Nucleoside conjugates. 10. Synthesis and antitumor activity of 1-.beta.-D-arabinofuranosylcytosine 5'-diphosphate-1,2-dipalmitins

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Abstract
Three 1-.beta.-D-arabinofuranosylcytosine 5''-diphosphate-1,2-dipalmitins from L-, D-, and DL-.alpha.-dipalmitoylphosphatidic acids have been synthesized and their antitumor activity against two ara-C2 resistant L1210 lymphoid leukemia sublines in mice were evaluated. These new prodrugs of ara-C include are-CDP L-dipalmitin (1), ara-CDP-dipalmitin (2), and ara-CDP-DL-dipalmitin (3). The L and DL isomers produced significant increase in life span (> 400%) and four to five long-term survivors (> 45 days) out of six animals bearing ip implanted partially ara-C resistant L1210 subline [L1210/ara-C (I)], while the D isomer displayed a marginal activity (ILS 100-121%). In contrast, the L isomer was completely ineffective against deoxycytidine kinase deficient ara-C resistant L1210 subline [L1210/ara-C (II)]. However, the results demonstrate that the L and DL isomers of ara-CDP-dipalmitin are promising new prodrugs of ara-C with improved efficacy.