Investigation of the configurational and conformational influences on the hormonal activity of 1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamines and of their platinum(II) complexes. 1. Synthesis, estradiol receptor affinity, and estrogenic activity of diastereomeric [N-alkyl- and N,N'-dialkyl-1,2- bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) complexes.
N-Monoalkylated (Et) and N,N'-dialkylated (Me and Et) 1,2-bis(2,6-dichloro-4-hydroxyphenyl)-ethylenediamines and their dichloroplatinum(II) complexes were synthesized, and their configuration and conformational behavior were 1H-NMR spectroscopically clarified. The latter was brought in relation to their relative binding affinity (RBA) to the estrogen receptor as well as to their estrogenic potency. In contrast to the RR/SS-configurated diamines, the R/S-configurated ones showed marked estrogenic properties which correlate with the RBA's. In the related R/S-configurated complexes the estrogenic activity is determined by the same structural requirements as in the diamine series. However, a correlation between RBA's and estrogenic potencies is missing. The connection between spatial structure and activity is discussed by use of a drug-receptor model recently proposed by Höltje and Dall.
Gust
R
R
Institut für Pharmazie, Lehrstuhl Pharmazeutische Chemie II, Universität Regensburg, Federal Republic of Germany.
Niebler
K
K
Schönenberger
H
H
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D005029:Ethylenediamines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D005029:Ethylenediamines; D009944:Organoplatinum Compounds; D011960:Receptors, Estrogen