Synthesis of novel 2',3'-didehydro-2',3'-dideoxyinosine phosphoramidate prodrugs and evaluation of their anticancer activity.

An efficient synthesis of 4-chlorophenyl N-alkyl phosphoramidates of 2 ',3 '-didehydro-2 ',3 '-dideoxyinosine employing 4-chlorophenyl phosphoroditetrazolide as a phosphorylating agent is reported. Improved method for the synthesis of 2 ',3 '-didehydro-2 ',3 '-dideoxyinosine starting from inosine is also described. The synthesized phosphoramidates 11-18 were examined for their cytotoxic activity in three human cancer cell lines: cervical (HeLa), oral (KB), and breast (MCF-7) employing sulforhodamine B assay. The highest activity in all investigated cancer cell lines was displayed by phosphoramidate 13 with N-n-propyl substituent.