Investigation of the conformational influences on the estrogenic activity of 1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamines and of their platinum(II) complexes, II: Synthesis and studies on the estrogenic activity of cis- and trans[bis(2,6-dichloro-4-hydroxybenzylamine)]dihaloplatinum(II)-c omplexes.
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]dichloroplatinum(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 A (complex) and of about 12 A (diamine). Therefore, we discuss two binding sites for estrogens in their receptor.
Gust
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R
Institut für Pharmazie, Universität Regensburg.
Schönenberger
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H
D000818:Animals; D045166:Estradiol Congeners / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000187:drug effects; D013237:Stereoisomerism; D014599:Uterus / Q000187:drug effects
D045166:Estradiol Congeners; D009944:Organoplatinum Compounds; D011960:Receptors, Estrogen