Additional Nitrogen Bonded Directly To The 2-position Of The Purine Ring System Patents (Class 536/27.61)
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Patent number: 7112574Abstract: Novel C2,8-disubstituted adenosine derivatives disclosed herein have been found to be potent adenosine receptor agonists, in particular for the A2A receptor. The said compounds have biological activity against conditions such as hypertension, ischemic heart disease, ischemic brain disease, psychosis and wound healing. Further, the invention also discloses a process for the preparation of such compounds and pharmaceutical compositions comprising them.Type: GrantFiled: March 3, 2002Date of Patent: September 26, 2006Assignees: Universiteit Leiden, Can-Fite Biopharma Ltd.Inventors: Erica Van Tilburg, Ad Ijzerman
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Patent number: 7109180Abstract: 2-adenosine C-pyrazole compounds having formula (a) and methods for using the compounds as A2A receptor agonists to stimulate mammalian coronary vasodilatation for therapeutic purposes and for purposes of imaging the heartType: GrantFiled: March 30, 2004Date of Patent: September 19, 2006Assignee: CV Therapeutics, Inc.Inventors: Jeff A. Zablocki, Elfatih O. Elzein, Venkata P. Palle
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Patent number: 7101993Abstract: Compounds are provided containing purine nucleotides that bear moieties X at the 2? position thereof wherein X is R1—(R2)n; R1 is C3-C20 alkyl, C4-C20 alkenyl or C2-C20 alkynyl; R2 is halogen, hydroxyl, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, polyether, a group that enhances the pharmacodynamic properties of oligonucleotides, or a group that enhances the pharmacokinetic properties of oligonucleotides; and n is an integer from 0 to about 6. Such compounds are useful for modulating the synthesis of proteins.Type: GrantFiled: October 27, 1992Date of Patent: September 5, 2006Assignee: ISIS Pharmaceuticals, Inc.Inventors: Phillip Dan Cook, Daniel Peter Claude McGee, Charles John Guinosso
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Patent number: 6949640Abstract: 2-Chloro-9-(2-deoxy-2-fluoro-?-D-arabinofuranosyl)-9H-purin-9-amine is synthesized by reacting a 2-chloro-6-substituted purine with a protected and activated 2-deoxy-2-fluoro-D-arabinofuranose; and reacting with a base such as ammonia to provide 2-chloro-9-(2-deoxy-2-fluoro-?-D-arabinofuranosyl)-9H-purin-6-amine. When the purine reactant is substituted in the 6 position with a halogen, a reaction step with an alkoxide is carried out prior to the reaction with ammonia.Type: GrantFiled: February 16, 2001Date of Patent: September 27, 2005Assignee: Southern Research InstituteInventors: John A. Montgomery, Anita T. Fowler, John A. Secrist, III
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Patent number: 6914053Abstract: Disclosed are novel adenosine A3 receptor agonists of Formula I: wherein: R is hydrogen or lower alkyl; R1 is optionally substituted lower alkoxy or optionally substituted cycloalkyloxy; R2 is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted trialkylsilyl; and R3 is hydroxymethyl or R4R5NC(Q)—; in which R4 and R5 are hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl.Type: GrantFiled: September 8, 2003Date of Patent: July 5, 2005Assignee: CV Therapeutics, Inc.Inventor: Gloria Cristalli
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Patent number: 6906190Abstract: A polymerase inhibitor has first moiety coupled to a second moiety via an optional linker in which the first moiety binds to an initiation nucleotide binding site of a polymerase and forms at least two hydrogen bonds with an RNA template strand that is associated with the polymerase, and in which the second moiety comprised a compound that binds to a site proximal to the nucleotide binding site of the polymerase and thereby increases the affinity of the polymerase inhibitor to the polymerase.Type: GrantFiled: December 27, 2002Date of Patent: June 14, 2005Assignee: Ribapharm Inc.Inventors: Nanhua Yao, Haoyun An, Todd Appleby, Shahul Nilar, Yili Ding, Zhi Hong
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Patent number: 6855817Abstract: 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: July 20, 2001Date of Patent: February 15, 2005Inventor: Mark B. Lyles
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Patent number: 6855818Abstract: 2-adenosine C-pyrazole compositions having the following formula: and methods for using the compositions as A2A receptor agonists to stimulate mammalian coronary vasodilatation for therapeutic purposes and for purposes of imaging the heart.Type: GrantFiled: March 19, 2001Date of Patent: February 15, 2005Assignee: CV Theraeputics, Inc.Inventors: Jeff A. Zablocki, Venkata P. Palle, Elfatih O. Elzein
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Patent number: 6770634Abstract: 2-adenosine C-pyrazole compounds having formula (a) and methods for using the compounds as A2A receptor agonists to stimulate mammalian coronary vasodilatation for therapeutic purposes and for purposes of imaging the heart.Type: GrantFiled: March 12, 2002Date of Patent: August 3, 2004Assignee: CV Therapeutics, Inc.Inventors: Jeff A. Zablocki, Elfatih O. Elzein, Venkata P. Palle
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Patent number: 6740644Abstract: A compound of formula (I), wherein R2 represents C1-3alkyl, halogen or hydrogen; R3 represents straight or branched alkyl group of 1-6 carbon atoms; with the proviso that, when R3 represents C1-3alkyl, R2 represents C1-3alkyl, R1 cannot represent phenyl optionally substituted by one or more substituents selected from halogen, C1-3alkyl, trifluoromethyl, nitro, cyano, —CO2Rc, —CONRcRd, —CORc, —SORe, —SO2Re, —SO3H, —SO2NRcRd, —ORc, —NHSO2Re, —NHCORc and —NRcRd; and salts and solvates thereof, in particular, physiologically acceptable solvates and salts thereof. These compounds are agonists at the Adenosine A1 receptor.Type: GrantFiled: February 26, 2003Date of Patent: May 25, 2004Assignee: Smithkline Beecham CorporationInventors: Colin David Eldred, Andrew Michael Kenneth Pennell
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Patent number: 6642210Abstract: N-pyrazole substituted 2-adenosine compounds and methods for using the compounds as A2A-adenosine receptor agonists useful to stimulate mammalian coronary vasodilation for therapeutic purposes and as adjuncts in cardiological imaging.Type: GrantFiled: April 12, 2002Date of Patent: November 4, 2003Assignee: CV Therapeutics, Inc.Inventors: Jeff A. Zablocki, Elfatih O. Elzein, Venkata P. Palle
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Patent number: 6576620Abstract: The present invention provides a method for identifying partial adenosine A1 receptor agonists that are useful in the treatment of arrhythmias. Partial adenosine A1 receptor agonists and methods for using partial adenosine A1 receptor agonists to treat arrhythmias in mammals.Type: GrantFiled: December 1, 2000Date of Patent: June 10, 2003Assignee: CV Therapeutics, Inc.Inventors: Luiz Belardinelli, Zhenhai Gao
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Patent number: 6525032Abstract: The present invention relates to compounds of the class of purin-2-ylcarboxamides, useful as anti-inflammatory agents, having the formula: and pharmaceutically acceptable salts and solvates thereof; wherein R1 is H, C1-C 6 alkyl or C3-C7 cycloalkyl, each optionally substituted by 1 or 2 of hydroxyl, fluorenyl, or optionally substituted phenyl or naphthyl ; A is a bond or C1-C6 alkylene; R2 is (i) H, C1-C6 alkyl, or optionally substituted C3-C7 cycloalkyl, phenyl, or naphthyl; or (ii) when A is C2-C6 alkylene, —NR3R3, —OR3, —COOR3, —OCOR4, —SO2R4, —CN, —SO2NR3R4, —NR3SO2R4, —NR3COR4 or —CONR3R3; or (iii) a C-linked, 4 to 11 membered, mono or bicyclic heterocycle having either from 1 to 4 ring nitrogen atom(s) or 1 or 2 nitrogen and 1 oxygen or 1 sulphur ring atoms, said heterocycle being optionally C-substituted or N-substituted; or (iv) when A is C2-C6 alkylene, optionally substituted N-linked azetidinyl, pyrrolidinyl, morpholinyl,Type: GrantFiled: February 20, 2001Date of Patent: February 25, 2003Assignee: Pfizer IncInventors: Simon John Mantell, Sandra Marina Monaghan, Peter Thomas Stephenson
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Patent number: 6498241Abstract: 2′-Deoxyisoguanosine, isosteric analogues and isoguanosine derivatives of formulae I-V, processes for their production via compounds of the general formulae a or b and reaction with aroyl isocyanates or from compounds of the general formulae VI-IX by photochemical irradiation. A further production process is the conversion of deoxyguanosines or guanosines by means of persilylation, reaction with ammonia and deamination in the 2 position. The compounds are suitable as pharmaceutical agents with antiviral efficacy.Type: GrantFiled: November 13, 2000Date of Patent: December 24, 2002Assignee: Roche Diagnostics GmbHInventors: Frank Seela, Zigmunt Kasimierczuk, Klaus Mühlegger, Herbert Von Der Eltz
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Patent number: 6495528Abstract: 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: GrantFiled: February 20, 2001Date of Patent: December 17, 2002Assignee: SmithKline Beecham CorporationInventors: 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
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Patent number: 6403567Abstract: 2-adenosine N-pyrazole compositions having the following formula: and methods for using the compositions as A2A receptor agonists to stimulate mammalian coronary vasodilatation for therapeutic purposes and for purposes of imaging the heart.Type: GrantFiled: June 22, 1999Date of Patent: June 11, 2002Assignee: CV Therapeutics, Inc.Inventors: Jeff A. Zablocki, Elfatih O. Elzein, Venkata P. Palle
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Patent number: 6355787Abstract: This invention discloses a method for the preparation of 2′-modified nucleosides, using a palladium catalyst and an alkene functionalized with a heteroatom. Included in the invention are the novel pyrimidines and purines that can be prepared according to the method of the invention and oligonucleotides containing said modified pyrimidines and purines.Type: GrantFiled: January 31, 2000Date of Patent: March 12, 2002Assignee: Gilead Sciences, Inc.Inventors: Jeffrey T. Beckvermit, Chi Tu
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Patent number: 6326359Abstract: The present invention provides compounds of formula (I): and pharmaceutically acceptable salts and solvates thereof, together with processes for the preparation of, compositions containing, uses of and intermediates used in the preparation of such compounds that have A2a receptor agonist activity.Type: GrantFiled: October 15, 1999Date of Patent: December 4, 2001Assignee: Pfizer IncInventors: Sandra M. Monaghan, Simon J. Mantell
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Patent number: 6294522Abstract: N6 heterocyclic 8 modified adenosine derivatives that are selective, partial or full adenosine A1 receptor partial or full agonists, and as such, are useful for modifying cardiac activity, modifying adipocyte function, treating central nervous system disorders, and treating diabetic disorders and obesity in mammals, and especially in humans.Type: GrantFiled: December 3, 1999Date of Patent: September 25, 2001Assignee: CV Therapeutics, Inc.Inventors: Jeff A. Zablocki, Venkata P. Palle, Prabha N. Ibrahim, Luiz Belardenelli
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Patent number: 6271212Abstract: Pharmaceutical prodrug compositions are provided comprising azide derivatives of drugs which are capable of being converted to the drug in vivo. Azide derivatives of drugs having amine, ketone and hydroxy substituents are converted in vivo to the corresponding drugs, increasing the half-life of the drugs. In addition azide prodrugs are often better able to penetrate the blood-brain barrier than the corresponding drugs. Especially useful are azide derivatives of cordycepin, 2′-F-ara-ddI, AraA, acyclovir, penciclovir and related drugs. Useful azide prodrugs are azide derivatives of therapeutic alicyclic amines, ketones, and hydroxy-substituted compounds, including aralkyl, heterocyclic aralkyl, and cyclic aliphatic compounds, where the amine or oxygen moiety is on the ring, or where the amine or oxygen moiety is on an aliphatic side chain, as well as therapeutic purines and pyrimidines, nucleoside analogs and phosphorylated nucleoside analogs.Type: GrantFiled: March 3, 1998Date of Patent: August 7, 2001Assignees: University of Georgia Research Foundation Inc., Emory UniversityInventors: Chung K. Chu, Lakshimi Kotra, Kostantine K. Manouilov, Jinfa Du, Raymond Schinazi
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Patent number: 6221851Abstract: The present invention is directed to reduce elevated levels of tumor necrosis factor-alpha (TNF-&agr;) found in a failing heart. The present invention is directed to a composition and method of regulating TNF-&agr; expression in myocardial tissue by treating the myocardial tissue with biological equivalents of endogenous adenosine. A composition and method of using the composition to treat patients with damaged myocardial tissue is provided which increases the cellular availability of adenosine with a resulting decrease of TNF-&agr; levels in the heart. The present invention provides a novel pharmacological intervention program in failing mammalian hearts, and more particularly provides a cardioprotective treatment to patients with congestive heart failure.Type: GrantFiled: December 7, 1999Date of Patent: April 24, 2001Inventor: Arthur M. Feldman
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Patent number: 6214807Abstract: 2-adenosine C-pyrazole compositions having the following formula: and methods for using the compositions as A2A receptor agonists to stimulate mammalian coronary vasodilatation for therapeutic purposes and for purposes of imaging the heart.Type: GrantFiled: June 22, 1999Date of Patent: April 10, 2001Assignee: CV Therapeutics, Inc.Inventors: Jeff A. Zablocki, Venkata P. Palle, Elfatih O. Elzein