Synthesis, characterization, and estrogen receptor binding affinity of flavone-, indole-, and furan-estradiol conjugates

Different flavone-, indole-, and furan-17 beta-estradiol conjugates, linked via alkyl spacer chains extending from the 17 alpha-position of the estradiol moiety, were synthesized by Pd-catalyzed cross-coupling reactions. Structures were assigned based on spectroscopic data. In vitro competitive binding assays for the estrogen receptor (alpha-ER), using [H-3]estradiol (RBA = 100) as a competitor, revealed that a two-carbon alkyl linker combined with a flavone conjugate provided the highest binding affinity (RBA similar to 9), warranting further studies on their potential use as selective estrogen-receptor modulators (SERMs) for hormone-replacement therapies. (C) 2007 Elsevier Ltd. All rights reserved.