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：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：US09907800B2

公开(公告)日：2018-03-06

申请号：US14823057

申请日：2015-08-11

Applicant: University Health Network

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

IPC: A61K31/5377 ,  C07D413/14 ,  C07D403/10 ,  C07D403/14 ,  C07D231/56 ,  C07D403/04 ,  A61K45/06

CPC classification number: C07D403/10 ,  A61K31/5377 ,  A61K45/06 ,  C07D231/56 ,  C07D403/04 ,  C07D403/14 ,  C07D413/14

Abstract: The invention is directed to a compound represented by the following structural formula and pharmaceutically acceptable salts thereof: Compounds represented by this structural formula are kinase inhibitors and are therefore disclosed herein for the treatment of cancer. Definitions for the variables in the structural formula are provided herein.

公开(公告)号：US20160045511A1

公开(公告)日：2016-02-18

申请号：US14823057

申请日：2015-08-11

Applicant: University Health Network

Inventor： Peter Brent Sampson ,  Yong Liu ,  Sze-Wan Li ,  Bryan T. Forrest ,  Heinz W. Pauls ,  Louise G. Edwards ,  Miklos Feher ,  Narendra Kumar B. Patel ,  Radoslaw Laufer ,  Guohua Pan

IPC: A61K31/5377

CPC classification number: C07D403/10 ,  A61K31/5377 ,  A61K45/06 ,  C07D231/56 ,  C07D403/04 ,  C07D403/14 ,  C07D413/14

Abstract: The invention is directed to a compound represented by the following structural formula and pharmaceutically acceptable salts thereof: Compounds represented by this structural formula are kinase inhibitors and are therefore disclosed herein for the treatment of cancer. Definitions for the variables in the structural formula are provided herein.

Abstract translation: 本发明涉及由以下结构式表示的化合物及其药学上可接受的盐：由该结构式表示的化合物是激酶抑制剂，因此本文公开了用于治疗癌症的化合物。 本文提供了结构式中变量的定义。

公开(公告)号：US20150133677A1

公开(公告)日：2015-05-14

申请号：US14580658

申请日：2014-12-23

Applicant: University Health Network

Inventor： Graham Cumming ,  Narendra Kumar B. Patel ,  Bryan T. Forrest ,  Yong Liu ,  Sze-Wan Li ,  Peter Brent Sampson ,  Louise G. Edwards ,  Heinz W. Pauls

IPC: C07D403/04 ,  C07D231/56

CPC classification number: C07D403/10 ,  A61K31/5377 ,  A61K45/06 ,  C07D231/56 ,  C07D403/04 ,  C07D403/14 ,  C07D413/14

Abstract: The present invention is directed to novel synthetic methods for preparing a spiro cyclopropyl indolinone compound represented by Structural Formula (A): or its pharmaceutically acceptable salt thereof. Also included are synthetic intermediates described herein.

Abstract translation: 本发明涉及用于制备由结构式（A）表示的螺环丙基吲哚啉酮化合物或其药学上可接受的盐的新型合成方法。 还包括本文所述的合成中间体。

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：US20180282306A1

公开(公告)日：2018-10-04

申请号：US15902143

申请日：2018-02-22

Applicant: University Health Network

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

IPC: C07D403/10 ,  A61K31/5377 ,  A61K45/06 ,  C07D413/14 ,  C07D231/56 ,  C07D403/14 ,  C07D403/04

CPC classification number: C07D403/10 ,  A61K31/5377 ,  A61K45/06 ,  C07D231/56 ,  C07D403/04 ,  C07D403/14 ,  C07D413/14

Abstract: The invention is directed to a compound represented by the following structural formula and pharmaceutically acceptable salts thereof: Compounds represented by this structural formula are kinase inhibitors and are therefore disclosed herein for the treatment of cancer. Definitions for the variables in the structural formula are provided herein.

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。