Synthesis and biologic activity of 2'-fluoro-2-halo derivatives of 9-beta-D-arabinofuranosyladenine.
The synthesis of 2-halo-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenines (4b and 4d) by coupling the 2,6-dihalopurine with 3-acetyl-5-benzoyl-2-deoxy-2-fluoro-D-arabinofuranosyl bromide (2) followed by replacement of the 6-halogen with concomitant removal of the acyl blocking groups is described. 2-Fluoroadenine derivative 4g had to be prepared by the diazotization-fluorination of 2-aminoadenine nucleoside 4e. All three nucleosides provided good increases in life span of mice inoculated with P388 leukemia. The best results were obtained when the compounds were administered q3h x 8 on days 1, 5, and 9 after implantation of the leukemia cells. The 2',3'-dideoxynucleoside 5b, prepared by deacetylation of 4f and deoxygenation of the resultant 4h followed by removal of the benzoyl group of 5a, was slightly active against HIV in cell culture.
Montgomery
J A
JA
Southern Research Institute, Organic Chemistry Research, Birmingham, Alabama 35255-5305.
Shortnacy-Fowler
A T
AT
Clayton
S D
SD
Riordan
J M
JM
Secrist
J A
JA
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D006678:HIV / Q000187:drug effects; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; D011683:Purine-Nucleoside Phosphorylase; D014740:Vidarabine