3-(4-benzylpiperidin-1-yl)-1-(7-hydroxy-3,5-dihydro-2H-1,4-benzothiazepin-4-yl)propan-1-one | 793725-11-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3-(4-benzylpiperidin-1-yl)-1-(7-hydroxy-3,5-dihydro-2H-1,4-benzothiazepin-4-yl)propan-1-one
• CAS: 793725-11-8
• 化学式: C₂₄H₃₀N₂O₂S
• 分子量: 410.58
• InChiKey: HSGUYFNFNBHYOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  69.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-benzylpiperidin-1-yl)-1-(7-hydroxy-3,5-dihydro-2H-1,4-benzothiazepin-4-yl)propan-1-one 、 bis(tritritiomethyl) sulfate 在 sodium hydride 作用下， 生成
  参考文献：
  名称：

  Novel anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof

  摘要：

  本发明提供了限制或预防受试者中RyR2结合FKBP12.6水平下降的方法。本发明进一步提供了治疗和预防受试者中心房和心室心律失常、心力衰竭以及运动诱发的突发性心脏死亡的方法。此外，本发明提供了在限制或预防受试者中RyR2结合FKBP12.6水平下降的方法中使用JTV-519的用途，该受试者患有或有可能患上心房颤动。还提供了1,4-苯并噻唑啉衍生物在治疗和预防受试者中心房和心室心律失常以及心力衰竭，以及预防运动诱发的突发性心脏死亡的方法中的用途。本发明还提供了用于识别用于治疗和预防心房颤动和心力衰竭的药剂的方法，以及通过这些方法识别的药剂。

  公开号：

  US20050215540A1
• 作为产物：
  描述：

  4-[3-(4-苯甲基哌啶-1-基)丙酰]-7-甲氧基-2,3,4,5-四氢-1,4-苯并硫氮杂卓 在 三溴化硼 作用下， 生成 3-(4-benzylpiperidin-1-yl)-1-(7-hydroxy-3,5-dihydro-2H-1,4-benzothiazepin-4-yl)propan-1-one
  参考文献：
  名称：

  Novel anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof

  摘要：

  本发明提供了限制或预防受试者中RyR2结合FKBP12.6水平下降的方法。本发明进一步提供了治疗和预防受试者中心房和心室心律失常、心力衰竭以及运动诱发的突发性心脏死亡的方法。此外，本发明提供了在限制或预防受试者中RyR2结合FKBP12.6水平下降的方法中使用JTV-519的用途，该受试者患有或有可能患上心房颤动。还提供了1,4-苯并噻唑啉衍生物在治疗和预防受试者中心房和心室心律失常以及心力衰竭，以及预防运动诱发的突发性心脏死亡的方法中的用途。本发明还提供了用于识别用于治疗和预防心房颤动和心力衰竭的药剂的方法，以及通过这些方法识别的药剂。

  公开号：

  US20050215540A1

文献信息

• Compounds and methods for treating and preventing exercise-induced cardiac arrhythmias
  申请人：——

  公开号：US20040229781A1

  公开（公告）日：2004-11-18

  The present invention provides a method for limiting or preventing a decrease in the level of RyR2-bound FKBP12.6 in a subject, a method for treating or preventing exercise-induced cardiac arrhythmia in a subject, and a method for preventing exercise-induced sudden cardiac death in a subject. Also provided are uses of JTV-519 in these methods. The present invention further provides methods for identifying agents for use in preventing exercise-induced sudden cardiac death, as well as agents identified by such methods. Also provided are methods for preventing exercise-induced sudden cardiac death by administering these agents. Additionally, the present invention provides methods for synthesizing JTV-519, radio-labeled JTV-519, and 1,4-benzothiazepine intermediates and derivatives.

  本发明提供了一种限制或预防受试者中RyR2-结合FKBP12.6水平下降的方法，一种治疗或预防受试者运动引起的心律失常的方法，以及一种预防受试者运动引起的猝死的方法。此外，本发明还提供了JTV-519在这些方法中的用途。本发明还提供了一种用于识别用于预防运动引起的猝死的药剂的方法，以及由这些方法识别出的药剂。此外，本发明还提供了通过给予这些药剂预防运动引起的猝死的方法。此外，本发明还提供了合成JTV-519，放射性标记的JTV-519以及1,4-苯并噻唑中间体和衍生物的方法。
• METHODS FOR SYNTHESIZING BENZOTHIAZEPINE COMPOUNDS
  申请人：Landry Donald W.

  公开号：US20090292119A1

  公开（公告）日：2009-11-26

  The present invention provides improved methods for synthesizing novel benzothiazepine compounds. In particular, the invention relates to a new method that generally is used to make the substituted 2,3,4,5-tetrahydro-1,4-benzothiazepine compounds of a general formula which then may be used to make many other benzothiazepine compounds.

  本发明提供了改进的合成新型苯并噻吩化合物的方法。具体来说，本发明涉及一种新方法，通常用于制备一般式的取代2,3,4,5-四氢-1,4-苯并噻吩化合物，然后可以用于制备许多其他苯并噻吩化合物。
• NOVEL ANTI-ARRHYTHMIC AND HEART FAILURE DRUGS THAT TARGET THE LEAK IN THE RYANODINE RECEPTOR (RyR2)
  申请人：Marks Andrew Robert

  公开号：US20100152440A1

  公开（公告）日：2010-06-17

  The present invention provides novel 1,4-benzothiazepine intermediates and derivatives, methods for synthesizing same, and methods for assaying same. The present invention also provides methods for using these novel compounds to limit or prevent a decrease in the level of RyR2-bound FKBP12.6 in a subject; to prevent exercise-induced sudden cardiac death in a subject; and to treat or prevent heart failure, atrial fibrillation, or exercise-induced cardiac arrhythmia in a subject. The present invention further provides methods for identifying an agent that enhances binding of RyR2 and FKBP12.6, and agents identified by these methods. Additionally, the present invention provides methods for identifying agents for use in treating or preventing heart failure, atrial fibrillation, or exercise-induced cardiac arrhythmia, and in preventing exercise-induced sudden cardiac death. Also provided are agents identified by such methods.

  本发明提供了新颖的1,4-苯并噻唑啉中间体和衍生物，以及合成这些化合物的方法和检测这些化合物的方法。本发明还提供了使用这些新化合物限制或预防受试者中RyR2-结合FKBP12.6水平下降的方法；预防受试者运动引起的突发性心脏死亡的方法；以及治疗或预防受试者心力衰竭、心房颤动或运动引起的心脏心律失常的方法。本发明还提供了用于识别增强RyR2和FKBP12.6结合的试剂的方法和由这些方法识别的试剂。此外，本发明还提供了用于识别用于治疗或预防心力衰竭、心房颤动或运动引起的心脏心律失常以及预防运动引起的突发性心脏死亡的试剂的方法，以及由这些方法识别的试剂。
• Benzothiazepine derivatives as ryanodine receptor (RYR2) inhibitors and their use in the treatment of cardiac diseases
  申请人：The Trustees of Columbia University in the City of New York

  公开号：EP2127654A1

  公开（公告）日：2009-12-02

  The present invention provides methods for limiting or preventing a decrease in the level of RyR2-bound FKBP12.6 in a subject. The present invention further provides methods for treating and preventing atrial and ventricular cardiac arrhythmias, heart failure, and exercise-induced sudden cardiac death in a subject. Additionally, the present invention provides use of JTV-519 in a method for limiting or preventing a decrease in the level of RyR2-bound FKBP12.6 in a subject who has, or is a candidate for, atrial fibrillation. Also provided are uses of 1,4-benzothiazepine derivatives in methods for treating and preventing atrial and ventricular cardiac arrhythmias and heart failure in a subject, and for preventing exercise-induced sudden cardiac death. The present invention also provides methods for identifying agents for use in treating and preventing atrial fibrillation and heart failure, and agents identified by these methods. To be accompanied, when published, by Figure 1 of the drawings.

  本发明提供了限制或预防受试者体内与 RyR2 结合的 FKBP12.6 水平下降的方法。本发明进一步提供了治疗和预防受试者房性和室性心律失常、心力衰竭和运动诱发的心脏性猝死的方法。此外，本发明还提供了 JTV-519 在限制或预防患有或可能患有心房颤动的受试者体内与 RyR2 结合的 FKBP12.6 水平下降的方法中的用途。本发明还提供了1,4-苯并硫氮杂卓衍生物在治疗和预防受试者房性和室性心律失常和心力衰竭以及预防运动诱发的心脏性猝死的方法中的用途。本发明还提供了鉴定用于治疗和预防心房颤动和心力衰竭的药剂的方法，以及通过这些方法鉴定的药剂。 出版时附图 1。
• METHOD FOR PRODUCING OPTICALLY ACTIVE 1, 4-BENZOTHIAZEPINE-1-OXIDE DERIVATIVE
  申请人：Aetas Pharma Co. Ltd.

  公开号：EP4019089A1

  公开（公告）日：2022-06-29

  The present invention addresses the problem of providing an efficient asymmetric synthesis method for an optically active 1,4-benzothiazepine-1-oxide derivative. [Solution] According to the present invention, an optically active 1,4-benzothiazepine-1-oxide derivative is efficiently produced by reacting a 1,4-benzothiazepine derivative or a salt thereof with a reagent containing a titanium compound, a chiral diol compound and water, and an oxidant in a solvent.

  本发明要解决的问题是提供一种光学活性 1，4-苯并硫氮杂卓-1-氧化物衍生物的高效不对称合成方法。[解]根据本发明，通过将 1,4-苯并硫氮杂卓衍生物或其盐与含有钛化合物、手性二元醇化合物和水的试剂以及氧化剂在溶剂中进行反应，可高效制得光学活性 1,4-苯并硫氮杂卓-1-氧化物衍生物。