Estrogen receptor ligands. Part 3: The SAR of dihydrobenzoxathiin SERMs.
A series of 3-alkyl, 3-cycloalkyl, and 3-heteroaryl dihydrobenzoxathiin analogs 1 were prepared and evaluated for estrogen/anti-estrogen activity in both in vitro and in vivo models. In general, the compounds were found to exhibit a high degree of selectivity for ER alpha over ER beta, but were less potent than the original lead compound 1a in the inhibition of estradiol-driven uterine proliferation.
Chen
Helen Y
HY
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. helen_chen@merck.com
Kim
Seongkon
S
Wu
Jane Y
JY
Birzin
Elizabeth T
ET
Chan
Wanda
W
Yang
Yi Tien
YT
Dahllund
Johanna
J
DiNinno
Frank
F
Rohrer
Susan P
SP
Schaeffer
James M
JM
Hammond
Milton L
ML
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014599:Uterus / Q000166:cytology
D006576:Heterocyclic Compounds, 4 or More Rings; D008024:Ligands; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators