(4-羟基-3,5-二碘苯基)(2-甲基-1-苯并呋喃-3-基)甲酮 | 10402-56-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (4-羟基-3,5-二碘苯基)(2-甲基-1-苯并呋喃-3-基)甲酮
• 英文名称: 2-methyl-3-(3,5-diiodo-4-hydroxybenzoyl)benzofuran
• 英文别名: (4-hydroxy-3,5-diiodo-phenyl)-(2-methyl-benzofuran-3-yl)-methanone；2-methyl-3-(3,5-diiodo-4-hydroxy-benzoyl)benzofuran；2-Methyl-3-<3,5-dijod-4-hydroxy-benzoyl>-benzofuran；3-(3,5-Diiodo-4-hydroxybenzoyl)-2-methyl-benzofuran；(4-hydroxy-3,5-diiodophenyl)-(2-methyl-1-benzofuran-3-yl)methanone
• CAS: 10402-56-9
• 化学式: C₁₆H₁₀I₂O₃
• 分子量: 504.063
• InChiKey: QLUUKNMPBTWGBB-UHFFFAOYSA-N

物化性质

• 熔点：
  171-172 °C
• 沸点：
  463.1±45.0 °C(Predicted)
• 密度：
  2.071±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  21
• 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-3,5-二碘苯基)(2-甲基-1-苯并呋喃-3-基)甲酮 在 18-冠醚-6 、 铁粉 、 potassium carbonate 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 反应 25.0h， 生成 [3,5-Diiodo-4-(2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-ylmethoxy)-phenyl]-(2-methyl-benzofuran-3-yl)-methanone
  参考文献：
  名称：

  Synthesis and evaluation of the permeability transition inhibitory characteristics of paramagnetic and diamagnetic amiodarone derivatives

  摘要：

  Several amiodarone analogues were synthesized varying the 2-substituent on the benzofuran ring and diethylaminoethyl side chain of phenolether by introducing 2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole and 1,2,5,6-tetrahydropyridine nitroxides or their amino or hydroxylamino precursors. The new compounds were screened on isolated mitochondria and perfused heart and their toxicity was evaluated on WRL-68 liver cells and H9C2 cardiomyocytes. Most of the newly synthesized derivatives exerted uncoupling effect on the mitochondrial oxidative phosphorilation at higher concentrations, compared to amiodarone and one of the modified amiodarone analogues showed an effect similar to that of arniodarone on the mitochondrial permeability transition and on restoring of mitochondrial high-energy phosphate metabolites in perfused hearts. This arniodarone analogue can be new leading compound among the experimental arniodarone analogues with the same or enhanced efficiency of amiodarone, but with less side effects. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.01.028
• 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 ammonium hydroxide 、 碘 、 吡啶盐酸盐 、 potassium iodide 作用下， 反应 48.5h， 生成 (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+

文献信息

• [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）。
• Benzofuranes and their use in the treatment of atrial fibrillation
  申请人：Brandts Bodo

  公开号：US20050065208A1

  公开（公告）日：2005-03-24

  This intention relates to new compounds and their pharmaceutical use, and to the pharmaceutical use of known compounds, which compounds inhibit certain transmembrane potassium currents in the atrium of the heart of a mammal without significantly affecting other ion channels, for the treatment of heart disease particularly atrial fibrillation. The invention also relates to pharmaceutical compositions comprising such compounds.

  本意图涉及新化合物及其药物用途，以及已知化合物的药物用途，这些化合物可抑制哺乳动物心房中某些跨膜钾电流，而不显著影响其他离子通道，用于治疗心脏疾病，特别是心房颤动。本发明还涉及包含这些化合物的药物组合物。
• 3,5,3'-triiodothyronine receptor ligands
  申请人：——

  公开号：US05585404A1

  公开（公告）日：1996-12-17

  Use of a compound selected from the group consisting of 3,5-diiodo-4-(2-N,N-diethylaminoethoxy)phenyl-(2-butylbenzofur-3-yl)methan ol 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-diethylaminoethoxy)benzophenon hydrochloride (024), 2-butyl-3-(3-iodo-4-hydroxybenzoyl)benzofuran (029), 4'4'-dihydroxy-3'3,5-triiododiphenylmethan (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).

  使用从以下组中选出的化合物，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)苯酰基)苯并呋喃盐酸盐(003)、2-正丁基-3-(3,5-二碘-4-羧甲氧基苯酰基)苯并呋喃(005)、2-甲基-3-(3,5-二碘-4-羟基苯酰基)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-二乙基氨基乙氧基)苯基酮盐酸盐(024)、2-丁基-3-(3-碘-4-羟基苯酰基)苯并呋喃(029)、4'4'-二羟基-3'3,5-三碘二苯甲烷(032)，该化合物是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于T-3调节基因表达的疾病的药物和包含上述化合物的制剂。此外，还公开了一种预防性或治疗性治疗患有依赖于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。该发明还包括对所有上述列出的化合物的产品保护，除了化合物(011)。
• Uses for thyroid hormone compounds
  申请人：KARO BIO AB

  公开号：EP1398024A2

  公开（公告）日：2004-03-17

  A skin treatment composition for topical application comprises: at least one thyroid hormone compound or thyroid hormone-like compound, wherein said thyroid hormone compound or thyroid hormone-like compound is a chemical entity which binds to TRα or TRβ with a dissociation constant, Kd, lower than 1µM, whereinKd = [R] • [L] / [RL], wherein [R] is the concentration of receptor, [L] is the concentration of ligand and [RL] is the concentration of the receptor-ligand complex; at least one ingredient selected from vitamin D, glucocorticoids, retinoids and retinoic acid receptor binding compounds, or analogues thereof; and a pharmacologically acceptable base.

  一种用于局部应用的皮肤治疗组合物包括至少一种甲状腺激素化合物或甲状腺激素样化合物，其中所述甲状腺激素化合物或甲状腺激素样化合物是与 TRα 或 TRβ 结合的化学实体，其解离常数 Kd 低于 1µM，其中 Kd = [R] - [L] / [RL]，其中 [R] 是受体的浓度，[L] 是配体的浓度，[RL] 是受体-配体复合物的浓度；至少一种选自维生素 D、糖皮质激素、维甲酸和维甲酸受体结合化合物或其类似物的成 分；以及药理学上可接受的碱。
• 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。