[Hydroxy substituted phenyltetralines: compounds with affinity for estrogen and androgen receptors].
Among nonsteroidal antiandrogens, mostly compounds of the Flutamide-type are described. For the development of new compounds with affinity to androgen receptors and antiandrogenic activity five new hydroxy-substituted phenyltetralines were prepared and tested. Synthesis was achieved by reaction of the respective 1-tetralones with phenyl magnesium bromides, dehydration of the carbinols, hydrogenation and ether cleavage. In addition to the expected affinity to estrogen receptors, especially the 6-OH, 4'-OH-substituted compound 11 showed an affinity to androgen receptors, too. Whereas none of the tested compounds had a marked estrogenicity, 11 and 15 (6-OH, 3'-OH) exerted antiestrogenic effects. Androgenic properties were not given. In the adult, intact mouse, 11 and 15 exhibited a pronounced inhibition of seminal vesicle weights concomitant with a reduction of the testosterone level. Since in castrated, androgen-substituted animals only relatively weak direct antiandrogenic effects were demonstrable, the antiandrogenic activity of these new phenyltetralines is more due to an inhibition of testosterone biosynthesis than to a direct, receptor-mediated effect.
Schneider
M R
MR
Sonderforschungsbereich 234, Institut für Pharmazie, Lehrstuhl Pharmazeutische Chemie II, Universität Regensburg.
Schiller
C D
CD
D000818:Animals; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D051379:Mice; D009281:Naphthalenes / Q000138:chemical synthesis*; D051381:Rats; D011944:Receptors, Androgen / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology
D009281:Naphthalenes; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013764:Tetrahydronaphthalenes
Hydroxy-substituierte Phenyltetraline: Verbindungen mit Affinität zu Ostrogen- und Androgenrezeptoren.