Synthesis and Evaluation of (1,4-Disubstituted)-1,2,3-triazoles as Estrogen Receptor Beta Agonists

Estrogen receptors (ER) are nuclear hormone which responsible for sex signaling in women. A series of (1,4-disubstituted)-1,2,3-triazoles 5–21 were prepared by reaction azidophenols with terminal alkynes under Fokin conditions. The products purified column chromatography or recrystallization and characterized NMR HRMS. compounds tested binding to ERβ via a ligand displacement assay, 1-(4-hydroxyphenyl)-α-phenyl-1,2,3-triazole-4-ethanol (21) was found be the most potent analog (EC50 = 1.59 μM). Molecular docking within pocket (pdb 2jj3) performed scores exhibited general qualitative trend consistent measured EC50 values.