Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Patent
1994-10-11
1997-09-02
Berch, Mark L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
544244, A61K 31675, C07F 96512, C07F 96584
Patent
active
056631596
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.
REFERENCES:
patent: 3929840 (1975-12-01), Christensen et al.
patent: 4724233 (1988-02-01), De Clercq et al.
patent: 4808716 (1989-02-01), Holy et al.
patent: 4816447 (1989-03-01), Ashton
patent: 4816570 (1989-03-01), Farquhar
patent: 4968788 (1990-11-01), Farquhar
patent: 5032680 (1991-07-01), Kawai
patent: 5055458 (1991-10-01), Bailey
patent: 5413996 (1995-05-01), Bodor
Rosenberg, Coll. Czech Chem. Comm 52, p. 2792 (1987).
Farquhar, J. Pharm Sci 72, 324 (1983).
Kunar, J Med Chem 33, 2368 (1990).
Germershauson, Anti. Agents. & Chemo. 29, 1025 (1986).
Farrow, J. Med Chem 33, 1400 (1990).
Iyer, Tet. Letters, 30, 7141 (1989).
Rosenberg, Coll. Czech. Chem Comm 53, 2753 (1988).
Srivastva, Bioorganic Chemistry 12, 118 (1984).
de Clercq, Anti Viral Research 8, 261 (1987).
Bacon, Antiviral Res 23, Suppl p. 99 (1994).
Spadavi, Drug News and Perspective .RTM.2, p. 333 (1989).
Berls J. Med. Chem. 29, 1243-1249 (1986).
Eto, Agric. Biol. Chem 55 (8) 1999 (1991).
Maccross, Biochem. Biophys. Res. Comm. 85, 714 (1978).
"Drug Evaluations Manual" 1993, p. 1723 (American Medical Assocation).
Orchin, "Vocabulary of Organic Chemistry" 1980, pp. 60-61.
Barditch-Crovo et al., "A Randomized, Double-Blind, Placebo-Controlled Phase I/II Evaluation of 9-[-2-(bispivaloyloxy-methyl)phosphonyl-methoxy]adenin (bis-POM PMEA), an Orally Bioavailable Prodrug of the Anti-HV Nucleotide, PMEA," 8th International Conference on Antiviral Research, Santa Fe, NM Abstract #9;A229 (Apr. 23-28, 1995).
Barditch-Crovo et al., "Copy of Slides of the Abstract #9 Presentation," 8th International Conference on Antiviral Research, Santa Fe, NM 14 pages (Apr. 23-28, 1995).
De Clercq, "Broad-Spectrum Anti-DNA Virus and Anti-Retrovirus Activity of Phosphonylmethoxyalkylpurines and -Pyrimidines," Biochem Pharm 42(5):963-972 (1991).
Naesens, "Pharmacokinetics in Mic of Bis(POM)-PMEA, the Bis(pivaloyloxymethyl) Ester Prodrug of 9-(2-Phosphonylmethoxyethyl)adenine," 8th International Conference on Antiviral Research, Santa Fe, NM Abstract #98:A277 (Apr. 23-28, 1995).
Naesens et al., "Antiviral Efficacy in Mice of Oral Bis(POM)-PMEA, the Bis(pivaloyloxymethyl) Ester of Prodrug of 9-(2-Phosphonylmethoxyethyhl)adenine," 8th International Conference on Antiviral Research, Santa Fe, NM Abstract #96:A229 (Apr. 23-28, 1995).
Rosenberg et al, "Synthesis of Potential Prodrugs and Metabolites of 9-(S)-(3-Hydroxy-2-Phosphonylmethoxypropyl)Adenines," Collect Czech Chem Commun 52;2792-2800 (1987).
Snoeck et al, "Antiviral activity of anti-cytomegalovirus agents (HPMPC, HPMPA) assessed by a flow cytometric method and DNA hybridization technique," Antiviral Res 16:1-9 (1991).
Vahlenkamp et al., "(R)-9-(2-Phosphonylmethoxypropyl)-2,6-Diaminopurine Is a Potent Inhibitor of Feline Immunodeficiency Virus Infection," Antimicro AG & Chemo 39(3):746-749 (1995).
De Clercq et al., "Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines," Antiviral Res 8:261-272 (1987).
De Clercq et al., "Efficacy of Phosphonylmethoxyalkyl Derivatives of Adenine in Experimental Herpes Simplex Virus and Vaccinia Virus Infections in Vivo," Antimicro AG & Chemo 33(2):185-191 (1989).
Lin et al, "Novel Acyclic Adenosine Analogs Inhibit Epstein-Barr Virus Replication," Antimicro AG & Chemo 31(9):1431-1433 (1987).
Yokota et al, "Comparative Activities of Several Nucleoside Analogs against Duck Hepatitis B Virus in Vitro," Antimicro AG & Chemo 34:1326-1330 (1990).
Snoeck et al., "New Acyclic Nucleoside Phosphonate Derivatives as Inhibitors of Human Cytomegalovirus," 29th International Conference on Antimicrobial Agents and Chemotherapy (1989) Abstract 1334 on p. 327.
Balzarini et al, Antimicrobial Agents and Chemotherapy, "Differential Antiherpesvirus and Antiretrovirus Effects of the (S) and (R) Enantiomers of Acyclic Nucleoside Phosphonates: Potent and Selective In Vitro and In Vivo Antiretrovirus Activities of (R)-9-(2-Phosphonomethoxypropyl)-2,6-Diaminopurine", 37(2):332-338 (Feb. 1993).
Bronson et al, Nucleotide Analogues, "Synthesis and Antiviral Activity of Phosphonylmethoxyethyl Derivatives of Purine and Pyrimidine Bases", 401:72-87 (1989).
Hartmann et al, Antiviral Chemistry & Chemotherapy, "In vitro activity of acyclic nucleoside phosphonate derivatives against feline immunodeficiency virus in Crandell feline kidney cells and feline peripheral blood lymphocytes", 5(1):13-19 (1994).
Holy et al, Nucleotide Analogues, "Phosphonylmethyl Ethers of Nucleosides and Their Acyclic Analogues", 51-71 (1989).
Hoover et al, Antiviral Research, "Early therapy of feline leukemia virus infection (FeLV-FAIDS) with 9-(2-phosphonylmethoxyethyl)adenine (PMEA)", 16:77-92 (1991).
Midoux, Biochem. Biophys. Res. Comm., "Drug Targeting: Anti-HSV-1 Activity of Mannosylated Polymer-Bound 9-(2-Phosphonylmethoxyethyl Adenine", 167(3):1044-1049 (1990).
Naesens et al, Antiviral Research, "Single-dose administration of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and 9-(2-phosphonylmethoxyethyl-2,6-diaminopurine (PMEDAP) in the prophylaxis of retrovirus infection in vivo", 16:53-64 (1991).
De Clercq et al, "Antiviral Activity of Phosphonylmethoxyalkyl Derivatives of Purines and Pyrimidines," Chemical Abstracts 108(21):179636k (1988).
Holy et al, "Synthesis of N-(2-Phosphonylmethoxyethyl) Derivatives of Heterocyclic Bases," Chemical Abstracts 112(19):179685h (1990).
Naesens et al, Journal of Medical Virology, "Efficacy of Oral 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) in the Treatment of Retrovirus and Cytomegalovirus Infections in Mice", 39:167-172 (1993).
Starrett et al, Antiviral Research, "Synthesis and in vitro evaluation of a phosphonate prodrug: bis(pivaloyloxymethyl) 9-(2-phosphonylmethoxyethyl)adenine", 19:267-273 (1992).
Starrett et al, J. Med. Chem., "Synthesis, Oral Bioavailability Determination, and in Vitro Evaluation of Prodrugs of the Antiviral Agent 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA)", 37:1857-1864 (1994).
Yokota et al, Antiviral Chemistry & Chemotherapy, "Inhibitory effects of acyclic nucleoside phosphonate analogues on hepatitis B virus DNA synthesis in HB6511 cells", 5(2):57-63 (1994).
Bronson Joanne J.
Mansuri Muzammil M.
Martin John C.
Starrett, Jr. John E.
Tortolani David R.
Berch Mark L.
Hensley Max D.
Institute of Organic Chemistry and Biochemistry of the Academy o
Rega Stichting v.z.w.
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