title: Novel 3-aryl indoles as progesterone receptor antagonists for uterine fibroids.
abstract: We report the synthesis and characterization of novel 3-aryl indoles as potent and efficacious progesterone receptor (PR) antagonists with potential for the treatment of uterine fibroids. These compounds demonstrated excellent selectivity over other steroid nuclear hormone receptors such as the mineralocorticoid receptor (MR). They were prepared from 2-bromo-6-nitro indole in four to six steps using a Suzuki cross-coupling as the key step. Compound 8f was orally active in the complement 3 model of progesterone antagonism in the rat uterus and demonstrated partial antagonism in the McPhail model of progesterone activity.
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Richardson
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Clarke
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Kuo-Long
authors.initials: KL
authors.lastname: Yu
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Ying K
authors.initials: YK
authors.lastname: Yee
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Bleisch
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Lopez
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Norman E
authors.initials: NE
authors.lastname: Hughes
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Muehl
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Lugar
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Terry L
authors.initials: TL
authors.lastname: Moore
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Shetler
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Zink
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: John J
authors.initials: JJ
authors.lastname: Osborne
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Chahrzad
authors.initials: C
authors.lastname: Montrose-Rafizadeh
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Nita
authors.initials: N
authors.lastname: Patel
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Geiser
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Rachelle J Sells
authors.initials: RJ
authors.lastname: Galvin
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Dodge
keywords: NR3C3; Progesterone; Suzuki cross-coupling reaction; progesterone receptor; progesterone receptor antagonist; uterine fibroids