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Synthesis, Conformational Studies, and Investigations on the Estrogen Receptor Binding of [ R/S ‐1‐(2,6‐Dichloro‐4‐hydroxyphenyl)‐ethylenediamine]platinum(II) Complexes
Author(s) -
Gust Ronald,
Lubczyk Veronika,
Schmidt Kathrin,
Shihada Undine
Publication year - 2001
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/1521-4184(200103)334:3<93::aid-ardp93>3.0.co;2-2
Subject(s) - ethylenediamine , chemistry , platinum , stereochemistry , estrogen receptor , receptor , combinatorial chemistry , medicinal chemistry , biochemistry , organic chemistry , catalysis , medicine , cancer , breast cancer
The syntheses, conformational studies, and investigations on the estrogen receptor binding of [ R/S ‐1‐(2,6‐dichloro‐4‐hydroxyphenyl) ethylenediamine]platinum(II) complexes ( 1‐PtL 2 , 2L = leaving groups) are described. A Strecker synthesis using the 2,6‐dichloro‐4‐methoxybenzaldehyde, NaCN, and NH 4 Cl afforded the cyanoamine 1b , which was subsequently reduced with LiAlH 4 to give the R/S ‐1‐(2,6‐dichloro‐4‐methoxyphenyl)ethylenediamine 1a . Ether cleavage with BBr3 yielded R/S ‐1‐(2,6‐dichloro‐ 4‐hydroxyphenyl)ethylenediamine 1 which was coordinated to platinum(II) by use of K 2 PtCl 4 ( 1‐PtCl 2 ) and K 2 PtI 4 ( 1‐PtI 2 ), respectively. Reaction of 1‐PtI 2 with Ag 2 SO 4 and coordination of tartronic acid led to the [ R/S ‐1‐(2,6‐dichloro‐4‐hydroxyphenyl) ethylenediamine][hydroxymalonato]platinum(II) complex ( 1‐Pt(MalOH )). The spatial structure of 1 and its complexes was evaluated by spectroscopic and molecular modeling methods. In solution the complexes adopt a structure very similar to estradiol. However, the in vitro and in vivo tests for the compounds indicated neither affinity to the estrogen receptor nor estrogenic properties.