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.

Yoshitomo Suhara, Masato Watanabe, Kimie Nakagawa, Akimori Wada, Yoichi Ito, Kazuyoshi Takeda, Kazuhiko Takahashi, Toshio Okano

Index: J. Med. Chem. 54 , 4269-73, (2011)

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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.