抗肿瘤剂。25. 尿嘧啶和胸腺嘧啶α-亚甲基-γ-内酯及相关衍生物的合成与抗肿瘤活性。

Antitumor agents. 25. Synthesis and antitumor activity of uracil and thymine alpha-methylene-gamma-lactones and related derivatives.

作者信息

Lee K H, Wu Y S, Hall I H

出版信息

J Med Chem. 1977 Jul;20(7):911-4. doi: 10.1021/jm00217a009.

Abstract

Uracil and thymine alpha-methylene-gamma-lactones and related derivatives have been synthesized as novel potential alkylating antitumor agents. The synthesis of these compounds involved the convenient Reformatsky-type reaction between ethyl-alpha-(bromomethyl)acrylate and the proper pyrimidinyl ketones. Preliminary in vivo tumor assay indicated that these compounds were active against the Walker 256 carcinosarcoma in rats and the P-388 lymphocytic leukemia as well as the B-16 melanotic melanoma in mice at 2.5-25 mg/kg.

摘要

尿嘧啶和胸腺嘧啶α-亚甲基-γ-内酯及其相关衍生物已被合成为新型潜在的烷基化抗肿瘤剂。这些化合物的合成涉及α-（溴甲基）丙烯酸乙酯与适当的嘧啶基酮之间便捷的Reformatsky型反应。初步体内肿瘤试验表明，这些化合物在2.5-25mg/kg剂量下对大鼠的Walker 256癌肉瘤、小鼠的P-388淋巴细胞白血病以及B-16黑色素瘤具有活性。