N-glycosides Wherein The N Is Part Of A Six-membered Hetero Ring (e.g., Diazines, Etc.) Patents (Class 536/28.1)
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Patent number: 11426398Abstract: Compositions containing a combination of nicotinamide riboside and pterostilbene for treating skin disorders, and methods of treating skin disorders using these compositions and their equivalents are described. The skin disorders that are treated using these compositions or methods include sun exposure-related skin disorders, inflammatory skin disorders, autoimmune disease-related skin disorders and cancer-related skin disorders. In one embodiment, the compositions containing a combination of nicotinamide riboside and pterostilbene are prepared as oral formulations.Type: GrantFiled: February 25, 2016Date of Patent: August 30, 2022Assignee: Elysium Health, Inc.Inventors: Eric A. Marcotulli, Daniel A. Alminana, Paul M. Bowen
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Patent number: 11103525Abstract: The invention relates to compounds that are useful in the treatment of parkinsonism, such as parkinsonism in connection with Parkinson's disease (PD); dementia with Lewy bodies (DLB); multiple system atrophy (MSA); corticobasal degeneration (CBD); or progressive supranuclear palsy (PSP). The said compounds include in particular idoxuridine and analogs thereof as well as their metabolic precursors, such as ropidoxuridine. The invention further relates to method for identifying compounds useful for the treatment of parkinsonism, said methods comprising detecting the capability of compound to increase the amount of GPR37 in cell membranes. The invention further relates to methods for the chemical synthesis of ropidoxuridine.Type: GrantFiled: February 6, 2018Date of Patent: August 31, 2021Inventors: Per Svenningsson, Lina Leinartaite, Magdalena Otrocka, Vedran Hasimbegovic, Birgitta Pettersson
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Patent number: 11072624Abstract: Disclosed are nucleoside 5?-triphosphates modified at the ?, (?, and/or ? phosphate to substitute one or more of the phosphate oxygen atoms with a borano, seleno, and/or thio group. Derivatives and pharmaceutically acceptable salts are also contemplated herein. Also disclosed are processes for preparing nucleoside 5?-triphosphates. Non-limiting, exemplary processes can include first reacting salicyl phosphorochloridite with a pyrophosphate reagent to provide P2, P3-dioxo-P1-(salicyl) cyclotriphosphite, and then reacting P2, P3-dioxo-P1-(salicyl) cyclotriphosphite with a nucleoside, followed by oxidation of the nucleoside-phosphite intermediate and hydrolysis to form the modified nucleoside 5?-triphosphate. Nucleoside 5?-triphosphates can be useful in nucleic acid replication, transcription, and translation.Type: GrantFiled: August 19, 2011Date of Patent: July 27, 2021Assignee: SENA RESEARCH, INCORPORATEDInventor: Zhen Huang
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Patent number: 11033568Abstract: Compositions containing nicotinamide riboside (NR) are provided. NR containing compositions are used in the care or treatment of skin and skin conditions. In some embodiments, the invention relates to pharmaceutical compositions and cosmetic compositions containing nicotinamide riboside. In further embodiments, the invention relates to methods of using nicotinamide riboside to promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival. A method of treating signs or symptoms of aging or skin wrinkles in an individual is provided, comprising topically administering to the individual in need of such treatment an effective amount of the compound nicotinamide riboside, or salts thereof.Type: GrantFiled: June 3, 2020Date of Patent: June 15, 2021Assignee: ChromaDex Inc.Inventors: Ann Deren-Lewis, Troy Rhonemus
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Patent number: 10688118Abstract: Compositions containing nicotinamide riboside (NR) are provided. NR containing compositions are used in the care or treatment of skin and skin conditions. In some embodiments, the invention relates to pharmaceutical compositions and cosmetic compositions containing nicotinamide riboside. In further embodiments, the invention relates to methods of using nicotinamide riboside to promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival. A method of treating signs or symptoms of aging or skin wrinkles in an individual is provided, comprising topically administering to the individual in need of such treatment an effective amount of the compound nicotinamide riboside, or salts thereof.Type: GrantFiled: October 30, 2014Date of Patent: June 23, 2020Assignee: ChromaDex Inc.Inventors: Ann Deren-Lewis, Troy Rhonemus
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Patent number: 10280190Abstract: Derivatives of nicotinic acid riboside (NAR), nicotinamide riboside (NR), and reduced NAR and NR, including 1-(2?,3?,5?-triacetyl-beta-D-ribofuranosyl)-1,4-dihydronicotinic acid (4a), and compositions containing the same and/or reduced derivative forms of nicotinamide riboside including 1-(2?,3?,5?-triacetyl-beta-D-ribofuranosyl)-1,4-nicotinamide (2), are provided for use in the care of treatment of skin and skin conditions. In some embodiments, the invention relates to pharmaceutical compositions and cosmetic compositions containing one or more NR, NAR, NRH, or NARH derivatives, or prodrugs or salts thereof. In further embodiments, the invention relates to methods of using one or more NR, NAR, NRH, or NARH derivatives, or prodrugs, solvates, or salts thereof, to promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival and overall cell and tissue health.Type: GrantFiled: March 16, 2016Date of Patent: May 7, 2019Assignees: ChromaDex, Inc., The Queen's University of BelfastInventors: Ryan Dellinger, Marie Eugenie Migaud, Philip Redpath, Troy Rhonemus, Richard Cunningham
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Patent number: 9029346Abstract: Methods and compounds are disclosed for irreversibly inhibiting a DNA repair enzyme that possesses lyase activity.Type: GrantFiled: December 13, 2013Date of Patent: May 12, 2015Assignee: The Johns Hopkins UniversityInventors: Marc M. Greenberg, Dumitru Arian, Theodore L. Deweese, Mohammad Hedayati
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Patent number: 9029335Abstract: Provided herein are novel bicyclic nucleosides, oligomeric compounds that include such bicyclic nucleosides and methods of using the oligomeric compounds. More particularly, the novel bicyclic nucleosides comprise a furanose ring system having a bridge comprising a 4?-methylene group attached to a 2?-sulfoxide or sulfone group and optionally including one or more substituent groups attached to the 4?-methylene and or the 5?-position. In certain embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.Type: GrantFiled: October 9, 2013Date of Patent: May 12, 2015Assignee: Isis Pharmaceuticals, Inc.Inventors: Thazha P. Prakash, Eric E. Swayze
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Patent number: 9012428Abstract: This invention relates to a stereochemically pure uracyl spirooxetane nucleoside phosphoramidate useful in the treatment of patients infected with the hepatitis C virus (HCV).Type: GrantFiled: November 10, 2011Date of Patent: April 21, 2015Assignees: Janssen Products, LP, Medivir ABInventors: Tim Hugo Maria Jonckers, Pierre Jean-Marie Bernard Raboisson, Koen Vandyck, Steven Maurice Paula Van Hoof, Lili Hu, Abdellah Tahri
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Patent number: 9000147Abstract: The invention relates to compositions of nicotinoyl ribosides and nicotinamide riboside derivatives and their methods of use. In some embodiments, the invention relates to methods of making nicotinoyl ribosides. In some embodiments, the invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinoyl riboside. In further embodiments, the invention relates to methods of using nicotinoyl ribosides and nicotinamide riboside derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival.Type: GrantFiled: January 17, 2012Date of Patent: April 7, 2015Assignee: Cornell UniversityInventors: Anthony A. Sauve, Tianle Yang Redanz
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Patent number: 8957201Abstract: A method for the prevention or treatment in a mammal of a disease preventable or treatable by the pharmacologically useful antisense or antigene activity of an oligonucleotide analogue or a pharmacologically acceptable salt thereof in the body of said mammal, which method comprises administering to said mammal in need of such prevention or treatment a pharmaceutically effective amount of an oligonucleotide analogue comprising two or more nucleoside units, wherein at least one of said nucleoside units is a structure of the formula (2): wherein A is methylene; and B is an unsubstituted purin-9-yl, an unsubstituted 2-oxo-pyrimidin-1-yl or a substituted purin-9-yl; or a pharmacologically acceptable salt thereof.Type: GrantFiled: July 22, 2010Date of Patent: February 17, 2015Assignee: Daiichi Sankyo Company, LimitedInventors: Masakatsu Kaneko, Koji Morita, Takeshi Imanishi
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Patent number: 8916536Abstract: The present invention relates to novel bisphosphonate duplex drugs, methods for preparing said compound; pharmaceutical compositions containing the same; as well as the use of said compounds in human and veterinary medicine, and, in particular, for treating tumors, viral infections; or dental disorders.Type: GrantFiled: August 3, 2011Date of Patent: December 23, 2014Inventor: Herbert Schott
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Patent number: 8916538Abstract: The present application relates to solid state forms, for example, crystalline forms of 2?-C-methyluridine-5?-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl)thiophosphoramidate, pharmaceutical compositions that can include one or more solid forms of 2?-C-methyluridine-5?-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl)thiophosphoramidate, and methods of treating or ameliorating diseases and/or conditions with one or more solid forms of 2?-C-methyluridine-5?-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl)thiophosphoramidate. Also disclosed herein are methods of treating diseases and/or conditions with one or more solid forms of 2?-C-methyluridine-5?-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl)thiophosphoramidate in combination with one or more other agents.Type: GrantFiled: March 11, 2013Date of Patent: December 23, 2014Assignee: Vertex Pharmaceuticals IncorporatedInventors: Anuj K. Kuldipkumar, Ales Medek, Lori Ann Ferris, Praveen Mudunuri, Young Chun Jung, David Richard Willcox, Michael Waldo, William Aloysius Nugent
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Patent number: 8846637Abstract: Provided herein are 2?-amino and 2?-thio bicyclic nucleosides and oligomenc compounds prepared therefrom. The novel bicyclic nucleosides provided herein are expected to be useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as nuclease resistance.Type: GrantFiled: June 2, 2011Date of Patent: September 30, 2014Assignee: Isis Pharmaceuticals, Inc.Inventors: Punit P. Seth, Thazha P. Prakash, Eric E. Swayze
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Patent number: 8815830Abstract: The invention provides a compound of formula (I), wherein R1-R6 and X have any of the values described, as well as pharmaceutical compositions comprising such compounds and therapeutic methods comprising the administration of such compounds.Type: GrantFiled: March 28, 2014Date of Patent: August 26, 2014Assignee: Regents of the University of MinnesotaInventor: Carston R. Wagner
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Patent number: 8791081Abstract: A method of treating a neoplastic disease in a subject includes administering to neoplastic cells of the subject an MGMT inhibitor and at least one of an antimitotic agent or a DNA damaging agent.Type: GrantFiled: February 29, 2008Date of Patent: July 29, 2014Assignee: Case Western Reserve UniversityInventors: Lili Liu, Stanton Gerson
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Patent number: 8691789Abstract: 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.Type: GrantFiled: December 10, 2012Date of Patent: April 8, 2014Assignee: Institute of Nuclear Energy Research, Atomic Energy CouncilInventors: Jenn-Tzong Chen, Ho-Lien Huang, Jia-Rong Chen, Chung-Shan Yu, Wen-Chin Su, Ching-Shiuann Yang, Wuu-Jyh Lin
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Patent number: 8637475Abstract: 2? and/or 3? prodrugs of 1?, 2?, 3? or 4?-branchednucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions.Type: GrantFiled: June 24, 2011Date of Patent: January 28, 2014Assignees: Idenix Pharmaceuticals, Inc., University of Cagliari, The Centre National de la Recherché Scientifique, L'Universite Montpelier IIInventors: Richard Storer, Gilles Gosselin, Jean-Pierre Sommadossi
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Patent number: 8637486Abstract: 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.Type: GrantFiled: March 13, 2009Date of Patent: January 28, 2014Assignee: Retrotope, Inc.Inventor: Mikhail S. Shchepinov
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Patent number: 8618075Abstract: The present invention provides certain tetrahydrouridine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of making and using such compounds.Type: GrantFiled: July 24, 2012Date of Patent: December 31, 2013Assignee: Eisai Inc.Inventors: Gregory S. Hamilton, Takashi Tsukamoto, Dana V. Ferraris, Bridget Duvall, Rena Lapidus
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Patent number: 8603999Abstract: 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.Type: GrantFiled: December 4, 2009Date of Patent: December 10, 2013Assignee: Commonwealth Scientific and Industrial Research OrganisationInventors: Calum John Drummond, Sharon Marie Sagnella, Minoo Jalili Moghaddam, Xiaojuan Gong
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Patent number: 8552021Abstract: Compounds of formula I: including any possible stereoisomers thereof, wherein: R1 is hydrogen, —C(?O)R6 or —C(?O)CHR7—NH2; R2 is hydrogen; or C1-C6alkyl or phenyl, either of which is optionally substituted with 1, 2 or 3 substituents each independently selected from halo, C1-C6alkyl, C2-C6-alkenyl and C1-C6alkoxy, hydroxy or amino, or R2 is naphtyl; or R2 is indolyl, R3 is hydrogen, C1-C6alkyl, benzyl; R4 is hydrogen, C1-C6alkyl, benzyl; or R3 and R4 together with the carbon atom to which they are attached form C3-C7cycloalkyl; R5 is C1-C10alkyl, C3-C7-cycloalkyl, benzyl, or phenyl, any of which being optionally substituted with 1, 2 or 3 substituents each independently selected from hydroxy, C1-C6alkoxy, amino, mono- and diC1-C6alkylamino; R6 is C1-C6 alkyl; R7 is C1-C6 alkyl; R8 is hydrogen or halogen; or a pharmaceutically acceptable salt or solvate thereof are useful in the prophylaxis or treatment of HCV infections.Type: GrantFiled: September 29, 2010Date of Patent: October 8, 2013Assignees: Janssen Products, L.P., Medivir ABInventors: Tim Hugo Maria Jonckers, Pierre Jean-Marie Bernard Raboisson, Koen Vandyck, Michael Pelcman, Bengt Christian Sund, Horst Jurgen Wahling, Pedro Manuel Passos Pinho, Anna Winqvist, Karl Magnus Nilsson
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Patent number: 8541562Abstract: It is an object of the present invention to provide a novel molecule for antisense therapies which is not susceptible to nuclease degradation in vivo and has a high binding affinity and specificity for the target mRNAs and which can efficiently regulate expression of specific genes. The novel artificial nucleoside of the present invention has an amide bond introduced into a bridge structure of 2?,4?-BNA/LNA. The oligonucleotide containing the 2?,4?-bridged artificial nucleotide has a binding affinity for a single-stranded RNA comparable to known 2?,4?-BNA/LNA and has an increased nuclease resistance over LNA. Particularly, it is expected to be applied to nucleic acid drugs because of its much stronger binding affinity for single-stranded RNAs than S-oligo's affinity.Type: GrantFiled: October 19, 2010Date of Patent: September 24, 2013Assignee: Osaka UniversityInventors: Satoshi Obika, Yoshiyuki Hari, Tetsuya Kodama, Aiko Yahara, Masaru Nishida
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Patent number: 8518908Abstract: 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.Type: GrantFiled: March 9, 2012Date of Patent: August 27, 2013Assignee: University of IdahoInventors: Patrick J. Hrdlicka, Pawan Kumar, Michael E. Østergaard
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Publication number: 20130203975Abstract: The present invention provides a compound of formula I; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.Type: ApplicationFiled: April 12, 2012Publication date: August 8, 2013Applicant: NOVARTIS AGInventors: Gregory Raymond Bebernitz, Mark Gary Bock
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Patent number: 8492537Abstract: The invention relates to special nucleosides, for example, a nucleoside of the formula I, wherein R1-R5 are as described herein, and also to drugs which contain these nucleosides. Furthermore, the invention relates to the use of such nucleosides in a method for suppressing or reducing the formation of resistance in the case of cytotstatic treatment of a cancer patient.Type: GrantFiled: August 13, 2007Date of Patent: July 23, 2013Assignee: RESprotect GmbHInventors: Rudolf Fahrig, Dieter Lohmann, Andreas Rolfs, Henrik Dieks, Janek Teubner, Jorg-Christian Heinrich
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Patent number: 8492362Abstract: The present invention relates to prodrug forms of ?-L-1-[5-(E-2-Bromovinyl)-2-(hydroxymethyl)-1,3-dioxolan-4-yl)]uracil (L-BHDU) and their use to treat viral infections of Varicella Zoster Virus, including recurrent VZV (shingles), especially including drug resistant Varicella Zoster Virus and related complications of this viral infection such as rash or post-herpetic neuralgia.Type: GrantFiled: November 8, 2011Date of Patent: July 23, 2013Assignee: University of Georgia Research Foundation, Inc.Inventor: Chung K. Chu
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Patent number: 8481510Abstract: Compounds of the formula I: including any possible stereoisomers thereof, wherein: R4 is a monophosphate, diphosphate or triphosphate ester; or R4 is R7 is optionally substituted phenyl, optionally substituted naphthyl, or optionally substituted indolyl; R8 and R8? are hydrogen, C1-C6alkyl, benzyl, or phenyl; or R8 and R8? form C3-C7cycloalkyl; R9 is C1-C10alkyl, C3-C7cycloalkyl, phenyl or phenyl-C1-C6alkyl, wherein the phenyl moiety in phenyl or phenyl-C1-C6alkyl is optionally substituted; or a pharmaceutically acceptable salt or solvate thereof; pharmaceutical formulations and the use of compounds I as HCV inhibitors.Type: GrantFiled: May 11, 2010Date of Patent: July 9, 2013Assignees: Janssen Products, LP, Medivir ABInventors: Tim Hugo Maria Jonckers, Pierre Jean-Marie Raboisson, Koen Vandyck, Steven Maurice Van Hoof, Lili Hu, Abdellah Tahri
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Patent number: 8399429Abstract: 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.Type: GrantFiled: December 8, 2009Date of Patent: March 19, 2013Assignees: Janssen Products, LP, Medivir ABInventors: Tim Hugo Maria Jonckers, Pierre Jean-Marie Bernard Raboisson, Steven Maurice Paula Van Hoof, Leen Anna Maria Vandekerckhove, Koen Vandyck
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Patent number: 8399420Abstract: The present invention is directed toward compounds of Formula (I) as follows: wherein, R is H, R5C(O), R5CH2OC(O), or R5CH2NHC(O); R1 is where the crossing dashed line illustrates the bond formed joining R1 to the molecule of Formula (I); R2 and R3 are independently OH or H, provided that R2 and R3 are not simultaneously OH; R4 is H, R5C(O), R5CH2OC(O), or R5CH2NHC(O), provided that R and R4 are not simultaneously H; and R5 has the general formula: CH3—(CH2)n—(CH?CH—CH2)m—CH?CH—(CH2)k—; k is an integer from 0 to 7; m is an integer from 0 to 2; and n is an integer from 0 to 10, or a pharmaceutical salt thereof. Methods of making and using these compounds are also disclosed.Type: GrantFiled: September 25, 2008Date of Patent: March 19, 2013Assignees: Mount Sanai School of Medicine, Clavis Pharma ASAInventors: Lewis Silverman, James Holland, Marit Liland Sandvold, Finn Myhren, Ole Henrik Eriksen
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Publication number: 20130059384Abstract: Compositions and methods comprising bioenergetic agents for restoring the quality of aged oocytes, enhancing oogonial stem cells or improving derivatives thereof (e.g., cytoplasm or isolated mitochondria) for use in fertility-enhancing procedures, are described.Type: ApplicationFiled: April 13, 2012Publication date: March 7, 2013Applicants: PRESIDENT AND FELLOWS OF HARVARD COLLEGE, THE GENERAL HOSPITAL CORPORATIONInventors: JONATHAN L. TILLY, DAVID A. SINCLAIR
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Patent number: 8389703Abstract: This invention relates to nucleoside, nucleotide, and oligonucleotide analogs that incorporate non-standard nucleobase analogs, defined to be those that present a pattern of hydrogen bonds to a paired nucleobase analog in a complementary strand that is different from the pattern presented by adenine, guanine, cytosine, and thymine. The invention is specifically concerned with nucleotide analogs that present the donor-donor-acceptor, hydrogen bonding patterns on pyrimidine analogs, and especially those that are analogs of ribonucleotides, including protected ribonucleotides suitable for phosphoramidite-based synthesis of RNA. The heterocycles on these nucleoside analogs are aminopyridones that have electron withdrawing groups attached to the position analogous to the 5-position of the ring in standard pyrimidines, including nitro, cyano, and carboxylic acid derivatives.Type: GrantFiled: November 2, 2011Date of Patent: March 5, 2013Inventors: Steven A. Benner, Hyo-Joong Kim
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Patent number: 8377905Abstract: Disclosed is a stable crystal of 1-(2?-cyano-2?-deoxy-?-D-arabinofuranosyl)cytosine monohydrochloride. There is provided a crystal of 1-(2?-cyano-2?-deoxy-?-D-arabinofuranosyl)cytosine monohydrochloride having characteristic peaks at 13.7°, 15.7°, 16.0°, 18.6°, 20.3°, and 22.7° as diffraction angles (2?±0.1°) measured by powder X-ray diffraction, and having a melting point of 192° C. to 197° C.Type: GrantFiled: May 14, 2010Date of Patent: February 19, 2013Assignee: Delta-Fly Pharma, Inc.Inventors: Shotaro Watanabe, Takahiro Hatakeyama
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Patent number: 8354524Abstract: The present invention provides selenium derivatives of nucleosides, nucleoside phosphoramidites, nucleotides, nucleotide triphosphates, oligonucleotides, polynucleotides, and larger nucleic acids and methods for their synthesis. Selenium derivatives of both ribonucleic acids and deoxyribonucleic acids, as well as methods for their synthesis, crystallization and uses in structural determinations, particularly by X-ray crystallographic techniques are disclosed. The selenium derivatives of the present invention are also useful as food supplements.Type: GrantFiled: June 29, 2011Date of Patent: January 15, 2013Assignee: Georgia State University Research Foundation, Inc.Inventor: Zhen Huang
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Publication number: 20130005675Abstract: The present invention provides a quinolone compound that inhibits the chronic progression of Parkinson's disease or protects dopamine neurons from disease etiology, thereby suppressing the progression of neurological dysfunction, so as to prolong the period of time until L-dopa is administered while also improving neuronal function; the quinolone compound of the invention is represented by Formula (1): wherein: R1 represents hydrogen or the like; R2 represents hydrogen or the like; R3 represents substituted or unsubstituted phenyl or the like; R4 represents halogen or the like; R5 represents hydrogen or the like; R6 represents hydrogen or the like; and R7 represents hydrogen or the like.Type: ApplicationFiled: September 14, 2012Publication date: January 3, 2013Applicant: OTSUKA PHARMACEUTICAL CO., LTD.Inventors: Kenji OTSUBO, Takahito YAMAUCHI, Yuji OCHI
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Patent number: 8329664Abstract: A compound for use in the treatment or prophylaxis of viral infections such, for example as chicken pox or shingles caused by the Varicella Zoster virus, said compound having the general formula (II): wherein X is O, S, NH or CH2, Y is O, S or NH, Z is O, S or CH2, R1 is C1-6 alkyl, preferably n-alkyl, e.g., n-pentyl or n-hexyl, and one of R2 and R3 is OH, and the other of R3 and R2 is a neutral, non-polar amino acid moiety, or a pharmaceutically acceptable salt or hydrate thereof. Said neutral, non-polar amino acid moiety R2 or R3 may be (IV): in which R4, R5, R6 and R7 are each independently H or C1-2 alkyl. In preferred embodiments, one of R2 or R3 is valine, leucine, isoleucine or alanine, particularly valine.Type: GrantFiled: May 9, 2007Date of Patent: December 11, 2012Assignees: University College Cardiff Consultants Limited, K.U. Leuven Research and DevelopmentInventors: Christopher McGuigan, Jan Balzarini, Marco Migliore
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Patent number: 8268800Abstract: The present invention provides certain tetrahydrouridine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of making and using such compounds.Type: GrantFiled: October 16, 2008Date of Patent: September 18, 2012Assignee: Eisai Inc.Inventors: Gregory S. Hamilton, Takashi Tsukamoto, Dana V. Ferraris, Bridget Duvall, Rena Lapidus
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Patent number: 8227431Abstract: The present patent application relates to the novel nucleoside derivatives and novel intermediates, which are useful to antiviral, anti tumor and immunomodulatory activity, method of treating diseases, conditions and/or disorders modulated by viral infections with them, and processes for preparing them.Type: GrantFiled: March 12, 2009Date of Patent: July 24, 2012Assignee: Hetero Drugs LimitedInventors: Bandi Parthasaradhi Reddy, Vedula Manohar Sharma, Kura Rathnakar Reddy, Musku Madhanmohan Reddy, Jennepalli Sreenu, Aryasomayajula Ratnakar
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Publication number: 20120172584Abstract: The invention relates to compositions of nicotinoyl ribosides and nicotinamide riboside derivatives and their methods of use. In some embodiments, the invention relates to methods of making nicotinoyl ribosides. In some embodiments, the invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinoyl riboside. In further embodiments, the invention relates to methods of using nicotinoyl ribosides and nicotinamide riboside derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival.Type: ApplicationFiled: January 17, 2012Publication date: July 5, 2012Applicant: CORNELL UNIVERSITYInventors: Anthony Andrew SAUVE, Tianle YANG
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Patent number: 8202984Abstract: A compound of the formula: wherein Ring A and Ring B are: (1) Ring A is an optionally substituted unsaturated monocyclic heterocyclic ring, and Ring B is an optionally substituted unsaturated monocyclic heterocyclic ring, an optionally substituted unsaturated fused heterobicyclic ring, or an optionally substituted benzene ring, (2) Ring A is an optionally substituted benzene ring, and Ring B is an optionally substituted unsaturated monocyclic heterocyclic ring or an optionally substituted unsaturated fused heterobicyclic ring, or (3) Ring A is an optionally substituted unsaturated fused heterobicyclic ring, and Ring B are independently an optionally substituted unsaturated monocyclic heterocyclic ring, an optionally substituted unsaturated fused heterobicyclic ring, or an optionally substituted benzene ring; X is a carbon atom or a nitrogen atom; Y is —(CH2)n— (n is 1 or 2); or a pharmaceutically acceptable salt thereof, or a prodrug thereof.Type: GrantFiled: January 13, 2011Date of Patent: June 19, 2012Assignee: Mitsubishi Tanabe Pharma CorporationInventors: Sumihiro Nomura, Eiji Kawanishi, Kiichiro Ueta
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Patent number: 8193338Abstract: A di(pyrimidine nucleoside 5?-)polyphosphate is synthesized by converting a pyrimidine nucleoside 5?-triphosphate into a pyrimidine nucleoside 5?-cyclic triphosphate by use of a condensing agent, and subsequently reacting the pyrimidine nucleoside 5?-cyclic triphosphate with a pyrimidine nucleotide in the presence of a salt of a metal selected from among magnesium, manganese, and iron. Through the method of the invention, a di(pyrimidine nucleoside 5?-)polyphosphate can be synthesized from an unprotected pyrimidine nucleoside 5?-phosphate serving as a starting material at a synthesis yield of 50% or higher. Therefore, the method of the invention is suitable for large-scale synthesis of a di(pyrimidine nucleoside 5?-)polyphosphate.Type: GrantFiled: July 25, 2007Date of Patent: June 5, 2012Assignee: Yamasa CorporationInventors: Satoru Kogo, Kohei Yamada, Yuko Iwai, Kazuomi Osawa, Hiroyuki Hayakawa
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Patent number: 8183216Abstract: A class of nucleoside derivatives of formula (I), as defined herein, that are useful as inhibitors of RNA-dependent RNA viral replication and in particular HCV replication, are provided. Also provided are processes for the synthesis and use of such compounds for treating or preventing HCV infection. formula (I).Type: GrantFiled: September 16, 2008Date of Patent: May 22, 2012Assignee: Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.p.A.Inventors: Maria Emilia Di Francesco, Vincenzo Summa, Gabriella Dessole
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Patent number: 8173620Abstract: The disclosure encompasses caged compounds such as caged nucleoside phosphoesters (caged nucleotides). In an embodiment, the caged nucleotides include compounds corresponding to those described by formula (I) that may be activated by two-photon excitation, and methods of synthesis of such compounds. 8-Bromo-7-hydroxyquinoline-caged ATP was synthesized and examined for its photochemistry as a biologically useful, temporally and spatially controlled ATP-releasing reagent. The combination of two-photon excitation hydrolysis and activation of caged ATP enables methods for finely focusing ATP activation at the sub-cellular level or to a greater depth of activation, thereby providing improved resolution of ATP-dependent processes at the cellular level.Type: GrantFiled: August 20, 2009Date of Patent: May 8, 2012Assignee: University of Georgia Research Foundation, Inc.Inventors: Timothy M. Dore, Yue Zhu, Khalilah G. Reddie, James D. Lauderdale
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Publication number: 20120108535Abstract: Disclosed are halogenated 2-deoxy-lactone, 2?-deoxy-nucleosides, and derivatives thereof, for example, a compound of formula (I). Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one compound or salt of the invention, and a method of treating a disorder is selected from the group consisting of an abnormal cellular proliferation, a viral infection, and an autoimmune disorder.Type: ApplicationFiled: July 1, 2010Publication date: May 3, 2012Applicant: CORNELL UNIVERSITYInventors: Anthony A. Sauve, Yana Cen
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Patent number: 8163707Abstract: The present invention discloses compounds of formula (I), or its ?-L enantiomer, or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, prodrug, or combination thereof: which inhibit, preventing or treating abnormal cellular proliferation and/or a viral infection, particularly by HIV, HCV or HBV. Consequently, the compounds of the present invention interfere with the replication cycle of a virus and are also useful as antiviral agents, or interfere with host cellular biochemical process and are also useful as antiproliferative agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from viral infection and/or cell proliferation. The invention also relates to methods of treating a viral infection and/or cell proliferation in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.Type: GrantFiled: September 11, 2009Date of Patent: April 24, 2012Assignee: Enanta Pharmaceuticals, Inc.Inventors: Yao-Ling Qiu, Ce Wang, Xiaowen Peng, Lu Ying, Yat Sun Or
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Patent number: 8158779Abstract: 4-Amino-1-((2R,3S,4S,5R)-5-azido-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydrofuran-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.Type: GrantFiled: March 28, 2011Date of Patent: April 17, 2012Assignee: Medivir ABInventors: Nils-Gunnar Johansson, Genaidy Kalyanov, Joseph Armstrong Martin, David Bernard Smith, Anna Winqvist
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Patent number: 8158605Abstract: The present invention is directed toward compounds of Formula (I) as follows: wherein, R is H, R5C(O); R1 is where the crossing dashed line illustrates the bond formed joining R1 to the molecule of Formula (I); R2 and R3 are independently OH or H, provided that R2 and R3 are not simultaneously OH; R4 is H or R5C(O), provided that R and R4 are not simultaneously H; and R5 is a C3-C26 alkenyl, or a pharmaceutical salt thereof. Methods of making and using these compounds are also disclosed.Type: GrantFiled: September 25, 2008Date of Patent: April 17, 2012Assignee: Mount Sinai School of MedicineInventors: Lewis Silverman, James Holland
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Patent number: 8106184Abstract: The invention relates to compositions of nicotinoyl ribosides and nicotinamide riboside derivatives and their methods of use. In some embodiments, the invention relates to methods of making nicotinoyl ribosides. In some embodiments, the invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinoyl riboside. In further embodiments, the invention relates to methods of using nicotinoyl ribosides and nicotinamide riboside derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival.Type: GrantFiled: November 17, 2006Date of Patent: January 31, 2012Assignee: Cornell UniversityInventors: Anthony Andrew Sauve, Tianle Yang
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Patent number: 8058261Abstract: To provide a compound which exhibits excellent anti-tumor activity and excellent oral absorption and which is a useful anti-tumor drug. The invention provides a 3?-ethynylcytidine derivative represented by formula (1): (wherein X represents a (substituted) alkylcarbonyl group, a (substituted) alkoxycarbonyl group, or a hydrogen atom; one of Y and Z represents a hydrogen atom or a group represented by (R1)(R2)(R3)Si— and the other represents a group represented by (R4)(R5)(R6)Si—; and R1, R2, R3, R4, R5, and R6 each represent a (substituted) alkyl group, a (substituted) cyclic alkyl group, or a (substituted) aryl group) or a salt thereof.Type: GrantFiled: July 23, 2007Date of Patent: November 15, 2011Assignees: Taiho Pharmaceutical Co., Ltd.Inventors: Motoaki Tanaka, Masakazu Fukushima
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Patent number: 8053212Abstract: This invention relates to nucleoside, nucleotide, and oligonucleotide analogs that incorporate non-standard nucleobase analogs, defined to be those that present a pattern of hydrogen bonds to a paired nucleobase analog in a complementary strand that is different from the pattern presented by adenine, guanine, cytosine, and thymine. The invention is specifically concerned with compositions of matter that present the donor-donor-acceptor, donor-acceptor-donor, and acceptor-donor-donor non-standard hydrogen bonding patterns on pyrimidine analogs, where nucleoside analogs bearing these pyrimidine analogs do not epimerize as easily as those known in the art. The heterocycles on these nucleoside analogs are diaminopyridines and aminopyridones that have electron withdrawing groups attached to the position analogous to the 5-position of the ring in standard pyrimidines, including nitro, cyano, and carboxylic acid derivatives.Type: GrantFiled: March 9, 2006Date of Patent: November 8, 2011Inventor: Steven Albert Benner