L-methyl-N-[3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenylacetyl]alanine | 280777-32-4

• 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-isopropylphenoxy)phenylacetyl]alanine
• 英文别名: methyl (2S)-2-[[2-[3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetyl]amino]propanoate
• CAS: 280777-32-4
• 化学式: C₂₁H₂₃Br₂NO₅
• 分子量: 529.225
• InChiKey: GHLOFBALFIYQLP-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 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-isopropylphenoxy)phenylacetyl]alanine 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 L-N-[3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenylacetyl]alanine
  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：

  L-丙氨酸甲酯盐酸盐 、 KB-131092 在 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 二氯甲烷 为溶剂， 生成 L-methyl-N-[3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenylacetyl]alanine
  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

• 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.