Patents Represented by Attorney Max D. Hensley
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Patent number: 5854228Abstract: A series of compounds of Formula I which have anti-tumor activity, and are useful in treating viral infections, their compositions and use. ##STR1## In Formula I B is a purine or pyrimidine base; alk.sub.1 alk.sub.2 and alk.sub.3 are chemical bonds or alkylene groups; Q is hydrogen or hydroxyl; and R.sub.1 -R.sub.4 are hydrogen or alkyl.Type: GrantFiled: June 7, 1995Date of Patent: December 29, 1998Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.Inventors: Robert W. Webb, II, Joanne J. Bronson, John C. Martin
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Patent number: 5837871Abstract: Provided are compounds of the following formulae:A phosphonomethoxymethyoxymethyl purine/pyrimidine derivative of the formula ##STR1## wherein X and X' are the same or different and are hydrogen or alkyl. R and R' are the same or different and are hydrogen, alkyl, hydroyalkyl or alkanoyl andB is a purine or pyrimidine base.Type: GrantFiled: June 7, 1995Date of Patent: November 17, 1998Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting, v.z.w.Inventors: Choung Un Kim, John C. Martin, Bing Uh Luh, Peter F. Misco
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Patent number: 5792756Abstract: There are disclosed novel oral prodrugs of phosphonate nucleotide analogs which are hydrolyzable under physiological conditions to yield compounds which are useful as antiviral agents, especially as agents effective against RNA and DNA viruses. They may also find use as antitumor agents.Type: GrantFiled: June 7, 1995Date of Patent: August 11, 1998Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.Inventors: John E. Starrett, Jr., Muzammil M. Mansuri, John C. Martin, David R. Tortolani, Joanne J. Bronson
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Patent number: 5767100Abstract: In accordance with this invention novel compounds are provided that are selected from saturated and unsaturated pyrans and furans substituted with at least a phosphonate group and a heterocyclic base. These compounds are useful as antiinfectives, flame retardants, diagnostic oligonucleotides and immunogens.Type: GrantFiled: March 13, 1996Date of Patent: June 16, 1998Assignee: Gilead Sciences, Inc.Inventors: Petr Alexander, Ernest J. Prisbe
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Patent number: 5763588Abstract: Compounds having particular interest as labels and various novel uses in diagnostics and therapeutics are provided which have structure (1) ##STR1## wherein R.sup.1 is a binding partner, a linker or H; a and b are 0 or 1, provided that the total of a and b is 0 or 1;A is N or C;X is S, O, --C(O)--, NH or NCH.sub.2 R.sup.6 ;Y is --C(O)--;Z is taken together with A to form an aryl or heteroaryl ring structure comprising 5 or 6 ring atoms wherein the heteroaryl ring comprises a single O ring heteroatom, a single N ring heteroatom, a single S ring heteroatom, a single O and a single N ring heteroatom separated by a carbon atom, a single S and a single N ring heteroatom separated by a carbon atom, 2 N ring heteroatoms separated by a carbon atom, or 3 N ring heteroatoms at least two of which are separated by a carbon atom, and wherein the aryl or heteroaryl ring carbon atoms are unsubstituted with other than H or at least 1 nonbridging ring carbon atom is substituted with R.sup.6 or .dbd.O;R.sup.Type: GrantFiled: June 7, 1995Date of Patent: June 9, 1998Assignee: Gilead Sciences, Inc.Inventors: Mark D. Matteucci, Robert J. Jones
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Patent number: 5756486Abstract: The internally cyclized congeners of hydroxy-substituted nucleotide analogues have been found to exhibit substantially lower toxicity in vivo than their uncyclized analogues, while retaining essentially the same antiviral activity. This was unexpected because the prior art suggested that the cyclic analogues offered no significant advantages in respect to toxicity. This finding permits the administration of much greater doses of the cyclic congeners than otherwise would have been possible and allows the clinician to omit toxicity ameliorating interventions. Novel compounds are provided for use in the method of this invention. Novel methods for the preparation of these compounds also are provided.Type: GrantFiled: September 5, 1996Date of Patent: May 26, 1998Assignee: Gilead Sciences, Inc.Inventors: Petr Alexander, Murty Arimilli, Norbert Bischofberger, Michael J. M. Hitchcock
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Patent number: 5750729Abstract: In accordance with this invention novel compounds are provided that are selected from saturated and unsaturated pyrans and furans substituted with at least a phosphonate group and a heterocyclic base. These compounds are useful as antiinfectives, flame retardants, diagnostic oligonucleotides and immunogens.Type: GrantFiled: February 25, 1997Date of Patent: May 12, 1998Assignee: Gilead Sciences,Inc.Inventors: Petr Alexander, Ernest J. Prisbe
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Patent number: 5733788Abstract: Purified preparations of PMPA are provided, together with analytical methods for the detection of undesired contaminants in PMPA preparations. The PMPA compositions of the invention are of particular utility in therapeutics intended for the treatment or prophylaxis of viral infections.Type: GrantFiled: July 26, 1996Date of Patent: March 31, 1998Assignee: Gilead Sciences, Inc.Inventor: Norbert W. Bischofberger
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Patent number: 5733896Abstract: N-(3-Fluoro-2-phosphonylmethoxypropyl) derivatives of purine and pyrimidine heterocyclic bases, method of producing them and their use as active principles of drugs.The invention relates to suppression of multiplication of viruses, particularly retroviruses, by application of the new compounds, N-(3-fluoro-2-phosphonylmethoxypropyl) derivatives of purine and pyrimidine heterocyclic bases. These compounds are obtained by the reaction of the N-(3-fluoro-2-hydroxypropyl) derivatives of purine and pyrimidine heterocyclic bases with diesters of p-toluenesulfonyloxymethylphosphonic acid in the presence of sodium hydride.Type: GrantFiled: March 18, 1994Date of Patent: March 31, 1998Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.Inventors: Antonin Holy, Jindrich Jindrich, Erik De Clercq, Jan Balzarini
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Patent number: 5726174Abstract: Provided are compounds of the following formulae:A phosphonomethoxymethyoxymethyl purine/pyridimidine derivative of the formula ##STR1## wherein X and X' are the same or different and are hydrogen or alkyl. R and R' are the same or different and are hydrogen, alkyl, hydroxyalkyl or alkanoyl andB is a purine or pyrimidine base.A compound of formula (II) or (VIII) ##STR2## wherein the broken line is an optional bond; X, R and X' are the same or different and are H or alkyl with 1 to 6 carbon atoms;wherein in the compound of formula (II), Y and Z are the same or different and are H; OH; alkyl having 1 to 6 carbon atoms; alkyl having 1 to 6 carbon atoms which is substituted with halogen, hydroxy, amino or azido; or Y and Z are taken together to form an oxygen atom or a methylene group; or Y is taken together with X' to complete a cyclic phosphonate having the structure of formula (III) ##STR3## wherein R.sup.Type: GrantFiled: June 7, 1995Date of Patent: March 10, 1998Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.Inventors: Choung Un Kim, John C. Martin, Bing Uh Luh, Peter F. Misco
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Patent number: 5696265Abstract: Provided are compounds of the following formulae:A phosphonomethoxymethyoxymethyl purine/pyrimidine derivative of the formula ##STR1## wherein X and X' are the same or different and are hydrogen or alkyl. R and R' are the same or different and are hydrogen, alkyl, hydroxyalkyl or alkanoyl andB is a purine or pyrimidine base.A 4'-phosphonomethoxytetrahydrofuranyl-1'-purine-pyrimidine of the formula ##STR2## wherein X and X' are the same or different and are hydrogen or alkyl, Y and Z are the same or different and are hydrogen, hydroxyl or alkyl or Y+Z is an alkenyl, an epoxide or cyclopropyl, andB is a purine or pyrimidine base.Type: GrantFiled: June 7, 1995Date of Patent: December 9, 1997Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.Inventors: Choung Un Kim, John C. Martin, Bing Uh Luh, Peter F. Misco
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Patent number: 5696263Abstract: Compounds are provided that generally have the structure BCH.sub.2 CH(R)OCH.sub.2 P(O)(OH).sub.2, wherein B is a purinyl or pyrimidinyl base and R is C.sub.1-2 alkyl substituted with azido or amino, straight or branched alkenyl of 2-6 carbon atoms or alkynyl of 2-6 carbon atoms, together with the monester and diesters of such compounds with a C.sub.1-5 alkanol, and the corresponding salts, hydrates, solvates, the (R) or (S) isomers and the racemic (RS) mixtures thereof. The compounds have desirable antiviral activity.Type: GrantFiled: December 6, 1994Date of Patent: December 9, 1997Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.Inventors: Kuo-Long Yu, Joanne J. Bronson, John C. Martin
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Patent number: 5693798Abstract: Provided are compounds of the following formulae:A phosphonomethoxymethyoxymethyl purine/pyrimidine derivative of the formula ##STR1## wherein X and X' are the same or different and are hydrogen or alkyl. R and R' are the same or different and are hydrogen, alkyl, hydroxyalkyl or alkanoyl andB is a purine or pyrimidine base.A 4'-phosphonomethoxytetrahydrofuranyl-1'-purine-pyrimidine of the formula ##STR2## wherein X and X' are the same or different and are hydrogen or alkyl, Y and Z are the same or different and are hydrogen, hydroxyl or alkyl or Y+Z is an alkenyl, an epoxide or cyclopropyl, andB is a purine or pyrimidine base.Type: GrantFiled: June 7, 1995Date of Patent: December 2, 1997Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.wInventors: Choung Un Kim, John C. Martin, Bing Uh Luh, Peter F. Misco
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Patent number: 5693771Abstract: In accordance with this invention novel compounds are provided that are selected from saturated and unsaturated pyrans and furans substituted with at least a phosphonate group and a heterocyclic base. These compounds are useful as antiinfectives, flame retardants, diagnostic oligonucleotides and immunogens.Type: GrantFiled: March 13, 1996Date of Patent: December 2, 1997Assignee: Gilead Sciences, Inc.Inventors: Petr Alexander, Ernest J. Prisbe
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Patent number: 5688778Abstract: Provided are compounds of the following formulae:A phosphonomethoxymethyoxymethyl purine/pyrimidine derivative of the formula ##STR1## wherein X and X' are the same or different and are hydrogen or alkyl. R and R' are the same or different and are hydrogen, alkyl, hydroxyalkyl or alkanoyl;B is a purine or pyrimidine base.optionally R is taken together with X' to complete a cyclic phosphonate having the formula ##STR2## A 4'-phosphonomethoxytetrahydrofuranyl-1'-purine-pyrimidine of the formula ##STR3## wherein X and X' are the same or different and are hydrogen or alkyl, the dashed line is an optional bond,Y and Z are the same or different and are hydrogen, hydroxyl or alkyl or Y+Z are taken together to form an epoxide or cyclopropyl, andB is a purine or pyrimidine base.Type: GrantFiled: February 17, 1995Date of Patent: November 18, 1997Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.Inventors: Choung Un Kim, John C. Martin, Bing Uh Luh, Peter F. Misco
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Patent number: 5686611Abstract: Provided are compounds of the following formulae: A phosphonomethoxymethyoxymethyl purine/pyrimidine derivative of the formula ##STR1## wherein X and X' are the same or different and are hydrogen or alkyl. R and R' are the same or different and are hydrogen, alkyl, hydroxyalkyl or alkanoyl andB is a purine or pyrimidine base.A compound of formula (VI) ##STR2## wherein X is halogen, Y is S-phenyl, Se-phenyl or halogen and B is hypoxanthine, xanthine, guanine, 8-bromoguanine, 8-chloroguanine, 8-methylguanine, 8-thioguanine, 3-deazaguanine, purine, 2-aminopurine, 2,6-diaminopurine, adenine, 3-deazaadenine, 8-aminoguanine, 8-hydrazinoguanine, 8-hydroxyguanine, cytosine, 5-ethylcytosine, 5-methylcytosine, thymine, uracil, 5-chlorouracil, 5-bromouracil, 5-ethyluracil, 5-iodouracil, 5-propyluracil or 5-vinyluracil, 2-acetamido-6-diphenylcarbamoylpurine, 6-N-dimethylamino-methyladenine or 6-N-pivaloyladenine.Type: GrantFiled: June 7, 1995Date of Patent: November 11, 1997Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.Inventors: Choung Un Kim, John C. Martin, Bing Uh Luh, Peter F. Misco
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Patent number: 5686629Abstract: An improved method for the preparation of acyclic nucleotide analogues comprises first condensing a cyclic carbonate with a purine or pyrimidine base and then reacting the alkylated base with an activated phosphonate. Novel cyclic carbonates are employed to yield the desired phosphonylmethoxyalkyl nucleotide analogues.Type: GrantFiled: December 27, 1995Date of Patent: November 11, 1997Assignee: Gilead Sciences, Inc.Inventors: Norbert W. Bischofberger, Kenneth M. Kent
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Patent number: 5663159Abstract: There are disclosed novel oral prodrugs of phosphonate nucleotide analogs which are hydrolyzable under physiological conditions to yield compounds which are useful as antiviral agents, especially as agents effective against RNA and DNA viruses. They may also find use as antitumor agents.Type: GrantFiled: October 11, 1994Date of Patent: September 2, 1997Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.Inventors: John E. Starrett, Jr., Muzammil M. Mansuri, John C. Martin, David R. Tortolani, Joanne J. Bronson
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Patent number: 5659023Abstract: In accordance with this invention novel compounds are provided that are selected from saturated and unsaturated pyrans and furans substituted with at least a phosphonate group and a heterocyclic base. These compounds are useful as antiinfectives, flame retardants, diagnostic oligonucleotides and immunogens.Type: GrantFiled: February 1, 1995Date of Patent: August 19, 1997Assignee: Gilead Sciences, Inc.Inventors: Petr Alexander, Ernest J. Prisbe
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Patent number: 5650510Abstract: A series of compounds of Formula I which have anti-tumor activity, and are useful in treating viral infections, their compositions and use. ##STR1## In Formula I B is a purine or pyrimidine base; alk.sub.1 alk.sub.2 and alk.sub.3 are chemical bonds or alkylene groups; Q is hydrogen or hydroxyl; and R.sub.1 -R.sub.4 are hydrogen or alkyl.Type: GrantFiled: January 31, 1992Date of Patent: July 22, 1997Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.Inventors: Robert W. Webb, II, Joanne J. Bronson, John C. Martin