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：US10919886B2

公开(公告)日：2021-02-16

申请号：US16675609

申请日：2019-11-06

Applicant: University Health Network

Inventor： Peter Brent Sampson ,  Miklos Feher ,  Heinz W. Pauls

IPC: C07D413/14

Abstract: A fumarate salt and a maleate salt of compound (I) represented by the following structural formula, as well as their corresponding pharmaceutical compositions, are disclosed. Particular single crystalline forms of 1:1 compound (I) fumarate and 1:1 compound (I) maleate are characterized by a variety of properties and physical measurements. Methods of preparing specific crystalline forms of 1:1 compound (I) fumarate and 1:1 compound (I) maleate are also disclosed. The present invention also provides methods of treating a subject with a cancer.

公开(公告)号：US20200270259A1

公开(公告)日：2020-08-27

申请号：US16806392

申请日：2020-03-02

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： Sze-Wan Li ,  Heinz W. Pauls ,  Peter Brent Sampson

IPC: C07D487/04 ,  A61P35/00 ,  C30B29/58 ,  C30B7/14 ,  C30B7/02 ,  A61K31/519

Abstract: The present invention relates to a novel co-crystal of the compound of formula (I): wherein the co-former molecule is bisphosphate hemihydrate, to processes for the preparation of the co-crystal, to pharmaceutical compositions containing the co-crystal, to the use of such a co-crystal in the manufacture of a medicament for use in the treatment of cancer and to methods of treating such diseases in the human or animal body by administering a therapeutically effective amount of such a co-crystal.

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：US20190292193A1

公开(公告)日：2019-09-26

申请号：US16318426

申请日：2017-07-13

Applicant: University Health Network

Inventor： Sze-Wan Li ,  Heinz W. Pauls ,  Peter Brent Sampson

IPC: C07D487/04

Abstract: The present invention relates to a novel co-crystal of the compound of formula (I): (Formula (I)) wherein the co-former molecule is bisphosphate hemihydrate, to processes for the preparation of the co-crystal, to pharmaceutical compositions containing the co-crystal, to the use of such a co-crystal in the manufacture of a medicament for use in the treatment of cancer and to methods of treating such diseases in the human or animal body by administering a therapeutically effective amount of such a co-crystal.

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：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：US09884855B2

公开(公告)日：2018-02-06

申请号：US15029373

申请日：2014-10-17

Applicant: University Health Network

Inventor： Peter Brent Sampson ,  Miklos Feher ,  Heinz W. Pauls

IPC: A61K31/535 ,  C07D413/14

CPC classification number: C07D413/14

Abstract: A fumarate salt and a maleate salt of compound (I) represented by the following structural formula, as well as their corresponding pharmaceutical compositions, are disclosed. Particular single crystalline forms of 1:1 compound (I) fumarate and 1:1 compound (I) maleate are characterized by a variety of properties and physical measurements. Methods of preparing specific crystalline forms of 1:1 compound (I) fumarate and 1:1 compound (I) maleate are also disclosed. The present invention also provides methods of treating a subject with a cancer. Compound

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。