公开(公告)号：US20050215540A1

公开(公告)日：2005-09-29

申请号：US10809089

申请日：2004-03-25

申请人： Andrew Marks ,  Donald Landry ,  Shi Deng ,  Zhen Cheng

发明人： Andrew Marks ,  Donald Landry ,  Shi Deng ,  Zhen Cheng

IPC分类号： A61K31/554

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。

公开(公告)号：US20050186640A1

公开(公告)日：2005-08-25

申请号：US11088123

申请日：2005-03-23

申请人： Andrew Marks ,  Donald Landry ,  Shi Deng ,  Zhen Cheng

发明人： Andrew Marks ,  Donald Landry ,  Shi Deng ,  Zhen Cheng

IPC分类号： G01N33/53 ,  G01N33/567

CPC分类号： G01N33/6887 ,  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 FKBPl2.6 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FKBP1.6.6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。