Synthesis, in vitro biological evaluation and oral bioavailability of 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) prodrugs

Antiviral Chemistry and Chemotherapy

Volumn 8, Issue 6, 1997, Pages 557-564

  Arimilli, M N ^a   Kim, C U ^a   Dougherty, J ^a   Mulato, A ^a   Oliyai, R ^a   Shaw, J P ^a   Cundy, K C ^a   Bischofberger, N ^a  

^a GILEAD SCIENCES   (United States)

Author keywords

Acyclic; Alkyl methyl carbonate; Antiretroviral; bis(POC)PMPA; Nucleoside; Oral bioavailability; Prodrug

Indexed keywords

ACYCLIC NUCLEOSIDE; PRODRUG; TENOFOVIR; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; BIOAVAILABILITY; CONTROLLED STUDY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; IN VITRO STUDY; PRIORITY JOURNAL;

EID: 0030782524     PISSN: 09563202     EISSN: None     Source Type: Journal    
DOI: 10.1177/095632029700800610     Document Type: Article

References (26)

1. Abrahamsson K, Eriksson BO, Holme E, Jodal U, Lindstedt S & Nordin I (1994) Impaired ketogenesis in carnitine depletion caused by short-term administration of pivalic acid prodrug. Biochemical Medicine and Metabolic Biology 52: 18-21.
2. Balzarini J Naesens L, Slachmuylders J Niphuis H, Rosenberg I Holy A, Schellekens H & De Clercq E (1991) 9-(2-Phosphonylmethoxy ethyl)adenine (PMEA) effectively inhibits retrovirus replication in vitro and simian immunodeficiency virus infection in rhesus monkeys. AIDS 5: 21-28.
3. Balzarini J, Holy A, Jindrich J, Naesens L, Snoeck R, Schols D & De Clercq E (1993) 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-phosphonylmethoxypropyl)-2,6-diaminopurine. Antimicrobial Agents and Chemotherapy 37: 332-338.
4. Balzarini J, Aquaro S, Perno C -F, Witvrouw M, Holy A & De Clercq E (1996) Activity of the (R)-enantiomers of 9-(2-phosphonylmethoxy propyl)adenine and 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine against human immunodeficiency virus in different human cell systems. Biochemical and Biophysical Research Communications 219: 337-341.
5. Barditch-Crovo P, Toole J, Hendrix CW, Cundy KC, Ebeling D, Jaffe HS and Lietman PS (1997) Anti-human immunodeficiency virus (HIV) activity, safety, and pharmacokinetics adefovir dipivoxil (9-[2-(bis-pivaloylomethyl)-phosphonomethyoxyethyl]adenine) in HIV-infected patients (1997) Journal of Infectious Diseases 176: 406-413.
6. Bohme H & Budde J (1971) Chloromethyl-, Mercaptomethyl-und Imidomethyl-carbonate. Synthesis: 588-590.
7. Bronson JJ, Kim CU, Ghazzouli I, Hitchcock MJM, Kern E & Martin JC (1989) Synthesis and pyrimidine bases. In Nucleosides as Antiviral Agents. Edited by JC Martin. Washington, DC: American Chemical Society, pp. 72-87.
8. Cundy KC, Fishback JA, Shaw JP, Lee ML, Soike KF, Visor GC & Lee W (1994) Oral bioavailability of the antiretroviral agent 9-(2-phosphonylmethoxyethyl)adenine (PMEA) from three formularions of the prodrug bis(pivaloyloxymethyl)-PMEA in fasted male cynomolgus monkeys. Pharmaceutical Research 11: 839-843.
9. De Clercq E, Holy A & Rosenberg I (1989) Efficacy of phosphonylmethoxy alkyl derivatives of adenine in experimental herpes simplex virus and vaccinia virus infections in vivo. Antimicrobial Agents and Chemotherapy 33: 185-191.
10. Egberink A, Borst M, Niphuis H, Balzarini J, Neu H, Schellekens H, De Clercq E, Horzinek M & Koolen M (1990) Suppression of feline immunodeficiency virus infection in vivo by 9-(2-phosphonylmethoxyethyl)adenine. Proceedings of National Academy of Sciences, USA 87: 3087-3091.
11. Farquhar D, Srivastava DN, Kuttesch NJ & Saunders PP (1983) Biologically reversable phosphate-protective groups. Journal of Pharmacological Sciences, USA 72: 324-325.
12. Ikeda S, Sakamoto F, Kondo H, Moriyama M & Tsukamoto G (1984) Studies on prodrugs. III. A convenient and practical preparation of ampicillin prodrugs. Chemical and Pharmaceutical Bulletin 32: 4316-4322.
13. Iyer RP, Phillips LR, Biddle JA, Thakker DR & Egan W (1989) Synthesis of acyloxyalkyl acylphosphonates as potential prodrugs of the antiviral, trisodium phosphonoformate (foscarnet sodium). Tetrahedron Letters 30: 7141-7144.
14. Naesens L, Balzarini J, Bischofberger N & De Clercq E (1996) Antiretroviral activity and pharmacokinetics in mice of oral bis(pivaloyloxymethyl) ester prodrug of 9-(2-phosphonylmethoxyethyl)-adenine. Antimicrobial Agents and Chemotherapy 40: 22-28.
15. Pauwels R, Balzarini J, Schols D, Baba M, Desmyter J, Rosenberg I, Holy A & De Clercq E (1988) Purine derivatives, a new class of anti-human immunodeficiency virus agents. Antimicrobial Agents and Chemotherapy 32: 1025-1030.
16. Safadi M, Oliyai R & Stella VJ (1993) Phosphoryloxymethyl carbamates and carbonates-novel water-soluble prodrugs for amines and hindered alcohols. Pharmaceutical Research 10: 1350-1355.
17. Sakamoto F, Ikeda S & Tsukamoto G (1983) Studies on prodrugs. I. Preparation and characterization of acyloxyallylester of ampicillin. Chemical and Pharmaceutical Bulletin 31: 2698-2707.
18. Shaw JP & Cundy KC (1993) Biological screening of PMEA prodrugs. Pharmaceutical Research 10: S294.
19. Srivastava D & Farquhar D (1984) Bioreversible phosphate protective groups: synthesis and stability of model acyloxymethyl phosphates. Bioorganic Chemistry 12: 118-129.
20. Srinivas RV, Robbins BL, Connelly MC, Gong YF, Bischofberger N & Fridland A (1993) Metabolism and in vitro antiviral activities of bis(pivaloyloxymethyl)prodrugs of acyclic nucleotide phosphonates. Antimicrobial Agents and Chemotherapy 37: 2247-2250.
21. Srinivas RV, Robbins BL, Connelly MC, Gong YF, Bischofberger N & Fridland A (1994) Pivaloyloxymethyl esters of acyclic nucleoside phosphonates. International Antiviral News. 2: 53-55.
22. Starrett JE Jr, Tortolani DR, Russell J, Hitchcock MJM, Whiterock V, Martin JC & Mansuri MM (1994) Synthesis, oral bioavailability determination, and in vitro evaluation of prodrugs of the antiviral agent 9-[2-(phosphonylmethoxy)ethyl]adenine (PMEA) Journal of Medicinal Chemistry 37: 1857-1864.
23. Tsai CC, Follis KE, Sabo A, Beck TW, Grant RF, Bischofberger N, Benveniste RE & Black R (1995) Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl)adenine. Science 270: 1197-1199.
24. Tsai CC, Follis KE, Beck TW, Sabo A, Bischofberger N & Dailey PJ (1997) Effects of (R)-9-(2-phosphonylmethoxypropyl)adenine monotherapy on chronic SIV infection in macaques. AIDS Research and Human Retroviruses 13: 707-712.
25. Van Rompay KKA, Cherrington JM, Marthas ML, Berardi CJ, Mulato AS, Spinner A, Tarara RP, Canfield DR, Telm S, Bischofberger N & Pederson NC (1996) 9-[2-(Phosphomethoxy)propyl]-adenine therapy of established simian immunodeficiency virus infection in infant rhesus macaques. Antimicrobial Agents and Chemotherapy 40: 2586-2591.
26. Weislow OS, Kiser R, Fine DL, Bader J, Shoemaker RH & Boyd MR (1989) New soluble-formazan assay for HIV-1 cytopathic effects: application to high-flux screening of synthetic and natural products for AIDS antiviral activity. Journal of the National Cancer Institute 81: 577-586.