公开(公告)号：US20190388419A1

公开(公告)日：2019-12-26

申请号：US16413458

申请日：2019-05-15

Applicant: Gilead Sciences, Inc.

Inventor： Peter A. Blomgren ,  Kevin S. Currie ,  Jeffrey E. Kropf ,  Seung H. Lee ,  Jennifer R. Lo ,  Scott A. Mitchell ,  Aaron C. Schmitt ,  Sundaramoorthi Swaminathan ,  Jin-Ming Xiong ,  Jianjun Xu ,  Zhongdong Zhao

IPC: A61K31/4985 ,  A61K31/5377 ,  A61K9/00 ,  C07D487/04

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 R1, R2, R3, and R4 are as described herein. The present disclosure further provides pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts or co-crystals thereof, and methods of using these compounds and compositions to treat conditions mediated by Syk.

公开(公告)号：US10342794B2

公开(公告)日：2019-07-09

申请号：US15945685

申请日：2018-04-04

Applicant: Gilead Sciences, Inc.

Inventor： Peter A. Blomgren ,  Kevin S. Currie ,  Jeffrey E. Kropf ,  Seung H. Lee ,  Jennifer R. Lo ,  Scott A. Mitchell ,  Aaron C. Schmitt ,  Sundaramoorthi Swaminathan ,  Jin-Ming Xiong ,  Jianjun Xu ,  Zhongdong Zhao

IPC: A61K31/4985 ,  C07D487/04 ,  A61K9/00 ,  A61K31/5377

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 R1, R2, R3, and R4 are as described herein. The present disclosure further provides pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts or co-crystals thereof, and methods of using these compounds and compositions to treat conditions mediated by Syk.

公开(公告)号：US20170298068A1

公开(公告)日：2017-10-19

申请号：US14971825

申请日：2015-12-16

Applicant: Gilead Sciences, Inc.

Inventor： CHRISTIAN GEGE ,  Claus Kremoser ,  Olaf Kinzel ,  Peter A. Blomgren ,  Kevin S. Currie ,  Jeffrey E. Kropf ,  Aaron C. Schmitt ,  William J. Watkins ,  Jianjun Xu

IPC: C07D471/08 ,  C07D413/12 ,  C07D261/08 ,  C07D401/14 ,  C07D417/14 ,  C07D413/14

CPC classification number: C07D471/08 ,  C07D261/08 ,  C07D401/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention relates to compounds which bind to the NR1H4 receptor (FXR) and act as agonists of FXR. The invention further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of said nuclear receptor by said compounds and to a process for the synthesis of said compounds.

公开(公告)号：US20180280387A1

公开(公告)日：2018-10-04

申请号：US15907858

申请日：2018-02-28

Applicant: Gilead Sciences, Inc.

Inventor： Peter A. Blomgren ,  Astrid Clarke ,  Kevin S. Currie ,  Julie A. Di Paolo ,  Jeffrey E. Kropf ,  Seung H. Lee ,  Jennifer R. Lo ,  Scott A. Mitchell ,  Aaron C. Schmitt ,  Sundaramoorthi Swaminathan ,  Jin-Ming Xiong ,  Jianjun Xu ,  Zhongdong Zhao

IPC: A61K31/4985 ,  A61K31/5377 ,  A61K31/519 ,  A61K31/475

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 R1, R2, R3, and R4 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. In certain embodiments, also disclosed are methods for treating a cancer in a subject (e.g., a human) in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, in combination with a vinca-alkaloid, or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20150038488A1

公开(公告)日：2015-02-05

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

IPC: C07D487/04 ,  C07D417/04 ,  C07D417/12 ,  C07D403/12 ,  C07D471/04 ,  C07D401/14

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：US20180325896A1

公开(公告)日：2018-11-15

申请号：US15945685

申请日：2018-04-04

Applicant: Gilead Sciences, Inc.

Inventor： Peter A. Blomgren ,  Kevin S. Currie ,  Jeffrey E. Kropf ,  Seung H. Lee ,  Jennifer R. Lo ,  Scott A Mitchell ,  Aaron C. Schmitt ,  Sundaramoorthi Swaminathan ,  Jin-Ming Xiong ,  Jianjun Xu ,  Zhongdong Zhao

IPC: A61K31/4985 ,  A61K31/5377 ,  C07D487/04 ,  A61K9/00

CPC classification number: A61K31/4985 ,  A61K9/0053 ,  A61K31/5377 ,  C07D487/04

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 R1, R2, R3, and R4 are as described herein. The present disclosure further provides pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts or co-crystals thereof, and methods of using these compounds and compositions to treat conditions mediated by Syk.

公开(公告)号：US10005774B2

公开(公告)日：2018-06-26

申请号：US15150038

申请日：2016-05-09

Applicant: Gilead Sciences, Inc.

Inventor： Peter A. Blomgren ,  Jayaraman Chandrasekhar ,  Kevin S. Currie ,  Zhimin Du ,  Julie Farand ,  Juan A. Guerrero ,  Ashley A. Katana ,  Darryl Kato ,  Jeffrey E. 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 ,  C07D401/14 ,  C07D403/12 ,  C07D417/04 ,  C07D417/12 ,  C07D487/04 ,  C07D407/14 ,  C07D417/14 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D491/08 ,  C07D498/04 ,  C07D519/00

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.

公开(公告)号：US20160058758A1

公开(公告)日：2016-03-03

申请号：US14795123

申请日：2015-07-09

Applicant: Gilead Sciences, Inc.

Inventor： Peter A. Blomgren ,  Astrid Clarke ,  Kevin S. Currie ,  Julie Di Paolo ,  Jeffrey E. Kropf ,  Seung H. Lee ,  Jennifer R. Lo ,  Scott A. Mitchell ,  Aaron C. Schmitt ,  Sundaramoorthi Swaminathan ,  Jin-Ming Xiong ,  Jianjun Xu ,  Zhongdong Zhao

IPC: A61K31/4985 ,  A61K31/5377 ,  A61K31/475

CPC classification number: A61K31/4985 ,  A61K31/475 ,  A61K31/519 ,  A61K31/5377 ,  A61K2300/00

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 R1, R2, R3, and R4 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. In certain embodiments, also disclosed are methods for treating a cancer in a subject (e.g., a human) in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, in combination with a vinca-alkaloid, or a pharmaceutically acceptable salt thereof.

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R 1，R 2，R 3和R 4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。 在某些实施方案中，还公开了用于治疗有需要的受试者（例如，人）中的癌症的方法，其包括给予受试者治疗有效量的式I化合物或其药学上可接受的盐，其组合 长春花生物碱或其药学上可接受的盐。

公开(公告)号：US10828299B2

公开(公告)日：2020-11-10

申请号：US16413458

申请日：2019-05-15

Applicant: Gilead Sciences, Inc.

Inventor： Peter A. Blomgren ,  Kevin S. Currie ,  Jeffrey E. Kropf ,  Seung H. Lee ,  Jennifer R. Lo ,  Scott A. Mitchell ,  Aaron C. Schmitt ,  Sundaramoorthi Swaminathan ,  Jin-Ming Xiong ,  Jianjun Xu ,  Zhongdong Zhao

IPC: A61K31/4985 ,  C07D487/04 ,  A61K9/00 ,  A61K31/5377

Abstract: The present disclosure relates to compounds that are Syk inhibitors or pharmaceutically acceptable salts or co-crystals thereof, and pharmaceutical compositions thereof, and to their use in the treatment of various disease states, including cancer and inflammatory conditions. In particular embodiments, a Syk inhibitor is a crystalline monomesylate salt of 6-(6-aminopyrazin-2-yl)-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)imidazo-[1,2-a]pyrazin-8-amine of formula 2:

公开(公告)号：US09931338B2

公开(公告)日：2018-04-03

申请号：US15298950

申请日：2016-10-20

Applicant: Gilead Sciences, Inc.

Inventor： Peter A. Blomgren ,  Astrid Clarke ,  Kevin S. Currie ,  Julie A. Di Paolo ,  Jeffrey E. Kropf ,  Seung H. Lee ,  Jennifer R. Lo ,  Scott A. Mitchell ,  Aaron C. Schmitt ,  Sundaramoorthi Swaminathan ,  Jin-Ming Xiong ,  Jianjun Xu ,  Zhongdong Zhao

IPC: A61K31/4985 ,  A61K31/475 ,  A61K31/5377 ,  A61K31/519

CPC classification number: A61K31/4985 ,  A61K31/475 ,  A61K31/519 ,  A61K31/5377 ,  A61K2300/00

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 R1, R2, R3, and R4 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. In certain embodiments, also disclosed are methods for treating a cancer in a subject (e.g., a human) in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, in combination with a vinca-alkaloid, or a pharmaceutically acceptable salt thereof.