Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 2: structure-activity relationship studies on the benzopyran scaffold

Timothy I Richardson; Bryan H Norman; Charles W Lugar; Scott A Jones; Yong Wang; Jim D Durbin; Venkatesh Krishnan; Jeffrey A Dodge

doi:10.1016/j.bmcl.2007.04.051

Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 2: structure-activity relationship studies on the benzopyran scaffold

Bioorg Med Chem Lett. 2007 Jul 1;17(13):3570-4. doi: 10.1016/j.bmcl.2007.04.051. Epub 2007 Apr 25.

Authors

Timothy I Richardson¹, Bryan H Norman, Charles W Lugar, Scott A Jones, Yong Wang, Jim D Durbin, Venkatesh Krishnan, Jeffrey A Dodge

Affiliation

¹ Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. [email protected] <[email protected]>

PMID: 17485205
DOI: 10.1016/j.bmcl.2007.04.051

Abstract

Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here we describe structure-activity relationship studies that led to the discovery of bezopyran 5b. X-ray crystal structures of 5b and a non-selective analog 5c in ERalpha help explain the observed selectivity of the benzopyran platform.

MeSH terms

Benzopyrans / pharmacology*
Chemistry, Pharmaceutical / methods*
Crystallography, X-Ray
Drug Design
Estrogen Receptor alpha / chemistry
Estrogen Receptor beta / agonists*
Estrogen Receptor beta / chemistry
Female
Humans
Ligands
Male
Models, Chemical
Models, Molecular
Selective Estrogen Receptor Modulators / pharmacology*
Structure-Activity Relationship
Transcription Factors / metabolism

Substances

Benzopyrans
Estrogen Receptor alpha
Estrogen Receptor beta
Ligands
Selective Estrogen Receptor Modulators
Transcription Factors