4-(pyrimidin-2-ylmethyl)-7-(4-(trifluoromethoxy)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one HCl salt | 1448754-43-5

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 4-(pyrimidin-2-ylmethyl)-7-(4-(trifluoromethoxy)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one HCl salt
• 英文别名: 7-(4-(trifluoromethoxy)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one monohydrochloride；Eleclazine hydrochloride；4-(pyrimidin-2-ylmethyl)-7-[4-(trifluoromethoxy)phenyl]-2,3-dihydro-1,4-benzoxazepin-5-one;hydrochloride
• CAS: 1448754-43-5
• 化学式: C₂₁H₁₆F₃N₃O₃*ClH
• 分子量: 451.832
• InChiKey: ZRYHNOXHGYUHFF-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMSO:100.0(最大浓度 mg/mL);221.32(最大浓度 mM)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  8

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  | 2-8℃ |

制备方法与用途

Elexacaine hydrochloride 是一种新的钠离子电流抑制剂，其 IC50 值为 0.7 μM。

反应信息

• 作为产物：
  描述：

  4-(pyrimidin-2-ylmethyl)-7-(4-(trifluoromethoxy)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 以24.8 g的产率得到4-(pyrimidin-2-ylmethyl)-7-(4-(trifluoromethoxy)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one HCl salt
  参考文献：
  名称：

  [EN] COMBINATION THERAPIES USING LATE SODIUM ION CHANNEL BLOCKERS AND POTASSIUM ION CHANNEL BLOCKERS
  [FR] THÉRAPIES DE COMBINAISON À L'AIDE DE BLOQUEURS DE CANAUX IONIQUES AU SODIUM TARDIFS ET DE BLOQUEURS DE CANAUX IONIQUES AU POTASSIUM

  摘要：

  本文描述了一种用于治疗或预防心房颤动和/或心房扑动的方法，包括给予有效量的一个或多个钾通道阻滞剂和一个或多个晚期钠通道阻滞剂。还提供了调节心室和心房节律和频率的方法。还提供了适合进行这种联合给药的药物配方。

  公开号：

  WO2013112932A1

文献信息

• METHODS OF TREATING HYPERTROPHIC CARDIOMYOPATHY
  申请人：Gilead Sciences, Inc.

  公开号：US20150038487A1

  公开（公告）日：2015-02-05

  The present disclosure relates to a compound of formula (I) or formula (II) or a pharmaceutically acceptable salt thereof, for use in the treatment of hypertrophic cardiomyopathy.

  本公开涉及一种具有化学式(I)或化学式(II)或其药学上可接受的盐的化合物，用于治疗肥厚型心肌病。
• COMPOUND AND METHODS FOR TREATING LONG QT SYNDROME
  申请人：Gilead Sciences, Inc.

  公开号：US20150038489A1

  公开（公告）日：2015-02-05

  Described herein is a method of treating long QT syndrome by administration of an effective amount of a potent and selective late sodium ion channel blocker

  本文描述了一种治疗长QT综合征的方法，通过给予有效剂量的强效和选择性晚期钠离子通道阻滞剂进行治疗。
• SOLID FORMS OF AN ION CHANNEL MODULATOR
  申请人：Gilead Sciences, Inc.

  公开号：US20150225383A1

  公开（公告）日：2015-08-13

  Crystalline solid forms of the selective late sodium current inhibitor 4-(pyrimidin-2-ylmethyl)-7-(4-(trifluoromethoxy)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using the crystalline forms.

  选择性晚期钠电流抑制剂4-(嘧啶-2-基甲基)-7-(4-(三氟甲氧基)苯基)-3,4-二氢苯并[f][1,4]噁唑啶-5(2H)-酮（化合物I）的晶体固态形式已经制备并表征：同时提供了制备过程和使用晶体形式的方法。
• Discovery of Dihydrobenzoxazepinone (GS-6615) Late Sodium Current Inhibitor (Late <i>I</i>_Nai), a Phase II Agent with Demonstrated Preclinical Anti-Ischemic and Antiarrhythmic Properties
  作者：Jeff A. Zablocki、Elfatih Elzein、Xiaofen Li、Dmitry O. Koltun、Eric Q. Parkhill、Tetsuya Kobayashi、Ruben Martinez、Britton Corkey、Haibo Jiang、Thao Perry、Rao Kalla、Gregory T. Notte、Oliver Saunders、Michael Graupe、Yafan Lu、Chandru Venkataramani、Juan Guerrero、Jason Perry、Mark Osier、Robert Strickley、Gongxin Liu、Wei-Qun Wang、Lufei Hu、Xiao-Jun Li、Nesrine El-Bizri、Ryoko Hirakawa、Kris Kahlig、Cheng Xie、Cindy Hong Li、Arvinder K. Dhalla、Sridharan Rajamani、Nevena Mollova、Daniel Soohoo、Eve-Irene Lepist、Bernard Murray、Gerry Rhodes、Luiz Belardinelli、Manoj C. Desai

  DOI：10.1021/acs.jmedchem.6b00939

  日期：2016.10.13

  Late sodium current (late I-Na) is enhanced during ischemia by reactive oxygen species (ROS) modifying the Na-v 1.5 channel, resulting in incomplete inactivation. Compound 4 (GS-6615, eleclazine) a novel, potent, and selective inhibitor of late INa, is currently in clinical development for treatment of long QT-3 syndrome (LQT-3), hypertrophic cardiomyopathy (HCM), and ventricular tachycardia-velitricular fibrillation (VT-VF). We will describe structure-activity relationship (SAR) leading to the discovery of 4 that is vastly improved from the first generation late I-Na inhibitor 1 (ranolazine). Compound 4 was 42 times more potent than 1 in reducing ischemic burden in vivo (S-T segment elevation, 15 min left anterioior descending, LAD, occlusion in rabbits); with EC50 values of 190 and 8000 nM, respectively. Compound 4 represents a new class of potent late I-Na inhibitors that will be useful in delineating the role of inhibitors of this current in the treatment of patients.
• US9273038B2
  申请人：——

  公开号：US9273038B2

  公开（公告）日：2016-03-01