2'-{[(4-methoxy-phenyl)-acetylamino]-methyl}biphenyl-2-carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2'-{[(4-methoxy-phenyl)-acetylamino]-methyl}biphenyl-2-carboxylic acid
• 英文别名: 2'-{[(4-methoxyphenylacetyl)amino]methyl}biphenyl-2-carboxylic acid；2'-{[2-(4-Methoxy-phenyl)-acetylamino]-methyl}-biphenyl-2-carboxylic acid；2-[2-[[[2-(4-methoxyphenyl)acetyl]amino]methyl]phenyl]benzoic acid
• 化学式: C₂₃H₂₁NO₄
• 分子量: 375.424
• InChiKey: HXYRIIDLHHAJHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2'-{[(4-methoxy-phenyl)-acetylamino]-methyl}biphenyl-2-carboxylic acid 、 对氨基苯酚 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 2'-{[(4-methoxy-phenyl)-acetylamino]-methyl}biphenyl-2-carboxylic acid 4-phenolamide
  参考文献：
  名称：

  [EN] RESVERATROL ANALOGS AND THERAPEUTIC USES THEREOF
  [FR] ANALOGUES DE RESVÉRATROL ET LEURS UTILISATIONS THÉRAPEUTIQUES

  摘要：

  白藜芦醇类似物及其用于抑制Kv1.5通道的方法已提供。这些白藜芦醇类似物在治疗心房心律失常，包括心房颤动（AF）方面很有用。示例白藜芦醇类似物是一般式（I）的化合物：

  公开号：

  WO2014183221A1
• 作为产物：
  描述：

  邻溴苯甲酸甲酯 在 四(三苯基膦)钯 、 sodium carbonate 、 N,N'-羰基二咪唑 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 2'-{[(4-methoxy-phenyl)-acetylamino]-methyl}biphenyl-2-carboxylic acid
  参考文献：
  名称：

  [EN] RESVERATROL ANALOGS AND THERAPEUTIC USES THEREOF
  [FR] ANALOGUES DE RESVÉRATROL ET LEURS UTILISATIONS THÉRAPEUTIQUES

  摘要：

  白藜芦醇类似物及其用于抑制Kv1.5通道的方法已提供。这些白藜芦醇类似物在治疗心房心律失常，包括心房颤动（AF）方面很有用。示例白藜芦醇类似物是一般式（I）的化合物：

  公开号：

  WO2014183221A1

文献信息

• Combination of phenylcarboxylic acid amides with beta-adrenoreceptor blockers and their use for the treatment of atrial arrhythmias
  申请人：Wirth Klaus

  公开号：US20050054673A1

  公开（公告）日：2005-03-10

  The invention relates to the combination of one or more beta-blockers and of one or more Kv1.5 blockers, in particular phenylcarboxamides of the formula la and/or lb and/or physiologically tolerable salts thereof, and the use of the combination for the treatment or prophylaxis of atrial arrhythmias.

  该发明涉及一种或多种β受体阻滞剂与一种或多种Kv1.5通道阻滞剂的组合，特别是公式la和/或lb和/或其生理耐受盐，以及利用该组合物治疗或预防心房心律失常。
• Combination of phenylcarboxamides with blockers of the IKr channel and their use for the treatment of atrial arrhythmias
  申请人：Brendel Joachim

  公开号：US20050038083A1

  公开（公告）日：2005-02-17

  The invention relates to the combination of one or more IK r channel blockers and of one or more Kv1.5 blockers, in particular phenyl-carboxamides of the formula Ia or Ib or pharmaceutically tolerable salts thereof, and the use of the combination for the treatment of atrial arrhythmias.

  本发明涉及一种IKr通道阻滞剂和一种或多种Kv1.5通道阻滞剂的组合，特别是公式Ia或Ib的苯基羧酰胺或其药学上可耐受的盐，以及该组合在治疗心房心律失常方面的应用。
• Characterization of a novel multifunctional resveratrol derivative for the treatment of atrial fibrillation
  作者：Istvan Baczko、David Liknes、Wei Yang、Kevin C Hamming、Gavin Searle、Kristian Jaeger、Zoltan Husti、Viktor Juhasz、Gergely Klausz、Robert Pap、Laszlo Saghy、Andras Varro、Vernon Dolinsky、Shaohua Wang、Vivek Rauniyar、Dennis Hall、Jason RB Dyck、Peter E Light

  DOI：10.1111/bph.12409

  日期：2014.1

  Background and PurposeAtrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk for stroke, heart failure and cardiovascular‐related mortality. Candidate targets for anti‐AF drugs include a potassium channel Kv1.5, and the ionic currents IKACh and late INa, along with increased oxidative stress and activation of NFAT‐mediated gene transcription. As pharmacological management of AF is currently suboptimal, we have designed and characterized a multifunctional small molecule, compound 1 (C1), to target these ion channels and pathways.Experimental ApproachWe made whole‐cell patch‐clamp recordings of recombinant ion channels, human atrial IKur, rat atrial IKACh, cellular recordings of contractility and calcium transient measurements in tsA201 cells, human atrial samples and rat myocytes. We also used a model of inducible AF in dogs.Key ResultsC1 inhibited human peak and late Kv1.5 currents, frequency‐dependently, with IC50 of 0.36 and 0.11 μmol·L−1 respectively. C1 inhibited IKACh (IC50 of 1.9 μmol·L−1) and the Nav1.5 sodium channel current (IC50s of 3 and 1 μmol·L−1 for peak and late components respectively). C1 (1 μmol·L−1) significantly delayed contractile and calcium dysfunction in rat ventricular myocytes treated with 3 nmol·L−1 sea anemone toxin (ATX‐II). C1 weakly inhibited the hERG channel and maintained antioxidant and NFAT‐inhibitory properties comparable to the parent molecule, resveratrol. In a model of inducible AF in conscious dogs, C1 (1 mg·kg−1) reduced the average and total AF duration.Conclusion and ImplicationsC1 behaved as a promising multifunctional small molecule targeting a number of key pathways involved in AF.
• KOMBINATION VON PHENYLCARBONSÄUREAMIDEN MIT BLOCKERN DES IKR-KANALS UND DEREN VERWENDUNG ZUR BEHANDLUNG VON VORHOFARRHYTHMIEN
  申请人：Sanofi-Aventis Deutschland GmbH

  公开号：EP1605976B1

  公开（公告）日：2010-02-24
• CRYSTALLINE PHASES OF 2'-{[2-(4-METHOXY-PHENYL)-ACETYLAMINO]-METHYL}-BIPHENYL-2-CARBOXYLIC ACID (2-PYRIDIN-3-YL-ETHYL)-AMIDE
  申请人：Sanofi-Aventis Deutschland GmbH

  公开号：EP2438045B1

  公开（公告）日：2016-10-05