Synthesis of Carborane-Containing Flavone and Flavonol Analogues as ER Agonists and COX Inhibitors.

Flavones and flavonols are natural products and privileged structures with diverse bioactivities. Carboranes are considered a three-dimensional bioisosteric surrogate for phenyl rings. Herein, the terminal phenyl group of flavones and flavonols was replaced with carborane, and a series of carborane-containing flavone and flavonol analogues were successfully prepared. These compounds exhibited estrogen receptor (ER) agonist activities. Compound 1 showed an EC50 of 0.87 ± 0.07 μM for ERα and a selectivity of 12.8-fold toward ERβ. These compounds also showed moderate inhibitory activities toward COX-1 and COX-2.