title: Estrogen receptor ligands. Part 11: Synthesis and activity of isochromans and isothiochromans.
abstract: The ring oxygen and sulfur analogs of lasofoxifene, 1a and 1b, were synthesized in an attempt to impart ERalpha selectivity, as found in the closely related dihydrobenzoxathiin compound I, recently discovered in these laboratories. The resulting isochroman and isothiochroman compounds were found to exhibit equipotent binding affinities to the ER isoforms and were less active in the inhibition of estradiol-triggered uterine growth when compared to I and lasofoxifene.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. jian_liu@merck.com
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Birzin
authors.forename: Wanda
authors.initials: W
authors.lastname: Chan
authors.forename: Yi Tien
authors.initials: YT
authors.lastname: Yang
authors.forename: Lee-Yuh
authors.initials: LY
authors.lastname: Pai
authors.forename: Carolyn
authors.initials: C
authors.lastname: Dasilva
authors.forename: Edward C
authors.initials: EC
authors.lastname: Hayes
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Mosley
authors.forename: Frank
authors.initials: F
authors.lastname: Dininno
authors.forename: Susan P
authors.initials: SP
authors.lastname: Rohrer
authors.forename: James M
authors.initials: JM
authors.lastname: Schaeffer
authors.forename: Milton L
authors.initials: ML
authors.lastname: Hammond
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000138:chemical synthesis* / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D020033:Protein Isoforms; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects / Q000254:growth & development
chemical_list: D002839:Chromans; D047628:Estrogen Receptor alpha; D008024:Ligands; D020033:Protein Isoforms; C011292:isothiochroman; D004958:Estradiol