Synthesis and antitumor evaluation of alpha-methylene-gamma-butyrolactone-linked to 5-substituted uracil nucleic acid bases

被引：10

作者：

Kim, JC

Kim, JA

Kim, SH

Park, JI

Kim, SH

Choi, SK

Park, WW

机构：

[1] PUSAN NATL UNIV,COLL MED,DEPT BIOCHEM,PUSAN 609735,SOUTH KOREA

[2] PUSAN NATL UNIV,DEPT BIOCHEM,COLL MED,PUSAN 609735,SOUTH KOREA

[3] DONG A UNIV,DEPT CHEM,PUSAN 609735,SOUTH KOREA

[4] PUASN JR COLL,PUSAN 609735,SOUTH KOREA

来源：

ARCHIVES OF PHARMACAL RESEARCH | 1996年 / 19卷 / 03期

关键词：

5'-Methyl-5'-(5-Substituted uracil-1-ylmethyl)-2'-oxo-3'-methylenetetrahydrofuran; alpha-methylene-gamma-butyrolactone; cytotoxic moiety; reformatsky reaction; antitumor activity; mouse mammary carcinoma (FM-3a); mouse lymphoid neoplasma (P-388); human histiocytic lymphoma (U-937); IC50;

D O I：

10.1007/BF02976897

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Six, heretofore undescribed, 5'-Methyl-5'-(5-Substituted uracil-1-ylmethyl)-2'-oxo-3'-methylenetetrahydrofurans (F, Cl, Br, I, CH3, H) (6a-f) were synthesized and evaluated against three cell lines (FM-3A, P-388 and U-937). For the preparation of alpha-methylene-gamma-butyrolactone bearing 5-substituted uracils (6a-f), the efficient Reformatsky type reaction was employed which involves the treatment of ethyl alpha-(bromomethyl) acrylate and zinc with the respective 5-substituted uracil-1-ylacetones (5a-f). The acetone derivatives (5a-f) were directly obtained by the respective alkylation reaction of 5-substituted uracils with chloroacetone in the presence of K2CO3 (or NaH). These lactone compounds 6a-f exhibited moderate to significant activity in all of the three cell lines, and 6b, 6c and 6e showed significant antitumor activities (inhibitory concentrations (IC50) ranged from 1.3-3.8 mu g/ml).

引用

页码：235 / 239

页数：5

共 35 条

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[35] Highly stereoselective synthesis of (Z)- and (E)-chloro-substituted-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\alpha $$\end{document}-methylene-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\gamma $$\end{document}-butyrolactone by possibly controlling cis- and trans-chloropalladation
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