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

Abstract

The synthesis of the bisacrylate I (R = CH2:CHCO2) (II), the bis-beta -chloropropionate I (R = ClCH2CH2CO2) (III) and the bis-beta -bromopropionate I (R = BrCH2CH2CO2) (IV) of the partial antiestrogen 2,3-bis(2-fluoro-4-hydroxyphenyl)-2,3-dimethylbutane I (R = OH) (V) by condensation V with corresponding acid chloride is described. In the case of III and IV the introduction of the beta -haloester functions moderately reduces the estrogen receptor affinity of V. However, it was quite strongly diminished in II. The hydrolytic stability under in vitro-receptor-assay conditions decreases in the order II > IV > III. Compared with the V the estrogenic potency of II-IV is increased to a great extent. The title compds. cause a strong inhibition of the hormone-dependent MXT-M3.2 mouse mammary tumor.