Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines.

Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.

Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines.

Antiviral Res. 1987 Dec;8(5-6):261-72. Unique Identifier : AIDSLINE MED/88239610
De Clercq E; Sakuma T; Baba M; Pauwels R; Balzarini J; Rosenberg I; Holy A; Rega Institute for Medical Research, Katholieke Universiteit; Leuven, Belgium.

Abstract: Various 3-hydroxy-2-phosphonylmethoxypropyl (HPMP) and 2-phosphonylmethoxyethyl (PME) derivatives of purine [adenine (A), guanine (G), 2,6-diaminopurine (DAP), 2-monoaminopurine (MAP), hypoxanthine (HX)] and pyrimidine [cytosine (C), uracil (U), thymine (T)] have been evaluated for their antiviral properties. PMEDAP, (S)-HPMPA [and the cyclic phosphonate thereof, (S)-cHPMPA)], (S)-HPMPC, PMEG, PMEA, HPMPG and HPMPDAP proved to be effective inhibitors of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). (S)-HPMPA and (S)-cHPMPA were the most effective inhibitors of varicella-zoster virus (VZV), and (S)-HPMPC was the most effective inhibitor of cytomegalovirus (CMV). Against adenovirus (types 2, 3 and 4) and vaccinia virus again (S)-HPMPA and (S)-cHPMPA showed the greatest inhibitory activity. As a rule, the PME derivates were much less inhibitory to VZV, CMV, vaccinia and adenovirus than the HPMP derivatives. However, PMEA, PMEDAP and PMEMAP showed marked and selective activity against the human immunodeficiency virus (HIV). (S)-HPMPA was selected for further evaluation in animal model infections. It proved efficacious in the topical treatment of HSV-1 keratitis in rabbits and cutaneous HSV-1 infection in hairless mice, and in the systemic treatment of both HSV-1 and vaccinia virus infections in mice.

Keywords: Animal *Antiviral Agents Cell Survival/DRUG EFFECTS Cells, Cultured Drug Screening DNA Viruses/*DRUG EFFECTS Human Mice Organophosphorus Compounds/*PHARMACOLOGY/TOXICITY Purines/*PHARMACOLOGY/TOXICITY Pyrimidines/*PHARMACOLOGY/TOXICITY Rabbits Structure-Activity Relationship Support, Non-U.S. Gov't Virus Diseases/DRUG THERAPY JOURNAL ARTICLE

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