Estrogen receptor ligands. Part 5: The SAR of dihydrobenzoxathiins containing modified basic side chains.
Dihydrobenzoxathiin analogs (1-11) with modifications on the basic side chain region were prepared and evaluated for estrogen/anti-estrogen activity in both in vitro and in vivo models. The compounds generally maintained a high degree of selectivity for ERalpha over ERbeta, similar to the original lead compound I. Many of the compounds also maintained high potency in the inhibition of human carcinoma MCF-7 cell growth. However, all were less potent in the inhibition of estradiol-triggered uterine growth. This work demonstrates the sensitive nature of modification to the antagonist basic side chain region.
Tan
Qiang
Q
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, 800B-107, Rahway, NJ 07065, USA. qiang_tan@merck.com
Birzin
Elizabeth T
ET
Chan
Wanda
W
Tien Yang
Yi
Y
Pai
Lee-Yuh
LY
Hayes
Edward C
EC
DaSilva
Carolyn A
CA
DiNinno
Frank
F
Rohrer
Susan P
SP
Schaeffer
James M
JM
Hammond
Milton L
ML
D001665:Binding Sites; D045744:Cell Line, Tumor; D004965:Estrogen Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors; D006801:Humans; D008024:Ligands; D010075:Oxathiins / Q000138:chemical synthesis* / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism*; D013329:Structure-Activity Relationship
D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D010075:Oxathiins; D011960:Receptors, Estrogen