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。