title: Synthesis and biological evaluation of novel thio-substituted chromanes as high-affinity partial agonists for the estrogen receptor.
abstract: Synthesis of (+/-)-cis-7-hydroxy-3-phenyl-4-(4-(2-piperidinoethanethio)phenyl)chromane (13) and (+/-)-cis-7-hydroxy-3-phenyl-4-(4-(2-pyrrolidinoethanethio)phenyl)chromane (15) is presented. These compounds are representatives of a novel class of compounds with high in vitro binding affinity for the estrogen receptor (IC(50)=7-10 nM), and very low in vitro uterotrophic activity (max stim.=5-17% rel to moxestrol; EC(50)=0.5-1.8 nM).
authors.affiliation: Health Care Discovery & Preclinical Development, Novo Nordisk A/S, Novo Nordisk Park, DK-2760, Måløv, Denmark. libc@novonordisk.com
authors.forename: Lise B
authors.initials: LB
authors.lastname: Christiansen
authors.forename: Martin
authors.initials: M
authors.lastname: Wenckens
authors.forename: Paul S
authors.initials: PS
authors.lastname: Bury
authors.forename: Birgitte
authors.initials: B
authors.lastname: Gissel
authors.forename: Birgit S
authors.initials: BS
authors.lastname: Hansen
authors.forename: Susan M
authors.initials: SM
authors.lastname: Thorpe
authors.forename: Poul
authors.initials: P
authors.lastname: Jacobsen
authors.forename: Anders
authors.initials: A
authors.lastname: Kanstrup
authors.forename: Anker S
authors.initials: AS
authors.lastname: Jørgensen
authors.forename: Lars
authors.initials: L
authors.lastname: Naerum
authors.forename: Karsten
authors.initials: K
authors.lastname: Wassermann
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism; D005260:Female; D011817:Rabbits; D011960:Receptors, Estrogen / Q000819:agonists*; D013329:Structure-Activity Relationship; D013457:Sulfur Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002839:Chromans; D011960:Receptors, Estrogen; D013457:Sulfur Compounds; D004958:Estradiol