公开(公告)号：US20230123591A1

公开(公告)日：2023-04-20

申请号：US17962305

申请日：2022-10-07

申请人： Rigel Pharmaceuticals, Inc.

发明人： Marina Gelman ,  Todd Kinsella ,  Somasekhar Bhamidipati ,  Ihab Darwish ,  Rajinder Singh ,  Jiaxin Yu

IPC分类号： C07D487/04 ,  C07D401/04 ,  C07D403/04 ,  C07D417/04 ,  C07D471/04 ,  C07D519/00

摘要： Disclosed are pyrazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein A, X, Z, m, p, and R2 are as described herein. In certain embodiments, a compound disclosed herein inhibits the activity of one or more members of the TGF-β superfamily, and can be used to treat disease by blocking such activity.

公开(公告)号：US20230113841A1

公开(公告)日：2023-04-13

申请号：US17939020

申请日：2022-09-07

申请人： Rigel Pharmaceuticals, Inc.

发明人： Esteban MASUDA ,  Simon SHAW ,  Vanessa TAYLOR ,  Somasekhar BHAMIDIPATI

IPC分类号： C07D267/14 ,  A61P35/00 ,  C07D413/12 ,  C07D413/14 ,  C07D487/04

摘要： Disclosed herein are kinase inhibitory compounds, such as a receptor-interacting protein-1 (RIP1) kinase inhibitor compounds, as well as pharmaceutical compositions and combinations comprising such inhibitory compounds. The disclosed compounds, pharmaceutical compositions, and/or combinations may be used to treat or prevent a kinase-associated disease or condition, particularly a RIP1-associated disease or condition.

公开(公告)号：US20230095835A1

公开(公告)日：2023-03-30

申请号：US17988062

申请日：2022-11-16

申请人： Rigel Pharmaceuticals, Inc.

发明人： Yan Chen ,  Rose Yen ,  Jiaxin Yu ,  Vanessa Taylor ,  Rajinder Singh

IPC分类号： C07D403/12 ,  C07D239/48 ,  C07D401/14 ,  C07D405/14

摘要： Compounds within the scope of the present invention have a Formula 1 or a salt or produg thereof, where ring A is selected from cycloaliphatic; ring B is aryl; R1 is selected from (C1-C10)alkyl, (C3-C10)cycloalkyl, halo, aryl, and heteroaryl; and R2 and R3 are independently selected from hydrogen and (C1-C6)alkyl. Disclosed compounds may have an IRAK4 IC50 of from 0.003 μM to 3.7 μM; a TAK1 IC50 of from 0.008 μM to 132 μM; and/or an IRAK4/TAK1 selectivity of from 1 to 450. Particular compounds may have an IRAK4/TAK1 selectivity of from 100 to 500. Disclosed compositions may be formulated as pharmaceutical compositions. A method for using the compounds and/or compositions also are disclosed. The method may comprise administering to a subject an effective amount of a compound within the scope of the present invention, particularly to selectively inhibit IRAK 1 and/or IRAK4 over TAK1.

公开(公告)号：US11584758B2

公开(公告)日：2023-02-21

申请号：US17221493

申请日：2021-04-02

申请人： Rigel Pharmaceuticals, Inc.

发明人： Ihab Darwish ,  Zhushou Luo ,  Vanessa Taylor

IPC分类号： C07D498/04 ,  C07D471/04 ,  C07D519/00 ,  A61K9/00

摘要： Disclosed herein are kinase inhibitory compounds, such as a receptor-interacting protein-1 (RIP1) kinase inhibitor compounds, as well as pharmaceutical compositions and combinations comprising such inhibitory compounds. The disclosed compounds, pharmaceutical compositions, and/or combinations may be used to treat or prevent a kinase-associated disease or condition, particularly a RIP1-associated disease or condition.

公开(公告)号：US11530194B2

公开(公告)日：2022-12-20

申请号：US17184199

申请日：2021-02-24

申请人： Rigel Pharmaceuticals, Inc.

发明人： Kin Tso ,  Hui Li ,  Yan Chen ,  Rose Yen ,  Vanessa Taylor ,  Thilo Heckrodt ,  Rajinder Singh ,  Simon Shaw

IPC分类号： C07D401/14 ,  C07D405/14 ,  C07D471/04 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14

摘要： Disclosed embodiments concern novel interleukin receptor associated kinases (IRAK) inhibitors and compositions comprising such inhibitors. Also disclosed are methods of making and using the compounds and compositions. The disclosed compounds and/or compositions may be used to treat or prevent an IRAK-associated disease or condition.

公开(公告)号：US11492349B2

公开(公告)日：2022-11-08

申请号：US17184182

申请日：2021-02-24

申请人： Rigel Pharmaceuticals, Inc.

发明人： Hui Li ,  Thilo Heckrodt ,  Yan Chen ,  Ryan Kelley ,  Darren McMurtrie ,  Kin Tso ,  Vanessa Taylor ,  Rajinder Singh ,  Rose Yen ,  Jack Maung

IPC分类号： C07D413/14 ,  A61P29/00

摘要： Disclosed embodiments concern interleukin receptor associated kinases (IRAK) inhibitors, such as oxazole compounds, and compositions comprising such inhibitors. Also disclosed are methods of making and using the compounds and compositions. The disclosed compounds and/or compositions may be used to treat or prevent an IRAK-associated disease or condition.

公开(公告)号：US11370765B2

公开(公告)日：2022-06-28

申请号：US17023149

申请日：2020-09-16

申请人： Rigel Pharmaceuticals, Inc.

发明人： Esteban Masuda ,  Simon Shaw ,  Vanessa Taylor ,  Somasekhar Bhamidipati

IPC分类号： A61K31/553 ,  A61P29/00 ,  A61P35/00 ,  A61P37/02 ,  C07D413/12 ,  C07D267/14 ,  C07D413/14 ,  C07D487/04

摘要： Disclosed herein are kinase inhibitory compounds, such as a receptor-interacting protein-1 (RIP1) kinase inhibitor compounds, as well as pharmaceutical compositions and combinations comprising such inhibitory compounds. The disclosed compounds, pharmaceutical compositions, and/or combinations may be used to treat or prevent a kinase-associated disease or condition, particularly a RIP1-associated disease or condition.

公开(公告)号：US20220000880A1

公开(公告)日：2022-01-06

申请号：US17290741

申请日：2019-10-31

申请人： Rigel Pharmaceuticals, Inc.

发明人： Sandra Tong ,  Vadim Markovtsov ,  Ann Lowe ,  Anne-Marie Duliege

IPC分类号： A61K31/5383 ,  A61K31/675 ,  A61K31/5377 ,  A61K31/7076 ,  A61K31/704 ,  A61K31/7068 ,  A61K31/635 ,  A61K31/4745 ,  A61K31/553 ,  A61K38/20 ,  A61K39/395 ,  A61K31/417 ,  A61K31/53 ,  A61P35/00

摘要： Disclosed herein are embodiments of a method and pharmaceutical composition for treating acute myeloid leukemia (AML). In particular, the method embodiments comprise treating AML with 6-((5-fluoro-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)amino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one, or a prodrug thereof, alone or in combination with one or more therapeutic agents that themselves are effective for treating AML. Also disclosed are embodiments of a pharmaceutical composition comprising 6-((5-fluoro-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)amino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one, or a prodrug thereof, either as the sole therapeutic agent or in combination with one or more therapeutic agents effective for treating AML.

公开(公告)号：US20210380703A1

公开(公告)日：2021-12-09

申请号：US17394228

申请日：2021-08-04

申请人： Rigel Pharmaceuticals, Inc.

发明人： Todd M. KINSELLA ,  Ramesh BHATT ,  Kristen BALTGALVIS

IPC分类号： C07K16/28 ,  A61K47/61 ,  A61K47/54 ,  A61K47/60 ,  A61K39/395 ,  A61P21/06

摘要： The present disclosure provides antibodies that specifically bind to and block signaling by ACVR2A, i.e., ACVR2A but not ACVR2B, as well as methods for using the same. The antibodies may be used for the treatment of a number of conditions associated with muscle atrophy, as well as other conditions.

公开(公告)号：US20210317135A1

公开(公告)日：2021-10-14

申请号：US17221493

申请日：2021-04-02

申请人： Rigel Pharmaceuticals, Inc.

发明人： Ihab Darwish ,  Zhushou Luo ,  Vanessa Taylor

IPC分类号： C07D498/04 ,  C07D519/00 ,  C07D471/04 ,  A61K9/00

摘要： Disclosed herein are kinase inhibitory compounds, such as a receptor-interacting protein-1 (RIP1) kinase inhibitor compounds, as well as pharmaceutical compositions and combinations comprising such inhibitory compounds. The disclosed compounds, pharmaceutical compositions, and/or combinations may be used to treat or prevent a kinase-associated disease or condition, particularly a RIP1-associated disease or condition.