The discovery of tetrahydrofluorenones as a new class of estrogen receptor beta-subtype selective ligands

R R Wilkening; R W Ratcliffe; E C Tynebor; K J Wildonger; A K Fried; M L Hammond; R T Mosley; P M D Fitzgerald; N Sharma; B M McKeever; S Nilsson; M Carlquist; A Thorsell; L Locco; R Katz; K Frisch; E T Birzin; H A Wilkinson; S Mitra; S Cai; E C Hayes; J M Schaeffer; S P Rohrer

doi:10.1016/j.bmcl.2006.03.098

The discovery of tetrahydrofluorenones as a new class of estrogen receptor beta-subtype selective ligands

Bioorg Med Chem Lett. 2006 Jul 1;16(13):3489-94. doi: 10.1016/j.bmcl.2006.03.098. Epub 2006 May 2.

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. robert_wilkening@merck.com

PMID: 16632357
DOI: 10.1016/j.bmcl.2006.03.098

Abstract

Synthesis and derivatization of a series of substituted tetrahydrofluorenone analogs giving potent, ERbeta subtype selective ligands are described. Several analogs possessing ERbeta binding affinities comparable to 17beta-estradiol but with greater than 75-fold selectivity over ERalpha are reported.

MeSH terms

Cell Line
Crystallography, X-Ray
Estrogen Receptor alpha / chemistry
Estrogen Receptor alpha / drug effects
Estrogen Receptor beta / chemistry
Estrogen Receptor beta / drug effects*
Fluorenes / chemical synthesis*
Fluorenes / classification
Fluorenes / pharmacology*
Humans
Ligands
Models, Molecular
Molecular Structure
Stereoisomerism
Structure-Activity Relationship

Substances

4-bromo-9a-butyl-7-hydroxy-1,2,9,9a-tetrahydro-3H-fluoren-3-one
Estrogen Receptor alpha
Estrogen Receptor beta
Fluorenes
Ligands