Abstract: A series of 2-(Purin-9-yl)-tetrahydrofuran-3,4-diol derivatives with broad anti-inflammatory properties which inhibit leukocyte recruitment and activation and which are agonists of the adenosine 2a receptor are described.
Type:
Grant
Filed:
February 20, 2001
Date of Patent:
December 17, 2002
Assignee:
SmithKline Beecham Corporation
Inventors:
David George Allen, Chuen Chan, Richard Peter Charles Cousins, Brian Cox, Joanna Victoria Geden, Heather Hobbs, Suzanne Elaine Keeling, Alison Judith Redgrave, Thomas Davis Roper, IV, Shiping Xie
Abstract: Novel purine L-nucleoside compounds are disclosed, in which both the purine rings and the sugar are either modified, functionalized or both. The novel compounds or pharmaceutically acceptable esters or salts thereof may be used in pharmaceutical compositions, and such compositions may be used to treat an infection, an infestation, a neoplasm, or an autoimmune disease. The novel compounds may also be used to modulate aspects of the immune system, including modulation of Th1 and Th2.
Type:
Grant
Filed:
June 16, 2000
Date of Patent:
November 12, 2002
Assignee:
ICN Pharmaceuticals, Inc.
Inventors:
Guangyi Wang, Robert Tam, Devron Averett
Abstract: This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside has the formula:
wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted.
Type:
Grant
Filed:
December 10, 1999
Date of Patent:
September 3, 2002
Assignees:
Novirio Pharmaceuticals Limited, Centre National da la Recherche Scientifique
Inventors:
Gilles Gosselin, Jean-Louis Imbach, Martin L. Bryant
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.
Abstract: The present invention relates to a support system for the solid phase synthesis of oligomers, such as oligonucleotide, wherein the starting compound is bound to the support via a disiloxyl linkage. Furthermore, the invention relates to a method for synthesis of oligonucleotides on a solid support. The support system comprises a stable disiloxyl linkage providing high nucleoside loadings to the support and the method allows convenient non-laborious oligomer synthesis.
Type:
Grant
Filed:
August 2, 2001
Date of Patent:
August 6, 2002
Assignee:
Quiatech AB
Inventors:
Marek Kwiatkowski, Mats Nilsson, Ulf Landegren
Abstract: This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside has the formula:
wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted.
Type:
Grant
Filed:
August 10, 1999
Date of Patent:
May 28, 2002
Assignees:
Novirio Pharmaceuticals Limited, Centre National da la Recherche Scientifique
Inventors:
Gilles Gosselin, Jean-Louis Imbach, Martin L. Bryant
Abstract: The invention provides 4′-C-ethynyl purine nucleosides represented by formula [I]:
wherein B represents a base selected from the group consisting of purine and derivatives thereof; X represents a hydrogen atom or a hydroxyl group; and R represents a hydrogen atom or a phosphate residue; and a pharmaceutical composition containing any one of the compounds and a pharmaceutically acceptable carrier. Preferably, the composition is used as an anti-HIV agent or a drug for treating AIDS.
Abstract: The invention relates to compositions comprising acyl derivatives of 2′-deoxyribonucleosides. The invention also relates to methods of treating or preventing radiation, mutagen and sunlight-induced biological damage, and methods for improving wound healing and tissue repair, comprising administering the compositions of the present invention to an animal.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
October 2, 2001
Assignee:
Pro-Neuron, Inc.
Inventors:
Reid Warren von Borstel, Michael Kevin Bamat
Abstract: 2′-O-modified ribosyl nucleosides and modified oligonucleotides containing such nucleotides are disclosed. Oligonucleotides are disclosed that have increased binding affinity as shown by molecular modeling experiments. The 2′-O-modified nucleosides of the invention include ring structures that position the sugar moiety of the nucleosides preferentially in 3′ endo geometries.
Type:
Grant
Filed:
July 27, 1998
Date of Patent:
August 7, 2001
Assignee:
Isis Pharmaceuticals, Inc.
Inventors:
Muthiah Manoharan, Venkatraman Mohan, Herb Boswell
Abstract: Nucleosides and linked nucleosides functionalized to include alkylthiol chemical functionality at ribofuranosyl positions, nucleosidic base positions, or on internucleoside linkages. In certain embodiments, the compounds of the invention further include steroids, reporter molecules, reporter enzymes, lipophilic molecules, peptides or proteins attached to the nucleosides through the alkylthio group.
Abstract: An efficient, regiocontrolled approach to the synthesis of 8-fluoropurines by direct fluorination of purines with dilute elemental fluorine, or acetyl hypofluorite, is provided. In a preferred embodiment, a purine compound is dissolved in a polar solvent and reacted with a dilute mixture of F2 in He or other inert gas.
Type:
Grant
Filed:
November 25, 1998
Date of Patent:
July 17, 2001
Assignee:
The Regents of Univ. of California
Inventors:
Jorge R. Barrio, Nagichettiar Satyamurthy, Mohammad Namavari, Michael E. Phelps
Abstract: A novel process for preparing 2-halo-6-aminopurine derivatives and their analogs is disclosed. The method comprises halogenation of 2,6-diaminopurine derivatives at the C-2 position in a specific combination of aprotic polar and nonpolar organic solvents to give the corresponding halogenated derivatives.
Abstract: Provided are very highly water soluble, stable, crystalline salts of 2′,3′-dideoxy-2′,3′-didehydrothymidine (“d4T”), 2′,3′-dideoxyinosine (“ddI”), and 2′,3′-dideoxy-2′-fluoroinosine (“F-ddI”). Such salts are useful as intermediates or as antiviral agents.
Type:
Grant
Filed:
December 6, 1991
Date of Patent:
March 27, 2001
Assignee:
Bristol-Myers Squibb Company
Inventors:
Joseph B. Bogardus, Murray A. Kaplan, Robert K. Perrone
Abstract: A method for inhibiting replication of reverse transcriptase dependent virus in plant or animal cells, comprising the step of administering to said cells a compound that depletes the intracellular pool of deoxyribonucleoside phosphate in an amount effective to inhibit replication of said virus. Hydroxyurea is one such suitable compound. Also disclosed is a method for producing incomplete reverse-transcriptase dependent viral DNA, by administering a deoxyribonucleoside phosphate-depleting drug to cells infected with such a virus.
Type:
Grant
Filed:
February 3, 2000
Date of Patent:
February 27, 2001
Assignee:
The United States of America as represented by the Department
of Health and Human Services
Inventors:
Franco Lori, Andrea Cara, Wen-Yi Gao, Robert C. Gallo
Abstract: Oligonucleotides and other macromolecules are provided which have increased nuclease resistance, substituent groups (such as 2′-aminooxy groups) for increasing binding affinity to complementary strand, and subsequences of 2′-deoxy-erythro-pentofuranosyl nucleotides that activate RNase H. Such oligonucleotides and macromolecules are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to oligonucleotide therapeutics.
Type:
Grant
Filed:
August 7, 1998
Date of Patent:
January 9, 2001
Assignee:
ISIS Pharmaceuticals Inc.
Inventors:
Muthiah Manoharan, Phillip Dan Cook, Thazha P. Prakash, Andrew M. Kawasaki