Estrogen receptor ligands. Part 4: The SAR of the syn-dihydrobenzoxathiin SERAMs.
A series of estrogen receptor ligands based on a dihydrobenzoxathiin scaffold is described and evaluated for estrogen/anti-estrogen activity in both in vitro and in vivo models. The most active analogue, 22, was found to be 40-fold ERalpha selective in a competitive binding assay, and 22 demonstrated very potent in vivo antagonism of estradiol driven proliferation in an immature rat uterine weight gain assay.
Kim
Seongkon
S
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, 800B-109, Rahway, NJ 07065, USA. seongkon_kim@merck.com
Wu
Jane
J
Chen
Helen Y
HY
Birzin
Elizabeth T
ET
Chan
Wanda
W
Yang
Yi Tien
YT
Colwell
Lawrence
L
Li
Susan
S
Dahllund
Johanna
J
DiNinno
Frank
F
Rohrer
Susan P
SP
Schaeffer
James M
JM
Hammond
Milton L
ML
D000818:Animals; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000737:chemistry*; D047629:Estrogen Receptor beta / Q000737:chemistry; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D009929:Organ Size; D010075:Oxathiins / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006576:Heterocyclic Compounds, 4 or More Rings; D008024:Ligands; D010075:Oxathiins; D020845:Selective Estrogen Receptor Modulators; C494669:syn-dihydrobenzoxathiin