Adenosyl Patents (Class 536/27.3)
  • Patent number: 10702482
    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.
    Type: Grant
    Filed: November 6, 2014
    Date of Patent: July 7, 2020
    Assignee: GNOSIS SPA
    Inventors: Daniele Giovannone, Niccolò Miraglia, Marco Berna
  • Patent number: 9029344
    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.
    Type: Grant
    Filed: June 1, 2011
    Date of Patent: May 12, 2015
    Assignee: The United States of America, as represented by the Secretary, Department of Health and Human Services
    Inventors: Genbin Shi, Gary X. Shaw, Xinhua Ji
  • Publication number: 20150011495
    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.
    Type: Application
    Filed: March 14, 2014
    Publication date: January 8, 2015
    Applicant: EPIZYME, INC.
    Inventor: Edward James Olhava
  • Patent number: 8927520
    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.
    Type: Grant
    Filed: December 22, 2011
    Date of Patent: January 6, 2015
    Assignees: Institut Pasteur, Institut Curie
    Inventors: Sylvie Pochet, Gilles Labesse, Muriel Gelin, Liliane Assairi, Olivier Dussurget, Guillaume Poncet-Montange
  • Publication number: 20140303106
    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.
    Type: Application
    Filed: October 26, 2012
    Publication date: October 9, 2014
    Inventors: Weihong Zheng, Minkui Luo, Glorymar del Valle Ibanzen Sanchez
  • Publication number: 20140128338
    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.
    Type: Application
    Filed: November 8, 2013
    Publication date: May 8, 2014
    Applicant: ARDEA BIOSCIENCES, INC.
    Inventors: Esmir GUNIC, Jean-Luc GIRARDET, Jean-Michel VERNIER, Martina E. TEDDER, David A. PAISNER
  • Publication number: 20140099283
    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.
    Type: Application
    Filed: October 7, 2013
    Publication date: April 10, 2014
    Inventors: Gilles GOSSELIN, Christophe Claude PARSY, Francois-Rene ALEXANDRE, Houcine RAHALI, Jean-Francois GRIFFON, Julien MILHAU, Dominique SURLERAUX, Cyril B. DOUSSON, Claire PIERRA, Adel M. MOUSSA, Benjamin Alexander MAYES
  • Publication number: 20140051654
    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.
    Type: Application
    Filed: October 16, 2013
    Publication date: February 20, 2014
    Applicant: EPIZYME, INC.
    Inventors: Edward J. Olhava, Richard Chesworth, Kevin W. Kuntz, Victoria M. Richon, Roy M. Pollock, Scott R. Daigle
  • Publication number: 20140051846
    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.
    Type: Application
    Filed: March 29, 2012
    Publication date: February 20, 2014
    Applicant: TheUnited ofAmerica,asrepresentedbythe Secre -tary,Department ofHealthand Human Service
    Inventors: Serge L. Beaucage, Jacek Cieslak
  • Publication number: 20140051605
    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.
    Type: Application
    Filed: October 23, 2013
    Publication date: February 20, 2014
    Applicant: NimbleGen Systems GmbH
    Inventor: Klaus-Peter Stengele
  • Publication number: 20140024611
    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.
    Type: Application
    Filed: May 20, 2013
    Publication date: January 23, 2014
    Inventors: Derek Shieh Tan, Luis E. N. Quadri, Jae-Sang Ryu, Justin Scott Cisar, Julian Alberto Ferreras, Xuequan Lu
  • Patent number: 8609833
    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.
    Type: Grant
    Filed: April 20, 2012
    Date of Patent: December 17, 2013
    Assignee: Inotek Pharmaceuticals Corporation
    Inventors: Prakash Jagtap, Csaba Szabo, Andrew L. Salzman
  • Publication number: 20130331351
    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.
    Type: Application
    Filed: December 22, 2011
    Publication date: December 12, 2013
    Applicants: Institut Pasteur, INSTITUT CURIE, Centre National De la Recherche Scientifique
    Inventors: Sylvie Pochet, Gilles Labesse, Muriel Gelin, Liliane Assairi, Olivier Dussurget, Guillaume Poncet-Montange
  • Patent number: 8361988
    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.
    Type: Grant
    Filed: January 17, 2008
    Date of Patent: January 29, 2013
    Assignee: Institut de Recherches Cliniques de Montreal
    Inventor: Yvan Guindon
  • Patent number: 8334364
    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.
    Type: Grant
    Filed: November 1, 2007
    Date of Patent: December 18, 2012
    Assignee: Nipon Kayaku Kabushiki Kaisha
    Inventors: Keiichiro Yamamoto, Kazutoshi Takashio
  • Publication number: 20120295863
    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).
    Type: Application
    Filed: November 12, 2010
    Publication date: November 22, 2012
    Inventors: Yun-Lian Lin, Yijuang Chern, Jim-Min Fang, Jung-Hsing Lin, Nai-Kuei Huang
  • Publication number: 20120258891
    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.
    Type: Application
    Filed: March 29, 2012
    Publication date: October 11, 2012
    Applicant: NIMBLEGEN SYSTEMS GMBH
    Inventor: Klaus-Peter Stengele
  • Patent number: 8258115
    Abstract: The present invention refers to new salts of S-adenosyknethionine (SAMe) with improved stability and containing at least 70% by weight of SAMe.
    Type: Grant
    Filed: October 22, 2007
    Date of Patent: September 4, 2012
    Assignee: Gnosis SpA
    Inventors: Ermanno Valoti, Daniele Giovannone, Marco Berna
  • Patent number: 8236778
    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.
    Type: Grant
    Filed: March 18, 2009
    Date of Patent: August 7, 2012
    Assignee: Proyecto de Biomedicina Cima, S.L.
    Inventors: Matías Antonio Ávila Zaragozá, Fernando José Corrales Izquierdo, Begoña Fernández Díez, Beatriz Moreno Bruna, Pablo Villoslada Díaz
  • Publication number: 20120184724
    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.
    Type: Application
    Filed: December 28, 2011
    Publication date: July 19, 2012
    Applicant: AGILENT TECHNOLOGIES, INC.
    Inventors: Agnieszka B. Sierzchala, Brian Phillip Smart, Douglas J. Dellinger, Geraldine Dellinger, Joel Myerson, Zoltan Timar
  • Patent number: 8202985
    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.
    Type: Grant
    Filed: March 23, 2006
    Date of Patent: June 19, 2012
    Assignees: Agilent Technologies, Inc., The Regents of the University of Colorado
    Inventors: Douglas J. Dellinger, Zoltan Timar, Agnieszka Sierzchala, Geraldino Dellinger, Marvin H. Caruthers
  • Patent number: 8188222
    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.
    Type: Grant
    Filed: November 6, 2007
    Date of Patent: May 29, 2012
    Assignee: Nippon Kayaku Kabushiki Kaisha
    Inventors: Keiichiro Yamamoto, Kazutoshi Takashio
  • Patent number: 8183225
    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.
    Type: Grant
    Filed: November 10, 2008
    Date of Patent: May 22, 2012
    Assignee: New York University
    Inventors: Bruce N. Cronstein, Zhong Sheng Peng
  • Patent number: 8183224
    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.
    Type: Grant
    Filed: August 4, 2008
    Date of Patent: May 22, 2012
    Assignee: Inotek Pharmaceuticals Corporation
    Inventors: Prakash Jagtap, Csaba Szabo, Andrew L. Salzman
  • Patent number: 8178509
    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).
    Type: Grant
    Filed: February 9, 2007
    Date of Patent: May 15, 2012
    Assignee: University of Virginia Patent Foundation
    Inventors: Joel M. Linden, Kori Wallace, Robert Alan Figler, Jayson M. Rieger
  • Patent number: 8168766
    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.
    Type: Grant
    Filed: August 31, 2009
    Date of Patent: May 1, 2012
    Assignee: ScnioPharm Taiwan Ltd.
    Inventors: Julian Paul Henschke, Yung Fa Chen, George Charles Schloemer
  • Patent number: 8153781
    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.
    Type: Grant
    Filed: June 20, 2008
    Date of Patent: April 10, 2012
    Assignees: The United States of America as represented by the Secretary, Department of Health and Human Services, Inserm
    Inventors: Kenneth A. Jacobson, Yoonkyung Kim, Athena Klutz, Beatrice Hechler, Christian Gachet
  • Publication number: 20110282045
    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.
    Type: Application
    Filed: May 13, 2011
    Publication date: November 17, 2011
    Inventors: William E. Bauta, Brian D. Burke, Brian E. Schulmeier, William R. Cantrell, JR., Dennis P. Lovett, Jose Puente
  • Publication number: 20110263545
    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.
    Type: Application
    Filed: May 20, 2009
    Publication date: October 27, 2011
    Inventors: Naweed Muhammad, Keith R. Bley, Jeffrey Tobias
  • Patent number: 7947824
    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.
    Type: Grant
    Filed: May 4, 2009
    Date of Patent: May 24, 2011
    Assignee: Genzyme Corporation
    Inventors: William E. Bauta, Brian D. Burke, Brian E. Schulmeier, William R. Cantrell, Jr., Dennis P. Lovett, Jose Puente
  • Patent number: 7943760
    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.
    Type: Grant
    Filed: September 2, 2009
    Date of Patent: May 17, 2011
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Robert Plourde, Jr., Sammy R. Shaver, James G. Douglass, III, Paul S. Watson, José L. Boyer, Chi Tu, Melwyn A. Abreo, Lorenzo J. Alfaro-Lopez, Yangbo Feng, Daniel F. Harvey, Tatyana V. Khasonova
  • Publication number: 20110086812
    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.
    Type: Application
    Filed: July 26, 2006
    Publication date: April 14, 2011
    Inventor: Vern L. Schramm
  • Patent number: 7897759
    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.
    Type: Grant
    Filed: June 30, 2008
    Date of Patent: March 1, 2011
    Assignee: MUSC Foundation for Research Development
    Inventors: Giuseppe Gumina, Roger L. White
  • Publication number: 20110039798
    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.
    Type: Application
    Filed: July 9, 2008
    Publication date: February 17, 2011
    Applicant: EASTERN VIRGINIA MEDICAL SCHOOL
    Inventors: Gustavo F. Doncel, Keykavous Parang, Hitesh Kumar Agarwal
  • Publication number: 20110039799
    Abstract: Provided are polymorphs of an A1 adenosine receptor partial agonist, compositions thereof, methods for their preparation, and methods for their uses.
    Type: Application
    Filed: August 10, 2010
    Publication date: February 17, 2011
    Applicant: Gilead Palo Alto, Inc.
    Inventors: Ernest Anthony Carra, Benjamin R. Graetz, DeMei Leung, Janaki Nyshadham, Robert Seemayer, Simon Kwok-Pan Yau
  • Publication number: 20110009354
    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.
    Type: Application
    Filed: August 1, 2008
    Publication date: January 13, 2011
    Inventors: John A. Secrist, III, Steve Ealick, Shridhar Bale, Anthony E. Pegg, Diane E. McCloskey, Wayne C. Guida
  • Patent number: 7868163
    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+.
    Type: Grant
    Filed: April 28, 2006
    Date of Patent: January 11, 2011
    Assignees: Universita' Degli Studi Di Genova, Centro Biotecnologie Avanzate
    Inventors: Giovanna Basile, Umberto Benatti, Santina Bruzzone, Gianluca Damonte, Antonio De Flora, Ernesto Fattorusso, Luisa Franco, Lucrezia Guida, Orazio Taglialatela-Scafati, Elena Zocchi
  • Patent number: 7820637
    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.
    Type: Grant
    Filed: March 17, 2005
    Date of Patent: October 26, 2010
    Assignee: Proyecto de Biomedicina Cima, S.L.
    Inventors: Pablo Villoslada Díaz, Matías Ávila Zaragoza, Beatriz Moreno Bruna, Fernando Corrales Izquierdo, Carmen Berasain Lasarte, Elena Ruiz García-Trevijano
  • Patent number: 7795236
    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.
    Type: Grant
    Filed: March 13, 2007
    Date of Patent: September 14, 2010
    Assignee: Kissei Pharmaceutical Co., Ltd.
    Inventors: Kazuya Tatani, Yoshinori Nonaka, Norihiko Kikuchi
  • Patent number: 7792576
    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.
    Type: Grant
    Filed: February 20, 2007
    Date of Patent: September 7, 2010
    Assignee: Purdue Research Foundation
    Inventors: Richard B. Borgens, Scott A. Shapiro
  • Patent number: 7737127
    Abstract: The invention provides compounds having the following general formula (I): wherein X, R1, R2, R7 and Z are as described here.
    Type: Grant
    Filed: March 26, 2007
    Date of Patent: June 15, 2010
    Assignee: University of Virginia Patent Foundation
    Inventors: Joel M. Linden, Jayson M. Rieger, Timothy L. Macdonald, Gail W. Sullivan, Lauren Jean Murphree, Robert Alan Figler
  • Patent number: 7696181
    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.
    Type: Grant
    Filed: August 24, 2006
    Date of Patent: April 13, 2010
    Assignee: CV Therapeutics, Inc.
    Inventors: Prabha Ibrahim, Elfatih Elzein, Kevin Shenk, Robert Jiang, Jeff Zablocki, Xiaofen Li, Christopher Morrison, Thao Perry, Dengming Xiao
  • Patent number: 7605143
    Abstract: The invention provides compounds having the following general formula (I): wherein X, R1, R2, R7 and Z are as described herein.
    Type: Grant
    Filed: August 2, 2005
    Date of Patent: October 20, 2009
    Assignee: University of Virginia Patent Foundation
    Inventors: Jayson M. Rieger, Joel M. Linden, Timothy L. Macdonald, Gail W. Sullivan, Lauren J. Murphree, Robert Alan Figler
  • Patent number: 7592445
    Abstract: This invention is directed to compounds of Formulae III and V, useful for treating diseases or conditions associated with platelet aggregation.
    Type: Grant
    Filed: January 4, 2008
    Date of Patent: September 22, 2009
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Robert Plourde, Jr., Sammy R. Shaver, James G. Douglass, III, Paul S. Watson, José L. Boyer, Chi Tu, Melwyn A. Abreo, Lorenzo J. Alfaro-Lopez, Yangbo Feng, Daniel F. Harvey, Tatyana V. Khasonova
  • Publication number: 20090170805
    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.
    Type: Application
    Filed: April 14, 2006
    Publication date: July 2, 2009
    Inventors: Derek Shieh Tan, Luis E. N. Quadri, Jae-Sang Ryu, Justin Scott Cisar, Julian Alberto Ferreras, Xuequan Lu
  • Patent number: 7553823
    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.
    Type: Grant
    Filed: September 15, 2006
    Date of Patent: June 30, 2009
    Assignee: CV Therapeutics, Inc.
    Inventors: Jeff A. Zablocki, Elfatih O. Elzein, Venkata P. Palle
  • Patent number: 7550442
    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):
    Type: Grant
    Filed: May 19, 2004
    Date of Patent: June 23, 2009
    Assignee: The Board of Trustees of the University of Illinois
    Inventors: Raven H. Huang, Xianjun Liu
  • Patent number: 7528247
    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.
    Type: Grant
    Filed: January 9, 2004
    Date of Patent: May 5, 2009
    Assignee: Genzyme Corporation
    Inventors: William E. Bauta, Brian D. Burke, Brian E. Schulmeier, William R. Cantrell, Jr., Dennis P. Lovett, Jose Puente
  • Publication number: 20090105468
    Abstract: 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: Application
    Filed: December 22, 2008
    Publication date: April 23, 2009
    Inventors: Sergei M. Gryaznov, Krisztina Pongracz, Daria Zielinska
  • Patent number: 7514417
    Abstract: Disclosed are novel compounds that are partial and full A1 adenosine receptor agonists having the structure of Formula I: which are useful for treating various disease states, in particular tachycardia and atrial flutter, angina, and myocardial infarction.
    Type: Grant
    Filed: May 19, 2006
    Date of Patent: April 7, 2009
    Assignee: CV Therapeutics, Inc.
    Inventors: Elfatih Elzein, Rao Kalla, Thao Perry, Jeff Zablocki, Xiaofen Li