Synthesis and biological evaluation of novel thio-substituted chromanes as high-affinity partial agonists for the estrogen receptor

Lise B Christiansen; Martin Wenckens; Paul S Bury; Birgitte Gissel; Birgit S Hansen; Susan M Thorpe; Poul Jacobsen; Anders Kanstrup; Anker S Jørgensen; Lars Naerum; Karsten Wassermann

doi:10.1016/s0960-894x(01)00679-5

Synthesis and biological evaluation of novel thio-substituted chromanes as high-affinity partial agonists for the estrogen receptor

Bioorg Med Chem Lett. 2002 Jan 7;12(1):17-9. doi: 10.1016/s0960-894x(01)00679-5.

Authors

Lise B Christiansen¹, Martin Wenckens, Paul S Bury, Birgitte Gissel, Birgit S Hansen, Susan M Thorpe, Poul Jacobsen, Anders Kanstrup, Anker S Jørgensen, Lars Naerum, Karsten Wassermann

Affiliation

¹ Health Care Discovery & Preclinical Development, Novo Nordisk A/S, Novo Nordisk Park, DK-2760, Måløv, Denmark. libc@novonordisk.com

PMID: 11738564
DOI: 10.1016/s0960-894x(01)00679-5

Abstract

Synthesis of (+/-)-cis-7-hydroxy-3-phenyl-4-(4-(2-piperidinoethanethio)phenyl)chromane (13) and (+/-)-cis-7-hydroxy-3-phenyl-4-(4-(2-pyrrolidinoethanethio)phenyl)chromane (15) is presented. These compounds are representatives of a novel class of compounds with high in vitro binding affinity for the estrogen receptor (IC(50)=7-10 nM), and very low in vitro uterotrophic activity (max stim.=5-17% rel to moxestrol; EC(50)=0.5-1.8 nM).

MeSH terms

Animals
Binding, Competitive
Chromans / chemical synthesis*
Chromans / chemistry
Chromans / pharmacology
Drug Evaluation, Preclinical
Endometrium / cytology
Endometrium / drug effects
Estradiol / metabolism
Female
Rabbits
Receptors, Estrogen / agonists*
Structure-Activity Relationship
Sulfur Compounds / chemical synthesis
Sulfur Compounds / chemistry
Sulfur Compounds / pharmacology

Substances

Chromans
Receptors, Estrogen
Sulfur Compounds
Estradiol