(R)-3-(4-bromophenoxy)propane-1,2-diol | 1186623-24-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (R)-3-(4-bromophenoxy)propane-1,2-diol
• 英文别名: (2R)-3-(4-bromophenoxy)propane-1,2-diol
• CAS: 1186623-24-4
• 化学式: C₉H₁₁BrO₃
• 分子量: 247.089
• InChiKey: FZGZDDRZAZBANV-MRVPVSSYSA-N

物化性质

• 沸点：
  390.7±27.0 °C(Predicted)
• 密度：
  1.563±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-3-(4-bromophenoxy)propane-1,2-diol 在 tris-(dibenzylideneacetone)dipalladium(0) 、 四丁基溴化铵 、 potassium acetate 、 sodium hydroxide 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 2-甲基四氢呋喃 、 水 为溶剂， 生成 (R)-2-(4-((1,4-dioxan-2-yl)methoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
  参考文献：
  名称：

  实现十克级大环 MCL-1 抑制剂 ABBV-467 的合成

  摘要：

  ABBV-467 是一种高效、选择性的 MCL-1 抑制剂，已进入治疗多发性骨髓瘤的 I 期临床试验。由于其尺寸大且结构复杂，ABBV-467 是一个具有挑战性的合成靶标。在此，我们描述了十克规模的 ABBV-467 的合成，这使得临床前表征成为可能。该策略是收敛和立体选择性的，以受阻联芳基交叉偶联、对映选择性氢化和通过 C-O 键形成的构象预组织大环化为关键步骤。

  DOI：

  10.1021/acs.joc.3c00939
• 作为产物：
  描述：

  4-溴苯酚 、 (R)-缩水甘油 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以88%的产率得到(R)-3-(4-bromophenoxy)propane-1,2-diol
  参考文献：
  名称：

  Synthesis of novel ketoconazole derivatives as inhibitors of the human Pregnane X Receptor (PXR; NR1I2; also termed SXR, PAR)

  摘要：

  PXR, pregnane X receptor, in its activated state, is a validated target for controlling certain drug-drug interactions in humans. In this context, there is a paucity of inhibitors directed toward activated PXR. Using prior observations with ketoconazole as a PXR inhibitor, the target compound 3 was synthesized from (s)-glycidol with overall 56% yield. (+)-Glycidol was reacted with 4-bromophenol and potassium carbonate in DMF to yield the ring opened compound 6. This was then heated to reflux in benzene along with 2', 4'-difluoroacetophenone and catalytic amount of para-toluene sulfonic acid to yield 8. The resultant acetal 8 was then functionalized using Palladium chemistry to yield the target compound 3. The activity of the compound was compared with ketoconazole and UCL2158H. However, in contrast with ketoconazole (IC50 similar to 0.020 mu M; similar to 100% inhibition), 3 has negligible effects on inhibition of microsomal CYP450 (maximum similar to 20% inhibition) at concentrations > 40 mu M. In vitro, micromolar concentration of ketoconazole is toxic to passaged human cell lines, while 3 does not exhibit cytotoxicity up to concentrations similar to 100 mu M(viability > 85%). This is the first demonstration of a chemical analog of a PXR inhibitor that retains activity against activated PXR. Furthermore, in contrast with ketoconazole, 3 is less toxic in human cell lines and has negligible CYP450 activity. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.06.018

文献信息

• Bacillus alcalophilus MTCC10234 catalyzed enantioselective kinetic resolution of aryl glycidyl ethers
  作者：Neeraj Bala、Swapandeep Singh Chimni、Harvinder Singh Saini、Bhupinder Singh Chadha

  DOI：10.1016/j.molcatb.2009.12.019

  日期：2010.5

  The phenyl glycidyl ether derivatives have been kinetically resolved with the growing cells of Bacillus alcalophilus MTCC10234 yielding (S)-epoxides with up to >99% ee and (R)-diols with up to 89% ee. The enantiomeric ratio (E) of up to 67 has been obtained for biohydrolysis process. The effect of different substituents of phenyl glycidyl ether on the biocatalytic efficiency of B. alcalophilus MTCC10234

  苯缩水甘油醚衍生物已经与嗜碱芽孢杆菌MTCC10234的生长细胞动力学分离，产生了（S）-环氧化合物，其ee含量高达> 99％，（R）-二醇的ee含量高达89％。对于生物水解过程，已获得高达67的对映体比率（E）。苯基缩水甘油基醚的不同取代基对嗜酸芽孢杆菌MTCC10234的生物催化效率的影响表明，甲基和氯取代的芳基缩水甘油基醚衍生物较为可取，而硝基衍生物的转化速度较慢。将含有在两个邻位均具有甲基的大体积芳基的2，6-二甲基苯基缩水甘油醚用N-甲基-N-二甲基苯甲酸酯进行拆分。E  = 39。
• KETOCONAZOLE-DERIVATIVE ANTAGONIST OF HUMAN PREGNANE X RECEPTOR AND USES THEREOF
  申请人：Mani Sridhar

  公开号：US20110105522A1

  公开（公告）日：2011-05-05

  The application discloses ketoconazole derivatives that are antagonists of the human pregnane X receptor (PXR), methods of preparing the derivatives, uses of the derivatives with drug therapy, and methods of inhibiting tumor cell proliferation and multidrug resistance using inhibitors of PXR.
• US8669260B2
  申请人：——

  公开号：US8669260B2

  公开（公告）日：2014-03-11
• [EN] KETOCONAZOLE-DERIVATIVE ANTAGONISTS OF HUMAN PREGNANE X RECEPTOR AND USES THEREOF<br/>[FR] ANTAGONISTES DE DÉRIVÉS DE KÉTOCONAZOLE DU RÉCEPTEUR X DE PRÉGNANE HUMAIN ET LEURS UTILISATIONS
  申请人：EINSTEIN COLL MED

  公开号：WO2009110955A2

  公开（公告）日：2009-09-11

  The application discloses ketoconazole derivatives that are antagonists of the human pregnane X receptor (PXR), methods of preparing the derivatives, uses of the derivatives with drug therapy, and methods of inhibiting tumor cell proliferation and multidrug resistance using inhibitors of PXR.
• Synthesis of novel ketoconazole derivatives as inhibitors of the human Pregnane X Receptor (PXR; NR1I2; also termed SXR, PAR)
  作者：Bhaskar C. Das、Ankanahlli V. Madhukumar、Jaime Anguiano、Sean Kim、Michael Sinz、Tatyana A. Zvyaga、Eoin C. Power、C. Robin Ganellin、Sridhar Mani

  DOI：10.1016/j.bmcl.2008.06.018

  日期：2008.7

  PXR, pregnane X receptor, in its activated state, is a validated target for controlling certain drug-drug interactions in humans. In this context, there is a paucity of inhibitors directed toward activated PXR. Using prior observations with ketoconazole as a PXR inhibitor, the target compound 3 was synthesized from (s)-glycidol with overall 56% yield. (+)-Glycidol was reacted with 4-bromophenol and potassium carbonate in DMF to yield the ring opened compound 6. This was then heated to reflux in benzene along with 2', 4'-difluoroacetophenone and catalytic amount of para-toluene sulfonic acid to yield 8. The resultant acetal 8 was then functionalized using Palladium chemistry to yield the target compound 3. The activity of the compound was compared with ketoconazole and UCL2158H. However, in contrast with ketoconazole (IC50 similar to 0.020 mu M; similar to 100% inhibition), 3 has negligible effects on inhibition of microsomal CYP450 (maximum similar to 20% inhibition) at concentrations > 40 mu M. In vitro, micromolar concentration of ketoconazole is toxic to passaged human cell lines, while 3 does not exhibit cytotoxicity up to concentrations similar to 100 mu M(viability > 85%). This is the first demonstration of a chemical analog of a PXR inhibitor that retains activity against activated PXR. Furthermore, in contrast with ketoconazole, 3 is less toxic in human cell lines and has negligible CYP450 activity. (c) 2008 Elsevier Ltd. All rights reserved.