(4-羟基苯基)(2-甲基-1-苯并呋喃-3-基)甲酮 | 52490-47-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (4-羟基苯基)(2-甲基-1-苯并呋喃-3-基)甲酮
• 英文名称: 2-methyl-3-(4'-hydroxybenzoyl)benzofuran
• 英文别名: 2-methyl-3-(4-hydroxybenzoyl)benzofuran；(4-hydroxy-phenyl)-(2-methyl-benzofuran-3-yl)-methanone；2-methyl-3(4-hydroxybenzoyl)benzofuran；2-Methyl-3-<4-hydroxy-benzoyl>-benzofuran；(4-Hydroxyphenyl)(2-methylbenzofuran-3-yl)methanone；(4-hydroxyphenyl)-(2-methyl-1-benzofuran-3-yl)methanone
• CAS: 52490-47-8
• 化学式: C₁₆H₁₂O₃
• 分子量: 252.269
• InChiKey: BCQDWIKXULTIHQ-UHFFFAOYSA-N

物化性质

• 沸点：
  414.8±35.0 °C(Predicted)
• 密度：
  1.266±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  50.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  (4-羟基苯基)(2-甲基-1-苯并呋喃-3-基)甲酮 在 ammonium hydroxide 、 碘 、 potassium iodide 作用下， 反应 48.0h， 以3.2 g的产率得到(4-羟基-3,5-二碘苯基)(2-甲基-1-苯并呋喃-3-基)甲酮
  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 吡啶盐酸盐 作用下， 反应 0.5h， 生成 (4-羟基苯基)(2-甲基-1-苯并呋喃-3-基)甲酮
  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

• 一种2-甲基-3-苯甲酰基苯并呋喃衍生物的制 备方法
  申请人：江南大学

  公开号：CN108484546B

  公开（公告）日：2019-11-08

  本发明公开了一种2‑甲基‑3‑苯甲酰基苯并呋喃衍生物的制备方法，该方法以1‑(苯基乙炔基)‑2‑(乙烯氧基)苯类取代物为原料，FeCl2为催化剂，Phen为配体，PMHS为还原剂，乙醇、异丙醇、正丁醇或叔丁醇为溶剂，在氧气气氛下，反应温度为60℃，反应12h，合成目标产物，该合成方法简单，条件温和，收率较高，具有良好的应用前景。
• [EN] RECEPTOR LIGANDS
  申请人：KAROBIO AKTIEBOLAG

  公开号：WO1992020331A1

  公开（公告）日：1992-11-26

  (EN) Use of a compound selected from the group consisting of 3,5-diiodo-4-(2-N,N-diethylaminoethoxy)phenyl-(2-butylbenzofur-3-yl)methanol hydrochloride (001), 2-methyl-3-(3,5-diiodo-4-(2-N,N-diethylaminoethoxy)-benzoyl)benzofuran hydrochloride (003), 2-n-butyl-3-(3,5-diiodo-4-carboxymethoxybenzoyl)benzofuran (005), 2-methyl-3-(3,5-diiodo-4-hydroxy-benzoyl)benzofuran (011), 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (015), 4'-hydroxy-3'-iodo-3,5-diiodo-4-(2-N,N-dimethylaminoethoxy)benzophenon hydrochloride (024), 2-butyl-3-(3-iodo-4-hydroxybenzoyl)benzofuran (029), 4',4-dihydroxy-3'3,5-triiodo-diphenylmethan (032), which compound is a 3,5,3'-triiodothyronine (T-3) receptor ligand, for the preparation of a medicament for the therapeutic or prophylactic treatment of a disorder which depends on the expression of T-3 regulated genes, and pharmaceutical preparations comprising said compounds, are disclosed. Further, a method of prophylactically or therapeutically treating a patient having a disorder which depends on the expression of 3,5,3'-triiodo-thyronine (T-3) regulated genes is also disclosed. The invention additionally comprises product protection for all the above listed compounds, except the compound (011).(FR) On décrit l'utilisation d'un composé choisi parmi le groupe suivant: hydrochlorure de 3,5-diiodo-4-(2-N,N-diéthylaminoéthoxy)phényl-(2-butylbenzofur-3-yl)méthanol (001); hydrochlorure de 2-méthyl-3-(3,5-diiodo-4-(2-N,N-diéthylaminoéthoxy)-benzoyl)benzofurane (003); 2-n-butyl-3-(3,5-diiodo-4-carboxyméthoxybenzoyl)benzofurane (005); 2-méthyl-3-(3,5-diiodo-4-hydroxy-benzoyl)benzofurane (011); 2-méthyl-3-(3,5-diiodo-4-carboxyméthoxybenzyl)benzofurane (015); hydrochlorure de 4'-hydroxy-3'-iodo-3,5 diiodo-4-(2-N,N-diméthylaminoéthoxy)benzophénone (024); 2-butyl-3-(3-iodo-4-hydroxybenzoyl)benzofurane (029); 4',4-dihydroxy-3'3,5-triiodo-diphénylméthane (032), ledit composé étant un ligand de récepteur de 3,5,3'-triiodothyronine (T-3), servant à la préparation d'un médicament pour le traitement thérapeutique ou prophylactique d'une affection qui dépend de l'expression de gènes à régulation T-3, ainsi que des préparations pharmaceutiques renfermant lesdits composés. De plus, on décrit une méthode de traitement prophylactique ou thérapeutique d'un patient atteint d'une affection qui dépend de l'expression de gènes à régulation 3,5,3'-triiodo-thyronine (T-3). Les produits dont la protection est également demandée sont tous les composés énumérés ci-dessus, à l'exception du composé (011).

  使用从以下组中选择的化合物，包括3,5-二碘-4-(2-N,N-二乙基氨基乙氧基)苯基-(2-丁基苯并呋喃-3-基)甲醇盐酸盐（001）、2-甲基-3-(3,5-二碘-4-(2-N,N-二乙基氨基乙氧基)苯甲酰)苯并呋喃盐酸盐（003）、2-正丁基-3-(3,5-二碘-4-羧甲氧基苯甲酰)苯并呋喃（005）、2-甲基-3-(3,5-二碘-4-羟基苯甲酰)苯并呋喃（011）、2-甲基-3-(3,5-二碘-4-羧甲氧基苯基)苯并呋喃（015）、4'-羟基-3'-碘-3,5-二碘-4-(2-N,N-二甲基氨基乙氧基)苯基酮盐酸盐（024）、2-丁基-3-(3-碘-4-羟基苯甲酰)苯并呋喃（029）、4',4-二羟基-3'3,5-三碘-二苯甲烷（032），该化合物为3,5,3'-三碘甲状腺素（T-3）受体配体，用于制备治疗或预防依赖T-3调节基因表达的疾病的药物，以及包含该化合物的制药制剂。此外，还公开了一种预防性或治疗性治疗患有依赖3,5,3'-三碘甲状腺素（T-3）调节基因表达的疾病的患者的方法。该发明还包括对以上列出的所有化合物的产品保护，但不包括化合物（011）。
• Use of small molecule inhibitors targeting EYA tyrosine phosphatase
  申请人：Children's Hospital Medical Center

  公开号：US10221151B2

  公开（公告）日：2019-03-05

  Inhibitors of EYA tyrosine phosphatase are provided herein, as well as pharmaceutical compositions and methods relating thereto.

  本文提供了 EYA 酪氨酸磷酸酶的抑制剂以及与之相关的药物组合物和方法。
• RECEPTOR LIGANDS
  申请人：KARO BIO AB

  公开号：EP0584186B1

  公开（公告）日：1996-08-21
• USE OF SMALL MOLECULE INHIBITORS TARGETING EYA TYROSINE PHOSPHATASE
  申请人：Children's Hospital Medical Center

  公开号：US20140128460A1

  公开（公告）日：2014-05-08

  Inhibitors of EYA tyrosine phosphatase are provided herein, as well as pharmaceutical compositions and methods relating thereto.