Ester derivatives of the mammary-tumor-inhibiting antiestrogen 2,3-bis(2-fluoro-4-hydroxyphenyl)-2,3-dimethylbutane.
The synthesis of the bisacetate (8), the bisdichloroacetate (9), the biscarbamate (10) and the bisphosphate (11) of the "partial" antiestrogen 2,3-bis(2-fluoro-4-hydroxyphenyl)-2,3-dimethylbutane (7) is described. In the case of 8-10 the introduction of ester functions slightly reduces the estrogen receptor affinity of 7. However, it was strongly diminished in 11. Compared with 7 the estrogenic potency of 8-11 is moderately increased. Compounds 8-11 cause a strong inhibition of the hormone-dependent MXT M3.2 mouse mammary tumor. Only 9 containing cytotoxic dichloroacetate groups shows a significantly better antitumor effect than 7.
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; D001667:Binding, Competitive; D004965:Estrogen Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D011959:Receptors, Estradiol / Q000187:drug effects
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D011959:Receptors, Estradiol