Synthesis of 11beta-(4-dimethylaminophenyl)-17beta-hydroxy-17alpha- (3-methyl-1-butynyl)-4, 9-estradien-3-one and 11beta-(4-acetophenyl)- 17beta-hydroxy-17alpha-(3-methyl-1-butynyl)-4, 9-estradien-3-one: two new analogs of mifepristone (RU-486).
From the structure activity relationship, two new analogs, 2 and 3, of the potent progesterone antagonist mifepristone 1 have been designed. The syntheses of these two analogs have been achieved in eleven steps through modified synthetic sequences and improved procedures starting from (+)-estrone. In comparison with mifepristone 1, the relative binding affinities of compound 2 for the progesterone receptor was found to be more, whereas that of compound 3 was less.
Hazra
B G
BG
Organic Chemistry Synthesis Division, National Chemical Laboratory, Pune, India. hazra@ems.ncl.res.in
Basu
S
S
Pore
V S
VS
Joshi
P L
PL
Pal
D
D
Chakrabarti
P
P
D000818:Animals; D001667:Binding, Competitive; D018360:Crystallography, X-Ray; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006727:Hormone Antagonists / Q000378:metabolism; D015735:Mifepristone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D015394:Molecular Structure; D011817:Rabbits; D011980:Receptors, Progesterone / Q000378:metabolism; D013329:Structure-Activity Relationship; D014599:Uterus / Q000166:cytology
C406717:11-(4-acetophenyl)-17-hydroxy-17-(3-methyl-1-butynyl)-4,9-estradien-3-one; C406716:11-(4-dimethylaminophenyl)-17-hydroxy-17-(3-methyl-1-butynyl)-4,9-estradien-3-one; D006727:Hormone Antagonists; D011980:Receptors, Progesterone; D015735:Mifepristone