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公开(公告)号：US07507545B2
公开(公告)日：2009-03-24
申请号：US10914841
申请日：2004-08-09
申请人： David Fedida , Gregory N. Beatch , Alan M. Ezrin , Peter Orth
发明人： David Fedida , Gregory N. Beatch , Alan M. Ezrin , Peter Orth
IPC分类号： G01N33/53
CPC分类号： A61K31/40 , A61K31/00 , A61K31/455 , A61K31/4965 , A61K31/519 , C07C217/52 , C07C2601/14 , C07D207/12 , C07D207/24 , C07D207/27 , C07D277/04 , C07D295/096 , C07D295/15 , C07D295/185 , C07D333/54 , C07D333/56 , C07D491/10
摘要： Methods, compositions, dosing regimes, and routes of administration for the treatment or prevention of arrhythmias. In these methods, arrythmias (e.g. atrial fibrillation, atrial flutter, early afterdepolarizations and prolongation of QT interval) may be reduced or eliminated by administering ion channel modulating compounds to a subject in need thereof. The ion channel modulating compounds may be cycloalkylamine ether compounds, particularly cyclohexylamine ether compounds. Also described are compositions of ion channel modulating compounds and drugs which induce early afterdepolarizations, prolongation of QT interval and/or Torsades de Pointes.
摘要翻译： 用于治疗或预防心律失常的方法，组合物，给药方案和给药途径。 在这些方法中，可以通过向有需要的受试者施用离子通道调节化合物来减少或消除心律失常（例如房颤，心房扑动，早期去极化和QT间期延长）。 离子通道调节化合物可以是环烷基胺醚化合物，特别是环己胺醚化合物。 还描述了诱导早期后极化，延长QT间期和/或Torsades de Pointes的离子通道调节化合物和药物的组合物。
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公开(公告)号：US20060199848A9
公开(公告)日：2006-09-07
申请号：US10914841
申请日：2004-08-09
申请人： David Fedida , Gregory Beatch , Alan Ezrin , Peter Orth
发明人： David Fedida , Gregory Beatch , Alan Ezrin , Peter Orth
IPC分类号： C07D211/82 , A61K31/455
CPC分类号： A61K31/40 , A61K31/00 , A61K31/455 , A61K31/4965 , A61K31/519 , C07C217/52 , C07C2601/14 , C07D207/12 , C07D207/24 , C07D207/27 , C07D277/04 , C07D295/096 , C07D295/15 , C07D295/185 , C07D333/54 , C07D333/56 , C07D491/10
摘要： Methods, compositions, dosing regimes, and routes of administration for the treatment or prevention of arrhythmias. In these methods, arrythmias (e.g. atrial fibrillation, atrial flutter, early afterdepolarizations and prolongation of QT interval) may be reduced or eliminated by administering ion channel modulating compounds to a subject in need thereof. The ion channel modulating compounds may be cycloalkylamine ether compounds, particularly cyclohexylamine ether compounds. Also described are compositions of ion channel modulating compounds and drugs which induce early afterdepolarizations, prolongation of QT interval and/or Torsades de Pointes.
摘要翻译： 用于治疗或预防心律失常的方法，组合物，给药方案和给药途径。 在这些方法中，可以通过向有需要的受试者施用离子通道调节化合物来减少或消除心律失常（例如房颤，心房扑动，早期去极化和QT间期延长）。 离子通道调节化合物可以是环烷基胺醚化合物，特别是环己胺醚化合物。 还描述了诱导早期后极化，延长QT间期和/或Torsades de Pointes的离子通道调节化合物和药物的组合物。
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公开(公告)号：US20050070552A1
公开(公告)日：2005-03-31
申请号：US10914864
申请日：2004-08-09
申请人： David Fedida , Gregory Beatch , Alan Ezrin , Peter Orth , Christian Hesketh
发明人： David Fedida , Gregory Beatch , Alan Ezrin , Peter Orth , Christian Hesketh
IPC分类号： A61K31/40 , A61K31/455 , A61K31/4965 , A61K31/519 , A61P9/06 , C07D207/12
CPC分类号： A61K31/40 , A61K31/455 , A61K31/4965 , A61K31/519 , C07D207/12
摘要： Methods, compositions, dosing regimes, and routes of administration for the treatment or prevention of arrhythmias. In these methods, early afterdepolarizations and prolongation of QT interval may be reduced or eliminated by administering ion channel modulating compounds to a subject in need thereof. The ion channel modulating compounds may be cycloalkylamine ether compounds, particularly cyclohexylamine ether compounds. Also described are compositions of ion channel modulating compounds and drugs which induce early afterdepolarizations, prolongation of QT interval and/or Torsades de Pointes.
摘要翻译： 用于治疗或预防心律失常的方法，组合物，给药方案和给药途径。 在这些方法中，可以通过向有需要的受试者施用离子通道调节化合物来减少或消除早期后消极和延长QT间期。 离子通道调节化合物可以是环烷基胺醚化合物，特别是环己胺醚化合物。 还描述了诱导早期后极化，延长QT间期和/或Torsades de Pointes的离子通道调节化合物和药物的组合物。
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公开(公告)号：US20050119315A1
公开(公告)日：2005-06-02
申请号：US10914841
申请日：2004-08-09
申请人： David Fedida , Gregory Beatch , Alan Ezrin , Peter Orth
发明人： David Fedida , Gregory Beatch , Alan Ezrin , Peter Orth
IPC分类号： A61K31/40 , A61K31/455 , A61K31/4965 , A61K31/519 , C07C217/52 , C07D207/12 , C07D207/26 , C07D207/27 , C07D277/04 , C07D295/096 , C07D295/15 , C07D295/185 , C07D333/54 , C07D333/56 , C07D491/10 , C07D211/82
CPC分类号： A61K31/40 , A61K31/00 , A61K31/455 , A61K31/4965 , A61K31/519 , C07C217/52 , C07C2601/14 , C07D207/12 , C07D207/24 , C07D207/27 , C07D277/04 , C07D295/096 , C07D295/15 , C07D295/185 , C07D333/54 , C07D333/56 , C07D491/10
摘要： Methods, compositions, dosing regimes, and routes of administration for the treatment or prevention of arrhythmias. In these methods, arrythmias (e.g. atrial fibrillation, atrial flutter, early afterdepolarizations and prolongation of QT interval) may be reduced or eliminated by administering ion channel modulating compounds to a subject in need thereof. The ion channel modulating compounds may be cycloalkylamine ether compounds, particularly cyclohexylamine ether compounds. Also described are compositions of ion channel modulating compounds and drugs which induce early afterdepolarizations, prolongation of QT interval and/or Torsades de Pointes.
摘要翻译： 用于治疗或预防心律失常的方法，组合物，给药方案和给药途径。 在这些方法中，可以通过向有需要的受试者施用离子通道调节化合物来减少或消除心律失常（例如房颤，心房扑动，早期去极化和QT间期延长）。 离子通道调节化合物可以是环烷基胺醚化合物，特别是环己胺醚化合物。 还描述了诱导早期后极化，延长QT间期和/或Torsades de Pointes的离子通道调节化合物和药物的组合物。
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公开(公告)号：US20060135536A9
公开(公告)日：2006-06-22
申请号：US10914864
申请日：2004-08-09
申请人： David Fedida , Gregory Beatch , Alan Ezrin , Peter Orth , Christian Hesketh
发明人： David Fedida , Gregory Beatch , Alan Ezrin , Peter Orth , Christian Hesketh
IPC分类号： A61K31/4965 , A61K31/519 , A61K31/455
CPC分类号： A61K31/40 , A61K31/455 , A61K31/4965 , A61K31/519 , C07D207/12
摘要： Methods, compositions, dosing regimes, and routes of administration for the treatment or prevention of arrhythmias. In these methods, early afterdepolarizations and prolongation of QT interval may be reduced or eliminated by administering ion channel modulating compounds to a subject in need thereof. The ion channel modulating compounds may be cycloalkylamine ether compounds, particularly cyclohexylamine ether compounds. Also described are compositions of ion channel modulating compounds and drugs which induce early afterdepolarizations, prolongation of QT interval and/or Torsades de Pointes.
摘要翻译： 用于治疗或预防心律失常的方法，组合物，给药方案和给药途径。 在这些方法中，可以通过向有需要的受试者施用离子通道调节化合物来减少或消除早期后消极和延长QT间期。 离子通道调节化合物可以是环烷基胺醚化合物，特别是环己胺醚化合物。 还描述了诱导早期后极化，延长QT间期和/或Torsades de Pointes的离子通道调节化合物和药物的组合物。
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6.发明申请MODIFIED TUMOR NECROSIS FACTOR-ALPHA CONVERTING ENZYME AND METHODS OF USE THEREOF 失效改良型肿瘤坏死因子-α转化酶及其使用方法公开(公告)号：US20100184111A1
公开(公告)日：2010-07-22
申请号：US12702760
申请日：2010-02-09
CPC分类号： C12N9/6489 , C07K2299/00
摘要： The present invention discloses a modified tumor necrosis factor-alpha converting enzyme (TACE) catalytic domain, that unlike the native TACE catalytic domain, is stable at high protein concentrations. The present invention further discloses methods for generating crystals of the modified TACE protein in protein-ligand complexes with a number of inhibitors. In addition, the present invention discloses methods of using the proteins, crystals and/or three-dimensional structures obtained to identify compounds that can modulate the enzymatic activity of TACE.
摘要翻译： 本发明公开了一种修饰的肿瘤坏死因子-α转化酶（TACE）催化结构域，其与天然TACE催化结构域不同，在高蛋白浓度下是稳定的。 本发明还公开了用多种抑制剂在蛋白质 - 配体复合物中产生修饰的TACE蛋白的晶体的方法。 此外，本发明公开了使用获得的蛋白质，晶体和/或三维结构来鉴定可调节TACE的酶活性的化合物的方法。
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7.发明申请MODIFIED TUMOR NECROSIS FACTOR-ALPHA CONVERTING ENZYME AND METHODS OF USE THEREOF 失效改良型肿瘤坏死因子-α转化酶及其使用方法公开(公告)号：US20090221016A1
公开(公告)日：2009-09-03
申请号：US12420323
申请日：2009-04-08
CPC分类号： C12N9/6489 , C07K2299/00
摘要： The present invention discloses a modified tumor necrosis factor-alpha converting enzyme (TACE) catalytic domain, that unlike the native TACE catalytic domain, is stable at high protein concentrations. The present invention further discloses methods for generating crystals of the modified TACE protein in protein-ligand complexes with a number of inhibitors. In addition, the present invention discloses methods of using the proteins, crystals and/or three-dimensional structures obtained to identify compounds that can modulate the enzymatic activity of TACE.
摘要翻译： 本发明公开了一种修饰的肿瘤坏死因子-α转化酶（TACE）催化结构域，其与天然TACE催化结构域不同，在高蛋白浓度下是稳定的。 本发明还公开了用多种抑制剂在蛋白质 - 配体复合物中产生修饰的TACE蛋白的晶体的方法。 此外，本发明公开了使用获得的蛋白质，晶体和/或三维结构来鉴定可调节TACE的酶活性的化合物的方法。
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公开(公告)号：US20090111803A1
公开(公告)日：2009-04-30
申请号：US12338353
申请日：2008-12-18
申请人： Wensheng Yu , Ling Tong , Lei Chen , Joseph A. Kozlowski , Brian J. Lavey , Neng-Yang Shih , Vincent S. Madison , Guowei Zhou , Peter Orth , Zhuyan Guo , Michael K.C. Wong , De-Yi Yang , Seong Heon Kim , Bandarpalle B. Shankat
发明人： Wensheng Yu , Ling Tong , Lei Chen , Joseph A. Kozlowski , Brian J. Lavey , Neng-Yang Shih , Vincent S. Madison , Guowei Zhou , Peter Orth , Zhuyan Guo , Michael K.C. Wong , De-Yi Yang , Seong Heon Kim , Bandarpalle B. Shankat
IPC分类号： A61K31/5377 , C07D233/02 , A61K31/4178 , C07D403/02 , C07D277/20 , A61K31/426 , C07D401/14 , A61K31/4709 , A61P19/02 , A61P37/00 , A61P9/00 , A61P29/00 , A61K31/4545 , C07D215/00 , A61K31/4439 , C07D403/14 , A61K31/506 , A61K31/497 , C07D413/14
CPC分类号： C07D401/14 , C07D403/06 , C07D409/14 , C07D413/14 , C07D417/14
摘要： This invention relates to compounds of the Formula (I): or a pharmaceutically acceptable salt, solvate or isomer thereof, which can be useful for the treatment of diseases or conditions mediated by MMPs, ADAMs, TACE, TNF—or combinations thereof.
摘要翻译： 本发明涉及式（I）化合物或其药学上可接受的盐，溶剂合物或异构体，其可用于治疗由MMP，ADAM，TACE，TNF-或其组合介导的疾病或病症。
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9.发明申请Modified tumor necrosis factor-alpha converting enzyme and methods of use thereof 失效改良型肿瘤坏死因子-α转化酶及其使用方法公开(公告)号：US20070148669A1
公开(公告)日：2007-06-28
申请号：US11582710
申请日：2006-10-18
申请人： Brian Beyer , Richard Ingram , Peter Orth , Corey Strickland
发明人： Brian Beyer , Richard Ingram , Peter Orth , Corey Strickland
CPC分类号： C12N9/6489 , C07K2299/00
摘要： The present invention discloses a modified tumor necrosis factor-alpha converting enzyme (TACE) catalytic domain, that unlike the native TACE catalytic domain, is stable at high protein concentrations. The present invention further discloses methods for generating crystals of the modified TACE protein in protein-ligand complexes with a number of inhibitors. In addition, the present invention discloses methods of using the proteins, crystals and/or three-dimensional structures obtained to identify compounds that can modulate the enzymatic activity of TACE.
摘要翻译： 本发明公开了一种修饰的肿瘤坏死因子-α转化酶（TACE）催化结构域，其与天然TACE催化结构域不同，在高蛋白浓度下是稳定的。 本发明还公开了用多种抑制剂在蛋白质 - 配体复合物中产生修饰的TACE蛋白的晶体的方法。 此外，本发明公开了使用获得的蛋白质，晶体和/或三维结构来鉴定可调节TACE的酶活性的化合物的方法。
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公开(公告)号：US5329127A
公开(公告)日：1994-07-12
申请号：US44731
申请日：1993-04-12
申请人： Arno Becker , Klaus Luttermann , Uwe Claussen , Peter Orth , Ludger Heiliger , Aziz E. Sayed
发明人： Arno Becker , Klaus Luttermann , Uwe Claussen , Peter Orth , Ludger Heiliger , Aziz E. Sayed
CPC分类号： C08F2/44 , B07C5/3427 , B29B2017/0279 , G01N21/6408 , Y02W30/622
摘要： A method of identifying different plastics, wherein each plastic is provided with a plurality of fluorescent dyes which differ in terms of their emission frequencies and/or in terms of the duration of their fluorescence, so that a fluorescence pattern, which is distinguished by the duration of the fluorescence and/or by the frequencies occurring, can unambiguously be assigned to each plastic.
摘要翻译： 一种识别不同塑料的方法，其中每个塑料都具有多个荧光染料，它们在其发射频率和/或其荧光持续时间方面不同，从而荧光图案被区分为持续时间 的荧光和/或发生的频率可以明确地分配给每个塑料。
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