Antiestrogens. Synthesis and evaluation of mammary tumor inhibiting activity of 1,1,2,2-tetraalkyl-1,2-diphenylethanes

Abstract

Among the newly synthesized 1,1,2,2-tetraalkyl-1,2-diphenylethanes, 1,1,2,2-tetramethyl-1,2-bis(4'-hydroxyphenyl)ethane (23) and 1,1,2,2-tetramethyl-1,2-bis(3'-hydroxyphenyl)ethane (26) were the most active compounds regarding estradiol receptor affinity, exhibiting Ka values of 0.73 X 10(8) and 0.67 X 10(8) M-1, respectively. In vivo, 23 and 26 showed only very small uterotrophic activity in the mouse. They strongly inhibited (73%) the estrone-stimulated mouse uterine growth. Tested on the 9,10-dimethyl-1,2-benzanthracene induced hormone-dependent mammary adenocarcinoma of the Sprague-Dawley rat, compounds 23 and 26 exhibited a dose-dependent inhibition of the tumor growth, having a strong effect at a dose of 20 (mg/kg)/day (compound 23).

Synthesis, Structural Evaluation, and Estrogen Receptor Interaction of 4, 5‐Bis(4‐hydroxyphenyl)imidazoles

“…The evaluation of the relative binding affinity (RBA) was performed in the competition experiment with [17]. Additionally, a luciferase assay was used to obtain information about the agonistic effects on molecular level [18].…”

“…The applied method was already described by Hartmann et al [17] and was used with some modifications. The relative binding affinity (RBA) of the test compounds to the estrogen receptor was determined by the displacement of 17β-[ 3 H]estradiol from its binding site.…”

Structure Activity Studies on Leaving Group Derivatives of [meso-1,2-Bis-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]-platinum(II)

“…The applied method was described already by Hartmann et al [19] and used with some modifications. The relative binding affinity (RBA) of the test compounds to the ER was determined by the displacement of 17β-[ 3 H]-estradiol from its binding site.…”

“…For the determination of the binding affinity to the ER the competition experiment with [ 3 H]-estradiol ([ 3 H]-E2) was used [19] . In this experiment the affinity of the platinum complexes to the binding site of E2 is quantified.…”

Synthesis, Conformational Studies, and Investigations on the Estrogen Receptor Binding of [R/S-1-(2,6-Dichloro-4-hydroxyphenyl)-ethylenediamine]platinum(II) Complexes

“…The applied method has already been described by Hartmann et al [15] and was used with some modifications. The relative binding affinity (RBA) of the test compounds to the ER was determined by the displacement of 17β-[ 3 H]estradiol from its binding site.…”