2,6-二碘-4-[(2-甲基-1-苯并呋喃-3-基)甲基]苯酚 | 401917-61-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 中文名称: 2,6-二碘-4-[(2-甲基-1-苯并呋喃-3-基)甲基]苯酚
• 英文名称: 2-methyl-3-(3,5-diiodo-4-hydroxybenzyl)benzofuran
• 英文别名: 2,6-Diiodo-4-[(2-methyl-1-benzofuran-3-yl)methyl]phenol
• CAS: 401917-61-1
• 化学式: C₁₆H₁₂I₂O₂
• 分子量: 490.079
• InChiKey: ZHAMIXFCKGNYMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  33.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,6-二碘-4-[(2-甲基-1-苯并呋喃-3-基)甲基]苯酚 在 sodium hydroxide 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 {2,6-二碘-4-[(2-甲基-1-苯并呋喃-3-基)甲基]苯氧基}乙酸
  参考文献：
  名称：

  Synthesis and Preliminary Characterization of a Novel Antiarrhythmic Compound (KB130015) with an Improved Toxicity Profile Compared with Amiodarone

  摘要：

  Recent developments in antiarrhythmic therapy have indicated that the best approach to pharmacologically controlling supraventricular arrhythmias and life-threatening ventricular tachyarrhythmias is by prolonging cardiac repolarization rather than by blocking conduction. In this context, amiodarone has emerged as the most potent compound, but its universal use has been limited by its toxicity profile. There are data to suggest that an important component of amiodarones antiarrhythmic action might be mediated via inhibition of thyroid hormone action in the heart. Therefore, a new series of carboxymethoxybenzoyl and benzyl derivatives of benzofuran has been prepared and evaluated as thyroid hormone receptor antagonists. Within this series, 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran KB130015 (7) was found to reveal the most promising in vitro data. It inhibits the binding of I-125-T-3 to the human thyroid hormone receptors (hThR) alpha(1) and beta(1). T-3-Antagonism was confirmed in reporter cell assays employing CHOKl cells (Chinese hamster ovary cells) stably transfected with hThRalpha(1) or hThRbeta(1) and an alkaline phosphatase reporter gene downstream a thyroid response element. The derived IC50 values were 2.2 muM for hThRalpha(1) and 4.1 muM for hThRbeta(1). Compound 7 was selected for further characterization of chronic effects on ventricular papillary muscle by transmembrane electrophysiology after daily intraperitoneal injection of the ligand (40 mg/kg body weight) in guinea pigs. Compound 7 was found to prolong the action potential duration at 90% (APD(90)) repolarization time (219 +/- 22 ms, control: 186 +/- 9 ms, p < 0.01) without exhibiting any reverse-rate dependency of action in a manner similar to that of amiodarone. In general, preliminary tolerance experiments with 7 demonstrated an improved safety profile compared to that of amiodarone. In summary, 7 appears to be less toxic than amiodarone while maintaining its electrophysiologic properties consistent with antiarrhythmic activity. Its potential antiarrhythmic actions warrant further investigations.

  DOI：

  10.1021/jm001126+
• 作为产物：
  描述：

  (4-甲氧基苯基)(2-甲基-1-苯并呋喃-3-基)甲酮 在 吗啉 、 sodium tetrahydroborate 、 tetramethylammonium dichloroiodate 、 吡啶盐酸盐 、 zinc(II) iodide 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 5.25h， 生成 2,6-二碘-4-[(2-甲基-1-苯并呋喃-3-基)甲基]苯酚
  参考文献：
  名称：

  Synthesis and Preliminary Characterization of a Novel Antiarrhythmic Compound (KB130015) with an Improved Toxicity Profile Compared with Amiodarone

  摘要：

  Recent developments in antiarrhythmic therapy have indicated that the best approach to pharmacologically controlling supraventricular arrhythmias and life-threatening ventricular tachyarrhythmias is by prolonging cardiac repolarization rather than by blocking conduction. In this context, amiodarone has emerged as the most potent compound, but its universal use has been limited by its toxicity profile. There are data to suggest that an important component of amiodarones antiarrhythmic action might be mediated via inhibition of thyroid hormone action in the heart. Therefore, a new series of carboxymethoxybenzoyl and benzyl derivatives of benzofuran has been prepared and evaluated as thyroid hormone receptor antagonists. Within this series, 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran KB130015 (7) was found to reveal the most promising in vitro data. It inhibits the binding of I-125-T-3 to the human thyroid hormone receptors (hThR) alpha(1) and beta(1). T-3-Antagonism was confirmed in reporter cell assays employing CHOKl cells (Chinese hamster ovary cells) stably transfected with hThRalpha(1) or hThRbeta(1) and an alkaline phosphatase reporter gene downstream a thyroid response element. The derived IC50 values were 2.2 muM for hThRalpha(1) and 4.1 muM for hThRbeta(1). Compound 7 was selected for further characterization of chronic effects on ventricular papillary muscle by transmembrane electrophysiology after daily intraperitoneal injection of the ligand (40 mg/kg body weight) in guinea pigs. Compound 7 was found to prolong the action potential duration at 90% (APD(90)) repolarization time (219 +/- 22 ms, control: 186 +/- 9 ms, p < 0.01) without exhibiting any reverse-rate dependency of action in a manner similar to that of amiodarone. In general, preliminary tolerance experiments with 7 demonstrated an improved safety profile compared to that of amiodarone. In summary, 7 appears to be less toxic than amiodarone while maintaining its electrophysiologic properties consistent with antiarrhythmic activity. Its potential antiarrhythmic actions warrant further investigations.

  DOI：

  10.1021/jm001126+

文献信息

• Synthesis and Preliminary Characterization of a Novel Antiarrhythmic Compound (KB130015) with an Improved Toxicity Profile Compared with Amiodarone
  作者：Bo Carlsson、B. N. Singh、Marcel Temciuc、Stefan Nilsson、Yi-Lin Li、Charlotta Mellin、Johan Malm

  DOI：10.1021/jm001126+

  日期：2002.1.1

  Recent developments in antiarrhythmic therapy have indicated that the best approach to pharmacologically controlling supraventricular arrhythmias and life-threatening ventricular tachyarrhythmias is by prolonging cardiac repolarization rather than by blocking conduction. In this context, amiodarone has emerged as the most potent compound, but its universal use has been limited by its toxicity profile. There are data to suggest that an important component of amiodarones antiarrhythmic action might be mediated via inhibition of thyroid hormone action in the heart. Therefore, a new series of carboxymethoxybenzoyl and benzyl derivatives of benzofuran has been prepared and evaluated as thyroid hormone receptor antagonists. Within this series, 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran KB130015 (7) was found to reveal the most promising in vitro data. It inhibits the binding of I-125-T-3 to the human thyroid hormone receptors (hThR) alpha(1) and beta(1). T-3-Antagonism was confirmed in reporter cell assays employing CHOKl cells (Chinese hamster ovary cells) stably transfected with hThRalpha(1) or hThRbeta(1) and an alkaline phosphatase reporter gene downstream a thyroid response element. The derived IC50 values were 2.2 muM for hThRalpha(1) and 4.1 muM for hThRbeta(1). Compound 7 was selected for further characterization of chronic effects on ventricular papillary muscle by transmembrane electrophysiology after daily intraperitoneal injection of the ligand (40 mg/kg body weight) in guinea pigs. Compound 7 was found to prolong the action potential duration at 90% (APD(90)) repolarization time (219 +/- 22 ms, control: 186 +/- 9 ms, p < 0.01) without exhibiting any reverse-rate dependency of action in a manner similar to that of amiodarone. In general, preliminary tolerance experiments with 7 demonstrated an improved safety profile compared to that of amiodarone. In summary, 7 appears to be less toxic than amiodarone while maintaining its electrophysiologic properties consistent with antiarrhythmic activity. Its potential antiarrhythmic actions warrant further investigations.