Patents Represented by Attorney Max D. Hensley
  • Patent number: 5854228
    Abstract: 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: Grant
    Filed: June 7, 1995
    Date of Patent: December 29, 1998
    Assignees: 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
  • Patent number: 5837871
    Abstract: 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: Grant
    Filed: June 7, 1995
    Date of Patent: November 17, 1998
    Assignees: 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
  • Patent number: 5792756
    Abstract: 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: Grant
    Filed: June 7, 1995
    Date of Patent: August 11, 1998
    Assignees: 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
  • Patent number: 5767100
    Abstract: 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: Grant
    Filed: March 13, 1996
    Date of Patent: June 16, 1998
    Assignee: Gilead Sciences, Inc.
    Inventors: Petr Alexander, Ernest J. Prisbe
  • Patent number: 5763588
    Abstract: 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: Grant
    Filed: June 7, 1995
    Date of Patent: June 9, 1998
    Assignee: Gilead Sciences, Inc.
    Inventors: Mark D. Matteucci, Robert J. Jones
  • Patent number: 5756486
    Abstract: 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: Grant
    Filed: September 5, 1996
    Date of Patent: May 26, 1998
    Assignee: Gilead Sciences, Inc.
    Inventors: Petr Alexander, Murty Arimilli, Norbert Bischofberger, Michael J. M. Hitchcock
  • Patent number: 5750729
    Abstract: 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: Grant
    Filed: February 25, 1997
    Date of Patent: May 12, 1998
    Assignee: Gilead Sciences,Inc.
    Inventors: Petr Alexander, Ernest J. Prisbe
  • Patent number: 5733788
    Abstract: 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: Grant
    Filed: July 26, 1996
    Date of Patent: March 31, 1998
    Assignee: Gilead Sciences, Inc.
    Inventor: Norbert W. Bischofberger
  • Patent number: 5733896
    Abstract: 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: Grant
    Filed: March 18, 1994
    Date of Patent: March 31, 1998
    Assignees: 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
  • Patent number: 5726174
    Abstract: 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: Grant
    Filed: June 7, 1995
    Date of Patent: March 10, 1998
    Assignees: 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
  • Patent number: 5696263
    Abstract: 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: Grant
    Filed: December 6, 1994
    Date of Patent: December 9, 1997
    Assignees: 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
  • Patent number: 5696265
    Abstract: 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: Grant
    Filed: June 7, 1995
    Date of Patent: December 9, 1997
    Assignees: 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
  • Patent number: 5693798
    Abstract: 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: Grant
    Filed: June 7, 1995
    Date of Patent: December 2, 1997
    Assignees: 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
  • Patent number: 5693771
    Abstract: 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: Grant
    Filed: March 13, 1996
    Date of Patent: December 2, 1997
    Assignee: Gilead Sciences, Inc.
    Inventors: Petr Alexander, Ernest J. Prisbe
  • Patent number: 5688778
    Abstract: 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: Grant
    Filed: February 17, 1995
    Date of Patent: November 18, 1997
    Assignees: 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
  • Patent number: 5686611
    Abstract: 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: Grant
    Filed: June 7, 1995
    Date of Patent: November 11, 1997
    Assignees: 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
  • Patent number: 5686629
    Abstract: 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: Grant
    Filed: December 27, 1995
    Date of Patent: November 11, 1997
    Assignee: Gilead Sciences, Inc.
    Inventors: Norbert W. Bischofberger, Kenneth M. Kent
  • Patent number: 5663159
    Abstract: 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: Grant
    Filed: October 11, 1994
    Date of Patent: September 2, 1997
    Assignees: 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
  • Patent number: 5659023
    Abstract: 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: Grant
    Filed: February 1, 1995
    Date of Patent: August 19, 1997
    Assignee: Gilead Sciences, Inc.
    Inventors: Petr Alexander, Ernest J. Prisbe
  • Patent number: 5650510
    Abstract: 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: Grant
    Filed: January 31, 1992
    Date of Patent: July 22, 1997
    Assignees: 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