Estrogen receptor beta-subtype selective tetrahydrofluorenones: use of a fused pyrazole as a phenol bioisostere.
Synthesis of a series of fused pyrazole tetrahydrofluorenone analogs which are potent, ERbeta subtype selective ligands is described. Analogs possessing subnanomolar ERbeta binding, greater than 100-fold ERbeta-selectivity, and oral bioavailability are reported.
Wilkening
R R
RR
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, 800-B116 Rahway, NJ 07065, USA. robert_wilkening@merck.com
Ratcliffe
R W
RW
Fried
A K
AK
Meng
D
D
Sun
W
W
Colwell
L
L
Lambert
S
S
Greenlee
M
M
Nilsson
S
S
Thorsell
A
A
Mojena
M
M
Tudela
C
C
Frisch
K
K
Chan
W
W
Birzin
E T
ET
Rohrer
S P
SP
Hammond
M L
ML
D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D003500:Cyclization; D047629:Estrogen Receptor beta / Q000187:drug effects* / Q000378:metabolism; D005449:Fluorenes / Q000097:blood / Q000737:chemistry* / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry*; D051381:Rats
D047629:Estrogen Receptor beta; D005449:Fluorenes; D011720:Pyrazoles