2β-(2-methoxycarbonylethyloxy)-1α,3β,25-trihydroxycholesta-5,7-diene | 246237-62-7

• 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: 2β-(2-methoxycarbonylethyloxy)-1α,3β,25-trihydroxycholesta-5,7-diene
• 英文别名: methyl 3-[[(1R,2R,3R,9S,10R,13R,14R,17R)-1,3-dihydroxy-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,9,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-2-yl]oxy]propanoate
• CAS: 246237-62-7
• 化学式: C₃₁H₅₀O₆
• 分子量: 518.734
• InChiKey: NOAFKGMJLKBQRA-PPAFLWOJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  96.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2β-(2-methoxycarbonylethyloxy)-1α,3β,25-trihydroxycholesta-5,7-diene 以 乙醇 为溶剂， 反应 2.03h， 以25%的产率得到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：

  (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 盐酸 作用下， 以 四氢呋喃 、 乙醚 、 二甲基亚砜 为溶剂， 反应 11.0h， 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

文献信息

• Vitamin D derivative having substituent at 2beta-position
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：US20020045772A1

  公开（公告）日：2002-04-18

  A steroid intermediate has the formula (II): 1 wherein A denotes alkylene of 2 to 10 carbons; X denotes halogen; R a , R b and R c denote, independently hydrogen or hydroxyl protecting group; and R p , R q , R y and R z are such that R p and R q together form a double bond between the 5-position and the 6-position and R y and R z together form a double bond between the 7-position and the 8-position, or R q and R y together form a double bond between the 6-position and the 7-position and R p and R z are bound to a dienophile capable of protecting conjugated double bonds.

  一种甾体中间体具有公式(II)：1，其中A代表2至10个碳原子的烷基；X代表卤素；Ra、Rb和Rc分别独立表示氢或羟基保护基团；而Rp、Rq、Ry和Rz是这样的，即Rp和Rq共同在5位和6位之间形成一个双键，Ry和Rz共同在7位和8位之间形成一个双键，或者Rq和Ry共同在6位和7位之间形成一个双键，而Rp和Rz则与能保护共轭双键的二烯烃基团结合。
• 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。
• VITAMIN D DERIVATIVES SUBSTITUTED AT THE 2$g(b)-POSITION
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1070704A1

  公开（公告）日：2001-01-24

  Vitamin D derivatives represented by general formula (I), intermediate compounds in the synthesis thereof, and medicinal compositions containing these vitamin D derivatives as the active ingredient wherein A represents linear or branched C2-10 alkylene; and R represents SO3R1 (wherein R1 represents hydrogen or linear or branched C1-3 alkyl) or COOR2 (wherein R2 represents hydrogen or linear or branched C1-3 alkyl). These compounds have affinities for vitamin D receptors and vitamin D-binding proteins and are useful as drugs such as remedies for diseases based on calcium metabolic errors. Moreover, these compounds are considered as the metabolites of vitamin D derivatives substituted at the 2β-position, in particular, 2β-(3-hydroxypropoxy)-1α,25-dihydroxyvitamin D3 and are useful as a specimen in identifying the same.

  通式(I)代表的维生素 D 衍生物、合成这些衍生物的中间化合物以及含有这些维生素 D 衍生物作为活性成分的药物组合物 其中 A 代表直链或支链 C2-10 烷基；R 代表 SO3R1（其中 R1 代表氢或直链或支链 C1-3 烷基）或 COOR2（其中 R2 代表氢或直链或支链 C1-3 烷基）。这些化合物对维生素 D 受体和维生素 D 结合蛋白具有亲和力，可用作药物，如治疗基于钙代谢错误的疾病。此外，这些化合物被认为是在 2β 位被取代的维生素 D 衍生物的代谢产物，特别是 2β-（3-羟基丙氧基）-1α,25-二羟基维生素 D3，可作为鉴别维生素 D3 的标本。