Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Synthesis and Evaluation of Estrogen Receptor β -Selective Ligands: Fluoroalkylated Indazole Estrogens

  • Moon, Byung-Seok (Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS)) ;
  • Katzenellenbogen, John A. (Department of Chemistry, University of Illinois) ;
  • Cheon, Gi-Jeong (Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS)) ;
  • Chi, Dae-Yoon (Department of Chemistry, Inha University) ;
  • Lee, Kyo-Chul (Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS)) ;
  • An, Gwang-Il (Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS))
  • Published : 2008.06.20
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Abstract

It is important to identify selective ligands for the estrogen receptor subtypes ER$\alpha$ or ER$\beta$ to evaluate them as pharmaceutical targets in breast cancer. To develop ER$\beta$-selective ligands as PET imaging agents, a series of aryl indazole estrogen analogues substituted at the C3 position with fluoroethyl and fluoropropyl groups were synthesized and evaluated for their relative binding affinities and selectivities for ER$\alpha$ vs ER$\beta$. The fluoroethylated indazole estrogen (FEIE, 1i) and fluoropropylated indazole estrogen (FPIE, 1h) showed 41- fold and 17-fold ER$\beta$/ER$\alpha$ selectivity, respectively. However, their binding affinities to ER$\alpha$ and ER$\beta$ were very low.

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References

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