Studies on biologically active nucleosides and nucleotides. 5. Synthesis and antitumor activity of some 2,2'-anhydro-1-(3',5'-di-O-acyl-beta-D-arabinofuranosyl)cytosine salts and 2,2'-anhydro-1-(3'-O-acyl-beta-D-arabinofuranoxyl)cytosine 5'-phosphates.
A series of 3',5'-diesters of a 2,2'-anhydro-1-(beta-D-arabinofuranosyl)cytosine salt bearing functional substituents on the ester side chains (4--16) have been synthesized. The synthesis of these diesters involved the reaction between cytidine and the corresponding acid anhydride or acid chloride in the presence of boron trifluoride etherate. Similar reaction of bis(cytidine 5'-)suberate (21) with pivaloyl chloride gave bis[2,2'-anhydro-1-(3'-O-pivaloyl-beta-D-arabinofuranosyl)cytosine 5'-]suberate dihydrochloride (22). The reaction could also be extended to a one-step synthesis of 3'-esters of 2,2'-anhydro-1-(beta-D-arabinofuranosyl)cytosine 5'-phosphate (24) from 5'-cytidylic acid. These compounds have been examined for antitumor activity against L1210 leukemia in BDF1 mice. The diesters with a long-chain carboxylic acid (4c, 7c, 12, and 24d) showed high activity when administered intraperitoneally. The compound 24d exhibited moderate activity when administered orally.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D001085:Arabinofuranosylcytosine Triphosphate / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001088:Arabinonucleotides / Q000138:chemical synthesis*; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy; D008722:Methods; D051379:Mice; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001088:Arabinonucleotides; D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate