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1. 发明授权

US07544678B2 Anti-arrythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) 失效
标题翻译：针对雷诺地尔受体（RyR2）泄漏的抗心律失常药物和心力衰竭药物
公开(公告)号：US07544678B2
公开(公告)日：2009-06-09
申请号：US11088058
申请日：2005-03-23
申请人： Andrew Robert Marks , Donald W. Landry , Shixian Deng , Zhen Zhuang Cheng
发明人： Andrew Robert Marks , Donald W. Landry , Shixian Deng , Zhen Zhuang Cheng
IPC分类号： A61P9/00 , A61K31/553 , A61K31/554 , A61K31/675 , C07F9/553 , C07D281/02
CPC分类号： C07D281/10 , C07D267/14 , C07D417/06 , C07D417/12 , G01N2800/325 , G01N2800/326
摘要： 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.
摘要翻译：本发明提供新的1,4-苯并硫氮杂中间体及其衍生物，其合成方法及其测定方法。本发明还提供了使用这些新化合物来限制或防止受试者中RyR2结合的FKBP12.6水平降低的方法; 以防止受试者运动性心源性猝死; 并且治疗或预防受试者的心力衰竭，心房颤动或运动引起的心律失常。本发明还提供用于鉴定增强RyR2和FKBP12.6的结合的试剂以及通过这些方法鉴定的试剂的方法。此外，本发明提供用于鉴定用于治疗或预防心力衰竭，心房颤动或运动诱导的心律失常以及预防运动性心源性猝死的药剂的方法。还提供了通过这种方法鉴定的药剂。

2. 发明授权

US07718644B2 Anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof 有权
标题翻译：抗心律失常药物和心力衰竭药物，针对兰诺定受体（RyR2）的泄漏及其应用
公开(公告)号：US07718644B2
公开(公告)日：2010-05-18
申请号：US10809089
申请日：2004-03-25
申请人： Andrew Robert Marks , Donald W. Landry , Shixian Deng , Zhen Zhuang Cheng
发明人： Andrew Robert Marks , Donald W. Landry , Shixian Deng , Zhen Zhuang Cheng
IPC分类号： A01N43/00 , A61K31/00
CPC分类号： A61K31/554
摘要： 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.
摘要翻译：本发明提供限制或预防受试者中RyR2结合的FKBP12.6水平降低的方法。本发明还提供了治疗和预防受试者心房心室心律失常心力衰竭和运动性心源性猝死的方法。另外，本发明提供了用于限制或预防具有或已经是心房颤动候选者的受试者中RyR2结合的FKBP12.6的水平降低的方法中的JTV-519的用途。还提供了1,4-苯并硫氮杂衍生物在治疗和预防受试者的心房心室心律失常和心力衰竭以及用于预防运动性心源性猝死的方法中的用途。本发明还提供了用于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。

3. 发明授权

US07704990B2 Agents for preventing and treating disorders involving modulation of the RyR receptors 有权
标题翻译：用于预防和治疗涉及RyR受体调节的病症的药剂
公开(公告)号：US07704990B2
公开(公告)日：2010-04-27
申请号：US11212413
申请日：2005-08-25
申请人： Donald W. Landry , Shixian Deng , Zhen Zhuang Cheng
发明人： Donald W. Landry , Shixian Deng , Zhen Zhuang Cheng
IPC分类号： C07D281/02 , A61K31/554
CPC分类号： C07D281/10 , C07D417/12 , C07D417/14
摘要： 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.
摘要翻译：本发明提供新的式I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式I化合物的方法。本发明另外提供包含式I化合物的药物组合物和使用式I药物组合物的方法，以治疗和预防与调节钙的RyR受体相关的疾病和疾病通道在单元格中起作用。这样的疾病和疾病仅包括心脏病和疾病，骨骼肌障碍和疾病，认知障碍和疾病，恶性高热，糖尿病和婴儿猝死综合征。心脏疾病和疾病包括但不限于不规则的心跳障碍和疾病; 运动引起的心律失常和疾病不规律; 心脏猝死; 运动性心源性猝死; 充血性心力衰竭; 慢性阻塞性肺疾病; 和高血压。不规律的心跳疾病和疾病包括运动诱发的心律失常和疾病的疾病包括但不限于心房和室性心律失常; 心房和心室颤动; 心房和心室快速性心律失常; 心房和室性心动过速; 儿茶酚胺能多态性室性心动过速（CPVT）; 和运动诱发的变体。骨骼肌障碍和疾病包括但不限于骨骼肌疲劳，运动引起的骨骼肌疲劳，肌营养不良，膀胱障碍和失禁。认知障碍和疾病包括但不限于阿尔茨海默病，记忆丧失的形式和年龄依赖性记忆丧失。

4. 发明申请

US20100152440A1 NOVEL ANTI-ARRHYTHMIC AND HEART FAILURE DRUGS THAT TARGET THE LEAK IN THE RYANODINE RECEPTOR (RyR2) 审中-公开
标题翻译：靶向RYANODE受体（RyR2）的新型抗神经和心脏衰竭药物
公开(公告)号：US20100152440A1
公开(公告)日：2010-06-17
申请号：US12480396
申请日：2009-06-08
申请人： Andrew Robert Marks , Donald W. Landry , Shi Xian Deng , Zhen Zhuang Cheng
发明人： Andrew Robert Marks , Donald W. Landry , Shi Xian Deng , Zhen Zhuang Cheng
IPC分类号： C07D417/06 , C07D281/08
CPC分类号： C07D281/10 , C07D267/14 , C07D417/06 , C07D417/12 , G01N2800/325 , G01N2800/326
摘要： 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.
摘要翻译：本发明提供新的1,4-苯并硫氮杂中间体及其衍生物，其合成方法及其测定方法。本发明还提供了使用这些新化合物来限制或防止受试者中RyR2结合的FKBP12.6水平降低的方法; 以防止受试者运动性心源性猝死; 并且治疗或预防受试者的心力衰竭，心房颤动或运动引起的心律失常。本发明还提供用于鉴定增强RyR2和FKBP12.6的结合的试剂以及通过这些方法鉴定的试剂的方法。此外，本发明提供用于鉴定用于治疗或预防心力衰竭，心房颤动或运动诱导的心律失常以及预防运动性心源性猝死的药剂的方法。还提供了通过这种方法鉴定的药剂。

5. 发明申请

US20050187386A1 Novel anti-arrythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) 失效
标题翻译：针对雷诺定受体（RyR2）漏出的新型抗心律失常药物和心力衰竭药物
公开(公告)号：US20050187386A1
公开(公告)日：2005-08-25
申请号：US11088058
申请日：2005-03-23
申请人： Andrew Robert Marks , Donald Landry , Shi Xian Deng , Zhen Zhuang Cheng
发明人： Andrew Robert Marks , Donald Landry , Shi Xian Deng , Zhen Zhuang Cheng
IPC分类号： C07D267/02
CPC分类号： C07D281/10 , C07D267/14 , C07D417/06 , C07D417/12 , G01N2800/325 , G01N2800/326
摘要： 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.
摘要翻译：本发明提供新的1,4-苯并硫氮杂中间体及其衍生物，其合成方法及其测定方法。本发明还提供了使用这些新化合物来限制或防止受试者中RyR2结合的FKBP12.6水平降低的方法; 以防止受试者运动性心源性猝死; 并且治疗或预防受试者的心力衰竭，心房颤动或运动引起的心律失常。本发明还提供用于鉴定增强RyR2和FKBP12.6的结合的试剂以及通过这些方法鉴定的试剂的方法。此外，本发明提供用于鉴定用于治疗或预防心力衰竭，心房颤动或运动诱导的心律失常以及预防运动性心源性猝死的药剂的方法。还提供了通过这种方法鉴定的药剂。

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