Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 2: structure-activity relationship studies on the benzopyran scaffold.
Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here we describe structure-activity relationship studies that led to the discovery of bezopyran 5b. X-ray crystal structures of 5b and a non-selective analog 5c in ERalpha help explain the observed selectivity of the benzopyran platform.
Richardson
Timothy I
TI
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. t_richardson@lilly.com <t_richardson@lilly.com>
Norman
Bryan H
BH
Lugar
Charles W
CW
Jones
Scott A
SA
Wang
Yong
Y
Durbin
Jim D
JD
Krishnan
Venkatesh
V
Dodge
Jeffrey A
JA
D001578:Benzopyrans / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray; D015195:Drug Design; D047628:Estrogen Receptor alpha / Q000737:chemistry; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000737:chemistry; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D008956:Models, Chemical; D008958:Models, Molecular; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism
D001578:Benzopyrans; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D020845:Selective Estrogen Receptor Modulators; D014157:Transcription Factors