title: Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 2: structure-activity relationship studies on the benzopyran scaffold.
abstract: 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.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. t_richardson@lilly.com <t_richardson@lilly.com>
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Richardson
authors.forename: Bryan H
authors.initials: BH
authors.lastname: Norman
authors.forename: Charles W
authors.initials: CW
authors.lastname: Lugar
authors.forename: Scott A
authors.initials: SA
authors.lastname: Jones
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Jim D
authors.initials: JD
authors.lastname: Durbin
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnan
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Dodge
mesh_terms: 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
chemical_list: D001578:Benzopyrans; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D020845:Selective Estrogen Receptor Modulators; D014157:Transcription Factors