公开(公告)号：WO2018014116A1

公开(公告)日：2018-01-25

申请号：PCT/CA2017/050848

申请日：2017-07-13

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： LI, Sze-Wan ,  PAULS, Heinz W. ,  SAMPSON, Peter Brent

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

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.

Abstract translation: 本发明涉及式（I）化合物的新颖共结晶：其中前成分分子为二磷酸半水合物的式（I）化合物，涉及制备 共晶体，含有该共晶体的药物组合物，涉及这种共晶体在制备用于治疗癌症的药物中的用途以及通过施用于人或动物体内治疗此类疾病的方法 治疗有效量的这种共晶体。

公开(公告)号：WO2013053051A1

公开(公告)日：2013-04-18

申请号：PCT/CA2012/000955

申请日：2012-10-12

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： PAULS, Heinz W. ,  LAUFER, Radoslaw ,  LIU, Yong ,  LI, Sze-Wan ,  FORREST, Bryan T. ,  LANG, Yunhui ,  PATEL, Narendra Kumar B. ,  EDWARDS, Louise G. ,  NG, Grace ,  SAMPSON, Peter Brent ,  FEHER, Miklos ,  AWREY, Donald E.

IPC: C07D401/00 ,  A61K31/416 ,  A61P35/00 ,  C07D231/56 ,  C07D401/02 ,  C07D401/14 ,  C07D403/02 ,  C07D405/14 ,  C07D409/14 ,  C07D451/06 ,  C07D491/107

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: 本教导提供由结构式（I）或（I'）表示的吲唑化合物或其药学上可接受的盐。 还描述了作为蛋白激酶抑制剂的药物组合物及其使用方法，例如对乳腺癌细胞，结肠癌细胞和卵巢癌细胞具有抗癌活性的TTK蛋白激酶，polo样激酶4（PLK4）和Aurora激酶。

公开(公告)号：WO2015070349A1

公开(公告)日：2015-05-21

申请号：PCT/CA2014/051091

申请日：2014-11-14

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： LAUFER, Radoslaw ,  NG, Grace ,  LI, Sze-Wan ,  PAULS, Heinz W. ,  LIU, Yong ,  PATEL, Narendra Kumar B.

IPC: C07D487/04 ,  A61K31/519 ,  A61P35/00

CPC classification number: 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.

Abstract translation: 本发明提供由以下结构式表示的化合物：（式（I））; 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：WO2015054793A1

公开(公告)日：2015-04-23

申请号：PCT/CA2014/051001

申请日：2014-10-17

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： SAMPSON, Peter Brent ,  FEHER, Miklos ,  PAULS, Heinz W.

IPC: C07D413/14 ,  A61K31/5377 ,  A61P35/00

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 (I)

Abstract translation: 公开了由以下结构式表示的化合物（I）的富马酸盐和马来酸盐，以及它们相应的药物组合物。 1：1富马酸化合物（I）和马来酸化合物（I）的特殊单晶形式的特征在于各种性能和物理测量。 还公开了制备1：1富马酸化合物（I）和1:1化合物（I）马来酸酯的特定结晶形式的方法。 本发明还提供了治疗患有癌症的受试者的方法。 化合物（I）

公开(公告)号：WO2016205942A1

公开(公告)日：2016-12-29

申请号：PCT/CA2016/050734

申请日：2016-06-23

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： SAMPSON, Peter Brent ,  PATEL, Narendra Kumar B. ,  PAULS, Heinz W. ,  LI, Sze-Wan ,  NG, Grace ,  LAUFER, Radoslaw ,  LIU, Yong ,  LANG, Yunhui

IPC: C07D495/04 ,  A61K31/4436 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/551 ,  A61K39/395 ,  A61P35/00

CPC classification number: C07D495/04 ,  A61K31/4436 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  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 X 1 ; X 2 , and X 3 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).

Abstract translation: 描述了式（I）的噻吩并吡啶酮化合物及其药学上可接受的盐。 在这些化合物中，X1中的一种; X 2和X 3为S，另外两个各自独立地为CR，其中R和所有其它变量如本文所定义。 显示这些化合物抑制HPK1激酶活性并具有体内抗肿瘤活性。 化合物可以有效地与药学上可接受的载体组合，也可以与其他免疫调节方法如检查点抑制或色氨酸氧化抑制剂组合。 式（I）。

公开(公告)号：WO2014056083A1

公开(公告)日：2014-04-17

申请号：PCT/CA2013/000859

申请日：2013-10-11

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： LIU, Yong ,  LANG, Yunhui ,  NG, Grace ,  LI, Sze-Wan ,  PAULS, Heinz W. ,  LAUFER, Radoslaw ,  PATEL, Narendra Kumar B. ,  SAMPSON, Peter Brent ,  FEHER, Miklos ,  AWREY, Donald E.

IPC: C07D451/06 ,  A61K31/416 ,  A61K31/4439 ,  A61P35/00 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  C07D498/08

CPC classification number: C07D498/08 ,  C07D231/56 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D451/06

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).

Abstract translation: 本发明是由结构式（I）表示的化合物或其药学上可接受的盐。 这里提供了变量的值。 还包括药物组合物，其包含由结构式（I）表示的化合物和药学上可接受的载体或稀释剂以及用结构式（I）的化合物治疗患有癌症的受试者的方法。

公开(公告)号：WO2011123937A1

公开(公告)日：2011-10-13

申请号：PCT/CA2011/000366

申请日：2011-04-06

Applicant: UNIVERSITY HEALTH NETWORK ,  LAUFER, Radoslaw ,  PAULS, Heinz W. ,  FEHER, Miklos ,  NG, Grace ,  LIU, Yong ,  EDWARDS, Louise G. ,  PATEL, Narendra Kumar B. ,  PAN, Guohua ,  MAK, Tak W.

Inventor： LAUFER, Radoslaw ,  PAULS, Heinz W. ,  FEHER, Miklos ,  NG, Grace ,  LIU, Yong ,  EDWARDS, Louise G. ,  PATEL, Narendra Kumar B. ,  PAN, Guohua ,  MAK, Tak W.

IPC: C07D231/56 ,  A61K31/416 ,  A61P35/00 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

CPC classification number: C07D231/56 ,  A61K31/00 ,  A61K31/517 ,  A61K31/522 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: The present teachings provide a compound represented by Strutural Formula (I): or a pharmaceutically acceptable salt thereof. Also described are a pharmaceutical composition and method of use thereof.

Abstract translation: 本发明提供由式（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：WO2016065461A1

公开(公告)日：2016-05-06

申请号：PCT/CA2015/051024

申请日：2015-10-09

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： LAUFER, Radoslaw ,  NG, Grace ,  BROKX, Richard ,  PAULS, Heinz W. ,  LI, Sze-wan ,  MASON, Jacqueline M. ,  BRAY, Mark R.

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

CPC classification number: A61K31/519 ,  A61K45/06 ,  C07D487/04

Abstract: The invention is a compound represented by Structural Formula (I): (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).

Abstract translation: 本发明是由结构式（I）表示的化合物：（I）; 或其药学上可接受的盐。 这里提供了变量的值。 还包括药物组合物，其包含由结构式（I）表示的化合物和药学上可接受的载体或稀释剂以及用结构式（I）的化合物治疗患有癌症的受试者的方法。

公开(公告)号：WO2014075168A1

公开(公告)日：2014-05-22

申请号：PCT/CA2013/000957

申请日：2013-11-15

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： LIU, Yong ,  PAULS, Heinz W. ,  LAUFER, Radoslaw ,  LI, Sze-Wan ,  SAMPSON, Peter Brent ,  FEHER, Miklos ,  NG, Grace ,  PATEL, Narendra Kumar B. ,  LANG, Yunhui

IPC: C07D487/04 ,  A61K31/519 ,  A61P35/00

CPC classification number: 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.

Abstract translation: 本发明提供由结构式（1-0）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：WO2011123947A1

公开(公告)日：2011-10-13

申请号：PCT/CA2011/000387

申请日：2011-04-06

Applicant: UNIVERSITY HEALTH NETWORK ,  CUMMINGS, Graham ,  PATEL, Narenda Kumar B. ,  FORREST, Bryan, T. ,  LIU, Yong ,  LI, Sze-Wan ,  SAMPSON, Peter Brent ,  EDWARDS, Louise, G. ,  PAULS, Heinz W.

Inventor： CUMMINGS, Graham ,  PATEL, Narenda Kumar B. ,  FORREST, Bryan, T. ,  LIU, Yong ,  LI, Sze-Wan ,  SAMPSON, Peter Brent ,  EDWARDS, Louise, G. ,  PAULS, Heinz W.

IPC: C07D403/04 ,  C07D231/56 ,  C07D413/14

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 cyclopropyl indolinone compound represented by Structural Formula (A): (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）表示的环丙基吲哚啉酮化合物的新型合成方法：（A）或其药学上可接受的盐。 还包括本文所述的合成中间体。