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。

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。

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。

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。

公开(公告)号：US20120190666A1

公开(公告)日：2012-07-26

申请号：US13319683

申请日：2010-05-12

申请人： Christiane Bode ,  Alessandro Boezio ,  Alan C. Cheng ,  Deborah Choquette ,  James Robert Coats ,  Katrina Woodin Copeland ,  Hongbing Huang ,  Daniel La ,  Richard Thomas Lewis ,  Hongyu Liao ,  Michele Potashman ,  John Stellwagen ,  Shuyan Yi ,  Mark H. Norman ,  Markian M. Stec ,  Emily Anne Peterson ,  Russell Graceffa

发明人： Christiane Bode ,  Alessandro Boezio ,  Alan C. Cheng ,  Deborah Choquette ,  James Robert Coats ,  Katrina Woodin Copeland ,  Hongbing Huang ,  Daniel La ,  Richard Thomas Lewis ,  Hongyu Liao ,  Michele Potashman ,  John Stellwagen ,  Shuyan Yi ,  Mark H. Norman ,  Markian M. Stec ,  Emily Anne Peterson ,  Russell Graceffa

IPC分类号： A61K31/52 ,  C07D401/14 ,  A61K31/506 ,  A61P35/02 ,  A61K31/53 ,  C07D487/04 ,  A61K31/5377 ,  A61P35/00 ,  C07D473/40 ,  C07D471/04

CPC分类号： C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D471/04 ,  C07D487/04 ,  C07D519/00

摘要： The present invention provides compounds that are PIKK inhibitors, more specifically, mTOR and/or PI3Kα kinase inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of kinases, specifically PI3 kinases, more specifically, mTOR and/or PI3Kα, such as cancer. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

摘要翻译： 本发明提供了PIKK抑制剂，更具体地，mTOR和/或PI3Kα激酶抑制剂的化合物，因此可用于治疗通过抑制激酶可治疗的疾病，特别是PI3激酶，更具体地，mTOR和/或PI3Kα，例如 癌症。 还提供含有这些化合物的药物组合物和制备这些化合物的方法。

公开(公告)号：US20240190892A1

公开(公告)日：2024-06-13

申请号：US18550332

申请日：2022-03-16

申请人： Natalija Cernaka ,  Anthony K. OGAWA ,  Alan C. CHENG ,  Jianming BAO ,  Phillip Patrick SHARP ,  Jovan Alexander LOPEZ ,  Dong XIAO ,  Haiqun TANG ,  Merck Sharp & Dohme LLC

发明人： Natalija Cernaka ,  Anthony K. Ogawa ,  Alan C. Cheng ,  Jianming Bao ,  Phillip Patrick Sharp ,  Jovan Alexander Lopez ,  Dong Xiao ,  Haiqun Tang

IPC分类号： C07D498/20 ,  A61K31/5386 ,  A61K45/06 ,  C07D519/00

CPC分类号： C07D498/20 ,  A61K31/5386 ,  A61K45/06 ,  C07D519/00

摘要： The present invention provides a compound of formula I and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

公开(公告)号：US20230416227A1

公开(公告)日：2023-12-28

申请号：US18043357

申请日：2021-09-09

申请人： Merck Sharp & Dohme LLC ,  Anthony Ken OGAWA ,  Christopher J. SINZ ,  Jacqueline D. HICKS ,  Alan C. CHENG ,  Song YANG ,  Jianming BAO ,  Donna A. A. W. HAYES ,  Simon B. LANG ,  Maoqun TIAN ,  Salman JABRI ,  Galen Paul SHEARN-NANCE ,  Rongze KUANG ,  Zhiqiang ZHAO ,  Zhicai WU

发明人： Anthony Ken Ogawa ,  Christopher J. Sinz ,  Jacqueline D. Hicks ,  Alan C. Cheng ,  Song Yang ,  Jianming Bao ,  Donna A. A. W. Hayes ,  Simon B. Lang ,  Maoqun Tian ,  Salman Jabri ,  Galen Paul Shearn-Nance ,  Rongze Kuang ,  Zhiqiang Zhao ,  Zhicai Wu

IPC分类号： C07D401/14 ,  A61K45/06 ,  A61P9/10

CPC分类号： C07D401/14 ,  A61P9/10 ,  A61K45/06

摘要： The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

公开(公告)号：US08716281B2

公开(公告)日：2014-05-06

申请号：US13697730

申请日：2011-05-04

申请人： Marian C. Bryan ,  Alan C. Cheng ,  Elizabeth M. Doherty ,  James R. Falsey ,  Ingrid M. Fellows ,  Joseph L. Kim ,  Richard T. Lewis ,  Michele H. Potashman ,  Douglas A. Whittington

发明人： Marian C. Bryan ,  Alan C. Cheng ,  Elizabeth M. Doherty ,  James R. Falsey ,  Ingrid M. Fellows ,  Joseph L. Kim ,  Richard T. Lewis ,  Michele H. Potashman ,  Douglas A. Whittington

IPC分类号： A61K31/18

CPC分类号： C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

摘要： The present invention describes pyrimidine compounds of Formula I that are useful as anaplastic lymphoma kinase inhibitors, pharmaceutically acceptable compositions thereof, and methods of using the same.

摘要翻译： 本发明描述了可用作间变性淋巴瘤激酶抑制剂，其药学上可接受的组合物的式I的嘧啶化合物及其使用方法。

公开(公告)号：US20130158019A1

公开(公告)日：2013-06-20

申请号：US13697730

申请日：2011-05-04

申请人： Marian C. Bryan ,  Alan C. Cheng ,  Elizabeth M. Doherty ,  James R. Falsey ,  Ingrid M. Fellows ,  Joseph L. Kim ,  Richard T. Lewis ,  Michele H. Potashman ,  Douglas A. Whittington

发明人： Marian C. Bryan ,  Alan C. Cheng ,  Elizabeth M. Doherty ,  James R. Falsey ,  Ingrid M. Fellows ,  Joseph L. Kim ,  Richard T. Lewis ,  Michele H. Potashman ,  Douglas A. Whittington

IPC分类号： C07D401/04 ,  C07D401/14 ,  C07D413/14 ,  C07D417/14 ,  C07D417/04 ,  C07D471/04 ,  C07D409/14 ,  C07D405/14 ,  C07D403/04

CPC分类号： C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

摘要： Compounds of Formula I are useful inhibitors of anaplastic lymphoma kinase. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

摘要翻译： 式I化合物是间变性淋巴瘤激酶的有用抑制剂。 式I的化合物具有以下结构：其中本文提供变量的定义。

公开(公告)号：US20120165334A1

公开(公告)日：2012-06-28

申请号：US13260715

申请日：2010-02-10

申请人： Alessandro Boezio ,  Alan C. Cheng ,  James Robert Coats ,  Katrina Woodin Copeland ,  Russell Graceffa ,  Jean-Christophe Harmanage ,  Hongbing Huang ,  Daniel La ,  Philip R. Olivieri ,  Emily Anne Peterson ,  Laurie Schenkel

发明人： Alessandro Boezio ,  Alan C. Cheng ,  James Robert Coats ,  Katrina Woodin Copeland ,  Russell Graceffa ,  Jean-Christophe Harmanage ,  Hongbing Huang ,  Daniel La ,  Philip R. Olivieri ,  Emily Anne Peterson ,  Laurie Schenkel

IPC分类号： A61K31/53 ,  A61P35/00 ,  C07D403/04 ,  A61K31/506 ,  C07D401/14 ,  C07D403/14

CPC分类号： C07D403/14 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

摘要： The present invention provides compounds that are kinase inhibitors, specifically PIK kinase inhibitors, more specifically, mTOR inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of kinases, specifically PIK kinase inhibitors, more specifically, mTOR such as cancer. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

摘要翻译： 本发明提供了化合物，其是激酶抑制剂，特别是PIK激酶抑制剂，更具体地，mTOR抑制剂，因此可用于治疗通过抑制激酶可治疗的疾病，特别是PIK激酶抑制剂，更具体地，mTOR如癌症。 还提供含有这些化合物的药物组合物和制备这些化合物的方法。