N9- and N7-(Chloromethyl Phenymethyl)Chloropurine Derivatives from α, α'-Dichloroxylenes: Synthesis and Anticancer Activity

A series of ortho- meta- and para-N9-(chloromethylphenyl)methyl]chloropurines 4-12 and N7-(chloromethylphenyl)methyl]chloropurines 13-21 were obtained by the reaction of various substituted chloropurines with α,α'-dichloroxylenes. Compounds 4-21 were evaluated for cytotoxic activity against a panel NCI-H460 (lung), MCF7 (breast) and SF-268 (CNS) cancer cell lines. The ‘active’ compounds, which reduced growth of cancer cells to ca. 32% or less, have been evaluated in a full panel of 60 human cancer cell lines over a 5-log dose range at the National Cancer Institute. Several compounds have demonstrated growth inhibitory effects (GI₅₀) in a wide range of cancer cell lines. The 2,6-dichloropurines in this series (5, 8, 11, 14, 17 and 20) exhibited significant antineoplastic activity.