Estrogen receptor ligands. Part 6: Synthesis and binding affinity of dihydrobenzodithiins.
Dihydrobenzodithiin compounds (1-6) were prepared to explore the expansion of the dihydrobenzoxathiin lead compounds I-III as SERAMs (Selective Estrogen Receptor Alpha Modulators). The dihydrobenzodithiin compounds generally maintained a high degree of selectivity for ERalpha over ERbeta, however, they lacked the in vivo antagonism/agonism activity exhibited by the lead class in an immature rat uterine growth model.
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
Yang
Yi Tien
YT
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
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008024:Ligands; D008954:Models, Biological; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006574:Heterocyclic Compounds, 2-Ring; D008024:Ligands; D010880:Piperidines; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators