3,5-dibromo-4-(4-hydroxy-5-chloro-3-isopropylphenoxy)phenylacetic acid | 948030-17-9

• 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: 3,5-dibromo-4-(4-hydroxy-5-chloro-3-isopropylphenoxy)phenylacetic acid
• 英文别名: 3,5-dibromo-4-(3-chloro-4-hydroxy-5-isopropylphenoxy)phenylacetic acid；2-[3,5-dibromo-4-(3-chloro-4-hydroxy-5-propan-2-ylphenoxy)phenyl]acetic acid
• CAS: 948030-17-9
• 化学式: C₁₇H₁₅Br₂ClO₄
• 分子量: 478.565
• InChiKey: WQLPQOCEFTVLQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,5-dibromo-4-(4-hydroxy-5-chloro-3-isopropylphenoxy)phenylacetic acid 在 lithium hydroxide 、 TEA 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (2S)-2-(1-{3,5-dibromo-4-[3-chloro-4-hydroxy-5-(propan-2-yl)phenoxy]phenyl}acetamido)-3-methylbutanoic acid
  参考文献：
  名称：

  Thyroid receptor ligands. Part 8: Thyromimetics derived from N-acylated-α-amino acid derivatives displaying modulated pharmacological selectivity compared with KB-141

  摘要：

  Based on the scaffold of the pharmacologically selective thyromimetic 2b, structurally a close analog to KB-141 (2a), a number of novel N-acylated-alpha-amino acid derivatives were synthesized and tested in a TR radioligand binding assay as well as in a reporter cell assay. On the basis of TR beta(1)-isoform selectivity and affinity, as well as affinity to the reporter cell assay, 3d was selected for further studies in the cholesterol-fed rat model. In this model 3d revealed an improved therapeutic window between cholesterol and TSH lowering but decreased margins versus tachycardia compared with 2a. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.049
• 作为产物：
  描述：

  KB-131092 在 benzyltrimethylazanium tetrachloro-λ³-iodanuide 、 溶剂黄146 作用下， 反应 1.0h， 以50%的产率得到3,5-dibromo-4-(4-hydroxy-5-chloro-3-isopropylphenoxy)phenylacetic acid
  参考文献：
  名称：

  Thyroid receptor ligands. Part 8: Thyromimetics derived from N-acylated-α-amino acid derivatives displaying modulated pharmacological selectivity compared with KB-141

  摘要：

  Based on the scaffold of the pharmacologically selective thyromimetic 2b, structurally a close analog to KB-141 (2a), a number of novel N-acylated-alpha-amino acid derivatives were synthesized and tested in a TR radioligand binding assay as well as in a reporter cell assay. On the basis of TR beta(1)-isoform selectivity and affinity, as well as affinity to the reporter cell assay, 3d was selected for further studies in the cholesterol-fed rat model. In this model 3d revealed an improved therapeutic window between cholesterol and TSH lowering but decreased margins versus tachycardia compared with 2a. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.049

文献信息

• Novel compounds
  申请人：Garg Neeraj

  公开号：US20060135614A1

  公开（公告）日：2006-06-22

  This invention relates to novel compounds, which are thyroid receptor ligands, and to methods of preparing such compounds. In addition, a method is provided for preventing, inhibiting or treating diseases or disorders associated with metabolism dysfunction or which are dependent upon the expression of a T3 regulated gene, wherein a compound as described herein is administered in a therapeutically effective amount.

  本发明涉及一种新型化合物，它们是甲状腺受体配体，并提供了制备这些化合物的方法。此外，本发明还提供了一种预防、抑制或治疗与代谢功能紊乱相关的疾病或随着T3调节基因表达而产生的疾病或障碍的方法，其中所述的化合物以治疗有效量的方式给予。
• Benzamide derivatives as thyroid receptor ligands
  申请人：Karo Bio AB

  公开号：US07153997B2

  公开（公告）日：2006-12-26

  This invention relates to novel compounds, which are thyroid receptor ligands, and to methods of preparing such compounds. In addition, a method is provided for preventing, inhibiting or treating diseases or disorders associated with metabolism dysfunction or which are dependent upon the expression of a T3 regulated gene, wherein a compound as described herein is administered in a therapeutically effective amount.

  本发明涉及新型化合物，它们是甲状腺受体配体，并涉及制备这种化合物的方法。此外，提供了一种方法，用于预防、抑制或治疗与代谢功能障碍或依赖于T3调节基因表达的疾病或疾病，其中以本文所述的化合物以治疗有效量的方式给予。
• [EN] BENZAMIDE OR PHENYLACETAMIDE DERIVATIVES USEFUL AS THYROID RECEPTOR LIGANDS<br/>[FR] NOUVEAUX COMPOSES
  申请人：KAROBIO AB

  公开号：WO2004007430A3

  公开（公告）日：2004-02-19
• BENZAMIDE OR PHENYLACETAMIDE DERIVATIVES USEFUL AS THYROID RECEPTOR LIGANDS
  申请人：KARO BIO AB

  公开号：EP1537073A2

  公开（公告）日：2005-06-08
• US7153997B2
  申请人：——

  公开号：US7153997B2

  公开（公告）日：2006-12-26