(22S)-butyl-2-methylidene-26,27-dimethyl-19,24-dinor-1α,25-dihydroxyvitamin D3 | 1374221-62-1

• 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-2-methylidene-26,27-dimethyl-19,24-dinor-1α,25-dihydroxyvitamin D3
• 英文别名: (1r,3r,7e,17beta)-17-[(2r,3s)-3-Butyl-5-Ethyl-5-Hydroxyheptan-2-Yl]-2-Methylidene-9,10-Secoestra-5,7-Diene-1,3-Diol；(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,3S)-3-butyl-5-ethyl-5-hydroxyheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol
• CAS: 1374221-62-1
• 化学式: C₃₂H₅₄O₃
• 分子量: 486.779
• InChiKey: OILLQCLQUXHGBN-PWPPSVFISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.81
• 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：

  ethyl (3S)-3-{1-[(1R,3R,7E,17β)-1,3-bis{[tert-butyl(dimethyl)silyl]oxy}-2-methylidene-9,10-secoestra-5,7-dien-17-yl]ethyl}heptanoate 在 camphor-10-sulfonic acid 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 3.5h， 生成 (22S)-butyl-2-methylidene-26,27-dimethyl-19,24-dinor-1α,25-dihydroxyvitamin D3
  参考文献：
  名称：

  Butyl Pocket Formation in the Vitamin D Receptor Strongly Affects the Agonistic or Antagonistic Behavior of Ligands

  摘要：

  Previously, we reported that 22S-butyl-25,26,27-trinor-1 alpha,24-dihydroxyvitamin D-3 2 represents a new class of antagonist for the vitamin D receptor (VDR). The crystal structure of the ligand-binding domain (LBD) of VDR complexed with 2 showed the formation of a butyl pocket to accommodate the 22-butyl group and insufficient interactions between ligand 2 and the C-terminus of VDR Here, we designed and synthesized new analogues 5a-c and evaluated their biological activities to probe whether agonistic activity is recovered when the analogue restores interactions with the C-terminus of VDR Analogues 5a-c exhibited full agonistic activity in transactivation. Interestingly, 5c, which bears a 24-diethyl group, completely recovered agonistic activity, although 3c and 4c act as an antagonist and a weak agonist, respectively. The crystal structures of VDR-LBD complexed with 3a, 4a, 5a, and 5c were solved, and the results confirmed that butyl pocket formation in VDR strongly affects the agonistic or antagonistic behaviors of ligands.

  DOI：

  10.1021/jm300230a

文献信息

• Butyl Pocket Formation in the Vitamin D Receptor Strongly Affects the Agonistic or Antagonistic Behavior of Ligands
  作者：Nobuko Yoshimoto、Yuta Sakamaki、Minoru Haeta、Akira Kato、Yuka Inaba、Toshimasa Itoh、Makoto Nakabayashi、Nobutoshi Ito、Keiko Yamamoto

  DOI：10.1021/jm300230a

  日期：2012.5.10

  Previously, we reported that 22S-butyl-25,26,27-trinor-1 alpha,24-dihydroxyvitamin D-3 2 represents a new class of antagonist for the vitamin D receptor (VDR). The crystal structure of the ligand-binding domain (LBD) of VDR complexed with 2 showed the formation of a butyl pocket to accommodate the 22-butyl group and insufficient interactions between ligand 2 and the C-terminus of VDR Here, we designed and synthesized new analogues 5a-c and evaluated their biological activities to probe whether agonistic activity is recovered when the analogue restores interactions with the C-terminus of VDR Analogues 5a-c exhibited full agonistic activity in transactivation. Interestingly, 5c, which bears a 24-diethyl group, completely recovered agonistic activity, although 3c and 4c act as an antagonist and a weak agonist, respectively. The crystal structures of VDR-LBD complexed with 3a, 4a, 5a, and 5c were solved, and the results confirmed that butyl pocket formation in VDR strongly affects the agonistic or antagonistic behaviors of ligands.