公开(公告)号：US09630956B2

公开(公告)日：2017-04-25

申请号：US13106476

申请日：2011-05-12

申请人： Jean-Damien Charrier ,  Hayley Marie Binch ,  Dennis James Hurley ,  Thomas Cleveland ,  Pramod Joshi ,  Lev Tyler Dewey Fanning ,  Joanne Pinder ,  Michael O'Donnell ,  Anisa Nizarali Virani ,  Ronald Marcellus Alphonsus Knegtel ,  Steven John Durrant ,  Stephen Clinton Young ,  Pierre-Henri Storck ,  David Kay ,  Philip Michael Reaper ,  Matthew Paul Grote

发明人： Jean-Damien Charrier ,  Hayley Marie Binch ,  Dennis James Hurley ,  Thomas Cleveland ,  Pramod Joshi ,  Lev Tyler Dewey Fanning ,  Joanne Pinder ,  Michael O'Donnell ,  Anisa Nizarali Virani ,  Ronald Marcellus Alphonsus Knegtel ,  Steven John Durrant ,  Stephen Clinton Young ,  Pierre-Henri Storck ,  David Kay ,  Philip Michael Reaper ,  Matthew Paul Grote

IPC分类号： A61K31/497 ,  A61K33/24 ,  C07D413/14 ,  C07D401/14 ,  C07D241/10

CPC分类号： C07D413/14

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 I: wherein the variables are as defined herein.

公开(公告)号：US20120027874A1

公开(公告)日：2012-02-02

申请号：US13106476

申请日：2011-05-12

申请人： Jean-Damien Charrier ,  Hayley Marie Binch ,  Dennis James Hurley ,  Thomas Cleveland ,  Pramod Joshi ,  Lev Tyler Dewey Fanning ,  Joanne Pinder ,  Michael O'Donnell ,  Anisa Nizarali Virani ,  Ronald Marcellus Alphonsus Knegtel ,  Steven John Durrant ,  Stephen Clinton Young ,  Pierre-Henri Storck ,  David Kay ,  Philip Michael Reaper

发明人： Jean-Damien Charrier ,  Hayley Marie Binch ,  Dennis James Hurley ,  Thomas Cleveland ,  Pramod Joshi ,  Lev Tyler Dewey Fanning ,  Joanne Pinder ,  Michael O'Donnell ,  Anisa Nizarali Virani ,  Ronald Marcellus Alphonsus Knegtel ,  Steven John Durrant ,  Stephen Clinton Young ,  Pierre-Henri Storck ,  David Kay ,  Philip Michael Reaper

IPC分类号： A61K31/497 ,  A61K33/24 ,  A61P35/00 ,  C07D413/14

CPC分类号： C07D413/14

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 I: wherein the variables are as defined herein.

公开(公告)号：US08410112B2

公开(公告)日：2013-04-02

申请号：US13104291

申请日：2011-10-27

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

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 ,  Hayley 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： A61K31/4965 ,  C07D403/00

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：US20120040020A1

公开(公告)日：2012-02-16

申请号：US13104291

申请日：2011-10-27

申请人： 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

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： A61K33/24 ,  C07D401/14 ,  C07D413/14 ,  A61K31/551 ,  A61K31/497 ,  A61K31/5377 ,  C07D417/14 ,  A61K31/541 ,  C07D405/14 ,  C07D471/04 ,  C07D491/113 ,  A61K31/506 ,  C07D513/04 ,  C07D409/14 ,  C07D487/04 ,  A61K31/4985 ,  C07D487/10 ,  A61K38/16 ,  A61K31/704 ,  A61K31/675 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/706 ,  A61K38/12 ,  A61P17/06 ,  A61P35/00 ,  A61P31/18 ,  A61P1/16 ,  A61P31/20 ,  C07D403/14

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：US08828996B2

公开(公告)日：2014-09-09

申请号：US13418737

申请日：2012-03-13

申请人： Sara Sabina Hadida-Ruah ,  Hayley Marie Binch ,  Michael Paul DeNinno ,  Lev Tyler Dewey Fanning ,  Bryan A. Frieman ,  Peter Diederik Jan Grootenhuis ,  Nicole Hilgraf ,  Pramod Joshi ,  Edward Adam Kallel ,  Mark Thomas Miller ,  Joseph Pontillo ,  Alina Silina ,  Urvi Jagdishbhai Sheth ,  Dennis James Hurley ,  Vijayalaksmi Arumugam

发明人： Sara Sabina Hadida-Ruah ,  Hayley Marie Binch ,  Michael Paul DeNinno ,  Lev Tyler Dewey Fanning ,  Bryan A. Frieman ,  Peter Diederik Jan Grootenhuis ,  Nicole Hilgraf ,  Pramod Joshi ,  Edward Adam Kallel ,  Mark Thomas Miller ,  Joseph Pontillo ,  Alina Silina ,  Urvi Jagdishbhai Sheth ,  Dennis James Hurley ,  Vijayalaksmi Arumugam

IPC分类号： C07D498/10 ,  A61K31/537

CPC分类号： C07D498/10

摘要： The invention relates to morpholine spirocyclic piperidine amide compounds useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

摘要翻译： 本发明涉及可用作离子通道抑制剂的吗啉螺环哌啶酰胺化合物。 本发明还提供包含本发明化合物的药学上可接受的组合物和使用该组合物治疗各种疾病的方法。

公开(公告)号：US20120264749A1

公开(公告)日：2012-10-18

申请号：US13418737

申请日：2012-03-13

申请人： Sara Sabina Hadida-Ruah ,  Hayley Marie Binch ,  Michael Paul DeNinno ,  Lev Tyler Dewey Fanning ,  Bryan A. Frieman ,  Peter Diederik Jan Grootenhuis ,  Nicole Hilgraf ,  Pramod Joshi ,  Edward Adam Kallel ,  Mark Thomas Miller ,  Joseph Pontillo ,  Alina Silina ,  Urvi Jagdishbhai Sheth ,  Dennis James Hurley ,  Vijayalaksmi Arumugam

发明人： Sara Sabina Hadida-Ruah ,  Hayley Marie Binch ,  Michael Paul DeNinno ,  Lev Tyler Dewey Fanning ,  Bryan A. Frieman ,  Peter Diederik Jan Grootenhuis ,  Nicole Hilgraf ,  Pramod Joshi ,  Edward Adam Kallel ,  Mark Thomas Miller ,  Joseph Pontillo ,  Alina Silina ,  Urvi Jagdishbhai Sheth ,  Dennis James Hurley ,  Vijayalaksmi Arumugam

IPC分类号： A61K31/537 ,  A61K31/5377 ,  A61P25/00 ,  A61P19/02 ,  A61P25/06 ,  A61P25/08 ,  A61P25/28 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P9/06 ,  A61P25/14 ,  A61P1/00 ,  A61P9/12 ,  A61P29/00 ,  A61P1/18 ,  A61P13/10 ,  A61P13/08 ,  A61P17/04 ,  C12N5/071 ,  C07D498/10

CPC分类号： C07D498/10

摘要： The invention relates to morpholine spirocyclic piperidine amide compounds useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

摘要翻译： 本发明涉及可用作离子通道抑制剂的吗啉螺环哌啶酰胺化合物。 本发明还提供包含本发明化合物的药学上可接受的组合物和使用该组合物治疗各种疾病的方法。

公开(公告)号：US08344147B2

公开(公告)日：2013-01-01

申请号：US12909750

申请日：2010-10-21

申请人： Narendra Bhalchandra Ambhaikar ,  Robert Hughes ,  Dennis James Hurley ,  Elaine Chungmin Lee ,  Benjamin Littler ,  Mehdi Numa ,  Stefanie Roeper ,  Urvi Sheth

发明人： Narendra Bhalchandra Ambhaikar ,  Robert Hughes ,  Dennis James Hurley ,  Elaine Chungmin Lee ,  Benjamin Littler ,  Mehdi Numa ,  Stefanie Roeper ,  Urvi Sheth

IPC分类号： C07D487/08 ,  C07D215/56

CPC分类号： C07D487/08 ,  C07D215/56

摘要： The present invention relates to processes for preparing solid state forms of N-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1, 4-dihydroquinoline-3-carboxamide, including Compound 1 Form A, Compound 1 Form A-HCl, Compound 1 Form B, and Compound 1 Form B-HCl, any combination of these forms, pharmaceutical compositions thereof, and methods of treatment therewith.

摘要翻译： 本发明涉及制备固体形式的N-（4-（7-氮杂双环[2.2.1]庚-7-基）-2-（三氟甲基）苯基）-4-氧代-5-（三氟甲基） -1,4-二氢喹啉-3-甲酰胺，包括化合物1形式A，化合物1形式A-HCl，化合物1形式B和化合物1形式B-HCl，这些形式的任何组合，其药物组合物，和 治疗。

公开(公告)号：US20120309758A1

公开(公告)日：2012-12-06

申请号：US13492164

申请日：2012-06-08

申请人： Urvi Sheth ,  Lev T.D. Fanning ,  Mehdi Numa ,  Hayley Binch ,  Dennis James Hurley ,  Jinglan Zhou ,  Sara S. Hadida Ruah ,  Anna R. Hazlewood ,  Alina Silina ,  Rajendran Vairagoundar ,  Fredrick F. Van Goor ,  Peter Diederik Jan Grootenhuis ,  Martyn C. Botfield

发明人： Urvi Sheth ,  Lev T.D. Fanning ,  Mehdi Numa ,  Hayley Binch ,  Dennis James Hurley ,  Jinglan Zhou ,  Sara S. Hadida Ruah ,  Anna R. Hazlewood ,  Alina Silina ,  Rajendran Vairagoundar ,  Fredrick F. Van Goor ,  Peter Diederik Jan Grootenhuis ,  Martyn C. Botfield

IPC分类号： A61K31/47 ,  A61K31/4709 ,  C12N5/071 ,  C07D215/56 ,  C07D413/12 ,  A61K31/5377 ,  A61P29/00 ,  A61P25/08 ,  A61P25/16 ,  A61P25/28 ,  A61P25/00 ,  A61P3/00 ,  A61P11/00 ,  A61P1/18 ,  A61P19/10 ,  A61P3/10 ,  A61P27/02 ,  A61P11/06 ,  A61P15/08 ,  C07D401/12

CPC分类号： A61K31/4725 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/5377 ,  A61K45/06 ,  C07D215/56 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  A61K2300/00

摘要： The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

摘要翻译： 本发明涉及ATP结合盒（ABC）转运蛋白或其片段的调节剂，包括囊性纤维化跨膜电导调节剂，其组合物及其方法。 本发明还涉及使用这种调节剂治疗ABC转运蛋白介导的疾病的方法。

公开(公告)号：US20110124869A1

公开(公告)日：2011-05-26

申请号：US12909750

申请日：2010-10-21

申请人： Narendra Bhalchandra Ambhaikar ,  Robert Hughes ,  Dennis James Hurley ,  Elaine Chungmin Lee ,  Benjamin Littler ,  Mehdi Numa ,  Stefanie Roeper ,  Urvi Sheth

发明人： Narendra Bhalchandra Ambhaikar ,  Robert Hughes ,  Dennis James Hurley ,  Elaine Chungmin Lee ,  Benjamin Littler ,  Mehdi Numa ,  Stefanie Roeper ,  Urvi Sheth

IPC分类号： C07D487/08 ,  C07D215/56

CPC分类号： C07D487/08 ,  C07D215/56

摘要： The present invention relates to processes for preparing solid state forms of N-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide, including Compound 1 Form A, Compound 1 Form A-HCl, Compound 1 Form B, and Compound 1 Form B-HCl, any combination of these forms, pharmaceutical compositions thereof, and methods of treatment therewith.

摘要翻译： 本发明涉及制备固体形式的N-（4-（7-氮杂双环[2.2.1]庚-7-基）-2-（三氟甲基）苯基）-4-氧代-5-（三氟甲基） -1,4-二氢喹啉-3-甲酰胺，包括化合物1形式A，化合物1形式A-HCl，化合物1形式B和化合物1形式B-HCl，这些形式的任何组合，其药物组合物和方法 治疗。

公开(公告)号：US08802700B2

公开(公告)日：2014-08-12

申请号：US13492164

申请日：2012-06-08

申请人： Urvi Sheth ,  Lev T. D. Fanning ,  Mehdi Numa ,  Hayley Binch ,  Dennis James Hurley ,  Jinglan Zhou ,  Sara S. Hadida Ruah ,  Anna R. Hazlewood ,  Alina Silina ,  Rajendran Vairagoundar ,  Fredrick F. Van Goor ,  Peter Diederik Jan Grootenhuis ,  Martyn C. Botfield

发明人： Urvi Sheth ,  Lev T. D. Fanning ,  Mehdi Numa ,  Hayley Binch ,  Dennis James Hurley ,  Jinglan Zhou ,  Sara S. Hadida Ruah ,  Anna R. Hazlewood ,  Alina Silina ,  Rajendran Vairagoundar ,  Fredrick F. Van Goor ,  Peter Diederik Jan Grootenhuis ,  Martyn C. Botfield

IPC分类号： A61K31/04 ,  A61K31/4725 ,  A61K31/4709

CPC分类号： A61K31/4725 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/5377 ,  A61K45/06 ,  C07D215/56 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  A61K2300/00

摘要： The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

摘要翻译： 本发明涉及ATP结合盒（“ABC”）转运蛋白或其片段的调节剂，包括囊性纤维化跨膜电导调节剂，其组合物及其方法。 本发明还涉及使用这种调节剂治疗ABC转运蛋白介导的疾病的方法。