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

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.