In vitro and in vivo evaluation of the antiviral activity of 1-hexadecyloxycarbonyl-2-(6-methyl-9H-purin-9-ylamino)ethane as an antiherpes agent. In the search for antiherpetic agents, a potent antiherpetic agent named 1-hexadecyloxycarbonyl-2-(6-methyl-9H-purin-9-ylamino)ethane (compound II) was synthesized from a mixture of (1R,2R)-(+)-glycidyl 3-nitrobenzyl ester and 7-(2,6-diamino-4-azatetralin)-1H-purine through six steps, and its activity against herpes simplex virus (HSV) type 1 was studied. As a result, compound II was found to be extremely potent in inhibiting the replication of HSV with an EC50 value of 9.6 microM. As a potent antiherpetic agent, compound II exhibited a dose-dependent reduction in HSV plaque formation in three different types of HSV-infected monolayers. In addition, compound II was shown to be a potent inhibitor of HSV replication in Vero cells and against a systemic HSV infection in mice. No signs of toxicity were seen in compound II-treated mice. It is therefore considered that compound II can be developed as a new potent antiherpetic agent.