Abstract: Methods and compositions are described for analyzing complex protein mixtures using fluorescent activity-based probes. In particular, probes that specifically react with and bind to the active form of one or more target proteins are employed. Fluorescent signals obtained from the labeled active target proteins can be related to the presence or amount of active members of the desired target protein class. The methods and compositions described herein can be used, for example, to provide diagnostic information concerning pathogenic states, in identifying proteins that may act as therapeutic targets, and in drug discovery.
Abstract: The present invention is directed to a method of reducing intraocular pressure. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a purinerginic receptor ligand, which is a mononucleoside polyphosphate or dinucleoside polyphosphate defined by general Formula I. The method of the present invention is useful in the treatment or prevention of ocular hypertension, such as glaucoma, including primary and secondary glaucoma. The method can be used alone to reduce intraocular pressure. The method can also be used in conjunction with other therapeutic agents or adjunctive therapy commonly used to treat glaucoma to enhance the therapeutic effect of reducing the intraocular pressure.
Type:
Grant
Filed:
January 15, 2003
Date of Patent:
August 1, 2006
Assignee:
Inspire Pharmaceuticals, Inc.
Inventors:
Benjamin R. Yerxa, Robert Plourde, Jr., Edward G. Brown, Ward M. Peterson
Abstract: A purine nucleoside analog includes a pyrido[2,3-d]pyrimidine or a pyrimido[4,5-d]pyrimidine and further has a sugar moiety that is optionally modified at the C2?, C3?, C4? and/or C5? position. Particularly contemplated compounds also include prodrug forms of the purine nucleoside analogs, and both purine nucleoside analogs and the corresponding prodrugs are employed in the reduction of growth of neoplastic cells.
Type:
Grant
Filed:
July 3, 2001
Date of Patent:
July 25, 2006
Assignee:
Valeant Research & Development
Inventors:
Zbigniew Pietrzkowski, Guangyi Wang, Johnson Lau, Zhi Hong, Jean-Luc Girardet, Esmir Gunic
Abstract: The invention relates to the use of morpholino-nucleosides of formula: in which R1 represents a nucleic base and R2 represents a group corresponding to one of the following formulae: —(CH2)n—NH2 —(CH2)n—SH —(CH2)n—COOH —(CH2)n—OH —(CH2)n—NH—R3 —(CH2)n—SR3 —(CH2)n—CO—R3 —(CH2)n—OR3 in which n is an interger ranging from 1 to 12 and R3 is a group derived from a label, from a protein, from an enzyme, from a fatty acid or from a peptide, as chain terminators in a process of DNA or RNA sequencing by the Sanger method, or for the labelling of DNA or RNA fragments.
Type:
Grant
Filed:
December 9, 2003
Date of Patent:
July 25, 2006
Assignees:
Commissariat a l'Energie Atomique, Centre National de la Recherche Scientifique
Abstract: The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The pharmaceutical formulation useful in this invention comprises a P2Y receptor agonist with enhanced resistance to extracellular hydrolysis, such as dinucleoside polyphosphate compounds, or hydrolysis-resistant mononucleoside triphosphates.
Abstract: Nucleoside phosphinoamidite carboxylates and analogs are provided that have the structure of formula (III) wherein A is hydrogen, hydroxyl, lower alkoxy, lower alkoxy-substituted lower alkoxy, halogen, SH, NH2, azide or DL wherein D is O, S or NH and L is a heteroatom-protecting group, unsubstituted hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; B is a nucleobase; and one of R11 and R12 is a blocking group and the other is (IV) or (VI) in which W, X, Y, Z, R1 and n are as defined herein.
Abstract: The present invention provides compounds having the formula: wherein A is chosen from a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group; both B and C are hydrogen, or either B or C is a halogen, amino, or thiol group and the other of B or C is hydrogen; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds.
Type:
Grant
Filed:
January 4, 2002
Date of Patent:
June 6, 2006
Assignee:
Albert Einstein College of Medicine of Yeshiva University
Abstract: The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds, which comprise a phosphocholine moiety covalently conjugated with one or more therapeutic agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt or a prodrug thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus.
Type:
Grant
Filed:
April 27, 2001
Date of Patent:
April 11, 2006
Assignees:
Wake Forest University School of Medicine, University of North Carolina at Chapel
Inventors:
Louis S. Kucera, Ronald A. Fleming, Khalid S. Ishaq, Gregory L. Kucera, Susan L. Morris-Natschke
Abstract: The present invention provides compounds having the formula: wherein A is a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group, the group being further substituted with an electron contributing moiety; B is hydrogen, or a halogen, amino, or thiol group; C is hydrogen, or a halogen, amino, or thiol group; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds.
Type:
Grant
Filed:
May 30, 2002
Date of Patent:
April 4, 2006
Assignee:
Albert Einstein College of Medicine of Yeshiva University
Abstract: A process for the synthesis in solution phase of a phosphorothioate triester is provided. The process comprises the solution phase coupling of an H-phosphonate with an alcohol in the presence of a coupling agent to form an H-phosphonate diester. The H-phosphonate diester is oxidised in situ with a sulfur transfer agent to produce the phosphorothioate triester. Preferably, the H-phosphonate and alcohol are protected nucleosides or oligonucleotides. Oligonucleotide H-phosphonates which can be used in the formation of phosphorothioate triesters are also provided.
Abstract: The present invention relates to novel water-soluble, stable derivatives of combretastatin A-4, and novel synthesis methods therefore. The combretastatin A-4 prodrugs described herein appear to be useful in the treatment of neoplastic disease.
Type:
Grant
Filed:
January 8, 1999
Date of Patent:
March 28, 2006
Assignee:
Arizona Broad of Regents acting for and on behalf of Arizona State University
Abstract: A novel compound, 2?/3?-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2? and 3? regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2?-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2?/3?-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2?/3?-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2?/3?-O-acetyl-ADP-ribose are also provided.
Type:
Grant
Filed:
November 21, 2002
Date of Patent:
January 17, 2006
Assignee:
Albert Einstein College of Medicine of Yeshiva University
Inventors:
Vern L. Schramm, Jef D. Boeke, Anthony Sauvé, Ivana Celic
Abstract: Uridine analogs and techniques for making and using uridine analogs are disclosed in this invention. These uridine analogs include nucleoside phosphates having a 5-aminouracil group. These nucleotides can be incorporated into a nucleic acid as an unnatural base, as a substitute for uridine or thymine. The nucleic acid can then be treated with an oxidizing agent and an alkaline solution, which causes cleavage of the nucleic acid at the position of the unnatural base. The nucleoside phosphate analogs can be used in many ways, including measuring chemical interactions between nucleic acids and other compounds, or sequencing nucleic acids. Additional compounds can also be derivitized onto the amino group, allowing other functionalities to be added to the nucleoside phosphate, or to the nucleic acid incorporating the nucleoside phosphate.
Type:
Grant
Filed:
February 7, 2002
Date of Patent:
January 17, 2006
Assignee:
President and Fellows of Harvard College
Abstract: The present invention relates to certain novel dinucleotides and formulations thereof which are highly selective agonists of the P2Y2 and/or P2Y4 purinergic receptor. They are useful in the treatment of chronic obstructive pulmonary diseases such as chronic bronchitis, PCD, cystic fibrosis, as well as prevention of pneumonia due to immobility. Furthermore, because of their general ability to clear retained mucus secretions and stimulate ciliary beat frequency, the compounds of the present invention are also useful in the treatment of sinusitis, otitis media and nasolacrimal duct obstruction. They are also useful for treatment of dry eye disease and retinal detachment as well as facilitating sputum induction and expectoration.
Type:
Grant
Filed:
November 6, 2001
Date of Patent:
December 20, 2005
Assignee:
Inspire Pharmaceuticals, Inc.
Inventors:
William Pendergast, Benjamin R. Yerxa, Janet L. Rideout, Suhaib M. Siddiqi
Abstract: The present invention is directed to nucleoside monomers wherein the 3?-O atom is replaced with a methylene group. The present invention also provides oligomers comprising a plurality of such monomers which are linked by methylene phosphonate linkages. Further, methods of preparing monomers and oligomers according to the present invention are provided.
Type:
Grant
Filed:
December 18, 2002
Date of Patent:
December 13, 2005
Assignee:
ISIS Pharmaceuticals, Inc.
Inventors:
Phillip Dan Cook, Muthiah Manoharan, Martin Maier, Haoyun An
Abstract: The present invention provides a nucleoside comprising a pyrazolopyrimidine base and a process for producing the same. In particular, the processes of the present invention comprises using a halogenated pyrazolopyrimidine base and removing the halogen after the base is coupled to a sugar moiety. The presence of the halogen on the nucleoside base allows facile and economical production of a large quantity of nucleosides.
Type:
Grant
Filed:
September 12, 2001
Date of Patent:
November 8, 2005
Assignee:
Epoch Biosciences, Inc.
Inventors:
Robert O. Dempcy, A. David Adams, Michael W. Reed, Yevgeniy S. Belousov
Abstract: The invention relates to a novel labeling reactant of formula (I) suitable for labeling an oligonucleotide wherein: R is a temporary protecting group. A is either a phosphorylating moiety or a solid support tethered to a bridge point Z via a linker arm E. E? is a linker arm between G and Z. G is a bivalent aromatic structure, tethered to two iminodiacetic acid ester groups N(COOR??)2 or G is a structure selected from a group consisting of G is a protected functional group. The invention further concerns a method for direct attachment of a conjugate group to an oligonucleotide structure enabling the attachment of a desired number of these groups during chain assembly. The method comprises a Mitsonobu alkylation.
Abstract: The present invention is directed to ?-modified nucleoside triphosphates and methods for their preparation. The present invention also provides for methods of inhibiting RNA and viral replication in cells, as well as methods for treating viral infections.
Abstract: The present invention is directed to a method of treating pain. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a P2X receptor antagonist. The methods of the present invention are useful in reducing pain, such as traumatic pain, neuropathic pain, organ pain and pain associated with diseases. The P2X receptor antagonists particularly useful for this invention are mononucleoside polyphosphate derivatives or dinucleoside polyphosphate derivatives of general Formula I. The compounds of the present method can be used alone to treat pain. The compounds of the present method can also be used in conjunction with other therapeutic agents or adjunctive therapies commonly used to treat pain, thus enhancing the overall pain-reducing effect in a subject in need of such treatment.
Type:
Grant
Filed:
January 31, 2003
Date of Patent:
April 19, 2005
Assignee:
Inspire Pharmaceuticals Inc.
Inventors:
Benjamin R. Yerxa, Ward M. Peterson, Christopher S. Crean
Abstract: The invention relates to a functionalized compound of general formula (I): in which W represents a nucleotide analog, L represents a linker arm comprising at least four atoms, R1 represents a linear or branched alkyl chain, A functionalized polynucleotide comprising at least one said compound and a labeled functionalized polynucleotide comprising at least one functionalized compound corresponding to the formula (I?). A method for detecting a target nucleic acid using a said compound is described.
Type:
Grant
Filed:
January 5, 2000
Date of Patent:
April 5, 2005
Assignee:
Bio Merieux
Inventors:
Eric DeFrancq, Ali Laayoun, Jean Lhomme, Emmanuelle Trevisiol
Abstract: The invention concerns compounds of the general formula (I) in which the residues R1 to R7 have the meanings given in the application as well as methods for their preparation.
Abstract: The present invention is directed to P1, P4-di(uridine 5?)-tetraphosphate, tetra-alkali metal salts such as tetrasodium, tetralithium, tetrapotassium, and mixed tetra-alkali metal cations thereof. The tetra alkali metal salts of P1, P4-di(uridine 5?)-tetraphosphate are water-soluble, nontoxic, and easy to handle during manufacture. These tetra-monovalent alkali metal salts are more resistant to hydrolysis than the mono-, di-, or tri-acid salts, therefore, they provide an improved stability and a longer shelf life for storage. The present invention also provides methods for the synthesis of P1, P4-di(uridine 5?)-tetraphosphate, and its pharmaceutically acceptably acceptable salts thereof, and demonstrates the applicability to the production of large quantities. The methods substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less.
Abstract: The invention provides a method for producing a cytosine nucleoside compound from pentose-1-phosphate and cytosine or a derivative thereof using a nucleoside phosphorylase reactive to cytosine or a bacterium having the enzyme activity. The invention also provides a method for specifically reducing an activity to degrade the substrates or the product, resulting in efficient production of the cytosine nucleoside compound. According to the invention, little by-product is produced in producing cytonucleocide compounds.
Abstract: A novel nucleoside analog is disclosed which comprises a piperazine ring in the place of the ring ribose or deoxyribose sugar. Monomers utilizing a broad variety of nucleobases are disclosed, as well as oligomers comprising the monomers disclosed herein linked by a variety of linkages, including amide, phosphonamide, and sulfonamide linkages. A method of synthesizing the nucleoside analogs is also disclosed.
Type:
Grant
Filed:
June 13, 2002
Date of Patent:
January 11, 2005
Assignee:
The Regents of the University of California
Inventors:
Jurgen Schmidt, Louis A. Silks, Ryszard Michalczyk
Abstract: The invention relates to the use of morpholino-nucleosides of formula: in which R1 represents a nucleic base and R2 represents a group corresponding to one of the following formulae: —(CH2)n—NH2 —(CH2)n—SH —(CH2)n—COOH —(CH2)n—OH —(CH2)n—NH—R3—(CH2)nS—R3 —(CH2)n—CO—R3 —(CH2)n—OR3 in which n is an integer ranging from 1 to 12 and R3 is a group derived from a label, from a protein, from an enzyme, from a fatty acid or from a peptide, as chain terminators in a process of DNA or RNA sequencing by the Sanger method, or for the labelling of DNA or RNA fragments.
Type:
Grant
Filed:
February 21, 2000
Date of Patent:
January 4, 2005
Assignees:
Commissariat a l'Energie Atomique, Centre National de la Recherche Scientifique
Abstract: The present invention provides new methods for the synthesis of the therapeutic dinucleotide, P1,P4-di(uridine 5′)-tetraphosphate, and demonstrates applicability to the production of large quantities. The methods of the present invention substantially reduce the time period required to synthesize diuridine tetraphosphate, preferably to three days or less. The novel tetrammonium and tetrasodium salts of P1,P4-di(uridine 5′)-tetraphosphate (Formula I) prepared by these methods are stable, soluble, nontoxic, and easy to handle during manufacture.
Abstract: The disclosed invention is a composition for and a method of treating Flaviviridae (Hepacivirus, Flavivirus, Pestivirus) infections, including BVDV and HCV, in a host, including animals, and especially humans, using a small molecule or its pharmaceutically acceptable salt or prodrug.
Type:
Application
Filed:
December 17, 2001
Publication date:
December 30, 2004
Inventors:
Michael J. Otto, Kyoichi A. Watanabe, Steve Patterson, Krysztof W. Pankiewicz, Lieven Stuyver
Abstract: A class of 2′-fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer.
Type:
Application
Filed:
March 8, 2004
Publication date:
December 16, 2004
Inventors:
Raymond F. Schinazi, Dennis C. Liotta, Chung K. Chu, J. Jeffrey McAtee, Junxing Shi, Yongseok Choi, Kyeong Lee, Joon H. Hong
Abstract: Nucleotide analogs characterized by the presence of an amidate linked amino acid or an ester linked group which is bonded to the phosphorus atom of phosphonate nucleotide analogs are disclosed. The analogs comprise a phosphoamidate or ester bond that is hydrolyzed in vivo to yield a corresponding phosphonate nucleotide analog. Methods and intermediates for their synthesis and use are described.
Type:
Application
Filed:
June 29, 2004
Publication date:
December 2, 2004
Inventors:
Norbert W. Bischofberger, Robert J. Jones, Murty N. Arimilli, Kuei-Ying Lin, Michael S. Louie, Lawrence R. McGee, Ernest J. Prisbe, William A. Lee, Kenneth C. Cundy
Abstract: The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The pharmaceutical formulation useful in this invention comprises a P2Y receptor agonist with enhanced resistance to extracellular hydrolysis, such as dinucleoside polyphosphate compounds, or hydrolysis-resistant mononucleoside triphosphates.
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. The method comprises administering to a subject a pharmaceutical composition comprising a therapeutic effective amount of P2Y12 receptor antagonist compound, wherein said amount is effective to bind the P2Y12 receptors on platelets and inhibit ADP-induced platelet aggregation. The P2Y12 receptor antagonist compounds useful for this invention include mononucleoside 5′-monophosphates, mononucleoside polyphosphates, and dinucleoside polyphosphates of general Formula I, or salts thereof. The present invention also provides novel compounds of mononucleoside 5′-monophosphates, mononucleoside polyphosphates, and dinucleoside polyphosphates. The present invention further provides pharmaceutical formulations comprising mononucleoside 5′-monophosphates, mononucleoside polyphosphates, or dinucleoside polyphosphates.
Type:
Application
Filed:
March 31, 2004
Publication date:
November 4, 2004
Inventors:
Jose L. Boyer, James G. Douglass, Sammy R. Shaver, Krzysztof Bednarski, Benjamin R. Yerxa, Gillian M. Olins
Abstract: Fluorescent glycosides containing aromatic hydrocarbon groups are useful in labelling and detection methods for a wide array of chemical and biological molecules. Assembly of multiple analogs to form “polyfluors” affords fluorescence properties that are different from the properties of the component analogs. This allows for the design and use of combinatorial libraries of molecules displaying widely varying fluorescence colors.
Type:
Application
Filed:
August 22, 2003
Publication date:
October 28, 2004
Applicant:
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
Abstract: Hydrazino, oxyamino and carbonyl-based monomers and methods for incorporation into oligonucleotides during enzymatic synthesis are provided. Modified oligonucleotides are provided that incorporate the monomers provided herein. Immobilized oligonucleotides and oligonucleotide conjugates that contain covalent hydrazone or oxime linkages are provided. Methods for preparation of surface bound oligonucleotides are provided. Methods for the preparation of oligonucleotide conjugates are also provided.
Abstract: The present invention relates to methods for the synthesis and purification of cyclic nucleotide derivatives. The present invention provides a method for separating a cyclic nucleotide derivative from a mixture resulting from a chemical reaction to produce a cyclic nucleotide derivative from a cyclic nucleotide. In one embodiment, this mixture may comprise a cyclic nucleotide derivative, a pyridine solvent, and at least one of an alkyl carboxylic acid, an alkyl acid halide, or an alkyl carboxylic acid anhydride. In another embodiment, this mixture may comprise a cyclic nucleotide derivative and at least one of an alkyl carboxylic acid, an alkyl acid halide, or an alkyl carboxylic acid anhydride.
Abstract: Extended rhodamine compounds exhibiting favorable fluorescence characteristics having the structure
are disclosed. In addition, novel intermediates for synthesis of these dyes are disclosed, such intermediates having the structure
In addition, methods of making and using the dyes as fluorescent labels are disclosed.
Type:
Grant
Filed:
February 9, 2001
Date of Patent:
August 24, 2004
Assignee:
Applera Corporation
Inventors:
Joe Y. L. Lam, Scott C. Benson, Steven M. Menchen
Abstract: Contemplated compounds and methods are directed towards a dinucleotide comprising a first and second nucleoside, wherein the dinucleotide inhibits a viral RNA polymerase, and wherein at least one of the nucleosides exhibits antiviral effect when cleaved from the dinucleotide.
Abstract: The present invention relates to 3′ substituted-2′, 3′-didehydro-2′, 3′-dideoxy-&bgr;-L-nucleosides and their pharmaceutically acceptable salts and prodrugs thereof, for the treatment of infectious viral diseases, in general, particularly HBV and HIV viral infections and more particularly, HBV and HIV viral infections that are resistant to other antiviral drugs.
Abstract: Bicyclonucleoside analogues which exhibit anti-AIDS activity and intermediates to produce oligonucleotide analogues which have anti-sense or anti-gene activity as well as in vivo stability. Compounds of the following formula (1) or their pharmaceutically acceptable salts.
Abstract: Nucleotide derivatives of formula (1) are described: wherein: G is a hydrogen atom or an optionally substituted aliphatic, heteroaliphatic, cycloaliphatic, polycycloaliphatic, aromatic or heteroaromatic group or a non-natural nucleoside as defined herein; G′ is a non-natural necleoside as defined herein; n is zero, or the integer 1 or 2; m is zero or the integer 1 or 2; and the salts, solvates, hydrates and N-oxides thereof. The compounds are P2Y receptor agonists and are of use in the prophylaxis and treatment of diseases and disorders involving abnormal secretory mechanisms such as inadequate functioning of mucociliary clearance mechanisms or abnormal tear secretion or in the treatment of diseases involving inappropriate cellular glucose uptake.
Type:
Application
Filed:
January 15, 2004
Publication date:
June 24, 2004
Inventors:
Jeremy Martin Davis, Stephen Robert Mack, Verity Margaret Sabin, Richard John Davenport
Abstract: The invention relates to nucleoside derivatives with photolabile protecting groups of general formula (I)
wherein
R1 is H, F, Cl, Br, I, or NO2; R2 is H or CN, provided that R1 and R2 are not simultaneously H; R3 is H, 1-4 C alkyl, or phenyl; R4 is H or a conventional functional group for the synthesis of oligonuleotides; R5 is H, OH, halogen or XR6, where X=O or S, and R6 is a conventional nucleotide protecting group; and B is 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 is 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:
Grant
Filed:
March 29, 2002
Date of Patent:
June 15, 2004
Assignee:
Nigu Chemie GmbH
Inventors:
Wolfgang Pfleiderer, Sigrid Bühler, Heiner Giegrich
Abstract: Purine nucleotide derivative disodium crystals having a minimized amount of remaining alcohol such as methanol, ethanol or a mixture thereof are produced by overdrying purine nucleotide derivative disodium crystals containing the alcohol; and bringing the overdried purine nucleotide derivative disodium crystals into contact with an aqueous solution containing a hydrophilic organic solvent to control the humidity of the purine nucleotide derivative disodium crystals under a high humidity condition.
Abstract: A process of purifying phosphoramidite precursors useful in inter alia synthesis of oligonucleotides comprises dissolving a crude phosphoramidite in a polar phase, adding a basic compound to the polar phase, adding a portion of water to the polar phase, contacting the polar phase with a first apolar phase to extract impurity into the apolar phase, separating the first apolar phase from the polar phase, adding a second aliquot of water to the polar phase, and contacting the polar phase with a second apolar phase, whereby the phosphoramidite partitions into the second apolar phase.
Abstract: The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The pharmaceutical formulation useful in this invention comprises a P2Y receptor agonist with enhanced resistance to extracellular hydrolysis, such as dinucleoside polyphosphate compounds, or hydrolysis-resistant mononucleoside triphosphates.