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

Benzopyrans are selective estrogen receptor (ER) β agonists (SERBAs), which bind the ER subtypes α and β 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 ERα, thus improving ERβ selectivity up to 100-fold. X-ray cocrystal structures confirm previously observed binding modes.

Graphical abstractStructure activity relationship studies of the C-ring on the benzopyran scaffold are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide