[5'-(4-tert-butoxycarbonylmethoxy-2,6-dimethylbenzyl)-3'-isopropyl-2'-methoxymethoxybiphenyl-4-ylamino]acetic acid tert-butyl ester | 417872-26-5

• 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: [5'-(4-tert-butoxycarbonylmethoxy-2,6-dimethylbenzyl)-3'-isopropyl-2'-methoxymethoxybiphenyl-4-ylamino]acetic acid tert-butyl ester
• CAS: 417872-26-5
• 化学式: C₃₈H₅₁NO₇
• 分子量: 633.825
• InChiKey: PJGDLZZNYVKZEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.14
• 重原子数：
  46.0
• 可旋转键数：
  13.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  92.32
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  [5'-(4-tert-butoxycarbonylmethoxy-2,6-dimethylbenzyl)-3'-isopropyl-2'-methoxymethoxybiphenyl-4-ylamino]acetic acid tert-butyl ester 在 盐酸 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 2.0h， 生成 [5'-(4-tert-Butoxycarbonylmethoxy-2,6-dimethyl-benzyl)-2'-hydroxy-3'-isopropyl-biphenyl-4-ylamino]-acetic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and biological activity of novel thyroid hormone analogues: 5′-aryl substituted GC-1 derivatives

  摘要：

  Compounds that selectively modulate thyroid hormone action by functioning as isoform-selective agonists or antagonists of the thyroid hormone receptors (TRs) might be useful for medical therapy. We have synthesized a high affinity TR beta -selective agonist ligand, GC-1,(1) and optimized the synthetic route to provide large quantities of the compound for animal testing.(2) In addition to an improvement in efficiency, the new synthetic route offers a chemical handle for selective modification of the thyronine skeleton to produce new derivatives. To explore the effect of GC-1 core structure modifications on binding to TR isoforms and activation of transcription, we developed here an efficient and flexible route to a new series of 5'-substituted GC-1 analogues. This route relies on ortho lithiation and in situ boration of the biarylmethane compound 1, a key intermediate of the revised GC-1 synthesis,(2) followed by Suzuki cross-coupling. Using this approach we prepared and tested eleven 5'-substituted GC-1 analogues. Substitution at the 5'-position decreased binding affinity, but retained TR beta -selectivity for most of the compounds. Transactivation assays reveal that most of these compounds function as thyroid hormone agonists, but one compound (GC-14) antagonizes the response to thyroid hormone. (C). 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00284-x
• 作为产物：
  描述：

  {5'-[2,6-dimethyl-4-(triisopropylsilanyloxy)benzyl]-3-isopropyl-2-methoxymethoxyphenyl}boronic acid 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 四丁基氟化铵 、 铁粉 、 caesium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 10.5h， 生成 [5'-(4-tert-butoxycarbonylmethoxy-2,6-dimethylbenzyl)-3'-isopropyl-2'-methoxymethoxybiphenyl-4-ylamino]acetic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and biological activity of novel thyroid hormone analogues: 5′-aryl substituted GC-1 derivatives

  摘要：

  Compounds that selectively modulate thyroid hormone action by functioning as isoform-selective agonists or antagonists of the thyroid hormone receptors (TRs) might be useful for medical therapy. We have synthesized a high affinity TR beta -selective agonist ligand, GC-1,(1) and optimized the synthetic route to provide large quantities of the compound for animal testing.(2) In addition to an improvement in efficiency, the new synthetic route offers a chemical handle for selective modification of the thyronine skeleton to produce new derivatives. To explore the effect of GC-1 core structure modifications on binding to TR isoforms and activation of transcription, we developed here an efficient and flexible route to a new series of 5'-substituted GC-1 analogues. This route relies on ortho lithiation and in situ boration of the biarylmethane compound 1, a key intermediate of the revised GC-1 synthesis,(2) followed by Suzuki cross-coupling. Using this approach we prepared and tested eleven 5'-substituted GC-1 analogues. Substitution at the 5'-position decreased binding affinity, but retained TR beta -selectivity for most of the compounds. Transactivation assays reveal that most of these compounds function as thyroid hormone agonists, but one compound (GC-14) antagonizes the response to thyroid hormone. (C). 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00284-x