(4aR,10aR)-7-hydroxy-4a-(1-propyl)-3,4,4a,9,10,10a-hexahydro-1H-phenanthren-2-one | 305824-49-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (4aR,10aR)-7-hydroxy-4a-(1-propyl)-3,4,4a,9,10,10a-hexahydro-1H-phenanthren-2-one
• 英文别名: (4aR,10aR)-7-hydroxy-4a-propyl-1,3,4,9,10,10a-hexahydrophenanthren-2-one
• CAS: 305824-49-1
• 化学式: C₁₇H₂₂O₂
• 分子量: 258.36
• InChiKey: QUCFOZYANMEGCO-CXAGYDPISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 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：

  (4aR,10aR)-7-hydroxy-4a-(1-propyl)-3,4,4a,9,10,10a-hexahydro-1H-phenanthren-2-one 、 丙炔 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.25h， 生成 [2R-(2α,4aα,10aβ)]-1,2,3,4,4a,9,10,10a-octahydro-4a-propyl-2-(1-propynyl)-2,7-phenanthrenediol
  参考文献：
  名称：

  Octahydrophenanthrene-2,7-diol Analogues as Dissociated Glucocorticoid Receptor Agonists: Discovery and Lead Exploration

  摘要：

  As exemplified by the lead compound 2, octahydrophenanthrene-2,7-diol analogues exhibit the profile of a pathway-selective or "dissociated" agonist of the glucocorticoid receptor (GR), retaining the potent activity that glucocorticoids have for transrepression (as measured by inhibition of IL-1 induced MMP-13 expression) but showing an attenuated capacity for transactivation (as measured in an MMTV luciferase reporter assay). With the guidance of a homology model of the GR ligand binding domain, structural modifications to 2 were carried out that were successful in replacing the allyl and propynyl side chains with groups likely to be more chemically stable and less likely to produce toxic metabolites. Key to success was the introduction of an additional hydroxyl group onto the tricyclic carbon framework of the series.

  DOI：

  10.1021/jm801512v
• 作为产物：
  描述：

  (4aS,10aR)-4a-allyl-7-hydroxy-3,4,4a,9,10,10a-hexahydro-1H-phenanthren-2-one 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以98%的产率得到(4aR,10aR)-7-hydroxy-4a-(1-propyl)-3,4,4a,9,10,10a-hexahydro-1H-phenanthren-2-one
  参考文献：
  名称：

  Octahydrophenanthrene-2,7-diol Analogues as Dissociated Glucocorticoid Receptor Agonists: Discovery and Lead Exploration

  摘要：

  As exemplified by the lead compound 2, octahydrophenanthrene-2,7-diol analogues exhibit the profile of a pathway-selective or "dissociated" agonist of the glucocorticoid receptor (GR), retaining the potent activity that glucocorticoids have for transrepression (as measured by inhibition of IL-1 induced MMP-13 expression) but showing an attenuated capacity for transactivation (as measured in an MMTV luciferase reporter assay). With the guidance of a homology model of the GR ligand binding domain, structural modifications to 2 were carried out that were successful in replacing the allyl and propynyl side chains with groups likely to be more chemically stable and less likely to produce toxic metabolites. Key to success was the introduction of an additional hydroxyl group onto the tricyclic carbon framework of the series.

  DOI：

  10.1021/jm801512v

文献信息

• Glucocorticoid receptor modulators
  申请人：Dow L. Robert

  公开号：US20070117805A1

  公开（公告）日：2007-05-24

  The present invention provides non-steroidal compounds of formula I which are selective modulators (i.e., agonists and antagonists) of a steroid receptor, specifically, the glucocorticoid receptor. The present invention also provides pharmaceutical compositions containing these compounds and methods for using these compounds to treat animals requiring glucocorticoid receptor agonist or antagonist therapy. Glucocorticoid receptor modulators are useful to the diseases, such as obesity, diabetes, inflammation and others as described below. The present invention also provides intermediates and processes for preparing these compounds.

  本发明提供公式I的非甾体化合物，它们是类固醇受体的选择性调节剂（即激动剂和拮抗剂），具体地，是糖皮质激素受体。本发明还提供含有这些化合物的药物组合物，并使用这些化合物治疗需要糖皮质激素受体激动剂或拮抗剂治疗的动物的方法。糖皮质激素受体调节剂对于肥胖症、糖尿病、炎症等疾病是有用的，如下所述。本发明还提供制备这些化合物的中间体和方法。
• US7713989B2
  申请人：——

  公开号：US7713989B2

  公开（公告）日：2010-05-11
• Octahydrophenanthrene-2,7-diol Analogues as Dissociated Glucocorticoid Receptor Agonists: Discovery and Lead Exploration
  作者：Ralph P. Robinson、Leonard Buckbinder、Amber I. Haugeto、Patricia A. McNiff、Michele L. Millham、Matthew R. Reese、Jean F. Schaefer、Yuriy A. Abramov、Jon Bordner、Yves A. Chantigny、Edward F. Kleinman、Ellen R. Laird、Bradley P. Morgan、John C. Murray、Eben D. Salter、Matthew D. Wessel、Sue A. Yocum

  DOI：10.1021/jm801512v

  日期：2009.3.26

  As exemplified by the lead compound 2, octahydrophenanthrene-2,7-diol analogues exhibit the profile of a pathway-selective or "dissociated" agonist of the glucocorticoid receptor (GR), retaining the potent activity that glucocorticoids have for transrepression (as measured by inhibition of IL-1 induced MMP-13 expression) but showing an attenuated capacity for transactivation (as measured in an MMTV luciferase reporter assay). With the guidance of a homology model of the GR ligand binding domain, structural modifications to 2 were carried out that were successful in replacing the allyl and propynyl side chains with groups likely to be more chemically stable and less likely to produce toxic metabolites. Key to success was the introduction of an additional hydroxyl group onto the tricyclic carbon framework of the series.