Reactions of 2-acyloxyisobutyryl halides with nucleosides. 6. Synthesis and biological evaluation of some 3'-acyl derivatives of 2,2'-anhydro-1-(.beta.-D-arabinofuranosyl)cytosine hydrochloride

• Published in: Journal of medicinal chemistry 1976-05, Vol.19 (5), p.654-662
• Main Authors: Hamamura, Ernest K, Prystasz, Miroslav, Verheyden, Julien P. H, Moffatt, John G, Yamaguchi, Kenji, Uchida, Naomi, Sato, Kosaburo, Nomura, Akio, Shiratori, Osamu
• Format: Article
• Language: English
• Subjects: Anhydrides - chemical synthesis; Animals; Butyrates; Cells, Cultured; Cytarabine - analogs & derivatives; Cytarabine - chemical synthesis; Cytarabine - pharmacology; Cytarabine - therapeutic use; HeLa Cells - drug effects; Leukemia L1210 - drug therapy; Measles virus - drug effects; Mice; Mice, Inbred Strains; Orthomyxoviridae - drug effects; Simplexvirus - drug effects; Structure-Activity Relationship; Vaccinia virus - drug effects
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00227a016

The reactions of cytidine with 22 different 2-O-acyloxyisobutyril chlorides lead to the isolation of the corresponding 2,2'-anhydro-1-(3'-O-acyl-beta-d-arabinofuranosyl)cytosine hydrochlorides 9. These compounds, which all show cytotoxicity against HeLa cells in tissue culture, have been examined for antiviral and antileukemic activity. Activity against DNA viruses (vaccinia and Herpes) in tissue culture is maximal in compounds containing acyl groups with 8--12 carbon atoms. Activity against L1210 leukemia in mice varies markedly according to the length of the acyl groups, and high activities were observed in the case of long-chain (C16--C22) esters. The reaction between cytidine and O-acetylsalicyloyl chloride provides an alternate route for the synthesis of 3'-O-Ac cycloC hydrochloride.