2'-脱氧尿苷和2'-脱氧-5-氟尿苷的3'-(氯乙基)亚硝基脲类似物的抗肿瘤活性。

Antineoplastic activity of 3'-(chloroethyl)nitrosourea analogues of 2'-deoxyuridine and 2'-deoxy-5-fluorouridine.

作者信息

Lin T S, Brubaker W F, Wang Z H, Park S, Prusoff W H

出版信息

J Med Chem. 1986 May;29(5):862-5. doi: 10.1021/jm00155a044.

Abstract

The (chloroethyl)nitrosourea analogues of 2'-deoxyuridine and 2'-deoxy-5-fluorouridine, 3'-[3-(2-chloroethyl)-3-nitrosoureido]-2',3'-dideoxyuridine (3'-CdUNU, 7) and 3'-[3-(2-chloroethyl)-3-nitrosoureido]-2,3'-dideoxy-5-fluorouridine (3'-CFdUNU, 8), have been synthesized by treatment of the corresponding 3'-amino nucleosides with chloroethyl isocyanate, followed by nitrosation of the resulting ureas. Nucleoside nitrosoureas 7 and 8 exhibited marked anticancer activity against L1210 leukemia in tumor-bearing mice. At an optimum dosage level of 40 mg/kg, 7 and 8 produced 90% and 60% "cures" (greater than 60-day survivors), respectively. The structure-activity relationships are discussed.

摘要

2'-脱氧尿苷和2'-脱氧-5-氟尿苷的（氯乙基）亚硝基脲类似物，即3'-[3-(2-氯乙基)-3-亚硝基脲基]-2',3'-二脱氧尿苷（3'-CdUNU，7）和3'-[3-(2-氯乙基)-3-亚硝基脲基]-2,3'-二脱氧-5-氟尿苷（3'-CFdUNU，8），是通过用氯乙基异氰酸酯处理相应的3'-氨基核苷，然后对所得脲进行亚硝化反应合成的。核苷亚硝基脲7和8在荷瘤小鼠中对L1210白血病表现出显著的抗癌活性。在40mg/kg的最佳剂量水平下，7和8分别产生了90%和60%的“治愈”（存活超过60天）。讨论了构效关系。