2-酰氧基异丁酰卤与核苷的反应。7. 某些2,2'-脱水-1(3',5'-二-O-酰基-β-D-阿拉伯呋喃糖基)胞嘧啶盐酸盐的合成及生物学评价。

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.

作者信息

Hamamura E K, Prystasz M, Verheyden J P, Moffatt J G

出版信息

J Med Chem. 1976 May;19(5):663-7. doi: 10.1021/jm00227a017.

Abstract

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.

摘要

对2,2'-脱水-1（β-D-阿拉伯呋喃糖基）胞嘧啶盐酸盐（环胞苷）在二甲基乙酰胺中与一系列饱和和不饱和酰氯进行直接酰化反应进行了研究。此类酰化反应已制得大量环胞苷的3',5'-二酯，并对其生物活性进行了检测。这些化合物在组织培养中均对HeLa细胞表现出细胞毒性，除了极难溶的长链二酯（C16 - C22）外，对痘苗病毒和单纯疱疹病毒均表现出显著活性。在小鼠L1210白血病模型中，这些化合物表现出不同的活性，C12 - C14饱和二酯和C18 - C22不饱和二酯具有高效性。其他仅相差几个亚甲基的二酯则显示出截然不同的结果。