Download MendeleyBenzopyrans as Selective Estrogen Receptor Beta Agonists (Serbas). Part 4: Functionalization of the Benzopyran A-Ring.
Norman, B.H., Richardson, T.I., Dodge, J.A., Pfeifer, L.A., Durst, G.L., Wang, Y., Durbin, J.D., Krishnan, V., Dinn, S.R., Liu, S., Reilly, J.E., Ryter, K.T.(2007) Bioorg Med Chem Lett 17: 5082
- PubMed: 17662603
- DOI: https://doi.org/10.1016/j.bmcl.2007.07.009
- Primary Citation of Related Structures:
2JJ3, 2QE4 - PubMed Abstract:
Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER receptor subtypes alpha and beta in opposite orientations. We have used structure based drug design to show that this unique phenomena can be exploited via substitution at the 8-position of the benzopyran A-ring to disrupt binding to ERalpha, thus improving ERbeta subtype selectivity. X-ray cocrystal structures with ERalpha and ERbeta are supportive of this approach to improve selectivity in this structural class.
Organizational Affiliation:
Discovery Chemistry Research, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. norman@lilly.com
