58 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.

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 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.

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 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.

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.

Compounds, compositions, and methods of treatment and prevention of HIV infection are disclosed. The compounds are pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidine JAK inhibitors. Combinations of these JAK inhibitors and additional antiretroviral compounds, such as NRTI, NNRTI, integrase inhibitors, entry inhibitors, protease inhibitors, and the like, are also disclosed. In one embodiment, the combinations include a combination of adenine, cytosine, thymidine, and guanine nucleoside antiviral agents, optionally in further combination with at least one additional antiviral agent that works via a different mechanism than a nucleoside analog. This combination has the potential to eliminate the presence of HIV in an infected patient.

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).