1α,3β-bis[(methoxycarbonyl)oxy]-22S-butyl-5,7-choladiene-24-al | 1127352-39-9

• 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: 1α,3β-bis[(methoxycarbonyl)oxy]-22S-butyl-5,7-choladiene-24-al
• 英文别名: [(1S,3R,9S,10R,13R,14R,17R)-1-methoxycarbonyloxy-10,13-dimethyl-17-[(2R,3S)-3-(2-oxoethyl)heptan-2-yl]-2,3,4,9,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-yl] methyl carbonate
• CAS: 1127352-39-9
• 化学式: C₃₂H₄₈O₇
• 分子量: 544.729
• InChiKey: XUNPENKNEJEKLV-BLXFNNAYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1α,3β-bis[(methoxycarbonyl)oxy]-22S-butyl-5,7-choladiene-24-al 、 异丙基氯化镁 以 四氢呋喃 为溶剂， 反应 0.42h， 以34%的产率得到(1α,3β,22S,24R)-bis[(methoxycarbonyl)oxy]-22-butylcholesta-5,7-dien-24-ol
  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
• 作为产物：
  描述：

  1α,3β-bis[(methoxycarbonyl)oxy]-22S-butyl-5,7-choladiene-24-ol 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以72%的产率得到1α,3β-bis[(methoxycarbonyl)oxy]-22S-butyl-5,7-choladiene-24-al
  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.