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1. 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。

2. 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。

3. 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。

4. 发明授权

US08685963B2 Compounds that inhibit NFκB and BACE1 activity 有权
标题翻译：抑制NF＆Kgr B和BACE1活性的化合物
公开(公告)号：US08685963B2
公开(公告)日：2014-04-01
申请号：US13094504
申请日：2011-04-26
申请人： Donald W. Landry , Shi Xian Deng , Gangli Gong , Yuli Xie , Yidong Liu , K. Alison Rinderspacher
发明人： Donald W. Landry , Shi Xian Deng , Gangli Gong , Yuli Xie , Yidong Liu , K. Alison Rinderspacher
IPC分类号： A61K31/54 , A01N43/42 , A61K31/47 , C07D215/36
CPC分类号： C07D215/40 , A61K31/47 , C07D401/12 , C07D409/12
摘要： The present invention relates to compounds with activity as BACE1 and NFκB modulators, and methods for treating, preventing, or ameliorating neurodegenerative diseases, such as Alzheimer's disease. The present invention is also directed to the treatment of diseases related to dysfunction of cell proliferation, the immune system and/or inflammation using such compounds or pharmaceutical compositions containing such candidate compounds.
摘要翻译：本发明涉及具有BACE1和NFκB调节剂活性的化合物，以及治疗，预防或改善神经变性疾病如阿尔茨海默氏病的方法。本发明还涉及使用这些化合物或包含这些候选化合物的药物组合物治疗与细胞增殖功能障碍，免疫系统和/或炎症有关的疾病。

5. 发明申请

US20120295853A1 NEURONAL PAIN PATHWAY 有权
标题翻译：神经痛痛途径
公开(公告)号：US20120295853A1
公开(公告)日：2012-11-22
申请号：US13569510
申请日：2012-08-08
申请人： Richard Ambron , Ying-Ju Sung , Donald W. Landry , Shi-Xian Deng
发明人： Richard Ambron , Ying-Ju Sung , Donald W. Landry , Shi-Xian Deng
IPC分类号： A61K31/55 , A61P25/00 , A61P25/04 , A61K38/02
CPC分类号： A61K38/06 , A61K9/0014 , A61K9/7023 , A61K31/352 , A61K31/4422 , A61K31/55 , A61K38/02 , A61K38/07 , A61K38/465 , 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。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。

6. 发明申请

US20210047337A1 TRIAZOLOPYRIMIDINES, THEIR PREPARATION AND USE 有权
公开(公告)号：US20210047337A1
公开(公告)日：2021-02-18
申请号：US17085791
申请日：2020-10-30
申请人： Konstantin Petrukhin , Kirsten Alison Rinderspacher , Shi-Xian Deng , Andras Varadi , Boglarka Racz , Peter Bernstein , Patricia C. Weber , Donald W. Landry , Andrew S. Wasmuth
发明人： Konstantin Petrukhin , Kirsten Alison Rinderspacher , Shi-Xian Deng , Andras Varadi , Boglarka Racz , Peter Bernstein , Patricia C. Weber , Donald W. Landry , Andrew S. Wasmuth
IPC分类号： C07D487/04 , C07D519/00 , A61P27/02
摘要： The present invention provides a compound having the structure: wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3, C1-C4 alkyl, aryl or heteroaryl; X is N or CR6, wherein R6 is H, OH, or halogen; A is absent or present, and when present is B has the structure: or a pharmaceutically acceptable salt thereof.

7. 发明授权

US09107868B2 Neuronal pain pathway 有权
标题翻译：神经元疼痛途径
公开(公告)号：US09107868B2
公开(公告)日：2015-08-18
申请号：US13569510
申请日：2012-08-08
申请人： Richard Ambron , Ying-Ju Sung , Donald W. Landry , Shi-Xian Deng
发明人： Richard Ambron , Ying-Ju Sung , Donald W. Landry , Shi-Xian Deng
IPC分类号： A61K31/55 , A61P25/00 , A61P25/04 , A61K38/02 , A61K38/06 , A61K38/07 , A61K47/48 , A61K38/46 , A61K31/352 , A61K31/4422 , C12N9/12 , A61K9/70
CPC分类号： A61K38/06 , A61K9/0014 , A61K9/7023 , A61K31/352 , A61K31/4422 , A61K31/55 , A61K38/02 , A61K38/07 , A61K38/465 , 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。

8. 发明授权

US08653273B2 Potent non-urea inhibitors of soluble epoxide hydrolase 有权
标题翻译：可溶性环氧化物水解酶的非尿素抑制剂
公开(公告)号：US08653273B2
公开(公告)日：2014-02-18
申请号：US13178117
申请日：2011-07-07
申请人： Kirsten Alison Rinderspacher , Donald W. Landry , Yuli Xie , Yidong Liu , Gangli Gong , Shi-Xian Deng
发明人： Kirsten Alison Rinderspacher , Donald W. Landry , Yuli Xie , Yidong Liu , Gangli Gong , Shi-Xian Deng
IPC分类号： C07D211/62
CPC分类号： C07D211/96 , C07D211/62 , C07D401/12 , C07D409/12 , C07F9/59 , C12N9/99
摘要： The present invention relates to compounds that exhibit vasodilatory and anti-inflammatory effects by inhibiting the activity of soluble epoxide hydrolase (sEH). The present invention is also directed to methods of identifying such compounds, and use of such compounds for the treatment of diseases related to dysfunction of vasodilation, inflammation, and/or endothelial cells. In particular non-limiting embodiments, components of the invention may be used to treat hypertension.
摘要翻译：本发明涉及通过抑制可溶性环氧化物水解酶（sEH）的活性而显示血管扩张和抗炎作用的化合物。本发明还涉及鉴定这些化合物的方法，以及这些化合物用于治疗与血管舒张功能障碍，炎症和/或内皮细胞相关的疾病的用途。特别是非限制性实施方案，本发明的组分可用于治疗高血压。

9. 发明授权

US08252754B2 Neuronal pain pathway 有权
标题翻译：神经元疼痛途径
公开(公告)号：US08252754B2
公开(公告)日：2012-08-28
申请号：US11385455
申请日：2006-03-21
申请人： Richard Ambron , Ying-Ju Sung , Donald W. Landry , Shi-Xian Deng
发明人： Richard Ambron , Ying-Ju Sung , Donald W. Landry , Shi-Xian Deng
IPC分类号： C12N15/11 , C07H21/02 , C07H21/04
CPC分类号： A61K38/06 , A61K9/0014 , A61K9/7023 , A61K31/352 , A61K31/4422 , A61K31/55 , A61K38/02 , A61K38/07 , A61K38/465 , 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。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。

10. 发明申请

US20120029022A1 Potent Non-Urea Inhibitors Of Soluble Epoxide Hydrolase 有权
标题翻译：可溶性环氧化物水解酶的有效非尿素抑制剂
公开(公告)号：US20120029022A1
公开(公告)日：2012-02-02
申请号：US13178117
申请日：2011-07-07
申请人： Donald W. Landry , Yuli Xie , Yidong Liu , Gangli Gong , Shi-Xian Deng , Kirsten Alison Rinderspacher
发明人： Donald W. Landry , Yuli Xie , Yidong Liu , Gangli Gong , Shi-Xian Deng , Kirsten Alison Rinderspacher
IPC分类号： A61K31/445 , A61P9/12 , A61P29/00 , C07D211/62 , A61P9/00
CPC分类号： C07D211/96 , C07D211/62 , C07D401/12 , C07D409/12 , C07F9/59 , C12N9/99
摘要： The present invention relates to compounds that exhibit vasodilatory and anti-inflammatory effects by inhibiting the activity of soluble epoxide hydrolase (sEH). The present invention is also directed to methods of identifying such compounds, and use of such compounds for the treatment of diseases related to dysfunction of vasodilation, inflammation, and/or endothelial cells. In particular non-limiting embodiments, components of the invention may be used to treat hypertension.
摘要翻译：本发明涉及通过抑制可溶性环氧化物水解酶（sEH）的活性而显示血管扩张和抗炎作用的化合物。本发明还涉及鉴定这些化合物的方法，以及这些化合物用于治疗与血管舒张功能障碍，炎症和/或内皮细胞相关的疾病的用途。特别是非限制性实施方案，本发明的组分可用于治疗高血压。

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