(5E)-(20S)-1α,25-dihydroxy-2-methylene vitamin D₃ | 1428946-59-1

• 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: (5E)-(20S)-1α,25-dihydroxy-2-methylene vitamin D₃
• 英文别名: (1R,3R,5E)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2S)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2,4-dimethylidenecyclohexane-1,3-diol
• CAS: 1428946-59-1
• 化学式: C₂₈H₄₄O₃
• 分子量: 428.656
• InChiKey: ZEVBNQULIOXDBE-LEHMOOCBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 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：

  methyl (3R,5R)-3,5-bis[(tert-butyldimethylsilyl)oxy]-1-hydroxy-4-methylenecyclohexanecarboxylate 在 copper(l) iodide 、 重铬酸吡啶 、 正丁基锂 、 双[Α,Α-双(三氟甲基)苯甲醇合]二苯硫 、 Pd(PPh₃)(OAc)2 、 四丁基氟化铵 、 氢气 、 碘 、 柠檬酸 作用下， 以 四氢呋喃 、 喹啉 、 四氯化碳 、 乙醚 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.75h， 生成 (5E)-(20S)-1α,25-dihydroxy-2-methylene vitamin D₃
  参考文献：
  名称：

  骨化三醇及相关化合物的2-亚甲基类似物的合成及生物活性

  摘要：

  在试图制备维生素d类似物是超级激动剂，（20 - [R ）-和（20小号）1α-羟基-2- methylenevitamin d的-异构体3和1α，25-二羟基-2- methylenevitamin d 3已被合成。为了制备所需的A环二烯炔片段，使用了两种不同的方法，均从（-）-奎尼酸开始。随后使用Sonogashira反应将获得的衍生物与衍生自相应的Grundmann酮的C，D-环烯醇三氟甲磺酸酯偶联。此外，（20 R）-和（20 S）-1α，25-二羟基-2-亚甲基维生素D 3化合物具有（5 E）-构型是通过碘催化的异构化制备的。天然激素的所有四个2-亚甲基类似物都具有很高的体外活性。如预期的那样，25-脱氧类似物的效力要低得多。在合成的化合物中，发现两个化合物1α，25-二羟基-2-亚甲基维生素D 3及其C-20差向异构体的活性几乎与2-亚甲基-19- nor- （20 S）-1α相同，骨骼上有25-二羟基维生素D

  DOI：

  10.1021/acs.jmedchem.5b01295

文献信息

• [EN] SYNTHESIS AND BIOLOGICAL ACTIVITY OF 2-METHYLENE ANALOGS OF CALCITRIOL AND RELATED COMPOUNDS<br/>[FR] SYNTHÈSE ET ACTIVITÉ BIOLOGIQUE D'ANALOGUES 2-MÉTHYLÈNE DU CALCITRIOL ET DE COMPOSÉS APPARENTÉS
  申请人：WISCONSIN ALUMNI RES FOUND

  公开号：WO2017023617A1

  公开（公告）日：2017-02-09

  Disclosed are 2-methylene analogs of vitamin D3 and related compounds, their biological activities, and various pharmaceutical uses for these analogs. Particularly disclosed are 1α-hydroxy-2-methylene-vitamin D3, (20S)-1α-hydroxy-2-methylene- vitamin D3, and (5E)- 1α,25-dihydroxy-2-methylene- vitamin D3, their biological activities, and various pharmaceutical uses for these compounds including methods of treating and/or preventing bone diseases and disorders.

  公开了维生素D3的2-亚甲基类似物及相关化合物，它们的生物活性以及这些类似物的各种药用用途。特别公开了1α-羟基-2-亚甲基-维生素D3、(20S)-1α-羟基-2-亚甲基-维生素D3和(5E)-1α,25-二羟基-2-亚甲基-维生素D3，它们的生物活性以及这些化合物的各种药用用途，包括治疗和/或预防骨骼疾病和失调的方法。
• 2-methylene-vitamin D analogs and their uses
  申请人：Wisconsin Alumni Research Foundation

  公开号：US08410080B1

  公开（公告）日：2013-04-02

  This invention discloses 2-methylene-vitamin D analogs, and specifically (20S)-1α,25 -dihydroxy-2-methylene-vitamin D3 as well as (5E)-(20S)-1α,25-dihydroxy-2 -methylene-vitamin D3 and (20R)-1α,25-dihydroxy-2-methylene-vitamin D3, as well as pharmaceutical uses therefor. These compounds exhibit relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent especially for the treatment or prevention of osteosarcoma, leukemia, colon cancer, breast cancer, skin cancer or prostate cancer. These compounds also have relatively high calcemic activities evidencing use in the treatment of bone diseases.

  本发明公开了2-亚甲基-维生素D类似物，特别是(20S)-1α,25-二羟基-2-亚甲基-维生素D3以及(5E)-(20S)-1α,25-二羟基-2-亚甲基-维生素D3和(20R)-1α,25-二羟基-2-亚甲基-维生素D3，以及它们的药物用途。这些化合物表现出相对较高的结合活性和显著抑制未分化细胞增殖并诱导其向单核细胞分化的活性，因此可作为抗癌剂，特别用于治疗或预防骨肉瘤、白血病、结肠癌、乳腺癌、皮肤癌或前列腺癌。这些化合物还具有相对较高的升高血钙活性，可用于治疗骨骼疾病。
• 2-METHYLENE-VITAMIN D ANALOGS AND THEIR USES
  申请人：Wisconsin Alumni Research Foundation

  公开号：US20130102574A1

  公开（公告）日：2013-04-25

  This invention discloses 2-methylene-vitamin D analogs, and specifically (20S)-1α,25-dihydroxy-2-methylene-vitamin D 3 as well as (5E)-(20S)-1α,25-dihydroxy-2-methylene-vitamin D 3 and (20R)-1α,25-dihydroxy-2-methylene-vitamin D 3 , as well as pharmaceutical uses therefor. These compounds exhibit relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent especially for the treatment or prevention of osteosarcoma, leukemia, colon cancer, breast cancer, skin cancer or prostate cancer. These compounds also have relatively high calcemic activities evidencing use in the treatment of bone diseases.
• SYNTHESIS AND BIOLOGICAL ACTIVITY OF 2-METHYLENE ANALOGS OF CALCITRIOL AND RELATED COMPOUNDS
  申请人：Wisconsin Alumni Research Foundation

  公开号：US20170036977A1

  公开（公告）日：2017-02-09

  Disclosed are 2-methylene analogs of vitamin D 3 and related compounds, their biological activities, and various pharmaceutical uses for these analogs. Particularly disclosed are 1α-hydroxy-2-methylene-vitamin D 3 , (20S)-1α-hydroxy-2-methylene-vitamin D 3 , and (5E)-1α,25-dihydroxy-2-methylene-vitamin D 3 , their biological activities, and various pharmaceutical uses for these compounds including methods of treating and/or preventing bone diseases and disorders.
• US8410080B1
  申请人：——

  公开号：US8410080B1

  公开（公告）日：2013-04-02