SYNTHESIS OF 5-SELENIUM-SUBSTITUTED URACIL DERIVATIVES - INHIBITION OF THYMIDYLATE SYNTHETASE BY 5-HYDROSELENO-2'-DEOXYURIDYLATE

被引：16

作者：

CHOI, S ^{[1
]}

KALMAN, TI ^{[1
]}

BARDOS, TJ ^{[1
]}

机构：

[1] SUNY BUFFALO,SCH PHARM,DEPT MED CHEM,AMHERST,NY 14260

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1979年 / 22卷 / 06期

关键词：

D O I：

10.1021/jm00192a004

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

5-Selenium-substituted derivatives (diselenides) of uracil, 2ʹ-deoxyuridine, and 2ʹ-deoxyuridylic acid were synthesized via the addition of methyl hypobromite to the 5, 6 double bond, followed by reaction of the adducts with sodium diselenide. The physical and chemical properties of these compounds (including their facile reduction by dithiothreitol and rapid reoxidation) were similar to those of the corresponding 5-sulfur analogues. 5-Hydroseleno-2ʹ-deoxyuridylic acid was as potent as 5-mercapto-2ʹ-deoxyuridylate in inhibiting thymidylate synthetase from L. casei (κi≈ 6 X 10-8M) but the nucleoside III was considerably less active than 5-mercapto-2ʹ-deoxyuridine in the inhibition of growth of the leukemia L1210 cell in culture. © 1979, American Chemical Society. All rights reserved.

引用

页码：618 / 621

页数：4

共 26 条

[1] SELENIUM DERIVATIVES IN INDOLE SERIES .1. ON SYNTHESIS OF 3-SELENOCYANO-INDOLE AND 3,3-DIINDOLYL DISELENIDE [J].