1-[(1S,3aR,4S,7aS)-Octahydro-4-hydroxy-7a-methyl-1H-inden-1-yl]ethanone | 300344-51-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[(1S,3aR,4S,7aS)-Octahydro-4-hydroxy-7a-methyl-1H-inden-1-yl]ethanone
• 英文别名: 1-[(1S,3aR,4S,7aS)-4-hydroxy-7a-methyl-1,2,3,3a,4,5,6,7-octahydroinden-1-yl]ethanone
• CAS: 300344-51-8
• 化学式: C₁₂H₂₀O₂
• 分子量: 196.29
• InChiKey: NRJLSFPSAFZKFV-NOOOWODRSA-N

物化性质

• 沸点：
  299.9±23.0 °C(Predicted)
• 密度：
  1.068±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-[(1S,3aR,4S,7aS)-Octahydro-4-hydroxy-7a-methyl-1H-inden-1-yl]ethanone 在 lead(IV) acetate 、 碘 、 calcium carbonate 作用下， 以 乙醇 、 环己烷 为溶剂， 反应 196.0h， 生成 de-A,B-8β-hydroxyandrostan-18-oic acid lactone
  参考文献：
  名称：

  在C-18上带有侧链的1α，25-二羟基维生素D 3的新类似物的合成

  摘要：

  通过一条通用途径合成了带有连接到C-18的侧链的1α，25-（OH）2 -D 3激素的新类似物，其中的关键步骤是C-对18-甲基的远程自由基诱导的官能化8β-羟基和通过在C-18-醛上的Wittig反应引入侧链。新的类似物的三烯系统是通过收敛的Lythgoe-Hoffmann la Roche方法构建的，该方法涉及氧化膦（环A片段）与酮（上部片段）的反应。

  DOI：

  10.1021/jo0498664
• 作为产物：
  描述：

  des-A,B-8β-[(triethylsilyl)oxy]-pregnane-20-one 在 四丁基氟化铵 作用下， 生成 1-[(1S,3aR,4S,7aS)-Octahydro-4-hydroxy-7a-methyl-1H-inden-1-yl]ethanone
  参考文献：
  名称：

  概念上新的激素1alpha，25-dihydroxyvitamin D（3）的20-epi-22-oxa砜类似物：合成和生物学评估。

  摘要：

  制备了具有天然1alpha，3beta-羟基基团但缺乏天然激素1alpha，25-dihydroxyvitamin D（3）（25）的25-羟基基团的新C，D环侧链改性砜4a和特点。新颖的合成功能包括：（1）在伯-仲双甲硅烷基醚中间体中仅对伯甲硅烷基醚进行化学选择氧化，以及（2）平滑还原醚化而不受相邻磺酰基的干扰。砜4a，但不是它的1beta，3alpha-非对映异构体4b，在体外具有强大的抗增殖和转录活性，但在体内则是非消钙的。尽管砜4a的设计类似于Leo Pharmaceutical Co.的KH-1060（3），但被分解代谢酶识别，

  DOI：

  10.1021/jm000215j

文献信息

• Chemical synthesis, biological activities and action on nuclear receptors of 20S(OH)D3, 20S,25(OH)2D3, 20S,23S(OH)2D3 and 20S,23R(OH)2D3
  作者：Pawel Brzeminski、Adrian Fabisiak、Radomir M. Slominski、Tae-Kang Kim、Zorica Janjetovic、Ewa Podgorska、Yuwei Song、Mohammad Saleem、Sivani B. Reddy、Shariq Qayyum、Yuhua Song、Robert C. Tuckey、Venkatram Atigadda、Anton M. Jetten、Rafal R. Sicinski、Chander Raman、Andrzej T. Slominski

  DOI：10.1016/j.bioorg.2022.105660

  日期：2022.4

  as indicated by molecular modeling. They functioned as substrates for CYP27B1 with enzymatic activity being the highest towards 20S,25(OH)2D3 and the lowest towards 20S(OH)D3. In conclusion, defining new routes for large scale synthesis of endogenously produced D3-hydroxy derivatives by pathways initiated by CYP11A1 opens an exciting era to analyze their common and differential activities in vivo, particularly

  维生素 D 3 (D 3 ) 羟基 (OH) 代谢物的化学合成新途径和更有效的途径，包括 20 S (OH)D 3、 20 S ,23 S (OH) 2 D 3和 20 S ,25(OH) 2 D 3，由 CYP11A1 在人体中内源性产生，以及 20 S ,23 R (OH) 2 D 3成立。生物学评价表明，这些化合物在抑制细胞增殖和诱导细胞分化方面表现出相似的特性，但在数量上存在细微差别。它们显示出对T细胞免疫活性的重叠和差异影响。它们还显示了与核受体的相似相互作用，所有类固醇激活维生素 D、肝 X、视黄酸孤儿和芳基烃受体在功能测定中，也如分子模型所示。它们充当 CYP27B1 的底物，酶活性对 20 S ,25(OH) 2 D 3最高，对 20 S (OH)D 3最低. 总之，定义通过 CYP11A1 启动的途径大规模合成内源性 D 3 -羟基衍生物的新途径开启了一个激动人心的时代，
• Antiproliferative, low-calcemic, fluorinated sulfone analogs of 1α,25-dihydroxyvitamin D3: Chemical synthesis and biological evaluation
  作者：Aimee R. Usera、Patrick M. Dolan、Thomas W. Kensler、Gary H. Posner

  DOI：10.1016/j.bmc.2007.05.051

  日期：2007.8

  Novel fluorinated sulfone analogs of the hormone 1 alpha,25-dihydroxyvitamm D-3 have been designed and synthesized in order to study the biological effects of fluorine incorporation at the terminus of the C,D-ring side chain. Although biologically active 26,27-hexafluorinated 1 alpha,25-dihydroxyvitamin D-3 analogs have been synthesized previously, this investigation reports the first successful fluorinated series in which trifluoromethyl sulfone analogs present a favorable biological profile. This study shows that two new analogs featuring incorporation of a synthetically simple single trifluoromethyl sulfone group have significantly increased antiproliferative activity while causing desirably low in vivo calciuria relative to that of calcitriol. Incorporation of additional fluorines, as in a perfluorobutyl analog, results in a loss of antiproliferative activity. (c) 2007 Elsevier Ltd. All rights reserved.
• US7888339B2
  申请人：——

  公开号：US7888339B2

  公开（公告）日：2011-02-15
• [EN] 2-METHYLENE-(20E)-20(22)-DEHYDRO-19-NOR-VITAMIN D ANALOGS<br/>[FR] ANALOGUES DE LA 2-MÉTHYLÈNE-(20E)-20(22)-DÉSHYDRO-19-NOR-VITAMINE D
  申请人：WISCONSIN ALUMNI RES FOUND

  公开号：WO2010006162A2

  公开（公告）日：2010-01-14

  This invention discloses 2-methylene-(20E)-20(22)-dehydro-19-nor-vitamin D analogs, and specifically 2-methylene-(20E)-20(22)-dehydro-19-nor-lα,25- dihydroxyvitamin D3, and pharmaceutical uses therefor. This compound exhibits relatively high transcription activity as well as pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. This compound also shows lower activity in vivo on bone calcium mobilization and similar in vivo intestinal calcium transport activity compared to the native hormone lα,25-dihydroxyvitamin D3, and therefore may be used to treat autoimmune disorders or inflammatory diseases in humans as well as renal osteodystrophy. This compound may also be used for the treatment or prevention of obesity.