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

Journal of Medicinal Chemistry
2011.0

Abstract

Vitamin K(2) is a ligand for a nuclear receptor, steroid and xenobiotic receptor (SXR), that induces the gene expressions of CYP3A4. We synthesized vitamin K(2) 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.

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