Author/Authors :
Bryan H. Norman، نويسنده , , Timothy I. Richardson، نويسنده , , Jeffrey A. Dodge، نويسنده , , Lance A. Pfeifer، نويسنده , , Gregory L. Durst، نويسنده , , Yong Wang، نويسنده , , Jim D. Durbin، نويسنده , , Venkatesh Krishnan، نويسنده , , Sean R. Dinn، نويسنده , , Shengquan Liu، نويسنده , , John E. Reilly، نويسنده , , Kendal T. Ryter، نويسنده ,
Abstract :
Benzopyrans are selective estrogen receptor (ER) β agonists (SERBAs), which bind the ER receptor subtypes α and β 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 ERα, thus improving ERβ subtype selectivity. X-ray cocrystal structures with ERα and ERβ are supportive of this approach to improve selectivity in this structural class.
