公开(公告)号：US20190307753A1

公开(公告)日：2019-10-10

申请号：US16301935

申请日：2017-05-11

申请人： Alan WHITEHEAD ,  Olga ORNOSKI ,  Subharekha RAGHAVAN ,  Raphaelle BERGER ,  Joie GARFUNKLE ,  Zhiqiang YANG ,  Gang JI ,  Falong JIANG ,  Jianmin FU ,  Merck Sharp & Dohme Corp.

发明人： Alan Whitehead ,  Olga Ornoski ,  Subharekha Raghavan ,  Raphaelle Berger ,  Joie Garfunkle ,  Zhiqiang Yang ,  Gang JI ,  Falong Jiang ,  Jianmin Fu

IPC分类号： A61K31/519 ,  C07D519/00 ,  A61P9/12

摘要： The invention provides certain fused pyrazine compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, R1, R3, R4a, R5a, R5b, R6, and the subscript t are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate (“cGMP”), and are generally suitable for the therapy and prophylaxis of diseases or disorders which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and disorders and for preparing pharmaceutical s for this purpose.

公开(公告)号：US10780092B2

公开(公告)日：2020-09-22

申请号：US16301935

申请日：2017-05-11

申请人： Merck Sharp & Dohme Corp. ,  Alan Whitehead ,  Olga Ornoski ,  Subharekha Raghavan ,  Raphaelle Berger ,  Joie Garfunkle ,  Zhiqiang Yang ,  Gang Ji ,  Falong Jiang ,  Jianmin Fu

发明人： Alan Whitehead ,  Olga Ornoski ,  Subharekha Raghavan ,  Raphaelle Berger ,  Joie Garfunkle ,  Zhiqiang Yang ,  Gang Ji ,  Falong Jiang ,  Jianmin Fu

IPC分类号： C07D487/04 ,  C07D519/00 ,  A61K31/519 ,  A61P9/12

摘要： The invention provides certain fused pyrazine compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, R1, R3, R4a, R5a, R5b, R6, and the subscript t are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate (“cGMP”), and are generally suitable for the therapy and prophylaxis of diseases or disorders which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and disorders and for preparing pharmaceuticals for this purpose.

公开(公告)号：US20170174693A1

公开(公告)日：2017-06-22

申请号：US15384429

申请日：2016-12-20

申请人： Raphaelle Berger ,  Yi-Heng Chen ,  Guoqing Li ,  Joie Garfunkle ,  Hong-Dong Li ,  Shouwu Miao ,  Subharekha Raghavan ,  Cameron J. Smith ,  John Stelmach ,  Alan Whitehead ,  Rui Zhang ,  Yong Zhang ,  Jianmin Fu ,  Gang Ji ,  Falong Jiang

发明人： Raphaelle Berger ,  Yi-Heng Chen ,  Guoqing Li ,  Joie Garfunkle ,  Hong-Dong Li ,  Shouwu Miao ,  Subharekha Raghavan ,  Cameron J. Smith ,  John Stelmach ,  Alan Whitehead ,  Rui Zhang ,  Yong Zhang ,  Jianmin Fu ,  Gang Ji ,  Falong Jiang

IPC分类号： C07D487/04 ,  A61K31/519 ,  C07D519/00 ,  A61K45/06

CPC分类号： C07D487/04 ,  A61K31/519 ,  A61K45/06 ,  C07D519/00

摘要： The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R1, R2, R4, Ra, and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate (“cGMP”), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose.

公开(公告)号：US20160304537A1

公开(公告)日：2016-10-20

申请号：US15103148

申请日：2014-12-05

申请人： Xiaoqing HAN ,  Alan WHITEHEAD ,  Subharekha RAGHAVAN ,  Timothy A. CERNAK ,  Spencer DREHER ,  Jonathan GROEPER ,  Jian GUO ,  Yong ZHANG ,  MERCK SHARP & DOHME CORP.

发明人： Xiaoqing Han ,  Alan Whitehead ,  Subharekha Raghavan ,  Timothy A. Cernak ,  Spencer Dreher ,  Jonathan Groeper ,  Jian Guo ,  Yong Zhang

IPC分类号： C07D519/00 ,  A61K45/06 ,  A61K31/519

CPC分类号： C07D519/00 ,  A61K31/519 ,  A61K31/52 ,  A61K45/06 ,  C07B2200/05 ,  A61K2300/00

摘要： A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula I or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20160304536A1

公开(公告)日：2016-10-20

申请号：US15103140

申请日：2014-12-05

申请人： Xiaoqing HAN ,  Alan WHITEHEAD ,  Subharekha RAGHAVAN ,  Jonathan GROEPER ,  Jian GUO ,  Yong ZHANG ,  MERCK SHARP & DOHME CORP.

发明人： Xiaoqing Han ,  Alan Whitehead ,  Subharekha Raghavan ,  Jonathan Groeper ,  Jian Guo ,  Yong Zhang

IPC分类号： C07D519/00 ,  A61K31/519 ,  A61K45/06

CPC分类号： C07D519/00 ,  A61K31/519 ,  A61K31/52 ,  A61K45/06 ,  A61K2300/00

摘要： A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula I or a pharmaceutically acceptable salt thereof.

摘要翻译： 式I化合物或其药学上可接受的盐能够调节身体产生环鸟苷酸（“cGMP”），并且通常适用于治疗和预防与受干扰的cGMP平衡有关的疾病。 本发明还涉及用于制备式I化合物或其药学上可接受的盐的方法，用于治疗和预防上述疾病和用于制备用于该目的的药物以及包含式I化合物的药物制剂 或其药学上可接受的盐。

公开(公告)号：US20130072492A1

公开(公告)日：2013-03-21

申请号：US13699046

申请日：2011-05-24

申请人： Subharekha Raghavan ,  John E. Stelmach ,  Cameron J. Smith ,  Hong Li ,  Alan Whitehead ,  Sherman T. Waddell ,  Yi-Heng Chen ,  Shouwu Miao ,  Olga A. Ornoski ,  Joie Garfunkle ,  Xibin Liao ,  Jiang Chang ,  Xiaoqing Han ,  Jian Guo ,  Jonathan A. Groeper ,  Linda L. Brockunier ,  Keith Rosauer ,  Emma R. Parmee

发明人： Subharekha Raghavan ,  John E. Stelmach ,  Cameron J. Smith ,  Hong Li ,  Alan Whitehead ,  Sherman T. Waddell ,  Yi-Heng Chen ,  Shouwu Miao ,  Olga A. Ornoski ,  Joie Garfunkle ,  Xibin Liao ,  Jiang Chang ,  Xiaoqing Han ,  Jian Guo ,  Jonathan A. Groeper ,  Linda L. Brockunier ,  Keith Rosauer ,  Emma R. Parmee

IPC分类号： C07D487/04 ,  C07D495/04 ,  A61K31/5025 ,  A61P9/00 ,  A61P9/10 ,  A61P9/12 ,  A61P9/04 ,  A61P7/02 ,  A61P15/00 ,  A61P11/06 ,  A61P13/12 ,  A61P3/10 ,  A61P1/16 ,  A61P9/08 ,  A61P3/00 ,  A61P3/06 ,  A61P7/10 ,  A61K31/519

CPC分类号： C07D487/04 ,  A61K31/519 ,  C07D519/00

摘要： A compound of Formula (I): or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula (I) or a pharmaceutically acceptable salt thereof.

摘要翻译： 式（I）的化合物或其药学上可接受的盐能够调节人体的环鸟苷酸（cGMP）的产生，并且通常适用于治疗和预防与扰动的cGMP平衡有关的疾病。 本发明还涉及用于制备式I化合物或其药学上可接受的盐的方法，用于治疗和预防上述疾病和用于制备用于该目的的药物以及包含式（III）化合物的药物制剂 I）或其药学上可接受的盐。

公开(公告)号：US09365574B2

公开(公告)日：2016-06-14

申请号：US13699046

申请日：2011-05-24

申请人： Subharekha Raghavan ,  John E. Stelmach ,  Cameron J. Smith ,  Hong Li ,  Alan Whitehead ,  Sherman T. Waddell ,  Yi-Heng Chen ,  Shouwu Miao ,  Olga A. Ornoski ,  Joie Garfunkle ,  Xibin Liao ,  Jiang Chang ,  Xiaoqing Han ,  Jian Guo ,  Jonathan A. Groeper ,  Linda L. Brockunier ,  Keith Rosauer ,  Emma R. Parmee

发明人： Subharekha Raghavan ,  John E. Stelmach ,  Cameron J. Smith ,  Hong Li ,  Alan Whitehead ,  Sherman T. Waddell ,  Yi-Heng Chen ,  Shouwu Miao ,  Olga A. Ornoski ,  Joie Garfunkle ,  Xibin Liao ,  Jiang Chang ,  Xiaoqing Han ,  Jian Guo ,  Jonathan A. Groeper ,  Linda L. Brockunier ,  Keith Rosauer ,  Emma R. Parmee

IPC分类号： C07D487/04 ,  C07D519/00 ,  A61K31/519 ,  A61P29/00 ,  A61P9/12 ,  A61P3/10 ,  A61P9/10 ,  A61P11/06 ,  A61P15/10 ,  A61P9/04 ,  A61P13/12 ,  A61P1/16

CPC分类号： C07D487/04 ,  A61K31/519 ,  C07D519/00

摘要： A compound of Formula (I): or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula (I) or a pharmaceutically acceptable salt thereof.

摘要翻译： 式（I）的化合物或其药学上可接受的盐能够调节身体的环鸟苷酸（“cGMP”）的产生，并且通常适用于治疗和预防与受干扰的cGMP平衡相关的疾病 。 本发明还涉及用于制备式I化合物或其药学上可接受的盐的方法，用于治疗和预防上述疾病和用于制备用于该目的的药物以及包含式（III）化合物的药物制剂 I）或其药学上可接受的盐。

公开(公告)号：US10925876B2

公开(公告)日：2021-02-23

申请号：US16301936

申请日：2017-05-12

申请人： Merck Sharp & Dohme Corp.

发明人： Raphaelle Berger ,  Guizhen Dong ,  Subharekha Raghavan ,  Zhiqiang Yang

IPC分类号： A61K31/519 ,  A61K45/06 ,  C07D519/00 ,  C07D235/00 ,  A61K31/505 ,  C07D249/16

摘要： Provided are methods for treating or preventing a fibrotic disease selected from systemic sclerosis, cystic fibrosis, non-alcoholic steatohepatitis, Peyronie's disease, or interstitial lung disease; the method comprising administering a therapeutically effective amount of a compound of Formula (I) (wherein R1, R2, R3, R4, and R5 are as herein described) or a pharmaceutically acceptable salt thereof, to a patient in need of such therapy.

公开(公告)号：US20170073355A2

公开(公告)日：2017-03-16

申请号：US14945576

申请日：2015-11-19

申请人： Merck Sharp & Dohme Corp.

发明人： Raphaelle Berger ,  Guizhen Dong ,  Subharekha Raghavan ,  Zhiqiang Yang

IPC分类号： C07D519/00 ,  A61K31/519 ,  A61K45/06

CPC分类号： C07D519/00 ,  A61K31/519 ,  A61K45/06 ,  C07D487/04

摘要： A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of Formula I or a pharmaceutically acceptable salt thereof.

摘要翻译： 或其药学上可接受的盐能够调节身体的环鸟苷酸（“cGMP”）的产生，并且通常适合于治疗和预防与受干扰的cGMP平衡相关的疾病。 本发明还涉及用于制备式I化合物或其药学上可接受的盐的方法，用于治疗和预防上述疾病和用于制备用于该目的的药物以及包含式I化合物的药物组合物 或其药学上可接受的盐。

公开(公告)号：US20160145272A1

公开(公告)日：2016-05-26

申请号：US14945576

申请日：2015-11-19

申请人： Merck Sharp & Dohme Corp.

发明人： Raphaelle Berger ,  Guizhen Dong ,  Subharekha Raghavan ,  Zhiqiang Yang

IPC分类号： C07D519/00 ,  A61K31/519 ,  A61K45/06

CPC分类号： C07D519/00 ,  A61K31/519 ,  A61K45/06 ,  C07D487/04

摘要： A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of Formula I or a pharmaceutically acceptable salt thereof.

摘要翻译： 式I化合物或其药学上可接受的盐能够调节身体产生环鸟苷酸（“cGMP”），并且通常适用于治疗和预防与受干扰的cGMP平衡有关的疾病。 本发明还涉及用于制备式I化合物或其药学上可接受的盐的方法，用于治疗和预防上述疾病和用于制备用于该目的的药物以及包含式I化合物的药物组合物 或其药学可接受的盐。