22S-butyl-1α,24-dihydroxy-24,25,26-trinorvitamin D3 | 167386-40-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 22S-butyl-1α,24-dihydroxy-24,25,26-trinorvitamin D3
• 英文别名: (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,3S)-3-(2-hydroxyethyl)heptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-cyclohexane-1,3-diol；(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,3S)-3-(2-hydroxyethyl)heptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
• CAS: 167386-40-5
• 化学式: C₂₈H₄₆O₃
• 分子量: 430.671
• InChiKey: MBUIFNPNESWHQQ-LGKYDQOKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  以 乙醇 为溶剂， 反应 288.0h， 以26%的产率得到22S-butyl-1α,24-dihydroxy-24,25,26-trinorvitamin D3
  参考文献：
  名称：

  A New Class of Vitamin D Analogues that Induce Structural Rearrangement of the Ligand-Binding Pocket of the Receptor

  摘要：

  To identify novel vitamin D receptor (VDR) ligands that induce a novel architecture within the ligand-binding pocket (LBP), we have investigated eight 22-butyl-1 alpha,24-dihydroxyvitamin D-3 derivatives (3-10), all having a butyl group as the branched alkyl side chain. We found that the 22S-butyl-20-epi-25,26,27-trinorvitamin D derivative 5 was a potent VDR agonist, whereas the corresponding compound 4 with the natural configuration at C(20) was a potent VDR antagonist. Analogues with the full vitamin D3 side chain were less potent agonist, and whether they were agonists or antagonists depended on the 24-configuration. X-ray crystal structures demonstrated that the VDR-LBD accommodating the potent agonist 5 has an architecture wherein the lower side and the helix 11 side of the LBP is simply expanded relative to the canonical active-VDR situation; in contrast, the potent antagonist 4 induces an extra cavity to accommodate the branched moiety. This is the first report of a VDR antagonist that generates a new cavity to alter the canonical pocket structure of the ligand occupied VDR.

  DOI：

  10.1021/jm8014348

文献信息

• A New Class of Vitamin D Analogues that Induce Structural Rearrangement of the Ligand-Binding Pocket of the Receptor
  作者：Yuka Inaba、Nobuko Yoshimoto、Yuta Sakamaki、Makoto Nakabayashi、Teikichi Ikura、Hirokazu Tamamura、Nobutoshi Ito、Masato Shimizu、Keiko Yamamoto

  DOI：10.1021/jm8014348

  日期：2009.3.12

  To identify novel vitamin D receptor (VDR) ligands that induce a novel architecture within the ligand-binding pocket (LBP), we have investigated eight 22-butyl-1 alpha,24-dihydroxyvitamin D-3 derivatives (3-10), all having a butyl group as the branched alkyl side chain. We found that the 22S-butyl-20-epi-25,26,27-trinorvitamin D derivative 5 was a potent VDR agonist, whereas the corresponding compound 4 with the natural configuration at C(20) was a potent VDR antagonist. Analogues with the full vitamin D3 side chain were less potent agonist, and whether they were agonists or antagonists depended on the 24-configuration. X-ray crystal structures demonstrated that the VDR-LBD accommodating the potent agonist 5 has an architecture wherein the lower side and the helix 11 side of the LBP is simply expanded relative to the canonical active-VDR situation; in contrast, the potent antagonist 4 induces an extra cavity to accommodate the branched moiety. This is the first report of a VDR antagonist that generates a new cavity to alter the canonical pocket structure of the ligand occupied VDR.