Lead identification of a potent benzopyranone selective estrogen receptor modulator.
Starting from a phenol screening hit (6), three series of benzopyranone selective estrogen receptor modulators (SERMs) have been designed, synthesized, and analyzed for both estrogen receptor alpha binding affinity and in vitro activity in two cell assays. The lead compound identified, SP500263 (13), was more potent than raloxifene and tamoxifen in a cell-based assay measuring inhibition of interleukin-6 release.
McKie
Jeffrey A
JA
Medicinal Chemistry, Celgene, San Diego, CA 92121, USA. jmckie@celgene.com
Bhagwat
Shripad S
SS
Brady
Helen
H
Doubleday
Mary
M
Gayo
Leah
L
Hickman
Mathew
M
Jalluri
Ravi K
RK
Khammungkhune
Sak
S
Kois
Adam
A
Mortensen
Deborah
D
Richard
Normand
N
Sapienza
John
J
Shevlin
Graziella
G
Stein
Bernd
B
Sutherland
May
M
D000818:Animals; D001665:Binding Sites; D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D004958:Estradiol / Q000737:chemistry / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism*; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology*; D020849:Raloxifene Hydrochloride / Q000737:chemistry / Q000494:pharmacology; D013629:Tamoxifen / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000093242:Interleukin-6 Inhibitors
D003374:Coumarins; D004958:Estradiol; D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D015850:Interleukin-6; D010880:Piperidines; D020849:Raloxifene Hydrochloride; D013629:Tamoxifen; D000093242:Interleukin-6 Inhibitors; C448221:SP500263