Estrogen receptor ligands. Part 11: Synthesis and activity of isochromans and isothiochromans.
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.
Liu
Jian
J
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. jian_liu@merck.com
Birzin
Elizabeth T
ET
Chan
Wanda
W
Yang
Yi Tien
YT
Pai
Lee-Yuh
LY
Dasilva
Carolyn
C
Hayes
Edward C
EC
Mosley
Ralph T
RT
Dininno
Frank
F
Rohrer
Susan P
SP
Schaeffer
James M
JM
Hammond
Milton L
ML
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
D002839:Chromans; D047628:Estrogen Receptor alpha; D008024:Ligands; D020033:Protein Isoforms; C011292:isothiochroman; D004958:Estradiol