Abstract: Provided herein are compounds, compositions, and methods for the treatment of viral infections, for example, 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 D-amino acid phosphoramidate halogeno pyrimidine nucleoside analog compounds which display remarkable efficacy and bioavailability for the treatment of, for example, HCV infection in a human. In certain embodiments, the compounds are of Formula I: or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form, or polymorphic form thereof, wherein: PD, X, R1, R2, RA, and RB are as described herein.

Abstract: The present invention relates to methods of synthesizing 18F-FMAU. In particular, 18F-FMAU is synthesized using one-pot reaction conditions in the presence of Friedel-Crafts catalysts. The one-pot reaction conditions are incorporated into a fully automated cGMP-compliant radiosynthesis module, which results in a reduction in synthesis time and simplifies reaction conditions. The one-pot reaction conditions are also suitable for the production of 5-substituted thymidine or cytidine analogs. The products from the one-pot reaction (e.g. the labeled thymidine or cytidine analogs) can be used as probes for imaging tumor proliferative activity. More specifically, these [18F]-labeled thymidine or cytidine analogs can be used as a PET tracer for certain medical conditions, including, but not limited to, cancer disease, autoimmunity inflammation, and bone marrow transplant.

Abstract: The present invention provides a manufacturing method that can easily manufacture a compound known as photoresponsive (photocoupling) nucleic acids at high yield in a shorter period of time than that of the conventional technology. The present invention relates to a method of manufacturing a photoresponsive nucleic acid which includes a step of reacting a nucleic acid having groups represented by the Formula I, the Formula III, the Formula IV, or the Formula V and a compound represented by the Formula II, or reacting a nucleic acid having groups represented by the Formula VI, the Formula VIII, the Formula IX, or the Formula X and a compound represented by the Formula VII by heating them by microwaves in the presence of a metal catalyst, a basic substance, and a solvent.

Abstract: A tumor radiation probe of iodine-123 marker thymidine (FLT) analogue [123I]-IaraU is disclosed. Commercial available uridine is used as the raw material for the synthesis of the precursor. A radioactive iodine-123 is marked on an alkaline group of uridine to obtain [123I]-IaraU, which is distinguishable from [18F]-FLT marking 18F on a glycosyl group to obtain a novel tumor radiation probe. The marking procedures include mixing the marker precursor with Na [123I] solution, acetic acid and hydrogen peroxide solution, and the solution of chloroform and sodium hydroxide. The sonication time increases from 1 minute to 10 minutes, so that [123I]-IaraU has radiologically chemical purity of higher than 98% and radiological specific activity of not less than 0.196 GBq/umole, and the yield can increase from 8% to 40%. Its radioactive specific activity, yield and purity reach to the degree for the use in biological experiments, while reducing production cost.

Abstract: A tumor radiation probe of iodine-123 marker thymidine (FLT) analogue [123I]-IaraU is disclosed. Commercial available uridine is used as the raw material for the synthesis of the precursor. A radioactive iodine-123 is marked on an alkaline group of uridine to obtain [123I]-IaraU, which is distinguishable from [18F]-FLT marking 18F on a glycosyl group to obtain a novel tumor radiation probe. The marking procedures include mixing the marker precursor with Na [123I] solution, acetic acid and hydrogen peroxide solution, and the solution of chloroform and sodium hydroxide. The sonication time increases from 1 minute to 10 minutes, so that [123I]-IaraU has radiologically chemical purity of higher than 98% and radiological specific activity of not less than 0.196 GBq/umole, and the yield can increase from 8% to 40%. Its radioactive specific activity, yield and purity reach to the degree for the use in biological experiments, while reducing production cost.

Abstract: Embodiments are disclosed herein that involve C5-functionalized nucleic acids, which can be used for detecting a target in a nucleic acid. Particular embodiments disclose methods for making these compounds, wherein the compounds can be formed by coupling of an intermediate with a linker. Certain embodiments disclose the use of these compounds for detecting single nucleotide polymorphisms, and for increasing the thermal affinity of nucleic acid complements as compared to unmodified nucleic acid complements. In addition, the disclosed compounds can decrease enzymatic degradation of nucleic acids.

Abstract: Amphiphilic prodrugs of general formula A-X are disclosed, wherein A is a biologically active agent or may be metabolised to a biologically active agent; and X is selected from the group consisting of R, or up to three R moieties attached to a linker, Y1, Y2 or Y3, wherein R is selected from a group consisting of alkyl, alkenyl, alkynyl, branched alkyl, branched alkenyl, branched alkynyl, substituted alkyl, substituted alkenyl and substituted alkynyl groups and their analogues; Y1 is a linker group which covalently attached to an R group at one site and is attached to A at a further independent site; Y2 is a linker group which is covalently attached to two R groups at two independent sites and is attached to A at a further independent site; and Y3 is a linker group which is covalently attached to three R groups at three independent sites and is attached to A at a further independent site.

Abstract: Conformationally locked 2?,4?-carbocylic nucleosides with improved thermal and nuclease stability are disclosed. Oligonucleotides incorporating the locked nucleosides, and methods of treating disease states, are also disclosed.

Abstract: Compounds of the formula I: including any possible stereoisomers thereof, wherein: R1 is hydrogen or halo; R4 is a monophosphate, diphosphate or triphosphate ester; or R4 is a group of formula R7 is optionally substituted phenyl; naphthyl; indolyl or N—C1-C6alkyloxycarbonyl-indolyl; R8 is hydrogen, C1-C6alkyl, benzyl; R8? is hydrogen, C1-C6alkyl, benzyl; or R8 and R8? together with the carbon atom to which they are attached form C3-C7cycloalkyl; R9 is C1-C10alkyl, benzyl, or optionally substituted phenyl; or a pharmaceutically acceptable salt or solvate thereof. pharmaceutical formulations and the use of compounds I as HCV inhibitors.

Abstract: The present invention comprises compounds useful as antiviral or antitumor agents. The compounds comprise nucleotide analogues that comprise tetrahydrofuranyl or tetrahydrothienyl moeities with quaternary centers at the 3? position. The nucleotide analogues can be used to inhibit cancer or viruses. Accordingly, the compounds of the present invention are useful for treating, preventing, and/or inhibiting diseases or conditions associated with cancers and viruses. Thus, the present invention also comprising pharmaceutical formulations comprising the compounds and methods of using the compounds and formulations to inhibit viruses or tumors and treat, prevent, or inhibit the foregoing diseases.

Abstract: A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1?, 2? or 3?-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Abstract: [Problems] A derivative of a nucleic acid antimetabolite is demanded which can show a high therapeutic effect at a low dose. [Means For Solving Problems] Disclosed is a high molecular weight derivative of a nucleic acid antimetabolite, which is characterized by comprising a high molecular weight compound comprising a polyethylene glycol moiety and a polymer moiety having a carboxyl group in a side chain and a nucleoside derivative which can act as a nucleic acid antimetabolite, wherein the carboxyl group in the side chain is bound to a hydroxyl group in the nucleoside derivative via an ester bond. Also disclosed is a method for producing the high molecular weight derivative.

Abstract: 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.

Abstract: Embodiments of the invention are to compounds, methods, and compositions for use in the treatment of viral infections. More specifically embodiments of the invention are 2?,4?-substituted nucleoside compounds useful for the treatment of viral infections, such as HIV, HCV, and HBV infections.

Abstract: Process for preparing a compound of the formula (I) R1-S(O)x—S(O)yR2 in which R1 represents a molecular hydrocarbon radical which can be substituted and/or interrupted by one or more atoms and/or by one or more groups containing one or more atoms, said atoms being selected from N, O, P, S, Si and X, where X represents a halogen; R2, independently of R1, represents a carbon-containing group or a molecular hydrocarbon radical which can be substituted and/or interrupted by one or more atoms and/or by one or more groups containing one or more atoms, said atoms being selected from N, O, P, S, Si and X, where X represents a halogen, and x and y are selected from 0 and 1 in such a way that the sum of x and y is not more than 1, characterized in that a compound of formula (II) R1-S(O)x—R3-Si(R4)(R5)(R6) in which R3 represents a hydrocarbon chain of two carbon atoms, which is optionally unsaturated and/or substituted, and R4, R5 and R6, which are identical or different, each represent, independently of one another, a

Abstract: Disclosed are nucleosides which are useful in diagnosing and treating viral infections, for example, infections caused by hepatitis B virus (HBV), and herpes viruses including Epstein Barr virus.

Abstract: This invention relates to a process of stereoselectively synthesizing a ?-nucleoside compound of formula (I): wherein R1, R2, and B are as defined in the specification; each of R3 and R4, independently, is H or fluoro. The process includes reacting, in the presence of a transition metal salt, a tetrahydrofuran compound of formula (II): wherein R1, R2, and L are as defined in the specification, with a nucleobase derivative; and each of R3 and R4, independently, is H or fluoro.

Abstract: [Problems] A derivative of a nucleic acid antimetabolite is demanded which can show a higher therapeutic effect at a lower dose. [Means for Solving Problems] Disclosed is a high molecular weight derivative a nucleic acid antimetabolite, which is characterized by comprising a high molecular weight compound comprising a polyethylene glycol moiety and a polymer moiety having a carboxyl group in a side chain and a nucleoside derivative which can act as a nucleic acid antimetabolite, wherein the nucleoside derivative is bound to the carboxyl group in the side chain of the high molecular weight compound via a highly hydrophobic linker.

Abstract: A drug using the magnetic properties of a metal salen complex as represented by the following general formula in order to magnetize the intended drug by chemically binding the drug to a metal salen complex so that the drug can be delivered to the target diseased site. The drug can be delivered to the diseased site using the magnetic properties of the drug per se without using a carrier made of a magnetic substance as in the conventional methods.

Abstract: The present invention features compositions and methods for detecting, selecting a treatment method for, monitoring, and treating a neoplasia associated with a viral infection.

Abstract: A therapeutic agent formed of a magnetic resonance imaging tracer conjugated with a chemotherapeutic agent. The therapeutic agents can be used in measuring drug delivery to a target tissue. The therapeutic agents allow for therapeutic MRI, in which 19F MRI techniques are used to detect, monitor, evaluate, and/or adjust chemotherapeutic drug dosage levels in a patient or a targeted tissue thereof.

Abstract: The present invention provides a manufacturing method that can easily manufacture a compound known as photoresponsive (photocoupling) nucleic acids at high yield in a shorter period of time than that of the conventional technology. The present invention relates to a method of manufacturing a photoresponsive nucleic acid which includes a step of reacting a nucleic acid having groups represented by the Formula I, the Formula III, the Formula IV, or the Formula V and a compound represented by the Formula II, or reacting a nucleic acid having groups represented by the Formula VI, the Formula VIII, the Formula IX, or the Formula X and a compound represented by the Formula VII by heating them by microwaves in the presence of a metal catalyst, a basic substance, and a solvent.

Abstract: Compounds represented by the formula 1: A is selected from the group consisting of wherein each R individually is H or acyl, Y is X, N3, NH2, monoalkylamino, or dialkylamino; Z is O or S; and X is selected from the group consisting of hydrogen, halo, hydroxy, alkoxy, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, amino, monoalkylamino, dialkylamino, thioaryl, thioalkyl, allylamino, cyano and nitro; tautomers thereof; and pharmaceutically acceptable salts thereof are provided along with methods for their fabrication. Various of these compounds can be used as anticancer agents, or antiviral agents or to inhibit DNA replication.

Abstract: A method for the treatment or prevention of Flaviviridae infections, in particular, hepatitis C virus infection, in a host, and in particular, a human, is provided that includes administering an effective amount of a ?-L- or ?-D-2?,3?-dideoxynucleoside or a pharmaceutically acceptable salt or prodrug thereof, optionally in a pharmaceutically acceptable diluent or excipient.

Abstract: Disclosed are nucleosides which are useful in diagnosing and treating viral infections, for example, infections caused by hepatitis B virus (HBV), and herpes viruses including Epstein Barr virus.

Abstract: Uracil reductase inactivators, notably a 5-substituted uracil or 5,6-dihydro-5-substituted uracil, potentiate 5-flourouracil and find use particularly in the treatment of cancer. The 5-substituent is selected from bromo, ido, cyano, halo-substituted C1-4 alkyl, C2-6 alkenyl, 1-halo-C2-6 alkenyl and halo-substituted C2-6 alkynyl.

Abstract: A polysialic acid compound is reacted with a hetero-bifunctional reagent to introduce a pendant functional group for site-specific conjugation to sulfhydryl groups, for instance side chains of cysteine units in drugs, drug delivery systems, proteins or peptides. The functional group is, for instance, an N-maleimide group.

Abstract: Disclosed are Mannich base N-oxides of drugs containing acidic N—H groups. Pharmaceutical compositions comprising a therapeutically effective amount of Mannich base N-oxides, or a N-oxide rearrangement product, pharmaceutically acceptable salt or prodrug thereof, are also disclosed. Further, disclosed are methods of using the compounds, alone or in combination with one or more other active agents or treatments.

Abstract: Deoxyuridine derivatives of Formula (I?); where A is O, S or CH2; B is O, S or CHR3; R1 is H, or various substituents; R2 is H, F; R3 is H, F, OH, NH2; or R2 and R3 together form a chemical bond; D is —NHCO—, —CONH—, —O—, —C(?O)—, —CH?CH, —C?C—, —NR5—; R4 is hydrogen or various substituents; R5 is H, C1-C4 alkyl, C1-C4 alkanoyl; E is Si or C; R6, R7 and R8 are independently selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, or a stable monocyclic, bicyclic or tricyclic ring system have utility in the prophylaxis of treatment of parasitic diseases such as malaria.

Abstract: The present invention relates to compounds according to the general formula: wherein B is or and the remaining variables are defined in the specification, and compositions comprising the compounds. The compounds are useful as anti-viral agents in viral therapy.

Abstract: Disclosed are nucleosides which are useful in diagnosing and treating viral infections, for example, infections caused by hepatitis B virus (HBV), and herpes viruses including Epstein Barr virus.

Abstract: The present invention relates to compounds, compositions and methods for the treatment of a host infected with a hepatitis B virus. Specifically, compound and compositions of 3?-esters of 2?-deoxy-?-L-pyrimidine nucleosides are disclosed, which can be administered either alone or in combination with other anti-hepatitis B agents. Compound and compositions of 3?,5?-diesters of 2?-deoxy-?-L-pyrimidine nucleosides are also disclosed, which can be administered either alone or in combination with other anti-hepatitis B agents.

Abstract: The invention relates to new side chain-fluorinated 3?-deoxythymidine derivatives of the general formula I or physiological acceptable esters thereof, wherein R?CH218F; CH18F2; CH2F or CHF2 and Y?H, N3 or Hal. The invention also relates to a simple and efficient method for the preparation of these 3?-deoxythymidines of formula I and to the use of the 18F-containing compounds of formula I or of a pharmaceutical composition comprising these compounds for the diagnosis of tumors in positron emission tomography (PET).

Abstract: This invention describes a novel family of polysaccharide prodrugs with enhanced colonic delivery advantage. The prodrugs are synthesized by chemically linking a parent compound with a specially selected polysaccharide (M.W. 105-107 Da) containing galactose residues. Its characteristics are that it is synthesized by chemically linking polysaccharides with the parent compound through different bridge links for targeted colonic delivery; that the polysaccharides contain galactose residues. Because of this, the polysaccharide component can protect the parent compound from absorption (or metabolism) in the upper gastrointestinal tract and deliver a high concentration of the bound compound to the colonic area.

Abstract: This invention relates to a quick-release tablet formulation with >99.19% pure fludara (high-purity fludara) as an active ingredient in a defined composition of residual contaminants.

Abstract: Uracil reductase inactivators, notably a 5-substituted uracil or 5,6-dihydro-5-substituted uracil, potentiate 5-flourouracil and find use particularly in the treatment of cancer. The 5-substituent is selected from bromo, ido, cyano, halo-substituted C1-4 alkyl, C2-6 alkenyl, 1-halo-C2-6 alkenyl and halo-substituted C2-6 alkynyl.

Abstract: A process for substantially enhancing the regio and stereoselective synthesis of 9-?-anomeric nucleoside analogs is described. The introduction of the sugar moiety onto a 6-substituted purine base was preformed so that only the 9-?-D- or L-purine nucleoside analogs were obtained. This regio and stereoselective introduction of the sugar moiety allows the synthesis of nucleoside analogs and in particular 2?-deoxy, 3?-deoxy, 2?-deoxy-2?-?-fluoro and 2?,3?-dideoxy-2?-?-fluoro purine nucleoside analogs in high yield without virtually any formation of the 7-positional isomers. The compounds are drugs or intermediates to drugs.

Abstract: The present invention relates to a linker nucleoside, its preparation and use for the covalent bonding of biomolecules to oligonucleotides, in particular p-RNA oligonucleotides.

Abstract: A process for the preparation of 5′-deoxy-5-fluorouridine, which comprises the transformation of 2′,3′-O-isopropylidene-5-fluorouridine in the corresponding 5′-O-sulfonyl derivative, subsequent reaction with alkaline or earth-alkaline iodides and, after hydrolysis of the isopropylidene group, reduction of the 5′-deoxy-5′-iodo-5-fluorouridine thus obtained, is described.

Abstract: This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside has the formula: wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted.

Abstract: Contraceptive activity as well as anti-viral protection can be provided by contraceptive compositions containing a pyrimidine-based nucleoside or nucleotide exhibiting spermicidal or sperm-immobilizing activity. In one example, the active ingredient contains a thymine ring (e.g. AZT) that has 5-halo, 6-alkoxy substitution. Additional improvements in anti-HIV activity for certain AZT derivatives are seen by providing the pentose ring of AZT with aryl phosphate substitution.

Abstract: A method for the treatment for hepatitis delta infection in a host, that includes administering an effective amount of a nucleoside or a nucleoside analog that suppresses the expression of the hepatitis B surface or preS1 antigen in the host 100-fold or more relative to pretreatment values in vivo; or to not more than 1 microgram per milliliter in vivo. In a preferred embodiment, the nucleoside is L-FMAU, or a pharmaceutically acceptable salt or prodrug thereof.

Abstract: Compounds of the formula I or corresponding monohydroxynucleoside derivatives wherein: R1 is hydroxy, amino or carboxy: optionally having esterified/amide bonded thereon; a C4-C22 saturated or unsaturated, optionally substituted fatty acid or alcohol, or an aliphatic L-amino acid; R2 is the residue of an aliphatic L-amino acid; L1 is a trifunctional linker group; L2 is absent or a difunctional linker group; and pharmaceutically acceptable salts thereof have favorable pharmacological properties and are antivirally active.

Abstract: A process for the preparation of 5′-deoxy-5-fluorouridine, which comprises, the transformation of, 2′,3′-O-isopropylidene-5-fluorouridine in the corresponding 5′-O-sulfonyl derivative subsequent reaction with alkaline or earth-alkaline iodides and after hydrolysis of the isopropylidene group, reduction of the 5′-deoxy-5′-iodo-5 -fluorouridine thus obtained, is described.

Abstract: Contraceptive activity as well as anti-viral protection can be provided by contraceptive compositions containing a pyrimidine-based nucleoside or nucleotide exhibiting spermicidal or sperm-immobilizing activity. In one example, the active ingredient contains a thymine ring (e.g. AZT) that has 5-halo, 6-alkoxy substitution. Additional improvements in anti-HIV activity for certain AZT derivatives are seen by providing the pentose ring of AZT with aryl phosphate substitution.

Abstract: The present invention relates to a novel and improved process for preparing 2′-fluoro-5-methyl-&bgr;-L-arabinofuranosyluridine represented by formula (1) which shows anti-viral activity, especially potent anti-viral activity against hepatitis B-virus and Epstein-Barr virus: 1

Abstract: Heavily fluorinated sugar analogs of formula wherein R1 is selected from alkyl, alkenyl, aryl, —CH2—O-alkyl, —CH2—O-aryl, —CH2OPO3H, —CH2—O-carbohydrate, —CH2—NH-peptide, or —CH2—O-peptide; wherein R2 is selected from hydroxy, —O-carbohydrate, —NH-peptide, wherein R3 is selected from H, halogen, lower alkyl, lower alkenyl, lower haloalkyl, lower haloalkenyl, amino, mono- or di-lower alkylamino; wherein R4 is selected from amino, hydroxy, alkoxy, or halogen; and wherein R5 is H or amino. The compounds of formula (I) are useful as antiviral and antineoplastic agents and the compounds of formula (II) are useful as plant growth inhibitors and herbicides.

Abstract: This invention provides a method for identifying potential therapeutic agents by contacting a target cell with a candidate therapeutic agent which is a selective substrate for an endogenous, intracellular enzyme in the cell which is enhanced in its expression as a result of selection by biologic or chemotherapy. This invention also provides methods and examples of molecules for selectively killing a pathological cell by contacting the cell with a prodrug that is a selective substrate for an endogenous, intracellular enzyme. The prodrug is subsequently converted to a cellular toxin. Further provided by this invention is a method for treating a pathology characterized by pathological, hyperproliferative cells in a subject by administering to the subject a prodrug that is a selective substrate for an endogenous, overexpressed, intracellular enzyme, and converted by the enzyme to a cellular toxin in the hyperproliferative cell.

Abstract: Uracil reductase inactivators, notably a 5-substituted uracil or 5,6-dihydro-5-substituted uracil, potentiate 5-fluorouracil and find use particularly in the treatment of cancer. The 5-substituent is selected from bromo, iodo, cyano, halo-substituted C1-4 alkyl, C2-6 alkenyl, 1-halo-C2-6 alkenyl and halo-substituted C2-6 aklynyl.

Abstract: The invention relates to a 3′-substituted nucleoside derivative represented by the following general formula (1): wherein B means a nucleic acid base which may have a substituent, Z represents a lower alkynyl or lower alkenyl group which may be substituted by a group represented by the formula: in which Ra, Rb and Rc are individually a lower alkyl group or a phenyl group, or an oxiranyl group which may have at least one lower alkyl group, R1 and R2 individually represent H or an ester-forming residue capable of easily leaving in a living body, and R3 is H, a mono- or polyphosphoric acid residue, or an ester-forming residue capable of easily leaving in a living body, with the proviso that the sugar moiety is ribose, or a pharmaceutically acceptable salt thereof. The 3′-substituted nucleoside derivative according to the invention has an excellent antitumor activity and is hence useful for treatment for and prevention of cancers.