N^1羟烷基-5-氟尿嘧啶和α-5-氟尿嘧啶-N^1-二羧酸的研究

Study on N^1-Hydroxyalkyl-5-Fluorouracils and α-5-Fluorouracil-N^1-Dicarboxylic Acids

5-氟尿嘧啶(5-FU)是一种广谱性的抗肿瘤药物,其主要缺点是脂溶性小,口服吸收困难,毒副作用较大。为此,多年来,对5-FU进行了大量的化学修饰工作。已成功用于临床的5-FU衍生物主要有呋喃啶(FT-207),双呋喃啶(Thf_2-5-FU)、氟尿嘧啶脱氧核苷(FUDR)及卡莫氟(HCFU)等。在前文中,我们报道了1,3-二羟烷基-5-氟尿嘧啶和氨基酸短肽负载的5-氟尿嘧啶的合成及其抗肿瘤活性。

N^1-Hydroxyalkyl-5-fluorouracils, diethyl α-5-fluorouracil-N^1-malonate, dimethylα-5-fluorouracil-N^1-methylsuccinate, α-5-fluorouracil-N^1-malonic acid and α-5-fluorouracil-N^1-methylsuccinic acid were synthesized and structurally confirmed by ~1H NMR, IR, UVand elemental analysis. The antitumor activity of five 5-fluorouracil derivatives were testedagainst Ehrlish ascites carcinoma (EAC) in mice and compared with that of 5-fluorouracil-N^1-acetic acid and 5-fluorouracil-N^1-propanoic acid. 5-Fluorouracil-N^1-substituted dicarboxy-lic acids exhibited no antitumor activity. N^1-Hydroxyethyl-5-fluorouracil and N^1-hydroxy-propyl-5-fluorouracil, with lower toxicity than 5-fluorouracil, showed an inhibition ratio of52.40% and 67.32%, respectively.