公开(公告)号：US20230123591A1

公开(公告)日：2023-04-20

申请号：US17962305

申请日：2022-10-07

Applicant: Rigel Pharmaceuticals, Inc.

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

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

Abstract: 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

Applicant: Rigel Pharmaceuticals, Inc.

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

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

Abstract: 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

Applicant: Rigel Pharmaceuticals, Inc.

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

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

Abstract: 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

Applicant: Rigel Pharmaceuticals, Inc.

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

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

Abstract: 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.

公开(公告)号：US20200031832A1

公开(公告)日：2020-01-30

申请号：US16360162

申请日：2019-03-21

Applicant: Rigel Pharmaceuticals, Inc. ,  Bristol-Myers Squibb Company

Inventor： 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: C07D487/04 ,  C07D471/04 ,  C07D417/04 ,  C07D403/04 ,  C07D401/04

Abstract: 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：US20190382395A1

公开(公告)日：2019-12-19

申请号：US16424619

申请日：2019-05-29

Applicant: Rigel Pharmaceuticals, Inc.

Inventor： Ihab Darwish ,  Jiaxin Yu ,  Rao Kolluri ,  Sacha Holland

IPC: C07D413/14 ,  C07D453/00 ,  C07D491/107 ,  C07D417/14

Abstract: 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 R1, X, Y1, Y2, Y3 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：US20190367472A1

公开(公告)日：2019-12-05

申请号：US16412217

申请日：2019-05-14

Applicant: Rigel Pharmaceuticals, Inc.

Inventor： Jiaxin Yu ,  Beth Fernandez ,  Gary Park ,  Ihab Darwish

IPC: C07D401/04 ,  C07D257/04 ,  C07C323/60 ,  C07D249/12 ,  A61P37/02

Abstract: Aspects of the present disclosure include prodrugs of compounds that activate Nrf2. Such prodrugs find use in the treatment of autoimmune and inflammatory diseases and disorders, such as for example psoriasis and multiple sclerosis. Embodiments of the present disclosure also relate to pharmaceutical compositions that include these prodrugs, methods of using these prodrugs in the treatment of various diseases and disorders, processes for preparing these prodrugs and intermediates useful in these processes.

公开(公告)号：US10287295B2

公开(公告)日：2019-05-14

申请号：US15860379

申请日：2018-01-02

Applicant: Rigel Pharmaceuticals, Inc. ,  Bristol-Myers Squibb Company

Inventor： 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: C07D487/04 ,  C07D471/04 ,  C07D401/04 ,  C07D403/04 ,  C07D417/04

Abstract: 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：US20180346487A1

公开(公告)日：2018-12-06

申请号：US15527908

申请日：2015-11-16

Applicant: Rigel Pharmaceuticals, Inc.

Inventor： Rajinder Singh ,  Todd Kinsella ,  Jiaxin Yu ,  Marina Gelman ,  Ihab S. Darwish

IPC: C07D519/00 ,  C07D487/04 ,  C07D498/04 ,  A61K45/06 ,  A61K31/437 ,  A61K31/4365 ,  A61K31/428 ,  A61K31/4709 ,  A61K31/498 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/4188 ,  A61K31/416 ,  A61K31/519

Abstract: Disclosed are imidazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure Formula (I) and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein A, Z, X, R1, R2 m, p and a 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

Applicant: Rigel Pharmaceuticals, Inc. ,  Bristol-Myers Squibb Company

Inventor： 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: C07D487/04 ,  C07D417/04 ,  C07D403/04 ,  C07D471/04 ,  C07D401/04

CPC classification number: C07D487/04 ,  C07D401/04 ,  C07D403/04 ,  C07D417/04 ,  C07D471/04

Abstract: 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.