公开(公告)号：US11999717B2

公开(公告)日：2024-06-04

申请号：US18061822

申请日：2022-12-05

Applicant: Gilead Sciences, Inc.

Inventor： Brian P. Bestvater ,  Zhimin Du ,  Julie Farand ,  Gregory Notte ,  Barton W. Phillips ,  Doris T. Tang ,  Chandrasekar Venkataramani ,  Peiyuan Wang ,  Kin S. Yang ,  Anna Zagorska

IPC: C07D401/04 ,  A61K31/4439 ,  A61K31/65 ,  A61P11/00 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/04 ,  C07D413/14 ,  C07D417/14 ,  C07D498/04

CPC classification number: C07D401/14 ,  C07D401/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07B2200/05

Abstract: The present disclosure relates generally to compounds that bind to Lysophosphatidic Acid Receptor 1 (LPAR1) and act as antagonists of LPAR1. The disclosure 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 LPAR1, including fibrosis and liver diseases such as non-alcoholic steatohepatitis (NASH).

公开(公告)号：US20210171500A1

公开(公告)日：2021-06-10

申请号：US17096150

申请日：2020-11-12

Applicant: Gilead Sciences, Inc.

Inventor： Brian P. Bestvater ,  Zhimin Du ,  Julie Farand ,  Gregory Notte ,  Barton W. Phillips ,  Doris T. Tang ,  Chandrasekar Venkataramani ,  Peiyuan Wang ,  Kin S. Yang ,  Anna Zagorska

IPC: C07D401/14 ,  C07D401/04 ,  C07D417/14 ,  C07D409/14 ,  C07D413/14 ,  C07D405/14

Abstract: The present disclosure relates generally to compounds that bind to Lysophosphatidic Acid Receptor 1 (LPAR1) and act as antagonists of LPAR1. The disclosure 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 LPAR1, including fibrosis and liver diseases such as non-alcoholic steatohepatitis (NASH).

公开(公告)号：US10508100B2

公开(公告)日：2019-12-17

申请号：US16246199

申请日：2019-01-11

Applicant: Gilead Sciences, Inc.

Inventor： Gregory Notte

IPC: A61K31/4439 ,  C07D213/127 ,  C07D401/14 ,  A61K45/06 ,  A61K9/20 ,  C07D401/04 ,  C07D233/56 ,  C07D213/56 ,  A61K9/00

Abstract: The present invention relates to a compound of formula (I): The compound has apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and is thus useful in the treatment of diseases such as kidney disease, diabetic nephropathy and kidney fibrosis.

公开(公告)号：US20190248762A1

公开(公告)日：2019-08-15

申请号：US16246199

申请日：2019-01-11

Applicant: Gilead Sciences, Inc.

Inventor： Gregory Notte

IPC: C07D401/14 ,  A61K45/06 ,  A61K9/20 ,  A61K9/00 ,  A61K31/4439 ,  C07D233/56 ,  C07D213/56 ,  C07D401/04

Abstract: The present invention relates to a compound of formula (I): The compound has apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and is thus useful in the treatment of diseases such as kidney disease, diabetic nephropathy and kidney fibrosis.

公开(公告)号：US20170233350A1

公开(公告)日：2017-08-17

申请号：US15413154

申请日：2017-01-23

Applicant: Gilead Sciences, Inc.

Inventor： Brandon Heath Brown ,  Brenda J. Burke Chan ,  Anna Chiu ,  Nolan Griggs ,  Lars V. Heumann ,  Stephen P. Lathrop ,  Gregory Notte ,  Troy Evan Reynolds ,  Keshab Sarma ,  David Allen Siler ,  Andrew S. Thompson ,  Tao Wang

IPC: C07D233/64

CPC classification number: C07D233/64 ,  C07B2200/13 ,  C07D233/56 ,  C07D401/14

Abstract: The present disclosure provides processes for the preparation of a compound of formula: which exhibits apoptosis signal-regulating kinase (“ASK1”) inhibitory activity and is thus useful in the treatment of diseases such as kidney disease, diabetic nephropathy and kidney fibrosis. The disclosure also provides compounds that are synthetic intermediates.

公开(公告)号：US20160362421A1

公开(公告)日：2016-12-15

申请号：US15188701

申请日：2016-06-21

Applicant: Gilead Sciences, Inc.

Inventor： Britton Kenneth Corkey ,  Elfatih Elzein ,  Michael Graupe ,  Juan Guerrero ,  Robert H. Jiang ,  Rao V. Kalla ,  Tetsuya Kobayashi ,  Dmitry Koltun ,  Xiaofen Li ,  Ruben Martinez ,  Gregory Notte ,  Eric Q. Parkhill ,  Thao Perry ,  Chandrasekar Venkataramani ,  Jeff Zablocki

IPC: C07D498/10 ,  C07D401/04 ,  C07D403/04 ,  C07D413/06 ,  C07D403/06 ,  C07D413/14 ,  C07D417/06 ,  C07D403/12 ,  C07D401/12 ,  C07D401/14 ,  C07D237/32 ,  C07D417/12 ,  C07D401/06 ,  C07D265/22 ,  C07D279/08 ,  C07D217/26 ,  C07D405/12 ,  C07D253/08

CPC classification number: C07D498/10 ,  C07D217/26 ,  C07D237/32 ,  C07D239/88 ,  C07D239/90 ,  C07D253/08 ,  C07D263/58 ,  C07D265/22 ,  C07D279/08 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/08 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D498/04

Abstract: The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I: wherein Q, R1, X1, X2, Y and R2 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.

Abstract translation: 其中Q，R 1，X 1，X 2，Y和R 2如本文所述，用于制备和使用化合物的方法以及含有该化合物的药物组合物。

公开(公告)号：US20160130251A1

公开(公告)日：2016-05-12

申请号：US14716526

申请日：2015-05-19

Applicant: Gilead Sciences, Inc.

Inventor： Michael Graupe ,  Keith Koch ,  Britton K. Corkey ,  Gregory Notte ,  Lawrence S. Melvin, JR.

IPC: C07D401/14 ,  C07D405/14 ,  C07D491/048 ,  C07D417/14 ,  C07D401/12 ,  C07D471/04

CPC classification number: A61K31/444 ,  A61K31/4439 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/497 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/585 ,  A61K45/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048

Abstract: The present invention relates to compounds of Formula (I): wherein X1, X2, X3, X4, X5, X6, X7, X8, R1, R2, R3 are as defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases. The invention also relates to pharmaceutical compositions comprising one or more of the compounds of Formula (I), and to methods of preparing the compounds of Formula (I).

Abstract translation: 本发明涉及式（I）的化合物：其中X 1，X 2，X 3，X 4，X 5，X 6，X 7，X 8，R 1，R 2，R 3如上所定义。 该化合物具有凋亡信号调节激酶（“ASK1”）抑制活性，因此可用于治疗ASK1介导的病症，包括自身免疫性疾病，炎性疾病，心血管疾病和神经变性疾病。 本发明还涉及包含一种或多种式（I）化合物的药物组合物和制备式（I）化合物的方法。

公开(公告)号：US09079901B2

公开(公告)日：2015-07-14

申请号：US14217011

申请日：2014-03-17

Applicant: Gilead Sciences, Inc.

Inventor： Tetsuya Kobayashi ,  Dmitry Koltun ,  Gregory Notte ,  Eric Parkhill ,  Jeff Zablocki

IPC: C07D401/14 ,  A61K31/437 ,  C07D471/04 ,  C07D519/00

CPC classification number: C07D471/04 ,  C07D519/00

Abstract: The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I: wherein R1, R2, R3, R4, and R5 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.

Abstract translation: 本公开涉及作为钠通道抑制剂的化合物及其用于治疗各种疾病状态（包括心血管疾病和糖尿病）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，R 4和R 5如本文所述，用于制备和使用化合物的方法以及含有该化合物的药物组合物。

公开(公告)号：US20130197037A1

公开(公告)日：2013-08-01

申请号：US13748901

申请日：2013-01-24

Applicant: Gilead Sciences, Inc.

Inventor： Gregory Notte

IPC: C07D401/14

CPC classification number: C07D401/14 ,  A61K9/0053 ,  A61K9/20 ,  A61K31/4439 ,  A61K45/06 ,  C07D213/56 ,  C07D233/56 ,  C07D401/04

Abstract: The present invention relates to a compound of formula (I): The compound has apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and is thus useful in the treatment of diseases such as kidney disease, diabetic nephropathy and kidney fibrosis.

Abstract translation: 本发明涉及式（I）化合物：该化合物具有凋亡信号调节激酶（“ASK1”）抑制活性，因此可用于治疗肾病，糖尿病性肾病和肾纤维化等疾病。

公开(公告)号：US11548871B2

公开(公告)日：2023-01-10

申请号：US17096150

申请日：2020-11-12

Applicant: Gilead Sciences, Inc.

Inventor： Brian P. Bestvater ,  Zhimin Du ,  Julie Farand ,  Gregory Notte ,  Barton W. Phillips ,  Doris T. Tang ,  Chandrasekar Venkataramani ,  Peiyuan Wang ,  Kin S. Yang ,  Anna Zagorska

IPC: C07D498/04 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D413/04 ,  A61K31/65 ,  A61P11/00 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present disclosure relates generally to compounds that bind to Lysophosphatidic Acid Receptor 1 (LPAR1) and act as antagonists of LPAR1. The disclosure 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 LPAR1, including fibrosis and liver diseases such as non-alcoholic steatohepatitis (NASH).