title: Development of 1,3-diphenyladamantane derivatives as nonsteroidal progesterone receptor antagonists.
abstract: Nonsteroidal progesterone receptor (PR) full antagonists are needed as tools for elucidating the physiological functions of PR and as candidates for treatment of various diseases. We designed and synthesized 1,3-diphenyladamantane derivatives, and investigated their PR-antagonistic activity in comparison with our recently developed boron cluster-based PR antagonists. Among the synthesized adamantane derivatives, compound 9a exhibited the most potent PR-antagonistic activity (IC50: 25nM) and showed high binding affinity for the PR ligand-binding domain, comparable with that of the boron cluster-based PR antagonists. These results suggest that disubstituted adamantane, like the boron cluster m-carborane, is a promising hydrophobic pharmacophore for further structural development of nonsteroidal PR antagonists.
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Mori
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takeuchi
authors.affiliation: Department of Chemistry, Faculty of Science, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan. Electronic address: tanatani.aya@ocha.ac.jp.
authors.forename: Aya
authors.initials: A
authors.lastname: Tanatani
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kagechika
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan; Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Fujii
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001880:Boranes / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D055808:Drug Discovery; D006801:Humans; D011485:Protein Binding; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001880:Boranes; D011980:Receptors, Progesterone; D000218:Adamantane
keywords: Adamantane; Antagonist; Hydrophobic pharmacophore; Progesterone