Reactions of 2-acyloxyisobutyryl halides with nucleosides. 7. Synthesis and biological evaluation of some 2,2'-anhydro-1(3',5'-di-O-acyl-beta-D-arabinofuranosyl)cytosine hydrochlorides.
The direct acylation of 2,2'-anhydro-1(beta-D-arabinofuranosyl)cytosine hydrochloride (cycloC) with a homologous series of saturated and unsaturated acyl chlorides in dimethylacetamide has been investigated. Such acylation reactions have made available a considerable number of 3',5'-diesters of cycloC that have been examined for biological activities. The compounds all show cytotoxicity against HeLa cells in tissue culture, and with the exception of the highly insoluble long-chain diesters (C16--C22), show pronounced activity against vaccinia and Herpes simplex viruses. Against L1210 leukemia in mice the compounds show varied activities, the C12--C14 saturated diesters and the C18--C22 unsaturated diesters being highly effective. Other diesters, varying by only a few methylene groups, show dramatically different results.
D000812:Anhydrides / Q000138:chemical synthesis; D000818:Animals; D002087:Butyrates; D002478:Cells, Cultured; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D006367:HeLa Cells / Q000187:drug effects; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D018139:Simplexvirus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014616:Vaccinia virus / Q000187:drug effects
D000812:Anhydrides; D002087:Butyrates; D003561:Cytarabine