6H-Benzo[c]chromen-6-one derivatives as selective ERbeta agonists

Wanying Sun; Lovji D Cama; Elizabeth T Birzin; Sudha Warrier; Louis Locco; Ralph Mosley; Milton L Hammond; Susan P Rohrer

doi:10.1016/j.bmcl.2005.12.057

6H-Benzo[c]chromen-6-one derivatives as selective ERbeta agonists

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1468-72. doi: 10.1016/j.bmcl.2005.12.057. Epub 2006 Jan 18.

Authors

Wanying Sun¹, Lovji D Cama, Elizabeth T Birzin, Sudha Warrier, Louis Locco, Ralph Mosley, Milton L Hammond, Susan P Rohrer

Affiliation

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

PMID: 16412638
DOI: 10.1016/j.bmcl.2005.12.057

Abstract

A series of 6H-benzo[c]chromen-6-one and 6H-benzo[c]chromene derivatives were prepared, and the affinity and selectivity for ERalpha and ERbeta was measured. Many of the analogs were found to be potent and selective ERbeta agonists. Bis hydroxyl at positions 3 and 8 is essential for activity in a HTRF coactivator recruitment assay. Additional modifications at both phenyl rings led to compounds with ERbeta<10nM potency and >100-fold selectivity over ERalpha.

Publication types

Comparative Study

MeSH terms

Benzene Derivatives / chemical synthesis*
Benzene Derivatives / chemistry
Benzene Derivatives / metabolism
Benzopyrans / chemical synthesis*
Benzopyrans / chemistry
Benzopyrans / metabolism
Estrogen Receptor alpha / agonists
Estrogen Receptor alpha / metabolism
Estrogen Receptor beta / agonists*
Estrogen Receptor beta / metabolism
Fluoroimmunoassay
Humans
Ligands
Molecular Structure
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Benzene Derivatives
Benzopyrans
Estrogen Receptor alpha
Estrogen Receptor beta
Ligands