2. Academic Validation
  3. Structure-activity relationship study of diphenylamine-based estrogen receptor (ER) antagonists

Structure-activity relationship study of diphenylamine-based estrogen receptor (ER) antagonists

  • Bioorg Med Chem. 2015 Feb 15;23(4):861-7. doi: 10.1016/j.bmc.2014.12.022.
Kiminori Ohta 1,  Yuki Chiba 1,  Asako Kaise 1,  Yasuyuki Endo 2
Affiliations

Affiliations

  • 1 Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
  • 2 Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. Electronic address: yendo@tohoku-pharm.ac.jp.
PMID: 25614118 DOI: 10.1016/j.bmc.2014.12.022
Abstract

We have reported the design and synthesis of novel Estrogen Receptor (ER) agonists with a diphenylamine skeleton, which has several advantages over the formerly used diphenylmethane skeleton for drug development. Here, we confirmed the versatility of the diphenylamine skeleton by designing and synthesizing ER antagonist candidates bearing a basic alkylamino side chain on one of the two phenol groups of the diphenylamine agonist core structure. Among the tested compounds, cyclic alkylamine-containing derivatives showed more potent ER-antagonistic activity than the corresponding acyclic derivatives in cell proliferation assay using the MCF-7 cell line. Compound 5e showed the most potent antiestrogenic activity (IC50: 1.3×10(-7)M), being 10times more potent than tamoxifen.

Keywords

Antagonist; Diphenylamine; Estrogen receptor; Privileged structure.

Figures