3'-(4-acetoxybutyl)-3,5-diiodo-O-methyl-N-(triflioroacetyl)-L-thyronine ethyl ester | 111088-12-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3'-(4-acetoxybutyl)-3,5-diiodo-O-methyl-N-(triflioroacetyl)-L-thyronine ethyl ester
• 英文别名: ethyl (2S)-3-[4-[3-(4-acetyloxybutyl)-4-methoxyphenoxy]-3,5-diiodophenyl]-2-[(2,2,2-trifluoroacetyl)amino]propanoate
• CAS: 111088-12-1
• 化学式: C₂₆H₂₈F₃I₂NO₇
• 分子量: 777.315
• InChiKey: YBXQDEXTZABRBM-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.74
• 重原子数：
  39.0
• 可旋转键数：
  13.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  100.16
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3'-(4-acetoxybutyl)-3,5-diiodo-O-methyl-N-(triflioroacetyl)-L-thyronine ethyl ester 在 三氯化铝 作用下， 以 二氯甲烷 、 乙硫醇 为溶剂， 反应 1.0h， 以86%的产率得到(2S)-3-[4-[3-(4-acetyloxybutyl)-4-hydroxyphenoxy]-3,5-diiodophenyl]-2-[(2,2,2-trifluoroacetyl)amino]propanoic acid
  参考文献：
  名称：

  Thyroid hormone analogs. Synthesis of 3'-substituted 3,5-diiodo-L-thyronines and quantitative structure-activity studies of in vitro and in vivo thyromimetic activities in rat liver and heart

  摘要：

  Twenty-nine novel 3'-substituted derivatives of the thyroid hormone 3,3',5-triiodo-L-thyronine (T3) have been synthesized by using established methods and by a new route involving manipulation of a 3'-formyl intermediate. In vitro hormone receptor binding (to intact nuclei) and in vivo thyromimetic activity (induction of mitochondrial 3-phosphoglycerate oxidoreductase, GPDH) were measured in rat liver and heart for these new analogues and for the 18 previously reported 3'-substituted 3,5-diiodo-L-thyronines. Analysis of the binding data using theoretical conformational and quantitative structure-affinity methods implies that the 3'-substituent recognition site on the thyroid hormone receptor is hydrophobic and limited in depth to the length of the natural iodo substituent, but has sufficient width to accommodate a phenyl or cyclohexyl group. Receptor binding is reduced by approximately 10-fold in 3'-acyl derivatives which form strong intramolecular acceptor hydrogen bonds with the adjacent 4'-hydroxyl. The compounds studied showed no differences in their relative affinities for heart and liver nuclei, suggesting that receptors in these tissues are similar. However, the relationships between thyromimetic activity (induction of GPDH) and nuclear binding showed some tissue differences. A high correlation between activity and binding is observed for full agonists in the heart, but an equally significant correlation for the liver data is only seen when 3'-substituent bulk (molar refractivity) is included in the analysis. These results suggest the possibility that differential tissue penetration or access to receptors may occur in vivo.

  DOI：

  10.1021/jm00396a008
• 作为产物：
  描述：

  5-(benzyloxy)-2-methoxybenzaldehyde 在 palladium on activated charcoal 二环己烷并-18-冠醚-6 、 硫酸 、 potassium tert-butylate 、 氢气 、 碘 、 甲基磺酰氯 、 potassium iodide 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 、 溶剂黄146 为溶剂， -7.0~25.0 ℃ 、275.79 kPa 条件下， 反应 2.67h， 生成 3'-(4-acetoxybutyl)-3,5-diiodo-O-methyl-N-(triflioroacetyl)-L-thyronine ethyl ester
  参考文献：
  名称：

  Thyroid hormone analogs. Synthesis of 3'-substituted 3,5-diiodo-L-thyronines and quantitative structure-activity studies of in vitro and in vivo thyromimetic activities in rat liver and heart

  摘要：

  Twenty-nine novel 3'-substituted derivatives of the thyroid hormone 3,3',5-triiodo-L-thyronine (T3) have been synthesized by using established methods and by a new route involving manipulation of a 3'-formyl intermediate. In vitro hormone receptor binding (to intact nuclei) and in vivo thyromimetic activity (induction of mitochondrial 3-phosphoglycerate oxidoreductase, GPDH) were measured in rat liver and heart for these new analogues and for the 18 previously reported 3'-substituted 3,5-diiodo-L-thyronines. Analysis of the binding data using theoretical conformational and quantitative structure-affinity methods implies that the 3'-substituent recognition site on the thyroid hormone receptor is hydrophobic and limited in depth to the length of the natural iodo substituent, but has sufficient width to accommodate a phenyl or cyclohexyl group. Receptor binding is reduced by approximately 10-fold in 3'-acyl derivatives which form strong intramolecular acceptor hydrogen bonds with the adjacent 4'-hydroxyl. The compounds studied showed no differences in their relative affinities for heart and liver nuclei, suggesting that receptors in these tissues are similar. However, the relationships between thyromimetic activity (induction of GPDH) and nuclear binding showed some tissue differences. A high correlation between activity and binding is observed for full agonists in the heart, but an equally significant correlation for the liver data is only seen when 3'-substituent bulk (molar refractivity) is included in the analysis. These results suggest the possibility that differential tissue penetration or access to receptors may occur in vivo.

  DOI：

  10.1021/jm00396a008

文献信息

• LEESON, PAUL D.;ELLIS, DAVID;EMMETT, JOHN C.;SHAH, VIRENDRA P.;SHOWELL, G+, J. MED. CHEM., 31,(1988) N 1, 37-54
  作者：LEESON, PAUL D.、ELLIS, DAVID、EMMETT, JOHN C.、SHAH, VIRENDRA P.、SHOWELL, G+

  DOI：——

  日期：——