L-methyl-N-[3,5-dibromo-4-(4-hydroxy-3-isopropyl-5-methylphenoxy)phenylacetyl]valinate | 649725-52-0

• 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: L-methyl-N-[3,5-dibromo-4-(4-hydroxy-3-isopropyl-5-methylphenoxy)phenylacetyl]valinate
• 英文别名: methyl (2S)-2-[[2-[3,5-dibromo-4-(4-hydroxy-3-methyl-5-propan-2-ylphenoxy)phenyl]acetyl]amino]-3-methylbutanoate
• CAS: 649725-52-0
• 化学式: C₂₄H₂₉Br₂NO₅
• 分子量: 571.306
• InChiKey: CYDZUDHMACDGGS-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  L-methyl-N-[3,5-dibromo-4-(4-hydroxy-3-isopropyl-5-methylphenoxy)phenylacetyl]valinate 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以140 mg的产率得到L-N-[3,5-dibromo-4-(4-hydroxy-3-isopropyl-5-methylphenoxy)phenylacetyl]valine
  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：

  methyl 3,5-dibromo-4-(4-hydroxy-5-formyl-3-isopropylphenoxy)phenyl acetate 在 氢氧化钾 、 TEA 、 1-羟基苯并三唑 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 乙二醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.25h， 生成 L-methyl-N-[3,5-dibromo-4-(4-hydroxy-3-isopropyl-5-methylphenoxy)phenylacetyl]valinate
  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：KARO BIO AB

  公开号：EP1862450A2

  公开（公告）日：2007-12-05

  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.

  本发明涉及作为甲状腺受体配体的新型化合物以及制备此类化合物的方法。此外，本发明还提供了一种用于预防、抑制或治疗与代谢功能障碍相关的疾病或失调，或依赖于 T3 调控基因表达的疾病或失调的方法，其中所述化合物以治疗有效量给药。
• [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
• Thyroid receptor ligands. Part 8: Thyromimetics derived from N-acylated-α-amino acid derivatives displaying modulated pharmacological selectivity compared with KB-141
  作者：Neeraj Garg、Yi-Lin Li、Ana Maria Garcia Collazo、Chris Litten、Denis E. Ryono、Minsheng Zhang、Yolanda Caringal、Robert P. Brigance、Wei Meng、William N. Washburn、Peter Agback、Karin Mellström、Stefan Rehnmark、Mahmoud Rahimi-Ghadim、Thomas Norin、Marlena Grynfarb、Johnny Sandberg、Gary Grover、Johan Malm

  DOI：10.1016/j.bmcl.2007.05.049

  日期：2007.8

  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.