Nitrogen, Other Than Nitro Or Nitroso, Bonded Directly To The 4-position, And Chalcogen Bonded Directly To The 2-position Of The Diazine Ring (e.g., Cytidines, Etc.) Patents (Class 536/28.5)
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Patent number: 7645745Abstract: Compounds having the formula I wherein R1 is as herein defined are Hepatitis C virus NS5b polymerase inhibitors.Type: GrantFiled: April 4, 2007Date of Patent: January 12, 2010Assignee: Roche Palo Alto LLCInventor: Keshab Sarma
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Publication number: 20090326214Abstract: The present application provides several crystalline forms of gemcitabine base and methods of making the same.Type: ApplicationFiled: June 12, 2009Publication date: December 31, 2009Inventors: Shu-Ping Chen, Chia-Lin Charlene Shieh
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Publication number: 20090318556Abstract: Disclosed herein are biomarkers for determining gamma radiation exposure by an animal or human. The biomarkers include 3-hydroxy-2-methylbenzoic acid 3-O-sulfate, N-hexanoylglycine, ?-thymidine, taurine, xanthine, xanthosine, 2?-deoxyuridine, 2?-deoxycytidine, 2?-deoxyxanthosine, or any salt, ion, or combination thereof. Also disclosed are methods for determining gamma radiation exposure by an animal or human, which include the step of measuring the amount of one or more biomarkers specific to gamma radiation in the biological fluid and correlating the amount of said biomarkers to the amount of gamma radiation exposure by the animal or human. Systems for determining gamma radiation exposure by an animal or human and methods of treating an animal or human for gamma radiation exposure are also disclosed.Type: ApplicationFiled: May 15, 2008Publication date: December 24, 2009Inventors: Jeffrey R. Idle, Frank J. Gonzalez, John B. Tyburski, Kristopher W. Krausz, Andrew David Patterson
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Publication number: 20090318380Abstract: Embodiments of the invention are to compounds, methods, and compositions for use in the treatment of viral infections. More specifically embodiments of the invention are 2?,4?-substituted nucleoside compounds useful for the treatment of viral infections, such as HIV, HCV, and HBV infections.Type: ApplicationFiled: November 14, 2008Publication date: December 24, 2009Applicant: PHARMASSET, INC.Inventors: MICHAEL JOSEPH SOFIA, JINFA DU
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Patent number: 7632940Abstract: The invention relates to a novel process for the preparation of 4?-azido-cytidine (I) or a pharmaceutically accepted salt thereof. The compound of formula I is useful for treating virus mediated diseases, particularly for treating HCV mediated diseases.Type: GrantFiled: December 7, 2007Date of Patent: December 15, 2009Assignee: Roche Palo Alto LLCInventors: Peter John Harrington, Stefan Hildbrand, Keshab Sarma
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Publication number: 20090306008Abstract: 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: ApplicationFiled: July 23, 2007Publication date: December 10, 2009Applicants: TAIHO PHARMACEUTICAL CO., LTDInventors: Motoaki Tanaka, Masakazu Fukushima
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Patent number: 7629447Abstract: The invention provides a 5?-amino-2?-fluoro-2?,5?-dideoxynucleoside compound represented by the formula [1]: wherein R1 represents a nucleic acid base which may have a protecting group; R2 represents a hydrogen atom or an amino protecting group; and R3 represents a hydrogen atom or a hydroxyl protecting group. The invention also provides a dideoxynucleoside-insoluble carrier bound substance and an oligonucleotide analogue involving the dideoxynucleoside compound.Type: GrantFiled: February 26, 2007Date of Patent: December 8, 2009Assignee: Wako Pure Chemical Industries, Ltd.Inventors: Yukio Kitade, Yoshihito Ueno
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Publication number: 20090281300Abstract: [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.Type: ApplicationFiled: November 1, 2007Publication date: November 12, 2009Inventors: Keiichiro Yamamoto, Kazutoshi Takashio
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Publication number: 20090258931Abstract: The present invention relates to novel chimeric oligomeric compounds having a plurality of alternating regions having either RNA like having northern or 3?-endo conformational geometry (3?-endo regions) or DNA like having southern or C2?-endo/O4?-endo conformational geometry. The oligomeric compounds of the present invention have shown reduction in mRNA levels in multiple in vitro and in vivo assay systems and are useful, for example, for investigative and therapeutic purposes.Type: ApplicationFiled: February 19, 2009Publication date: October 15, 2009Applicant: ISIS PHARMACEUTICALS, INC.Inventors: Brett P. Monia, Madeline M. Butler, Robert McKay, Brenda F. Baker
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Patent number: 7601702Abstract: Deoxyuridine derivatives of Formula (I?); where A is O, S or CH2; B is O, S or CHR3; R1 is H, or various substituents; R2 is H, F; R3 is H, F, OH, NH2; or R2 and R3 together form a chemical bond; D is —NHCO—, —CONH—, —O—, —C(?O)—, —CH?CH, —C?C—, —NR5—; R4 is hydrogen or various substituents; R5 is H, C1-C4 alkyl, C1-C4 alkanoyl; E is Si or C; R6, R7 and R8 are independently selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, or a stable monocyclic, bicyclic or tricyclic ring system have utility in the prophylaxis of treatment of parasitic diseases such as malaria.Type: GrantFiled: January 6, 2005Date of Patent: October 13, 2009Assignee: Medivir ABInventors: Ian Gilbert, Corinne Nguyen, Gian Filippo Ruda, Alessandro Schipani, Ganasan Kasinathan, Nils-Gunnar Johansson, Dolores Gonzalez Pacanowska
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Patent number: 7595390Abstract: An industrially scalable two-step process for preparing a ?-L-2?-deoxy-nucleoside that results in a predominance of the ?- over the ?-anomeric form of the compound is described. An optional third step may be used to prepare 3?-prodrugs of desirable ?-L-2?-deoxy-nucleosides for the delivery of these pharmaceuticals effective for treating viral diseases. The synthetic process is applicable in particular to the formation of ?-L-2?-deoxy-cytidine, a pharmaceutically acceptable salt or prodrug thereof. The process can provide a relatively uncontaminated product that may require no further isolation or purification, thereby making the synthesis easily scalable for industrial manufacture.Type: GrantFiled: April 28, 2004Date of Patent: September 29, 2009Assignee: Novartis AGInventors: Adel Moussa, Jing Yang Wang, Richard Storer
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Patent number: 7589077Abstract: Disclosed are nucleosides which are useful in diagnosing and treating viral infections, for example, infections caused by hepatitis B virus (HBV), and herpes viruses including Epstein Barr virus.Type: GrantFiled: May 17, 2002Date of Patent: September 15, 2009Inventors: Rakesh Kumar, Babita Agrawal, D. Lorne J. Tyrrell
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Patent number: 7589078Abstract: The present invention relates to compounds according to the general formula: wherein B is or and the remaining variables are defined in the specification, and compositions comprising the compounds. The compounds are useful as anti-viral agents in viral therapy.Type: GrantFiled: February 18, 2004Date of Patent: September 15, 2009Assignee: Yale UniversityInventors: Yung-chi Cheng, Hiromichi Tanaka, Masanori Baba
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Patent number: 7585851Abstract: The present invention relates to compounds, compositions and methods for the treatment of a host infected with a hepatitis B virus. Specifically, compound and compositions of 3?-esters of 2?-deoxy-?-L-pyrimidine nucleosides are disclosed, which can be administered either alone or in combination with other anti-hepatitis B agents. Compound and compositions of 3?,5?-diesters of 2?-deoxy-?-L-pyrimidine nucleosides are also disclosed, which can be administered either alone or in combination with other anti-hepatitis B agents.Type: GrantFiled: October 25, 2004Date of Patent: September 8, 2009Assignees: Idenix Pharmaceuticals, Inc., Centre National de la Recherche Scientifique, L'Universite Montpellier IIInventors: Martin L. Bryant, Gilles Gosselin, Jean-Louis Imbach
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Publication number: 20090221811Abstract: The present invention provides processes for preparing intermediates useful in the preparation of gemcitabine and other nucleosides, and processes for preparing gemcitabine therewith. Exemplary intermediates include mixtures of D-erythro and D-threo isomers of 3-(hydroxy)-2,2-difluoro-3-(2,2-dimethyldioxolan-4-yl)-propionic acid salts. Also provided is a process for selectively isolating the D-erythro and D-threo isomers of D-erythro and D-threo isomers of 3-(hydroxy)-2,2-difluoro-3-(2,2-dimethyldioxolan-4-yl)-propionic acid salts, and processes for using such isomers in the preparation of nucleoside analogs such as, e.g., gemcitabine, intermediates thereof, and analogs thereof.Type: ApplicationFiled: April 27, 2009Publication date: September 3, 2009Applicant: CHEMAGIS LTD.Inventors: Vladimir NADDAKA, Eyal KLOPFER, Shady SAEED, Dionne MONTVILISKY, Oded ARAD, Joseph KASPI
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Publication number: 20090209479Abstract: Aspects of the invention include 2? protected nucleoside monomers that are protected at the 2? site with thiocarbon protecting groups. Thiocarbon protecting groups of interest include thiocarbonate, thionocarbonate, dithiocarbonate groups, as well as thionocarbamate protecting groups. Aspects of the invention further include nucleic acids that include the protecting groups of the invention, as well as methods of synthesizing nucleic acids using the protecting groups of the invention.Type: ApplicationFiled: May 9, 2008Publication date: August 20, 2009Inventors: Douglas J. Dellinger, Agnieszka Sierzchala, John Turner, Joel Myerson, Zoltan Kupihar, Fernando Ferreira, Marvin H. Caruthers
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Publication number: 20090203640Abstract: The present invention relates to novel crystal forms of an amide prodrug of gemcitabine, compositions thereof and methods for using.Type: ApplicationFiled: June 20, 2007Publication date: August 13, 2009Inventor: Alexandr Yevgenyevich Oblezov
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Publication number: 20090197825Abstract: Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of 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.Type: ApplicationFiled: November 26, 2008Publication date: August 6, 2009Applicant: ARDEA BIOSCIENCES, INC.Inventors: Barry D. QUART, Jean-Luc GIRARDET, Esmir GUNIC, Li-Tain YEH
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Patent number: 7544794Abstract: This invention relates to the field of nucleic acid chemistry, more specifically to the field of compositions and processes that are nucleic acid analogs. More specifically, this invention relates to compositions that allow the sequencing of oligonucleotides by synthesis, and processes for sequencing by synthesis that exploit these compositions. Most specifically, the instant invention discloses compositions of matter that are 5?-triphosphates of ribo- and 2?-deoxyribonucleosides wherein the 3?-OH group is replaced by a 3?-ONHR group in the alpha configuration, wherein R is either a H or CH3 group. Also disclosed are these triphosphates where the nucleobase carries, via a linker, a reporter groups, such as a fluorescent species that can be used in single- or multi-copy DNA sequencing, or a tag that can be visualized by ultramicroscopy. Also disclosed are processes that use these compositions to do sequencing by synthesis.Type: GrantFiled: March 11, 2006Date of Patent: June 9, 2009Inventor: Steven Albert Benner
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Publication number: 20090105186Abstract: The invention relates to ?-L-N4-hydroxycytosine nucleo-sides, pharmaceutical agents comprising same, and to the use of said ?-L-N4-hydroxycytosine nucleosides and pharmaceutical agents in the prophylaxis or therapy of an infection caused by hepatitis B virus (HBV) or human immunodeficiency virus (HIV). The invention also relates to a method for the preparation of said ?-L-nucleoside analogs.Type: ApplicationFiled: October 21, 2005Publication date: April 23, 2009Applicant: MAX-DELBRUECK-CENTRUM FUER MOLEKULARE MEDIZINInventors: Eckart Matthes, Martin von Janta-Lipinski, Hans Will, Huseyin Sirma, Anneke Funk
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Publication number: 20090099126Abstract: The present invention provides ribonucleoside 2?,3?-cyclic acetals of structural formula I which are precursors or prodrugs of inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors of inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as pre-cursors or prodrugs of inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors or prodrugs of inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such ribonucleoside 2?,3?-cyclic acetals alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection.Type: ApplicationFiled: August 4, 2006Publication date: April 16, 2009Inventors: Gabor Butora, Kenneth Alan Koeplinger, Malcolm MacCoss, Daniel R. McMasters, David B. Olsen, Lihu Yang
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Publication number: 20090068751Abstract: Dibenzorhodamine compounds having the structure are disclosed, including nitrogen- and aryl-substituted forms thereof. In addition, two intermediates useful for synthesizing such compounds are disclosed, a first intermediate having the structure including nitrogen- and aryl-substituted forms thereof, and a second intermediate having the structure including nitrogen- and aryl-substituted forms thereof, wherein substituents at positions C-14 to C18 taken separately are selected from the group consisting of hydrogen, chlorine, fluorine, lower alkyl, carboxylic acid, sulfonic acid, —CH2OH, alkoxy, phenoxy, linking group, and substituted forms thereof. The invention further includes energy transfer dyes comprising the dibenzorhodamine compounds, nucleosides labeled with the dibenzorhodamine compounds, and nucleic acid analysis methods employing the dibenzorhodamine compounds.Type: ApplicationFiled: July 8, 2008Publication date: March 12, 2009Applicant: Applied Biosystems Inc.Inventors: Scott C. BENSON, Joe Y.L. Lam, Steven Michael Menchen
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Patent number: 7485717Abstract: Orthogonally protected 3?-amino nucleoside monomers and efficient methods for their synthesis are described. The methods employ selective protection of the 3?-amino group in the presence of the unprotected nucleoside base.Type: GrantFiled: June 30, 2005Date of Patent: February 3, 2009Assignee: Geron CorporationInventors: Sergei M. Gryaznov, Krisztina Pongracz, Daria Zielinska
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Patent number: 7456155Abstract: The 3?-L-valine ester of ?-D-2?-C-methyl-ribofuranosyl cytidine provides superior results against flaviviruses and pestiviruses, including hepatitis C virus. Based on this discovery, compounds, compositions, methods and uses are provided for the treatment of flaviviridae, including HCV, that include the administration of an effective amount of val-mCyd or its salt, ester, prodrug or derivative, optionally in a pharmaceutically acceptable carrier. In an alternative embodiment, val-mCyd is used to treat any virus that replicates through an RNA-dependent RNA polymerase.Type: GrantFiled: June 27, 2003Date of Patent: November 25, 2008Assignees: Idenix Pharmaceuticals, Inc., Universita Degli Studi Di Cagliari, Centre National de la Recherche ScientifiqueInventors: Jean-Pierre Sommadossi, Paolo LaColla, Gilles Gosselin
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Publication number: 20080262215Abstract: Provided is a process for preparing gemcitabine or a salt thereof, which preferably includes selectively precipitating the ?-anomer of a 3?,5?-di-O-protected-N4-trimethylsilyl-2?-deoxy-2?,2?-difluorocytidine, removing the protecting groups to produce gemcitabine, and, optionally, converting the gemcitabine into a salt. Preferably, the 3? and 5? protecting groups are the same or different, and at least one of the 3? and 5? protecting groups is cinnamoyl, naphthoyl, naphthylmethylcarbonyl, 2-methylbenzylcarbonyl, 4-methylbenzylcarbonyl or 9-fluorenylmethyloxycarbonyl. Also provided are methods for enriching the ?-anomer from an anomeric mixture of a 3?,5?-di-O-protected-N4-trimethylsilyl-2?-deoxy-2?,2?-difluorocytidine, e.g., a N4-trimethylsilyl-2?-deoxy-2?,2?-difluoro-cytidine-3?,5?-diester, e.g., 3?,5?-dicinnamoyl-N4-trimethylsilyl-2?-deoxy-2?,2?-difluorocytidine, using a slurrying process, and methods for converting the ?-anomer-enriched product into gemcitabine or a salt thereof.Type: ApplicationFiled: April 23, 2007Publication date: October 23, 2008Applicant: Chemagis Ltd.Inventors: Lior ZELIKOVITCH, Oded FRIEDMAN, Tamir FIZITZKY, Josef MANASCU
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Patent number: 7427679Abstract: Precursors for use in the synthesis of polynucleotides are disclosed. The precursors include a heterocyclic base having an exocyclic amine group and a substituted or unsubstituted triaryl methyl protecting group bound to the exocyclic amine group.Type: GrantFiled: August 30, 2003Date of Patent: September 23, 2008Assignee: Agilent Technologies, Inc.Inventors: Douglas J. Dellinger, Agnieszka B. Sierzchala, Marvin H. Caruthers
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Publication number: 20080193452Abstract: The present invention is directed to new therapeutic compounds isolated from spider venom and methods of using these new compounds. The compounds are sulfated nucleoside derivatives including ribonucleoside mono- and disulfates derived from guanine, adenosine, and cytidine. Some of these compounds are glycosylated or fucosylated bearing one or more sugar residues.Type: ApplicationFiled: July 21, 2005Publication date: August 14, 2008Applicant: Cornell Research Foundation, Inc.Inventors: Jerrold Meinwald, Andrew Edmund Taggi, Frank Clemens Schroeder
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Publication number: 20080161550Abstract: The invention relates to a novel process for the preparation of 4?-azido-cytidine (I) or a pharmaceutically accepted salt thereof. The compound of formula I is useful for treating virus mediated diseases, particularly for treating HCV mediated diseases.Type: ApplicationFiled: December 7, 2007Publication date: July 3, 2008Inventors: Peter John Harrington, Stefan Hildbrand, Keshab Sarma
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Publication number: 20080152621Abstract: 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.Type: ApplicationFiled: October 10, 2007Publication date: June 26, 2008Inventors: Nils-Gunnar Johansson, Genadiy Kalyanov, Joseph Armstrong Martin, David Bernard Smith, Anna Winqvist
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Publication number: 20080139802Abstract: The present process provides an improved method for converting 2?-deoxy-2?-fluoro-2?-methyl-D-ribonolactones derivatives to 3-fluoro-3-methyl-2-chlorofuran compounds which are useful for the synthesis of nucleosides and improved processes for the synthesis of the D-ribonolactone compounds.Type: ApplicationFiled: October 10, 2007Publication date: June 12, 2008Inventors: Steven D. Axt, Byoung-Kwon Chun, Qingwu Jin, Suguna Rachakonda, Bruce Ross, Keshab Sarma, Justin Vitale, Jiang Zhu
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Patent number: 7385050Abstract: Functionalized supports for polynucleotide synthesis are disclosed. The supports have linker moieties that are stable to conditions used in polynucleotide synthesis, but may be cleaved to release synthesized polynucleotides from the support. Methods of making the functionalized supports and methods of using are also disclosed.Type: GrantFiled: August 30, 2003Date of Patent: June 10, 2008Assignee: Agilent Technologies, Inc.Inventors: Douglas J Dellinger, Geraldine F Dellinger, Marvin H Caruthers
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Patent number: 7378402Abstract: 4-Amino-1-((2R,3S,4S,5R)-5-azido-3,4-dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one (I:R1=R2=R3=R4=H) 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: August 22, 2005Date of Patent: May 27, 2008Assignee: Roche Palo Alto LLCInventors: Joseph Armstrong Martin, Keshab Sarma, David Bernard Smith, Mark Smith
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Publication number: 20080103110Abstract: The invention provides a water-soluble prodrug compound comprising a therapeutically effective moiety coupled via a metabolically cleavable bond to a protein binding moiety, wherein said therapeutically effective moiety has an anticancer, antiinflammatory, antiinfective or antipain effect, said protein binding moiety binds non-covalently to blood proteins, and the protein binding of said compound is at least 100% higher than that of the therapeutically effective moiety itself, with the exclusion of (i) the monoester of gemcitabine with azelaic acid, (ii) the monoester of dideoxycytidine with 1,12-dodecanedicarboxylic acid, (iii) 2-amino-1,9-dihydro-9(2?-(1-(10-acetyl-decanoyloxy)ethoxymethyl))-guanine, (iv) 5?-cytarabine monoester with 1,4-phenylene diacetic acid, (v) the monoester of metronidazole with 1,4-butanedicarboxylic acid, and (vi) the monoester of metronidazole with 1,6-phenylene diacetic acid; and pre-prodrugs metabolizable thereto.Type: ApplicationFiled: September 15, 2005Publication date: May 1, 2008Applicant: DRUG DISCOVERY LABORATORY ASInventors: Jo Klaveness, Bjarne Brudeli
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Publication number: 20070249823Abstract: The present invention provides novel intermediates, which preferably include 3-substituted, alkyl 2,2-difluoro-3-hydroxy-3-(2,2-dialkyldioxolan-4-yl)-propionate derivatives, and 3,5-disubstituted-2-deoxy-2,2-difluoro-1-oxo-D-ribose derivatives. The present invention also provides processes for producing such intermediates and processes for producing gemcitabine therewith.Type: ApplicationFiled: April 6, 2007Publication date: October 25, 2007Applicant: Chemagis Ltd.Inventors: Vladimir Naddaka, Eyal Klopfer, Shady Saeed, Dionne Montvilisky, Oded Arad, Joseph Kaspi
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Patent number: 7276228Abstract: Methods are provided for treating hematological disorders by inhibition of DNA hypomethylation and histone deacetylase. Such disorders include, for example, acute promyelocytic leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, myelodysplastic syndromes, and sickle cell anemia. The methods comprise: administering to a patient suffering from the disease a therapeutically effective amount of a DNA methylation inhibitor such as a cysteine analog such as decitabine, in combination with an effective amount of histone deacetylase inhibitor such as hydroxamic acid, cyclic peptide, benzamide, butyrate, and depudecin.Type: GrantFiled: March 15, 2005Date of Patent: October 2, 2007Assignee: SuperGen, Inc.Inventor: Jorge F. DiMartino
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Patent number: 7271258Abstract: The invention provides methods for synthesizing oligonucleotides using nucleoside monomers having carbonate protected hydroxyl groups that are deprotected with ?-effect nucleophiles. The ?-effect nucleophile irreversibly cleave the carbonate protecting groups while simultaneously oxidizing the internucleotide phosphite triester linkage to a phosphodiester linkage. The procedure may be carried out in aqueous solution at neutral to mildly basic pH. The method eliminates the need for separate deprotection and oxidation steps, and, since the use of acid to remove protecting groups is unnecessary, acid-induced depurination is avoided. Fluorescent or other readily detectable carbonate protecting groups can be used, enabling monitoring of individual reaction steps during oligonucleotide synthesis. The invention is particularly useful in the highly parallel, microscale synthesis of oligonucleotides.Type: GrantFiled: June 15, 2006Date of Patent: September 18, 2007Assignee: Agilent Technologies, Inc.Inventors: Douglas J. Dollinger, Marvin H. Caruthers, Jason R. Betley
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Patent number: 7247621Abstract: Pharmaceutical compositions comprise a nucleotide analog with a phosphonate group at a concentration effective to act as a substrate and/or inhibitor of a viral polymerase, and especially of the HCV RNA dependent RNA polymerase.Type: GrantFiled: April 29, 2003Date of Patent: July 24, 2007Assignee: Valeant Research & DevelopmentInventors: Zhi Hong, Yung-hyo Koh, Jae Hoon Shim, Jean-Luc Girardet
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Patent number: 7235647Abstract: The present invention provides a highly stereoselective, simple and economical glycosylation process for preparation of ?-anomer enriched 21-deoxy-21,21-D-ribofuranosyl difluoronucleosides of formula (II), and physiologically acceptable slats thereof, in particular, the ?-enriched anomer of gemcitabine hydrochloride of formula (IIb) in purity of >99% is provided through utilization of a novel trichloroacetimidate of formula (I).Type: GrantFiled: January 13, 2006Date of Patent: June 26, 2007Assignee: Dabur Pharma LimitedInventors: Golak Chandra Maikap, Deependra Bhatt, Bijan Kumar Panda
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Patent number: 7148207Abstract: This invention relates to a quick-release tablet formulation with >99.19% pure fludara (high-purity fludara) as an active ingredient in a defined composition of residual contaminants.Type: GrantFiled: December 20, 2002Date of Patent: December 12, 2006Assignee: Schering AktiengesellschaftInventors: Wolfgang Heil, Ulf Tistam, Ralph Lipp, Johannes-Wilhelm Tack
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Patent number: 7145000Abstract: What is described are compounds wherein R represents Br, I or R1—SO3, where R1 is an unsubstituted or substituted C1–C5-alkyl group, or an unsubstituted or substituted phenyl group; X is O or NR?, where R? is a usual protective group for N; and R? represents hydrogen, a halogen, such as F, Cl, and Br, a substituted or unsubstituted C1–C7-alkyl group, such as methyl and ethyl, a substituted or unsubstituted C2–C7-alkenyl group, or a substituted or unsubstituted C2–C7-alkynyl group.Type: GrantFiled: August 21, 2002Date of Patent: December 5, 2006Assignee: Deutsches Krebsforschungszentrum Stiftung des Offentlichen RechtsInventors: Joseph Antonius Maria Eisenbarth, Stefan Johannes Martin, Ulrike Wagner-Utermann, Michael Eisenhut
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Patent number: 7132409Abstract: 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.Type: GrantFiled: January 11, 2005Date of Patent: November 7, 2006Assignees: Toa Eiyo Ltd., Yamasa CorporationInventors: Takashi Konno, Kazuhiro Uemoto, Shinya Onuma, Yoshikazu Kato
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Patent number: 7105499Abstract: The present invention provides nucleoside derivatives which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside derivatives alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside derivatives of the present invention.Type: GrantFiled: January 18, 2002Date of Patent: September 12, 2006Assignees: Merck & Co., Inc., Isis Pharmaceuticals, Inc.Inventors: Steven S. Carroll, David B. Olsen, Malcolm MacCoss, Balkrishen Bhat, Phillip Dan Cook, Anne B. Eldrup, Thazha P. Prakash
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Patent number: 7105498Abstract: The invention relates to compositions comprising acyl derivatives of cytidine and uridine. The invention also relates to methods of treating hepatopathies, diabetes, heart disease, cerebrovascular disorders, Parkinson's disease, infant respiratory distress syndrome and for enhancement of phospholipid biosynthesis comprising administering the acyl derivatives of the invention to an animal.Type: GrantFiled: September 28, 2001Date of Patent: September 12, 2006Assignee: Wellstat Therapeutics CorporationInventors: Reid Warren von Borstel, Michael Kevin Bamat
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Patent number: 7038038Abstract: The present invention provides a method for the preparation of 5-azacytidine, wherein 5-azacytidine is represented by the structure: The method involves the silylation of 5-azacytosine, followed by the coupling of silylated 5-azacytosine to a protected ?-D-ribofuranose derivative. The coupling reaction is catalyzed by trimethylsilyl trifluoromethanesulfonate (TMS-Triflate).Type: GrantFiled: March 17, 2003Date of Patent: May 2, 2006Assignee: Pharmion CorporationInventors: Dumitru Ionescu, Peter Blumbergs
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Patent number: 7005425Abstract: Methods are provided for treating arrhythmia in a manner that minimizes undesirable side effects, comprising administration of a therapeutically effective minimal dose of an A1 adenosine receptor agonist with a therapeutically effective minimal dose of a beta blocker, calcium channel blocker, or a cardiac glycoside.Type: GrantFiled: April 18, 2003Date of Patent: February 28, 2006Assignee: CV Therapeutics, Inc.Inventors: Luiz Belardinelli, Arvinder Dhalla
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Patent number: 6992072Abstract: The invention relates to the use of active ingredients, which increase the concentration of pyrimidine-based elements for nucleic acid biosynthesis in the body, in particular to the use of pyrimidine nucleosides and/or prodrugs produced therefrom, for reducing the side-effects of inhibitors of nucleic acid biosynthesis or their precursors, in particular by activating the biosynthesis of mitochondrial DNA (mtDNA). The invention also relates to the use of said active ingredients, in particular pyrimidine nucleosides and/or prodrugs for producing pharmaceutical preparations for reducing the aforementioned side-effects and to combinations or products for administering active ingredients of this type, in particular pyrimidine nucleosides and/or prodrugs produced therefrom, comprising inhibitors of nucleic acid biosynthesis or their precursors.Type: GrantFiled: February 27, 2002Date of Patent: January 31, 2006Assignee: Pharma Nord ApSInventor: Ulrich Walker
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Patent number: 6972330Abstract: Process for chemical synthesis of methoxy nucleosides.Type: GrantFiled: May 8, 2003Date of Patent: December 6, 2005Assignee: Sirna Therapeutics, Inc.Inventors: Leonid Beigelman, Peter Haeberli, Alexander Karpeisky, David Sweedler
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Patent number: 6960568Abstract: The invention provides novel nucleosides and related processes, pharmaceutical compositions, and methods. The novel nucleosides are useful in a wide variety of antiviral, antineoplastic, and antibacterial applications. Preferred embodiments of the instant invention include novel 2 halogen-substituted, 3 halogen-substituted, and 2?,3?dihalogen-substituted analogues of 3-deazaadenosine, and novel 3 halogen-substituted analogues of 3-deazaguanosine. Compounds of the instant invention, including 4-Amino-6-fluoro-1-(?-D-ribofuranosyl)imidazo[4,5-c]pyridine and 6-Amino-7-bromo-1,5-dihydro-1-?-D-ribofuranosylimidazo[4,5-c]pyridin-4-one, have exhibited potent antiviral and anticancer activity in vitro. The compounds are also useful in the concomitant treatment of bacterial infections associated with viral infections such as AIDS.Type: GrantFiled: December 17, 2002Date of Patent: November 1, 2005Assignee: Yale UniversityInventors: Alan C. Sartorelli, Yung-Chi Cheng, Mao-Chin Liu
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Patent number: 6936597Abstract: Polymeric prodrugs of the formula: wherein B is selected from the group consisting of OH, leaving groups, residues of amine-containing moieties and a residues of hydroxyl-containing moieties; Y1 is selected from the group consisting of O, S, and NR5; M is NR3, O or S; Ar is a moiety which when included in Formula I forms a multi-substituted aromatic or heteroaromatic hydrocarbon or a multi-substituted heterocyclic group; (m) is zero or a positive integer; R1-3 and R5 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy and C1-6 heteroalkoxy; and R4 is a polymeric residue; as well as methods of making and using the same are disclosed.Type: GrantFiled: March 21, 2002Date of Patent: August 30, 2005Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Yun H. Choe
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Patent number: 6936596Abstract: 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.Type: GrantFiled: September 7, 2001Date of Patent: August 30, 2005Assignees: Toa Eiyo Ltd., Yamasa CorporationInventors: Takashi Konno, Kazuhiro Uemoto, Shinya Onuma, Yoshikazu Kato