title: Structure-activity relationships of SERMs optimized for uterine antagonism and ovarian safety.
abstract: 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.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. t_richardson@lilly.com <t_richardson@lilly.com>
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Richardson
authors.forename: Scott A
authors.initials: SA
authors.lastname: Frank
authors.forename: Minmin
authors.initials: M
authors.lastname: Wang
authors.forename: Christian A
authors.initials: CA
authors.lastname: Clarke
authors.forename: Scott A
authors.initials: SA
authors.lastname: Jones
authors.forename: Bai-Ping
authors.initials: BP
authors.lastname: Ying
authors.forename: Dan T
authors.initials: DT
authors.lastname: Kohlman
authors.forename: Owen B
authors.initials: OB
authors.lastname: Wallace
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Shepherd
authors.forename: Robert D
authors.initials: RD
authors.lastname: Dally
authors.forename: Alan D
authors.initials: AD
authors.lastname: Palkowitz
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Geiser
authors.forename: Henry U
authors.initials: HU
authors.lastname: Bryant
authors.forename: Judith W
authors.initials: JW
authors.lastname: Henck
authors.forename: Ilene R
authors.initials: IR
authors.lastname: Cohen
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Rudmann
authors.forename: Denis J
authors.initials: DJ
authors.lastname: McCann
authors.forename: David E
authors.initials: DE
authors.lastname: Coutant
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Oldham
authors.forename: Conrad W
authors.initials: CW
authors.lastname: Hummel
authors.forename: Kin C
authors.initials: KC
authors.lastname: Fong
authors.forename: Ronald
authors.initials: R
authors.lastname: Hinklin
authors.forename: George
authors.initials: G
authors.lastname: Lewis
authors.forename: Hongqi
authors.initials: H
authors.lastname: Tian
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Dodge
mesh_terms: 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
chemical_list: D004967:Estrogens; D020845:Selective Estrogen Receptor Modulators