Abstract: The present teachings generally relate to fluorescent dyes, linkable forms of fluorescent dyes, energy transfer dyes, reagents labeled with fluorescent dyes and uses thereof.

Abstract: Compositions and methods of preparing carboranes and metallacarboranes, which can be used as a new type of electrochemically active label for biological compounds, are disclosed. Nucleic acid derivatives labelled with carborane or metallacarborane can be detected by electrochemical methods and can find several practical applications, such as materials for nanoconstruction, in DNA array technology or for the construction of biosensors, especially electrochemical biosensors. Other applications can include use as modified primers in amplification of RNA and DNA, antisense drugs, boron carriers for BNCT, radiopharmaceuticals bearing a range of isotopes useful in different types of radiotherapy, molecular probes, elements of biosensors, materials for nanotechnology and others.

Abstract: The present invention relates to a process for preparing a compound of formula 682-4, said process comprising the steps of: (i) converting a compound of formula 682-1 into a compound of formula 682-2; (ii) converting said compound of formula 682-2? into a compound of formula 682-3; and (iii) converting said compound of formula 682-3 into a compound of formula 682-4. Further aspects of the invention relate to the use of the above process in the preparation of 2?-cyano-2?-deoxy-N4-palmitoyl-1-?-D-arabmofuranosylcytosine, a pyrimidine nucleoside which is therapeutically useful in the treatment and/or prevention of cancer.

Abstract: The current inventions relates to a strain of Lactobacillus amylovorus designated FST 2.11 as deposited under the accession no DSM 19280 on 13 Apr. 2007 in the DSMZ depository, and strains substantially similar thereto also encoding anti-fungal and bread antistaling properties and applications thereof.

Abstract: Disclosed is a method for preparing 2?-deoxy-2?,2?-difluorocytidine of Formula I comprising, preparing an optically pure 3R-hydroxypropane amide compound of Formula VIII from an optical ester compound of Formula IX using an optically active chiral amine, preparing an optically pure D-erythro-2,2-difluoro-2-deoxy-1-oxoribose compound of Formula V from the compound of Formula VIII, glycosylating the compound of Formula V with a nucleobase to prepare the 2?-deoxy-2?,2?-difluorocytidine of Formula I as a ?-nucleoside. With the present invention, it is possible to prepare an optically pure compound of Formula I in a high purity and a high yield. In the Formulae, R1 and R2 are protecting groups and are each independently benzoyl, 4-methylbenzoyl, 3-methylbenzoyl, 4-cyanobenzoyl, 3-cyanobenzoyl, 4-propylbenzoyl, 2-ethoxybenzoyl, 4-t-butylbenzoyl, 1-naphthoyl or 2-naphthoyl, R3, R4 and R7 are each independently C1-C3 alkyl, R5 is methyl or ethyl, R6 is hydrogen, methyl or methoxy.

Abstract: In its many embodiments, the present invention provides a novel class of pyrimidine analogs of formula (V) as targeted mechanism-based modulators of cell cycle checkpoints. Cancers and/or malignancies can be treated by administration of a cell cycle checkpoint modulator of the invention. Also discussed are suitable combinations of the cell cycle checkpoint modulator with a checkpoint kinase inhibitor to produce synergistic apoptosis in cancer cells. The invention includes methods of treating cancers by administering the combination of the cell cycle checkpoint modulator and the checkpoint kinase inhibitor, pharmaceutical compositions comprising the activator as well as the combination and pharmaceutical kits.

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: Cyanine-type fluorescent dyes modified with an alkynyl linker arm of formula (I), suitable for the conjugation of biomolecules, such as for example nucleosides, nucleotides, oligonucleotides, nucleic acids, proteins, peptides, vitamins and hormones. A method and intermediates for the synthesis of the alkynyl cyanines of the invention are also described, as well as alkynyl cyanine-biomolecule conjugates and methods for preparing thereof. The alkynyl cyanines can be advantageously used as markers for biomolecules or as quenchers.

Abstract: 4-Amino-1-((2R,3S,4S,5R)-5-azido-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one (22) and prodrugs thereof are hepatitis C (HCV) polymerase inhibitors. Also disclosed are compositions and methods for inhibiting HCV and treating HCV-mediated diseases, processes for making the compounds and synthetic intermediates employed in the process.

Abstract: The present invention provides a new patentable class of purine analog compounds, as well as compositions and methods of using them, for example, to prevent or treat various diseases and disorders in human and non-human animals.

Abstract: A method of generating a chronic myelogenic leukemia (CML) acquired chemoresistant culture model is provided. Such a method may comprise providing a naïve blast crisis CML cell line; administering/contacting the cell line with a mutation-inducing dose of imatinib; maintaining a culture of the treated cell line for a period of time until the treated cell line relapses and repopulates the culture; and determining the repopulated cell culture is a CML acquired chemoresistant cell line by detecting a BCR-ABL mutation, wherein the acquired chemoresistance is achieved by a BCR-ABL mutation.

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: Compounds containing nucleic acid bases or their precursors modified by enrichment at specific sites with heavy stable isotopes of elements naturally present at those sites in minute amount are useful for the treatment of diseases characterized by altered gene expression and altered pattern of epigenomic control. These compounds, when used as nutrients or in other medicinal application methods, can alter the DNA methylation pattern in a simple way through the well-understood mechanism of kinetic isotope effect (KIE). This effect could also be useful for modifying methylation kinetics in stem cell technology, cloning and as disease therapeutics.

Abstract: This disclosure provides novel reversibly terminated ribonucleotides which can be used as a reagent for DNA sequencing reactions. Methods of sequencing nucleic acids using the disclosed nucleotides are also provided.

Abstract: The present invention relates to fatty acid and fatty alcohol substituted nucleoside derivatives and nucleoside and nucleoside derivatives substituted on multivalent scaffolds (e.g., polymers, peptides, polycarboxylic acid substituted compounds, compounds containing polycycloSaligenyl groups) that display potent anti-HIV activity. Furthermore, they show enhanced activity against multi-drug resistant, R5, and cell-associated virus. Some of them also display activity against other sexually transmitted pathogens and sperm. The present invention provides their methods of synthesis, composition of matter, and methods of use. Emphasis is placed on their application as topical microbicides to treat or prevent sexual transmission of disease, especially HIV/AIDS.

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: This Divisional application of patent application Ser. No. 10/768,996, entitled “Novel Oligonucleotides And Related Compounds” discloses a class of chemical compounds which have been demonstrated to possess cancer fighting properties. The parent application disclosed oligonucleotides for selectively killing cancerous cells over noncancerous cells by incorporating and covalently linking antimetabolite prodrugs via CpG moieties, for the anitmetabolite Gemcitabine and other compounds with known cancer fighting properties. This application discloses modifications of Gemcitabine for incorporation into CpG oligonucleotides for improved biochemical and biological properties.

Abstract: The present invention provides an agent that modulates physiological condition of pests, wherein the agent has an ability to modulate the activity of an insect choline acetyltransferase; a method for assaying pesticidal activity of a test substance, which comprises measuring the activity of a choline acetyltransferase in a reaction system in which the choline acetyltransferase contacts with a test substance, and the like.

Abstract: This invention relates to synthesis of novel -N-FMOC protected nucleosides, succinates, phosphoramidites, corresponding solid supports that are suitable for oligo deoxy nucleosides and RNA oligonucleotide synthesis. Our discovery using N-FMOC as nucleoside base protecting group, which is highly base labile protecting group is a novel approach to obtain highest purity oligonucleotides. This approach is designed to lead to very high purity and very clean oligonucleotide, after efficient removal of the protecting groups and to produce high purity therapeutic grade DNA oligonucleotides, RNA oligonucleotides, diagnostic DNA, diagnostic RNA for microarray platform. The deprotection of FMOC protecting groups of the natural deoxy and ribonucleosides occurs under very mild deprotection conditions such as mild bases, secondary and tertiary amines for removal of such groups under such conditions would allows synthesis of various DNA and RNA of highest purity for diagnostics and therapeutic application.

Abstract: 4-Amino-1-((2R,3S,4S,5R)-5-azido-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one (22) and prodrugs thereof are hepatitis C (HCV) polymerase inhibitors. Also disclosed are compositions and methods for inhibiting HCV and treating HCV-mediated diseases, processes for making the compounds and synthetic intermediates employed in the process.

Abstract: The subject invention concerns platinum complexes that exhibit antitumor cell and/or antiparasitic activity. The subject invention also concerns the use of platinum complexes of the invention to treat oncological and inflammatory disorders. The platinum complexes of the invention can also be used to treat or prevent infection by a virus or a bacterial or parasitic organism in vivo or in vitro.

Abstract: The subjects of the present invention are the method of preparation of 4-furfurylcytosine and/or its derivatives, its use in the manufacture of anti-aging compositions and an anti-aging composition. As 4-furfurylcytosine and/or its derivatives possesses a series of biological properties it might be use as a composition having excellent anti-aging effect to prevent the sagging of skin and loss of luster and to improve sufficiently its aesthetic appearance without significantly change the growth rate and the total growth ability of the skin. Optimal methods of manufacturing this compound, while at the same time obtaining the highest possible process efficiency, with particular emphasis on its utility in the pharmaceutical and cosmetic industries are presented.

Abstract: The invention refers to the use of L19IL2 for treatment of pancreatic cancer. In another embodiment, the invention relates to a combination (i) of a fusion protein, comprising an Interleukin 2 part and an antibody part, specifically recognizing the extra domain B of fibronectin (ED-B-fibronectin), and (ii) gemcitabine.

Abstract: The invention relates to the use of a genetic marker in a process for analysis of leukemia patients, especially for use in the prediction of the suitability of chemotherapy in a group of leukemia patients. Further, the invention relates to chemotherapeutical agents for use in the therapy of leukemia patients that have been diagnosed to be at least heterozygous for the relevant allele of the genetic marker.

Abstract: The present invention relates to process and intermediates for the preparation of substituted 1,3-oxathiolanes. The present invention specifically relates to a process for the preparation of lamivudine.

Abstract: Provided is a pyrimidine nucleoside compound represented by the following formula (1): or a pharmaceutically acceptable salt thereof, wherein one of X and Y represents a cyano group, and the other represents a hydrogen atom; one of R1 and R2 represents a hydrogen atom, a carbonyl group having a C1-C6 alkyl group which has been mono-substituted by an amino group, or a group represented by (R3)(R4)(R5)Si—, and the other represents a group represented by (R6)(R7)(R8)Si—, or R1 and R2 together form a 6-membered cyclic group represented by —Si(R9)(R10)—; R3, R4, R5, R6, R7, and R8 each represent a C1-C10 linear or branched alkyl group which may have a substituent, a C3-C6 cycloalkyl group which may have a substituent, a C6-C14 aryl group which may have a substituent, or a C1-C6 alkyl group which has been substituted by one or two C6-C14 aryl groups and which may have a substituent; and R9 and R10 each represent a C1-C6 linear or branched alkyl group which may have a substituent.

Abstract: Provided is an improved method for stereoselectively preparing 2?-deoxy-2?,2?-difluorocytidine of formula (I), which includes reacting a 1-halo ribofuranose compound with a nucleobase of formula (IV) in a solvent to obtain a nucleo side of formula (II) with removal of a silyl halide ((alkyl)3SiX (X=halide)); and deprotecting the nucleoside of formula (II) to obtain 2?-deoxy-2?,2?-difluorocytidine of formula (I). 2?-Deoxy-2?,2?-difluorocytidine of formula (I) is effective for treating various cancers such as non-small cell lung (NSCLC), pancreatic, bladder, breast or ovarian cancers.

Abstract: The present invention provides (i) a process for preparing a 2-deoxy-2-fluoro-2-methyl-D-ribonolactone derivative, (ii) conversion of the lactone to nucleosides with potent anti-HCV activity, and their analogues, and (iii) a method to prepare the anti-HCV nucleosides containing the 2-deoxy-2-fluoro-2-C-methyl-?-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside.

Abstract: The subject invention discloses compounds, compositions and methods for treatment and prevention of toxicity due to chemotherapeutic agents and antiviral agents. Disclosed are acylated derivatives of non-methylated pyrimidine nucleosides. These compounds are capable of attenuating damage to the hematopoietic system in animals receiving antiviral or antineoplastic chemotherapy.

Abstract: This invention provides highly regioselective and stereoselective processes for preparing synthetic nucleosides. A process for the preparation of synthetic nucleosides is provided that comprises a) preparing a bicycloamide derivative, b) reacting the bicycloamide derivative with a nucleic acid base or heterocyclic base or salt thereof in the presence of a transition metal catalyst to form a cyclopentenecarboxamide, and c) cleaving a carboxamide group from the cyclopentenecarboxamide to form the synthetic nucleoside. The processes according to the invention can be used for the synthesis of a variety of anti-viral agents, including Abacavir, Carbovir, and Entecavir, as well as derivatives thereof.

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: A first aspect of the invention relates to a combination comprising a CDK inhibitor and 1-(2-C-cyano-2-dioxy-?-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof. A second aspect of the invention relates to a pharmaceutical product comprising a CDK inhibitor and 1-(2-C-cyano-2-dioxy-?-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, as a combined preparation for simultaneous, sequential or separate use in therapy. A third aspect of the invention relates to a method of treating a proliferative disorder, said method comprising simultaneously, sequentially or separately administering a CDK inhibitor and 1-(2-C-cyano-2-dioxy-?-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, to a subject.

Abstract: The present invention discloses novel and improved nucleosidic and nucleotidic compounds that are useful in the light-directed synthesis of oligonucleotides, as well as, methods and reagents for their preparation. These compounds are characterized by novel photolabile protective groups that are attached to either the 5?- or the 3?-hydroxyl group of a nucleoside moiety. The photolabile protective group is comprised of a 2-(2-nitrophenyl)-ethyoxycarbonyl skeleton with at least one substituent on the aromatic ring that is either an aryl, an aroyl, a heteroaryl or an alkoxycarbonyl group. The present invention includes the use of the aforementioned compounds in light-directed oligonucleotide synthesis, the respective assembly of nucleic acid microarrays and their application.

Abstract: Compounds having the formula I wherein R1 is as herein defined are Hepatitis C virus NS5b polymerase inhibitors.

Abstract: The use of squalenic acid or a derivative thereof in formulating at least one polar active principle with a molecular weight of 100 Da or more, in the form of nanoparticles, and pharmaceutical compositions thereof.

Abstract: The present invention is directed to a processes for the synthesis of trans isomer of 4,6-disubstituted-tetrahydro-furo, thieno, pyrrolo and cyclopenta-[3,4][1,3]dioxoles (Formula I). The process comprises the steps of: (a) obtaining a compound of Formula II, which is a mixture of cis and trans-diastereomers, and (b) chemically decomposing the compound of Formula II in a solution comprising a solvent and an acid that is a hydrogen donor or an electron pair acceptor, whereby the cis diastereomer is decomposed and the compound of Formula I is obtained. The compounds prepared by the present invention are useful in treating diseases or conditions associated with platelet aggregation and/or platelet activation.

Abstract: The present invention relates to the use of carbodine and 5-F carbodine and analogs thereof for use in the treatment or prophylaxis of influenza, in particular the H5N1 strain of Avian Influenza A virus or “bird flu” strain of influenza as well as the treatment or prophylaxis of Venezuela equine encephalitis virus or VEE.

Abstract: The present invention provides luminescent metal ion complexes for use in a wide range of biological and chemical studies. The luminescent metal ion complexes of the invention comprise a metal ion chelating component covalently bound to a carrier molecule. Also provided are methods of making and using the luminescent metal ion complexes.

Abstract: To provide a method for administering ECyd to a patient, which realizes a continuous therapy without expressing peripheral neurotoxicity caused by ECyd and which exhibits an excellent therapeutic effect with ensuring prolongation of the survival of the patient. The invention provides an antitumor agent containing ECyd or a salt thereof, which is administered to a cancer patient through continuous intravenous administration at a dose of 1.30 to 8.56 mg/m2 as reduced to ECyd, for each administration period of 2 to 336 hours.

Abstract: Disclosed are water-soluble compositions of gemcitabine and docetaxel formed by conjugating the gemcitabine or docetaxel to a water-soluble polymer such as N-2-hydroxypropyl methacrylamide (HPMA). Also disclosed are methods of using the compositions of the invention for the treatment of cancer.

Abstract: The invention relates to the structure, production and use of modified nucleotide and nucleoside building blocks, (nuc-macromolecules).

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 polymeric compounds which are useful as prodrugs, comprising a chain of monomeric nucleosides, nucleoside analogs or abasic nucleosides, wherein at least one of the nucleosides or nucleoside analogs or a heterocyclic derivative thereof is pharmaceutically active and the nucleosides, nucleoside analogs or abasic nucleosides are linked by a phosphodiester group, a phosphorothioate group or an H—, alkyl or alkenyl phosphonate group.

Abstract: Disclosed is a method for preparing 2?-deoxy-2?,2?-difluorocytidine of Formula I comprising, preparing an optically pure 3R-hydroxypropane amide compound of Formula VIII from an optical ester compound of Formula IX using an optically active chiral amine, preparing an optically pure D-erythro-2,2-difluoro-2-deoxy-1-oxoribose compound of Formula V from the compound of Formula VIII, glycosylating the compound of Formula V with a nucleobase to prepare the 2?-deoxy-2?,2?-difluorocytidine of Formula I as a ?-nucleoside. With the present invention, it is possible to prepare an optically pure compound of Formula I in a high purity and a high yield. In the Formulae, R1 and R2 are protecting groups and are each independently benzoyl, 4-methylbenzoyl, 3-methylbenzoyl, 4-cyanobenzoyl, 3-cyanobenzoyl, 4-propylbenzoyl, 2-ethoxybenzoyl, 4-t-butylbenzoyl, 1-naphthoyl or 2-naphthoyl, R3, R4 and R7 are each independently C1-C3 alkyl, R5 is methyl or ethyl, R6 is hydrogen, methyl or methoxy.

Abstract: The present process provides an improved method for the preparation of 4-amino-1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-hydrox-ymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one of the formula (IV) which is a potent inhibitor of Hepatitis C Virus (HCV) NS5B polymerase.

Abstract: The present invention includes methods of treating or preventing cancer by administering an effective amount of 6-substituted pyrimidine derivatives of the Formula I to a subject need thereof:

Abstract: The present invention provides a pyrimidine nucleoside compound represented by the following formula (1): [wherein one of X and Y is cyano and the other is hydrogen; and i) R1 is hydrogen, and R2 is alkyloxycarbonyl wherein the alkyl moiety is straight or branched C5-12 alkyl (the alkyl may be substituted), or alternatively, ii) R1 is alkyloxycarbonyl wherein the alkyl moiety is straight or branched C9 alkyl or alkenyloxycarbonyl wherein the alkenyl moiety is straight or branched C9 alkenyl, and R2 is hydrogen] or a salt thereof. The pyrimidine nucleoside compound or a salt thereof of the present invention shows a higher antitumor effect than existing pyrimidine nucleoside compounds.

Abstract: Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of making and using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

Abstract: 4-Amino-1-((2R,3S,4S,5R)-5-azido-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one (22) and prodrugs thereof are hepatitis C (HCV) polymerase inhibitors. Also disclosed are compositions and methods for inhibiting HCV and treating HCV-mediated diseases, processes for making the compounds and synthetic intermediates employed in the process.

Abstract: The present invention provides gemcitabine prodrugs, methods of making gemcitabine prodrugs, pharmaceutical compositions of gemcitabine prodrugs and methods of using gemcitabine prodrugs and pharmaceutical compositions of using gemcitabine prodrugs to treat or prevent diseases or disorders such as cancer or viral infections.