4-[2-(4-benzylpiperidin-1-yl)ethylsulfonyl]-7-methoxy-3,5-dihydro-2H-1,4-benzothiazepine | 865432-96-8

• 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: 4-[2-(4-benzylpiperidin-1-yl)ethylsulfonyl]-7-methoxy-3,5-dihydro-2H-1,4-benzothiazepine
• CAS: 865432-96-8
• 化学式: C₂₄H₃₂N₂O₃S₂
• 分子量: 460.662
• InChiKey: ZOIRCWBPDQGUKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  83.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-[2-(4-benzylpiperidin-1-yl)ethylsulfonyl]-7-methoxy-3,5-dihydro-2H-1,4-benzothiazepine 在 双氧水 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以91%的产率得到4-[2-(4-benzylpiperidin-1-yl)ethylsulfonyl]-7-methoxy-3,5-dihydro-2H-1lambda4,4-benzothiazepine 1-oxide
  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-ethenylsulfonyl-7-methoxy-3,5-dihydro-2H-1,4-benzothiazepine 、 4-苄基哌啶 以 二氯甲烷 为溶剂， 以98%的产率得到4-[2-(4-benzylpiperidin-1-yl)ethylsulfonyl]-7-methoxy-3,5-dihydro-2H-1,4-benzothiazepine
  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

• Novel agents for preventing and treating disorders involving modulation of the RyR receptors
  申请人：Marks R. Andrew

  公开号：US20070049572A1

  公开（公告）日：2007-03-01

  The present invention provides novel compounds of Formula I and salts, hydrates, solvates, complexes, and prodrugs thereof. The present invention further provides methods for synthesizing compounds of Formula I. The invention additionally provides pharmaceutical compositions comprising the compounds of Formula I and methods of using the pharmaceutical compositions of Formula I to treat and prevent disorders and diseases associated with the RyR receptors that regulate calcium channel functioning in cells. Such disorders and diseases include, by way of example only, cardiac disorders and diseases, skeletal muscular disorders and diseases, cognitive disorders and diseases, malignant hyperthermia, diabetes, and sudden infant death syndrome. Cardiac disorder and diseases include, but are not limited to, irregular heartbeat disorders and diseases; exercise-induced irregular heartbeat disorders and diseases; sudden cardiac death; exercise-induced sudden cardiac death; congestive heart failure; chronic obstructive pulmonary disease; and high blood pressure. Irregular heartbeat disorders and diseases include and exercise-induced irregular heartbeat disorders and diseases include, but are not limited to, atrial and ventricular arrhythmia; atrial and ventricular fibrillation; atrial and ventricular tachyarrhythmia; atrial and ventricular tachycardia; catecholaminergic polymorphic ventricular tachycardia (CPVT); and exercise-induced variants thereof. Skeletal muscular disorder and diseases include, but are not limited to, skeletal muscle fatigue, exercise-induced skeletal muscle fatigue, muscular dystrophy, bladder disorders, and incontinence. Cognitive disorders and diseases include, but are not limited to, Alzheimer's Disease, forms of memory loss, and age-dependent memory loss.

  本发明提供了Formula I的新化合物及其盐、水合物、溶剂合物、络合物和前药。本发明还提供了合成Formula I化合物的方法。此外，该发明还提供了包含Formula I化合物的药物组合物，以及使用Formula I药物组合物治疗和预防与调节细胞中钙通道功能的RyR受体相关的疾病和疾病的方法。这些疾病包括但不限于心脏疾病、骨骼肌肉疾病、认知障碍和疾病、恶性高热、糖尿病和婴儿猝死综合征。心脏疾病包括但不限于心律不齐疾病、运动诱发的心律不齐疾病、猝死、运动诱发的猝死、充血性心力衰竭、慢性阻塞性肺疾病和高血压。心律不齐疾病和疾病包括运动诱发的心律不齐疾病，但不限于心房和心室心律失常、心房和心室颤动、心房和心室快速心律失常、心房和心室快速心跳、儿茶酚胺多形性心室心动过速（CPVT）及其运动诱发的变体。骨骼肌肉疾病包括但不限于骨骼肌疲劳、运动诱发的骨骼肌疲劳、肌肉萎缩、膀胱疾病和失禁。认知障碍和疾病包括但不限于阿尔茨海默病、各种记忆丧失形式和年龄相关的记忆丧失。
• 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。
• Agents for preventing and treating disorders involving modulation of the RyR receptors
  申请人：The Trustees of Columbia University in the City of New York

  公开号：EP2177224A2

  公开（公告）日：2010-04-21

  The present invention provides compounds of Formula I, (I) and salts, hydrates, solvates, complexes, and prodrugs thereof. The present invention further provides methods for synthesizing compounds of Formula I. The invention additionally provides pharmaceutical compositions comprising the compounds of Formula I and methods of using the pharmaceutical compositions of Formula I to treat and prevent disorders and diseases associated with the RyR receptors that regulate calcium channel functioning in cells.

  本发明提供了式I、(I)化合物及其盐类、水合物、溶质、络合物和原药。本发明进一步提供了合成式 I 化合物的方法。本发明还提供了包含式I化合物的药物组合物，以及使用式I药物组合物治疗和预防与调节细胞中钙离子通道功能的RyR受体有关的紊乱和疾病的方法。
• Agents for preventing and treating disorders involving modulation of the ryr receptors
  申请人：The Trustees of Columbia University in the City of New York

  公开号：EP2311464A1

  公开（公告）日：2011-04-20

  The present invention provides compounds of Formula I, (I) and salts, hydrates, solvates, complexes, and prodrugs thereof. The present invention further provides methods for synthesizing compounds of Formula I. The invention additionally provides pharmaceutical compositions comprising the compounds of Formula I and methods of using the pharmaceutical compositions of Formula I to treat and prevent disorders and diseases associated with the RyR receptors that regulate calcium channel functioning in cells.

  本发明提供了式I、(I)化合物及其盐类、水合物、溶质、络合物和原药。本发明进一步提供了合成式 I 化合物的方法。本发明还提供了包含式I化合物的药物组合物，以及使用式I药物组合物治疗和预防与调节细胞中钙离子通道功能的RyR受体有关的紊乱和疾病的方法。