Chalcogen Bonded Directly To The 6- Or 2-position Of A Purine Ring System (e.g., Inosine, Etc.) Patents (Class 536/27.8)
-
Patent number: 8877731Abstract: 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: GrantFiled: September 19, 2011Date of Patent: November 4, 2014Assignee: Alios Biopharma, Inc.Inventors: Leonid Beigelman, Jerome Deval, David Bernard Smith, Guangyi Wang, Vivek Kumar Rajwanshi
-
Patent number: 8809520Abstract: The invention is directed to processes of preparing phosphonate nucleosides comprising a phosphonalkoxy-substituted five-membered, saturated or unsaturated, oxygen-containing ring coupled to a heterocyclic nucleobase such as a pyrimidine or purine base.Type: GrantFiled: July 11, 2013Date of Patent: August 19, 2014Assignee: K.U. Leuven Research & DevelopmentInventors: Piet Herdewijn, Christophe Pannecouque, Tongfei Wu, Erik De Clercq
-
Patent number: 8637485Abstract: 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: GrantFiled: August 1, 2008Date of Patent: January 28, 2014Assignees: Southern Research Institute, Cornell University, H. Lee Moffitt Cancer and Research Institute, The Penn State Research FoundationInventors: John A. Secrist, III, Steven Ealick, Shridhar Bale, Anthony E. Pegg, Diane E. McCloskey, Wayne C. Guida
-
Publication number: 20140011763Abstract: The present invention relates to novel 1,2,3-triazolyl purine derivatives. The invention also relates to using the derivatives to treat cancer and various viral infections.Type: ApplicationFiled: July 8, 2013Publication date: January 9, 2014Applicant: RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORKInventor: Mahesh K. Lakshman
-
Publication number: 20130324491Abstract: 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-?-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2?-deoxy-?-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. The 2?-deoxy-?-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof may be administered either alone or in combination with another 2?-deoxy-?-L-erythro-pentofuranonucleoside or in combination with another anti-hepatitis B agent.Type: ApplicationFiled: March 22, 2013Publication date: December 5, 2013Applicants: Idenix Pharmaceuticals, Inc., L'Universite Montpellier II, Centre National de la Recherche ScientifiqueInventors: Gilles Gosselin, Jean-Louis Imbach, Martin L. Bryant
-
Patent number: 8501931Abstract: The present invention is directed to convertible nucleosides and polymer supported convertible nucleosides for use in SNAr displacement reactions. The convertible nucleosides can be used to synthesize numerous substituted purine and pyrimidine derivatives.Type: GrantFiled: October 12, 2007Date of Patent: August 6, 2013Assignee: Research Foundation of the City University of New YorkInventors: Mahesh K. Lakshman, Suyeal Bae
-
Publication number: 20130017171Abstract: A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1?, 2? or 3?-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.Type: ApplicationFiled: September 20, 2012Publication date: January 17, 2013Applicants: UNIVERSITA DEGLI STUDI DI CAGLIARI, IDENIX PHARMACEUTICALS, INC.Inventors: Idenix Pharmaceuticals, Inc., Universita Degli Studi di Cagliari
-
Publication number: 20120264707Abstract: 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-?-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2?-deoxy-?-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. The 2?-deoxy-?-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof may be administered either alone or in combination with another 2?-deoxy-?-L-erythro-pentofuranonucleoside or in combination with another anti-hepatitis B agent.Type: ApplicationFiled: May 4, 2012Publication date: October 18, 2012Applicants: IDENIX PHARMACEUTICALS, INC., L'UNIVERSITE MONTPELLIER II, CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUEInventors: Gilles Gosselin, Jean-Louis Imbach, Martin L. Bryant
-
Patent number: 8288526Abstract: The present invention provides a method for producing an inosine derivative represented by the following general formula (1) including the steps of subjecting an inosine derivative of general formula (3) to dithiocarbonylation and carrying out radical reduction of the obtained compound. According to the present invention there can be produced compounds useful as anti-AIDS drugs on industrial scale. wherein R1 may be the same or different and are each benzyl group, benzhydryl group or trityl group, each of which may have a substituent in general formulas (1) and (3).Type: GrantFiled: July 30, 2010Date of Patent: October 16, 2012Assignee: Ajinomoto Co., Inc.Inventors: Takayoshi Torii, Kunisuke Izawa, Doo Ok Jang, Dae Hyan Cho
-
Publication number: 20120245335Abstract: The disclosed invention provides compositions and methods of treating a Flaviviridae infection, including hepatitis C virus, West Nile Virus, yellow fever virus, and a rhinovirus infection in a host, including animals, and especially humans, using a (2?R)-2?-deoxy-2?-fluoro-2?-C-methyl nucleosides, or a pharmaceutically acceptable salt or prodrug thereof.Type: ApplicationFiled: June 7, 2012Publication date: September 27, 2012Applicant: GILEAD PHARMASSET LLCInventor: Jeremy Clark
-
Publication number: 20120232029Abstract: 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: December 13, 2011Publication date: September 13, 2012Applicant: Pharmasset, Inc.Inventors: MICHAEL JOSEPH SOFIA, Jinfa Du
-
Patent number: 8252920Abstract: The present invention provides a method for producing an inosine derivative represented by the following general formula (1) including the steps of subjecting an inosine derivative of general formula (3) to dithiocarbonylation and carrying out radical reduction of the obtained compound. According to the present invention there can be produced compounds useful as anti-AIDS drugs on industrial scale. wherein R1 may be the same or different and are each benzyl group, benzhydryl group or trityl group, each of which may have a substituent in general formulas (1) and (3).Type: GrantFiled: July 30, 2010Date of Patent: August 28, 2012Assignee: Ajinomoto Co., Inc.Inventors: Takayoshi Torii, Kunisuke Izawa, Doo Ok Jang, Dae Hyan Cho
-
Patent number: 8193339Abstract: This invention relates to a process of stereoselectively synthesizing a ?-nucleoside compound of formula (I): wherein R1, R2, and B are as defined in the specification; each of R3 and R4, independently, is H or fluoro. The process includes reacting, in the presence of a transition metal salt, a tetrahydrofuran compound of formula (II): wherein R1, R2, and L are as defined in the specification, with a nucleobase derivative; and each of R3 and R4, independently, is H or fluoro.Type: GrantFiled: November 6, 2008Date of Patent: June 5, 2012Assignee: Pharmaessentia Corp.Inventors: Chi-Yuan Chu, Wei-Der Lee, Wensen Li, Chan Kou Hwang
-
Patent number: 8188055Abstract: Disclosed are compounds that are AGT inactivators that include a folate residue, e.g., a compound of formula (I), wherein X1, X2, R1, and R2 are as described herein. Also disclosed is a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable carrier. Also disclosed are methods of enhancing the chemotherapeutic treatment of tumor cells and inactivating AGT in a tumor cell. The methods comprise, inter alia, administering a compound or pharmaceutically acceptable salt of formula (I).Type: GrantFiled: March 12, 2008Date of Patent: May 29, 2012Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services, The Penn State Research FoundationInventors: Robert C. Moschel, Matthew Karl Moschel, legal representative, Anthony E. Pegg, Sahar Javanmard, Natalia Loktionova, Gary Pauly
-
Patent number: 8173797Abstract: 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: GrantFiled: July 21, 2005Date of Patent: May 8, 2012Assignee: Cornell Research Foundation, Inc.Inventors: Jerrold Meinwald, Andrew Edmund Taggi, Frank Clemens Schroeder
-
Publication number: 20110130285Abstract: A composition for promoting root nodule formation, which can be easily applied to soil or plants, and enables efficient formation of root nodules, and a method for promoting root nodule formation using the composition are provided. A composition for promoting root nodule formation, which comprises a compound selected from the group consisting of a nucleoside, a nucleotide, and a nucleobase such as inosine, as an active ingredient, is applied to a leguminous plant to promote root nodule formation of the plant.Type: ApplicationFiled: November 30, 2010Publication date: June 2, 2011Inventors: Kazuhiko Watanabe, Daisuke Yokoi
-
Patent number: 7915232Abstract: 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 which inhibit HCV polymerase and are useful for treating a patient suffering from a HCV infection and to pharmaceutical compositions containing such compounds.Type: GrantFiled: September 14, 2009Date of Patent: March 29, 2011Assignee: Roche Palo Alto LLCInventors: Joseph Armstrong Martin, John Herbert Merrett, Isabel Najera, Rene Robert Devos, Christopher John Hobbs, Wen Rong Jiang, Nobuo Shimma, Takuo Tsukuda
-
Publication number: 20100324279Abstract: The present invention provides novel crystal forms of 2-[2-(4-chlorophenyl)ethoxy]adenosine of the formula processes for the production of such crystal forms, and methods for the manufacture of pharmaceutical compositions for the treatment of diseases or conditions modulated by the adenosine A2 receptors, in particular the A2A receptor, in a mammal in need thereof, by employing such crystal forms. The crystal forms of the present invention are especially useful in the preparation of topical compositions for accelerating wound healing, e.g., for the treatment of diabetic foot ulcers.Type: ApplicationFiled: December 18, 2008Publication date: December 23, 2010Inventors: Patricia M.J. Andres, Ron C. Kelly, Allan R. Moorman, Matthew Strange
-
Patent number: 7816513Abstract: The present invention provides a method for producing an inosine derivative represented by the following general formula (1) including the steps of subjecting an inosine derivative of general formula (3) to dithiocarbonylation and carrying out radical reduction of the obtained compound. According to the present invention there can be produced compounds useful as anti-AIDS drugs on industrial scale. wherein R1 may be the same or different and are each benzyl group, benzhydryl group or trityl group, each of which may have a substituent in general formulas (1) and (3).Type: GrantFiled: December 16, 2005Date of Patent: October 19, 2010Assignee: Ajinomoto Co., Inc.Inventors: Takayoshi Torii, Kunisuke Izawa, Doo Ok Jang, Dae Hyan Cho
-
Patent number: 7807653Abstract: The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.Type: GrantFiled: June 14, 2007Date of Patent: October 5, 2010Assignee: Biota Scientific Management Pty LtdInventors: Phillip D. Cook, Guangyi Wang, Thomas W. Bruice, Nicholas A. Boyle, Janet M. Leeds, Jennifer L. Brooks, Marija Prhavc, Maria Eugenia Ariza, Patrick C. Fagan, Yi Jin, Vivek K. Rajwanshi, Kathleen D. Tucker
-
Patent number: 7781432Abstract: Analogs or derivatives of nitrobenzylthioinosine corresponding to formula I: in which R represents an unsubstituted or mono- or polysubstituted phenyl, benzyl or heteroaryl group or a phenyl group condensed with heteroaryl, and R? represents an unsubstituted or mono- or polysubstituted NH—C1-6-alkyl, NH-aryl, NH-heteroaryl, NH—C3-8-cycloalkyl, NH—C1-3-alkyl-aryl, NH—C1-3-alkyl-heteroaryl, N(C1-6-alkyl)2, N(C1-3-alkyl-aryl)2, N(C1-3-alkyl-heteroaryl)2, piperidine, piperazine, morpholine or pyrrolidine group; pharmaceutical compositions comprising such analogs or derivatives, and the use of such analogs or derivatives for treating pain and/or various other diseases.Type: GrantFiled: December 29, 2006Date of Patent: August 24, 2010Assignees: Gruenenthal GmbH, Leiden UniversityInventors: Adriaan Pieter Ijzermann, Reynier Tromp
-
Publication number: 20100129317Abstract: Azole nucleosides represented by the formulae (I) and (II); wherein A=C or N B?C or N X?H; C1-C6 alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, heterocyclo, halogen such as F, Cl, Br and I; OH, NH2, NH—(C1-C6 alkyl, cycloalkyl, aryl or heterocyclo); Z?H; C1-C6 alkyl, cycloalkyl, alkynyl, aryl, heterocyclo, halogen such as F, Cl, Br, I; OH NH2, NH—(C1-C6 alkyl, cycloalkyl, aryl or heterocyclo; E=(CH2)HONHR; n is an interger from 0-6 and more typically 0-3; R1= aryl or heterocyclo; each of W, Y, R is individually selected from the group consisting of H; C1-C6 alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, heterocyclo, halogen such as F, Cl, Br, and I; O, OH, Oalkyl, Oaryl, NH2, NH(C1-C6 alkyl, cycloalkyl, aryl or heterocyclo); provided that at least one of W, Y, and R is other than H and wherein both W and Y together can be ?O; and each D individually is OH, Oalkyl, Oaryl, FL and H; pharmaceutically acceptable salts thereof, prodrugs thereof and mixtures thereof are provided.Type: ApplicationFiled: September 11, 2007Publication date: May 27, 2010Applicant: SOUTHERN RESEARCH INSTITUTEInventors: Jeffrey B. Arterburn, Colleen B. Jonsson, William B. Parker
-
Publication number: 20100069319Abstract: The invention provides novel mercaptopurine derivatives, e.g., S-allylthio-6-mercaptopurine and S-allylthio-6-mercaptopurine 9-riboside, as well as pharmaceutical compositions thereof. These compounds are highly efficient anti-proliferative agents, thus can be useful for treatment of various diseases or disorders, in particular, proliferative, inflammatory, skin and immune diseases or disorders.Type: ApplicationFiled: March 2, 2008Publication date: March 18, 2010Inventors: Talia Miron, Aharon Rabinkov, David Mirelman, Meir Wilchek
-
Publication number: 20100048500Abstract: The present invention relates to novel compounds according to the general formulas I, II, III, IV or V: wherein B is nucleoside base according to the structure: and the remaining variables as defined in the specification, and pharmaceutical compositions comprising the compounds. The compounds are useful interalia as anti-viral agents in viral therapy.Type: ApplicationFiled: August 17, 2009Publication date: February 25, 2010Inventors: Yung-chi Cheng, Hiromichi Tanaka, Masanori Baba
-
Patent number: 7605143Abstract: The invention provides compounds having the following general formula (I): wherein X, R1, R2, R7 and Z are as described herein.Type: GrantFiled: August 2, 2005Date of Patent: October 20, 2009Assignee: University of Virginia Patent FoundationInventors: Jayson M. Rieger, Joel M. Linden, Timothy L. Macdonald, Gail W. Sullivan, Lauren J. Murphree, Robert Alan Figler
-
Publication number: 20090068125Abstract: This invention relates to a medicament for protecting human mucosal cells from chemotherapy or radiotherapy induced cell death using formulations comprising adenosine or adenosine analogues as a reversible inhibitor of epithelial cell proliferation. The invention also relates to formulations containing adenosine for the prevention of or reduction in mucositis symptoms.Type: ApplicationFiled: January 25, 2006Publication date: March 12, 2009Applicant: HEPTAGEN LTDInventors: Richard Mark Edwards, John Martin Clements
-
Patent number: 7495095Abstract: The present invention provides a thionucleoside-S-nitrosyl derivative of the following Formula I or a salt thereof: [wherein R1 represents ribose, 2-deoxyribose or a derivative of either, and R2 represents a hydrogen atom, an amino group, a hydroxyl group, a halogen atom, a R3-oxy group or a R3-amino group (wherein R3 represents an optionally substituted C1-15 alkyl group or an optionally substituted C1-15 acyl group)].Type: GrantFiled: March 12, 2004Date of Patent: February 24, 2009Assignee: Kyushu University, National University CorporationInventor: Shigeki Sasaki
-
Patent number: 7358235Abstract: 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: GrantFiled: October 6, 2004Date of Patent: April 15, 2008Assignees: Gruenenthal GmbH, Leiden UniversityInventors: Claudia Puetz, Corinna Sundermann, Bernd Sundermann, Adriaan Pieter Ijzerman, Reynier Tromp, Jacobien Von Frijtag Drabbe Kuenzel
-
Patent number: 7323451Abstract: Physical forms of beta-L-2?-deoxythymidine are disclosed that can be characterized by physical appearance, purity levels, Infra-Red and Raman spectroscopy, X-ray powder diffraction patterns, thermal properties, and methods of manufacture. These forms of beta-L-2?-deoxythymidine can be used in the manufacture of other forms of beta-L-2?-deoxythymidine, or in pharmaceutical compositions. Particularly preferred uses are in the treatment of hepatitis B.Type: GrantFiled: August 6, 2003Date of Patent: January 29, 2008Assignee: Idenix Pharmaceuticals, Inc.Inventors: David Jonaitis, Richard Storer
-
Patent number: 7307166Abstract: The invention relates to certain oxypurine nucleosides, congeners of such oxypurine nucleosides, and acyl derivatives thereof, and compositions which contain at least one of these compounds. The invention also relates to methods of treating or preventing hematopoietic disorders and modifying hematopoiesis, and treating or preventing inflammatory diseases and bacterial infections by administering a compound or composition of the present invention to an animal.Type: GrantFiled: June 5, 1995Date of Patent: December 11, 2007Assignee: Wellstat Therapeutics CorporationInventors: Reid W. von Borstel, Michael K. Bamat, Bradley M. Hiltbrand, James C. Butler, Shyam Shirali
-
Patent number: 7247721Abstract: Surfaces containing high purity silica (silicon dioxide) exhibit high loading potential for nucleic acids. Formulations containing nucleic acids and materials which mask the electrostatic interactions between the nucleic acids and surfaces are disclosed. By masking the phosphate charges of the nucleic acids, undesired interactions may be minimized or eliminated, thereby allowing the covalent bonding of the nucleic acids to the surface to proceed. The use of such formulations additionally minimizes nonspecific binding of the nucleic acids to the surface. Examples of materials to be included in such formulations include cations, xanthines, hexoses, purines, arginine, lysine, polyarginine, polylysine, and quaternary ammonium salts.Type: GrantFiled: February 14, 2005Date of Patent: July 24, 2007Inventor: Mark B. Lyles
-
Patent number: 6914138Abstract: 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: GrantFiled: August 9, 2002Date of Patent: July 5, 2005Assignee: Gilead Sciences, Inc.Inventors: Gary Kirschenheuter, Bruce Eaton
-
Patent number: 6903079Abstract: 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 carbocyclType: GrantFiled: December 16, 2002Date of Patent: June 7, 2005Assignee: Inotek Pharmaceuticals CorporationInventors: Prakash Jagtap, Garry Southan, Andrew Salzman, Csaba Szabo, Siya Ram
-
Patent number: 6900307Abstract: There are provided 2-aminopurine derivatives represented by the following general formula (1): where R represents any species selected from the group consisting of hydrogen and acyl groups, X represents any species selected from the group consisting of phosphoramidite and oligonucleotides, Y represents any species selected from the group consisting of dimethyltrityl groups and oligonucleotides, and Z1, Z2, Z3, Z4 and Z5 are the same or different and represent any species selected from the group consisting of hydrogen and hydroxyl, amino, lower alkyl, alkoxy, carboxyl and sulfonic acid groups, provided that Z1, Z2, Z3, Z4 and Z5 are not all hydrogen, as well as gene expression-regulating compositions characterized by comprising the derivatives. By introducing the 2-aminopurine derivatives into oligonucleotides it is possible to achieve crosslinking reaction with high reactivity for target nucleic acids and notably high base sequence specificity.Type: GrantFiled: November 2, 2000Date of Patent: May 31, 2005Assignee: Hisamitsu Pharmaceutical Co., Inc.Inventors: Shigeki Sasaki, Fumi Nagatsugi, Minoru Maeda
-
Publication number: 20040175804Abstract: A method of making didanosine (ddI) including the steps of: (a) obtaining an enzyme expressing ddA deaminase activity; (b) immobilizing the enzyme onto an insoluble support; (c) contacting the enzyme with a dideoxyadenosine (ddA) solution of at least about 4% weight volume ddA in water for a time and under conditions to produce a ddI solution; and (d) isolating the ddI from the ddI solution. Optionally, the ddI mother liquor is reused in subsequent runs to improve yield.Type: ApplicationFiled: February 26, 2004Publication date: September 9, 2004Inventors: Paul M. Skonezny, Michael Politino, Suo W. Liu, Alfred W. Boyle, Jason G. Chen, Gregory L. Stein, Thomas Franceschini, Wendy L. Anderson
-
Patent number: 6699978Abstract: The present invention relates to a linker nucleoside, its preparation and use for the covalent bonding of biomolecules to oligonucleotides, in particular p-RNA oligonucleotides.Type: GrantFiled: July 11, 2000Date of Patent: March 2, 2004Assignee: Nanogen Recognomics GmbHInventors: Christian Miculka, Norbert Windhab, Tilmann Brandstetter, Stefan Scherer
-
Patent number: 6677345Abstract: A range is disclosed of pyrimidine derivatives (I) which can act as inhibitors of cyclin dependent kinases (CDK's) and which thereby can provide useful therapeutic compounds for use in treatment of tumours or other cell proliferation disorders. The compounds of this invention bind to CDK molecules in a manner that appears to differ from that of known CDK inhibitors such as olomoucine and roscovitine.Type: GrantFiled: September 28, 2000Date of Patent: January 13, 2004Assignee: Cancer Research Campaign Technology LimitedInventors: Roger J Griffin, Alan H Calvert, Nicola J Curtin, David R Newell, Bernard T Golding, Jane A Endicott, Martin E M Noble, Francis T Boyle, Philip J Jewsbury
-
Patent number: 6646118Abstract: The present invention relates to a support system for solid phase synthesis of oligomers, such as oligonucleotides, 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: GrantFiled: March 25, 2002Date of Patent: November 11, 2003Assignee: Quiatech ABInventors: Marek Kwiatkowski, Mats Nilsson, Ulf Landegren
-
Patent number: 6620796Abstract: The invention provides new methods for synthesis of nucleotide-based compounds and new libraries of such compounds. Compounds of the invention are useful for a variety of therapeutic applications, including treatment of viral or bacterial infections and associated diseases and disorders.Type: GrantFiled: November 8, 2000Date of Patent: September 16, 2003Assignee: Micrologix Biotech Inc.Inventors: Wenqiang Zhou, Yi Jin, Arlene Roland, Radhakrishnan Iyer
-
Patent number: 6596858Abstract: 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.Type: GrantFiled: March 12, 2001Date of Patent: July 22, 2003Assignee: Reliable Biopharmaceutical, Inc.Inventors: UmaShanker Sampath, Lawrence Bartlett
-
Patent number: 6579976Abstract: There can be provided an excellent industrial process for producing compounds having sugar-moiety hydroxyl groups or halogen atoms reduced in nucleic acids or in derivatives thereof by allowing O-thiocarbonyl derivatives of sugar-moiety hydroxyl groups or allowing halogenated derivatives in the sugar-moiety, in the nucleic acids or in derivatives thereof to react with any one of hypophosphorous acids (including salts thereof) and phosphites (esters) which are inexpensive, non-toxic and safely usable as radical reducing agents in industrial scale, in the presence of a radical reaction initiator. The process of the present invention is an industrially useful and highly safe process for reducing sugar-moiety hydroxyl groups and halogen atoms in nucleic acids or derivatives thereof (including nucleic acid-related compounds) at low costs.Type: GrantFiled: October 26, 1999Date of Patent: June 17, 2003Assignee: Ajinomoto Co., Inc.Inventors: Satoshi Takamatsu, Satoshi Katayama, Naoko Hirose, Kunisuke Izawa
-
Patent number: 6555676Abstract: Compounds of formula RS—P(═O)(QR)—Nu where: R is a radical —(CH2)n—W—X; X is a radical —C(═Z)(Y) or —S—U; Z is O or S; W is O or S; Q is O or S; Y and U are an alkyl, aryl or saccharide radical which is optionally substituted with, for example, an OH, SH or NH group; n is equal to 1 to 4, preferably 1 or 2; and Nu is a radical consisting of a residue of a biologically active compound or the dephosphorylated residue of a compound which is biologically active when it bears a phosphate or phosphonate group.Type: GrantFiled: September 21, 2001Date of Patent: April 29, 2003Assignee: Centre National de la Recherche ScientifiqueInventors: Gilles Gosselin, Jean-Louis Imbach, Christian Perigaud
-
Patent number: 6531589Abstract: The invention provides new methods for synthesizing oligonucleotides that allow for deprotection of the oligonucleotides under more mild conditions than existing methods. The invention further provides a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups, as well as nucleoside synthons having such base protecting groups.Type: GrantFiled: February 8, 1996Date of Patent: March 11, 2003Assignee: Hybridon, Inc.Inventors: Radhakrishnan P. Iyer, Theresa Devlin, Ivan Habus, Dong Yu, Sudhir Agrawal, Nan-Hui Ho
-
Patent number: 6528042Abstract: Non-naturally-occurring compositions for use in amelioration of disruption of energy metabolism secondary to stress are described. These compositions comprise a flavonoid or derivative thereof and a synergist. Synergists include, but are not limited to, amino acids, carbohydrates, carnitines, flavonoids, nucleosides, and tocopherols and/or derivatives thereof. Methods of making these compositions and methods of ameliorating disruption of energy metabolism secondary to stress, comprising administering such synergistic compositions, are also disclosed.Type: GrantFiled: October 6, 2000Date of Patent: March 4, 2003Assignee: Galileo Laboratories, Inc.Inventors: Lesley A. Brown, Guy Miller
-
Patent number: 6506888Abstract: Novel nucleoside or nucleotide analogs comprising 2′-O-amino residues, processes for their synthesis and incorporation into polynucleotides.Type: GrantFiled: September 19, 2000Date of Patent: January 14, 2003Assignee: Ribozyme Pharmaceuticals, Inc.Inventors: Alexander Karpeisky, Leonid Beigelman
-
Patent number: 6504024Abstract: Propargylethoxyamino nucleosides are disclosed having the structure wherein R1 and R2 are —H, lower alkyl, or label; B is a 7-deazapurine, purine, or pyrimidine nucleoside base; W1 is —H or —OH; W2 is —OH or a moiety which renders the nucleoside incapable of forming a phosphodiester bond at the 3′-position; and W3 is —PO4, —P2O7, —P3O10, phosphate analog, or —OH. Additionally, a primer extension method is provided employing the above propargylethoxyamino nucleosides.Type: GrantFiled: June 14, 2001Date of Patent: January 7, 2003Assignee: PE Corporation (NY)Inventors: Shaheer H. Khan, Steven M. Menchen, Barnett B. Rosenblum
-
Patent number: 6500946Abstract: 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: GrantFiled: May 10, 2000Date of Patent: December 31, 2002Assignee: Ajinomoto Co., Inc.Inventors: Satoshi Takamatsu, Satoshi Katayama, Naoko Hirose, Kunisuke Izawa, Tokumi Maruyama
-
Patent number: 6498149Abstract: The present invention provides substances having an efficacy against tumors and viruses on which the conventional anti-tumor agents and anti-virus agents exhibit only insufficient effects, and having carcinostatic effect and anti-virus effect on various resistant tumors as well as a reduced side effect such that normal human cells will not be impaired. The present invention relates to an anti-tumor or anti-viral substance represented by the formula (1) wherein R1 represents a nucleic acid base represented by a specific formula, and R2 represents a hydrogen atom, a hydroxy group or a methoxy group, or a pharmaceutically acceptable salt thereof.Type: GrantFiled: December 3, 1999Date of Patent: December 24, 2002Assignees: Techno Seven Co., Ltd.Inventors: Tsuneatsu Mori, Maowu Guo, Etsuko Mori
-
Patent number: RE38090Abstract: The invention relates to a 3′-substituted nucleoside derivative represented by the following general formula (1): wherein B means a nucleic acid base which may have a substituent, Z represents a lower alkynyl or lower alkenyl group which may be substituted by a group represented by the formula: in which Ra, Rb and Rc are individually a lower alkyl group or a phenyl group, or an oxiranyl group which may have at least one lower alkyl group, R1 and R2 individually represent H or an ester-forming residue capable of easily leaving in a living body, and R3 is H, a mono- or polyphosphoric acid residue, or an ester-forming residue capable of easily leaving in a living body, with the proviso that the sugar moiety is ribose, or a pharmaceutically acceptable salt thereof. The 3′-substituted nucleoside derivative according to the invention has an excellent antitumor activity and is hence useful for treatment for and prevention of cancers.Type: GrantFiled: May 26, 2000Date of Patent: April 22, 2003Assignees: Taiho Pharmaceutical Co., Ltd.Inventors: Akira Matsuda, Takuma Sasaki
-
Patent number: RE38416Abstract: This invention is directed to novel substituted nucleotide bases with a crosslinking arm which accomplish crosslinking between specific sites on adjoining strands of oligonucleotides a oligodeoxynucleotides. The invention is also directed to oligonucleotides comprising at least one of these crosslinking agents and to the use of the resulting novel oligonucleotides for diagnostic and therapeutic purposes.Type: GrantFiled: October 19, 2000Date of Patent: February 3, 2004Assignee: Epoch Biosciences, Inc.Inventors: Charles R. Petrie, Rich B. Meyer, John C. Tabone, Gerald D. Hurst