(E/Z)-3-bromo-2-chloro-6-(prop-1-enyl)phenol | 1014625-99-0

• 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: (E/Z)-3-bromo-2-chloro-6-(prop-1-enyl)phenol
• 英文别名: 3-bromo-2-chloro-6-(prop-1-enyl)phenol；3-bromo-2-chloro-6-prop-1-enylphenol
• CAS: 1014625-99-0
• 化学式: C₉H₈BrClO
• 分子量: 247.519
• InChiKey: QSNIVCJORDXDJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.84
• 重原子数：
  12.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 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：

  (E/Z)-3-bromo-2-chloro-6-(prop-1-enyl)phenol 、 3-氟-4-甲氧基苯硼酸 在 palladium diacetate 、 sodium carbonate 、 三苯基膦 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 16.0h， 生成 (Z)-2-chloro-3-(3-fluoro-4-methoxyphenyl)-6-(prop-1-enyl)phenol 、 (E)-2-chloro-3-(3-fluoro-4-methoxyphenyl)-6-(prop-1-enyl)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

• Monoaryl-Substituted Salicylaldoximes as Ligands for Estrogen Receptor β
  作者：Filippo Minutolo、Rosalba Bellini、Simone Bertini、Isabella Carboni、Annalina Lapucci、Letizia Pistolesi、Giovanni Prota、Simona Rapposelli、Francesca Solati、Tiziano Tuccinardi、Adriano Martinelli、Fabio Stossi、Kathryn E. Carlson、Benita S. Katzenellenbogen、John A. Katzenellenbogen、Marco Macchia

  DOI：10.1021/jm701396g

  日期：2008.3.13

  Salicylaldoximes possess a hydrogen-bonded pseudocyclic A' ring in place of the typical phenolic A ring that is characteristic of most estrogen receptor (ER) ligands. Monoaryl-substituted salicylaldoximes were obtained by replacing the phenol moiety (ring A) of the ER beta pharmacophore with the pseudocycle A' ring, which has previously been shown to behave as a bioequivalent of phenols in nonselective ER ligands. In this series, small substituents (CH(3), CN, Cl) were introduced into the central phenyl scaffold. An efficient sequential halogen-selective double cross-coupling reaction was developed for the synthesis of the methylsubstituted ER ligand. The measured ER beta affinity proved to be very sensitive to the effect of central core substituents. The binding affinities of the compounds herein reported were in good agreement with the results of computational docking analysis. The chloro-substituted derivative showed the highest beta affinity and selectivity, and it also proved to be an ER beta partial agonist with an EC(50) of 11 nM.