公开(公告)号：US09701674B2

公开(公告)日：2017-07-11

申请号：US14467175

申请日：2014-08-25

申请人： Vertex Pharmaceuticals Incorporated

发明人： Jean-Damien Charrier ,  Steven Durrant ,  David Kay ,  Ronald Knegtel ,  Somhairle MacCormick ,  Michael Mortimore ,  Michael O'Donnell ,  Joanne Pinder ,  Alistair Rutherford ,  Anisa Nizarali Virani ,  Stephen Young ,  Philip Michael Reaper

IPC分类号： A61K31/4965 ,  C07D241/28 ,  C07D413/14 ,  C07D401/14 ,  C07D403/12 ,  C07D409/14 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D471/04 ,  C07D401/10 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D417/14 ,  C07D401/04 ,  C07D403/10 ,  C07D405/04 ,  C07D405/12 ,  C07D409/04

CPC分类号： C07D413/14 ,  A61P35/00 ,  C07D241/28 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

摘要： The present invention relates to pyrazine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.Certain compounds of this invention are of formula II, V, and/or VII: wherein the variables are as defined herein.

公开(公告)号：US20160271129A1

公开(公告)日：2016-09-22

申请号：US15074375

申请日：2016-03-18

申请人： Vertex Pharmaceuticals Incorporated

发明人： Jean-Damien Charrier ,  Steven John Durrant ,  Ronald Marcellus Alphonsus Knegtel ,  Anisa Nizarali Virani ,  Philip Michael Reaper

IPC分类号： A61K31/4965 ,  A61K33/24 ,  A61K31/497 ,  C07D241/24 ,  C07D413/04

CPC分类号： A61K31/4965 ,  A61K31/497 ,  A61K33/24 ,  C07D239/46 ,  C07D241/24 ,  C07D413/04

摘要： The present invention relates to pyrazine and pyridine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.The compounds of this invention have formula IV: wherein the variables are as defined herein.

公开(公告)号：US20140288347A1

公开(公告)日：2014-09-25

申请号：US14105778

申请日：2013-12-13

申请人： Vertex Pharmaceuticals Incorporated

发明人： Jean-Damien Charrier ,  Joanne Pinder ,  Ronald Marcellus Alphonsus Knegtel ,  Steven John Durrant ,  Damien Fraysse ,  Somhairle MacCormick ,  Anisa Nizarali Virani ,  Philip Michael Reaper

IPC分类号： C07D487/04 ,  A61N5/10 ,  C07D471/04 ,  C07D495/04 ,  A61K45/06 ,  A61K31/4985

CPC分类号： C07D487/04 ,  A61K31/4985 ,  A61K45/06 ,  A61N5/10 ,  A61N2005/1098 ,  C07D471/04 ,  C07D495/04 ,  A61K2300/00

摘要： The present invention relates to pyrrolopyrazines compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.The compounds of this invention have formula I: wherein the variables are as defined herein.

摘要翻译： 本发明涉及可用作ATR蛋白激酶抑制剂的吡咯并吡嗪化合物。 本发明还涉及包含本发明化合物的药学上可接受的组合物; 使用本发明化合物治疗各种疾病，病症和病症的方法; 制备本发明化合物的方法; 用于制备本发明化合物的中间体; 以及在体外应用中使用化合物的方法，如生物和病理现象中激酶的研究; 由这种激酶介导的细胞内信号转导途径的研究; 和新型激酶抑制剂的比较评估。 本发明的化合物具有式I：其中变量如本文所定义。

公开(公告)号：US20180170922A1

公开(公告)日：2018-06-21

申请号：US15608630

申请日：2017-05-30

申请人： Vertex Pharmaceuticals Incorporated

发明人： Jean-Damien Charrier ,  Steven Durrant ,  David Kay ,  Ronald Knegtel ,  Somhairle MacCormick ,  Michael Mortimore ,  Michael O'Donnell ,  Joanne Pinder ,  Alistair Rutherford ,  Anisa Nizarali Virani ,  Stephen Young ,  Philip Michael Reaper

IPC分类号： C07D413/14 ,  C07D471/04 ,  C07D241/28 ,  C07D417/12 ,  C07D417/04 ,  C07D413/12 ,  C07D409/14 ,  C07D409/04 ,  C07D405/14 ,  C07D405/12 ,  C07D405/04 ,  C07D403/14 ,  C07D403/12 ,  C07D403/10 ,  C07D403/04 ,  C07D401/14 ,  C07D401/10 ,  C07D401/04 ,  C07D417/14

CPC分类号： C07D413/14 ,  A61P35/00 ,  C07D241/28 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

摘要： The present invention relates to pyrazine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.The compounds of this invention have formula I: wherein the variables are as defined herein.

公开(公告)号：US20150051187A1

公开(公告)日：2015-02-19

申请号：US14467175

申请日：2014-08-25

申请人： Vertex Pharmaceuticals Incorporated

发明人： Jean-Damien Charrier ,  Steven Durrant ,  David Kay ,  Ronald Knegtel ,  Somhairle MacCormick ,  Michael Mortimore ,  Michael O'Donnell ,  Joanne Pinder ,  Alistair Rutherford ,  Anisa Nizarali Virani ,  Stephen Young ,  Philip Michael Reaper

IPC分类号： C07D413/14 ,  C07D401/04 ,  C07D241/28 ,  C07D405/12 ,  C07D409/04 ,  C07D413/04 ,  C07D403/04 ,  C07D405/14 ,  C07D403/10 ,  C07D405/04

CPC分类号： C07D413/14 ,  A61P35/00 ,  C07D241/28 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

摘要： The present invention relates to pyrazine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.The compounds of this invention have formula I: wherein the variables are as defined herein.

公开(公告)号：US20150031661A1

公开(公告)日：2015-01-29

申请号：US14223109

申请日：2014-03-24

申请人： Vertex Pharmaceuticals Incorporated

发明人： Jean-Damien Charrier ,  Steven Durrant ,  David Kay ,  Ronald Knegtel ,  Somhairle MacCormick ,  Michael Mortimore ,  Michael O'Donnell ,  Joanne Pinder ,  Alistair Rutherford ,  Anisa Nizarali Virani ,  Stephen Young ,  Philip Michael Reaper

IPC分类号： C07D417/14 ,  C07D403/04 ,  C07D401/14 ,  C07D413/04 ,  C07D405/14 ,  C07D403/14 ,  C07D401/10 ,  C07D409/14 ,  C07D413/14 ,  C07D241/28 ,  C07D417/04

CPC分类号： C07D413/14 ,  A61P35/00 ,  C07D241/28 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

摘要： The present invention relates to pyrazine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.The compounds of this invention have formula I: wherein the variables are as defined herein.

摘要翻译： 本发明涉及可用作ATR蛋白激酶抑制剂的吡嗪化合物。 本发明还涉及包含本发明化合物的药学上可接受的组合物; 使用本发明化合物治疗各种疾病，病症和病症的方法; 制备本发明化合物的方法; 用于制备本发明化合物的中间体; 以及在体外应用中使用化合物的方法，如生物和病理现象中激酶的研究; 由这种激酶介导的细胞内信号转导途径的研究; 和新型激酶抑制剂的比较评估。 本发明的化合物具有式I：其中变量如本文所定义。

公开(公告)号：US20140113005A1

公开(公告)日：2014-04-24

申请号：US13742948

申请日：2013-01-16

申请人： Vertex Pharmaceuticals Incorporated

发明人： Jean-Damien Charrier ,  Steven John Durrant ,  David Kay ,  Michael O'Donnell ,  Ronald Marcellus Alphonsus Knegtel ,  Somhairle MacCormick ,  Joanne Pinder ,  Stephen Clinton Young ,  Haley Marie Binch ,  Thomas Cleveland ,  Lev Tyler Dewey Fanning ,  Dennis James Hurley ,  Pramod Joshi ,  Urvi Jagdishbhai Sheth ,  Alina Silina ,  Philip Michael Reaper ,  Anisa Nizarali Virani

IPC分类号： C07D403/14 ,  A61K31/497 ,  C07D403/04 ,  A61K31/541 ,  C07D417/14 ,  A61K45/06 ,  C07D413/04 ,  C07D241/28 ,  C07D405/14 ,  C07D471/04 ,  C07D491/113 ,  C07D409/04 ,  A61K31/551 ,  C07D417/04

CPC分类号： C07D403/14 ,  A61K31/497 ,  A61K31/541 ,  A61K31/551 ,  A61K45/06 ,  C07D241/28 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D487/10 ,  C07D491/113

摘要： The present disclosure relates to pyrazine compounds of formula I: wherein L, n, R1, and R2 are as described in the specification. These compounds are useful as inhibitors of ATR protein kinase. The disclosure also relates to pharmaceutically acceptable compositions comprising the compounds of the disclosure; methods of treating of various diseases, disorders, and conditions using the compounds of the disclosure; processes for preparing the compounds of the disclosure; intermediates for the preparation of the compounds of the disclosure; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.

摘要翻译： 本公开涉及式I的吡嗪化合物：其中L，n，R 1和R 2如说明书中所述。 这些化合物可用作ATR蛋白激酶的抑制剂。 本公开还涉及包含本公开内容的化合物的药学上可接受的组合物; 使用本公开的化合物治疗各种疾病，病症和病症的方法; 制备本公开的化合物的方法; 用于制备本公开的化合物的中间体; 以及在体外应用中使用化合物的方法，如生物和病理现象中激酶的研究; 由这种激酶介导的细胞内信号转导途径的研究; 和新型激酶抑制剂的比较评估。

公开(公告)号：US11919887B2

公开(公告)日：2024-03-05

申请号：US17982983

申请日：2022-11-08

申请人： Vertex Pharmaceuticals Incorporated

发明人： Steven John Durrant ,  Nadia M. Ahmad ,  Elizabeth Mary Beck ,  Lidio Marx Carvalho Meireles ,  Ewa Iwona Chudyk ,  Gorka Etxebarria Jardi ,  Bhairavi Galan ,  Sara S. Hadida Ruah ,  Dennis James Hurley ,  Ronald Marcellus Knegtel ,  Timothy Donald Neubert ,  Joanne Louise Pinder ,  Joseph Pontillo ,  Robert Pullin ,  Yvonne Schmidt ,  David Matthew Shaw ,  Sarah Skerratt ,  Dean Stamos ,  Stephen Andrew Thomson ,  Anisa Nizarali Virani ,  Christopher Wray

IPC分类号： C07D307/24 ,  C07D405/12 ,  C07D405/14

CPC分类号： C07D405/12 ,  C07D307/24 ,  C07D405/14 ,  C07B2200/13

摘要： Compounds, and pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels are provided. Also provided are pharmaceutical compositions comprising the compounds or pharmaceutically acceptable salts and methods of using the compounds, pharmaceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain.

公开(公告)号：US11827627B2

公开(公告)日：2023-11-28

申请号：US17831842

申请日：2022-06-03

申请人： VERTEX PHARMACEUTICALS INCORPORATED

发明人： Elizabeth Mary Beck ,  Steven John Durrant ,  Sarah Skerratt ,  Robert Pullin ,  Gorka Etxebarria Jardi ,  David Matthew Shaw ,  Nadia M. Ahmad ,  Christopher Wray ,  Anisa Nizarali Virani ,  Kiri North ,  James Dodd ,  Michael Edward O'Donnell ,  Bhairavi Galan ,  Ronald Marcellus Knegtel ,  Ewa Iwona Chudyk ,  Joanne Louise Pinder ,  Stephen Andrew Thomson ,  Lidio Marx Carvalho Meireles ,  Dean Stamos ,  Yvonne Schmidt ,  Joseph Pontillo ,  Sara S. Hadida Ruah ,  Timothy Donald Neubert ,  Dennis James Hurley ,  Jinglan Zhou

IPC分类号： C07D405/12

CPC分类号： C07D405/12

摘要： Compounds, and pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels are provided. Also provided are pharmaceutical compositions comprising the compounds or pharmaceutically acceptable salts and methods of using the compounds, pharmaceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain.

公开(公告)号：US10479784B2

公开(公告)日：2019-11-19

申请号：US15967110

申请日：2018-04-30

申请人： Vertex Pharmaceuticals Incorporated

发明人： Jean-Damien Charrier ,  Steven John Durrant ,  David Kay ,  Ronald Marcellus Alphonsus Knegtel ,  Somhairle MacCormick ,  Michael Paul Mortimore ,  Michael Edward O'Donnell ,  Joanne Pinder ,  Alistair Rutherford ,  Anisa Nizarali Virani ,  Stephen Clinton Young ,  Philip Michael Reaper

IPC分类号： A61K31/497 ,  C07D403/04 ,  C07D413/14 ,  C07D401/14 ,  C07D403/12 ,  C07D409/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D471/04 ,  C07D241/28 ,  C07D401/10 ,  C07D403/14 ,  C07D405/14 ,  C07D417/14 ,  C07D401/04 ,  C07D403/10 ,  C07D405/04 ,  C07D405/12 ,  C07D409/04 ,  A61P35/00

摘要： The present invention relates to pyrazine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.The compounds of this invention have formula I: wherein the variables are as defined herein.