Carbonyl, Thiocarbonyl, Or Nitrogen, Other Than As Nitro Or Nitroso, Bonded Directly To The Sugar Ring Patents (Class 536/27.22)
  • Patent number: 8987228
    Abstract: Clinical finding shows that twice daily administrations of 2 mg of 1-deoxy-1-[N6-(3-iodobenzyl)-adenin-9-yl]-N-methyl-?-D-ribofuronamide (IB-MECA) (total daily administration of 4 mg) to subjects having moderate to severe psoriasis, was significantly more effective in treatment of the psoriatic plaques than treatment of psoriasis at two administration doses of 1 mg or 4 mg (total daily doses of 2 or 8 mg, respectively). A pharmaceutical composition for the treatment of psoriasis includes as the active ingredient IB-MECA in an amount suitable for a total daily dose administration of about 4 mg. In one preferred embodiment, IB-MECA is administered twice a day to a subject in need of psoriasis treatment, the pharmaceutical composition including an administration dose of 2 mg.
    Type: Grant
    Filed: September 6, 2010
    Date of Patent: March 24, 2015
    Assignee: Can-Fite Biopharma Ltd.
    Inventor: Pnina Fishman
  • Publication number: 20150072345
    Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one 2?-arabino-fluoronucleoside and an internucleoside 3?-NH—P(—O)(OR)—O-5? linkage, where R is a positively charged counter ion or hydrogen, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive phosphoramidate 2?-arabino-fluorooligonucleotides have a high RNA binding affinity to complementary nucleic acids and are base and acid stable.
    Type: Application
    Filed: September 11, 2014
    Publication date: March 12, 2015
    Inventors: Sergei M. Gryaznov, Ronald G. Schultz
  • Publication number: 20140235563
    Abstract: 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: Application
    Filed: April 30, 2014
    Publication date: August 21, 2014
    Applicants: Gilead Sciences, Inc., Gilead Pharmasset LLC
    Inventors: Michael Joseph Sofia, Jinfa Du
  • Publication number: 20140037538
    Abstract: The present invention provides N-alkyl 2-(disubstituted)alkynyladenosine-5?-uronamides and derivatives thereof and pharmaceutical compositions containing the same that are selective agonists of A2A adenosine receptors (ARs). These compounds and compositions are useful as pharmaceutical agents.
    Type: Application
    Filed: July 31, 2013
    Publication date: February 6, 2014
    Inventors: Robert D. Thompson, Anthony Beauglehole, Guoquan Wang
  • Publication number: 20130237491
    Abstract: The present invention relates to the use of nucleoside derivatives of formula Ia wherein the symbols are as defined in the specification, and of pharmaceutically acceptable salts thereof and to pharmaceutical compositions containing such compounds.
    Type: Application
    Filed: April 12, 2013
    Publication date: September 12, 2013
    Applicant: Roche Palo Alto LLC
    Inventors: Rene Robert Devos, Christopher John Hobbs, Wen-Rong Jiang, Joseph Armstrong Martin, John Herbert Merrett, Isabel Najera, Nobuo Shimma, Takuo Tsukuda
  • Publication number: 20130122535
    Abstract: Synthesis of many proteins is tightly controlled at the level of translation and plays an essential role in fundamental processes such as cell growth and proliferation, signaling, differentiation or death. Methods that allow imaging and identification of nascent proteins allow for dissecting regulation of translation, both spatially and temporally, including in whole organisms. Described herein are robust chemical methods for imaging and affinity-purifying nascent polypeptides in cells and in animals, based on puromycin analogs. Puromycin analogs of the present invention form covalent conjugates with nascent polypeptide chains, which are rapidly turned over by the proteasome and can be visualized and specifically captured by a bioorthogonal reaction (e.g., [3+2]cycloaddition). The methods of the present invention have broad applicability for imaging protein synthesis and for identifying proteins synthesized under various physiological and pathological conditions in vivo.
    Type: Application
    Filed: November 9, 2012
    Publication date: May 16, 2013
    Applicant: President and Fellows of Harvard College
    Inventor: President and Fellows of Harvard College
  • Publication number: 20130055417
    Abstract: The invention provides tissue culture system for primary cells (e.g. normal mammalian primary epithelial progenitors). This system includes: a) a serum-free, chemically defined cell culture media; and, b) methods for isolation and in vitro long-term propagation of primary cells (e.g. primary epithelial cells). Primary cells so isolated and cultured can be kept undifferentiated and proliferate for many weeks (>15 weeks) or population doubling (>35 PD) without senescence, or any detectable genetic alterations. Upon changing media/culture conditions, these cells can be induced to differentiate. The invention also provides methods to transform normal primary cells so cultured into “cancer stem cells.” The genetically defined cancer stem cell tumor model mimics the behavior of the disease closely, e.g., the cells are invasive, hormone responsive and metastatic when injected into mice. The tumor cells express genes that are specific to cancer stem cells identified in patient samples.
    Type: Application
    Filed: July 23, 2012
    Publication date: February 28, 2013
    Applicants: The Brigham and Women's Hospital, Whitehead Institute for Biomedical Research
    Inventors: Tan A. Ince, Robert A. Weinberg
  • 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: 20120296076
    Abstract: The invention provides synthetic processes and synthetic intermediates that can be used to prepare compounds having useful anti-HIV properties.
    Type: Application
    Filed: May 18, 2012
    Publication date: November 22, 2012
    Inventors: Richard Hung Chiu Yu, Brandon Heath Brown, Richard P. Polniaszek, Benjamin R. Graetz, Keiko Sujino, Duong Duc-Phi Tran, Alan Scott Triman, Kenneth M. Kent, Steven Pfeiffer
  • Publication number: 20120232029
    Abstract: 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: Application
    Filed: December 13, 2011
    Publication date: September 13, 2012
    Applicant: Pharmasset, Inc.
    Inventors: MICHAEL JOSEPH SOFIA, Jinfa Du
  • 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
  • Publication number: 20120208991
    Abstract: 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.
    Type: Application
    Filed: October 19, 2010
    Publication date: August 16, 2012
    Applicant: OSAKA UNIVERSITY
    Inventors: Satoshi Obika, Yoshiyuki Hari, Tetsuya Kodama, Aiko Yahara, Masaru Nishida
  • Patent number: 8242258
    Abstract: Aspects of the invention include 2? protected nucleoside monomers that are protected at the 2? site with orthoester-type protecting groups. The 2? protected monomers also include a second, aryl carbonate-type, protecting group. 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: Grant
    Filed: December 3, 2007
    Date of Patent: August 14, 2012
    Assignees: Agilent Technologies, Inc., The Regents of the University of Colorado
    Inventors: Douglas J. Dellinger, Brian Stell, Marvin H. Caruthers
  • Publication number: 20120165284
    Abstract: The present invention is based on the clinical finding that twice daily administrations of 2 mg of 1-[N6-(3-iodobenzyl)-adenin-9-yl]-?-D-ribofuronamide (IB-MECA) (total daily administration of 4 mg) to subjects having moderate to severe psoriasis, was significantly more effective in treatment of the psoriatic plaques than treatment of psoriasis at two administration doses of 1 mg or 4 mg (total daily doses of 2 or 8 mg, respectively). Thus, the present invention provides a pharmaceutical composition for the treatment of psoriasis comprising as the active ingredient IB-MECA in an amount suitable for a total daily dose administration of about 4 mg. In one preferred embodiment IB-MECA is administered twice a day to a subject in need of psoriasis treatment, the pharmaceutical composition comprising an administration dose of 2 mg.
    Type: Application
    Filed: September 6, 2010
    Publication date: June 28, 2012
    Applicant: Can-Fite Biopharma Ltd.
    Inventor: Pnina Fishman
  • 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: 8158604
    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: February 24, 2010
    Date of Patent: April 17, 2012
    Assignee: University of Virginia Patent Foundation
    Inventors: Joel M. Linden, Jayson M. Rieger, Timothy L. Macdonald, Gail W. Sullivan, Lauren J. Murphree, Robert Alan Figler
  • Publication number: 20120070415
    Abstract: Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof. Examples of viral infections include a respiratory syncytial viral (RSV) and influenza infection.
    Type: Application
    Filed: September 19, 2011
    Publication date: March 22, 2012
    Applicant: ALIOS BIOPHARMA, INC.
    Inventors: Leonid Beigelman, Jerome Deval, David Bernard Smith, Guangyi Wang, Vivek Kumar Rajwanshi
  • Publication number: 20120010164
    Abstract: Compounds of structural formula (I): and pharmaceutically acceptable salts thereof; as defined herein, are described for use in the prevention and/or treatment of HCV infections. Novel compounds of the formula (I) and pharmaceutical formulations containing them are also described.
    Type: Application
    Filed: January 19, 2010
    Publication date: January 12, 2012
    Inventors: Vincenzo Surnma, Maria Emilia Di Francesco, Marco Pompei
  • Patent number: 7985740
    Abstract: The invention provides novel compounds which are agonists of the adenosine 2A receptor along with pharmaceutical compositions thereof, and methods of administering such compounds.
    Type: Grant
    Filed: July 17, 2006
    Date of Patent: July 26, 2011
    Assignee: Glaxo Group Limited
    Inventors: David George Allen, Michael David Barker, Richard Peter Charles Cousins
  • Publication number: 20110091385
    Abstract: A2A agonists of formula (I) is provided, wherein R1, R2, R4, R5, X, Y, Z, n, p, and q are as described herein. Also provided are compositions comprising and methods of using compounds of formula (I).
    Type: Application
    Filed: December 29, 2010
    Publication date: April 21, 2011
    Applicant: PGxHealth, LLC
    Inventors: Jayson M. RIEGER, Robert D. THOMPSON
  • Publication number: 20110059915
    Abstract: The invention relates to Purine Derivatives; compositions comprising an effective amount of a Purine Derivative; and methods for treating or preventing an ischemic condition, reperfusion injury, a cellular proliferative disorder, a cardiovascular disease, a neurological disorder, a skin disorder, a radiation-induced injury, a wound, or an inflammatory disease comprising administering an effective amount of a Purine Derivative to a subject in need thereof.
    Type: Application
    Filed: November 12, 2010
    Publication date: March 10, 2011
    Applicant: INOTEK PHARMACEUTICALS CORPORATION
    Inventors: Prakash JAGTAP, Andrew L. SALZMAN, Csaba SZABO
  • 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: 20110003766
    Abstract: Provided herein are alkoxy-carbonyl-amino-alkynyl-adenosine compounds and derivatives thereof and pharmaceutical compositions containing the same that are selective agonists of A2A adenosine receptors (ARs). These compounds and compositions are useful as pharmaceutical agents.
    Type: Application
    Filed: June 30, 2010
    Publication date: January 6, 2011
    Inventors: Anthony R. Beauglehole, Frank W. Schmidtmann, Jayson M. Rieger, Robert Thompson
  • Publication number: 20100279969
    Abstract: The present invention is directed to compounds, compositions and methods for treating or preventing viral infections, in particular, HIV, HBV, and HCV, in human patients or other animal hosts. The compounds are 3?-azido-2?,3?-dideoxy purine nucleosides or phosphonates, and pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof. In particular, the compounds show potent antiviral activity against HIV-1 resistance mutants including HIV-1K65R, HTV-1K70E, HIV-1L74V, HIV-1M184V, HIV-1Q151M and inhibitory activity against HIV-1 RT harboring TAMS or insertion mutations including HIV-1AZT3, HIV-1AZT7, HIV-1AZT9, HIV-1Q151M, or HIV-169insertion. In one embodiment, the compounds are 3?-azido-ddA, 3?-azido-ddG, or combinations thereof, administered with one or more additional antiviral agents that select for TAM mutations and/or the M 184V mutation, along with a pharmaceutically acceptable carrier.
    Type: Application
    Filed: May 14, 2008
    Publication date: November 4, 2010
    Applicants: RFS PHARMA, LLC, EMORY UNIVERSITY, UNIVERSITY OF PITTSBURGH
    Inventors: Raymond F. Schinazi, John W. Mellors, Nicolas Paul Sluis-Cremer, Frank Amblard, Steven J. Coats, Junxing Shi, Richard Anthony Whitaker
  • 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
  • Publication number: 20100152434
    Abstract: Therapeutically active nucleosides and associated methods are provided. In one aspect, a nucleoside molecule having a general structural similar to ATP. Such nucleosides have a structure that allows binding to, and subsequent regulation of, protein kinase molecules. As such, the nucleosides of the present invention have may be capable of treating a variety of kinase-related medical disorders.
    Type: Application
    Filed: November 30, 2009
    Publication date: June 17, 2010
    Inventor: Matt A. Peterson
  • Publication number: 20090324708
    Abstract: The present invention relates to a compound having inhibitory activity on a Rho-GTPase cell protein, the compound having the formula I (Formula I) wherein A is selected from N and N—H, R1 is selected from H and NHR3, R2 is selected from NHR4, OR4, O and halogen, R3 is selected from H and —COR5, R4 is selected from H, a C1-C6 alkyl and a substituted or unsubstituted phenyl, R5 is selected from a C1-C12 alkyl and a substituted or unsubstituted phenyl, R6 is selected from H, —COR5, —CO2R5, —PR7R8 and —PR7R8OPR7R8R8R7, R7 is selected from O and S, R8 is selected from H, OR4 and OSATE (—OCH2CH2SCOR5), and wherein each represents a single bond or a double bond, provided that when one of them is a double bond the other one is a single bond, and pharmaceutically acceptable salts and derivatives thereof. In particular, the compounds of the invention may be used as antitumor agents the action of which interfere with the signaling pathways normally involved in tumor development processes.
    Type: Application
    Filed: November 5, 2007
    Publication date: December 31, 2009
    Applicants: Universidad Nacional De Quilmes, Consejo Nacional De Investigaciones Cientificas Y Tecnicas
    Inventors: Daniel Fernando Alonso, Daniel Eduardo Gomez, Luis Emilio Iglesias, Maria Alejandra Zinni, Adolfo Marcelo Iribarren, Pablo Lorenzano Menna
  • Publication number: 20090280059
    Abstract: A2A agonists of formula (I) is provided, wherein R1, R2, R4, R5, X, Y, Z, n, p, and q are as described herein. Also provided are compositions comprising and methods of using compounds of formula (I).
    Type: Application
    Filed: July 13, 2009
    Publication date: November 12, 2009
    Applicant: PGXHEALTH, LLC
    Inventors: Jayson M. Rieger, Robert D. Thompson
  • Publication number: 20090162282
    Abstract: The present invention provides substituted 4-{3-[6-amino-9-(3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid esters and pharmaceutical compositions containing the same that are selective agonists of A2A adenosine receptors (ARs). These compounds and compositions are useful as pharmaceutical agents.
    Type: Application
    Filed: December 18, 2008
    Publication date: June 25, 2009
    Inventors: Robert Douglas Thompson, Anthony Beauglehole, Frank W. Schmidtmann, Jayson M. Rieger
  • Patent number: 7511133
    Abstract: The compounds of the following formula: wherein Ar, R and R1 have the meanings given in the specification. This series of sulfonamido derivatives with a conserved uronamide group at the 5? position provide superior A3 receptor affinity as well as selectivity. These new adenosine agonists are sulfonamido derivatives N-substituted with aliphatic groups (cyclic or linear) or aromatic radicals.
    Type: Grant
    Filed: September 17, 2004
    Date of Patent: March 31, 2009
    Assignee: King Pharmaceuticals Research and Development, Inc.
    Inventors: Pier Giovanni Baraldi, Allan R. Moorman, Pier A. Borea
  • Patent number: 7423025
    Abstract: Disclosed herein are compounds having Formula I, which are non-natural L-adenosine analogs. Also disclosed are their methods of making. Still further, disclosed are the uses of the disclosed compounds to treat cardiovascular disease, ischemia related injuries; and neurodegenerative diseases. The compounds disclosed herein have the formula: wherein R1 and R2 are, independently, H, branched or straight-chain, substituted or unsubstituted alkyl, alkenyl, alkynyl, or aryl; R3 is branched or straight-chain, substituted or unsubstituted alkyl, hydroxy-alkyl, or —C(?O)NR6R7; and R4 and R5 are, independently, H, hydroxy, halogen, and NR8R9, wherein R6, R7, R8, and R9 are, independently, H, branched or straight-chain, substituted or unsubstituted alkyl, alkenyl, alkynyl, or aryl.
    Type: Grant
    Filed: September 8, 2006
    Date of Patent: September 9, 2008
    Assignee: MUSC Foundation for Research Development
    Inventors: Giuseppe Gumina, Craig C. Beeson, Gary L. Wright
  • Publication number: 20080177055
    Abstract: Disclosed are methods for preparing 2-alkynyladenosine derivatives of formula A: or a stereoisomer, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate or isomorphic crystalline form thereof, the method comprising the step of: contacting 2-iodoadenosine-5?-N-ethyluronamide with a compound of formula B: wherein Z is —C(?O)OR or —CH2C(?O)R, where R is a C1 to C5 alkyl, preferably The methods are useful for preparing 2-alkynyladenosine derivatives that are, in certain embodiments, adenosine receptor agonists.
    Type: Application
    Filed: October 17, 2007
    Publication date: July 24, 2008
    Inventors: Iain F. Pickersgill, Edward H. Cheesman
  • Patent number: 7381714
    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: June 3, 2008
    Assignee: CV Therapeutics, Inc.
    Inventors: Elfatih Elzein, Rao Kalla, Thao Perry, Jeff Zablocki, Xiaofen Li
  • Patent number: 7358235
    Abstract: Analogs or derivatives of nitrobenzylthioinosine compounds. The use of these new analogs of nitrobenzylthioinosine and methods for the treatment of pain and various other indications using these analogs of nitrobenzylthioinosine as well as pharmaceutical compositions including analogs of nitrobenzylthioinosine.
    Type: Grant
    Filed: October 6, 2004
    Date of Patent: April 15, 2008
    Assignees: Gruenenthal GmbH, Leiden University
    Inventors: Claudia Puetz, Corinna Sundermann, Bernd Sundermann, Adriaan Pieter Ijzerman, Reynier Tromp, Jacobien Von Frijtag Drabbe Kuenzel
  • Patent number: 7199127
    Abstract: Disclosed are purine nucleoside compounds that are selective to A3 adenosine receptors and are useful for the treatment of cancer and inflammatory diseases. The compounds are shown by the following general formula (I), including isomers thereof: wherein X is sulfur or oxygen; R1 is hydrogen, alkyl, benzyl, halobenzyl, or phenylalkyl; R2 is hydrogen, halogen, alkoxy, alkenyl, alkynyl, alkylthio, or thio; R3 and R3? are hydrogen, hydroxyalkyl, alkoxycarbonyl, or alkylaminocarbonyl, whereas R3 and R3? do not have identical substituents simultaneously; and R4 is hydrogen or alkyl. Also disclosed are a pharmaceutical composition comprising a compound of formula (I), an isomer, or its pharmacologically acceptable salt as an active ingredient and a method for preventing or treating various diseases, state, or condition, including asthma, inflammation, cerebral ischemia, heart diseases, and cancer.
    Type: Grant
    Filed: October 24, 2003
    Date of Patent: April 3, 2007
    Assignees: United States of America, Represented by the Secretary, Department of Health and Human Services, Ewha Womans University
    Inventors: Lak Shin Jeong, Kenneth A. Jacobson, Hyung Ryong Moon, Hea Ok Kim
  • Patent number: 7141553
    Abstract: The present invention concerns a method for the treatment of inflammatory arthritis, and in particular rheumatoid arthritis, by administering to the subject specific low dosages of N6-(3-iodobenzyl)-adenosine 5?-N-methyl-uronamide (IB-MECA) and 2-chloro-N6-(3-iodobenzyl)-adenosine-5?-N-methyl-uronamide (CL-IB-MECA).
    Type: Grant
    Filed: November 19, 2003
    Date of Patent: November 28, 2006
    Assignee: Can-Fite Biopharma Ltd. Israel
    Inventor: Pnina Fishman
  • Patent number: 7132409
    Abstract: 2-(6-Cyano-1-hexyn-1-yl)adenosine, 2-(6-cyano-1-hexyn-1-yl)adenosine 5?-monophosphate, or salts thereof; and drugs containing the same as an active ingredient. The compounds have excellent effects of lowering ocular tension, promoting blood flow in retina, and protecting optic nerve failure and are highly soluble in water. Owing to these characteristics, the compounds are useful as drugs such as remedies for glaucoma and ocular hypertension.
    Type: Grant
    Filed: January 11, 2005
    Date of Patent: November 7, 2006
    Assignees: Toa Eiyo Ltd., Yamasa Corporation
    Inventors: Takashi Konno, Kazuhiro Uemoto, Shinya Onuma, Yoshikazu Kato
  • Patent number: 7078499
    Abstract: Nucleotides comprising a reporter moiety and a polymerase enzyme blocking moiety in which the reporter moiety does not also act as a polymerase enzyme blocking moiety are described. Also described are compounds of Formula (I): wherein W is a phosphate group, B is a base, Y is a linker comprising an enzyme-cleavable group, R2 is a reporter moiety, R3 is selected from H or OH, Z and Z? are selected from H, OH, or a group X—R1, wherein X is a linker comprising an enzyme-cleavable group and R1 is a polymerase enzyme blocking group, provided that at least one of Z and Z? is X—R1.
    Type: Grant
    Filed: May 31, 2001
    Date of Patent: July 18, 2006
    Assignee: GE Healthcare UK Limited
    Inventors: Raj Odedra, Adrian Simmonds, Lee Pickering
  • Patent number: 7022727
    Abstract: The present invention relates to a crystalline form of 6-[(2,2-diphenylethyl)amino]-9-(N-ethyl-?-D-ribofuranosyluronamide)-N-(2-{N?-[1-(2-pyridyl)-4-piperidyl]ureido}ethyl)-9H-purine-2-carboxamide and to a process for the preparation of, compositions containing and the uses of such a crystalline form.
    Type: Grant
    Filed: September 3, 2004
    Date of Patent: April 4, 2006
    Assignee: Pfizer Inc
    Inventors: Terence Vernon Silk, Julian Duncan Smith
  • Patent number: 7005425
    Abstract: 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: Grant
    Filed: April 18, 2003
    Date of Patent: February 28, 2006
    Assignee: CV Therapeutics, Inc.
    Inventors: Luiz Belardinelli, Arvinder Dhalla
  • Patent number: 6936596
    Abstract: 2-(6-Cyano-1-hexyn-1-yl)adenosine, 2-(6-cyano-1-hexyn-1-yl)adenosine 5?-monophosphate, or salts thereof; and drugs containing the same as an active ingredient. The compounds have excellent effects of lowering ocular tension, promoting blood flow in retina, and protecting optic nerve failure and are highly soluble in water. Owing to these characteristics, the compounds are useful as drugs such as remedies for glaucoma and ocular hypertension.
    Type: Grant
    Filed: September 7, 2001
    Date of Patent: August 30, 2005
    Assignees: Toa Eiyo Ltd., Yamasa Corporation
    Inventors: Takashi Konno, Kazuhiro Uemoto, Shinya Onuma, Yoshikazu Kato
  • Patent number: 6903079
    Abstract: The invention provides a novel class of substituted nucleoside derivatives having the formula: A-Z1-L-Z2-G wherein: A and G are connected via Z1 and Z2 respectively, to a linker, L; and A is: wherein: X1 and X2 are N; X3 is —N?CH; R1 and R2 are independently H, alkyl, NH2, OH, SH, Cl, NHR9, or N?NR9, where R9 is alkyl, aryl, or arylalkyl; R5 and R6 are independently alkyl, or R5 and R6 taken together form a —C(CH3)2— group; Z1 is —CH2O—, —CH2NR10—, —CH2NR10C(O)—, —CONR10—, —CO2—, —CH2NHCONH—, —CH2—, —CH2NHCSNH—, —CO—, —CH2CO2—, —NHCO2—, —S—, —SO2—, —CH2S—, or —SO—; Z2 is —NR10CO—, —C(O)NR10—, —NHCONH—, —OC(O)—, —C(O)O—, NHCS, —CSNH—, —NHCSNH—, —O—, —CO—, —OCO—, —OCONH—, —NH—, —CH2—, —CH—alkyl—, —NHCO2—, —S—, —SO2—, CS—, or —SO—; L is H, O, S, C1-15 alkylene chain optionally substituted in one or more positions, a 5, 6 or 7 membered carbocycle, piperidine, piperazine, pyrole, imidazole, benzimidazole, tetrazoles, indole, isoquinoline, quinoline, or pyrrolidine, any of the 5, 6 or 7 membered carbocycl
    Type: Grant
    Filed: December 16, 2002
    Date of Patent: June 7, 2005
    Assignee: Inotek Pharmaceuticals Corporation
    Inventors: Prakash Jagtap, Garry Southan, Andrew Salzman, Csaba Szabo, Siya Ram
  • Patent number: 6852746
    Abstract: The present invention relates to a crystalline form of 6-[(2,2-diphenylethyl)amino]-9-(N-ethyl-?-D-ribofuranosyluronamide)-N-(2-{N?-[1-(2-pyridyl)-4-piperidyl]ureido}ethyl)-9H-purine-2-carboxamide and to a process for the preparation of, compositions containing and the uses of such a crystalline form.
    Type: Grant
    Filed: December 3, 2002
    Date of Patent: February 8, 2005
    Assignee: Pfizer Inc
    Inventors: Terence Vernon Silk, Julian Duncan Smith
  • Patent number: 6803457
    Abstract: A3 agonists, methods of using such A3 agonists and pharmaceutical compositions containing such A3 agonists. The A3 agonists are useful for the reduction of tissue damage resulting from tissue ischemia or hypoxia.
    Type: Grant
    Filed: August 17, 2000
    Date of Patent: October 12, 2004
    Assignee: Pfizer, Inc.
    Inventors: Michael P. DeNinno, Hiroko Masamune, Robert W. Scott
  • Patent number: 6784165
    Abstract: The present invention discloses a method for treating heart rhythm disturbances in a mammal in need thereof by the administration of N6-substituted-5′(N-substituted)carboxamidoadenosines. More particularly, the invention is directed to a method for treatment of heart rhythm disturbances in a mammal that would benefit from the induction of negative dromotropic and/or negative chronotropic actions, comprising the administration to said mammal an effective amount of a compound of the Formula: or a pharmaceutically acceptable salt or ester thereof; wherein R1 is C3-7 secondary alkyl, or C3-8 cycloalkyl; and R2 is C1-4 alkyl or C3-5 cycloalkyl The invention is also directed to novel dosage forms comprising said compounds.
    Type: Grant
    Filed: November 16, 2000
    Date of Patent: August 31, 2004
    Assignee: Aderis Pharmaceuticals, Inc.
    Inventor: Pauline L. Martin
  • Publication number: 20030204080
    Abstract: Novel intermediates of nucleoside derivatives, of which the 6-position of the nucleic acid base moiety is substituted with a halogen atom, are produced. Using those novel intermediates, even substrates, of which the 3′-position of the saccharide moiety is deoxylated, can be substituted at the 2′-position at an extremely high yield. Specifically, by subjecting a 3′-deoxy derivative of inosine to 6-halogenation to give a 6-halide of the derivative, and then subjecting it to 2′-deoxylation/substitution with a fluorine atom or the like, followed by further subjecting it to substitution with an amino group, a hydroxyl group or any other intended substituent at the 6-positioned halogen atom, nucleoside derivatives are produced at a high yield.
    Type: Application
    Filed: May 12, 2003
    Publication date: October 30, 2003
    Applicant: AJINOMOTO CO. INC
    Inventors: Satoshi Takamatsu, Satoshi Katayama, Naoko Hirose, Kunisuke Izawa, Tokumi Maruyama
  • Publication number: 20030158145
    Abstract: The present invention relates to a crystalline form of 6-[(2,2-diphenylethyl)amino]-9-(N-ethyl-&bgr;-D-ribofuranosyluronamide)-N-(2-{N′-[1-(2-pyridyl)-4-piperidyl]ureido}ethyl)-9H-purine-2-carboxamide and to a process for the preparation of, compositions containing and the uses of such a crystalline form.
    Type: Application
    Filed: December 3, 2002
    Publication date: August 21, 2003
    Inventors: Terence Vernon Silk, Julian Duncan Smith
  • Publication number: 20030069414
    Abstract: Modified nucleosides and methods of making and using the nucleosides are disclosed. The compounds can be prepared by reacting nucleoside starting materials that contain a suitable leaving group at one or more of the carbon atoms in the purine or pyrimidine ring, with a vinylstannane, carbon monoxide, and a palladium catalyst to provide 1-ene-3-one intermediates. These intermediates are then reacted with suitably functionalized primary or secondary amines via a Michael reaction. When the intermediate is a 5-position modified pyrimidine ring, and the amine contains a second hydrogen, it can do a second Michael reaction with the ene-one or the ene-imine in the pyrimidine ring. Appropriate modification of the amine reactant can yield products with various bioactivities. The nucleosides can be used therapeutically as anti-cancer, anti-bacterial or anti-viral drugs. The nucleosides can also be used for diagnostic applications, for example, by incorporating a radiolabel or fluorescent label into the molecule.
    Type: Application
    Filed: August 9, 2002
    Publication date: April 10, 2003
    Applicant: GILEAD SCIENCES, INC.
    Inventors: Gary P. Kirschenheuter, Bruce Eaton
  • Patent number: 6541626
    Abstract: Methods for selectively protecting the exocyclic amino function of a purine nucleoside are provided using activating agents to effect acylation at the exocyclic amino site. Methods are also provided for recycling polymer bound coupling supports from the reaction mixtures produced upon N-acylation.
    Type: Grant
    Filed: April 17, 2001
    Date of Patent: April 1, 2003
    Assignees: ISIS Pharmaceuticals, Inc., University of Allahabad
    Inventors: Yogesh S. Sanghvi, Krishna Misra, Snehlata Tripathi
  • Publication number: 20020146737
    Abstract: The invention relates to nucleoside derivatives with photolabile protecting groups of general formula (I), where R1=H, F, Cl, Br, I, NO2; R2=H, CN, where R1 and R2 are not simultaneously H; R3=H, 1-4 C alkyl, phenyl; R4=H or a conventional functional group for the synthesis of oligonucleotides; R5=H, OH, halogen or XR6, where X=O or S and R6=a conventional nucleotide protecting group; B=adenine, cytosine, guanine, thymine, uracil, 2,6-diaminopurin-9-yl, hypoxanthin-9-yl, 5-methylcytosin-1-yl, 5-amino-4-imidazolcarboxamid-1-yl or 5-amino-4-imidazolcarboxamid-3-yl, where, if B=adenine, cytosine or guanine the primary amine functionality, optionally, carries a permanent protecting group. Furthermore, these derivatives may be used for the light-controlled synthesis of oligonucleotides on a DNA chip.
    Type: Application
    Filed: March 29, 2002
    Publication date: October 10, 2002
    Inventors: Wolfgang Pfleiderer, Sigrid Buhler, Heiner Giegrich