Effects of alkyl side chains and terminal hydrophilicity on vitamin D receptor (VDR) agonistic activity based on the diphenylpentane skeleton

• Published in: Bioorganic & medicinal chemistry letters Vol. 25; no. 22; pp. 5362 - 5366
• Main Authors: Misawa, Takashi, Yorioka, Momoko, Demizu, Yosuke, Noguchi-Yachide, Tomomi, Ohoka, Nobumichi, Kurashima-Kinoshita, Megumi, Motoyoshi, Hitomi, Nojiri, Hisao, Kittaka, Atsushi, Makishima, Makoto, Naito, Mikihiko, Kurihara, Masaaki
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-11-2015
• Subjects: Alkylation; Biological Assay; Cell Differentiation - drug effects; HL-60 Cells; Humans; Hydrophobic and Hydrophilic Interactions; Ligands; Long alkyl chain; Models, Molecular; Molecular Docking Simulation; Molecular Structure; Non-secosteroidal VDR ligands; Pentanes - chemical synthesis; Pentanes - chemistry; Pentanes - pharmacology; Receptors, Calcitriol - agonists; Receptors, Calcitriol - chemistry; Receptors, Calcitriol - genetics; Structure-Activity Relationship; Transcription, Genetic - drug effects; Vitamin D receptor; Non-secosteroidal VDR ligands; Long alkyl chain; Vitamin D receptor
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.09.030

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Vitamin D receptor (VDR) is a family of nuclear receptors (NR) that regulates physiological effects such as the immune system, calcium homeostasis, and cell proliferation. We synthesized non-secosteroidal VDR ligands bearing a long alkyl chain based on the diphenylpentane skeleton. The VDR-mediated transcriptional activities of the synthesized compounds were evaluated using a reporter gene assay and HL-60 cell differentiation-inducing assay. We herein described the structure–activity relationship and effects of alkyl-chain length on VDR-mediated transcriptional activity.