Patents Assigned to Rega Stichting, V.Z.W.
  • Patent number: 6818633
    Abstract: Novel compounds are provided having formula (I) where R1, R2, R3, R4, Z, X and * are defined herein. Also provided are antiviral methods for use and processes for synthesis of the compounds of formula (I).
    Type: Grant
    Filed: June 28, 2002
    Date of Patent: November 16, 2004
    Assignees: Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.
    Inventors: Jan M. R. Balzarini, Erik D. A. De Clercq, Antonin Holy
  • Patent number: 6653296
    Abstract: Resolved enantiomers of the formula (IA) and (IB) wherein B is a purine or pyrimidine base or aza and/or deaza analogs thereof are useful in antiviral pharmaceutical compositions to treat retroviral infections.
    Type: Grant
    Filed: February 2, 1995
    Date of Patent: November 25, 2003
    Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.
    Inventors: Antonin Holy, Hana Dvorakova, Erik Desire Alice De Clercq, Jan Marie Rene Balzarini
  • Patent number: 6479673
    Abstract: Resolved enantiomers of the formula wherein B is a purine or pyrimidine base or aza and/or deaza analogs thereof are useful in antiviral pharmaceutical compositions to treat retroviral infections.
    Type: Grant
    Filed: February 8, 2000
    Date of Patent: November 12, 2002
    Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting, V.Z.W.
    Inventors: Antonin Holý, Hana Dvo{haeck over (r)}áková, Erik Desire Alice DeClercq, Jan Marie Rene Balzarini
  • Patent number: 6057305
    Abstract: Resolved enantiomers of the formula ##STR1## wherein B is a purine or pyrimidine base or aza and/or deaza analogs thereof are useful in antiviral pharmaceutical compositions to treat retroviral infections.
    Type: Grant
    Filed: August 5, 1992
    Date of Patent: May 2, 2000
    Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting, v.z.w.
    Inventors: Antonin Holy, Hana Dvorakova, Erik Desire Alice DeClercq, Jan Marie Rene Balzarini
  • Patent number: 5977061
    Abstract: Novel PMP, PME and HPMP and related compounds containing N-6 substituted 2,6-diaminopurine and adenine bases are provided. These compounds are useful in a variety of utilities, including as intermediates in the preparation of flame retardants, diagnostic reagents and therapeutics, including antivirals. Of particular note are compounds otherwise not known to possess anti-DNA viral activity that become potent inhibitors of DNA viruses upon substitution of the N-6 site, thereby providing a novel and unexpected and surprising use for such compounds.
    Type: Grant
    Filed: April 21, 1995
    Date of Patent: November 2, 1999
    Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting, v.z.w.
    Inventors: Antonin Holy, Erik Desire Alice De Clercq
  • Patent number: 5869467
    Abstract: This invention relates to new nucleotide analogues and solves the technical problem of their use as biologically active compounds. The subject of this invention are N-(2-phosphonylmethoxyethyl) and N-(3-hydroxy-2-phosphonylmethoxypropyl) derivatives of pyrimidine and purine bases, easily accessible from heterocyolic bases and their N-(2-hydroxyethyl) or N-(2,3-dihydroxypropyl) derivatives. Some of the compounds, according to this invention, exhibit a marked antiviral activity or can be converted into such active compounds by chemical transformations.
    Type: Grant
    Filed: March 28, 1995
    Date of Patent: February 9, 1999
    Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.
    Inventors: Antonin Holy, Ivan Rosenberg, Erik D. A. De Clercq
  • 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: 5744600
    Abstract: A compound of the Formula I or Formula II ##STR1## wherein R.sup.1 and R.sup.2 are independently hydrogen, hydroxy, chlorine, fluorine, bromine, or an organic substituent having 1 to 5 carbon atoms and selected from acyloxy having a hydrocarbon stem of 1 to 4 carbon atoms, alkoxy, alkylthio, amino, alkylamino and dialkylamino;R.sup.3 and R.sup.4 are independently hydrogen, or organic phosphonic ester substituents having 1 to 12 carbon atoms and selected from alkyl, alkenyl, aryl, and aralkyl; andB is a heterocyclic group selected from the group consisting of pyrimidine, purine, triazine, deazapurine, and triazole, attached through a ring nitrogen atom thereof optionally substituted with 1 to 3 substituents selected from the group consisting of hydroxy, mercapto, amino, hydrazino, fluoro, chloro, bromo, iodo, C.sub.1 to C.sub.3 alkyl, C2-C3 alkenyl, C2-C3 haloalkenyl, C1-C3 alkoxy, and C1-C3 alkylthio;and the pharmaceutically acceptable acid addition, metal, and amine salts thereof.
    Type: Grant
    Filed: December 16, 1994
    Date of Patent: April 28, 1998
    Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.
    Inventors: Muzammil M. Mansuri, John C. Martin, Thomas W. Hudyma, Joanne J. Bronson, Louis M. Ferrara
  • 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: 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: 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: 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
  • Patent number: 5641763
    Abstract: This invention relates to new nucleotide analogues and solves the technical problem of their use as biologically active compounds. The subject of this invention are N-(2-phosphonylmethoxyethyl) and N-(3-hydroxy-2-phosphonylmethoxypropyl) derivatives of pyrimidine and purine bases, easily accessible from heterocyclic bases and their N-(2-hydroxyethyl) or N-(2,3-dihydroxypropyl) derivatives. Some of the compounds, according to this invention, exhibit a marked antiviral activity or can be converted into such active compounds by chemical transformations.
    Type: Grant
    Filed: October 11, 1994
    Date of Patent: June 24, 1997
    Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.
    Inventors: Antonin Holy, Ivan Rosenberg, Erik D. A. De Clercq