title: Estrogen receptor ligands. Part 16: 2-Aryl indoles as highly subtype selective ligands for ERalpha.
abstract: A novel class of indole ligands for estrogen receptor alpha have been discovered which exhibit potent affinity and high selectivity. Substitution of the bazedoxifene skeleton to the linker present in the HTS lead 1a provided 22b which was found to be 130-fold alpha-selective and acted as an antagonist of estradiol activity in uterine tissue and MCF-7 cancer cells.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, 800B-109 Rahway, NJ 07065, USA. kevin_dykstra@merck.com
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Dykstra
authors.forename: Liangqin
authors.initials: L
authors.lastname: Guo
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Birzin
authors.forename: Wanda
authors.initials: W
authors.lastname: Chan
authors.forename: Yi Tien
authors.initials: YT
authors.lastname: Yang
authors.forename: Edward C
authors.initials: EC
authors.lastname: Hayes
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: DaSilva
authors.forename: Lee-Yuh
authors.initials: LY
authors.lastname: Pai
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Mosley
authors.forename: Bryan
authors.initials: B
authors.lastname: Kraker
authors.forename: Paula M D
authors.initials: PM
authors.lastname: Fitzgerald
authors.forename: Frank
authors.initials: F
authors.lastname: DiNinno
authors.forename: Susan P
authors.initials: SP
authors.lastname: Rohrer
authors.forename: James M
authors.initials: JM
authors.lastname: Schaeffer
authors.forename: Milton L
authors.initials: ML
authors.lastname: Hammond
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D004965:Estrogen Antagonists / Q000737:chemistry / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000493:pharmacokinetics*; D020128:Inhibitory Concentration 50; D008024:Ligands; D014599:Uterus / Q000187:drug effects
chemical_list: D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D007211:Indoles; D008024:Ligands