title: Structure-activity relationship study of diphenylamine-based estrogen receptor (ER) antagonists.
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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Kiminori
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Kaise
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. Electronic address: yendo@tohoku-pharm.ac.jp.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Endo
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004159:Diphenylamine / Q000737:chemistry* / Q000494:pharmacology*; D065171:Estrogen Receptor Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D013329:Structure-Activity Relationship
chemical_list: D065171:Estrogen Receptor Antagonists; D047628:Estrogen Receptor alpha; D004159:Diphenylamine
keywords: Antagonist; Diphenylamine; Estrogen receptor; Privileged structure