(1R,4S,7aR)-1-((R)-hexan-2-yl)-7a-methyloctahydro-1H-inden-4-ol | 1428964-35-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1R,4S,7aR)-1-((R)-hexan-2-yl)-7a-methyloctahydro-1H-inden-4-ol
• 英文别名: (8S,20R)-des-A,B-20-butylpregnan-8-ol
• CAS: 1428964-35-5
• 化学式: C₁₆H₃₀O
• 分子量: 238.414
• InChiKey: CEUAYIHGUFKUHG-RBGFHDKUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.39
• 重原子数：
  17.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  20.23
• 氢给体数：
  1.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  (1R,4S,7aR)-1-((R)-hexan-2-yl)-7a-methyloctahydro-1H-inden-4-ol 在 pyridinium dichromate 、 4-甲基苯磺酸吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以95%的产率得到(20R)-des-A,B-20-butylpregnan-8-one
  参考文献：
  名称：

  26- and 27-Methyl groups of 2-substituted, 19-nor-1α,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo

  摘要：

  Twelve new analogs of 19-nor-1 alpha,25-dihydroxyvitamin D-3 6-17, were prepared by a multi-step procedure from known alcohols 18 and 19. We have examined the influence of removing two methyl groups located at C-25, as well as the 25-hydroxy group, on the biological in vitro and in vivo biological activity. Surprisingly, removal of the 26- and 27-methyl groups from either the 2 alpha-methyl or 2-methylene-19-nor-1 alpha,25-dihydroxyvitamin D-3 reduced vitamin D receptor binding, HL-60 differentiation, and 25-hydroxylase transcription in vitro only slightly to moderately (compounds 6-13). However, these compounds were devoid of in vivo bone mobilization activity and had markedly reduced activity on intestinal calcium transport. The analogs 14-17 with a 2 beta-methyl substitution had little or no activity in vitro and in vivo as expected from previous work. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2013.01.001
• 作为产物：
  描述：

  (8S,20R)-des-A,B-20-[(3'-iso-propoxycarbonyl)propyl]pregnan-8-ol 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 40.5h， 生成 (1R,4S,7aR)-1-((R)-hexan-2-yl)-7a-methyloctahydro-1H-inden-4-ol
  参考文献：
  名称：

  26- and 27-Methyl groups of 2-substituted, 19-nor-1α,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo

  摘要：

  Twelve new analogs of 19-nor-1 alpha,25-dihydroxyvitamin D-3 6-17, were prepared by a multi-step procedure from known alcohols 18 and 19. We have examined the influence of removing two methyl groups located at C-25, as well as the 25-hydroxy group, on the biological in vitro and in vivo biological activity. Surprisingly, removal of the 26- and 27-methyl groups from either the 2 alpha-methyl or 2-methylene-19-nor-1 alpha,25-dihydroxyvitamin D-3 reduced vitamin D receptor binding, HL-60 differentiation, and 25-hydroxylase transcription in vitro only slightly to moderately (compounds 6-13). However, these compounds were devoid of in vivo bone mobilization activity and had markedly reduced activity on intestinal calcium transport. The analogs 14-17 with a 2 beta-methyl substitution had little or no activity in vitro and in vivo as expected from previous work. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2013.01.001

文献信息

• Design, synthesis, and evaluation of hybrid vitamin D3 side chain analogues as hedgehog pathway inhibitors
  作者：Upasana Banerjee、Albert M. DeBerardinis、M. Kyle Hadden

  DOI：10.1016/j.bmc.2014.12.005

  日期：2015.2

  CD-ring side chain that afford enhancement of selectivity for Hh modulation thereby diminishing the detrimental effects of concomitant vitamin D receptor activation. In general, linear or moderately branched alkyl chains of five or six carbons were optimal for potent and selective inhibition of Hh signaling. Moreover, hybrid VD3 side chain derivative 20 demonstrated 4-fold improvement in Hh antagonistic

  维生素D3（VD3）是刺猬（Hh）信号级联反应的中度有效和非选择性抑制剂。先前的研究已经确定，VD3的CD环区域可作为Hh抑制药效团。随后，化合物3，酯连接的芳族A环和CD环衍生物被鉴定为改进的选择性Hh抑制剂。在本文中，我们报告了CD环侧链的修饰，该修饰可增强Hh调节的选择性，从而减少伴随的维生素D受体激活的有害作用。通常，具有5或6个碳原子的直链或中支链烷基链对于Hh信号的有效和选择性抑制是最佳的。此外，混合VD3侧链衍生物20与VD3相比，Hh拮抗活性提高了4倍（IC 50  = 1.1–1.6μM），而维生素D受体途径的规范激活使Hh信号选择性提高了1000倍以上。