Methyl 4-(3-chloro-4-fluorophenyl)-1-benzothiophene-2-carboxylate | 861218-28-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: Methyl 4-(3-chloro-4-fluorophenyl)-1-benzothiophene-2-carboxylate
• CAS: 861218-28-2
• 化学式: C₁₆H₁₀ClFO₂S
• 分子量: 320.772
• InChiKey: NJXNDLIYRFWMBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Methyl 4-(3-chloro-4-fluorophenyl)-1-benzothiophene-2-carboxylate 、 胍 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-carbamimidoyl-4-(3-chloro-4-fluorophenyl)-1-benzothiophene-2-carboxamide
  参考文献：
  名称：

  4-Substituted (benzo[b]thiophene-2-carbonyl)guanidines as novel Na+/H+ exchanger isoform-1 (NHE-1) inhibitors

  摘要：

  A series of 4-substituted (benzo[b]thiophene-2-carbonyl)guanidines was synthesized and evaluated for the NHE-1 inhibitory activity and cardioprotective efficacy both in vitro and in vivo. Several analogs exhibited a strong inhibition on NHE-1, and which was generally well correlated with their cardioprotective efficacy. Especially the 4-nitro 20 and cyano 50 compounds excellently improved the cardiac function and reduced infarct size against ischemia/reperfusion injury. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.04.046
• 作为产物：
  描述：

  间溴氟苯 在 四(三苯基膦)钯 、 potassium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 Methyl 4-(3-chloro-4-fluorophenyl)-1-benzothiophene-2-carboxylate
  参考文献：
  名称：

  4-Substituted (benzo[b]thiophene-2-carbonyl)guanidines as novel Na+/H+ exchanger isoform-1 (NHE-1) inhibitors

  摘要：

  A series of 4-substituted (benzo[b]thiophene-2-carbonyl)guanidines was synthesized and evaluated for the NHE-1 inhibitory activity and cardioprotective efficacy both in vitro and in vivo. Several analogs exhibited a strong inhibition on NHE-1, and which was generally well correlated with their cardioprotective efficacy. Especially the 4-nitro 20 and cyano 50 compounds excellently improved the cardiac function and reduced infarct size against ischemia/reperfusion injury. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.04.046

文献信息

• Benzothiophen-2-carbonylguanidine derivatives, preparation thereof, and pharmaceutical composition containing the same
  申请人：Yi Kyu Yang

  公开号：US20100004466A1

  公开（公告）日：2010-01-07

  The present invention is related to benzothiophen-2-carbonylguanidine derivatives, a preparation method thereof, and pharmaceutical compositions containing the same. The derivatives have potent inhibitory effect on the sodium/hydrogen exchanger NHE-I, improve the functional recovery of ischemia/reperfusion-induced heart injury in isolated ischemic heart models, and significantly reduce the myocardiac infarct size in in vivo ischemic animal models, thereby showing excellent cardioprotective effects. Also, the derivatives are protective of both neuronal cells and the brain as proven by their protective effects on neuronal cells from necrosis and apoptosis and by their ability to significantly reduce cerebral infarct sizes in in vivo ischemic brain models. The derivatives can be effectively used for the prevention and treatment of ischemic heart diseases such as myocardiac infarction, arrhythmia, angina pectoris and the like, and cerebrovascular diseases such as cerebral stroke and be used as cardioprotective agents to the patients undergoing reperfusion therapy including chemicals such as thrombolytic agents, or surgery such as coronary artery bypass and percutaneous transluminal coronary angioplasty.

  本发明涉及苯并噻吩-2-羧酰基胍衍生物、其制备方法以及含有其的制药组合物。这些衍生物对钠/氢交换NHE-I具有强效的抑制作用，在离体缺血心脏模型中提高了缺血/再灌注所致的心脏损伤的功能恢复，并在体内缺血动物模型中显著减少心肌梗死面积，因此表现出优异的心脏保护作用。此外，这些衍生物通过对神经元细胞的保护作用和在体内缺血脑模型中显著减少脑梗死面积的能力，也能保护神经元和大脑。这些衍生物可有效用于预防和治疗缺血性心脏疾病，如心肌梗死、心律失常、心绞痛等，以及脑血管疾病，如脑卒中，并可用作心脏保护剂，用于接受再灌注治疗的患者，包括使用溶栓剂等化学药物或手术，如冠状动脉旁路移植术和经皮冠状动脉成形术。
• EP1831192A4
  申请人：——

  公开号：EP1831192A4

  公开（公告）日：2009-08-19
• BENZOTHIOPHEN-2-CARBONYLGUANIDINE DERIVATIVES, PREPARATION THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY

  公开号：EP1831192A1

  公开（公告）日：2007-09-12
• US8143307B2
  申请人：——

  公开号：US8143307B2

  公开（公告）日：2012-03-27
• [EN] BENZOTHIOPHEN-2-CARBONYLGUANIDINE DERIVATIVES, PREPARATION THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME<br/>[FR] DÉRIVÉS DE BENZOTHIOPHÈNE-2-CARBONYLGUANIDINE, LEUR SYNTHÈSE, ET PRÉPARATION PHARMACEUTIQUE CONTENANT LESDITS DÉRIVÉS
  申请人：KOREA RES INST CHEM TECH

  公开号：WO2006071047A1

  公开（公告）日：2006-07-06

  [EN] The present invention is related to benzothiophen-2-carbonylguanidine derivatives, a preparation method thereof, and pharmaceutical compositions containing the same. The derivatives have potent inhibitory effect on the sodium/hydrogen exchanger NHE-I, improve the functional recovery of ischemia/reperfusion-induced heart injury in isolated ischemic heart models, and significantly reduce the myocardiac infarct size in in vivo ischemic animal models, thereby showing excellent cardioprotective effects. Also, the derivatives are protective of both neuronal cells and the brain as proven by their protective effects on neuronal cells from necrosis and apoptosis and by their ability to significantly reduce cerebral infarct sizes in in vivo ischemic brain models. The derivatives can be effectively used for the prevention and treatment of ischemic heart diseases such as myocardiac infarction, arrhythmia, angina pectoris and the like, and cerebrovascular diseases such as cerebral stroke and be used as cardioprotective agents to the patients undergoing reperfusion therapy including chemicals such as thrombolytic agents, or surgery such as coronary artery bypass and percutaneous transluminal coronary angioplasty.
  [FR] La présente invention concerne des dérivés de benzothiophène-2-carbonylguanidine, ainsi qu'une méthode de synthèse desdits dérivés, et des préparations pharmaceutiques contenant lesdits dérivés. Ces composés exercent un puissant effet inhibiteur sur l'échangeur sodium/hydrogène NHE-I, améliorent la capacité de récupération de l'organisme suite à une ischémie ou à une blessure au coer due à une reperfusion dans des modèles de coer ischémique isolés, et réduisent de façon significative la taille de l'infarctus du myocarde chez des modèles d'animaux ischémiques in vivo, constituant ainsi d'excellents agents cardioprotecteurs. Ces composés préservent également les cellules neuronales ainsi que le cerveau, comme le prouve le fait qu'ils exercent un effet protecteur sur les cellules neuronales vis-à-vis de la nécrose et de l'apoptose, ainsi que leur capacité à réduire de façon significative la taille des infarctus cérébraux dans des modèles de cerveau ischémique in vivo. Ces composés peuvent être employés de façon efficace dans le traitement prophylactique et thérapeutique de maladies ischémiques du coer, telles que l'infarctus du myocarde, l'arythmie cardiaque, les angines de poitrine et les maladies similaires, ainsi que de maladies cérébrovasculaires telles que les accidents cérébrovasculaires. Ces composés peuvent également être employés en tant qu'agents cardioprotecteurs pour des patients soumis à une thérapie par reperfusion impliquant des substances chimiques telles que les agents thrombolytiques, ou subissant une opération de chirurgie telle qu'un pontage coronarien ou une angioplastie coronarienne transluminale percutanée.