Abstract: 2-(6-Cyano-1-hexyn-1-yl)adenosine, 2-(6-cyano-1-hexyn-1-yl)adenosine 5′-monophosphate, or salts thereof; and drugs containing the same as an active ingredient. The compounds have excellent effects of lowering ocular tension, promoting blood flow in retina, and protecting optic nerve failure and are highly soluble in water. Owing to these characteristics, the compounds are useful as drugs such as remedies for glaucoma and ocular hypertension.

Abstract: Disclosed are novel compounds that are partial and full A1 adenosine receptor agonists, useful for treating various disease states, in particular the supraventricular tachycardias, emesis, angina, myocardial infarction and hyperlipidemia.

Abstract: 2-adenosine N-pyrazole compounds having the following formula: 1

Abstract: A process for substantially enhancing the regio and stereoselective synthesis of 9-&bgr;-anomeric nucleoside analogs is described. The introduction of the sugar moiety onto a 6-substituted purine base was preformed so that only the 9-&bgr;-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′-&bgr;-fluoro and 2′,3′-dideoxy-2′-&bgr;-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 provides methods for the chemical synthesis of nucleosides and derivatives thereof, including 2′-amino, 2′-N-phthaloyl, 2′-O-methyl, 2′-O-silyl, 2′-OH nucleosides, C-nucleosides, nucleoside phosphoramidites, C-nucleoside phosphoramidites, and non-nucleoside derivatives.

Abstract: The present invention provides for the preparation &bgr;-adenine nucleosides by coupling an adenine derivative containing an unprotected exocyclic amino group at the C-6 position and a blocked arabinofuranosyl derivative, in the presence of a base and solvent. The present invention also provides for the stereoselective preparation of 2-deoxy-&bgr;-D-adenine nucleosides wherein a blocked 2-deoxy-&agr;-D-arabinofuranosyl halide is coupled with the salt of an adenine derivative. The forgoing aspects of the present invention are utilized in the preparation of a clofarabine composition wherein the ratio of &bgr; to &agr;-anomer is at least 99:1.

Abstract: A method of treating a patient suffering from or susceptible to ischemic heart disease, peripheral vascular disease or stroke or which subject is suffering pain, a CNS disorder or sleep apnea which comprises administering a therapeutically effective amount of an adenosine derivative which is an agonist at the adenosine A1 receptor and which exhibits little or no agonist activity of the A3 receptor.

Abstract: A compound, method and composition for treating a host infected with a hepatitis C viral comprising administering an effective hepatitis C treatment amount of a described 4′-disubstituted nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Abstract: Disclosed are novel compounds that are partial and full A1 adenosine receptor agonists, useful for treating various disease states, in particular tachycardia and atrial flutter, angina, myocardial infarction and hyperlipidemia.

Abstract: The present invention provides a process for the removal of protecting groups, i.e. deprotection, from chemically synthesized oligonucleotides. In one embodiment, the invention provides reagents suitable for use in such a process, and kits incorporating such reagents in a convenient, ready-to-use format. By use of the process and reagents of the invention, side-reactions leading to certain impurities that contaminate the synthesized oligonucleotides can be minimized. Methods and reagents are provided for deprotection of an oligonucleotide by reacting a protected oligonucleotide with a deprotection reagent wherein the deprotection reagent comprises an active methylene compound and an amine reagent. The active methylene compound has the structure: where substituent EWG is an electron-withdrawing group and R is hydrogen, C1-C12 alkyl, C6-C20 aryl, heterocycle or an electron-withdrawing group.

Abstract: The present invention provides combinatorial libraries of nucleoside analog compounds and methods of making the libraries. In addition, the present invention provides methods of assaying the libraries for agonists or antagonists of a broad array of targets of therapeutic importance.

Abstract: This invention relates to the production of new & stable salts of S-adenosyl-L-methionine SAMe). The source of SAMe used in the salt formation is from chemical process wherein stereoselective methylation of S-adenosyl-L-homocysteine is achieved. The process for the salt preparation is simple, efficient & reproducible on large scale. The new salts were found to be stable at accelerated temperature for minimum 3 months.

Abstract: Stable salts of S-adenosyl-1-methionine with polycations such as chitosan are described. The salts according to the invention are very stable and are valuable for use as active constituents in pharmaceutical compositions.

Abstract: This application relates to monomers of the general formula (I) for the preparation of PNA (peptide nucleic acid) oligomers and provides method for the synthesis of both predefined sequence PNA oligomers and random sequence PNA oligomers: 1

Abstract: Various substituted nitrogen heterocyclic derivatives and their pharmaceutically acceptable salt derivatives are provided for use as medicaments, and particularly, as antimitotic, anti-viral, anti-cancer, anti-degenerative, immunosuppressive, and anti-microbial drugs or, vaccines. These heterocyclic derivatives can be used as an active agent in a pharmaceutical, as well as a diagnostic utility. To this end, several families of heterocyclic derivatives are provided including pyrrolopyrimidines, pyrazolopyrimidines, purines, and imidazopyridines. In particular, certain tri-substituted and tetra-substituted purines and pyrazolopyrimidines and their deaza analogues are provided for inhibiting cyclin-dependent kinase (“cdk”) proteins, viruses, and immunostimulation.

Abstract: The invention provides compounds having the following general formula (I): 1

Abstract: A glyoxal-guanosine-group compound is prepared either by reacting glyoxal-guanine with any one of ribose-1-phosphate and 2-deoxyribose-1-phosphate in the presence of purine nucleoside phosphorylase, or by reacting glyoxal-guanine with any one selected from the group consisting of uridine, 2′-deoxyuridine and thymidine, together with phosphate ion, in the presence of purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase. The glyoxal-guanosine-group compound is then decomposed by alkali, whereby a guanosine-group compound consisting of guanosine and 2′-deoxyguanosine is prepared.

Abstract: The present invention provides a method for synthesizing 1-(acyloxy)-alkyl derivatives from 1-acyl-alkyl derivatives, which typically proceeds stereospecifically, in high yield, does not require the use of activated intermediates and/or toxic compounds and is readily amenable to scale-up. The current invention also provides 1-acyl-alkyl derivatives of known drug compounds and methods for synthesizing these 1-acyl-alkyl derivatives.

Abstract: Compositions for oral administration of compounds having A2A adenosine receptor antagonist activity are provided. These compositions are useful for treatment of inflammatory conditions.

Abstract: Processes are disclosed for the preparation of either an N-acyl deoxyadenosine or an N-acyl deoxyguanosine by acylating the hydroxyl groups and the exocyclic amino group of a corresponding deoxyadenosine or deoxyguanosine with anhydride to form a 3′-, 5′-O-acyl, N-acyl deoxyneucloside and then selectively removing the acyl groups from the hydroxyl groups to form an N-acyl deoxyadenosine or N-acyl deoxyguanosine.

Abstract: A double-stranded cDNA molecule which includes DNA encoding human manganese superoxide dismutase has been created. The sequence of one strand of a double-stranded DNA molecule which encodes human manganese superoxide dismutase has been discovered. Such molecules may be introduced in procaryotic, e.g., bacterial, or eukaryotic, e.g., yeast or mammalian, cells and the resulting cells cultured or grown under suitable conditions so as to produce human manganese superoxide dismutase or analogs thereof which may then be recovered. By this invention, human MnSOD gene fragments from various plasmids may be ligated to yield a complete genomic human MnSOD gene fragment. Human MnSOD or analogs thereof may be used to catalyze the reduction of superoxide radicals, reduce reperfusion injury, prolong the survival time of isolated organs, or treat inflammations.

Abstract: A compound of formula (I), wherein R2 represents C1-3alkyl, halogen or hydrogen; R3 represents straight or branched alkyl group of 1-6 carbon atoms; with the proviso that, when R3 represents C1-3alkyl, R2 represents C1-3alkyl, R1 cannot represent phenyl optionally substituted by one or more substituents selected from halogen, C1-3alkyl, trifluoromethyl, nitro, cyano, —CO2Rc, —CONRcRd, —CORc, —SORe, —SO2Re, —SO3H, —SO2NRcRd, —ORc, —NHSO2Re, —NHCORc and —NRcRd; and salts and solvates thereof, in particular, physiologically acceptable solvates and salts thereof. These compounds are agonists at the Adenosine A1 receptor.

Abstract: N6 heterocyclic 5′ modified adenosine derivatives that are adenosine A1 receptor partial or full agonists, and as such, are useful for modifying cardiac activity, modifying adipocyte function, treating central nervous system disorders, and treating diabetic disorders and obesity in mammals, and especially in humans.

Abstract: Propargylethoxyamino nucleosides are disclosed having the structure 1

Abstract: Novel compounds are provided which are useful as linking groups in chemical synthesis, preferably in the solid phase synthesis of oligonucleotides and polypeptides. These compounds are generally photolabile and comprise protecting groups which can be removed by photolysis to unmask a reactive group.

Abstract: The present invention is directed to a method to produce 8-amino-2′deoxyadenosine by treating 8-azido-2′deoxyadenosine with an aqueous solution of methylamine or dimethylamine.

Abstract: The present invention provides improved ingress of therapeutic and other moieties into cellular targets. In accordance with preferred embodiments, complexes are provided which carry primary moieties, chiefly therapeutic moieties, to such target cells. Such complexes preferably feature cell surface receptor ligands to provide specificity. Such ligands are preferably bound to primary moieties through polyfunctional manifold compounds.

Abstract: The present invention provides for the preparation &bgr;-adenine nucleosides by coupling an adenine derivative containing an unprotected exocyclic amino group at the C-6 position and a blocked arabinofuranosyl derivative, in the presence of a base and solvent. The present invention also provides for the stereoselective preparation of 2-deoxy-&bgr;-D-adenine nucleosides wherein a blocked 2-deoxy-&agr;-D-arabinofuranosyl halide is coupled with the salt of an adenine derivative. The forgoing aspects of the present invention are utilized in the preparation of a clofarabine composition wherein the ratio of &bgr; to &agr;-anomer is at least 99:1.

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-&bgr;-L-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-&bgr;-L-nucleosides are disclosed, which can be administered either alone or in combination with other anti-hepatitis B agents, are also disclosed.

Abstract: Orthomolecular Sulpho-Adenosylmethionine derivative compounds, compositions, and their uses for effecting a biological activity in an animal, such as neurochemical activity; liver biology activity; heart and artery function; cartilage, bone and joint health; stomach and/or intestinal lining resistance to ulceration; immune function; cell membrane integrity; and pain and inflammation. The compounds of the present invention are further useful for preventing or treating diseases or conditions; treating viral infections, infectious diseases, leukemia, and obesity; and reducing the risk of Sudden Infant Death Syndrome in an animal.

Abstract: Disclosed are novel compounds that are A3 adenosine receptor agonists, useful for treating various disease states, including cancer, cardiac ischemia, leukopenia, and neutropennia.

Abstract: Modified nucleosides and methods of making and using the nucleosides are disclosed. The compounds can be prepared by reacting nucleoside starting materials that contain a suitable leaving group at one or more of the carbon atoms in the purine or pyrimidine ring, with a vinylstannane, carbon monoxide, and a palladium catalyst to provide 1-ene-3-one intermediates. These intermediates are then reacted with suitably functionalized primary or secondary amines via a Michael reaction. When the intermediate is a 5-position modified pyrimidine ring, and the amine contains a second hydrogen, it can do a second Michael reaction with the ene-one or the ene-imine in the pyrimidine ring. Appropriate modification of the amine reactant can yield products with various bioactivities. The nucleosides can be used therapeutically as anti-cancer, anti-bacterial or anti-viral drugs. The nucleosides can also be used for diagnostic applications, for example, by incorporating a radiolabel or fluorescent label into the molecule.

Abstract: Processes for the preparation of 3′,4′-cyclic acetals of pentopyranosylnucleosides, in which the pentopyranosyl nucleoside is reacted with an aldehyde, ketone, acetal, or ketal under reduced pressure of less than about 500 mbar.

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

Abstract: A3 agonists having Formula I are described herein as well as methods of using such A3 agonists and pharmaceutical compositions containing such A3 agonists.

Abstract: Disclosed are novel compounds that are partial and full A1 adenosine receptor agonists, useful for treating various disease states, in particular tachycardia and atrial flutter, angina, and myocardial infarction.

Abstract: Oligomers which have substituents on the 2′ position are resistant to oligonucleases and furthermore can be derivatized to deliver reagents or drugs, to carry label, or to provide other properties.

Abstract: Methods for selectively protecting the exocyclic amino function of a purine nucleoside are provided using activating agents to effect acylation at the exocyclic amino site. Methods are also provided for recycling polymer bound coupling supports from the reaction mixtures produced upon N-acylation.

Abstract: Certain known and novel pyruvate derivatives are particularly active in restoring or preserving metabolic integrity in oxidatively competent cells that have been subjected to oxygen deprivation. These pyruvate-derived compounds include, but are not limited to oximes, amides, pyruvate analogues, modified pyruvate analogues, esters of pyruvate (e.g., polyol-pyruvate esters, pyruvate thioesters, glycerol-pyruvate esters and dihydroxyacetone-pyruvate esters). Such pyruvate derivatives (including single tautomers, single stereoisomers and mixtures of tautomers and/or stereoisomers, and the pharmaceutically acceptable salts thereof) are useful in the manufacture of pharmaceutical compositions for treating a number of conditions characterized by oxidative stress.

Abstract: Orthomolecular Vitamin E derivative compounds, compositions, and their uses for effecting aging and longevity, nerve activity, hematopoiesis and maintenance of blood cells, hepatic activity, nephritic activity, heart and cardiovascular function, pulmonary function, muscular function, cartilage, bone, and joint health, gastrointestinal function, reproductive system function, vision, immune function, cell membrane integrity, and pain and inflammation; preventing or treating diseases or conditions; treating cancers or obesity; and reducing the risk of Sudden Infant Death Syndrome in an animal.

Abstract: A method for efficiently purifying 5′ protected 2′-deoxypurine nucleosides, efficient production of which has previously been difficult. Impurities can be separated by obtaining the 5′ protected 2′-deoxypurine nucleoside as an inclusion crystal including a solvent such as that having a nitrile structure in order to purify the 5′ protected 2′-deoxypurine nucleoside at a high purity. This invention enables synthesis of highly purified protected deoxypurine nucleosides easily on a large scale, which has previously been performed by column chromatography method.

Abstract: 2′-deoxy-2′-alkylnucleotides useful for stabilizing enzymatic nucleic acid molecules and antisense molecules.

Abstract: A compound of formula (I) which is an agonist at the adenosine Al receptor, wherein Y, Z, and W represent heteroatoms, and salts and solvates thereof, in particular, physiologically acceptable solvates and salts thereof for use in therapy.

Abstract: The present invention relates to isotopically enriched nucleic acids and methods for their production and purification. The invention further relates to methods for the use of said nucleic acids in analysis with mass spectrometry. Use of isotopically enriched nucleic acids in creating second generation products is also provided.

Abstract: The present invention includes a novel class of synthetic adenosine derivatives having clinically relevant and useful properties. These adenosine cyclic ketal compounds will be useful for treatment of a variety of conditions including, but not limited to, hypertension, vasodilation and ischemia.

Abstract: A compound of formula (I) which is an agonist at the adenosine A1 receptor wherein R2 represents C1-3alkyl, halogen or hydrogen; R3 represents a fluorinated straight or branched alkyl group of 1-6 carbon atoms and salts and solvates thereof, in particular, physiologically acceptable solvates and salts thereof. These compounds are agonists at the adenosine A1 receptor.

Abstract: The present invention provides methods for the chemical synthesis of nucleosides and derivatives thereof, including 2′-amino, 2′-N-phthaloyl, 2′-O-methyl, 2′-O-silyl, 2′OH nucleosides, C-nucleosides, nucleoside phosphoramidites, C-nucleoside phosphoramidites, and non-nucleoside derivatives.

Abstract: Method for the sterospecific preparation of 2′ or 3′ deoxy and 2′, 3′-dideoxy-&bgr;-L-pentofuranonucleoside compounds. 2′ or 3′ deoxy and 2′, 3′-dideoxy-&bgr;-L-pentofuranonucleoside compounds are also described. Finally, the invention concerns the use of these compounds, and particularly 2′, 3′ dideoxy-&bgr;-L-fluorocytidine, as drugs, and especially as anti-viral agents.

Abstract: Modified nucleosides and methods of making and using the nucleosides are disclosed. The compounds can be prepared by reacting nucleoside starting materials that contain a suitable leaving group at one or more of the carbon atoms in the purine or pyrimidine ring, with a vinylstannane, carbon monoxide, and a palladium catalyst to provide 1-ene-3-one intermediates. These intermediates are then reacted with suitably functionalized primary or secondary amines via a Michael reaction. When the intermediate is a 5-position modified pyrimidine ring, and the amine contains a second hydrogen, it can do a second Michael reaction with the ene-one or the ene-imine in the pyrimidine ring. Appropriate modification of the amine reactant can yield products with various bioactivities. The nucleosides can be used therapeutically as anti-cancer, anti-bacterial or anti-viral drugs. The nucleosides can also be used for diagnostic applications, for example, by incorporating a radiolabel or fluorescent label into the molecule.

Abstract: This invention relates to adenosine derivatives and analogues which possess biological activity and are useful as anti-hypertensive, cardioprotective, anti-ischemic, and antilipolytic agents, to pharmaceutical compositions including such compounds, and to their use in treating hypertension, myocardial ischemia, ameliorating ischemic injury and myocardial infarct size consequent to myocardial ischemia, and treating hyperlipidemia and hypercholesterolemia, and to methods and intermediates used in the preparation of such compounds.