Studies on modified estrogens: towards the synthesis of novel 14,15-cyclopropa[a]estra-1,3,5(10),8-tetraenes.
To improve the ratio of non-hormonal to hormonal activity, estrogens 3 and 4 were modified at various molecule positions. Isomerization of the 14 alpha,15 alpha-methylene bridge, controlled 3-methoxy group cleavage with respect to the 14 alpha,15 alpha-methylene bridge stereochemistry, reduction of the 8-double bond, and substitution of the oxyfunctionality at C-17 by a methylene and a difluoromethylene moiety were in the focus. As a result of in vivo and in vitro tests, compounds 27 and 29 were selected as potential follow-up candidates of lead 3.
Schwarz
S
S
Division of Research and Development, Jenapharm GmbH & Co. KG, Jena, Germany. Sigfrid.schwarz@web.de
Thieme
I
I
Kosemund
D
D
Undeutsch
B
B
Kummer
M
M
Görls
H
H
Römer
W
W
Kaufmann
G
G
Elger
W
W
Hillisch
A
A
Schneider
B
B
D000975:Antioxidants / Q000737:chemistry; D003521:Cyclopropanes / Q000737:chemistry; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D045166:Estradiol Congeners / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation
D000975:Antioxidants; D003521:Cyclopropanes; D045166:Estradiol Congeners; D007202:Indicators and Reagents; D004958:Estradiol