Structure-activity relationships of SERMs optimized for uterine antagonism and ovarian safety.
Structure-activity relationship studies are described, which led to the discovery of novel selective estrogen receptor modulators (SERMs) for the potential treatment of uterine fibroids. The SAR studies focused on limiting brain exposure and were guided by computational properties. Compounds with limited impact on the HPO axis were selected using serum estrogen levels as a biomarker for ovarian stimulation.
Richardson
Timothy I
TI
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. t_richardson@lilly.com <t_richardson@lilly.com>
Frank
Scott A
SA
Wang
Minmin
M
Clarke
Christian A
CA
Jones
Scott A
SA
Ying
Bai-Ping
BP
Kohlman
Dan T
DT
Wallace
Owen B
OB
Shepherd
Timothy A
TA
Dally
Robert D
RD
Palkowitz
Alan D
AD
Geiser
Andrew G
AG
Bryant
Henry U
HU
Henck
Judith W
JW
Cohen
Ilene R
IR
Rudmann
Daniel G
DG
McCann
Denis J
DJ
Coutant
David E
DE
Oldham
Samuel W
SW
Hummel
Conrad W
CW
Fong
Kin C
KC
Hinklin
Ronald
R
Lewis
George
G
Tian
Hongqi
H
Dodge
Jeffrey A
JA
D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004967:Estrogens / Q000097:blood; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy*; D008956:Models, Chemical; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry / Q000494:pharmacology*; D012984:Software; D013329:Structure-Activity Relationship
D004967:Estrogens; D020845:Selective Estrogen Receptor Modulators