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1. 发明申请

WO2006019685A2 COMPOUNDS AND THEIR PREPARATION FOR THE TREATMENT OF ALZHEIMER'S DISEASE BY INHIBITING BETA-AMYLOID PEPTIDE PRODUCTION 审中-公开
标题翻译：通过抑制β-淀粉样蛋白肽生产来治疗阿尔茨海默病的化合物及其制备方法
公开(公告)号：WO2006019685A2
公开(公告)日：2006-02-23
申请号：PCT/US2005024533
申请日：2005-07-11
申请人： UNIV COLUMBIA , LANDRY DONALD W , DENG SHIXIAN , KIM TAE-WAN , PARK JEONG HILL
发明人： LANDRY DONALD W , DENG SHIXIAN , KIM TAE-WAN , PARK JEONG HILL
IPC分类号： C07J17/00 , A61K31/704
CPC分类号： C07J17/00
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：本发明提供了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苷化合物的方法。此外，本发明提供了用于抑制β-淀粉样肽产生的方法以及使用这些人参皂苷化合物治疗或预防病理状态，特别是神经变性疾病（例如阿尔茨海默氏病）的方法。

2. 发明申请

WO2007024717A3 AGENTS FOR PREVENTING AND TREATING DISORDERS INVOLVING MODULATION OF THE RYR RECEPTORS 审中-公开
标题翻译：涉及RYR受体调节的预防和治疗疾病的药剂
公开(公告)号：WO2007024717A3
公开(公告)日：2009-01-08
申请号：PCT/US2006032405
申请日：2006-08-17
申请人： UNIV COLUMBIA , MARKS ANDREW ROBERT , LANDRY DONALD W , DENG SHIXIAN , CHENG ZHEN ZHUANG , LEHNART STEPHAN E
发明人： MARKS ANDREW ROBERT , LANDRY DONALD W , DENG SHIXIAN , CHENG ZHEN ZHUANG , LEHNART STEPHAN E
IPC分类号： A61K31/553 , C07D281/02
CPC分类号： C07D281/10 , C07D417/12 , C07D417/14
摘要： 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.
摘要翻译：本发明提供式I，（I）的化合物及其盐，水合物，溶剂化物，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。

3. 发明申请

WO2006101497A3 NOVEL ANTI-ARRYTHMIC AND HEART FAILURE DRUGS THAT TARGET THE LEAK IN THE RYANODINE RECEPTOR (RYR2) 审中-公开
标题翻译：靶向雷诺星受体（RYR2）的新型抗ARRYTHMIC和心脏衰竭药物
公开(公告)号：WO2006101497A3
公开(公告)日：2007-08-02
申请号：PCT/US2005010056
申请日：2005-03-24
申请人： UNIV COLUMBIA , MARKS ANDREW R , LANDRY DONALD W , DENG SHIXIAN , CHENG ZHEN ZHUANG
发明人： MARKS ANDREW R , LANDRY DONALD W , DENG SHIXIAN , CHENG ZHEN ZHUANG
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 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 exerciseinduced 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，本发明提供了用于鉴定用于治疗或预防心力衰竭，心房颤动或运动性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。

4. 发明申请

WO2005094457A3 NOVEL ANTI-ARRHYTHMIC AND HEART FAILURE DRUGS THAT TARGET THE LEAK IN THE RYANODINE RECEPTOR (RYR2) AND USES THEREOF 审中-公开
标题翻译：目标靶向受体（RYR2）中的漏出的新型抗精神病药和心脏衰竭药物及其用途
公开(公告)号：WO2005094457A3
公开(公告)日：2006-04-27
申请号：PCT/US2005009495
申请日：2005-03-22
申请人： UNIV COLUMBIA , MARKS ANDREW R , LANDRY DONALD W , DENG SHIXIAN , CHENG ZHEN ZHUANG
发明人： MARKS ANDREW R , LANDRY DONALD W , DENG SHIXIAN , CHENG ZHEN ZHUANG
IPC分类号： A61K31/553 , 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。

5. 发明申请

WO2015009930A2 NOVEL PHOSPHODIESTERASE INHIBITORS AND USES THEREOF 审中-公开
标题翻译：新型磷酸二酯酶抑制剂及其用途
公开(公告)号：WO2015009930A2
公开(公告)日：2015-01-22
申请号：PCT/US2014047031
申请日：2014-07-17
申请人： UNIV COLUMBIA , LANDRY DONALD W , DENG SHIXIAN , FIORITO JOLE , ARANCIO OTTAVIO , WASMUTH ANDREW
发明人： LANDRY DONALD W , DENG SHIXIAN , FIORITO JOLE , ARANCIO OTTAVIO , WASMUTH ANDREW
IPC分类号： A61K31/554
CPC分类号： C07D471/04 , C07D471/14
摘要： The invention provides for novel benzonaphthyridine derivatives and compositions comprising novel benzonaphthyridine derivatives. In some embodiments, the compounds are phosphodiesterase inhibitors. The invention further provides for methods for inhibition of phosphodiesterase comprising contacting phosphodiesterase with novel benzonaphthyridine derivatives or compositions comprising novel benzonaphthyridine derivatives. The invention further provides for methods for treatment of neurodegenerative diseases, increasing memory or long term potentiation with novel benzonaphthyridine derivatives or compositions comprising novel benzonaphthyridine derivatives. In some embodiments, the phosphodiesterase is PDE5.
摘要翻译：本发明提供新的苯并萘啶衍生物和包含新型苯并萘啶衍生物的组合物。在一些实施方案中，化合物是磷酸二酯酶抑制剂。本发明还提供了抑制磷酸二酯酶的方法，包括使磷酸二酯酶与新的苯并萘啶衍生物或包含新的苯并萘啶衍生物的组合物接触。本发明进一步提供治疗神经退行性疾病的方法，增加新的苯并萘啶衍生物或包含新型苯并萘啶衍生物的组合物的记忆或长期增强作用。在一些实施方案中，磷酸二酯酶是PDE5。

6. 发明申请

WO2009124119A3 PHOSPHODIESTERASE INHIBITORS AND USES THEREOF 审中-公开
标题翻译：磷酸二酯酶抑制剂及其用途
公开(公告)号：WO2009124119A3
公开(公告)日：2009-12-30
申请号：PCT/US2009039129
申请日：2009-04-01
申请人： TRUSTES OF COLUMBIA UNIVERSITY , ARANCIO OTTAVIO , PUZZO DANIELA , LANDRY DONALD W , DENG SHIXIAN
发明人： ARANCIO OTTAVIO , PUZZO DANIELA , LANDRY DONALD W , DENG SHIXIAN
IPC分类号： A01N43/42
CPC分类号： G01N33/5088 , C12Q1/37 , G01N2333/96472
摘要： The invention provides for a method for screening compounds that bind to and modulate a phosphosdiesterase protein. The invention further 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：本发明提供了用于筛选结合并调节磷酸二酯酶蛋白的化合物的方法。本发明进一步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-β肽沉积物积聚有关的病症的方法。

7. 发明申请

WO2009124119A2 PHOSPHODIESTERASE INHIBITORS AND USES THEREOF 审中-公开
标题翻译：磷酸二酯酶抑制剂及其用途
公开(公告)号：WO2009124119A2
公开(公告)日：2009-10-08
申请号：PCT/US2009039129
申请日：2009-04-01
申请人： TRUSTES OF COLUMBIA UNIVERSITY , ARANCIO OTTAVIO , PUZZO DANIELA , LANDRY DONALD W , DENG SHIXIAN
发明人： ARANCIO OTTAVIO , PUZZO DANIELA , LANDRY DONALD W , DENG SHIXIAN
IPC分类号： A01K67/027 , G01N33/53
CPC分类号： G01N33/5088 , C12Q1/37 , G01N2333/96472
摘要： The invention provides for a method for screening compounds that bind to and modulate a phosphosdiesterase protein. The invention further 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。

8. 发明申请

WO2006102267A2 NEW NEURONAL PAIN PATHWAY 审中-公开
标题翻译：新神经痛路径
公开(公告)号：WO2006102267A2
公开(公告)日：2006-09-28
申请号：PCT/US2006010107
申请日：2006-03-21
申请人： UNIV COLUMBIA , AMBRON RICHARD , SUNG YING-JU , LANDRY DONALD W , DENG SHI-ZIAN
发明人： AMBRON RICHARD , SUNG YING-JU , LANDRY DONALD W , DENG SHI-ZIAN
IPC分类号： A61K38/10 , A61K9/70 , A61K38/05 , A61K38/08
CPC分类号： A61K38/06 , A61K9/0014 , A61K9/7023 , A61K31/352 , A61K31/4422 , A61K31/55 , A61K38/02 , A61K38/07 , A61K38/465 , A61K47/48246 , A61K47/64 , C12N9/1205 , C12Y301/04017
摘要： The present invention relates to the discovery of a novel molecular pathway involved in long-term hyperexcitability of sensory neurons, which, in higher animals, is associated with persistent pain. It is based on the discovery that, following injury to an axon of a neuron, an increase in nitric oxide synthase activity results in increased nitric oxide production, which, in turn, activates guanylyl cyclase, thereby increasing levels of cGMP. Increased cGMP results in activation of protein kinase G ("PKG"), which then is retrogradely transported along the axon to the neuron cell body, where it phosphorylates MAPKerk.
摘要翻译：本发明涉及发现涉及感觉神经元的长期兴奋性的新型分子途径，其在高等动物中与持续性疼痛相关。它是基于这样的发现：在神经元轴突损伤之后，一氧化氮合酶活性的增加导致一氧化氮产生增加，这反过来激活鸟苷酸环化酶，从而增加cGMP的水平。增加的cGMP导致蛋白激酶G（“PKG”）的激活，其然后沿着轴突逆行转运到神经元细胞体，其中磷酸化MAPKerk。

9. 发明申请

WO2007095586A3 NEURONAL PAIN PATHWAY MODULATORS 审中-公开
标题翻译：神经痛路径调制器
公开(公告)号：WO2007095586A3
公开(公告)日：2008-03-13
申请号：PCT/US2007062154
申请日：2007-02-14
申请人： UNIV COLUMBIA , AMBRON RICHARD , SUNG YING-JU , GREENWOOD JEREMY , FRYE LEAH , DENG SHI-XIAN , XIE YULI , LANDRY DONALD W
发明人： AMBRON RICHARD , SUNG YING-JU , GREENWOOD JEREMY , FRYE LEAH , DENG SHI-XIAN , XIE YULI , LANDRY DONALD W
IPC分类号： A01N43/02 , A61K31/335
CPC分类号： A61K31/40 , A61K31/235 , A61K31/335
摘要： The present invention relates to compounds that may be used to inhibit activation of protein kinase G ("PKG"). It is based, at least in part, on the discovery of the tertiary structure of PKG and the identification of molecules that either bind to the active site of PKG and/or are analogs of balanol.
摘要翻译：本发明涉及可用于抑制蛋白激酶G（“PKG”）活化的化合物。至少部分基于PKG的三级结构的发现以及与PKG的活性位点结合的分子的鉴定和/或是平衡醇的类似物。

10. 发明申请

WO2007101116A2 GLUR2 RECEPTOR MODULATORS 审中-公开
标题翻译： GLUR2受体调节剂
公开(公告)号：WO2007101116A2
公开(公告)日：2007-09-07
申请号：PCT/US2007062737
申请日：2007-02-23
申请人： UNIV COLUMBIA , GOUAUX ERIC , SONG LANGZHOU , XIE YULIE , LANDRY DONALD W
发明人： GOUAUX ERIC , SONG LANGZHOU , XIE YULIE , LANDRY DONALD W
CPC分类号： C07C311/03
摘要： The present invention provides for compositions and methods for modulating the GluR2 receptor. It is based, at least in part, on the discovery, by X-ray crystallography, that a known GluR2 agonist binds to the receptor in two different orientations, thereby diminishing its potency. The present invention provides for structural alternatives in which alternative binding possibilities are substantially eliminated.
摘要翻译：本发明提供了用于调节GluR2受体的组合物和方法。至少部分地基于X射线晶体学发现，已知的GluR2激动剂以两种不同取向与受体结合，从而降低其效力。本发明提供了其中基本上消除了替代结合可能性的结构替代物。

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