Abstract: The present invention relates to novel salts and crystalline forms of (S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate having the structure: for use in treating viral infections. One crystalline form of the compound can be characterized by an X-ray powder diffraction (XRPD) pattern having peaks at 22.3°, 16.9°, and 16.2° 2-?±0.2° 2-?. In some embodiments, the viral infection is caused by a virus selected from the group consisting of Arenaviridae, Coronaviridae, Filoviridae, Flaviviridae, and Paramyxoviridae.

Abstract: A process and composition for improvement of the moisturization state of the stratum corneum of human skin epidermis comprising applying to the skin an effective amount of a composition (C) for topical use comprising at least one cosmetically acceptable excipient and a composition C1 consisting of 20-50% by weight of composition C2, which in turn includes from 3-25% by weight of a polyol, from 25-45% by weight anhydrides of the polyol, and from 30-72% by weight of polyol glycosides of the polyol, with the remainder of composition C2 to 100% by weight being made up of water; and from 50-80% by weight of glycerol and/or glycerol oligomers, with the ratio of polyol glycosides to glycerol and/or glycerol oligomers greater than or equal to 1/10 and less than or equal to 1/2.

Abstract: The present invention relates to ligand conjugates of iRNA agents (such as siRNA) of the formula

Abstract: The invention provides novel methods and kits for fully automated high-throughput method for isolation of extracellular vesicles and co-isolation of cell-free DNA from biofluids, including cell-free DNA and/or cell-free DNA and nucleic acids including at least RNA from microvesicles, novel methods and kits for isolation of extracellular vesicles and co-isolation of cell-free DNA from biofluids, including cell-free DNA and/or cell-free DNA and nucleic acids including at least RNA from microvesicles that do not require the use of phenol or chloroform, and for extracting nucleic acids from the extracellular vesicles and/or from the biological samples.

Abstract: The disclosure generally relates to compositions and methods for the extraction of nucleic acids from biological samples. In particular embodiments the extraction involves mixing dibromochloromethane, iodochloromethane or mixtures thereof with a biological sample that has been mixed with a phenol-based extraction solution. Centrifugation of the sample is not needed to achieve phase separation which occurs using the present methods in as little as one to two minutes with no phenol carryover.

Abstract: Phosphoramidate esters and related nucleotide analogs useful in polynucleotide sequencing techniques, and synthetic methods for preparing those compounds, are disclosed, including compounds having the following structure: wherein R1, R2, R3 and R4 are as defined herein. These compounds include nucleotide phosphoramidates analogs that are modified on the alpha-phosphate to enable attachment of a variety of application-specific substituents such as tether molecules.

Abstract: Disclosed is a method for the preparation of intermediates useful in the synthesis of gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate. Also disclosed is a method of preparing gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate.

Abstract: The present invention is directed to modified oligonucleotides having the following Formula (I) wherein one or more of phosphate groups are substituted at phosphorus, and methods for their synthesis. The modified oligonucleotides are useful for diagnostic applications involving sequence specific recognition of a nucleic acid and for use in a method of medical treatment.

Abstract: A method for preparing a ?-nucleoside compound, including the following steps: 1) performing a silylation reaction of a nitrogenous base or an analogue thereof in the presence of TMSOTf to give the nitrogenous base or the analogue thereof being protected by trimethylsilyl; 2) performing a direct glycosylation reaction of the reaction liquid, without being isolated, and a five- or six-membered ring saccharide or a derivative thereof closed by a hydroxyl protecting group to give a closed ?-nucleoside compound; and 3) performing a deprotection reaction to give the ?-nucleoside compound. The method uses a one-pot process to prepare the key intermediates of the ?-nucleoside compound, and the yield of materials in ?-configuration increases significantly. The method has the benefits of simple operations, being energy conservation and environment protection, and being suitable for industrial applications.

Abstract: A method for reducing or maintaining platelet inhibition in a patient by administering cangrelor prior to an invasive procedure is described. The method of this invention can be used for patients in need of antiplatelet therapy or at risk of thrombosis. The method can further be used in patients who were previously treated with long-acting platelet inhibitors without increasing the risk of excessive bleeding.

Abstract: The invention relates to deoxynucleotide prodrugs and pharmaceutical preparations thereof. The deoxynucleotide prodrugs include, but are not limited to, The invention further relates to methods of treatment of a mitochondrial DNA (mtDNA) depletion syndrome (MDS) by administering a therapeutically-effective amount of a deoxynucleotide prodrug of the present invention.

Abstract: In this method, an oligonucleotide represented by formula (II) [wherein Y1, Q, Base, r and r? are each as defined in claim 1] is prepared by using, as a synthesis unit, a novel nucleoside monomer compound represented by formula (I) [wherein X, R1, Y, Base, Z, Ar, R2, R3 and n are each as defined in claim 1]. The novel nucleoside monomer compound is a nucleoside, the base moiety of which is substituted with an aromatic-hydrocarbon-ring-carbonyl or -thiocarbonyl group having at least one hydrophobic group. The method can dispense with column-chromatographic purification in every reaction, and enables base elongation not only in the 3?-direction but also in the 5?-direction, thus attaining efficient liquid-phase mass synthesis of an oligonucleotide.

Abstract: Compositions and compounds of nucleoside phosphoramidites and modified oligonucleotides, each comprising one or more charge-neutralizing moieties according to the formula V wherein represents the point of attachment to the nucleoside phosphoramidite or the oligonucleotide, optionally through a spacer group. The nucleoside phosphoramidites permit facile attachment of the neutralizing moieties on the backbones of the modified oligonucleotides. The modified oligonucleotides can be used as therapeutic agents (i.e., oligotherapeutics) for the treatment of cancer, autoimmune disorders, genetic diseases, infectious diseases, neurological diseases, inflammatory diseases, metabolic diseases and others.

Abstract: Provided herein is a method for synthesizing polynucleic acids, comprising the steps of (a) providing an acidic solution substantially free of nucleic acid polymerase and lipids, but containing mononucleotides and a monovalent salt; (b) drying and resolubilizing the mixture of step (a) a plurality of times; and (c) recovering polynucleic acids from a resolubilized mixture of step (b). In certain aspects, the method further uses a low pH, e.g. about 3; it can utilize monophosphates, such as AMP rather than ATP; and it can be used with a polynucleotide template to form a sequence at least partially complementary to said template. Thus, both single-stranded and double-stranded polynucleic acids are provided. Ammonia salts have been used to obtain RNA lengths from 10 to 300 nucleotides after 16 half hour cycles and an effective temperature includes between 80° C. and 100° C.

Abstract: Provided is a preparation method of a composition enriched in compound Sp-1. The method performs isomer separation on a reaction product from the first step, and then performs a two-step chemical synthesis, so as to prepare a composition comprising high-purity compound Sp-1, wherein the HPLC purity of the single isomer Sp-1 is 90% or more. Provided is a composition enriched in compound Sp-1. The composition has an inhibitory effect on tumor cell proliferation in vitro significantly higher than that of NUC-1031 and compound Rp-1. Also provided are the use of the composition, and a pharmaceutical composition comprising the composition and at least one pharmaceutically acceptable excipient.

Abstract: Provided are methods of treating feline Coronavirus infections using carbanucleoside compounds having a 1?-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl) substituent, or a pharmaceutically acceptable salt thereof. An exemplary compound is (2R,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carbonitrile.

Abstract: Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 4?-OR nucleosides of Formula I: or a pharmaceutically acceptable salt thereof, wherein Base, PD, R, Z1, Z2, Z3, and Z4 are as defined herein.

Abstract: The present disclosure provides double stranded nucleic acid comprising first and second oligonucleotides wherein the second oligonucleotide is complementary to the first oligonucleotide. At least one of the first and second oligonucleotides comprises a 5? modified nucleoside or 5? modified nucleotide having Formula IIb: wherein Bx is a heterocyclic base moiety, T2 is an internucleoside linking group linked to one of the oligonucleotides, and each of q1 to q7 are selected from a list of substituents. In certain embodiments, T2 is a phosphodiester or phosphorothioate linkage and formula IIb is a 5?-nucleotide. In certain embodiments, T2 is a non-phosphate linkage and formula IIb is a 5?-nucleoside. In certain embodiments, the present double stranded nucleic acid provides oligonucleotides that are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

Abstract: Methods of preparing synthetic oligonucleotides containing at least one phosphotriester linkage conjugated to a monosaccharide are disclosed, where the synthetic oligonucleotides are prepared from nucleosidic phosphoramidite building blocks, preferably followed by removal of protecting groups to provide monosaccharide-conjugated oligonucleotides.

Abstract: Disclosed are methods of separating the diastereoisomers of gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-phosphate (NUC-1031), or salts thereof, using crystallisation. In particular, crystallisation from isopropyl alcohol provides gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-(S)-phosphate in high diastereoisomeric purity: Also disclosed is a crystalline form of gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-(S)-phosphate.