公开(公告)号：US20180305315A1

公开(公告)日：2018-10-25

申请号：US15957739

申请日：2018-04-19

Applicant: Gilead Sciences, Inc.

Inventor： Evangelos Aktoudianakis ,  Todd Appleby ,  Aesop Cho ,  Zhimin Du ,  Michael Graupe ,  Juan A. Guerrero ,  Salman Y. Jabri ,  Lateshkumar Thakorlal Lad ,  Paulo A. Machicao Tello ,  Jonathan William Medley ,  Samuel E. Metobo ,  Prasenjit Kumar Mukherjee ,  Devan Naduthambi ,  Gregory Notte ,  Eric Q. Parkhill ,  Barton W. Phillips ,  Scott Preston Simonovich ,  Neil H. Squires ,  Chandrasekar Venkataramani ,  Peiyuan Wang ,  William J. Watkins ,  Jie Xu ,  Kin Shing Yang ,  Christopher Allen Ziebenhaus

IPC: C07D213/69 ,  A61K45/06 ,  A61K31/444 ,  C07D401/14 ,  A61K31/4545 ,  C07D213/85 ,  A61K31/44 ,  C07D213/30 ,  C07D295/088 ,  A61K31/5377

CPC classification number: C07D213/69 ,  A61K31/44 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/497 ,  A61K31/5377 ,  A61K45/06 ,  C07D213/30 ,  C07D213/61 ,  C07D213/64 ,  C07D213/85 ,  C07D295/088 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D487/08 ,  C07D487/10 ,  C07D491/107 ,  C07D498/04 ,  C07D519/00

Abstract: Compounds according to formula (I), methods of using said compounds singly or in combination with additional agents and compositions of said compounds for the treatment of cancer are disclosed.

公开(公告)号：US20180243281A1

公开(公告)日：2018-08-30

申请号：US15873568

申请日：2018-01-17

Applicant: Gilead Sciences, Inc.

Inventor： Mark Andres ,  Brenda J. Burke Chan ,  Eenest A. Carra ,  Anna Chiu ,  Olga Viktorovna Lapina ,  Stephen P. Lathrop ,  Gregory Notte ,  Valeriya Smolenskaya ,  Lok Him Yu

IPC: A61K31/4439 ,  A61K31/541 ,  A61K31/422

CPC classification number: A61K31/4439 ,  A61K31/422 ,  A61K31/541 ,  C07C55/07 ,  C07C57/145 ,  C07C57/15 ,  C07C59/06 ,  C07C309/04 ,  C07D401/14 ,  C07D413/12

Abstract: Crystalline forms of 5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using the crystalline forms.

公开(公告)号：US09943521B2

公开(公告)日：2018-04-17

申请号：US15357878

申请日：2016-11-21

Applicant: Gilead Sciences, Inc.

Inventor： Gregory Notte

IPC: A61K31/44 ,  A61K31/5377 ,  A61K31/4439 ,  C07D409/14 ,  C07D413/14

CPC classification number: A61K31/5377 ,  A61K31/4439 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention relates to compounds of Formula (I): Wherein variables are as defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases, diabetes, diabetic nephropathy, cardio-renal diseases, including kidney disease, fibrotic diseases, respiratory diseases, COPD, idiopathic pulmonary fibrosis, acute lung injury, acute and chronic liver diseases, and neurodegenerative diseases.

公开(公告)号：US09907790B2

公开(公告)日：2018-03-06

申请号：US15481365

申请日：2017-04-06

Applicant: Gilead Sciences, Inc.

Inventor： Gregory Notte

IPC: C07D249/08 ,  A61K31/4439 ,  A61K31/422 ,  A61K31/541

CPC classification number: A61K31/4439 ,  A61K31/422 ,  A61K31/541 ,  C07C55/07 ,  C07C57/145 ,  C07C57/15 ,  C07C59/06 ,  C07C309/04 ,  C07D401/14 ,  C07D413/12

Abstract: Crystalline forms of 5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using the crystalline forms.

公开(公告)号：US20170217933A1

公开(公告)日：2017-08-03

申请号：US15491689

申请日：2017-04-19

Applicant: Gilead Sciences, Inc.

Inventor： Gregory Notte

IPC: C07D401/14

CPC classification number: C07D401/14 ,  A61K9/0053 ,  A61K9/20 ,  A61K31/4439 ,  A61K45/06 ,  C07D213/56 ,  C07D233/56 ,  C07D401/04

Abstract: The present invention relates to a compound of formula (I): The compound has apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and is thus useful in the treatment of diseases such as kidney disease, diabetic nephropathy and kidney fibrosis.

公开(公告)号：US20170196844A1

公开(公告)日：2017-07-13

申请号：US15413101

申请日：2017-01-23

Applicant: Gilead Sciences, Inc.

Inventor： MICHAEL GRAUPE ,  Keith Koch ,  Britton Kenneth Corkey ,  Gregory Notte ,  Lawrence S. Melvin, JR.

IPC: A61K31/444 ,  A61K31/585 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/506 ,  A61K31/4709 ,  A61K31/497 ,  A61K45/06 ,  A61K31/4439

CPC classification number: A61K31/444 ,  A61K31/4439 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/497 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/585 ,  A61K45/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048

Abstract: The present invention relates to compounds of Formula (I): wherein X1, X2, X3, X4, X5, X6, X7, X8, R1, R2, R3 are as defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases. The invention also relates to pharmaceutical compositions comprising one or more of the compounds of Formula (I), and to methods of preparing the compounds of Formula (I).

公开(公告)号：US09586932B2

公开(公告)日：2017-03-07

申请号：US14716526

申请日：2015-05-19

Applicant: Gilead Sciences, Inc.

Inventor： Michael Graupe ,  Keith Koch ,  Britton K. Corkey ,  Gregory Notte ,  Lawrence S. Melvin, Jr.

IPC: C07D401/14 ,  C07D401/12 ,  C07D471/04 ,  C07D491/048 ,  C07D417/14 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14

CPC classification number: A61K31/444 ,  A61K31/4439 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/497 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/585 ,  A61K45/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048

Abstract: The present invention relates to compounds of Formula (I): wherein X1, X2, X3, X4, X5, X6, X7, X8, R1, R2, R3 are as defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases. The invention also relates to pharmaceutical compositions comprising one or more of the compounds of Formula (I), and to methods of preparing the compounds of Formula (I).

Abstract translation: 本发明涉及式（I）化合物：其中X 1，X 2，X 3，X 4，X 5，X 6，X 7，X 8，R 1，R 2，R 3如上所定义。 该化合物具有凋亡信号调节激酶（“ASK1”）抑制活性，因此可用于治疗ASK1介导的病症，包括自身免疫性疾病，炎性疾病，心血管疾病和神经变性疾病。 本发明还涉及包含一种或多种式（I）化合物的药物组合物和制备式（I）化合物的方法。

公开(公告)号：US20160368918A1

公开(公告)日：2016-12-22

申请号：US15150038

申请日：2016-05-09

Applicant: Gilead Sciences, Inc.

Inventor： Peter Blomgren ,  Jayaraman Chandrasekhar ,  Kevin S. Currie ,  Zhimin Du ,  Julie Farand ,  Juan A. Guerrero ,  Ashley A. Katana ,  Darryl Kato ,  Jeffrey Kropf ,  Scott E. Lazerwith ,  Seung H. Lee ,  Jiayao Li ,  John O. Link ,  Jennifer R. Lo ,  Nicholas Mai ,  Scott A. Mitchell ,  Gregory Notte ,  Hyung-jung Pyun ,  Michael Sangi ,  Aaron C. Schmitt ,  Adam J. Schrier ,  Kirk L. Stevens ,  Chandrasekar Venkataramani ,  William J. Watkins ,  Jin Ming Xiong ,  Jianjun Xu ,  Zheng-Yu Yang ,  Jeff Zablocki ,  Zhongdong Zhao ,  Sheila Zipfel

IPC: C07D471/04 ,  C07D403/14 ,  C07D401/14 ,  C07D519/00 ,  C07D487/04 ,  C07D498/04 ,  C07D413/14 ,  C07D405/14 ,  C07D417/12 ,  C07D417/14 ,  C07D403/12 ,  C07D491/08

CPC classification number: C07D471/04 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D407/14 ,  C07D413/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D487/04 ,  C07D491/08 ,  C07D498/04 ,  C07D519/00

Abstract: The present disclosure relates to compounds that are Syk inhibitors and to their use in the treatment of various disease states, including cancer and inflammatory conditions. In particular embodiments, the structure of the compounds is given by Formula I: wherein X1, X2, X3, R2, R3, R4, R5, and Y are as described herein. The present disclosure further provides pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts thereof, and methods of using these compounds and compositions to treat conditions mediated by Syk.

Abstract translation: 其中X1，X2，X3，R2，R3，R4，R5和Y如本文所述。 本公开进一步提供包含式I化合物或其药学上可接受的盐的药物组合物，以及使用这些化合物和组合物治疗由Syk介导的病症的方法。

公开(公告)号：US09376441B2

公开(公告)日：2016-06-28

申请号：US14448160

申请日：2014-07-31

Applicant: Gilead Sciences, Inc.

Inventor： Kevin S. Currie ,  Zhimin Du ,  Julie Farand ,  Juan A. Guerrero ,  Ashley A. Katana ,  Darryl Kato ,  Scott E. Lazerwith ,  Jiayao Li ,  John O. Link ,  Nicholas Mai ,  Gregory Notte ,  Hyung-jung Pyun ,  Michael Sangi ,  Aaron C. Schmitt ,  Adam J. Schrier ,  Kirk L. Stevens ,  Chandrasekar Venkataramani ,  William J. Watkins ,  Zheng-Yu Yang ,  Jeff Zablocki ,  Sheila Zipfel ,  Jennifer R. Lo ,  Seung H. Lee ,  Zhongdong Zhao ,  Jeffrey Kropf ,  Jianjun Xu ,  Peter Blomgren ,  Scott A. Mitchell ,  JinMing Xiong ,  Jayaraman Chandrasekhar

IPC: A61K31/4015 ,  C07D207/12 ,  C07D487/04 ,  C07D401/14 ,  C07D403/12 ,  C07D417/04 ,  C07D417/12 ,  C07D471/04 ,  C07D407/14 ,  C07D417/14

CPC classification number: C07D471/04 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D407/14 ,  C07D413/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D487/04 ,  C07D491/08 ,  C07D498/04 ,  C07D519/00

Abstract: The present disclosure relates to compounds that are Syk inhibitors and to their use in the treatment of various disease states, including cancer and inflammatory conditions. In particular embodiments, the structure of the compounds is given by Formula I: wherein X1, X2, X3, R2, R3, R4, R5, and Y are as described herein. The present disclosure further provides pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts thereof, and methods of using these compounds and compositions to treat conditions mediated by Syk.

Abstract translation: 本公开涉及作为Syk抑制剂的化合物及其在治疗各种疾病状态（包括癌症和炎性病症）中的用途。 在具体实施方案中，化合物的结构由式I给出：其中X 1，X 2，X 3，R 2，R 3，R 4，R 5和Y如本文所述。 本公开进一步提供包含式I化合物或其药学上可接受的盐的药物组合物，以及使用这些化合物和组合物治疗由Syk介导的病症的方法。

公开(公告)号：US09067933B2

公开(公告)日：2015-06-30

申请号：US13934020

申请日：2013-07-02

Applicant: Gilead Sciences, Inc.

Inventor： Britton Kenneth Corkey ,  Michael Graupe ,  Keith Koch ,  Lawrence S. Melvin, Jr. ,  Gregory Notte

IPC: C07D471/04 ,  C07D401/14 ,  C07D401/12 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D491/048

CPC classification number: A61K31/444 ,  A61K31/4439 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/497 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/585 ,  A61K45/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048

Abstract: The present invention relates to compounds of Formula (I): wherein X1, X2, X3, X4, X5, X6, X7, X8, R1, R2, R3 are as defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases. The invention also relates to pharmaceutical compositions comprising one or more of the compounds of Formula (I), and to methods of preparing the compounds of Formula (I).

Abstract translation: 本发明涉及式（I）的化合物：其中X 1，X 2，X 3，X 4，X 5，X 6，X 7，X 8，R 1，R 2，R 3如上所定义。 该化合物具有凋亡信号调节激酶（“ASK1”）抑制活性，因此可用于治疗ASK1介导的病症，包括自身免疫性疾病，炎性疾病，心血管疾病和神经变性疾病。 本发明还涉及包含一种或多种式（I）化合物的药物组合物和制备式（I）化合物的方法。