Abstract: The present disclosure provides methods and pharmaceutical compositions for treating or slowing the progression of cancer, i.e., pancreatic cancer or esophageal cancer, by administering to a human subject in need thereof a therapeutically effective amount of an inhibitor of the histone methyltransferase, SETD2.

Abstract: K-Ras is the most frequently mutated oncogene in human cancer. Disclosed herein are compositions and methods for modulating K-Ras and treating cancer.

Abstract: K-Ras is the most frequently mutated oncogene in human cancer. Disclosed herein are compositions and methods for modulating K-Ras and treating cancer.

Abstract: The present invention relates to a slow-release solid oral nutraceutical and/or pharmaceutical composition comprising: a core containing a donor of methyl groups and at least one pharmaceutically acceptable excipient, and an outer coating containing shellac and/or a pharmaceutically acceptable salt thereof, magnesium stearate, and at least one pharmaceutically acceptable excipient. The coating of said solid oral composition allows the donor of methyl groups, preferably SAMe and/or a pharmaceutically acceptable salt thereof, to cross intact the gastric barrier and release the same in a continuous and complete manner along the entire digestive tract.

Abstract: The disclosure provides linked purine pterin compounds and analogs thereof that are novel HPPK inhibitors. The HPPK inhibitors described herein are compounds and the pharmaceutically acceptable salts thereof of general Formula I The variables, e.g. A1 to A3, R1 to R4, L1, L2, B1, and B2 are described herein. Compounds and salts of Formula I bind to HPPK with high affinity and specificity. Pharmaceutical compositions containing an HPPK inhibitor of Formula I and methods of treating a bacterial infection in a patient by providing one or more HPPK inhibitors of Formula I to the patient are also provided. Processes and intermediates useful for preparing compounds of Formula I are also provided. Methods of using the disclosed compounds to guide the development of additional novel anti-bacterial agents are also provided.

Abstract: The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.

Abstract: The present invention relates to compounds of formula (I): wherein Rj, R2, R3, R4, Xi, X2, X3 and Z are as defined in claim 1. The compounds are useful in the prevention and/or treatment of bacterial infections.

Abstract: Compounds having methyltransferase inhibitory activity are disclosed. The compounds have the structure and are useful in the treatment of cancer and similar diseases associated with inappropriate methyltransferase activity.

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: 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 2?-chloro nucleosides according to Formula 2001: or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein B, Z and PD are as described herein.

Abstract: The present disclosure relates to photoactivable protecting groups containing a diarylsulfide chromophore, a method for the synthesis thereof and their use as photoactivable protecting groups using maskless photolithography based array synthesis.

Abstract: Disclosed are O-protected compounds of the formula (I): wherein B is an optionally protected nucleobase, and R1-R3 are as described herein, a method of preparing such compounds, and a method of preparing oligonucleotides such as RNA starting from such compounds. The O-protected compounds have one or more advantages, for example, the 2?-O-protected compound is stable during the various reaction steps involved in oligonucleotide synthesis; the protecting group can be easily removed after the synthesis of the oligonucleotide, for example, by reaction with tetrabutylammonium fluoride; and/or the O-protected groups do not generate DNA/RNA alkylating side products, which have been reported during removal of 2?-O-(2-cyanoethyl)oxymethyl or 2?-O-[2-(4-tolylsulfonyl)ethoxymethyl groups under similar conditions.

Abstract: The present invention relates to substituted purine and 7-deazapurine compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Abstract: Many pathogens, including Mycobacterium tuberculosis and Yersinia pestis, rely on an iron acquisition system based on siderophores, secreted iron-chelating compounds with extremely high Fe(III) affinity. The compounds of the invention are inhibitors of domain salicylation enzymes, which catalyze the salicylation of an aroyl carrier protein (ArCP) domain to form a salicyl-ArCP domain thioester intermediate via a two-step reaction. The compounds include the intermediate mimic 5?-O—[N-(salicyl)sulfamoyl]-adenosine (salicyl-AMS) and analogs thereof. These compounds are inhibitors of the salicylate activity of MbtA, YbtE, PchD, and other domain salicylation enzymes involved in the biosynthesis of siderophores. Therefore, these compounds may be used in the treatment of infection caused by microorganisms which rely on siderphore-based iron acquisition systems.

Abstract: The invention relates to Purine Derivatives; compositions comprising an effective amount of a Purine Derivative; and methods for reducing an animal's rate of metabolism, protecting an animal's heart against myocardial damage during cardioplegia; or for treating or preventing a cardiovascular disease, a neurological disorder, an ischemic condition, a reperfusion injury, obesity, a wasting disease, or diabetes, comprising administering an effective amount of a Purine Derivative to an animal in need thereof.

Abstract: The present invention relates to compounds of formula (I): wherein Rj, R2, R3, R4, Xi, X2, X3 and Z are as defined in claim 1. The compounds are useful in the prevention and/or treatment of bacterial infections.

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: [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: The present invention provides therapeutic agents for preventing and treating neurodegenerative diseases. These agents synergistically target both the adenosine A2A receptor (A2AR) and the equilibrative nucleoside transporter 1 (ENT1).

Abstract: The present disclosure relates to photoactivable protecting groups containing a diarylsulfide chromophore, a method for the synthesis thereof and their use as photoactivable protecting groups using maskless photolithography based array synthesis.

Abstract: The present invention refers to new salts of S-adenosyknethionine (SAMe) with improved stability and containing at least 70% by weight of SAMe.

Abstract: The present invention relates to combinations of 5?-methylthioadenosine and glatiramer acetate, and to their use in the treatment of multiple sclerosis. In a particular embodiment, the present invention relates to a product comprising 5?-methylthioadenosine and glatiramer acetate as a combined preparation for the simultaneous, separate, or sequential use thereof for the prevention and/or treatment of multiple sclerosis.

Abstract: A nucleoside monomer that is protected by a thionocarbamate protecting group and contains one or more 2H, 13C, or 15N isotopes in the ribose and/or base part is provided, as well as a method for making a polynucleotide that uses the same. Also provided is a polynucleotide synthesis method that employs a diamine to deprotect a protected polynucleotide.

Abstract: Nucleotide monomers, polynucleotides, methods of making each, and methods of deprotecting each, are disclosed. An embodiment of the nucleotide monomer, among others, includes a nucleotide monomer having a heterobase protecting group selected from structures I through III as described herein. An embodiment of the polynucleotide, among others, includes a plurality of nucleotide moieties having a heterobase protecting group selected from one of structures I through III as described herein.

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: The invention provides methods and compositions for reducing or inhibiting bone resorption, osteoclast differentiation and stimulation and the loosening of medical prostheses by administering a compound or agent that modulates an adenosine receptor such as the adenosine A2A receptor, in particular, an agonist of an adenosine A2A receptor. The invention also extends to pharmaceutical compositions comprising such an agent that modulates an adenosine receptor such as an adenosine A2A agonist and to prosthetic devices containing such an agent that modulates an adenosine receptor such as an A2A agonist on one or more surfaces or within the prosthetic device such as, for example, suspended in the cement forming the prosthetic device.

Abstract: The invention relates to Purine Derivatives; compositions comprising an effective amount of a Purine Derivative; and methods for reducing an animal's rate of metabolism, protecting an animal's heart against myocardial damage during cardioplegia; or for treating or preventing a cardiovascular disease, a neurological disorder, an ischemic condition, a reperfusion injury, obesity, a wasting disease, or diabetes, comprising administering an effective amount of a Purine Derivative to an animal in need thereof.

Abstract: The present invention provides a therapeutic method for treating an inflammatory response caused by a sickle cell crisis, comprising administration of an effective amount of an A2A adenosine receptor agonist. Optionally, the method includes administration of a type IV PDE inhibitor (e.g., rolipram).

Abstract: A compound of formula (A) or salt thereof: wherein each of R1, R2, and R3 independently represents hydrogen, alkyl, aryl, acyl, sulfonyl, or silyl; P represents hydrogen or a hydroxy protective group. This compound may be used an intermediate for making a 2-deoxy-2,2-difluoro-D-ribofuranosyl nucleosides, such as gemcitabine.

Abstract: Disclosed are conjugates comprising a dendrimer and a ligand, which is a functionalized congener of an agonist or antagonist of a receptor of the G-protein coupled receptor (GPCR) superfamily, for example, wherein the functionalized congener is an A1 adenosine receptor agonist having a purine nucleoside moiety and a functional group at the N6 position of the purine nucleoside moiety, wherein the functional group has the formula (I): N6H—Ar1—CH2—C(?O)NH—R1 (I), wherein Ar1 and R1 as defined herein. Also disclosed are pharmaceutical compositions, methods of treating various diseases, and a diagnostic method employing such conjugates.

Abstract: The present invention for the stereoselective preparation of 2-deoxy-?-D-adenine nucleosides wherein a blocked 2-deoxy-?-D-arabinofuranosyl halide is coupled with the salt of an adenine derivative.

Abstract: The present invention provides hepatoprotectant acetaminophen mutual prodrugs, which have an acetaminophen moiety covalently linked to a second moiety that may act as a hepatoprotectant against acetaminophen hepatotoxicity. Additionally, acetaminophen mutual prodrugs may have improved water solubility which may provide better suitability for parenteral and other dosage forms relative to administration of acetaminophen. Also provided are methods of treating a disease or condition that is responsive to acetaminophen (such as fever, pain and ischemic injury) using hepatoprotectant acetaminophen mutual prodrugs, as well as kits and unit dosages.

Abstract: The present invention for the stereoselective preparation of 2-deoxy-?-D-adenine nucleosides wherein a blocked 2-deoxy-?-D-arabinofuranosyl halide is coupled with the salt of an adenine derivative.

Abstract: This invention is directed to a method of preventing or treating diseases or conditions associated with platelet aggregation. The method is also directed to a method of treating thrombosis or related disorders. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a non-nucleotide compound, preferably a P2Y12 receptor antagonist compound, wherein said amount is effective to inhibit platelet aggregation. The compounds useful for this invention include compounds of general Formulae I and III-XII, or salts, hydrates, and solvates thereof. The present invention also provides novel compounds of Formulae I and III-XII.

Abstract: Provided are methods of designing a putative inhibitor of a 5?-methylthioadenosine/S-adenosylhomocysteine nucleosidase. The methods comprise designing a chemically stable compound that resembles the charge and geometry of the 5?-methylthioadenosine/S-adenosylhomocysteine nucleosidase transition state. Also provided are methods of inhibiting 5?-methylthioadenosine/S-adenosylhomocysteine nucleosidases using the inhibitors found by the above methods.

Abstract: Disclosed are structurally modified, metabolically stable nucleosides having antitumor activity wherein the formation of toxic metabolites is blocked and antimicrobial activity. The disclosure further relates to pharmaceutical compositions comprising one or more disclosed modified nucleosides and to methods of use thereof.

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: Provided are polymorphs of an A1 adenosine receptor partial agonist, compositions thereof, methods for their preparation, and methods for their uses.

Abstract: The crystal structure of the complex of S-adenosylmethionine methyl ester with h?doMetDC F223A, a mutant where the stacking of the aromatic rings of F7, adenine and F223 would be eliminated. The structure of this mutant with the ester shows that the ligand still maintains a syn conformation aided by pi-pi interactions to F7, hydrogen bonds to the backbone of Glu67, and electrostatic interactions. Several series of AdoMet substrate analogues with a variety of substituents at the 8 position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. To understand these results, virtual modeling of the enzyme inhibitor complexes and the crystal structures of human AdoMetDC with 5?-deoxy-5?-[N-methyl-N-[2-(aminooxy)ethyl]amino-8-methyl]adenosine (MAOEMA) and 5?-deoxy-5?-[N-methyl-N-[4-(aminooxy)butyl]amino-8-ethyl]adenosine (MAOBEA) at the active site have been determined experimentally.

Abstract: The invention relates to novel adenyl dinucleotides which are isomers of the dinucleotide Ap2A, having formulae (I) and (II). The dinucleotides of the invention have antitumour activity, particularly against tumours of haematological origin, such as for example leukaemias and lymphomas. The invention further relates to the use of such dinucleotides as antitumour medicaments. Finally, the invention relates to an enzymatic method for preparing the dinucleotides of formulae (I) and (II) and to an enzymatic assay method for the dinucleotide of formula (I) which is based on its complete conversion to NAD+.

Abstract: 5?-methylthioadenosine (MTA), its pharmaceutically acceptable salts and/or prodrugs may be used in the prevention and/or treatment of autoimmune diseases, such as, for example, Multiple Sclerosis (MS), as well as in the prevention and/or treatment of transplant rejection.

Abstract: The present invention provides an 8-modified purinenucleoside derivative which is useful for diseases associated with an abnormality of plasma uric acid level. An 8-modified purinenucleoside derivative represented by the following formula (I), a prodrug thereof or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, is useful for the prevention or treatment of gout, hyperuricemia, urinary lithiasis, hyperuricemic nephropathy or the like. In the formula, n is 1 or 2; RA is a hydrogen atom or a hydroxyl group; R1 is a hydrogen atom, a hydroxyl group, a thiol group, an amino group or a chlorine atom; ring J represents an optionally substituted 2-naphthyl group, or a group represented by the following general formula (II) wherein Y represents a single bond or a connecting group; ring Z represents an optionally substituted aryl group or heteroaryl group or the like; and R2 to R4, P1 and Q represents a halogen atom, a cyano group or the like.

Abstract: Injuries to the central nervous system, particularly spinal cord injuries, are treated by administering a purine nucleoside or analog to the patient and, optionally, electrically stimulating the site of injury.

Abstract: The invention provides compounds having the following general formula (I): wherein X, R1, R2, R7 and Z are as described here.

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. The structure of the compounds is given by Formula (I): wherein R1, R2, R3, R4, R5, X, Y, Z, and T are as described herein.

Abstract: The invention provides compounds having the following general formula (I): wherein X, R1, R2, R7 and Z are as described herein.

Abstract: This invention is directed to compounds of Formulae III and V, useful for treating diseases or conditions associated with platelet aggregation.

Abstract: Many pathogens, including Mycobacterium tuberculosis and Yersinia pestis, rely on an iron acquisition system based on siderophores, secreted iron-chelating compounds with extremely high Fe(III) affinity. The compounds of the invention are inhibitors of domain salicylation enzymes, which catalyze the salicylation of an aroyl carrier protein (ArCP) domain to form a salicyl-ArCP domain thioester intermediate via a two-step reaction. The compounds include the intermediate mimic 5?-O—[N-(salicyl)sulfamoyl]-adenosine (salicyl-AMS) and analogs thereof. These compounds are inhibitors of the salicylate activity of MbtA, YbtE, PchD, and other domain salicylation enzymes involved in the biosynthesis of siderophores. Therefore, these compounds may be used in the treatment of infection caused by microorganisms which rely on siderphore-based iron acquisition systems.

Abstract: 2-adenosine C-pyrazole compounds having formula (a) and methods for using the compounds as A2A receptor agonists to stimulate mammalian coronary vasodilatation for therapeutic purposes and for purposes of imaging the heart.

Abstract: Compounds of formula (XXIII), or pharmaceutically acceptable salts or esters thereof, are inhibitors of reverse transcriptase: R4 is a nucleoside with Q substituting a 3? hydroxyl group, and Q is a moiety of formulas (XXIV)-(XXXII):