10.1021/acs.jmedchem.8b00427.s001 Rocio Otero Rocio Otero Michiyasu Ishizawa Michiyasu Ishizawa Nobutaka Numoto Nobutaka Numoto Teikichi Ikura Teikichi Ikura Nobutoshi Ito Nobutoshi Ito Hiroaki Tokiwa Hiroaki Tokiwa Antonio Mouriño Antonio Mouriño Makoto Makishima Makoto Makishima Sachiko Yamada Sachiko Yamada 25<i>S</i>‑Adamantyl-23-yne-26,27-dinor-1α,25-dihydroxyvitamin D<sub>3</sub>: Synthesis, Tissue Selective Biological Activities, and X‑ray Crystal Structural Analysis of Its Vitamin D Receptor Complex American Chemical Society 2018 1 VDR-LBD complexes Vitamin D Receptor Complex alkenyl-boronic ester 8 4 b 24A 25 S isomer vitamin D receptor MG 25 S -25- adamantyl -23-yne D 3 rat VDR-ligand binding domain HEK SW helix 11. Helix 11 CYP 2018-07-10 00:00:00 Dataset https://acs.figshare.com/articles/dataset/25_i_S_i_Adamantyl-23-yne-26_27-dinor-1_25-dihydroxyvitamin_D_sub_3_sub_Synthesis_Tissue_Selective_Biological_Activities_and_X_ray_Crystal_Structural_Analysis_of_Its_Vitamin_D_Receptor_Complex/6848429 Both 25<i>R</i>- and 25<i>S</i>-25-adamantyl-23-yne-26,27-dinor-1α,25-dihydroxy­vitamin D<sub>3</sub> (<b>4a</b> and <b>4b</b>) were stereoselectively synthesized by a Pd(0)-catalyzed ring closure and Suzuki–Miyaura coupling between enol-triflate <b>7</b> and alkenyl-boronic ester <b>8</b>. The 25<i>S</i> isomer (<b>4b</b>) showed high vitamin D receptor (VDR) affinity (50% of that of the natural hormone 1α,25-dihydroxy­vitamin D<sub>3</sub>, <b>1</b>) and transactivation potency (kidney HEK293, 90%). In endogenous gene expression, it showed high cell-type selectivity for kidney cells (HEK293, CYP24A1 160% of <b>1</b>), bone cells (MG63, osteocalcin 64%), and monocytes (U937, CAMP 96%) over intestine (SW480, CYP24A1 8%) and skin (HaCaT, CYP24A1 7%) cells. The X-ray crystal structural analysis of <b>4b</b> in complex with rat VDR-ligand binding domain (LBD) showed the highest Cα positional shift from the <b>1/</b>VDR-LBD complex at helix 11. Helix 11 of the <b>4b</b> and <b>1</b> VDR-LBD complexes also showed significant differences in surface properties. These results suggest that <b>4b</b> should be examined further as another candidate for a mild preventive osteoporosis agent.