2-氯-3'-氟-3,4'-二羟基-[1,1-联苯]-4-羧甲醛肟 | 1111084-78-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-氯-3'-氟-3,4'-二羟基-[1,1-联苯]-4-羧甲醛肟
• 英文名称: (E)-3-chloro-4-(3-fluoro-4-hydroxyphenyl)salicylaldoxime
• 英文别名: 2-chloro-3-(3-fluoro-4-hydroxyphenyl)-6-[(E)-hydroxyiminomethyl]phenol
• CAS: 1111084-78-6
• 化学式: C₁₃H₉ClFNO₃
• 分子量: 281.671
• InChiKey: LRRMQNGSYOUANY-OMCISZLKSA-N

物化性质

• 沸点：
  410.8±45.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)
• 溶解度：
  在 DMSO 中溶解度为 100 mM，在乙醇中溶解度为 100 mM

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  73
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-chloro-4-(3-fluoro-4-hydroxyphenyl)salicylaldehyde 在 盐酸羟胺 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 以80%的产率得到2-氯-3'-氟-3,4'-二羟基-[1,1-联苯]-4-羧甲醛肟
  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

• [EN] INDUCTION OF ESTROGEN RECEPTOR BETA BY CHOLESTEROL BIOSYNTHESIS INHIBITORS AND METHODS OF TREATMENT OF CANCER<br/>[FR] INDUCTION DU RÉCEPTEUR BÊTA DES OESTROGÈNES PAR DES INHIBITEURS DE LA BIOSYNTHÈSE DU CHOLESTÉROL ET MÉTHODES DE TRAITEMENT DU CANCER
  申请人：UNIV MISSOURI

  公开号：WO2014004854A1

  公开（公告）日：2014-01-03

  Disclosed herein are methods and compositions related to the discovery that cholesterol inhibitors induce the anti-proliferative protein, estrogen receptor beta (ERβ), in both ERα- positive and ERα-negative breast cancer cell lines, including triple negative cells.

  本文揭示了与发现胆固醇抑制剂在ERα阳性和ERα阴性乳腺癌细胞系，包括三阴性细胞中诱导抗增殖蛋白雌激素受体β（ERβ）相关的方法和组合物。
• INDUCTION OF ESTROGEN RECEPTOR BETA BY CHOLESTEROL BIOSYNTHESIS INHIBITORS AND METHODS OF TREATMENT OF CANCER
  申请人：The Curators Of The University Of Missouri

  公开号：EP2866810A1

  公开（公告）日：2015-05-06
• 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.