Homoacyclovir analogues of unnatural bases and their activity against hepatitis B virus.

The ambident nucleophilic nature of the sodium salts of 2(1H)-qunioxalinone (2) and the phthalazinedione (3) has been realized from their alkylation with 2-(2-chloroethoxy)ethylacetate (1) to afford 1-[2-(2-acetoxyethoxy)ethyl]-2(1H)-quinoxalinone (8) and 2-[2-(2-acetoxyethoxy)ethoxy]qunioxaline (9) as well as 10 and 11, respectively. The corresponding derivatives 12-15 were similarly prepared by the alkylation of the unnatural bases 4-7 with 1. Treatment of the alkylated derivatives 8-15 with methanolic ammonia solution (1:1) at room temperature gave the corresponding hydroxyalkyl derivatives 16-23. The site of the alkylation was deduced from the spectral characteristics of the products. The activity of compounds 16-22 against Hepatitis B virus (HBV) in HepG2 cell has been tested. Some of the compounds showed high viral replication inhibition with low cytotoxicity.