公开(公告)号：US10738030B2

公开(公告)日：2020-08-11

申请号：US16089703

申请日：2017-03-31

申请人： Vertex Pharmaceuticals Incorporated

发明人： Brian Bear ,  Jeremy Clemens ,  Thomas Cleveland ,  Timothy Richard Coon ,  Peter Diederik Jan Grootenhuis ,  Bryan A. Frieman ,  Sara S. Hadida Ruah ,  Haripada Khatuya ,  Paul J. Krenitsky ,  Mark Thomas Miller ,  Alina Silina ,  Johnny Uy ,  Jinglan Zhou

IPC分类号： C07D401/14 ,  C07D213/82 ,  A61P11/00 ,  C07D401/12 ,  C07D471/04

摘要： The present disclosure features a compound of formula I: or a pharmaceutically acceptable salt thereof, where R1, R2, W, X, Z, n, p, and Rings A and B are defined herein, for the treatment of CFTR mediated diseases, such as cystic fibrosis. The present disclosure also features pharmaceutical compositions, method of treating, and kits thereof.

公开(公告)号：US20190269683A1

公开(公告)日：2019-09-05

申请号：US16258024

申请日：2019-01-25

申请人： Vertex Pharmaceuticals Incorporated

发明人： Mark Thomas Miller ,  Corey Anderson ,  Vijayalaksmi Arumugam ,  Brian Richard Bear ,  Haley Marie Binch ,  Jeremy J. Clemens ,  Thomas Cleveland ,  Erica Conroy ,  Timothy Richard Coon ,  Bryan A. Frieman ,  Peter Diederik Jan Grootenhuis ,  Raymond Stanley Gross ,  Sara Sabina Hadida-Ruah ,  Haripada Khatuya ,  Pramod Virupax Joshi ,  Paul John Krenitsky ,  Chun-Chieh Lin ,  Gulin Erdogan Marelius ,  Vito Melillo ,  Jason McCartney ,  Georgia McGaughey Nicholls ,  Fabrice Jean Denis Pierre ,  Alina Silina ,  Andreas P. Termin ,  Johnny Uy ,  Jinglan Zhou

IPC分类号： A61K31/506 ,  A61K31/4525 ,  C07D403/12 ,  A61K31/4709 ,  A61K31/4545 ,  C07D405/14 ,  C07D417/12 ,  A61K31/497 ,  C07D231/12 ,  C07D401/14 ,  A61K31/4439 ,  C07D401/12 ,  A61K31/404 ,  C07D209/42 ,  A61K31/415 ,  C07D231/14 ,  C07D213/84 ,  A61K31/44 ,  A61K31/444 ,  A61K31/4418 ,  C07D213/82 ,  A61J1/03 ,  C07D213/64 ,  C07D209/49 ,  C07D209/18 ,  C07D407/12 ,  C07D239/34 ,  C07D403/10 ,  C07D235/24 ,  C07D401/04 ,  C07D231/20 ,  C07D213/73 ,  C07D413/14 ,  A61K31/496

摘要： The present invention features a compound of formula I: or a pharmaceutically acceptable salt thereof, where R1, R2, R3, W, X, Y, Z, n, o, p, and q are defined herein, for the treatment of CFTR mediated diseases, such as cystic fibrosis. The present invention also features pharmaceutical compositions, method of treating, and kits thereof.

公开(公告)号：US10233191B2

公开(公告)日：2019-03-19

申请号：US14903475

申请日：2014-07-08

申请人： Vertex Pharmaceuticals Incorporated

发明人： Michael Paul Deninno ,  Corey Anderson ,  Erica Lynn Conroy ,  Bryan A. Frieman ,  Peter Diederik Jan Grootenhuis ,  Sara Sabina Hadida-Ruah ,  Dennis James Hurley ,  Fabrice Jean Denis Pierre ,  Alina Silina ,  Johnny Uy ,  Jinglan Zhou

IPC分类号： C07D491/056 ,  C07D221/04 ,  C07D401/06 ,  C07D405/06 ,  C07D405/12 ,  C07D487/04 ,  C07D491/044 ,  C07D491/048 ,  C07D401/04 ,  C07D403/06

摘要： The invention relates to fused piperidine amides useful as inhibitors of ion channels for the treatment of pain. 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.

公开(公告)号：US09550761B2

公开(公告)日：2017-01-24

申请号：US13972151

申请日：2013-08-21

申请人： Vertex Pharmaceuticals Incorporated

发明人： Sara Sabina Hadida-Ruah ,  Peter Diederik Jan Grootenhuis ,  Mark Thomas Miller ,  Matthew Hamilton

IPC分类号： C07D231/40 ,  C07D233/08 ,  C07D263/48 ,  C07D271/113 ,  C07D277/46 ,  C07D277/54 ,  C07D277/82 ,  C07D285/135 ,  C07D405/12 ,  C07D407/12 ,  C07D493/10 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D233/88

CPC分类号： C07D417/12 ,  C07D231/40 ,  C07D233/88 ,  C07D263/48 ,  C07D271/113 ,  C07D277/46 ,  C07D277/54 ,  C07D277/82 ,  C07D285/135 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D417/04 ,  C07D417/06 ,  C07D417/14 ,  C07D493/10

摘要： The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”), 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”）转运体或其片段的调节剂，包括囊性纤维化跨膜电导调节剂（“CFTR”），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：US20160022664A2

公开(公告)日：2016-01-28

申请号：US14629097

申请日：2015-02-23

申请人： Vertex Pharmaceuticals Incorporated

发明人： Fredrick F. Van Goor ,  Rossitza Gueorguieva Alargova ,  Tim Edward Alcacio ,  Hayley Marie Binch ,  Martyn Curtis Botfield ,  Lev Tyler Dewey Fanning ,  Peter Diederik Jan Grootenhuis ,  Dennis James Hurley ,  Irina Nikolaevna Kadiyala ,  Ritu Rohit Kaushik ,  Ali Keshavarz-Shokri ,  Mariusz Krawiec ,  Elaine Chungmin Lee ,  Brian Luisi ,  Ales Medek ,  Mehdi Numa ,  Urvi Jagdishbhai Sheth ,  Alina Silina ,  Marinus Jacobus Verwijs ,  Xiaoqing Yang ,  Christopher Ryan Young ,  Noreen Tasneem Zaman ,  Beili Zhang ,  Yuegang Zhang ,  Gregor Zlokarnik

IPC分类号： A61K31/4709 ,  A61K31/404 ,  C12Q1/34 ,  A61K31/443

CPC分类号： A61K31/4709 ,  A61K31/404 ,  A61K31/443 ,  A61K31/4704 ,  A61K45/06 ,  C07D405/12 ,  C12Q1/34 ,  G01N2500/04 ,  G01N2500/20 ,  A61K2300/00

摘要： The present invention relates to pharmaceutical compositions comprising a compound of Formula I in combination with one or both of a Compound of Formula II and/or a Compound of Formula III. The invention also relates to solid forms and to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis.

公开(公告)号：US20140309220A1

公开(公告)日：2014-10-16

申请号：US14355325

申请日：2012-11-02

申请人： VERTEX PHARMACEUTICALS INCORPORATED

发明人： Sara Sabina Hadida-Ruah ,  Peter Diederik Jan Grootenhuis ,  Mark Thomas Miller ,  Corey Anderson ,  Joseph Pontillo ,  Edward Adam Kallel ,  Mehdi Michael Djamel Numa ,  Bryan A. Frieman ,  Jason McCartney ,  Jennings Franklin Worley, III ,  Vijayalaksmi Arumugam ,  Johnny Uy ,  Nicole Hilgraf ,  Brian Richard Bear

IPC分类号： C07D498/20 ,  C07D491/20

CPC分类号： C07D498/20 ,  C07D491/20

摘要： The invention relates to benzoxazines 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苯并恶嗪。 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：US20140080826A1

公开(公告)日：2014-03-20

申请号：US14036286

申请日：2013-09-25

申请人： VERTEX PHARMACEUTICALS INCORPORATED

发明人： SARA SABINA HADIDA RUAH ,  Peter Diederik Jan Grootenhuis ,  Frederick F. Van Goor ,  Jinglan Zhou ,  Brian Richard Bear ,  Mark Thomas Miller ,  Jason Mc Cartney ,  Mehdi Numa ,  Xiaoqing Yang

IPC分类号： C07D405/12 ,  C07D405/14 ,  C07D403/12

CPC分类号： A61K31/47 ,  A61K31/404 ,  A61K31/4045 ,  A61K31/405 ,  A61K31/407 ,  A61K31/41 ,  A61K31/4184 ,  A61K31/4192 ,  A61K31/454 ,  A61K31/5377 ,  A61K45/06 ,  C07D209/08 ,  C07D233/64 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D471/04 ,  C07D487/04 ,  G01N33/5035 ,  G01N2333/705 ,  G01N2500/10

摘要： Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

摘要翻译： 本发明的化合物及其药学上可接受的组合物可用作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（“CFTR”）。 本发明还涉及使用本发明化合物治疗ABC转运蛋白介导的疾病的方法。

公开(公告)号：US20230357191A1

公开(公告)日：2023-11-09

申请号：US17880720

申请日：2022-08-04

申请人： Vertex Pharmaceuticals Incorporated

发明人： Alexander Russell Abela ,  Timothy Alcacio ,  Corey Anderson ,  Paul Timothy Angell ,  Minson Baek ,  Jeremy J. Clemens ,  Thomas Cleveland ,  Lori Ann Ferris ,  Peter Diederik Jan Grootenhuis ,  Raymond Stanley Gross ,  Anton V. Gulevich ,  Sara Sabina Hadida Ruah ,  Clara Kuang-Ju Hsia ,  Robert M. Hughes ,  Pramod Virupax Joshi ,  Ping Kang ,  Ali Keshavarz-Shokri ,  Haripada Khatuya ,  Paul John Krenitsky ,  Jason McCartney ,  Mark Thomas Miller ,  Prasuna Paraselli ,  Fabrice Jean Denis Pierre ,  Yi Shi ,  Muna Shrestha ,  David Andrew Siesel ,  Kathy Stavropoulos ,  Andreas P. Termin ,  Fredrick F. Van Goor ,  Johnny Uy ,  Timothy John Young ,  Jinglan Zhou

IPC分类号： C07D401/14 ,  C07D471/14 ,  A61P11/00 ,  C07D498/14 ,  C07D401/04 ,  C07D231/20

CPC分类号： C07D401/14 ,  A61P11/00 ,  C07D231/20 ,  C07D401/04 ,  C07D471/14 ,  C07D498/14 ,  C07B2200/13

摘要： Compounds of Formula (I):





pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed. Also disclosed are solid state forms of Compound 1 and salts and solvates thereof.

公开(公告)号：US10987348B2

公开(公告)日：2021-04-27

申请号：US15949404

申请日：2018-04-10

申请人： Vertex Pharmaceuticals Incorporated

发明人： Sara Sabina Hadida Ruah ,  Peter Diederik Jan Grootenhuis ,  Fredrick F. Van Goor ,  Jinglan Zhou ,  Brian Richard Bear ,  Mark Thomas Miller ,  Jason McCartney ,  Mehdi Michel Djamel Numa

IPC分类号： C07D209/08 ,  A61K31/47 ,  C07D471/04 ,  C07D405/12 ,  C07D405/14 ,  C07D233/64 ,  C07D403/12 ,  A61K31/4045 ,  A61K31/407 ,  A61K31/41 ,  A61K31/4184 ,  A61K31/4192 ,  A61K31/454 ,  A61K31/5377 ,  A61K45/06 ,  C07D487/04 ,  G01N33/50 ,  A61K31/405 ,  A61K31/404

摘要： Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

公开(公告)号：US10793547B2

公开(公告)日：2020-10-06

申请号：US15836627

申请日：2017-12-08

申请人： Vertex Pharmaceuticals Incorporated

发明人： Alexander Russell Abela ,  Timothy Alcacio ,  Corey Anderson ,  Paul Timothy Angell ,  Minson Baek ,  Jeremy J. Clemens ,  Thomas Cleveland ,  Lori Ann Ferris ,  Peter Diederik Jan Grootenhuis ,  Raymond Stanley Gross ,  Anton V. Gulevich ,  Sara Sabina Hadida Ruah ,  Clara Kuang-Ju Hsia ,  Robert M. Hughes ,  Pramod Virupax Joshi ,  Ping Kang ,  Ali Keshavarz-Shokri ,  Haripada Khatuya ,  Paul John Krenitsky ,  Jason McCartney ,  Mark Thomas Miller ,  Prasuna Paraselli ,  Fabrice Jean Denis Pierre ,  Yi Shi ,  Muna Shrestha ,  David Andrew Siesel ,  Kathy Stavropoulos ,  Andreas P. Termin ,  Fredrick F. Van Goor ,  Johnny Uy ,  Timothy John Young ,  Jinglan Zhou

IPC分类号： C07D401/14 ,  C07D471/14 ,  A61P11/00 ,  C07D498/14 ,  C07D401/04 ,  C07D231/20

摘要： Compounds of Formula (I): pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed. Also disclosed are solid state forms of Compound 1 and salts and solvates thereof.