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公开(公告)号：US08618282B2
公开(公告)日：2013-12-31
申请号：US12397212
申请日：2009-03-03
申请人： Shixian Deng , Sandro Belvedere , Jiaming Yan , Donald Landry
发明人： Shixian Deng , Sandro Belvedere , Jiaming Yan , Donald Landry
IPC分类号： C07D281/08 , C07D281/10
CPC分类号： C07D281/02 , C07D281/10 , C07D513/04 , Y02P20/55
摘要： The invention provides a process for preparing a 2,3,4,5-tetrahydro[1,4]benzothiazepine of formula: by reacting a [2-(acylaminoethyl)thio]arene of formula with an aldehyde or a multimer thereof, and with an acid. The invention also provides for first reacting the [2-(acylaminoethyl)thio]arene with the aldehyde or multimer thereof and a base to form an [N-hydroxymethyl-2-[acylaminoethyl)thio]arene of formula then treating the [N-hydroxymethyl-2-(acylaminoethyl)thio]arene with the acid to form the 2,3,4,5-tetrahydro[1,4]benzothiazepine.
摘要翻译： 本发明提供了制备下式的2,3,4,5-四氢[1,4]苯并硫氮杂的方法：通过使式的[2-（酰基氨基乙基）硫代]芳烃或其多聚体与 酸。 本发明还提供了使[2-（酰基氨基乙基）硫代]芳烃与其醛或多聚体和碱反应以形成式的[N-羟甲基-2- [酰氨基乙基]硫代]芳烃，然后将[N- 羟基甲基-2-（酰氨基乙基）硫代]芳烃与酸形成2,3,4,5-四氢[1,4]苯并硫氮杂。
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2.发明申请公开(公告)号：US20090227788A1
公开(公告)日：2009-09-10
申请号：US12397212
申请日：2009-03-03
申请人： Shixian Deng , Sandro Belvedere , Jiaming Yan , Donald Landry
发明人： Shixian Deng , Sandro Belvedere , Jiaming Yan , Donald Landry
IPC分类号： C07D417/12 , C07D281/10
CPC分类号： C07D281/02 , C07D281/10 , C07D513/04 , Y02P20/55
摘要： The invention provides a process for preparing a 2,3,4,5-tetrahydro[1,4]benzothiazepine of formula: by reacting a [2-(acylaminoethyl)thio]arene of formula with an aldehyde or a multimer thereof, and with an acid. The invention also provides for first reacting the [2-(acylaminoethyl)thio]arene with the aldehyde or multimer thereof and a base to form an [N-hydroxymethyl-2-[acylaminoethyl)thio]arene of formula then treating the [N-hydroxymethyl-2-(acylaminoethyl)thio]arene with the acid to form the 2,3,4,5-tetrahydro[1,4]benzothiazepine.
摘要翻译： 本发明提供了制备下式的2,3,4,5-四氢[1,4]苯并硫氮杂的方法：通过使式的[2-（酰基氨基乙基）硫代]芳烃或其多聚体与 酸。 本发明还提供了使[2-（酰基氨基乙基）硫代]芳烃与其醛或多聚体和碱反应以形成式的[N-羟甲基-2- [酰氨基乙基]硫代]芳烃，然后将[N- 羟基甲基-2-（酰氨基乙基）硫代]芳烃与酸形成2,3,4,5-四氢[1,4]苯并硫氮杂。
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3.发明申请Novel agents for preventing and treating disorders involving modulation of the RyR receptors 有权用于预防和治疗涉及RyR受体调节的疾病的新型药剂公开(公告)号：US20070049572A1
公开(公告)日：2007-03-01
申请号：US11212413
申请日：2005-08-25
申请人： Andrew Marks , Donald Landry , Shixian Deng , Zhen Cheng , Stephan Lehnart
发明人： Andrew Marks , Donald Landry , Shixian Deng , Zhen Cheng , Stephan Lehnart
IPC分类号： C07D291/08 , 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。
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4.发明申请Agents for preventing and treating disorders involving modulation of the RyR receptors 有权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：US20070173482A1
公开(公告)日：2007-07-26
申请号：US11506285
申请日：2006-08-17
申请人： Andrew Marks , Donald Landry , Shixian Deng
发明人： Andrew Marks , Donald Landry , Shixian Deng
IPC分类号： A61K31/675 , A61K31/554
CPC分类号： C07D281/10 , C07D417/12 , C07D417/14
摘要： The present invention provides 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.
摘要翻译： 本发明提供式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。
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5.发明申请Novel agents for preventing and treating disorders involving modulation of the RyR receptors 有权用于预防和治疗涉及RyR受体调节的疾病的新型药剂公开(公告)号：US20060194767A1
公开(公告)日：2006-08-31
申请号：US11212309
申请日：2005-08-25
申请人： Andrew Marks , Donald Landry , Shixian Deng , Zhen Cheng , Stephan Lehnart
发明人： Andrew Marks , Donald Landry , Shixian Deng , Zhen Cheng , Stephan Lehnart
IPC分类号： A61K31/675 , A61K31/655 , C07D291/08 , C07D417/02
CPC分类号： C07D417/12 , C07D281/10 , C07D417/06 , 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。
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6.发明申请Compounds and their preparation for the treatment of Alzheimer's disease by inhibiting beta-amyloid peptide production 审中-公开化合物及其通过抑制β-淀粉样蛋白肽生产治疗阿尔茨海默氏病的制剂公开(公告)号：US20060014729A1
公开(公告)日：2006-01-19
申请号：US10963214
申请日：2004-10-12
申请人： Donald Landry , Tae-Wan Kim , Shixian Deng
发明人： Donald Landry , Tae-Wan Kim , Shixian Deng
摘要： The present invention provides novel dammarane compounds, compositions (e.g., pharmaceutical compositions) comprising the dammarane compounds, and methods for the synthesis of these dammarane compounds. Additionally, the present invention provides methods for inhibiting beta-amyloid peptide production and methods for treating or preventing a pathological condition, particularly, neurodegeneration diseases (e.g., Alzheimer's disease), using these dammarane compounds.
摘要翻译： 本发明提供了新型的抗坏血酸化合物，包含该抗坏血酸化合物的组合物（例如，药物组合物），以及用于合成这些抗坏血酸化合物的方法。 此外，本发明提供了用于抑制β-淀粉样蛋白肽产生的方法以及使用这些抗坏血酸化合物治疗或预防病理状况，特别是神经变性疾病（例如阿尔茨海默氏病）的方法。
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7.发明申请Compounds and their preparation for the treatment of Alzheimer's disease by inhibiting beta-amyloid peptide production 审中-公开化合物及其通过抑制β-淀粉样蛋白肽生产治疗阿尔茨海默氏病的制剂公开(公告)号：US20060014704A1
公开(公告)日：2006-01-19
申请号：US10961346
申请日：2004-10-07
申请人： Donald Landry , Tae-Wan Kim , Shixian Deng
发明人： Donald Landry , Tae-Wan Kim , Shixian Deng
IPC分类号： C07J17/00 , A61K31/704
摘要： The present invention provides novel ginsenoside compounds, compositions (e.g. pharmaceutical compositions) comprising the ginsenoside compounds, and methods for the synthesis of these ginsenoside compounds. Additionally, the present invention provides methods for inhibiting beta-amyloid peptide production and methods for treating or preventing a pathological condition, particularly, neurodegeneration diseases (e.g. Alzheimer's disease), using these ginsenoside compounds.
摘要翻译： 本发明提供新型人参皂苷化合物，包含人参皂苷化合物的组合物（例如药物组合物），以及合成这些人参皂甙化合物的方法。 此外，本发明提供了使用这些人参皂苷化合物抑制β-淀粉样蛋白肽生产的方法和用于治疗或预防病理状况，特别是神经变性疾病（例如阿尔茨海默氏病）的方法。
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8.发明授权Anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof 有权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
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。
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公开(公告)号：US20090292119A1
公开(公告)日：2009-11-26
申请号：US12263435
申请日：2008-10-31
申请人： Donald W. Landry , Shixian Deng , Zhen Z. Cheng
发明人： Donald W. Landry , Shixian Deng , Zhen Z. Cheng
IPC分类号： C07D417/02 , C07D285/36 , C07D413/02
CPC分类号： C07D281/10 , C07D417/12 , C07D417/14
摘要： 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.
摘要翻译： 本发明提供了合成新的苯并硫氮杂化合物的改进方法。 特别地，本发明涉及一种通常用于制备通式的取代的2,3,4,5-四氢-1,4-苯并硫氮杂化合物的新方法，其可用于制备许多其它苯并硫氮杂化合物。
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公开(公告)号：US08697875B2
公开(公告)日：2014-04-15
申请号：US13167540
申请日：2011-06-23
申请人： Yan Feng , Ottavio Arancio , Shixian Deng , Donald W. Landry
发明人： Yan Feng , Ottavio Arancio , Shixian Deng , Donald W. Landry
IPC分类号： A61P25/00 , A61P25/28 , C07D215/44
CPC分类号： A61K31/4706 , C07D215/48 , C07D215/54
摘要： The invention provides for compounds that are phosphodiesterase inhibitors. The invention further provides for a method for screening compounds that bind to and modulate a phosphosdiesterase protein. The invention also provides methods for treating conditions associated with accumulated amyloid-beta peptide deposit accumulations by administering a phosphodiesterase-binding compound to a subject.
摘要翻译： 本发明提供了磷酸二酯酶抑制剂的化合物。 本发明进一步提供了一种筛选结合并调节磷酸二酯酶蛋白质的化合物的方法。 本发明还提供了通过向受试者施用磷酸二酯酶结合化合物来治疗与累积的淀粉样蛋白-β肽沉积物积累相关的病症的方法。
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