Structural development of non-secosteroidal vitamin D receptor (VDR) ligands without any asymmetric carbon

  • Bioorg Med Chem. 2018 Dec 15;26(23-24):6146-6152. doi: 10.1016/j.bmc.2018.11.008.
Takashi Misawa  1 ,  Genichiro Tsuji  2 ,  Takeo Takahashi  2 ,  Eiji Ochiai  3 ,  Ken-Ichiro Takagi  3 ,  Kyohei Horie  3 ,  Shinji Kakuda  3 ,  Midori Takimoto-Kamimura  3 ,  Masaaki Kurihara  4 ,  Yosuke Demizu  5
Affiliations
  • 1. Division of Organic Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-9501, Japan. Electronic address: [email protected].
  • 2. Division of Organic Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-9501, Japan.
  • 3. Teijin Institute for Bio-Medical Research, Teijin Pharma Ltd., Tokyo 191-8512, Japan.
  • 4. Division of Organic Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-9501, Japan; Department of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Kitakanemaru, Otawara City, Tochigi 324-8501, Japan. Electronic address: [email protected].
  • 5. Division of Organic Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-9501, Japan. Electronic address: [email protected].
PMID: 30446437 DOI: 10.1016/j.bmc.2018.11.008
Abstract

Non-secosteroidal VDR ligands without any assymmetric carbon were designed and synthesized based on the structure of the previously reported non-secosteroidal VDR agonist LG190178. The VDR-agonistic activity of all synthesized compounds was evaluated, and 7b emerged as a potent agonist activity with an EC50 value of 9.26 nM. Moreover, a docking simulation analysis was also performed to determine the binding mode of 7b with VDR-LBD.

Keywords
Asymmetric carbon; Docking study; Non-secosteroid; Vitamin D receptor.