6-acetyl-2-chloro-3-(4-hydroxyphenyl)phenol | 1111084-97-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-acetyl-2-chloro-3-(4-hydroxyphenyl)phenol
• 英文别名: 1-[3-Chloro-2-hydroxy-4-(4-hydroxyphenyl)phenyl]ethanone
• CAS: 1111084-97-9
• 化学式: C₁₄H₁₁ClO₃
• 分子量: 262.693
• InChiKey: WBVVBMKUZIGMAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-acetyl-2-chloro-3-(4-hydroxyphenyl)phenol 在 盐酸羟胺 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 以84%的产率得到(E)-1-(3-chloro-2-hydroxy-4-(4-hydroxyphenyl)phenyl)ethanone oxime
  参考文献：
  名称：

  Structural Evolutions of Salicylaldoximes as Selective Agonists for Estrogen Receptor β

  摘要：

  The bioisosteric replacement of the phenol ring, a signature functional group of most estrogen receptor (ER) ligands, with a hydrogen-bonded pseudocyclic ring, led to the development of a novel class of nonsteroidal ER-ligands based on a salicylaldoxime template. A series of structural modifications were applied to selected molecules belonging to the monoaryl-salicylaldoxime chemical class in an attempt to improve further their ER beta-selective receptor affinity and agonist properties. Among several modifications, the best results were obtained by the simultaneous introduction of a meta-fluorine atom into the para-hydroxyphenyl substituent present in the 4-position of salicylaldoxime, together with the insertion of a chloro group in the 3-position of the central scaffold. The resulting compound showed the best affinity (K-i = 7.1 nM) and selectivity for ER beta over ER alpha. Moreover, in transcription assays, it proved to be a selective and potent ER beta-full agonist with an EC50 of 4.8 nM.

  DOI：

  10.1021/jm801458t
• 作为产物：
  描述：

  1-(2-chloro-3-hydroxy-4’-methoxy-[1,1’-biphenyl]-4-yl)ethanone 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以77%的产率得到6-acetyl-2-chloro-3-(4-hydroxyphenyl)phenol
  参考文献：
  名称：

  Structural Evolutions of Salicylaldoximes as Selective Agonists for Estrogen Receptor β

  摘要：

  The bioisosteric replacement of the phenol ring, a signature functional group of most estrogen receptor (ER) ligands, with a hydrogen-bonded pseudocyclic ring, led to the development of a novel class of nonsteroidal ER-ligands based on a salicylaldoxime template. A series of structural modifications were applied to selected molecules belonging to the monoaryl-salicylaldoxime chemical class in an attempt to improve further their ER beta-selective receptor affinity and agonist properties. Among several modifications, the best results were obtained by the simultaneous introduction of a meta-fluorine atom into the para-hydroxyphenyl substituent present in the 4-position of salicylaldoxime, together with the insertion of a chloro group in the 3-position of the central scaffold. The resulting compound showed the best affinity (K-i = 7.1 nM) and selectivity for ER beta over ER alpha. Moreover, in transcription assays, it proved to be a selective and potent ER beta-full agonist with an EC50 of 4.8 nM.

  DOI：

  10.1021/jm801458t

文献信息

• Structural Evolutions of Salicylaldoximes as Selective Agonists for Estrogen Receptor β
  作者：Filippo Minutolo、Simone Bertini、Carlotta Granchi、Teresa Marchitiello、Giovanni Prota、Simona Rapposelli、Tiziano Tuccinardi、Adriano Martinelli、Jillian R. Gunther、Kathryn E. Carlson、John A. Katzenellenbogen、Marco Macchia

  DOI：10.1021/jm801458t

  日期：2009.2.12

  The bioisosteric replacement of the phenol ring, a signature functional group of most estrogen receptor (ER) ligands, with a hydrogen-bonded pseudocyclic ring, led to the development of a novel class of nonsteroidal ER-ligands based on a salicylaldoxime template. A series of structural modifications were applied to selected molecules belonging to the monoaryl-salicylaldoxime chemical class in an attempt to improve further their ER beta-selective receptor affinity and agonist properties. Among several modifications, the best results were obtained by the simultaneous introduction of a meta-fluorine atom into the para-hydroxyphenyl substituent present in the 4-position of salicylaldoxime, together with the insertion of a chloro group in the 3-position of the central scaffold. The resulting compound showed the best affinity (K-i = 7.1 nM) and selectivity for ER beta over ER alpha. Moreover, in transcription assays, it proved to be a selective and potent ER beta-full agonist with an EC50 of 4.8 nM.