Synthesis, conformational studies, and investigations on the estrogen receptor binding of [R/S-1-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]platinum(II) complexes

Citation
R. Gust et al., Synthesis, conformational studies, and investigations on the estrogen receptor binding of [R/S-1-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]platinum(II) complexes, ARCH PHARM, 334(3), 2001, pp. 93-100
Citations number
16
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
ARCHIV DER PHARMAZIE
ISSN journal
0365-6233 → ACNP
Volume
334
Issue
3
Year of publication
2001
Pages
93 - 100
Database
ISI
SICI code
0365-6233(200103)334:3<93:SCSAIO>2.0.ZU;2-6
Abstract
The syntheses, conformational studies, and investigations on the estrogen r eceptor binding of [R/S-1-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] pl atinum(II) complexes (1-PtL2, 2L = leaving groups) are described. A Strecke r synthesis using the 2,6-dichloro-4-methoxybenzaldehyde, NaCN, and NH4Cl a fforded the cyanoamine 1b, which was subsequently reduced with LiAlH4 to gi ve the R/S-1-(2,6-dichloro-4-methoxyphenyl)ethyl-enediamine la. Ether cleav age with BBr3 yielded R/S-1-(2,6-di-chloro-4-hydroxyphenyl)ethylenediamine 1 which was coordinated to platinum(II) by use of K2PtC4 (1-PtCl2) and K2Pt I4 (1-PtI2), respectively. Reaction of 1-PtI2 with Ag2SO4 and coordination of tartonic acid led to the [R/S-1-(2,6-dichloro-4-hydroxyphenyl) ethylened iamine] [hydroxymalonato] platinum(II) complex (1-Pt(MalOH)). The spatial s tructure of 1 and its complexes was evaluated by spectroscopic and molecula r modeling methods. In solution the complexes adopt a structure very simila r to estradiol. However, the in vitro and in vivo tests for the compounds i ndicated neither affinity to the estrogen receptor nor estrogenic propertie s.