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

• Published in: Bioorganic & medicinal chemistry Vol. 26; no. 23-24; pp. 6146 - 6152
• Main Authors: Misawa, Takashi, Tsuji, Genichiro, Takahashi, Takeo, Ochiai, Eiji, Takagi, Ken-ichiro, Horie, Kyohei, Kakuda, Shinji, Takimoto-Kamimura, Midori, Kurihara, Masaaki, Demizu, Yosuke
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.12.2018; Elsevier
• Subjects: Asymmetric carbon; Biochemistry & Molecular Biology; Biphenyl Compounds - chemical synthesis; Biphenyl Compounds - chemistry; Biphenyl Compounds - pharmacology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Docking study; Dose-Response Relationship, Drug; Humans; Life Sciences & Biomedicine; Ligands; Models, Molecular; Molecular Structure; Non-secosteroid; Pharmacology & Pharmacy; Physical Sciences; Receptors, Calcitriol - agonists; Science & Technology; Structure-Activity Relationship; Vitamin D receptor; Non-secosteroid; Docking study; Asymmetric carbon; Vitamin D receptor; TARGET; COMPLEX; ANALOGS; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; NUCLEAR RECEPTOR; POTENT; INHIBITION; GENE; ANTAGONISTS; DERIVATIVES
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2018.11.008

[Display omitted] 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.