Synthesis and biological activity of 3,5-dinitro-4- and -2-(1H-purin-6-ylthio)benzoates, prodrugs of 6-mercaptopurine.
A series fo prodrug modifications of 6-mercaptopurine (6-MP) containing dinitrobenzoate ester moieties with varying chain length has been prepared. These compounds were shown to be cytotoxic in several cell culture screens and also exhibited significant activity against L1210 lymphoid leukemia in vivo. The possibility exists that the transport and distribution of these compounds in vivo will be determined, in part, by increased lipophilic character, with a consequent selective localization in lymphatic and CNS tissue.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000188:drug therapy; D015122:Mercaptopurine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice
D000970:Antineoplastic Agents; D015122:Mercaptopurine