The discovery of tetrahydrofluorenones as a new class of estrogen receptor beta-subtype selective ligands.
Synthesis and derivatization of a series of substituted tetrahydrofluorenone analogs giving potent, ERbeta subtype selective ligands are described. Several analogs possessing ERbeta binding affinities comparable to 17beta-estradiol but with greater than 75-fold selectivity over ERalpha are reported.
Wilkening
R R
RR
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. robert_wilkening@merck.com
Ratcliffe
R W
RW
Tynebor
E C
EC
Wildonger
K J
KJ
Fried
A K
AK
Hammond
M L
ML
Mosley
R T
RT
Fitzgerald
P M D
PM
Sharma
N
N
McKeever
B M
BM
Nilsson
S
S
Carlquist
M
M
Thorsell
A
A
Locco
L
L
Katz
R
R
Frisch
K
K
Birzin
E T
ET
Wilkinson
H A
HA
Mitra
S
S
Cai
S
S
Hayes
E C
EC
Schaeffer
J M
JM
Rohrer
S P
SP
D002460:Cell Line; D018360:Crystallography, X-Ray; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000187:drug effects; D047629:Estrogen Receptor beta / Q000737:chemistry / Q000187:drug effects*; D005449:Fluorenes / Q000138:chemical synthesis* / Q000145:classification / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C545987:4-bromo-9a-butyl-7-hydroxy-1,2,9,9a-tetrahydro-3H-fluoren-3-one; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005449:Fluorenes; D008024:Ligands