Oestrogenic, Anti‐oestrogenic and Fertility Effects of Some Triphenylethanes and Triphenylethylenes Related to Ethamoxytriphetol (Mer 25)

Abstract

Five triphenylethylenes, a triphenylethane and a triphenylethanol, carrying methyl substituents ortho to one or both of the ring oxygen functions, have been examined for oestrogenic, and anti‐oestrogenic activity in mice, and three of the compounds, α‐[4‐(β‐diethylaminoethoxy)‐3, 5‐xylyl]‐α‐phenyl‐β‐4‐methoxyphenyl‐ethanol (IV), α′‐[4‐(β‐diethylaminoethoxy)‐3, 5‐xylyl]‐4‐methoxy‐bibenzyl (V) and α′‐[4‐(β‐diethylaminoethoxy)‐3, 5‐xylyl]‐4‐methoxy‐stilbene (VI), were tested for their effects on fertility in mice. Orthomethylation reduces oestrogenic and/or anti‐oestrogenic activity compared with the reported activities of non‐methylated analogues. The anti‐oestrogenic ethamoxytriphetol (MER 25) reduced fertility in mice whereas its inactive dimethylated analogue (IV) was ineffective. The weakly active anti‐oestrogens, V and VI, did not affect fertility in mice.

Geometric Isomers of Substituted Triphenylethylenes and Antiestrogen Action

“…This argument has been stressed previously (30,31). However, the biological properties of cis-monohydroxytamoxifen seem to be inconsistent with the binding model, unless the affinity of the phenolic group for the complementary 3-phenolic/hydroxyl site on the receptor can overcome the steric inhibition implicit in the cis structure.…”

Turning scientific serendipity into discoveries in breast cancer research and treatment: a tale of PhD students and a 50-year roaming tamoxifen team

“…However, the introduction of ring methyl groups into triphenylethylene and triphenylethane antiestrogens ortho to the alkylaminoethoxy side chain is disadvantageous. This suggests that the side chain cannot be inhibited from rotation [162]. a from [41] and A, B from [106] with copy right permission Anna Riegel makes discoveries with antibodies from the Jensen/Greene laboratory to support the "crocodile model" of estrogen/antiestrogen action I wanted to deploy Elwood's antibodies to determine whether Anna could identify differences between estrogens and antiestrogens once bound at the ligand-binding site of the ER.…”

“…However, the introduction of ring methyl groups into triphenylethylene and triphenylethane antiestrogens ortho to the alkylaminoethoxy side chain is disadvantageous. This suggests that the side chain cannot be inhibited from rotation [ 162 ]. a from [ 41 ] and A, B from [ 106 ] with copy right permission …”

Selective Estrogen Receptor Modulators

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