Synthesis of 2α-Heteroarylalkyl Active Vitamin D3 with Therapeutic Effect on Enhancing Bone Mineral Density in Vivo
Authors:
- 31 May 2013
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Medicinal Chemistry Letters
- Vol. 4 (7) , 671-674
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.Keywords
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