Estrogen receptor ligands. Part 6: Synthesis and binding affinity of dihydrobenzodithiins

Qiang Tan; Elizabeth T Birzin; Wanda Chan; Yi Tien Yang; Lee-Yuh Pai; Edward C Hayes; Carolyn A DaSilva; Frank DiNinno; Susan P Rohrer; James M Schaeffer; Milton L Hammond

doi:10.1016/j.bmcl.2004.04.101

Estrogen receptor ligands. Part 6: Synthesis and binding affinity of dihydrobenzodithiins

Bioorg Med Chem Lett. 2004 Jul 16;14(14):3753-5. doi: 10.1016/j.bmcl.2004.04.101.

Authors

Qiang Tan¹, Elizabeth T Birzin, Wanda Chan, Yi Tien Yang, Lee-Yuh Pai, Edward C Hayes, Carolyn A DaSilva, Frank DiNinno, Susan P Rohrer, James M Schaeffer, Milton L Hammond

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, 800B-107, Rahway, NJ 07065, USA. qiang_tan@merck.com

PMID: 15203156
DOI: 10.1016/j.bmcl.2004.04.101

Abstract

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.

MeSH terms

Animals
Binding Sites
Cells, Cultured
Estrogen Receptor alpha
Estrogen Receptor beta
Female
Heterocyclic Compounds, 2-Ring / chemical synthesis*
Heterocyclic Compounds, 2-Ring / pharmacology
Inhibitory Concentration 50
Ligands
Models, Biological
Piperidines / chemical synthesis*
Piperidines / pharmacology
Rats
Receptors, Estrogen / metabolism*
Selective Estrogen Receptor Modulators / chemical synthesis*
Selective Estrogen Receptor Modulators / pharmacology
Structure-Activity Relationship
Uterus / drug effects
Uterus / metabolism

Substances

Estrogen Receptor alpha
Estrogen Receptor beta
Heterocyclic Compounds, 2-Ring
Ligands
Piperidines
Receptors, Estrogen
Selective Estrogen Receptor Modulators