Abstract: A novel nucleoside phosphoramidate compound of the formula below, or a stereoisomer, salt, hydrate, solvate or crystal thereof for the treatment of Flaviviridae family viral infection, especially hepatitis C viral infection, and having a good anti-HCV effect; a pharmaceutical composition having the compound, or a stereoisomer, salt, hydrate, solvate or crystal thereof:

Abstract: The present invention relates to a pharmaceutical product comprising a) as a first component an inhibitor of the MDM2-p53 interaction such as, for example: and b) as a second component cytarabine; as a combined preparation for the sequential or simultaneous use in the treatment of cancer.

Abstract: Compositions and techniques for the extraction, enrichment and isolation of nucleic acids from cellular source material using an ammonium hydroxide-based solution are disclosed herein.

Abstract: Provided herein are novel irreversible sialidase inhibitors. These compounds can be conjugated with a detectable tagging moiety such as azide-annexed biotin via CuAAC for isolation and identification of sialidases. The provided compounds and the corresponding detectable conjugates are useful for detecting sialidase-containing pathogens and imaging in situ sialidase activities under physiological conditions.

Abstract: Disclosed herein are methods of preparing a nucleoside analog (I) by a reaction that includes an intermediate (GG): Nucleoside analog (I) is useful in treating diseases and/or conditions such as viral infections.

Abstract: The present invention is directed to a compound that can be used in the treatment of cancer. The compound is represented by formula (I) Further, X is In addition, R1 is selected from H, and substituted or unsubstituted cyclic terpene moieties; R7 and R8 are independently selected from C1 to C30 alkyl; n is an integer ranging 1 to 4; and a is an integer ranging from 1 to 20. Moreover, R2 is H; a Mono-phosphate, Di-phosphate, Tri-phosphate or phosphoamidite moiety; or —Y—X1 or —Y-L-Y1—X1, where Y and Y1 are independently from each other a single bond or a functional connecting moiety, X1 is a colloid-active compound, a fluorescence marker, or a polynucleotide moiety having up to 50 nucleotide residues.

Abstract: The present invention relates to disulfide masked prodrug compounds of formula I, compositions and methods that are amenable to bioactivation by a reducing agent such as glutathione: W—P(V)LG??(Formula I), wherein P(V)LG is a pentavalent phosphorus leaving group; and W is: wherein R1, R2, R3, R4, R5, R6, R7 and R8 are as defined in the specification. Such disulfide based compounds, compositions, and methods can be useful, for example, in providing novel prodrugs for use as therapeutics. Once administered, the prodrug is metabolized in vivo into an active metabolite in a process termed bioactivation.

Abstract: The present disclosure relates to the synthesis of non-natural analogs of S-adenosyl-L-methionine (SAM) and/or of Se-adenosyl-L-methionine (SeAM) by reacting a methionine analog and adenosine triphosphate (ATP) in the presence of at least one methionine adenosyltransferase (MAT), and to use thereof with downstream SAM and/or SeAM utilizing enzymes. The non-natural analogs of SAM and/or SeAM have the general formula: where X is S or Se, and R1 is an alkyl group.

Abstract: The present disclosure provides cytidine derivative dimers, salts and compositions of the cytidine derivative dimers, and methods of making and using the cytidine derivative dimers. The compounds that useful for treating a neoplasm in mammalian subjects. The cytidine derivative dimer has the following general formula (I): where R1 is C1-C10 alkyl, C1-C10 substituted alkyl, —(CH2)n-Ph, or substituted —(CH2)n-Ph; R2 is C1-C10 alkyl, C1-C10 substituted alkyl, —(CH2)n-Ph, or substituted —(CH2)n-Ph; R3 is hydrogen, alkoxycarbonyl or substituted alkoxycarbonyl; R4 is hydrogen, alkoxycarbonyl or substituted alkoxycarbonyl; and R5 is —(CH2)n—, substituted —(CH2)n—, or —(CH2)n—X1—X2—, X1 being O or S, and X2 being —(CH2)n-Ph, pyrimidyl, pyranyl, imidazolyl, pyrazinyl, or pyridyl. The disclosed cytidine derivative dimers/salts provide high anti-tumor activity with low toxicity and are useful for treating cancers.

Abstract: The present invention discloses a method of harnessing versatile phosphoramidation reactions to regioselectively link a group of alkynyl-/azido-containing compounds to post-synthetic nucleic acids primed with phosphate at the 5? termini. The method includes steps of: (a) monophosphoramidating H2N(CH2)nNH2 to the 5? end of the nucleic acid to form an intermediate 1 where n is an integer from 2 to 6, and the intermediate 1 has a formula of: (b) amidating the free —NH2 group of the intermediate 1 with to form an intermediate 2; and (c) reacting the terminal —N3 group of the intermediate 2 with 1-{3-{[4-(2-cyclooctyn-1-ylmethyl)benzoyl]amino}propyl}-4-{2-[4-(dimethylamino)phenyl]ethenyl}pyridinium hexafluorophosphate (Alkyne MegaStokes dye 608) by the SPAAC reaction to form modified nucleic acids. Without the presence of Cu(I), the modified nucleic acids were subjected to azide-alkyne cycloaddition in an aqueous solution to obtain various nucleic acid conjugates with a high yield.

Abstract: Methods and formulations are provided for treating migraine and other acute pain episodes using diclofenac, and formulations of diclofenac that provide both rapid and sustained relief from acute pain. Methods and formulations are also provided for treating symptoms that often accompany migraine and acute pain such as photophobia, phonophobia, nausea and vomiting.

Abstract: Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same, of the Formula (I). Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a norovirus, with a nucleoside, a nucleotide and an analog thereof.

Abstract: The compounds are of the class of N4-hydroxycytidine nucleosides, modified monophosphate and phosphonates prodrugs analogs, and pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof, useful in treating HCV or Norovirus infections.

Abstract: The present disclosure provides nucleoside compounds and oligonucleotides including an unnatural 6-amino-2-pyridone heterocyclic base where the 6-amino and 2-positions are protected. The 2-position of the heterocyclic base can be protected with an acyl-oxy-methyl protecting group. In some embodiments, the protected heterocyclic base has the following structure where AcOM is an acetyl-oxy-methyl group and R is a ribose or deoxyribose sugar: Methods for synthesizing an oligonucleotide are provided in which the subject compounds find use. The method can include protecting an unnatural (e.g., Z) nucleotide with an acetyl-oxy-methyl group; incorporating the protected unnatural nucleotide into a nucleotide sequence on a solid support; and removing the acetyl-oxy-methyl group from the unnatural nucleotide incorporated into the nucleotide sequence. The compounds and methods find use in the synthesis of long oligonucleotides including Z nucleotides.

Abstract: A multi-step stabilization method for connective tissue is described. Stabilized tissues can exhibit increased resistance to degradation due to enzyme activity, fatigue and storage. The multi-step method includes a first step during which the tissue can be incubated with a glycosaminoglycanase inhibitor such as a sulfated oligosaccharide, one example of which being neomycin, a second step during which the tissue can be incubated with a crosslink activator such as a carbodiimide crosslink activator and/or a crosslinking agent such as a heterobifunctional crosslinking agent and/or a phenolic compound such as a tannin, examples of which include tannic acid and pentagalloylglucose, and a third step during which the tissue can be incubated with a second crosslink activator that can be the same or different as the first crosslink activator.

Abstract: A fat-binding composition contains an inclusion complex with a host molecule and a guest molecule. The guest molecule includes one or more amino acids, vitamins, flavorants or related compounds, rutin, betanin, derivatives thereof, and mixtures thereof. The fat-binding composition may be in the form of a tablet or powder, for example, and may be incorporated into a food or beverage product. If in the form of a powder or tablet, the composition may optionally contain a carbonation-forming component and may be dissolved in carbonated or non-carbonated water. The fat-binding composition may also be employed in a method for binding fat ingested by an animal which includes having the animal ingest the composition, or a food or beverage product containing the same.

Abstract: The present invention relates to polymorphic forms of 5-Azacytidine and the process for preparation thereof. The present invention further relates to Crystalline 5-azacytidine 5 designated as Form-SA-1 characterized by an X-ray powder diffraction pattern having at least four characteristic diffraction angle peaks at about 12.00, 12.60, 13.90, 15.15 and 31.40±0.20 2?°, which is useful as active pharmaceutical ingredient in pharmaceutical compositions for the treatment of myelodysplastic syndrome.

Abstract: Processes for synthesis of conformationally restricted nucleomonomers (CRN) by ozonolysis or oxidation of a 2?-vinyl substituted nucleoside precursor with protected 3?-hydroxyl, 4?-hydroxymethyl and 5?-hydroxyl positions. The CRN nucleomonomers can be used to prepare nucleic acid compounds. CRN nucleomonomers for nucleic acid compounds can be prepared in high yields and in multi-gram scale. The nucleic acid compounds can be of various regulatory classes such as antisense RNA for therapeutic modalities useful for treating or preventing diseases or disorders by up- or down-regulating the expression of genes and other nucleic acid based regulatory systems in a cell.

Abstract: The invention relates to the development of drugs intended for the prophylaxis and/or treatment of viral diseases caused, in particular, by herpes viruses. What are proposed are complex compounds of germanium having the general structural formula: Gex[AD][CA]y[AA]2 ??(1), where AD is a derivative of a nitrogenous base of the purine series that has antiviral activity and can be selected from guanine derivatives, such as acyclovir, valacyclovir, gancyclovir and pencyclovir, or from adenine derivatives, such as vidarabine; CA is a hydroxycarboxylic acid which can be selected from acids such as (but not limited to) citric acid, lactic acid and malic acid; AA is an amino acid which can be selected from various a-amino acids, such as arginine, gylcine, lysine and threonine, and where x=1-2, y=2-4 and z=0-2. Complex compounds of germanium have a high level of antiviral and immune-stimulating activity and are readily soluble in water.

Abstract: A compound represented by the general formula (III) which serves as an intermediate of an oligonucleotide analog having stable and excellent antisense or antigene activity or having excellent activity as a detection reagent (probe) for a specific gene or as a primer for the initiation of amplification of a specific gene can be produced at high yields regardless of the type of nucleobase by a method comprising reacting a compound represented by the general formula (II) or a salt thereof with a trimethylsilylated compound obtained from a compound represented by the general formula (IVb), wherein X, Y, Z, A, R, and B are as defined in claim 1.