Otero, Rocio Ishizawa, Michiyasu Numoto, Nobutaka Ikura, Teikichi Ito, Nobutoshi Tokiwa, Hiroaki Mouriño, Antonio Makishima, Makoto Yamada, Sachiko 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 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. 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
    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
10.1021/acs.jmedchem.8b00427.s001