title: Lead identification of a potent benzopyranone selective estrogen receptor modulator.
abstract: 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.
authors.affiliation: Medicinal Chemistry, Celgene, San Diego, CA 92121, USA. jmckie@celgene.com
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: McKie
authors.forename: Shripad S
authors.initials: SS
authors.lastname: Bhagwat
authors.forename: Helen
authors.initials: H
authors.lastname: Brady
authors.forename: Mary
authors.initials: M
authors.lastname: Doubleday
authors.forename: Leah
authors.initials: L
authors.lastname: Gayo
authors.forename: Mathew
authors.initials: M
authors.lastname: Hickman
authors.forename: Ravi K
authors.initials: RK
authors.lastname: Jalluri
authors.forename: Sak
authors.initials: S
authors.lastname: Khammungkhune
authors.forename: Adam
authors.initials: A
authors.lastname: Kois
authors.forename: Deborah
authors.initials: D
authors.lastname: Mortensen
authors.forename: Normand
authors.initials: N
authors.lastname: Richard
authors.forename: John
authors.initials: J
authors.lastname: Sapienza
authors.forename: Graziella
authors.initials: G
authors.lastname: Shevlin
authors.forename: Bernd
authors.initials: B
authors.lastname: Stein
authors.forename: May
authors.initials: M
authors.lastname: Sutherland
mesh_terms: 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
chemical_list: 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