公开(公告)号：US11059832B2

公开(公告)日：2021-07-13

申请号：US16705458

申请日：2019-12-06

Applicant: University Health Network

Inventor： Peter Brent Sampson ,  Narendra Kumar B. Patel ,  Heinz W. Pauls ,  Sze-Wan Li ,  Grace Ng ,  Radoslaw Laufer ,  Yong Liu ,  Yunhui Lang

IPC: C07D495/04 ,  A61K31/496 ,  A61K39/395 ,  C07K16/28 ,  A61K31/4355 ,  A61K31/5355 ,  A61K31/551 ,  A61P35/00 ,  A61K31/5377 ,  A61K45/06 ,  A61K39/00

Abstract: Thienopyridinone compounds of Formula (I) and pharmaceutically acceptable salts thereof are described. In these compounds, one of X1; X2, and X3 is S and the other two are each independently CR, wherein R and all other variables are as defined herein. The compounds are shown to inhibit HPK1 kinase activity and to have in vivo antitumor activity. The compounds can be effectively combined with pharmaceutically acceptable carriers and also with other immunomodulatory approaches, such as checkpoint inhibition or inhibitors of tryptophan oxidation. Formula (I).

公开(公告)号：US10570143B2

公开(公告)日：2020-02-25

申请号：US16155846

申请日：2018-10-09

Applicant: University Health Network

Inventor： Yong Liu ,  Heinz W. Pauls ,  Radoslaw Laufer ,  Sze-Wan Li ,  Peter Brent Sampson ,  Miklos Feher ,  Grace Ng ,  Narendra Kumar B. Patel ,  Yunhui Lang

IPC: C07D487/04 ,  C07D519/00

Abstract: The present teachings provide a compound represented by structural formula (1-0), or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof.

公开(公告)号：US20190225617A1

公开(公告)日：2019-07-25

申请号：US16258753

申请日：2019-01-28

Applicant: University Health Network

Inventor： Radoslaw Laufer ,  Grace Ng ,  Richard Brokx ,  Heinz W. Pauls ,  Sze-Wan Li ,  Jacqueline M. Mason ,  Mark R. Bray

IPC: C07D487/04 ,  A61P35/00 ,  A61P29/00 ,  A61K31/519 ,  A61K45/06 ,  A61P37/06

Abstract: The invention is a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof. Values for the variables are provided herein. Also included is a pharmaceutical composition comprising the compound represented by Structural Formula (I) and a pharmaceutically acceptable carrier or diluent and methods of treating a subject with cancer with the compound of Structural Formula (I).

公开(公告)号：US20180179221A1

公开(公告)日：2018-06-28

申请号：US15738286

申请日：2016-06-23

Applicant: University Health Network

Inventor： Peter Brent Sampson ,  Narendra Kumar B. Patel ,  Heinz W. Pauls ,  Sze-Wan Li ,  Grace Ng ,  Radoslaw Laufer ,  Yong Liu ,  Yunhui Lang

IPC: C07D495/04 ,  A61K45/06 ,  A61P35/00 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/551

CPC classification number: C07D495/04 ,  A61K31/4355 ,  A61K31/496 ,  A61K31/5355 ,  A61K31/5377 ,  A61K31/551 ,  A61K39/395 ,  A61K45/06 ,  A61K2039/505 ,  A61P35/00 ,  C07K16/2818 ,  A61K2300/00

Abstract: Thienopyridinone compounds of Formula (I) and pharmaceutically acceptable salts thereof are described. In these compounds, one of X1; X2, and X3 is S and the other two are each independently CR, wherein R and all other variables are as defined herein. The compounds are shown to inhibit HPK1 kinase activity and to have in vivo antitumor activity. The compounds can be effectively combined with pharmaceutically acceptable carriers and also with other immunomodulatory approaches, such as checkpoint inhibition or inhibitors of tryptophan oxidation. Formula (I).

公开(公告)号：US20240287077A1

公开(公告)日：2024-08-29

申请号：US18391047

申请日：2023-12-20

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： Radoslaw Laufer ,  Grace Ng ,  Sze-Wan Li ,  Heinz W. Pauls ,  Yong Liu ,  Narendra Kumar B. Patel

IPC: C07D487/04 ,  C07D519/00

CPC classification number: C07D487/04 ,  C07D519/00

Abstract: The present teachings provide a compound represented by the following structural formula:




or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof.

公开(公告)号：US20210261554A1

公开(公告)日：2021-08-26

申请号：US17134270

申请日：2020-12-26

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： Radoslaw Laufer ,  Grace Ng ,  Richard Brokx ,  Heinz W. Pauls ,  Sze-Wan Li ,  Jacqueline M. Mason ,  Mark R. Bray

IPC: C07D487/04 ,  A61K31/519 ,  A61K45/06 ,  A61P37/06 ,  A61P29/00 ,  A61P35/00

Abstract: The invention is a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof. Values for the variables are provided herein. Also included is a pharmaceutical composition comprising the compound represented by Structural Formula (I) and a pharmaceutically acceptable carrier or diluent and methods of treating a subject with cancer with the compound of Structural Formula (I).

公开(公告)号：US20170217966A1

公开(公告)日：2017-08-03

申请号：US15434275

申请日：2017-02-16

Applicant: University Health Network

Inventor： Yong Liu ,  Heinz W. Pauls ,  Radoslaw Laufer ,  Sze-Wan Li ,  Peter Brent Sampson ,  Miklos Feher ,  Grace Ng ,  Narendra Kumar B. Patel ,  Yunhui Lang

IPC: C07D487/04

CPC classification number: C07D487/04 ,  C07D519/00

Abstract: The present teachings provide a compound represented by structural formula (I-0), or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof.

公开(公告)号：US09580390B2

公开(公告)日：2017-02-28

申请号：US14351381

申请日：2012-10-12

Applicant: University Health Network

Inventor： Heinz W. Pauls ,  Radoslaw Laufer ,  Yong Liu ,  Sze-Wan Li ,  Bryan T. Forrest ,  Yunhui Lang ,  Narendra Kumar B. Patel ,  Louise G. Edwards ,  Grace Ng ,  Peter Brent Sampson ,  Miklos Feher ,  Donald E. Awrey

IPC: C07D231/56 ,  C07D401/14 ,  C07D413/14 ,  C07D409/12 ,  C07D409/14 ,  C07D405/14 ,  C07D451/06 ,  C07D491/107 ,  C07D401/10 ,  C07D401/12 ,  C07D403/10 ,  C07D413/04 ,  C07D413/10 ,  C07D493/10

CPC classification number: C07D231/56 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14 ,  C07D451/06 ,  C07D491/107 ,  C07D493/10

Abstract: The present teaching provide indazole compounds represented by Structural Formulae (I) or (I′) or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof as protein kinase inhibitors, such as TTK protein kinase, polo-like kinase 4 (PLK4) and Aurora kinases having anticancer activity against breast cancer cells, colon cancer cells, and ovarian cancer cells.

Abstract translation: 本发明提供由结构式（I）表示的化合物或其药学上可接受的盐。 还描述了药物组合物及其使用方法。

公开(公告)号：US20220002313A1

公开(公告)日：2022-01-06

申请号：US17372717

申请日：2021-07-12

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： Peter Brent Sampson ,  Narendra Kumar B. Patel ,  Heinz W. Pauls ,  Sze-Wan Li ,  Grace Ng ,  Radoslaw Laufer ,  Yong Liu ,  Yunhui Lang

IPC: C07D495/04 ,  A61K31/496 ,  A61K39/395 ,  C07K16/28 ,  A61K31/4355 ,  A61K31/5355 ,  A61K31/551 ,  A61P35/00 ,  A61K31/5377 ,  A61K45/06

Abstract: Thienopyridinone compounds of Formula (I) and pharmaceutically acceptable salts thereof are described. In these compounds, one of X1; X2, and X3 is S and the other two are each independently CR, wherein R and all other variables are as defined herein. The compounds are shown to inhibit HPK1 kinase activity and to have in vivo antitumor activity. The compounds can be effectively combined with pharmaceutically acceptable carriers and also with other immunomodulatory approaches, such as a checkpoint inhibition or inhibitors of tryptophan oxidation. Formula (I).

公开(公告)号：US20210009595A1

公开(公告)日：2021-01-14

申请号：US16880192

申请日：2020-05-21

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： Radoslaw Laufer ,  Grace Ng ,  Sze-Wan Li ,  Heinz W. Pauls ,  Yong Liu ,  Narendra Kumar B. Patel

IPC: C07D487/04 ,  C07D519/00

Abstract: The present teachings provide a compound represented by the following structural formula: (Formula (I)); or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof.