Estrogen receptor ligands. Part 16: 2-Aryl indoles as highly subtype selective ligands for ERalpha.
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.
Dykstra
Kevin D
KD
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, 800B-109 Rahway, NJ 07065, USA. kevin_dykstra@merck.com
Guo
Liangqin
L
Birzin
Elizabeth T
ET
Chan
Wanda
W
Yang
Yi Tien
YT
Hayes
Edward C
EC
DaSilva
Carolyn A
CA
Pai
Lee-Yuh
LY
Mosley
Ralph T
RT
Kraker
Bryan
B
Fitzgerald
Paula M D
PM
DiNinno
Frank
F
Rohrer
Susan P
SP
Schaeffer
James M
JM
Hammond
Milton L
ML
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
D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D007211:Indoles; D008024:Ligands