(3R)-4-[(1R,3R,7E,17β)-1,3-bis{[tert-butyl(dimethyl)silyl]oxy}-2-methylidene-9,10-secoestra-5,7-dien-17-yl]-3-ethylpentyl 4-methyl benzenesulfonate | 1608457-82-4

• 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: (3R)-4-[(1R,3R,7E,17β)-1,3-bis{[tert-butyl(dimethyl)silyl]oxy}-2-methylidene-9,10-secoestra-5,7-dien-17-yl]-3-ethylpentyl 4-methyl benzenesulfonate
• CAS: 1608457-82-4
• 化学式: C₄₅H₇₆O₅SSi₂
• 分子量: 785.332
• InChiKey: QMYYJUKHAYUDGM-CDHJXJBCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.95
• 重原子数：
  53.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  61.83
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (3R)-4-[(1R,3R,7E,17β)-1,3-bis{[tert-butyl(dimethyl)silyl]oxy}-2-methylidene-9,10-secoestra-5,7-dien-17-yl]-3-ethylpentyl 4-methyl benzenesulfonate 在 sodium tetrahydroborate 、 camphor-10-sulfonic acid 、 二异丁基氢化铝 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 5.0h， 生成 (1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,3R)-3-ethyl-6-hydroxyhexan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol
  参考文献：
  名称：

  A Mixed Population of Antagonist and Agonist Binding Conformers in a Single Crystal Explains Partial Agonism against Vitamin D Receptor: Active Vitamin D Analogues with 22R-Alkyl Group

  摘要：

  We are continuing to study the structural basis of vitamin D receptor (VDR) agonism and antagonism by using 22S-alkyl vitamin D analogues. Here we report the synthesis and biological evaluation of 22R-alkyl analogues and the X-ray crystallographic analysis of vitamin D receptor ligand-binding domain (VDR-LBD) complexed with a 22R-analogue. VDR-LBD complexed with the partial agonist 8a showed that 8a binds to VDR-LBD with two conformations, one of which is the antagonist/VDR-LBD complex structure and the other is the agonist/VDR-LBD complex structure. The results indicate that the partial agonist activity of 8a depends on the sum of antagonistic and agonistic activities caused by the antagonist and agonist binding conformers, respectively. The structural basis observed here must be applicable to the partial agonism of other ligand-dependent nuclear receptors. This is the first report describing the trapping of a conformational subset of the ligand and the nuclear receptor in a single crystal.

  DOI：

  10.1021/jm500392t
• 作为产物：
  描述：

  ethyl (3R)-4-[(1R,3R,7E,17β)-1,3-bis{[tert-butyl(dimethyl)silyl]oxy}-2-methylidene-9,10-secoestra-5,7-dien-17-yl]-3-ethylpentanoate 在 吡啶 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 38.5h， 生成 (3R)-4-[(1R,3R,7E,17β)-1,3-bis{[tert-butyl(dimethyl)silyl]oxy}-2-methylidene-9,10-secoestra-5,7-dien-17-yl]-3-ethylpentyl 4-methyl benzenesulfonate
  参考文献：
  名称：

  A Mixed Population of Antagonist and Agonist Binding Conformers in a Single Crystal Explains Partial Agonism against Vitamin D Receptor: Active Vitamin D Analogues with 22R-Alkyl Group

  摘要：

  We are continuing to study the structural basis of vitamin D receptor (VDR) agonism and antagonism by using 22S-alkyl vitamin D analogues. Here we report the synthesis and biological evaluation of 22R-alkyl analogues and the X-ray crystallographic analysis of vitamin D receptor ligand-binding domain (VDR-LBD) complexed with a 22R-analogue. VDR-LBD complexed with the partial agonist 8a showed that 8a binds to VDR-LBD with two conformations, one of which is the antagonist/VDR-LBD complex structure and the other is the agonist/VDR-LBD complex structure. The results indicate that the partial agonist activity of 8a depends on the sum of antagonistic and agonistic activities caused by the antagonist and agonist binding conformers, respectively. The structural basis observed here must be applicable to the partial agonism of other ligand-dependent nuclear receptors. This is the first report describing the trapping of a conformational subset of the ligand and the nuclear receptor in a single crystal.

  DOI：

  10.1021/jm500392t