31 results about "Nucleoside analogue" patented technology

The invention relates to substituted nucleoside analogues of formula (I), pharmaceutically acceptable salts thereof and pharmaceutical compositions for treating diseases, disorders or conditions associated with the overexpression of PRMT5 enzyme. The invention also relates to methods of treating diseases, disorders or conditions associated with the overexpression of PRMT5 enzyme.

Nucleoside analogues and compositions containing said nucleoside analogues are provided, according to a general formula (I) disclosed herein. Processes are provided for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the diagnosis, prevention and / or treatment of parasitic infections, more specifically for use in the diagnosis, prevention and / or treatment of a Trypanosoma infection.

The present disclosure relates to a nucleoside analogue and a use thereof. The nucleoside analogue is a compound shown in formula (Ia) or a prodrug thereof. The nucleoside analogue can enhance targeted delivery of oligonucleotide drugs to nervous system cells, thereby increasing the inhibition rate of the oligonucleotide drugs delivered in a targeted manner on expression of specific genes in the nervous system cells, or enabling the oligonucleotide drugs delivered in a targeted manner to achieve the purpose of preventing and / or treating pathological conditions or diseases caused by abnormal expression of the specific genes in the nervous system cells. The present disclosure also relates to a nucleotide analogue-containing double-stranded oligonucleotide and a use thereof. The double-stranded oligonucleotide comprises a sense strand and an antisense strand, each strand has 17-25 modified and / or unmodified nucleotides, and the antisense strand and the sense strand are complementary to form a duplex region; the sense strand and / or the antisense strand contains at least one nucleotide analogue represented by the structure of formula (100), or a tautomer, or stereoisomer, or pharmaceutically acceptable salt thereof; the double-stranded oligonucleotide can effectively treat and / or prevent pathological conditions or diseases caused by abnormal expression of specific genes in nervous system cells.

The present invention provides a kind of nucleoside analogue compounds, and a composition comprising the compound and pentostatin, their use for modulating circadian rhythm, preferably, for shifting circadian phase, and methods for modulating circadian rhythm, preferably, for shifting circadian phase via the compound or the composition.

An injectable bifunctional hydrogel has antibacterial activity. The bifunctional hydrogel is a hydrogel prepared by dissolving nucleoside analogues in a solvent. The nucleoside analog has a structure of formula I. It can be a candidate drug for the local injection treatment of periodontal disease, and it also has potential application prospects in the minimally invasive treatment of craniofacial bone tissue defects.

The invention discloses an anti-tumor 1, 2, 3-triazole-alpha-L-threose nucleoside phosphonate compound as well as a preparation method and application thereof, and the 1, 2, 3-triazole-alpha-L-threose nucleoside phosphonate analogue has a chemical structure as shown in a general formula 1, r1 is phenyl, 2-methylphenyl, 3-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 2-chlorphenyl, 3-chlorphenyl, 4-chlorphenyl, 4-bromophenyl, 3-fluorophenyl, 3-nitrophenyl, 4-methoxyphenyl, 4-cyanophenyl, 3, 4-dichlorophenyl, 3, 4-dichlorophenyl, 3, 4-dichlorophenyl, 3, 4-dichlorophenyl, 3, 4-dichlorophenyl, 3, 4-dichlorophenyl, 3, 4-dichlorophenyl, 3, 4-dichlorophenyl, 3, 4-dichlorophenyl, 3, 4-dichlorophenyl, 3, 4-dichlorophenyl R1, R2, R3, R4, R5, R6, R7, R7, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, R8, the technical route for preparing the 1, 2, 3-triazole-alpha-L-threose nucleoside phosphonate compound is simple to operate, concise in route and relatively high in yield, the used reagents are common reagents and suitable for large-scale preparation, and in-vitro antitumor activity research finds that the compound has good antitumor activity and can be used for preparing the 1, 2, 3-triazole-alpha-L-threose nucleoside phosphonate compound. The compound is expected to be used as an anti-tumor drug or a primer of the anti-tumor drug.

The present application relates to the field of biological medicine, and in particular to a nucleoside analogue and its application in reducing off-target activity of oligonucleotide drugs. The nucleoside analogue provided by the present application can be used for preparation of oligonucleotide drugs, and can be coupled to a seed region of siRNA, thereby efficiently improving the specificity of siRNA, reducing the off-target effect of siRNA, and maintaining the silencing effect of target genes.

The invention discloses a nucleoside analogue as shown in a formula I and pharmaceutically acceptable salts thereof, and a preparation method and medical application of the nucleoside analogue and the pharmaceutically acceptable salts thereof, pharmacological experiments prove that the nucleoside analogue and the pharmaceutically acceptable salts thereof have relatively good inhibitory activity on RNA-dependent RNA polymerase, and can inhibit replication of various RNA viruses in the aspect of inhibiting virus replication, so that the nucleoside analogue and the pharmaceutically acceptable salts thereof have good application prospects. Particularly, the compound has relatively good biological activity for treating influenza virus and vesicular stomatitis virus infection. Therefore, the compound provided by the invention has good broad-spectrum antiviral activity, can be used as a broad-spectrum antiviral drug to treat various virus infections, and enriches the inventory of antiviral drugs. The nucleoside analogue has anti-RNA (Ribonucleic Acid) virus activity.

Fluorescent nucleobase surrogates capable of Watson-Crick hydrogen bonding are essential probes of nucleic acid structure and dynamics. Their limited brightness and short absorption and emission wavelengths have rendered them unsuitable for single-molecule detection. Herein, we synthesized a new tricyclic pyrimidine nucleoside analogue with a push-pull conjugated system. The resulting C-linked 8-(diethylamino)benzo[b][1,8] naphthyridin-2(1H)-one nucleoside (ABN), exhibits ε442=20,000 M−1 cm−1 and Φem,540=0.39 in water, increasing to Φem=0.50-0.53 when base paired with adenine in duplex DNA oligonucleotides. Single-molecule fluorescence measurements of ABN using both one-photon and two-photon excitation demonstrate its excellent photostability and indicate that the nucleoside is present to >95% in a bright state with count rates of at least 15 kHz per molecule. This new fluorescent nucleobase analogue, which, in duplex DNA, is the brightest and most red-shifted known, is first to offer robust single-molecule fluorescence detection capabilities.

The present disclosure provides a lipid nanoparticle, the lipid nanoparticle comprises a cationic lipid, a neutral lipid, a PEG lipid and an active pharmaceutical ingredient, the cationic lipid comprises DOTAP, and the active pharmaceutical ingredient comprises one or more of nucleoside, a nucleoside analogue or a compound with a phosphate group. The lipid nanoparticles are high in stability and bioavailability, and the effect of the lipid nanoparticles is better than that of a drug monomer.

The present invention relates to a method for the synthesis of nucleoside analogues. More specifically, the present invention relates to a process for the preparation of a compound of formula (IV) which is an intermediate for producing the 2',4'-BNANC of formula A. The present invention relates to a process for the preparation of the 2',4'-BNANC of formula A.

The present invention relates to the field of analyzing cells and cell division, and in particular to means and methods for detecting low numbers of dividing immune cells in blood samples. An in vitro method of detecting proliferating cells is provided, comprising the steps of: (i) culturing cells in the presence of a nucleoside analogue comprising a first reactive unsaturated group to allow incorporation of the nucleoside analogue into the DNA of the cells; (ii) concentrating the nucleoside-labelled cells by covalent immobilization to a solid surface comprising a (3-aminopropyl)triethoxysilane (APTES) or branched polyethyleneimine (PEI) coating layer activated with 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 reactive unsaturated group and the second reactive unsaturated group; and (v) determining the amount of detection probe attached to the DNA of the immobilized cells to measure cell proliferation.

The invention provides application of a targeted Hsp90 alpha compound in treatment of infectious encephalitis and improvement of clinical drug resistance, and belongs to the technical field of medicines. The targeted Hsp90 alpha compound disclosed by the invention has a structure as shown in a formula 1, and a parent nucleus structure of the targeted Hsp90 alpha compound is (3, 6, 6-trimethyl-4-oxo-4, 5, 6, 7-tetrahydro-1H-indazole-1-yl) benzamide. The targeted Hsp90 alpha compound can effectively treat infectious encephalitis, can treat infectious encephalitis caused by acyclovir and other nucleoside drug resistance viruses, and improves the clinical drug resistance problem of infectious encephalitis.

Provided herein are dendrimers comprising a core unit, five generations of building units being a lysine residue or analogue thereof, a plurality of first terminal groups each comprising a residue of a nucleoside analogue, and a plurality of second terminal groups each comprising a hydrophilic polymeric group. Also provided herein are pharmaceutical compositions comprising the dendrimer, and methods and uses of the dendrimers in therapy of disorders such as cancer.

The present invention relates to methods for the synthesis of nucleoside analogues. More specifically, the present invention provides methods for the synthesis of 6-disubstituted nucleoside analogues of Formula (I).

The application provides a nucleoside analogue-loaded delivery system and a preparation method and application thereof, and relates to the technical field of medicines.In the application, a guisitebine delivery system with high encapsulation rate and high drug loading is obtained by loading guisitebine on a wrapping material obtained by hybridizing a platelet membrane and MSC extracellular vesicles through membrane engineering, and the system has excellent stability; the platelet membrane drug delivery system loaded with guisitebine can effectively improve the treatment effect of guisitebine on pancreatic cancer, and provides a new functional drug form for the treatment of pancreatic cancer.

The application discloses a kind of non-natural nucleoside analogues as shown in the following formula 1 and its pharmaceutically acceptable salt, racemic mixture, enantiomer, optical isomer, tautomer and solvate, and pharmaceutical composition comprising them, and its purposes in preparing antiviral infection and antitumor drug and its use method.The non-natural nucleoside analogues have good broad-spectrum antiviral activity or antitumor cytotoxicity.

The invention discloses a crystal form compound of a nucleoside analogue and a preparation method and application thereof, the crystal form compound of the nucleoside analogue comprises an organic carboxylate crystal of a compound shown as a formula I, and the molar ratio of organic carboxylate to the compound shown as the formula I is (0.8-1.2): 1; after the compound shown in the formula I and organic carboxylate form a salt crystal, the stability is obviously improved, and detection shows that the crystal form of the salt crystal does not change.

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.

The invention belongs to the technical field of cellular immunity, and particularly relates to a DC-CIK cell culture method based on an HBV protective antibody positive healthy donor and application, the cell culture method comprises the following steps: selecting HBsAg negative and anti-HBs antibody positive healthy donor peripheral blood mononuclear cells, loading a dendritic cell (DC) by using a mixed antigen of HBcAg and HBsAg, and culturing the DC-CIK cell by using a cell culture medium. And co-culturing the DC cells and cytokine-induced killer cells (CIK) to finally obtain the allogenic DC-CIK cells. According to the invention, DC cells of healthy donors and CIK cells are co-cultured to obtain allogenic DC-CIK cells, an HBcAg and HBsAg mixed antigen loading technology is adopted to significantly improve the antigen presentation capability of the DC cells, an optimized culture system enhances the targeting killing function of the cells, and the HBsAg clearance rate and the cccDNA inhibition rate can be effectively improved in combination with nucleoside analogue treatment, so that the DC-CIK cells can be used for preparing the DC-CIK cells. The synergistic breakthrough of efficient virus removal, immune function reconstruction and low recurrence rate in hepatitis B treatment is realized.

The invention provides a nucleoside analogue-loaded delivery system as well as a preparation method and application thereof, and relates to the technical field of medicines. The gemcitabine delivery system has the advantages that the gemcitabine is loaded by the wrapping material obtained by hybridizing the platelet membrane and the MSC exosome for the first time through membrane engineering modification, the gemcitabine delivery system with high encapsulation efficiency and high drug loading capacity is obtained, and the system has excellent stability; according to the gemcitabine-loaded platelet membrane drug delivery system, the pancreatic cancer treatment effect of gemcitabine can be effectively improved, and a new functional drug form is provided for pancreatic cancer treatment.

The invention relates to a compound shown in a formula I or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the compound or the pharmaceutically acceptable salt thereof as an active component, and application of the compound or the pharmaceutically acceptable salt thereof in preparation of antiviral drugs. .

The invention discloses a double-enzyme system catalytic synthesis method of deoxyadenosine triphosphate. A reaction system comprises deoxyadenosine, a metal cofactor, a phosphorus donor, deoxynucleotide kinase and polyphosphate kinase. According to the method disclosed by the invention, the deoxyadenosine triphosphate is generated through double-enzyme catalysis, and compared with a chemical method, the environmental pressure caused by treating byproducts is reduced; through cyclic regeneration of deoxyadenosine triphosphate, the cost is remarkably reduced, doping of exogenous nucleoside similar substances is reduced, and the separation and purification cost of the product is reduced; the method also has the advantages of mild reaction conditions, simple process, greenness and environmental protection.

The present invention falls within the technical field of medicinal chemistry, and specifically relates to an antiviral nucleoside analogue, and a pharmaceutical composition and the use thereof. The nucleoside analogue of the present invention has a structure as represented by formula (I), and has a good chemical stability, a high oral bioavailability, and a significant antiviral activity. The nucleoside analogue can be used in the preparation of an inhibitor for inhibiting viral replication and / or a drug for preventing, alleviating and / or treating diseases caused by viral infection.

The invention relates to an oligonucleotide chimera with a structure shown in a formula II or a pharmaceutically acceptable salt thereof, and a leech repelling composition formed by the oligonucleotide chimera and any one or a combination of the oligonucleotide chimera and the pharmaceutically acceptable salt with icaridin, citronellal and decyl dimethyl ammonium chloride. The leech repelling composition has the advantages of good leech repelling effect, good stability, few side effects and the like.

The present application relates to an antiviral composition, an immunity enhancing composition, a feed or a feed additive comprising a nucleoside analog derived from a nucleotide.

The present invention falls within the technical field of medicinal chemistry, and specifically relates to an antiviral nucleoside analogue, and a pharmaceutical composition and the use thereof. The nucleoside analogue of the present invention has a structure as represented by formula (I), and has a good chemical stability, a high oral bioavailability, and a significant antiviral activity. The nucleoside analogue can be used in the preparation of an inhibitor for inhibiting viral replication and / or a drug for preventing, alleviating and / or treating diseases caused by viral infection.

According to the application of the antiviral nucleoside analogue shown in the general formula (I) in preparation of the medicine for treating or preventing the feline coronavirus, the antiviral nucleoside analogue can effectively resist the feline coronavirus and has the advantages of being short in treatment cycle, high in treatment index and high in safety.

Disclosed are methods of synthesizing a modified nucleoside by providing a chiral intermediate scaffold molecule where a ketone and a dialkyl acetal provide two points for structural diversification while simultaneously serving to enable ribose ring formation, with a intramolecular trans-acetalization reaction to construct the modified ribose core, followed by glycosylation to produce a C4ʹ-modified nucleoside. Also disclosed are novel C4ʹ-modified nucleoside analogues.

The present invention relates to the field of biomedicine, and more particularly to a nucleoside analog and its use in reducing the off-target activity of oligonucleotide drugs. The nucleoside analog provided by the present invention can be used in the preparation of oligonucleotide drugs and can be coupled to the seed region of siRNA, thereby effectively improving the specificity of the siRNA, reducing the off-target effects of the siRNA while maintaining the silencing effect of the target gene.