Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 3: synthesis of cyclopentanone and cyclohexanone intermediates for C-ring modification.

Article Details

Citation

Richardson TI, Dodge JA, Durst GL, Pfeifer LA, Shah J, Wang Y, Durbin JD, Krishnan V, Norman BH

Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 3: synthesis of cyclopentanone and cyclohexanone intermediates for C-ring modification.

Bioorg Med Chem Lett. 2007 Sep 1;17(17):4824-8. Epub 2007 Jun 20.

PubMed ID
17614275 [ View in PubMed
]
Abstract

Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here we describe the syntheses of cyclopentanone and cyclohexanone intermediates for SAR studies of the C-ring on the benzopyran scaffold. Modification of the C-ring disrupts binding to ERalpha, thus improving ERbeta selectivity up to 100-fold. X-ray cocrystal structures confirm previously observed binding modes.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
(3AS,4R,9BR)-2,2-DIFLUORO-4-(4-HYDROXYPHENYL)-1,2,3,3A,4,9B-HEXAHYDROCYCLOPENTA[C]CHROMEN-8-OLEstrogen receptor alphaKi (nM)8.37.522Details
(3AS,4R,9BR)-2,2-DIFLUORO-4-(4-HYDROXYPHENYL)-1,2,3,3A,4,9B-HEXAHYDROCYCLOPENTA[C]CHROMEN-8-OLEstrogen receptor betaKi (nM)0.447.522Details
ErteberelEstrogen receptor alphaKi (nM)2.77.522Details
ErteberelEstrogen receptor betaKi (nM)0.197.522Details