methyl 3-[[(1S,2R,5R,6R,9R,10R,11R,12R,13R,15S)-11,13-dihydroxy-5-[(2R)-6-hydroxy-6-methylheptan-2-yl]-6,10-dimethyl-17,19-dioxo-18-phenyl-16,18,20-triazahexacyclo[13.5.2.01,9.02,6.010,15.016,20]docos-21-en-12-yl]oxy]propanoate | 246237-61-6

• 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: methyl 3-[[(1S,2R,5R,6R,9R,10R,11R,12R,13R,15S)-11,13-dihydroxy-5-[(2R)-6-hydroxy-6-methylheptan-2-yl]-6,10-dimethyl-17,19-dioxo-18-phenyl-16,18,20-triazahexacyclo[13.5.2.01,9.02,6.010,15.016,20]docos-21-en-12-yl]oxy]propanoate
• CAS: 246237-61-6
• 化学式: C₃₉H₅₅N₃O₈
• 分子量: 693.881
• InChiKey: GUGZXTOBOYFOCH-QVQWSRPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.87
• 重原子数：
  50.0
• 可旋转键数：
  10.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  145.15
• 氢给体数：
  3.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  methyl 3-[[(1S,2R,5R,6R,9R,10R,11R,12R,13R,15S)-11,13-dihydroxy-5-[(2R)-6-hydroxy-6-methylheptan-2-yl]-6,10-dimethyl-17,19-dioxo-18-phenyl-16,18,20-triazahexacyclo[13.5.2.01,9.02,6.010,15.016,20]docos-21-en-12-yl]oxy]propanoate 以 乙醇 为溶剂， 反应 3.03h， 生成 2β-(2-methoxycarbonylethyloxy)-1α,3β,25-trihydroxy-9,10-secocholesta-5,7,10(19)-triene
  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：

  2β-(2-hydroxyethyloxy)-1α, 3β, 25-tris(triethylsilyloxy)cholesta-5,7-diene 在 咪唑 、 盐酸 、 碘 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 11.83h， 生成 methyl 3-[[(1S,2R,5R,6R,9R,10R,11R,12R,13R,15S)-11,13-dihydroxy-5-[(2R)-6-hydroxy-6-methylheptan-2-yl]-6,10-dimethyl-17,19-dioxo-18-phenyl-16,18,20-triazahexacyclo[13.5.2.01,9.02,6.010,15.016,20]docos-21-en-12-yl]oxy]propanoate
  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

文献信息

• Vitamin D derivatives substituted at the 2beta-position
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US06410523B1

  公开（公告）日：2002-06-25

  The present invention provides a vitamin D derivative of the general formula (I): wherein A denotes a straight chain or branched chain alkylene group with 2 to 10 carbon atoms and R denotes SO3R1 in which R1 represents a hydrogen atom or a straight chain or branched chain alkyl group with 1 to 3 carbon atoms or COOR2 in which R2 represents a hydrogen atom or a straight chain or branched chain alkyl group with 1 to 3 carbon atoms; an intermediate compound for synthesis of the vitamin D derivative; and a pharmaceutical composition containing the vitamin D derivative as an active ingredient. The compound of the invention has affinity for a vitamin D receptor and a vitamin D binding protein, and is useful as a drug, such as a drug for treatment of diseases due to abnormal of calcium metabolism. The compound is considered to be a metabolite of a vitamin D derivative having a substituent at the 2&bgr;-position, especially, 2&bgr;-(3-hydroxypropoxy)-1&agr;,25-dihydroxyvitamin D3. This compound can advantageously be used as an authentic sample to identify the derivative.

  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。