乳腺肿瘤抑制性抗雌激素2,3-双（2-氟-4-羟基苯基）-2,3-二甲基丁烷的细胞毒性酯衍生物

Cytotoxic ester derivatives of the mammary tumor inhibiting antiestrogen 2,3-bis(2-fluoro-4-hydroxyphenyl)-2,3-dimethylbutane.

作者信息

Schwarz W, Hartmann R W, Engel J, Schneider M R, Schönenberger H

机构信息

Institut für Pharmazie, Lehrstuhl Pharmazeutische Chemie II, Universität Regensburg, Federal Republic of Germany.

出版信息

Arch Pharm (Weinheim). 1990 Feb;323(2):121-4. doi: 10.1002/ardp.19903230213.

DOI:10.1002/ardp.19903230213

PMID:2159273

Abstract

The synthesis of the bis-acrylate 12, the bis-beta-chloropropionate 13 and the bis-beta-bromopropionate 14 of the "partial" antiestrogen 2,3-bis(2-fluoro-4-hydroxyphenyl)-2,3-dimethylbutane (7) is described. In the case of 13 and 14 the introduction of the beta-haloester-functions moderately reduces the estrogen receptor affinity of 7. However, it was quite strongly diminished in 12. The hydrolytic stability under in vitro-receptor-assay conditions decreases in the order 12 greater than 14 greater than 13. Compared with 7 the estrogenic potency of 12-14 is increased to a great extent. The title compounds cause a strong inhibition of the hormone-dependent MXT-M3.2 mouse mammary tumor.

摘要

描述了“部分”抗雌激素2,3-双（2-氟-4-羟基苯基）-2,3-二甲基丁烷（7）的双丙烯酸酯12、双β-氯丙酸酯13和双β-溴丙酸酯14的合成。在13和14的情况下，β-卤代酯官能团的引入适度降低了7的雌激素受体亲和力。然而，在12中其亲和力大幅降低。在体外受体测定条件下的水解稳定性按12＞14＞13的顺序降低。与7相比，12 - 14的雌激素活性大幅增加。标题化合物对激素依赖性MXT - M3.2小鼠乳腺肿瘤有强烈抑制作用。