4-methylideneisoxazolidin-5-ones -: A new class of α-methylidene-γ-lactones with high cytostatic activity

被引：31

作者：

Janecki, T ^{[1
]}

Wasek, T

Rózalski, M

Krajewska, U

Studzian, K

Janecka, A

机构：

[1] Tech Univ Lodz, Inst Organ Chem, PL-90924 Lodz, Poland

[2] Med Univ Lodz, Dept Pharmaceut Biochem, Fac Pharm, PL-90151 Lodz, Poland

[3] Med Univ Lodz, Dept Med Chem, PL-92215 Lodz, Poland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 05期

关键词：

alpha-methylidene-beta-lactones; isoxazolidin-5-ones; cytostatic activity; Horner-Wadsworth-Emmons olefination;

D O I：

10.1016/j.bmcl.2005.11.032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel, general method of synthesis of 4-methylideneisoxazolidin-5-ones 10 is described. The target compounds were synthesized starting from ethyl 2-diethoxyphosphoryl-2-alkenoates 6 or dicyclohexylammonium 4-diethoxyphosphoryl-2-alkenoates 7. Addition of N-methylhydroxylamine hydrochloride to these Michael acceptors, lactonization to 4-diethoxyphosphorylisoxazolidin-5-ones 9, and Horner-Wadsworth-Emmons olefination of formaldehyde using 9 gave the title isoxazolidinones 10. All obtained compounds were tested against L-1210, HL-60, and NALM-6 leukemia cell lines. Several isoxazolidinones 10 were found to be very potent with IC50 < 1 mu M. The highest cytostatic activity against HL-60 was observed for 10a and against NALM-6 for 10b with IC50 values of 0.74 and 0.34 mu M, respectively. (C) 2005 Elsevier Ltd. All rights reserved.

引用

页码：1430 / 1433

页数：4

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