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：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.

公开(公告)号：US20210238153A2

公开(公告)日：2021-08-05

申请号：US17023138

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： 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：US10947216B2

公开(公告)日：2021-03-16

申请号：US16529995

申请日：2019-08-02

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 ,  C07D471/04 ,  C07D405/14 ,  C07D401/12 ,  C07D403/14 ,  C07D403/12 ,  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：US20200087293A1

公开(公告)日：2020-03-19

申请号：US16551431

申请日：2019-08-26

申请人： Rigel Pharmaceuticals, Inc.

发明人： Esteban Masuda ,  Rajinder Singh ,  Vanessa Taylor ,  Donald G. Payan

IPC分类号： C07D413/12 ,  C07F9/653 ,  A61K31/675 ,  A61K45/06 ,  A61K31/506

摘要： Compounds and embodiments of a method for treating and/or preventing autoimmune diseases are disclosed. The method includes administering to a subject having an autoimmune disease, such as an inflammatory bowel disease, a therapeutically effective amount of a compound according to formula I wherein X and Y independently are O or NR1; each R1 is independently H or C1-C6 alkyl; ring A is aryl; each R2 independently is H, alkyl, alkoxy, amide, cyano, halo, haloalkyl, hydroxyalkyl, heteroalkyl, heterocyclyl, sulfonyl, sulfonamide, or two R2 groups, taken together with the atom or atoms to which they are attached, combine to form a 4-10 membered ring system; p is 0, 1, 2, 3, or 4; R3 and R4 independently are H or C1-C6 alkyl; and R5 is halo, cyano, or C1-C6 alkyl.

公开(公告)号：US10414758B2

公开(公告)日：2019-09-17

申请号：US15875897

申请日：2018-01-19

申请人： Rigel Pharmaceuticals, Inc.

发明人： Esteban Masuda ,  Rajinder Singh ,  Vanessa Taylor ,  Donald G. Payan

IPC分类号： A61K31/506 ,  A61K31/675 ,  C07D413/12 ,  C07F9/653 ,  A61K45/06

摘要： Compounds and embodiments of a method for treating and/or preventing autoimmune diseases are disclosed. The method includes administering to a subject having an autoimmune disease, such as an inflammatory bowel disease, a therapeutically effective amount of a compound according to formula I wherein X and Y independently are O or NR1; each R1 is independently H or C1-C6 alkyl; ring A is aryl; each R2 independently is H, alkyl, alkoxy, amide, cyano, halo, haloalkyl, hydroxyalkyl, heteroalkyl, heterocyclyl, sulfonyl, sulfonamide, or two R2 groups, taken together with the atom or atoms to which they are attached, combine to form a 4-10 membered ring system; p is 0, 1, 2, 3, or 4; R3 and R4 independently are H or C1-C6 alkyl; and R5 is halo, cyano, or C1-C6 alkyl.