公开(公告)号：US20150182526A1

公开(公告)日：2015-07-02

申请号：US14543379

申请日：2014-11-17

申请人： INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE) ,  CANCER RESEARCH TECHNOLOGY LIMITED

发明人： Caroline Joy SPRINGER ,  Dan NICULESCU-DUVAZ ,  Ion NICULESCU-DUVAZ ,  Richard MARAIS ,  Bartholomeus Marinus Josephus Marie Suijkerbuijk ,  Alfonso ZAMBON ,  Arnaud NOURRY ,  Delphine MENARD

IPC分类号： A61K31/4985

CPC分类号： C07D471/04 ,  A61K31/4985

摘要： The present invention pertains generally to the field of therapeutic compounds for treating proliferative disorders, cancer, etc., and more specifically to certain pyrido[2,3-b]pyrazin-8-substituted compounds, as described herein, which, inter alia, inhibit RAF (e.g., B-RAF) activity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., BRAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and disorders that are ameliorated by the inhibition of RAF, RTK, etc., proliferative disorders such as cancer (e.g., colorectal cancer, melanoma), etc.

摘要翻译： 本发明一般涉及用于治疗增殖性疾病，癌症等的治疗化合物领域，更具体地涉及本文所述的某些吡啶并[2,3-b]吡嗪-8-取代的化合物，其特别地， 抑制RAF（例如，B-RAF）活性。 本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在体外和体内的用途，以抑制RAF（例如BRAF）活性，抑制受体酪氨酸激酶（RTK）活性抑制 细胞增殖，以及通过抑制RAF，RTK等改善增殖性疾病如癌症（例如结肠直肠癌，黑素瘤）等疾病和病症的治疗。

公开(公告)号：US20140357663A1

公开(公告)日：2014-12-04

申请号：US14331653

申请日：2014-08-21

申请人： CANCER RESEARCH TECHNOLOGY LIMITED ,  INSTITUTE OF CANCER RESEARCH ROYAL CANCER HOSPITAL (THE)

发明人： Caroline SPRINGER ,  Ion NICULESCU-DUVAZ ,  Richard MARAIS ,  Dan NICULESCU-DUVAZ ,  Alfonso ZAMBON ,  Delphine MENARD

IPC分类号： C07D471/04

CPC分类号： A61K31/437 ,  A61K31/4353 ,  C07D401/02 ,  C07D471/04

摘要： The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain compounds of the following formula (for convenience, collectively referred to herein as “IP compounds”), which, inter alia, are useful in the treatment of cancer, e.g., cancer characterised by (e.g., driven by) mutant RAS (“mutant RAS cancer”). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions in the treatment of cancer, e.g., mutant RAS cancer.

摘要翻译： 本发明一般涉及治疗化合物领域，更具体地涉及下列化学式的某些化合物（为方便起见，统称为“IP化合物”），其特别可用于治疗癌症， 例如以突变RAS（“突变RAS癌”）为特征的癌症（例如，驱动）。 本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在治疗癌症中的用途，例如突变RAS癌症。

公开(公告)号：US09820976B2

公开(公告)日：2017-11-21

申请号：US15254103

申请日：2016-09-01

申请人： CANCER RESEARCH TECHNOLOGY LIMITED ,  INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE)

发明人： Caroline Joy Springer ,  Ion Niculescu-Duvaz ,  Richard Marais ,  Dan Niculescu-Duvaz ,  Alfonso Zambon ,  Delphine Menard

IPC分类号： A61K31/444 ,  A61K31/437 ,  C07D471/04 ,  A61K31/4353 ,  C07D401/02

CPC分类号： A61K31/437 ,  A61K31/4353 ,  C07D401/02 ,  C07D471/04

摘要： The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain compounds of the following formula (for convenience, collectively referred to herein as “IP compounds”), which, inter alia, are useful in the treatment of cancer, e.g., cancer characterized by (e.g., driven by) mutant RAS (“mutant RAS cancer”). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions in the treatment of cancer, e.g., mutant RAS cancer.

公开(公告)号：US09193689B2

公开(公告)日：2015-11-24

申请号：US14381712

申请日：2013-03-07

申请人： INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE)

发明人： Alan Ashworth ,  Christopher James Lord ,  Richard James Rowland Elliot ,  Dan Niculescu-Duvaz ,  Roderick Porter ,  Raymond John Boffey ,  Melanie Jayne Bayford ,  Stuart Firth-Clark ,  Ashley Nicholas Jarvis ,  Trevor Robert Perrior ,  Rebekah Elisabeth Key

IPC分类号： C07D401/04 ,  A61K31/4725 ,  C07D217/24 ,  C07D401/14 ,  C07D217/14 ,  C07D217/16 ,  C07D401/10 ,  C07D401/12 ,  C07D405/12 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10

CPC分类号： C07D217/24 ,  C07D217/14 ,  C07D217/16 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10

摘要： The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3-aryl-5-substituted-2H-isoquinolin-1-one compounds that, inter alia, inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.) and/or Wnt signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to inhibit Wnt signalling; to treat disorders that are ameliorated by the inhibition of PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to treat disorders that are ameliorated by the inhibition of Wnt signalling; to treat proliferative conditions such as cancer, etc.

摘要翻译： 本发明一般涉及治疗化合物领域。 更具体地，本发明涉及特别是抑制PARP（例如PARP1，TNKS1，TNKS2等）和/或Wnt信号传导的某些3-芳基-5-取代-2H-异喹啉-1-酮化合物。 本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在体外和体内的用途，以抑制PARP（例如PARP1，TNKS1，TNKS2等）; 抑制Wnt信号; 治疗通过抑制PARP而改善的疾病（例如PARP1，TNKS1，TNKS2等）; 治疗通过抑制Wnt信号传导而改善的病症; 治疗癌症等增殖性疾病

公开(公告)号：US20150099732A1

公开(公告)日：2015-04-09

申请号：US14381712

申请日：2013-03-07

申请人： INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE)

发明人： Alan Ashworth ,  Christopher James Lord ,  Richard James Rowland Elliot ,  Dan Niculescu-Duvaz ,  Roderick Porter ,  Raymond John Boffey ,  Melanie Jayne Bayford ,  Stuart Firth-Clark ,  Ashley Nicholas Jarvis ,  Trevor Robert Perrior ,  Rebekah Elisabeth Key

IPC分类号： C07D217/24 ,  C07D401/14 ,  C07D487/08 ,  C07D401/12 ,  C07D487/10 ,  C07D405/12 ,  C07D401/10 ,  C07D401/04 ,  C07D487/04

CPC分类号： C07D217/24 ,  C07D217/14 ,  C07D217/16 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10

摘要： The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3-aryl-5-substituted-2H-isoquinolin-1-one compounds that, inter alia, inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.) and/or Wnt signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to inhibit Wnt signalling; to treat disorders that are ameliorated by the inhibition of PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to treat disorders that are ameliorated by the inhibition of Wnt signalling; to treat proliferative conditions such as cancer, etc.

摘要翻译： 本发明一般涉及治疗化合物领域。 更具体地，本发明涉及特别是抑制PARP（例如PARP1，TNKS1，TNKS2等）和/或Wnt信号传导的某些3-芳基-5-取代-2H-异喹啉-1-酮化合物。 本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在体外和体内的用途，以抑制PARP（例如PARP1，TNKS1，TNKS2等）; 抑制Wnt信号; 治疗通过抑制PARP而改善的疾病（例如PARP1，TNKS1，TNKS2等）; 治疗通过抑制Wnt信号传导而改善的病症; 治疗癌症等增殖性疾病

公开(公告)号：US11207321B2

公开(公告)日：2021-12-28

申请号：US16623953

申请日：2018-06-19

申请人： Institute of Cancer Research: Royal Cancer Hospital (The) ,  Breast Cancer Now

发明人： Lesley-Ann Martin ,  Joanna Nikitorwicz-Buniak

IPC分类号： A61K31/5025 ,  A61K31/437 ,  A61K31/506 ,  A61K31/517 ,  A61K31/519 ,  A61K31/53 ,  A61P35/00

摘要： The invention described herein provides a method for the treatment of an oestrogen receptor positive breast cancer in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound capable of inhibiting MPS1, wherein: (i) said subject has previously been treated with a CDK4/6 inhibitor; and/or (ii) said breast cancer is resistant to treatment with a CDK4/6 inhibitor.

公开(公告)号：US10100053B2

公开(公告)日：2018-10-16

申请号：US15635925

申请日：2017-06-28

申请人： CANCER RESEARCH TECHNOLOGY LIMITED ,  INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE)

发明人： Alfonso Zambon ,  Dan Niculescu-Duvaz ,  Richard Chubb ,  Caroline Joy Springer

IPC分类号： C07D471/04

摘要： The present invention pertains generally to the field of organic chemical synthesis, and in particular to certain methods for the synthesis of 8-(4-aminophenyoxy)-4H-pyrido[2,3-b]pyrazin-3-one and related compounds (denoted herein as (3)) from 4-(4-aminophenyoxy)pyridine-2,3-diamine and related compounds (denoted herein as (1)), by reaction with glyoxylic acid (denoted herein as (2)). The compounds (3) are useful in the synthesis of known anti-cancer agents, such as 1-(5-tert-butyl-2-(4-methyl-phenyl)-pyrazol-3-yl)-3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea.

公开(公告)号：US20170298066A1

公开(公告)日：2017-10-19

申请号：US15637365

申请日：2017-06-29

申请人： CANCER RESEARCH TECHNOLOGY LIMITED ,  INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE)

发明人： Caroline Joy SPRINGER ,  Richard MARAIS ,  Romina GIROTTI ,  Dan NICULESCU-DUVAZ ,  Ion NICULESCU-DUVAZ ,  Alfonso ZAMBON

IPC分类号： C07D471/04

CPC分类号： C07D471/04

摘要： The present invention pertains generally to the field of therapeutic compounds.More specifically the present invention pertains to certain 1-(5-tert-butyl-2-aryl-pyrazol-3-yl)-3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea compounds (referred herein as “TBAP compounds”) that, inter alia, inhibit RAF (e.g., BRAF, CRAF, etc.).The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., BRAF, CRAF, etc.); and to treat disorders including: proliferative disorders; cancer (including, e.g., malignant melanoma, colorectal carcinoma, pancreatic adenocarcinoma); inflammation; immunological disorders; viral infections; fibrotic disorders; disorders associated with a mutated form of RAF (e.g., BRAF, CRAF, etc.); disorders ameliorated by the inhibition of RAF (e.g., BRAF, CRAF, etc.); disorders ameliorated by the inhibition of mutant BRAF; disorders ameliorated by the inhibition of BRAF and CRAF; disorders associated with RAS mutations and/or MAPK pathway activation; disorders ameliorated by the inhibition of SRC, p38, FGFRA, VEGFR-2 (KDR), and/or LCK; etc.

公开(公告)号：US09708317B2

公开(公告)日：2017-07-18

申请号：US15038337

申请日：2014-11-25

申请人： CANCER RESEARCH TECHNOLOGY LIMITED ,  INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE)

发明人： Alfonso Zambon ,  Dan Niculescu-Duvaz ,  Richard Chubb ,  Caroline Joy Springer

IPC分类号： C07D471/04

CPC分类号： C07D471/04

摘要： The present invention pertains generally to the field of organic chemical synthesis, and in particular to certain methods for the synthesis of 8-(4-aminophenyoxy)-4H-pyrido[2,3-b]pyrazin-3-one and related compounds (denoted herein as (3)) from 4-(4-aminophenyoxy)pyridine-2,3-diamine and related compounds (denoted herein as (1)), by reaction with glyoxylic acid (denoted herein as (2)). The compounds (3) are useful in the synthesis of known anti-cancer agents, such as 1-(5-tert-butyl-2-(4-methyl-phenyl)-pyrazol-3-yl)-3-[2-fluoro-4-[(3-oxo-4H-pyrido[2,3-b]pyrazin-8-yl)oxy]phenyl]urea.

公开(公告)号：US09611223B2

公开(公告)日：2017-04-04

申请号：US14917788

申请日：2014-09-11

申请人： INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE)

发明人： Alan Ashworth ,  Christopher James Lord ,  Richard James Rowland Elliott ,  Dan Niculescu-Duvaz ,  Roderick Alan Porter ,  Rehan Aqil ,  Raymond John Boffey ,  Melanie Jayne Bayford ,  Stuart Firth-Clark ,  Anna Hopkins ,  Ashley Nicholas Jarvis ,  Trevor Robert Perrior ,  Philip Alan Skone ,  Rebekah Elisabeth Key

IPC分类号： C07D217/24 ,  C07D401/14 ,  C07D413/14 ,  C07D401/10 ,  C07D413/10 ,  C07D471/08 ,  C07C53/06 ,  C07C53/18 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D487/08 ,  C07F7/18

CPC分类号： C07D217/24 ,  C07C53/06 ,  C07C53/18 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D413/10 ,  C07D413/12 ,  C07D413/14 ,  C07D471/08 ,  C07D487/08 ,  C07F7/1804

摘要： The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3-aryl-5-substituted-2/-/-isoquinolin-1-one compounds that, inter alia, inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.) and/or Wnt signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to inhibit Wnt signalling; to treat disorders that are ameliorated by the inhibition of PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to treat disorders that are ameliorated by the inhibition of Wnt signalling; to treat proliferative conditions such as cancer, etc.