Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 4: functionalization of the benzopyran A-ring.

Article Details

Citation
Copy to clipboard

Norman BH, Richardson TI, Dodge JA, Pfeifer LA, Durst GL, Wang Y, Durbin JD, Krishnan V, Dinn SR, Liu S, Reilly JE, Ryter KT

Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 4: functionalization of the benzopyran A-ring.

Bioorg Med Chem Lett. 2007 Sep 15;17(18):5082-5. Epub 2007 Jul 13.

PubMed ID
17662603 [ View in 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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-6-(METHOXYMETHYL)-1,2,3,3A,4,9B-HEXAHYDROCYCLOPENTA[C]CHROMEN-8-OLEstrogen receptor alphaKi (nM)117.522Details
(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-6-(METHOXYMETHYL)-1,2,3,3A,4,9B-HEXAHYDROCYCLOPENTA[C]CHROMEN-8-OLEstrogen receptor betaKi (nM)0.287.522Details
ErteberelEstrogen receptor alphaKi (nM)2.297.522Details
ErteberelEstrogen receptor betaKi (nM)0.177.522Details