43 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.

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.

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.

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.

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 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.

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.

This invention belongs to the field of organic synthesis technology and provides an N-protected pyrrolotriazine compound, its preparation method, and its application. Specifically, this invention discloses a method for preparing N-protected pyrrolotriazine compounds and their intermediates, and their application in the synthesis of cyano-containing carbon-nucleoside antiviral drugs. This invention has advantages such as shortening the synthetic route of carbon-nucleoside analogs; low cost; simple and efficient operation; high yield; high product purity; and avoiding the formation of difficult-to-remove amide or primary amine impurities, which is beneficial for industrial production.

Human herpesviruses can infect barrier and immune cells of the intestinal tract to cause microbiome dysbiosis and inflammation. Microbiome dysbiosis can affect the availability of nutrients required for normal brain function. Inflammation can compromise the intestinal barrier and lead to microbial translocation. Microbial translocation can cause brain infection or a mimicry auto-immune response. The embodiments restrict herpesvirus activity and injury by 1) the oral administration of exosomes containing factors to inhibit viral activity and restore homeostasis, and 2) the oral administration of recombinant bacteria that produce exosomes containing factors to inhibit viral activity and restore homeostasis. Another embodiment is the treatment of alpha-HHVs mediated intestinal dysfunction by nucleoside analogs, such as famciclovir, which may be combined with anti-viral exosome therapy.

Disclosed herein are compositions and methods for one step CMC production of RNA therapeutic complexes (nanostructures) that contain nucleoside analogues. In some embodiments, the nucleoside analogues are incorporated into RNA oligonucleotides that self-assemble into an RNA complex during RNA synthesis in a one-step production. Therefore, no additional conjugation or synthesis processes are required.

The invention relates to the technical field of organic synthesis, and particularly discloses a 4 '-fluoronucleoside analogue and a synthesis process thereof.The synthesis process comprises the steps that 2'-O-methyladenosine serves as an initial raw material and is subjected to a condensation reaction with benzoyl chloride, and an intermediate 1 is synthesized; carrying out halogenation reaction on the intermediate 1 and iodine, then carrying out elimination reaction on the intermediate 1 and bicyclic amidine, and finally carrying out double-bond addition reaction on the intermediate 1, N-iodosuccinimide and triethylamine trihydrofluoride to synthesize a compound 4; the compound 4 is subjected to an esterification reaction, a nucleophilic substitution reaction and a hydrolysis reaction in sequence, and a target product can be synthesized. The target product disclosed by the invention can be applied to the fields of nucleoside analogs, high stability and antiviral and antitumor chemotherapeutic drugs, and has a wide application prospect.

The present invention relates to 1 '-cyano nucleoside analogs and uses thereof, and discloses compounds of formula (I) and methods of using the compounds alone or in combination with additional agents and pharmaceutical compositions of the compounds for the treatment of viral infections.

The invention discloses 2-deoxy-2-fluoro-4-azido-N-hydroxycytidine shown as a formula (F4) as well as a preparation method and application of the 2-deoxy-2-fluoro-4-azido-N-hydroxycytidine. Compared with the prior art, the 2-deoxy-2-fluoro-4-azido-N-hydroxycytidine (F4) and the phosphate prodrugs (F6 and F12) thereof provided by the invention show relatively strong cell viability to HepG2 / 2.2. 15 cells capable of continuously and stably expressing HBV (Hepatitis B Virus), the cell viability can reach a nanomole level, and the 2-deoxy-2-fluoro-4-azido-N-hydroxycytidine (F4) and the phosphate prodrugs (F6 and F12) thereof can be used for remarkably inhibiting HBV DNA (Deoxyribonucleic Acid) replication to serum and liver of a hepatitis B virus model mouse; the compound has a liver targeting property and has a good application prospect in the aspect of treating HBV (Hepatitis B Virus). The development of the medicine lays a foundation for the research of fluorine-containing nucleoside analogues. And (F4).

To provide a synthesis method of 4'-ethynyl 2'-deoxy nucleosides and analogs thereof that eliminates the use of protecting groups on intermediates, improves the stereoselectivity of glycosylation, and reduces the number of process steps needed to make the compounds.SOLUTION: A method for synthesizing a 4'-ethynyl 2'-deoxy nucleoside or an analog thereof comprises combining compound 6.5 in the figure [where 2X+ is (a) two protons, (b) one proton and one monovalent cation, (c) two monovalent cations which are the same or different, or (d) one divalent cation] with purine nucleoside phosphorylase and a nucleobase or an analog thereof, in a buffered solution containing a manganese (II) salt.SELECTED DRAWING: None

Disclosed herein are telomere-targeting phosphatidyl-thio conjugates comprising the nucleoside analogs 6-thio-2'-deoxyguanosine and 6-thioguanosine, which target telomeres in cancer cells, and pharmaceutical compositions thereof, and therapeutic methods for administering a therapeutically effective amount of the telomere-targeting phosphatidyl-thio conjugate compounds to treat cancers such as colorectal cancer, non-small cell lung cancer, and hepatocellular carcinoma.

Provided herein are nucleoside analogs and nucleotide analogs for suppressing virus proliferation in a cell, or for suppressing a viral infection in a patient in need thereof. Also provided herein are methods of use. The nucleoside analogs disclosed herein are converted to nucleotide analogs by phosphorylation. Nucleotide analogs are incorporated into elongating nucleic acid chains, causing elongation to terminate, thereby inhibiting viral nucleic acid synthesis.

The present invention relates to compositions and methods of treating a subject having cancer by stimulating the subject's immune system and / or enhancing immunotherapies. Specifically, the present invention relates to methods of treating a subject by administering (1) a catechin ester or a derivative or metabolite thereof (e.g., EGCG) and (2) a nucleoside analogue (e.g., DAC), in combination with a checkpoint inhibitor or T-cell therapy.

The present application provides nucleoside analog compounds of Formula I-V for use in the treatment of dengue (DF). The present application further provides compositions and combinations thereof and methods of treating dengue fever using the nucleoside compounds of Formula I-V and compositions and combinations thereof.

The present invention relates to a method for synthesizing nucleoside analogs. More specifically, the present invention relates to a method for synthesizing nucleoside analogs in which the C4' position is substituted.

The present invention relates to nucleoside analogs useful for 5 'modification and oligonucleotides prepared therefrom, and more particularly, to modified nucleosides and analogs thereof useful for incorporation into the ends of oligonucleotides, which can be incorporated into double stranded oligonucleotides (short interfering RNAs) or single stranded oligonucleotides (e.g., antisense oligonucleotides). The oligonucleotide provided is expected to hybridize to a portion of the target RNA, resulting in loss of normal function of the target RNA.

The application relates to the technical field of medicines, in particular to application of a VER155008 compound in preparation of a coronavirus-dependent RNA polymerase antagonist. Through construction of a reliable screening model of SARS-CoV-2 RdRp inhibitors, the application tests the inhibiting effect of a plurality of nucleoside analogs on SARS-CoV-2 RdRp, finds that the VER155008 compound has obvious inhibiting effect on SARS-CoV-2 RdRp, the VER155008 compound has SARS-CoV-2 exonuclease nsp14 resistance, and can effectively inhibit replication of coronaviruses HCoV-OC43 and HCoV-NL63. Therefore, the application provides key data for research and development of a novel anti-new coronavirus lead compound, and provides a theoretical basis for research and development of an effective coronavirus treatment drug.

The present invention relates to a method for the synthesis of nucleoside analogs. More specifically, the present invention relates to a method for the synthesis of C4 '-substituted nucleoside analogs.

This application provides a method for the electrocatalytic synthesis of multisubstituted ribose derivatives, comprising using an organotin compound as a catalyst to catalyze the reaction of the compound shown in formula (I) under electrochemical conditions to obtain the compound shown in formula (II); wherein, R 1 C is an optional replacement 1‑10 hydrocarbon group; R 2 and R 3 One of them is -C(=O)OR, and the other is -H; R is the C that can be substituted. 1‑4 Alkyl; R 4 C is a hydrogen atom or an optional substituted C 1‑10 The method involves the use of a hydrocarbon group as the reaction solvent, a reaction temperature of 40-80℃, and a quaternary ammonium bromide as the electrolyte. This method enables the efficient and highly stereoselective synthesis of tetrasubstituted riboses modified with 2'- and 3'-ester groups, and is easily scaled up, showing promising prospects for industrial application. The products obtained by this method possess excellent potential for later derivatization and can be used to synthesize various novel nucleoside analogs, demonstrating significant application value in the development of antiviral and antitumor drugs.