Triazolo-tetrahydrofluorenones as selective estrogen receptor beta agonists.
Several tetrahydrofluorenones with a triazole fused across C7-C8 showed high levels of ERbeta-selectivity and were found to be potent ERbeta-agonists. As a class they demonstrate improved oral bioavailability in the rat over a parent class of 7-hydroxy-tetrahydrofluorenones. The most selective agonist displayed 5.7 nM affinity and 333-fold selectivity for ERbeta.
Parker
Dann L
DL
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. dann_parker@merck.com
Meng
Dongfang
D
Ratcliffe
Ronald W
RW
Wilkening
Robert R
RR
Sperbeck
Donald M
DM
Greenlee
Mark L
ML
Colwell
Lawrence F
LF
Lambert
Sherrie
S
Birzin
Elizabeth T
ET
Frisch
Katalin
K
Rohrer
Susan P
SP
Nilsson
Stefan
S
Thorsell
Ann-Gerd
AG
Hammond
Milton L
ML
D000818:Animals; D001391:Azo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000378:metabolism; D005449:Fluorenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship
D001391:Azo Compounds; D047629:Estrogen Receptor beta; D005449:Fluorenes; D008024:Ligands; C041509:fluorene