, the present invention relates to uses of nucleoside analogs and a pharmaceutical composition thereof as: (a) inhibitors for inhibiting the replication of coronaviruses, influenza viruses, respiratory syncytial viruses, flaviviridae viruses, filoviridae viruses and / or porcine epidemic diarrhea virus (PEDV); and / or (b) medicines for treating and / or preventing and mitigating diseases caused by coronavirus, influenza virus, respiratory syncytial virus, flaviviridae virus, filoviridae virus and / or porcine epidemic diarrhea virus (PEDV) infections. The nucleoside analogs according to the invention may treat and / or prevent and mitigate respiratory infection, pneumonia (COVID-19) and other related diseases caused by 2019 novel coronavirus infection.

The invention belongs to the technical field of bioengineering, and particularly provides a preparation method of a nucleoside analogue, which comprises the following steps: by taking 2 '-fluoro-2'-deoxyuridine and a compound as shown in a formula I as substrates, reacting under the catalysis of an enzyme to generate a compound as shown in a formula II.

Provided are siRNA compositions comprising gemcitabine (GEM) substituted for cytosine moieties in siRNAs. Provided are pharmaceutical compositions containing these siRNA molecules, and methods of using these compositions to treat diseases, such as cancer.

Disclosed herein are prokaryotic homologs of viperin (pVips), and nucleotide and nucleoside analogs produced from pVips. These nucleotide and nucleoside analogs stop nucleotide chain synthesis and provide host cells with resistance to viral infections by targeting actively replicating viral genome. Further, these nucleotide and nucleoside analogs decrease DNA replication in malignant cells. Further disclosed are methods of identifying pVips, and nucleotide and nucleoside analogs produced thereof.

A self-assembling composition includes molecules of a first polymer, molecules of a positively charged second polymer, and a nucleic add. First pendant groups conjugated to pendant amine group of the first polymer include a hydrophilic polymer. Second pendant groups conjugated to the pendant amine groups include a hydrophobic group. Third pendant groups conjugated to the pendant amine groups include a group selected from a nucleoside and a nucleoside analog. Fourth pendant groups conjugated to the second polymer via pendant amine groups thereof include the hydrophilic polymer. Fifth pendant groups are conjugated to the amine groups of the second polymer include the hydrophobic group. The second polymer also includes repeat units wherein the pendant amine groups are positively charged in vivo.

The invention relates to the field of analyzing cells and cell division, in particular to means and methods for detecting low numbers of dividing immune cells in blood samples. Provided is an in vitro method for detecting proliferating cells, comprising the steps of: (i) culturing cells in the presence of a nucleoside analog comprising a first reactive unsaturated group to allow for incorporation of the nucleoside analog in the DNA of the cells; (ii) concentrating the nucleoside-labeled cells by covalent immobilization to a solid surface comprising a coating of (3-aminopropyl)triethoxysilane (APTES) or branched polyethyleneimine (PEI) that is activated by glutaraldehyde (GA); (iii) optionally fixing the concentrated and covalently immobilized cells with formaldehyde; (iv) contacting the covalently immobilized cells with a detection probe comprising a second reactive unsaturated group, such that a [3+2] or [4+2] cycloaddition occurs between the first and second reactive unsaturated groups; and (v) determining the amount of detection probe attached to the DNA of the immobilized cells to measure cellular proliferation.

Disclosed herein are compositions and methods for one step CMC production of RNA therapeutic complexes (nanostructures) containing nucleoside analogs. In some embodiments, nucleoside analogs are incorporated into RNA oligonucleotides that self-assemble into RNA complexes during RNA synthesis in one step production. Thus, no additional conjugation or synthesis process is required.

The present invention belongs to the field of medicinal chemistry and relates to a class of 4'-fluoro-1,2,3-triazole nucleoside analogs, their preparation methods, and their use as anti-rabies virus inhibitors. The structural formula of the triazole nucleoside analogs of the present invention is: #imgabs0#;R 1 、R 2 is benzyl, 4-methoxybenzyl, 4-bromobenzyl or 2-naphthylbenzyl; R 3 The present invention relates to a method for preparing a cyclopropyl group, a phenyl group, a 1-methyl-1-hydroxyethyl group, or a methoxycarbonyl group. Most reactions in the preparation method of the present invention are insensitive to air and water, and multi-step reactions can be continued without purification, greatly simplifying the operation, reducing the difficulty of synthesis, and being suitable for large-scale preparation. Such compounds have anti-rabies virus activity and can be used to prepare anti-rabies virus inhibitors.

This document discloses compositions for use with engineered human cells, the compositions comprising a cell regulator or a carrier encoding a cell regulator. This document describes compositions comprising engineered cells, wherein the engineered cells are engineered human cells and contain modifications that make the engineered cells more resistant to alkylating drugs or nucleoside analogs compared to non-engineered human cells. Various methods for treating diseases are provided, including methods for treating cancer in a subject by administering cell regulators and / or engineered cells as therapeutic agents.

The invention discloses a nucleoside analogue and application thereof. The invention discloses a nucleoside compound with a relatively good inhibiting effect on RNA (Ribonucleic Acid) viruses. The structure of the nucleoside compound is as shown in a formula I which is described in the specification. The compound shows good inhibitory activity on coronavirus, and has great potential and application prospects in the aspect of being developed into a coronavirus inhibitor. # imgabs0 #

A solid or semi-solid state anti-viral lip balm composition comprising a direct or indirect nucleoside analog inhibitor of herpes simplex viral DNA polymerase or a pharmaceutically acceptable salt thereof mixed with at least one wax, at least one carrier oil selected from the group consisting of coconut oil including refined coconut oil and sunflower oil and a butter or butter substitute as a softening agent.

Provided herein are methods of treating cancer by administering a combination therapy comprising a KRAS G12D inhibitor, a nucleoside analog, and a microtubule inhibitor.

The application discloses application of a low-dose anti-PD-1 antibody in a limited course of treatment in treatment of hepatitis B. Anti-PD-1 antibody treatment is carried out on a chronic hepatitis B patient receiving nucleoside analogue or nucleotide analogue treatment, 100 mg is injected intravenously each time, once every three weeks, and the course of treatment is ended after 12 weeks or 24 weeks. The application blocks the combination of the PD-1 receptor highly expressed on the surface of T cells of the CHB patient with a ligand by blocking the CHB patient T cell surface high expression of the PD-1 receptor, thereby reversing the T cell exhaustion state, enhancing the HBV specific T cell immune response, and promoting HBsAg clearance. The application uses a limited course of treatment and a low-dose alpha PD-1 to enhance the HBV specific T cell immune response of the patient and promote the clearance of HBsAg while ensuring good safety. Compared with the traditional 48-week Peg-IFN alpha or several years or even decades of NAs treatment of the CHB patient, the 12-week or 24-week course of alpha PD-1 is shorter and has a smaller economic burden on the patient.

A bifunctional compound for use as a medicament. The compound comprises a rifamycin or a rifamycin derivative moiety; a linker; and a nucleobase analogue or a nucleoside analogue moiety.

The present disclosure provides methods for treating or preventing cancer comprising administering antigen binding molecules and taxane and / or nucleoside analogs that bind HER3. Also provided are methods for treating or preventing cancer comprising administering an antigen-binding molecule that binds HER3 and an antigen-binding molecule that binds EGFR. Also provided are pharmaceutical compositions and pharmaceutical combinations comprising such medicaments, as well as therapeutic and prophylactic methods of using the pharmaceutical compositions / pharmaceutical combinations.

The invention provides an oligonucleotide conjugate for inhibiting virus infection, a pharmaceutical composition and application of the oligonucleotide conjugate and the pharmaceutical composition, and belongs to the technical field of small nucleic acid drug delivery. The oligonucleotide conjugates provided by the present disclosure comprise a double-stranded oligonucleotide and a targeting ligand moiety chimeric with one or more antiviral nucleoside analogs, the targeting ligand moiety for targeted delivery of the oligonucleotide to the liver. The oligonucleotide conjugate and the pharmaceutical composition thereof provided by the invention can be used for treating HBV infection in a subject, and have relatively high in-vivo liver tissue delivery efficiency and relatively high antiviral effect.

The present invention relates to an enzymatic synthesis of 4'-ethynyl 2'-deoxynucleosides and analogs thereof, such as EFdA, that eliminates the use of protecting groups on intermediates, improves the stereoselectivity of glycosylation, and reduces the number of process steps required to produce the compounds. It also relates to novel intermediates used in the process.

The present invention relates to 5'-modified nucleoside analogs and oligonucleotides produced therefrom, and more specifically, to modified nucleosides and their analogs that can be used to be incorporated into the oligonucleotide terminus, which can be bound to double-stranded oligonucleotides (short interfering RNA) or single-stranded oligonucleotides (e.g., antisense oligonucleotides). The oligonucleotides provided herein are expected to result in the loss of normal function of the target RNA by hybridizing to a portion of the target RNA.

The application discloses a monomerized pyrimidine nucleoside phosphorylase mutant and a construction method and application thereof, and belongs to the field of enzyme engineering and biological catalysis technology.The mutant is obtained by amino acid substitution mutation of wild-type pyrimidine nucleoside phosphorylase shown in SEQ ID NO:1, and the amino acid sequence is shown in SEQ ID NO:2.The mutant is transformed into a stable monomer form by dimer interface remodeling and hinge region stabilization of the closed active conformation, the natural dimer PyNP is transformed into a stable monomer form, and the catalytic activity of the mutant to uridine, 2'-deoxyuridine and similar substrates is maintained in the monomer state.Compared with the wild-type enzyme, the mutant has lower oligomer dependence, better temperature stability, pH stability and storage stability, and can be used for biological catalytic synthesis of nucleosides and nucleoside analogs.

The invention provides a preparation method of an antiviral nucleoside analogue prodrug, specifically, the method comprises the following steps: carrying out first contact treatment on a compound 8 and a compound 3; and performing second contact treatment on the first contact treatment product and a compound 12 so as to obtain the compound shown in the formula I. By adopting the method disclosed by the invention, the cost can be reduced, the industrial production is easy, and the yield of the prepared compound I can be improved. # imgabs0 #

The present invention discloses methods and intermediates for synthesizing nucleosides and nucleoside analogs (NAs). More specifically, the present invention discloses methods for synthesizing nucleosides and NAs using simple achiral materials through a "one-step" proline-catalyzed halogenation reaction of heteroaryl-substituted acetaldehydes, followed by a tandem enantioselective aldol condensation reaction, and then a reduction or organometallic addition and cyclization (cyclization) reaction, including a cyclization halide displacement reaction.

This document describes methods and materials for treating cancer. In some cases, one or more diterpenoid epoxide compounds can be administered to a mammal (e.g., a human) having cancer to treat that mammal. For example, one or more diterpenoid epoxide compounds and one or more inhibitors (e.g., nucleoside-analog inhibitors) of a nucleoside DNA methyltransferase (DNMT) polypeptide can be administered to a mammal (e.g., a human) having cancer to treat that mammal.

The invention provides a nucleoside analogue as shown in a formula (I), a preparation method and a pharmaceutical composition thereof. The invention also discloses application of the compound or the pharmaceutical composition thereof in preparation of anti-cancer drugs.

This invention discloses a method for preparing monohydroxymethylcyclopropane nucleoside analogs. The method includes: sequentially adding a vinyl nucleobase derivative and a propynyl thioacetal compound to a mixture of a gold-nitrogen heterocyclic carbene catalyst and a silver salt under inert gas protection. After reaction, a highly stereospecific and selective disulfide vinylcyclopropane nucleoside analog is obtained. Following hydrodesulfurization, a vinylcyclopropane nucleoside analog is obtained. Further oxidation, reduction, or deprotection in three steps yields the monohydroxymethylcyclopropane nucleoside analog. This invention provides a concise new route for the synthesis of vinylcyclopropane nucleoside and monohydroxymethylcyclopropane nucleoside analogs, with mild reaction conditions, overcoming the potential explosiveness and lengthy synthetic routes of traditional methods. The raw materials are readily available, and the product can be converted into various other useful potential bioactive molecules, demonstrating strong practicality.

Provided are methods for identification of DNA repair locations in a genome of a non-dividing cell, by incorporating a reactive nucleoside analogs into the genome of the non-dividing cell, then sequencing the regions of the genome that incorporated the nucleoside analog.

In one aspect, the present disclosure relates to treating or preventing a respiratory disease or disorder, by administering one or more compositions comprising an isolated polypeptide derived from an alpha Connexin and an anti-viral agent such as, for example, nucleoside analogs. Exemplary respiratory diseases or disorders include acute respiratory distress syndrome (ARDS), alcoholic lung syndrome, acute lung injury (ALI), pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF), and / or chronic obstructive pulmonary disease (COPD). In some aspects, the respiratory disease or disorder is a complication of a respiratory viral disease.