8β-[(tert-butyldimethylsilyl)oxy]-(20S,23S)-epoxymethano-25-hydroxy-des-A,B-cholestane | 933987-48-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 8β-[(tert-butyldimethylsilyl)oxy]-(20S,23S)-epoxymethano-25-hydroxy-des-A,B-cholestane
• 英文别名: 1-((3S,5S)-tetrahydro-5-((3S,3aS,7S,7aR)-octahydro-7-(tert-butyldimethylsilyloxy)-3a-methyl-1H-inden-3-yl)-5-methylfuran-3-yl)-2-methylpropan-2-ol；1-[(3S,5S)-5-[(1S,3aR,4S,7aS)-4-[tert-butyl(dimethyl)silyl]oxy-7a-methyl-1,2,3,3a,4,5,6,7-octahydroinden-1-yl]-5-methyloxolan-3-yl]-2-methylpropan-2-ol
• CAS: 933987-48-5
• 化学式: C₂₅H₄₈O₃Si
• 分子量: 424.74
• InChiKey: SGBWVVXKESEPAC-FYVXYBBASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.55
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8β-[(tert-butyldimethylsilyl)oxy]-(20S,23S)-epoxymethano-25-hydroxy-des-A,B-cholestane 在 四丁基氟化铵 、 水 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 90.0h， 以93%的产率得到(1S,3aR,4S,7aS)-octahydro-1-((2S,4S)-tetrahydro-4-(2-hydroxy-2-methylpropyl)-2-methylfuran-2-yl)-7a-methyl-1H-inden-4-ol
  参考文献：
  名称：

  Vitamin D derivatives active on the vitamin D nuclear receptor, preparation and uses thereof

  摘要：

  本发明涉及维生素D衍生物及其用途，特别是在制药业中的应用。本发明揭示了具有不同有趣生物学特性的化合物，包括维生素D核受体（VDR）激动剂活性，以及通过给予这些化合物的治疗方法，特别是用于治疗癌症、银屑病、自身免疫疾病、骨营养不良和骨质疏松症。本发明还涉及包含这些化合物的制药组合物和制备这些组合物的方法。

  公开号：

  EP1777220A1
• 作为产物：
  描述：

  C₂₅H₄₆O₄Si 、 甲基锂 以 四氢呋喃 、 乙醚 为溶剂， 反应 1.08h， 以45 mg的产率得到8β-[(tert-butyldimethylsilyl)oxy]-(20S,23S)-epoxymethano-25-hydroxy-des-A,B-cholestane
  参考文献：
  名称：

  Structure−Function Relationships and Crystal Structures of the Vitamin D Receptor Bound 2α-Methyl-(20S,23S)- and 2α-Methyl-(20S,23R)-epoxymethano-1α,25-dihydroxyvitamin D₃

  摘要：

  The vitamin D nuclear receptor is a ligand-dependent transcription factor that controls multiple biological responses such as cell proliferation, immune responses, and bone mineralization. Numerous 1 alpha,25(OH)(2)D-3 analogues, which exhibit low calcemic side effects and/or antitumoral properties, have been synthesized. We recently showed that the synthetic analogue (20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (2a) acts as a 1 alpha,25(OH)(2)D-3 superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1 alpha,25(OH)(2)D-3,2 alpha-methyl-1 alpha,25(OH)(2)D-3, or 2a, we designed a novel analogue, 2 alpha-methyl-(20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes.

  DOI：

  10.1021/jm9014636

文献信息

• VITAMIN D DERIVATIVES ACTIVE ON THE VITAMIN D NUCLEAR RECEPTOR, PREPARATION AND USES THEREOF
  申请人：Moras Dino

  公开号：US20090131378A1

  公开（公告）日：2009-05-21

  The invention relates to vitamin D derivatives and their uses, particularly in the pharmaceutical industry. The invention discloses compounds having different interesting biological properties, including vitamin D nuclear receptor (VDR) agonist activity, as well as therapeutics methods by administering said compounds, in particular for treating cancer, psoriasis, autoimmune diseases, osteodistrophy and osteoporosis. It further relates to pharmaceutical compositions comprising said compounds and methods for preparing the same.

  本发明涉及维生素D衍生物及其用途，特别是在制药工业中的应用。本发明揭示了具有不同有趣生物学性质的化合物，包括维生素D核受体（VDR）激动剂活性，以及通过给予该化合物的治疗方法，特别是用于治疗癌症、银屑病、自身免疫疾病、骨发育不良和骨质疏松症。此外，本发明还涉及包含该化合物的制药组合物及其制备方法。
• Structure−Function Relationships and Crystal Structures of the Vitamin D Receptor Bound 2α-Methyl-(20<i>S</i>,23<i>S</i>)- and 2α-Methyl-(20<i>S</i>,23<i>R</i>)-epoxymethano-1α,25-dihydroxyvitamin D₃
  作者：Pierre Antony、Rita Sigüeiro、Tiphaine Huet、Yoshiteru Sato、Nick Ramalanjaona、Luis Cezar Rodrigues、Antonio Mouriño、Dino Moras、Natacha Rochel

  DOI：10.1021/jm9014636

  日期：2010.2.11

  The vitamin D nuclear receptor is a ligand-dependent transcription factor that controls multiple biological responses such as cell proliferation, immune responses, and bone mineralization. Numerous 1 alpha,25(OH)(2)D-3 analogues, which exhibit low calcemic side effects and/or antitumoral properties, have been synthesized. We recently showed that the synthetic analogue (20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (2a) acts as a 1 alpha,25(OH)(2)D-3 superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1 alpha,25(OH)(2)D-3,2 alpha-methyl-1 alpha,25(OH)(2)D-3, or 2a, we designed a novel analogue, 2 alpha-methyl-(20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes.
• Vitamin D derivatives active on the vitamin D nuclear receptor, preparation and uses thereof
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

  公开号：EP1777220A1

  公开（公告）日：2007-04-25

  The invention relates to vitamin D derivatives and their uses, particularly in the pharmaceutical industry. The invention discloses compounds having different interesting biological properties, including vitamin D nuclear receptor (VDR) agonist activity, as well as therapeutics methods by administering said compounds, in particular for treating cancer, psoriasis, autoimmune diseases, osteodistrophy and osteoporosis. It further relates to pharmaceutical compositions comprising said compounds and methods for preparing the same.

  本发明涉及维生素D衍生物及其用途，特别是在制药业中的应用。本发明揭示了具有不同有趣生物学特性的化合物，包括维生素D核受体（VDR）激动剂活性，以及通过给予这些化合物的治疗方法，特别是用于治疗癌症、银屑病、自身免疫疾病、骨营养不良和骨质疏松症。本发明还涉及包含这些化合物的制药组合物和制备这些组合物的方法。