公开(公告)号：US20160074374A1

公开(公告)日：2016-03-17

申请号：US14787061

申请日：2014-04-25

申请人： VERTEX PHARMACEUTICALS INCORPORATED ,  THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL

发明人： Fredrick F. Van Goor ,  Beth Jennifer Hoffman ,  Oxana Adolfovna de la Rosa ,  Douglas Cyr

IPC分类号： A61K31/443 ,  C07K16/28 ,  G01N33/68 ,  A61K39/395 ,  A61K45/06 ,  A61K38/05 ,  A61K38/02 ,  A61K31/47

CPC分类号： A61K31/443 ,  A61K31/47 ,  A61K31/69 ,  A61K38/02 ,  A61K38/05 ,  A61K39/3955 ,  A61K45/06 ,  C07K16/28 ,  G01N33/6872 ,  G01N2500/10 ,  G01N2800/7052 ,  A61K2300/00

摘要： The present disclosure provides methods for treating Cystic Fibrosis in a subject by administering to the subject a corrector agent capable of acting through MSD1 during the biosynthesis of CFTR protein. The disclosure also provides methods of screening for new corrector agents capable of acting through MSD1 during the biosynthesis of a CFTR protein.

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：US20130338188A9

公开(公告)日：2013-12-19

申请号：US13657321

申请日：2012-10-22

申请人： VERTEX PHARMACEUTICALS INCORPORATED

发明人： Fredrick F. Van Goor ,  Rossitza Gueorguieva Alargova ,  Tim Edward Alcacio ,  Sneha G. Arekar ,  Steven C. Johnston ,  Irina Nikolaevna Kadiyala ,  Ali Keshavarz-Shokri ,  Mariusz Krawiec ,  Elaine Chungmin Lee ,  Ales Medek ,  Praveen Mudunuri ,  Mark Jeffrey Sullivan ,  Noreen Tasneem Zaman ,  Beili Zhang ,  Yuegang Zhang ,  Gregor Zlokarnik

IPC分类号： A61K31/47 ,  A61P11/00 ,  A61P1/18 ,  C12Q1/02 ,  A61P3/10 ,  A61P35/00 ,  A61P25/28 ,  A61P25/16 ,  A61P11/06 ,  A61P1/16

CPC分类号： A61K31/47 ,  A61K31/404 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4704 ,  G01N33/5032 ,  G01N2500/04 ,  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：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.

公开(公告)号：US09974781B2

公开(公告)日：2018-05-22

申请号：US15234877

申请日：2016-08-11

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： A61K31/47 ,  A61K31/404

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.

公开(公告)号：US09751839B2

公开(公告)日：2017-09-05

申请号：US15160100

申请日：2016-05-20

申请人： Vertex Pharmaceuticals Incorporated

发明人： John Demattei ,  Adam R. Looker ,  Bobbianna Neubert-Langille ,  Martin Trudeau ,  Stefanie Roeper ,  Michael P. Ryan ,  Dahrika Milfred Yap Guerette ,  Brian R. Krueger ,  Peter D. J. Grootenhuis ,  Fredrick F. Van Goor ,  Martyn C. Botfield ,  Gregor Zlokarnik

IPC分类号： C07D215/56 ,  C07C229/66 ,  C07D215/233 ,  C07C69/96 ,  G01N33/50 ,  G01N33/68 ,  C07C68/02 ,  C07C201/08 ,  C07C213/02

CPC分类号： C07C205/43 ,  C07C68/02 ,  C07C69/96 ,  C07C201/08 ,  C07C213/02 ,  C07C229/66 ,  C07D215/233 ,  C07D215/56 ,  G01N33/5041 ,  G01N33/6872 ,  Y02P20/55

摘要： The invention provides a process for the preparation of a compound of Formula 1, comprising coupling a carboxylic acid of Formula 2 with an aniline of Formula 3 in the presence of a coupling agent.

公开(公告)号：US09371287B2

公开(公告)日：2016-06-21

申请号：US14286708

申请日：2014-05-23

申请人： Vertex Pharmaceuticals Incorporated

发明人： John DeMattei ,  Adam R. Looker ,  Bobbianna Neubert-Langille ,  Martin Trudeau ,  Stefanie Roeper ,  Michael P. Ryan ,  Dahrika Milfred Yap Guerette ,  Brian R. Krueger ,  Peter D. J. Grootenhuis ,  Fredrick F. Van Goor ,  Martyn C. Botfield ,  Gregor Zlokarnik

IPC分类号： C07D215/56 ,  G01N33/50 ,  G01N33/68 ,  C07C229/66 ,  C07D215/233 ,  C07C69/96 ,  C07C68/02 ,  C07C201/08 ,  C07C213/02

CPC分类号： C07C205/43 ,  C07C68/02 ,  C07C69/96 ,  C07C201/08 ,  C07C213/02 ,  C07C229/66 ,  C07D215/233 ,  C07D215/56 ,  G01N33/5041 ,  G01N33/6872 ,  Y02P20/55

摘要： The invention provides a process for the preparation of a compound of Formula 1, comprising coupling a carboxylic acid of Formula 2 with an aniline of Formula 3 in the presence of a coupling agent.

公开(公告)号：US20150315151A2

公开(公告)日：2015-11-05

申请号：US14286708

申请日：2014-05-23

申请人： Vertex Pharmaceuticals Incorporated

发明人： John DeMattei ,  Adam R. Looker ,  Bobbianna Neubert-Langille ,  Martin Trudeau ,  Stefanie Roeper ,  Michael P. Ryan ,  Dahrika Milfred Yap Guerette ,  Brian R. Krueger ,  Peter D.J. Grootenhuis ,  Fredrick F. Van Goor ,  Martyn C. Botfield ,  Gregor Zlokarnik

IPC分类号： C07D215/56 ,  G01N33/50 ,  G01N33/68 ,  C07C229/66

CPC分类号： C07C205/43 ,  C07C68/02 ,  C07C69/96 ,  C07C201/08 ,  C07C213/02 ,  C07C229/66 ,  C07D215/233 ,  C07D215/56 ,  G01N33/5041 ,  G01N33/6872 ,  Y02P20/55

摘要： The invention provides a process for the preparation of a compound of Formula 1, comprising coupling a carboxylic acid of Formula 2 with an aniline of Formula 3 in the presence of a coupling agent.

摘要翻译： 本发明提供了制备式1化合物的方法，包括在偶联剂存在下将式2的羧酸与式3的苯胺偶联。