3-[[(1S,2R,5R,6R,9R,10R,11R,12R,13R,15S)-6,10-dimethyl-5-[(2R)-6-methyl-6-triethylsilyloxyheptan-2-yl]-17,19-dioxo-18-phenyl-11,13-bis(triethylsilyloxy)-16,18,20-triazahexacyclo[13.5.2.01,9.02,6.010,15.016,20]docos-21-en-12-yl]oxy]propanenitrile | 246237-60-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-[[(1S,2R,5R,6R,9R,10R,11R,12R,13R,15S)-6,10-dimethyl-5-[(2R)-6-methyl-6-triethylsilyloxyheptan-2-yl]-17,19-dioxo-18-phenyl-11,13-bis(triethylsilyloxy)-16,18,20-triazahexacyclo[13.5.2.01,9.02,6.010,15.016,20]docos-21-en-12-yl]oxy]propanenitrile
• CAS: 246237-60-5
• 化学式: C₅₆H₉₄N₄O₆Si₃
• 分子量: 1003.64
• InChiKey: UWDLYJLEEOXWJQ-NQCKDPJISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.31
• 重原子数：
  69.0
• 可旋转键数：
  24.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  109.64
• 氢给体数：
  0.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  3-[[(1S,2R,5R,6R,9R,10R,11R,12R,13R,15S)-6,10-dimethyl-5-[(2R)-6-methyl-6-triethylsilyloxyheptan-2-yl]-17,19-dioxo-18-phenyl-11,13-bis(triethylsilyloxy)-16,18,20-triazahexacyclo[13.5.2.01,9.02,6.010,15.016,20]docos-21-en-12-yl]oxy]propanenitrile 在 盐酸 作用下， 以 乙醚 为溶剂， 反应 7.5h， 生成 2β-(2-methoxycarbonylethyloxy)-1α,3β,25-trihydroxycholesta-5,7-diene
  参考文献：
  名称：

  Synthesis of putative metabolites of 1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (ED-71)

  摘要：

  1 alpha,25-Dihydroxy-2 beta-(3-hydroxypropoxy)vitamin D-3 (ED-71), an analog of active vitamin D-3, 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] is under phase III clinical trials in Japan for the treatment of osteoporosis and bone fracture prevention. Since ED-71 has a substituent at the 2 beta-position of the A-ring, it is recognized that the metabolic pathway of ED-71 might be more complicated than 1,25(OH)(2)D-3 because of metabolism at the 2 beta-position substituent in addition to the inherent metabolism of the side chain. To clarify the metabolism of hydroxypropoxy substituent of the 2 beta-positon and a combination of metabolism between side chain and 2 beta-positon, four putative metabolites of ED-71 have been prepared as authentic samples. The metabolites at the 2 beta-positon, the methyl ester derivative considered as an ester standard of the oxidized metabolite and the tetraol derivative as the truncated metabolite were synthesized from alpha-epoxide, a key intermediate of ED-71 synthesis. The combination metabolites between side chain and 2 beta-positon, the 24(S)- and 24(R)-pentaols were synthesized using Trost's convergent method. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2005.11.001
• 作为产物：
  描述：

  (1S,2R,5R,6R,9R,10R,11R,12R,13R,15S)-12-(2-iodoethoxy)-6,10-dimethyl-5-[(2R)-6-methyl-6-triethylsilyloxyheptan-2-yl]-18-phenyl-11,13-bis(triethylsilyloxy)-16,18,20-triazahexacyclo[13.5.2.01,9.02,6.010,15.016,20]docos-21-ene-17,19-dione 在 氰化钠 作用下， 以 四氢呋喃 、 dimethyl sulfoxide 为溶剂， 反应 3.5h， 以87%的产率得到3-[[(1S,2R,5R,6R,9R,10R,11R,12R,13R,15S)-6,10-dimethyl-5-[(2R)-6-methyl-6-triethylsilyloxyheptan-2-yl]-17,19-dioxo-18-phenyl-11,13-bis(triethylsilyloxy)-16,18,20-triazahexacyclo[13.5.2.01,9.02,6.010,15.016,20]docos-21-en-12-yl]oxy]propanenitrile
  参考文献：
  名称：

  Vitamin D derivatives substituted at the 2beta-position

  摘要：

  本发明提供了一般式(I)的维生素D衍生物：其中A表示具有2至10个碳原子的直链或支链亚烷基，R表示SO3R1，其中R1代表氢原子或具有1至3个碳原子的直链或支链烷基，或表示COOR2，其中R2代表氢原子或具有1至3个碳原子的直链或支链烷基；合成该维生素D衍生物的中间化合物；以及包含该维生素D衍生物作为活性成分的药物组合物。发明的化合物对维生素D受体和维生素D结合蛋白具有亲和力，并且可用作药物，例如用于治疗由于钙代谢异常引起的疾病的药物。该化合物被认为是具有2β-位取代基的维生素D衍生物的代谢物，特别是2β-(3-羟基丙氧基)-1α,25-二羟基维生素D3。这种化合物可以有利地用作识别衍生物的真实样本。

  公开号：

  US06410523B1