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1. 发明授权

US08957083B2 Spiro-amino-imidazolone and spiro-amino-dihydro-pyrimidinone compounds as beta-secretase modulators and methods of use 有权
标题翻译：螺 - 氨基 - 咪唑啉酮和螺 - 氨基 - 二氢 - 嘧啶酮化合物作为β-分泌酶调节剂和使用方法
公开(公告)号：US08957083B2
公开(公告)日：2015-02-17
申请号：US13988745
申请日：2011-11-18
申请人： Ana Elena Minatti , Oleg Epstein , Ryan White , Matthew Weiss , Wenge Zhong , Jonathan D. Low
发明人： Ana Elena Minatti , Oleg Epstein , Ryan White , Matthew Weiss , Wenge Zhong , Jonathan D. Low
IPC分类号： C07D491/107 , C07D491/20
CPC分类号： C07D491/107 , C07D491/20
摘要： The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A1, A3, A4, A5, A6, A8, L, R2, R7, R9, W and Y of Formula I are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to plaque formation and deposition, resulting from the activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas II and III, sub-Formula embodiments of Formulas I, II and III, intermediates and processes and methods useful for the preparation of compounds of Formulae I-III.
摘要翻译：本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。化合物具有通式I：其中式I的变量A1，A3，A4，A5，A6，A8，L，R2，R7，R9，W和Y在本文中定义。本发明还提供包含该化合物的药物组合物，以及用于治疗由于BACE的活性而导致的斑块形成和沉积相关疾病和/或病症的化合物和组合物的相应用途。这种BACE介导的疾病包括例如阿尔茨海默病，认知缺陷，认知障碍，精神分裂症和其他中枢神经系统疾病。本发明还提供式II和III的化合物，式I，II和III的次级实施方案，可用于制备式I-III化合物的中间体和方法和方法。

2. 发明申请

US20130338177A1 Spiro-Amino-Imidazolone and Spiro-Amino-Dihydro-Pyrimidinone Compounds as Beta-Secretase Modulators and Methods of Use 有权
标题翻译：螺氨基 - 咪唑啉酮和螺 - 氨基 - 二氢 - 嘧啶酮化合物作为β-分泌酶调节剂和使用方法
公开(公告)号：US20130338177A1
公开(公告)日：2013-12-19
申请号：US13988745
申请日：2011-11-18
申请人： Ana Elena Minatti , Oleg Epstein , Ryan White , Matthew Weiss , Wenge Zhong , Jonathan D. Low
发明人： Ana Elena Minatti , Oleg Epstein , Ryan White , Matthew Weiss , Wenge Zhong , Jonathan D. Low
IPC分类号： C07D491/107 , C07D491/20
CPC分类号： C07D491/107 , C07D491/20
摘要： The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula (I), wherein variables A1, A3, A4, A5, A6, A8, L, R2, R7, R9, W and Y of Formula (I) are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to plaque formation and deposition, resulting from the activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas (II) and (III), sub-Formula embodiments of Formulas (I), (II) and (III), intermediates and processes and methods useful for the preparation of compounds of Formulae (I-III).
摘要翻译：本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。化合物具有通式（I），其中式（I）的变量A1，A3，A4，A5，A6，A8，L，R2，R7，R9，W和Y如本文所定义。本发明还提供包含该化合物的药物组合物，以及用于治疗由于BACE的活性而导致的斑块形成和沉积相关疾病和/或病症的化合物和组合物的相应用途。这种BACE介导的疾病包括例如阿尔茨海默病，认知缺陷，认知障碍，精神分裂症和其他中枢神经系统疾病。本发明还提供式（II）和（III）的化合物，式（I），（II）和（III）的分式实施方案，可用于制备式（I-III）化合物的中间体和方法和方法）。

3. 发明申请

US20110251190A1 SPIRO-TETRACYCLIC RING COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE 有权
标题翻译：作为β-分泌酶调节剂的螺环四环化合物及其使用方法
公开(公告)号：US20110251190A1
公开(公告)日：2011-10-13
申请号：US13047734
申请日：2011-03-14
申请人： Yuan CHENG , Ryan White , Albert Amegadzie , James Brown , Alan C. Cheng , Erin F. Dimauro , Thomas Dineen , Oleg Epstein , Vijay Keshav Gore , Jason Brooks Human , Ted Judd , Charles Kreiman , Qingyian Liu , Patricia Lopez , Vu Van Ma , Isaac Marx , Ana Minatti , Hanh Nho Nguyen , Nick A. Paras , Vinod F. Patel , Wenyuan Qian , Matthew Weiss , Qiufen Xue , Xiao Mei Zheng , Wenge Zhong
发明人： Yuan CHENG , Ryan White , Albert Amegadzie , James Brown , Alan C. Cheng , Erin F. Dimauro , Thomas Dineen , Oleg Epstein , Vijay Keshav Gore , Jason Brooks Human , Ted Judd , Charles Kreiman , Qingyian Liu , Patricia Lopez , Vu Van Ma , Isaac Marx , Ana Minatti , Hanh Nho Nguyen , Nick A. Paras , Vinod F. Patel , Wenyuan Qian , Matthew Weiss , Qiufen Xue , Xiao Mei Zheng , Wenge Zhong
IPC分类号： A61K31/538 , A61K31/436 , C07D413/14 , C07D417/14 , A61K31/444 , A61P25/00 , C07D513/10 , A61K31/4545 , C07D498/10 , A61K31/497 , A61P25/28 , A61P25/16 , C07D513/20 , A61K31/506
CPC分类号： C07D491/10 , A61K31/42 , A61K31/422 , A61K31/4439 , A61K31/506 , A61K31/5377 , C07D221/20 , C07D235/02 , C07D263/08 , C07D295/135 , C07D498/10 , C07D498/20 , C07D513/10 , C09B11/28
摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and other related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, R2, R7, X and Y of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.
摘要翻译：本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默氏病（AD））和其它相关病症的新一类化合物。在一个实施方案中，化合物具有通式I，其中式I中的A1，A2，A3，A4，A5，A6，R2，R7，X和Y如本文所定义。本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的病症和病症的用途。这种病症包括例如阿尔茨海默氏病，认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。本发明还包括式I的其它实施方案，可用于制备式I化合物的中间体和方法。

4. 发明授权

US08883782B2 Spiro-tetracyclic ring compounds as beta-secretase modulators and methods of use 有权
标题翻译：螺四环环化合物作为β-分泌酶调节剂和使用方法
公开(公告)号：US08883782B2
公开(公告)日：2014-11-11
申请号：US13047734
申请日：2011-03-14
申请人： Yuan Cheng , Ryan White , Albert Amegadzie , James Brown , Alan C. Cheng , Erin F. Dimauro , Thomas Dineen , Oleg Epstein , Vijay Keshav Gore , Jason Brooks Human , Ted Judd , Charles Kreiman , Qingyian Liu , Patricia Lopez , Vu Van Ma , Isaac Marx , Ana Minatti , Hanh Nho Nguyen , Nick A. Paras , Vinod F. Patel , Wenyuan Qian , Matthew Weiss , Qiufen Xue , Xiao Mei Zheng , Wenge Zhong
发明人： Yuan Cheng , Ryan White , Albert Amegadzie , James Brown , Alan C. Cheng , Erin F. Dimauro , Thomas Dineen , Oleg Epstein , Vijay Keshav Gore , Jason Brooks Human , Ted Judd , Charles Kreiman , Qingyian Liu , Patricia Lopez , Vu Van Ma , Isaac Marx , Ana Minatti , Hanh Nho Nguyen , Nick A. Paras , Vinod F. Patel , Wenyuan Qian , Matthew Weiss , Qiufen Xue , Xiao Mei Zheng , Wenge Zhong
IPC分类号： A61K31/42 , A61K31/422 , A61K31/506 , A61K31/4439 , A61K31/5377 , C07D221/20 , C07D235/02 , C07D263/08 , C07D295/135 , C07D491/10 , C07D498/10
CPC分类号： C07D491/10 , A61K31/42 , A61K31/422 , A61K31/4439 , A61K31/506 , A61K31/5377 , C07D221/20 , C07D235/02 , C07D263/08 , C07D295/135 , C07D498/10 , C07D498/20 , C07D513/10 , C09B11/28
摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and other related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, R2, R7, X and Y of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.
摘要翻译：本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默氏病（AD））和其它相关病症的新一类化合物。在一个实施方案中，化合物具有通式I，其中式I中的A1，A2，A3，A4，A5，A6，R2，R7，X和Y如本文所定义。本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的病症和病症的用途。这种病症包括例如阿尔茨海默氏病，认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。本发明还包括式I的其它实施方案，可用于制备式I化合物的中间体和方法。

5. 发明授权

US08426447B2 Spiro-tricyclic ring compounds as beta-secretase modulators and methods of use 有权
标题翻译：螺三环环化合物作为β-分泌酶调节剂和使用方法
公开(公告)号：US08426447B2
公开(公告)日：2013-04-23
申请号：US12558426
申请日：2009-09-11
申请人： Ryan White , Albert Amegadzie , Marian C. Bryan , Jian Jeffrey Chen , Alan C. Cheng , Thomas Dineen , Oleg Epstein , Vijay Keshav Gore , Zihao Hua , Jason Brooks Human , Hongbing Huang , Charles Kreiman , Daniel La , Qingyian Liu , Vu Van Ma , Isaac Marx , Vinod F Patel , Wenyuan Qian , Matthew Weiss , Chester Chenguang Yuan
发明人： Ryan White , Albert Amegadzie , Marian C. Bryan , Jian Jeffrey Chen , Alan C. Cheng , Thomas Dineen , Oleg Epstein , Vijay Keshav Gore , Zihao Hua , Jason Brooks Human , Hongbing Huang , Charles Kreiman , Daniel La , Qingyian Liu , Vu Van Ma , Isaac Marx , Vinod F Patel , Wenyuan Qian , Matthew Weiss , Chester Chenguang Yuan
IPC分类号： A61K31/44 , C07D311/82 , C07D401/00 , C07D413/00
CPC分类号： C07D498/10 , C07D513/10
摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, T1, T2, W, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.
摘要翻译：本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。在一个实施方案中，化合物具有通式I，其中式I的A1，A2，A3，A4，A5，A6，T1，T2，W，X，Y和Z如本文所定义。本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的病症和病症的用途。这种病症包括例如阿尔茨海默氏病，认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。本发明还包括式I的其它实施方案，可用于制备式I化合物的中间体和方法。

6. 发明申请

US20100087429A1 SPIRO-TRICYCLIC RING COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE 有权
标题翻译： SPIRO-TRICYCLIC环化合物作为β-分泌酶调节剂和使用方法
公开(公告)号：US20100087429A1
公开(公告)日：2010-04-08
申请号：US12558426
申请日：2009-09-11
申请人： Ryan White , Albert Amegadzie , Marian C. Bryan , Jian Jeffrey Chen , Alan C. Cheng , Thomas Dineen , Oleg Epstein , Vijay Keshav Gore , Zihao Hua , Jason Brooks Human , Hongbing Huang , Charles Kreiman , Daniel La , Qingyian Liu , Vu Van Ma , Isaac Marx , Vinod F. Patel , Wenyuan Qian , Matthew Weiss , Chester Chenguang Yuan
发明人： Ryan White , Albert Amegadzie , Marian C. Bryan , Jian Jeffrey Chen , Alan C. Cheng , Thomas Dineen , Oleg Epstein , Vijay Keshav Gore , Zihao Hua , Jason Brooks Human , Hongbing Huang , Charles Kreiman , Daniel La , Qingyian Liu , Vu Van Ma , Isaac Marx , Vinod F. Patel , Wenyuan Qian , Matthew Weiss , Chester Chenguang Yuan
IPC分类号： A61K31/421 , C07D498/10 , C07D513/10 , C07D498/20 , A61K31/506 , A61K31/4439 , A61K31/5377 , A61P25/00 , A61P25/28
CPC分类号： C07D498/10 , C07D513/10
摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, T1, T2, W, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.
摘要翻译：本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。在一个实施方案中，化合物具有通式I，其中式I的A1，A2，A3，A4，A5，A6，T1，T2，W，X，Y和Z如本文所定义。本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的病症和病症的用途。这种病症包括例如阿尔茨海默氏病，认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。本发明还包括式I的其它实施方案，可用于制备式I化合物的中间体和方法。

7. 发明授权

US08962859B2 Spiro-amino-imidazo-fused heterocyclic compounds as beta-secretase modulators and methods of use 有权
标题翻译：螺氨基 - 咪唑稠合杂环化合物作为β-分泌酶调节剂和使用方法
公开(公告)号：US08962859B2
公开(公告)日：2015-02-24
申请号：US13982096
申请日：2012-02-13
申请人： Oleg Epstein , Ryan White , Vinod F. Patel , Jason Brooks Human
发明人： Oleg Epstein , Ryan White , Vinod F. Patel , Jason Brooks Human
IPC分类号： C07D487/10 , C07D313/00 , C07D491/20 , A61K31/353
CPC分类号： C07D491/20 , A61K31/353
摘要： The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A1, A3, A5, A6, A8, R2, R7, X, Y and Z of Formula I are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to plaque formation and deposition, resulting from the activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits and impairments, schizophrenia and other central nervous system conditions and disorders. The invention further provides compounds of Formulas II and III, and of sub-formulas of Formulas I, II and III, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III.
摘要翻译：本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。化合物具有通式I：其中式I的变量A1，A3，A5，A6，A8，R2，R7，X，Y和Z如本文所定义。本发明还提供包含该化合物的药物组合物，以及用于治疗由于BACE的活性而导致的斑块形成和沉积相关疾病和/或病症的化合物和组合物的相应用途。这种BACE介导的病症包括例如阿尔茨海默病，认知缺陷和损伤，精神分裂症和其他中枢神经系统病症和障碍。本发明还提供了式II和III的化合物和式I，II和III的分子式，可用于制备式I-III化合物的中间体和方法和方法。

8. 发明申请

US20140038954A1 Spiro-Amino-Imidazo-Fused Heterocyclic Compounds as Beta-secretase Modulators and Methods of Use 有权
标题翻译：螺氨基 - 咪唑并 - 杂环化合物作为β-分泌酶调节剂和使用方法
公开(公告)号：US20140038954A1
公开(公告)日：2014-02-06
申请号：US13982096
申请日：2012-02-13
申请人： Oleg Epstein , Ryan White , Vinod F. Patel , Jason Human
发明人： Oleg Epstein , Ryan White , Vinod F. Patel , Jason Human
IPC分类号： C07D491/20
CPC分类号： C07D491/20 , A61K31/353
摘要： The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I, wherein variables A1, A3, A4, A5, A6, A8, R2, R7, X, Y and Z of Formula I are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to plaque formation and deposition, resulting from the activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits and impairments, schizophrenia and other central nervous system conditions and disorders. The invention further provides compounds of Formulas II and III, and of sub-formulas of Formulas I, II and III, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III.
摘要翻译：本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。化合物具有通式I，其中式I的变量A1，A3，A4，A5，A6，A8，R2，R7，X，Y和Z如本文所定义。本发明还提供包含该化合物的药物组合物，以及用于治疗由于BACE的活性而导致的斑块形成和沉积相关疾病和/或病症的化合物和组合物的相应用途。这种BACE介导的病症包括例如阿尔茨海默病，认知缺陷和损伤，精神分裂症和其他中枢神经系统病症和障碍。本发明还提供了式II和III的化合物和式I，II和III的分子式，可用于制备式I-III化合物的中间体和方法和方法。

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