Triarylethylene bisphenols with a novel cycle are ligands for the estrogen receptor

Research output: Contribution to journalArticlepeer-review


We have prepared a series of triarylethylene and triarylethane systems, analogues of the selective antiestrogen tamoxifen, in which the alkyl substituent is tethered to the distal, rather than the proximal aryl ring by a 5-, 6-, or 7-membered carbocycle. This unusual cyclic structure rigidifies the ligand and adds bulk in a manner that is different from the more typical cyclization to the proximal aryl ring, as in the antiestrogen nafoxidine. These new systems were prepared efficiently by the addition of a benzylic sodium reagent, generated from the corresponding chloride by treatment with sodium naphthalenide, to a doubly protected 4,4'-dihydroxybenzophenone, followed by dehydration and deprotection. In all cases, formation of the exocyclic alkene was preferred. Two of the corresponding alkanes could be obtained by catalytic hydrogenation. All of these compounds have relatively high binding affinity for the estrogen receptor, and some of them demonstrate a significant level of affinity selectivity for the estrogen receptor alpha subtype. Accommodation of these newly rigidified cyclic triarylethylene systems into the ligand-binding pocket of the estrogen receptor can be visualized by molecular modeling. (C) 2000 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)785-793
Number of pages9
JournalBioorganic and Medicinal Chemistry
Issue number4
StatePublished - Apr 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


Dive into the research topics of 'Triarylethylene bisphenols with a novel cycle are ligands for the estrogen receptor'. Together they form a unique fingerprint.

Cite this