Lipid derivatives of phosphonoacids for liposomal incorporation

Details Lipid derivatives of phosphonoacids for liposomal incorporation Lipid derivatives of phosphonoacids for liposomal incorporation

1989-11-22

1993-03-16

Lee, Mary C.

Organic compounds -- part of the class 532-570 series

Organic compounds

Phosphorus esters

558169, 558170, 558180, 558181, 558182, C07F 940

Patent

active

051946548

ABSTRACT:
Compounds are disclosed for treating viral infections due to herpes, influenza, hepatitis B, Epstein-Barr, and varicella zoster viruses, as well as cytomegalovirus and human immunodeficiency virus (HIV) by means of lipid derivatives of antiviral agents. The compounds consist of lipid derivatives of phosphonoacids having antiviral activity which are linked, commonly through the phosphate group of the phosphonoacid, to one of a selected group of lipids.
The lipophilic nature of these compounds provides advantages over the use of the phosphonoacids alone. It also makes it possible to incorporate them into the lamellar structure of liposomes when combined with similar molecules. In the form of liposomes, these antiviral molecules are preferentially taken up by macrophages and monocytes, cells which have been found to harbor the target human immunodeficiency virus (HIV). Additional site specificity may be incorporated into the liposomes with the addition of ligands, such as monoclonal antibodies or other peptides or proteins which bind to viral proteins.
Effective phosphonoacids are phosphonoformic acid or phosphonoacetic acid; lipid groups may be glycolipids, sphingolipids, phospholipids, glycerolipids, or fatty acids. The compounds persist, after intracellular hydrolysis, as the antiviral phosphonoacids. The compounds are effective in improving the efficacy of antiviral phosphonoacids by prolonging the antiviral activity after the administration of the drug has ended, and in preventing retroviral replication in HIV infections which have become resistant to therapy with conventional forms of the antiretroviral agents.

REFERENCES:
patent: 4215113 (1980-07-01), Eriksson et al.
patent: 4771041 (1988-09-01), Ericksson et al.
E. Helgestrand et al., (1978) Science (Washington, D.C.) 201: 819.
M. S. Fischl et al., (1987) New Eng. J. Med., 317: 185-191.
D. D. Richman et al., (1987) New Eng. J. Med., 317: 192-197.
D. D. Richman et al., (1987) J. Exp. Med., 166: 1144-1149.
R. Lambert et al., (1989) J. Med. Chem., 32: 367-374.
T. Matsushita et al., (1981) Cancer Res., 41: 2707-2713.
D. H. W. Ho and G. L. Neil, (1977) Cancer Res., 37: 1640-1643.
A. D. Bangham et al., (1965) J. Mol. Biol., 13: 238-252.
C. D. V. Black et al., (1977) Trans. Roy. Soc. Trop. Med. Hyg., 71: 550-552.
C. R. Alving et al., (1978) Proc. Natl. Acad. Sci. USA, 75: 2959-2963.
G. Lopez-Berestein, (1986) Ann. Int. Med., 105: 130-131.
E. H. Herman et al., Cancer Res., 43: 5427-5431.
M. Ostro, (1987) Sci. Am., 256: 103-111.
B. Oberto, (1983) Pharmacol. Ther., 19: 387-415.
F. C. Szoka, Jr. and C. J. Chu, (1988) Antimicrobial Agents and Chemotherapy, 32 (6): 858-864.
S. Z. Salahuddin et al., (1986) Blood, 68: 281-284.
S. Koenig et al., (1986) Science, 233: 1089-1093.
G. Poste et al., (1984) Liposome Technology, vol. III, G. Gregoriadis, ed., CRC Press Boca Raton, pp. 1.gtoreq.28.
G. Scherphof, (2986) Lipids and Biomembranes, Past, Present and Future, J. A. F. Op den Kamp et al., Eds., Elsevier North Holland, Amsterdam, pp. 113-136.
B. W. Agranoff and W. D. Suomi, (1963) Biochemical Preparations, 10: 47-51.
F. Olson et al., (1979) Biochim. Biophys. Acta, 577: 9-23.
F. Szoka, Jr. et al., (1978) Proc. Nat. Acad. Sci. USA, 75: 4194-4198.
E. Mayhew et al., (1984) Biochim. Biophys. Acta, 775: 169-174.
S. Kin et al., (1983) Biochim. Biophys. Acta, 728: 339-348.
L. D. Mayer et al., (1986) Biochim. Biophys. Acta, 858: 161-168.
A. F. Rosenthal and R. P. Geyer, (1960) J. Biol. Chem., 235 (8): 2202-2206.
L. D. Leserman et al., (1980) Nature, 288: 602-604.
B. A. Larder et al., (1989) Science, 243: 1731-1734.
E. G. Bligh and W. J. Dyer, (1959) Can. J. Biochem. & Physiol., 37: 911-917.

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