Synthesis and biological testing of 4'-(dimethylamino)-17 beta-hydroxy-17 alpha-(1-propynyl)benzo[12,12a]-11 alpha,18-cyclo-12a,12b-dihomo-13 alpha-estr-4-en-3-one: an interesting RU 38 486 analog.
A partial synthesis of the title compound, 4'-(dimethylamino)-17 beta-hydroxy-17 alpha-(1-propynyl)benzo[12,12a]-11 alpha,18-cyclo-12a,12b- dihomo-13 alpha-estr-4-en-3-one 1, is reported. The key step in this synthesis represents an intramolecular alkenylaryl radical cyclization. Treatment of 18-[bromo-5-(dimethylamino)phenyl]gona-5,9(11)-diene-3,17-dione-3, 17- bis[cyclic 1,2-ethanediyl acetal] 5 with tributyl tin hydride and a radical initiator introduces the desired 11 beta,18-bridge. The reduced progesterone receptor affinity of this RU 38 486 analog contributes valuable information to the empirical characterization of the steroid binding site of the receptor protein and explains the observed lack of in vivo antigestational activity.
Ottow
E
E
Research Laboratories, Schering AG Berlin, Germany.
Beier
S
S
Elger
W
W
Fritzemeier
K H
KH
Neef
G
G
Wiechert
R
R
D000028:Abortion, Induced / Q000379:methods; D000818:Animals; D001667:Binding, Competitive; D005260:Female; D005609:Free Radicals; D015735:Mifepristone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D015394:Molecular Structure; D011247:Pregnancy; D011374:Progesterone / Q000037:antagonists & inhibitors*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D005609:Free Radicals; D011980:Receptors, Progesterone; C088569:4'-(dimethylamino)-17-hydroxy-17-(1-propynyl)benzo(12,12a)-11,18-cyclo-12a,12b-dihomo-estr-4-en-3-one; D015735:Mifepristone; D011374:Progesterone