公开(公告)号：US20210188863A1

公开(公告)日：2021-06-24

申请号：US16755172

申请日：2018-10-08

申请人： David Annunziato CANDITO ,  Thomas, H. GRAHAM ,  John ACTON ,  Ryan Wing-Kun CHAU ,  Joanna L. CHEN ,  J. Michael ELLIS ,  Peter H. FULLER ,  Anmol GULATI ,  Hakan GUNAYDIN ,  Solomon KATTAR ,  Mitchell Henry KEYLOR ,  Blair T. LAPOINTE ,  Ping LIU ,  Weiguo LIU ,  Joey L. METHOT ,  Santhosh F. NEELAMKAVIL ,  Vladimir SIMOV ,  Ling TONG ,  Harold B. WOOD ,  Merck Sharp & Dohme Corp.

发明人： David Annunziato Candito ,  Thomas H. Graham ,  John Acton ,  Ryan Wing-Kun Chau ,  Joanna L. Chen ,  J. Michael Ellis ,  Peter H. Fuller ,  Anmol Gulati ,  Hakan Gunaydin ,  Solomon Kattar ,  Mitchell Henry Keylor ,  Blair T. Lapointe ,  Ping Liu ,  Weiguo Liu ,  Joey L. Methot ,  Santhosh F. Neelamkavil ,  Vladimir Simov ,  Ling Tong ,  Harold B. Wood

IPC分类号： C07D491/10 ,  C07D403/14 ,  C07D487/08 ,  C07D405/14 ,  C07D401/14 ,  C07D413/14 ,  C07D498/10 ,  C07D519/00 ,  C07D498/04 ,  C07D403/04

摘要： The present invention is directed to substituted certain reversed indazolyl-spiro[2.2]pentane-carbonitrile derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, X, Y, and Z are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

公开(公告)号：US20230023066A1

公开(公告)日：2023-01-26

申请号：US17769814

申请日：2020-10-20

申请人： Mitchell H. KEYLOR ,  Michael j. ARDOLINO ,  Ryan W. CHAU ,  Peter H. FULLER ,  Anmol GULATI ,  Rebecca Elizabeth JOHNSON ,  Solomon D. KATTAR ,  Kaila A. MARGREY ,  Gregori J. MOREIELLO ,  Santhosh F. NEELAMKAVIL ,  Xin YAN ,  Elsie C. YU ,  Cayetena Carmela ZARATE SAEZ ,  Merck Sharp & Dohme Corp.

发明人： Mitchell H. Keylor ,  Michael J. Ardolino ,  Ryan W. Chau ,  Peter H. Fuller ,  Anmol Gulati ,  Rebecca Elizabeth Johnson ,  Solomon D. Kattar ,  Kaila A. Margrey ,  Gregori J. Morriello ,  Santhosh F. Neelamkavil ,  Xin Yan ,  Elsie C. Yu ,  Cayetana Carmela Zarate Saez

IPC分类号： C07D403/14 ,  C07D405/14 ,  C07D403/12 ,  C07D417/14 ,  C07D401/14 ,  C07D413/14 ,  C07D409/14

摘要： The present invention is directed to substituted certain N-(heteroaryl)quinazolin-2-amine derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein J, R3, and R4, are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of diseases, such as Parkinson's disease, in which LRRK-2 kinase is involved.

公开(公告)号：US09944643B2

公开(公告)日：2018-04-17

申请号：US15116547

申请日：2015-02-06

申请人： MERCK SHARP & DOHME CORP. ,  Santhosh F. Neelamkavil ,  Scott D. Edmondson ,  Alan W. Hruza ,  Zahid Hussain ,  Charles Lesburg ,  Remond Moningka

发明人： Santhosh F. Neelamkavil ,  Scott D. Edmondson ,  Alan W. Hruza ,  Zahid Hussain ,  Charles Lesburg ,  Remond Moningka

IPC分类号： C07D471/08 ,  C07D487/08

CPC分类号： C07D471/08 ,  C07D487/08

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 thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.

公开(公告)号：US20160347757A1

公开(公告)日：2016-12-01

申请号：US15116659

申请日：2015-02-06

申请人： Santhosh F. NEELAMKAVIL ,  Scott D. EDMONDSON ,  Zhuyan GUO ,  Alan W. HRUZA ,  Zahid HUSSAIN ,  Charles A. LESBURG ,  Remond MONINGKA ,  Anthony K. OGAWA ,  Rudrajit MAL ,  MERCK SHARP & DOHME CORP

发明人： Santhosh F. Neelamkavil ,  Scott D. Edmondson ,  Zhuyan Guo ,  Alan W. Hruza ,  Zahid Hussain ,  Charles A. Lesburg ,  Remond Moningka ,  Anthony K. Ogawa ,  Rudrajit Mal

IPC分类号： C07D487/08 ,  C07D471/08

CPC分类号： C07D487/08 ,  C07D471/08

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 thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.

摘要翻译： 本发明提供式（I）的化合物和包含一种或多种所述化合物的药物组合物，以及使用所述化合物治疗或预防血栓形成，栓塞，高凝状态或纤维变化的方法。 该化合物是选择性因子XIa抑制剂或因子XIa和血浆激肽释放酶的双重抑制剂。

公开(公告)号：US11161854B2

公开(公告)日：2021-11-02

申请号：US16755172

申请日：2018-10-08

申请人： Merck Sharp & Dohme Corp. ,  David Annunziato Candito ,  Thomas H. Graham ,  John Acton ,  Ryan Wing-Kun Chau ,  Joanna L. Chen ,  J. Michael Ellis ,  Peter H. Fuller ,  Anmol Gulati ,  Hakan Gunaydin ,  Solomon Kattar ,  Mitchell Henry Keylor ,  Blair T. Lapointe ,  Ping Liu ,  Weiguo Liu ,  Joey L. Methot ,  Santhosh F. Neelamkavil ,  Vladimir Simov ,  Ling Tong ,  Harold B. Wood

发明人： David Annunziato Candito ,  Thomas H. Graham ,  John Acton ,  Ryan Wing-Kun Chau ,  Joanna L. Chen ,  J. Michael Ellis ,  Peter H. Fuller ,  Anmol Gulati ,  Hakan Gunaydin ,  Solomon Kattar ,  Mitchell Henry Keylor ,  Blair T. Lapointe ,  Ping Liu ,  Weiguo Liu ,  Joey L. Methot ,  Santhosh F. Neelamkavil ,  Vladimir Simov ,  Ling Tong ,  Harold B. Wood

IPC分类号： C07D491/10 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D487/08 ,  C07D498/04 ,  C07D498/10 ,  C07D519/00

摘要： The present invention is directed to substituted certain reversed indazolyl-spiro[2.2]pentane-carbonitrile derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, X, Y, and Z are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

公开(公告)号：US20220259188A1

公开(公告)日：2022-08-18

申请号：US17614732

申请日：2020-06-01

申请人： Hua ZHOU ,  John J. ACTON, III ,  Michael J. ARDOLINO ,  Yi-Heng CHEN ,  Peter H. FULLER ,  Anmol GULATI ,  Rebecca Elizabeth JOHNSON ,  William P. KAPLAN ,  Solomon D. KATTAR ,  Mitchell H. KEYLOR ,  Derun LI ,  Kaitlyn Marie LOGAN ,  Min LU ,  Gregori J. MORRIELLO ,  Santhosh F. NEELAMKAVIL ,  Barbara PIO ,  Nunzio SCIAMMETTA ,  Vladimir SIMOV ,  Jing SU ,  Luis TORRES ,  Xin YAN ,  Merck Sharp & Dohme Corp.

发明人： Hua Zhou ,  John J. Acton, III ,  Michael J. Ardolino ,  Yi-Heng Chen ,  Peter H. Fuller ,  Anmol Gulati ,  Rebecca Elizabeth Johnson ,  William P. Kaplan ,  Solomon D. Kattar ,  Mitchell H. Keylor ,  Derun Li ,  Kaitlyn Marie Logan ,  Min Lu ,  Gregori J. Morriello ,  Santhosh F. Neelamkavil ,  Barbara Pio ,  Nunzio Sciammetta ,  Vladimir Simov ,  Jing Su ,  Luis Torres ,  Xin Yan

IPC分类号： C07D405/14 ,  C07D487/08 ,  C07D409/14 ,  C07D403/04 ,  C07D403/14 ,  C07D498/04 ,  C07D498/08 ,  C07D487/10 ,  C07D401/14 ,  C07D471/10 ,  C07D491/107 ,  C07D471/04 ,  C07D487/04 ,  A61P25/16

摘要： The present invention is directed to substituted certain 1-pyrazolyl, 5-, 6-disubstituted indazole derivatives of Formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, and ring A are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of diseases, such as Parkinson's disease, in which LRRK-2 kinase is involved.

公开(公告)号：US20170044183A1

公开(公告)日：2017-02-16

申请号：US15305421

申请日：2015-04-21

申请人： Yeon-Hee Lim ,  Zhuyan Guo ,  Amjad Ali ,  Scott D. Edmondson ,  Weiguo Liu ,  Giocanda V. Gallo-Etienne ,  Heping Wu ,  Ying-Duo Gao ,  Andrew W. Stamford ,  Younong Yu ,  Nancy J. Kevin ,  Rajan Anand ,  Deyou Sha ,  Santhosh F. Neelamkavil ,  Zahid Hussain ,  Puneet Kumar ,  Remond Moningka ,  Joseph L. Duffy ,  Jiayi Xu ,  Yu Jiang ,  Anjan Chakrabarti ,  Hiroki Sone

发明人： Yeon-Hee Lim ,  Zhuyan Guo ,  Amjad Ali ,  Scott D. Edmondson ,  Weiguo Liu ,  Giocanda V. Gallo-Etienne ,  Heping Wu ,  Ying-Duo Gao ,  Andrew W. Stamford ,  Younong Yu ,  Nancy J. Kevin ,  Rajan Anand ,  Deyou Sha ,  Santhosh F. Neelamkavil ,  Zahid Hussain ,  Puneet Kumar ,  Remond Moningka ,  Joseph L. Duffy ,  Jiayi Xu ,  Yu Jiang ,  Anjan Chakrabarti ,  Hiroki Sone

IPC分类号： C07D498/20 ,  C07F9/6561 ,  C07D487/10 ,  C07D498/10 ,  C07D471/10

CPC分类号： C07D498/20 ,  C07D471/10 ,  C07D487/10 ,  C07D498/10 ,  C07F9/6561

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 thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.

摘要翻译： 本发明提供式（I）的化合物和包含一种或多种所述化合物的药物组合物，以及使用所述化合物治疗或预防血栓形成，栓塞，高凝状态或纤维变化的方法。 该化合物是选择性因子XIa抑制剂或因子XIa和血浆激肽释放酶的双重抑制剂。