公开(公告)号：US20160257690A1

公开(公告)日：2016-09-08

申请号：US15054895

申请日：2016-02-26

申请人： Rigel Pharmaceuticals, Inc. ,  Bristol-Myers Squibb Company

发明人： Todd Kinsella ,  Marina Gelman ,  Hui Hong ,  Ihab S. Darwish ,  Rajinder Singh ,  Jiaxin Yu ,  Robert M. Borzilleri ,  Upender Velaparthi ,  Peiying Liu ,  Chetan Darne ,  Hasibur Rahaman ,  Jayakumar Sankara Warrier

IPC分类号： C07D487/04 ,  C07D471/04

CPC分类号： C07D487/04 ,  C07D401/04 ,  C07D403/04 ,  C07D417/04 ,  C07D471/04

摘要： Disclosed are imidazole and thiazole 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 X, A, Z, R1 and R′ are as described herein. In certain embodiments, a compound disclosed herein inhibits TGF-β, and can be used to treat disease by blocking TGF-β signaling.

摘要翻译： 公开了咪唑和噻唑化合物，以及药物组合物及其使用方法。 一个实施方案是具有其结构和药学上可接受的盐，前药和N-氧化物（及其溶剂化物和水合物）的化合物，其中X，A，Z，R 1和R'如本文所述。 在某些实施方案中，本文公开的化合物抑制TGF-β，并且可用于通过阻断TGF-β信号传导治疗疾病。

公开(公告)号：US20200031832A1

公开(公告)日：2020-01-30

申请号：US16360162

申请日：2019-03-21

申请人： Rigel Pharmaceuticals, Inc. ,  Bristol-Myers Squibb Company

发明人： Todd Kinsella ,  Marina Gelman ,  Hui Hong ,  Ihab S. Darwish ,  Rajinder Singh ,  Jiaxin Yu ,  Robert M. Borzilleri ,  Upender Velaparthi ,  Peiying Liu ,  Chetan Padmakar Darne ,  Hasibur Rahaman ,  Jayakumar Sankara Warrier

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

摘要： Disclosed are imidazole and thiazole 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 X, A, Z, R1 and R′ are as described herein. In certain embodiments, a compound disclosed herein inhibits TGF-β, and can be used to treat disease by blocking TGF-β signaling.

公开(公告)号：US10287295B2

公开(公告)日：2019-05-14

申请号：US15860379

申请日：2018-01-02

申请人： Rigel Pharmaceuticals, Inc. ,  Bristol-Myers Squibb Company

发明人： Todd Kinsella ,  Marina Gelman ,  Hui Hong ,  Ihab S. Darwish ,  Rajinder Singh ,  Jiaxin Yu ,  Robert M. Borzilleri ,  Upender Velaparthi ,  Peiying Liu ,  Chetan Padmakar Darne ,  Hasibur Rahaman ,  Jayakumar Sankara Warrier

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

摘要： Disclosed are imidazole and thiazole 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 X, A, Z, R1 and R′ are as described herein. In certain embodiments, a compound disclosed herein inhibits TGF-β, and can be used to treat disease by blocking TGF-β signaling.

公开(公告)号：US20180127426A1

公开(公告)日：2018-05-10

申请号：US15860379

申请日：2018-01-02

申请人： Rigel Pharmaceuticals, Inc. ,  Bristol-Myers Squibb Company

发明人： Todd Kinsella ,  Marina Gelman ,  Hui Hong ,  Ihab S. Darwish ,  Rajinder Singh ,  Jiaxin Yu ,  Robert M. Borzilleri ,  Upender Velaparthi ,  Peiying Liu ,  Chetan Darne ,  Hasibur Rahaman ,  Jayakumar Sankara Warrier

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

CPC分类号： C07D487/04 ,  C07D401/04 ,  C07D403/04 ,  C07D417/04 ,  C07D471/04

摘要： Disclosed are imidazole and thiazole 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 X, A, Z, R1 and R′ are as described herein. In certain embodiments, a compound disclosed herein inhibits TGF-β, and can be used to treat disease by blocking TGF-β signaling.

公开(公告)号：US11352360B2

公开(公告)日：2022-06-07

申请号：US16360162

申请日：2019-03-21

申请人： Rigel Pharmaceuticals, Inc. ,  Bristol-Myers Squibb Company

发明人： Todd Kinsella ,  Marina Gelman ,  Hui Hong ,  Ihab S. Darwish ,  Rajinder Singh ,  Jiaxin Yu ,  Robert M. Borzilleri ,  Upender Velaparthi ,  Peiying Liu ,  Chetan Padmakar Dame ,  Hasibur Rahaman ,  Jayakumar Sankara Warrier

IPC分类号： C07D487/04 ,  C07D401/04 ,  C07D403/04 ,  C07D471/04 ,  A61P35/00 ,  C07D417/04

摘要： Disclosed are imidazole and thiazole 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 X, A, Z, R1 and R′ are as described herein. In certain embodiments, a compound disclosed herein inhibits TGF-β, and can be used to treat disease by blocking TGF-β signaling.

公开(公告)号：US09884868B2

公开(公告)日：2018-02-06

申请号：US15054895

申请日：2016-02-26

申请人： Rigel Pharmaceuticals, Inc. ,  Bristol-Myers Squibb Company

发明人： Todd Kinsella ,  Marina Gelman ,  Hui Hong ,  Ihab S. Darwish ,  Rajinder Singh ,  Jiaxin Yu ,  Robert M. Borzilleri ,  Upender Velaparthi ,  Peiying Liu ,  Chetan Darne ,  Hasibur Rahaman ,  Jayakumar Sankara Warrier

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

CPC分类号： C07D487/04 ,  C07D401/04 ,  C07D403/04 ,  C07D417/04 ,  C07D471/04

摘要： Disclosed are imidazole and thiazole 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 X, A, Z, R1 and R′ are as described herein. In certain embodiments, a compound disclosed herein inhibits TGF-β, and can be used to treat disease by blocking TGF-β signaling.

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：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：US11110082B2

公开(公告)日：2021-09-07

申请号：US16575852

申请日：2019-09-19

申请人： Rigel Pharmaceuticals, Inc.

发明人： Sacha Holland ,  Rajinder Singh ,  Somasekhar Bhamidipati ,  Pingyu Ding ,  Rao Kolluri ,  Ihab Darwish ,  Esteban Masuda ,  Jiaxin Yu

IPC分类号： A61K31/519 ,  A61K31/4545 ,  C07D471/04 ,  C07D519/00

摘要： Disclosed are imidazole 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 X, Y and Z are as described herein. In certain embodiments, a compound disclosed herein inhibits a cellular TAM receptor, and can be used to treat disease mediated by or involving the TAM receptor family.

公开(公告)号：US20200155531A1

公开(公告)日：2020-05-21

申请号：US16600873

申请日：2019-10-14

申请人： Rigel Pharmaceuticals, Inc.

发明人： Matthew Duncton ,  Somasekhar Bhamidipati ,  Jiaxin Yu ,  Ihab Darwish ,  Rajinder Singh

IPC分类号： A61K31/4439 ,  C07D405/04 ,  C07D401/04 ,  C07D257/04 ,  C07D405/06 ,  C07D403/12 ,  A61K31/41

摘要： Aspects of the present disclosure include compounds that find use for the treatment of a variety of autoimmune and inflammatory diseases and disorders. Embodiments of the present disclosure also relate to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.