R. Gust, H. Schönenberger
1994
Citations
0
Influential Citations
3
Citations
Quality indicators
Journal
Archiv der Pharmazie
Abstract
2,6‐Dichloro‐4‐hydroxybenzylamine (1) and its N‐methyl (2) and N‐ethyl (3) derivatives were synthesized and tested for estrogen receptor affinity as well as for estrogenic activity. In contrast to their related highly active 1,2‐bis(2,6‐dichloro‐4‐hydroxyphenyl)ethylenediamines (meso‐4 ‐ meso‐6) none of the benzylamines showed hormonal activity. The coordination of the benzylamine 1 to platinum did not lead to an estrogenic compound. The reasons for the different activity of [meso‐1,2(bis‐2,6‐dichloro‐4‐hydroxyphenyl)ethylenediamine]dichloroplatium(II) (meso‐4‐PtCl2) and cis[bis(2,6‐dichloro‐4‐hydroxybenzylamine)]dichloroplatinum(II) (cis‐1‐PtCl2), the latter of which can be considered as a ring‐opened counterpart of the highly active meso‐4‐PtCl2, are thoroughly discussed under inclusion of conformational facts. The results of this and the preceding work show, that the pharmacophore meso‐1,2‐bis(2,6‐dichloro‐4‐hydroxyphenyl)ethylenediamine (meso‐4) which is exclusively responsible for the estrogenic activity of meso‐4‐PtCl2 causes comparable hormonal effects in two different conformations with O‐O distances of about 8 Å (complex) and of about 12 Å (diamine). Therefore, we discuss two binding sites for estrogens in their receptor.