Synthesis of novel vitamin K₂ analogues with modification at the Ω-terminal position and their biological evaluation as potent steroid and xenobiotic receptor (SXR) agonists

Vitamin K₂ is a ligand for a nuclear receptor, steroid and xenobiotic receptor (SXR), that induces the gene expressions of CYP3A4. We synthesized vitamin K₂ analogues with hydroxyl or phenyl groups at the Ω-terminal of the side chain. The up-regulation of SXR-mediated transcription of the target gene by the analogues was dependent on the length of the side chain and the hydrophobicity of the Ω-terminal residues. Phenyl analogue menaquinone-3 was as active as the known SXR ligand rifampicin.