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ID: ALA2407046
Journal: ACS Med Chem Lett
Title: Synthesis of 2α-heteroarylalkyl active vitamin d3 with therapeutic effect on enhancing bone mineral density in vivo.
Authors: Matsuo M, Hasegawa A, Takano M, Saito H, Kakuda S, Chida T, Takagi K, Ochiai E, Horie K, Harada Y, Takimoto-Kamimura M, Takenouchi K, Sawada D, Kittaka A.
Abstract: 2α-Heteroarylethyl-1α,25-dihydroxyvitamin D3 analogues, which were designed to form a hydrogen bond between Arg274 of human vitamin D receptor (hVDR) and a nitrogen atom of the heteroaromatic ring at the 2α-position, were synthesized. Among them, 2α-[2-(tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D3 showed higher osteocalcin promoter transactivation activity in human osteosarcoma (HOS) cells and a greater therapeutic effect in ovariectomized (OVX) rats, osteoporosis model animals, on enhancing bone mineral density than those of active vitamin D3. X-ray cocrystallographic analysis of the hVDR-ligand complex confirms that the new hydrogen bond formation stabilized the complex.
CiteXplore: 24900728
DOI: 10.1021/ml400098w