Cytotoxic ester derivatives of the mammary tumor inhibiting antiestrogen 2,3-bis(2-fluoro-4-hydroxyphenyl)-2,3-dimethylbutane.
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.
Schwarz
W
W
Institut für Pharmazie, Lehrstuhl Pharmazeutische Chemie II, Universität Regensburg, Federal Republic of Germany.
Hartmann
R W
RW
Engel
J
J
Schneider
M R
MR
Schönenberger
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects*; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004965:Estrogen Antagonists / Q000138:chemical synthesis*; D006589:Hexestrol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D006589:Hexestrol; C063969:2,3-bis(2-fluoro-4-hydroxyphenyl)-2,3-dimethylbutane