公开(公告)号：US11098015B2

公开(公告)日：2021-08-24

申请号：US17171752

申请日：2021-02-09

Applicant: Exelixis, Inc.

Inventor： Adrian St. Clair Brown ,  Peter Lamb ,  William P. Gallagher

IPC: C07D215/22 ,  C07D215/233

Abstract: Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1, 1-dicarboxamide.

公开(公告)号：US20210139430A1

公开(公告)日：2021-05-13

申请号：US17149365

申请日：2021-01-14

Applicant: Exelixis, Inc.

Inventor： Adrian St. Clair Brown ,  Peter Lamb ,  William P. Gallagher

IPC: C07D215/22 ,  C07D215/233

Abstract: Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclo-propane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1, 1-dicarboxamide.

公开(公告)号：US20170275251A1

公开(公告)日：2017-09-28

申请号：US15621527

申请日：2017-06-13

Applicant: Exelixis, Inc.

Inventor： Adrian St. Clair Brown ,  Peter Lamb ,  William P. Gallagher

IPC: C07D215/22 ,  C07D215/233

CPC classification number: C07D215/22 ,  C07D215/233

Abstract: Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclo-propane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide.

公开(公告)号：US20240279181A1

公开(公告)日：2024-08-22

申请号：US18612538

申请日：2024-03-21

Applicant: Exelixis, Inc.

Inventor： Adrian St. Clair Brown ,  Peter Lamb ,  William P. Gallagher

IPC: C07D215/22 ,  C07D215/233

CPC classification number: C07D215/22 ,  C07D215/233

Abstract: Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclo-propane-1,1-dicarboxamide, including a (L)-malate salt, a (D))-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide.

公开(公告)号：US20220259151A9

公开(公告)日：2022-08-18

申请号：US17371372

申请日：2021-07-09

Applicant: Exelixis, Inc.

Inventor： Adrian St. Clair Brown ,  Peter Lamb ,  William P. Gallagher

IPC: C07D215/22 ,  C07D215/233

Abstract: Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-ffuorophenyl)cyclopropane-1,1-dicarboxamide.

公开(公告)号：US20180346442A1

公开(公告)日：2018-12-06

申请号：US15852280

申请日：2017-12-22

Applicant: Exelixis, Inc.

Inventor： Adrian St. Clair Brown

IPC: C07D401/04 ,  A61P35/02

Abstract: This disclosure relates to the crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone. The disclosure also relates to pharmaceutical compositions comprising the crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone. The disclosure also relates to methods of treating cancers comprising administering to a patient in need thereof the crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl] [3-hydroxy-3-(piperidin-2-yl) azetidin-1-yl]-methanone.

公开(公告)号：US12275706B2

公开(公告)日：2025-04-15

申请号：US18958628

申请日：2024-11-25

Applicant: Exelixis, Inc.

Inventor： Adrian St. Clair Brown ,  Peter Lamb ,  William P. Gallagher

IPC: C07D215/22 ,  C07D215/233

Abstract: Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-ffuorophenyl)cyclopropane-1,1-dicarboxamide.

公开(公告)号：US11091439B2

公开(公告)日：2021-08-17

申请号：US17070514

申请日：2020-10-14

Applicant: Exelixis, Inc.

Inventor： Adrian St. Clair Brown ,  Peter Lamb ,  William P. Gallagher

IPC: C07D215/22 ,  C07D215/233

Abstract: Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide.

公开(公告)号：US20210024467A1

公开(公告)日：2021-01-28

申请号：US17070514

申请日：2020-10-14

Applicant: Exelixis, Inc.

Inventor： Adrian St. Clair Brown ,  Peter Lamb ,  William P. Gallagher

IPC: C07D215/22 ,  C07D215/233

Abstract: Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide.

公开(公告)号：US20210332013A1

公开(公告)日：2021-10-28

申请号：US17371372

申请日：2021-07-09

Applicant: Exelixis, Inc.

Inventor： Adrian St. Clair Brown ,  Peter Lamb ,  William P. Gallagher

IPC: C07D215/22 ,  C07D215/233

Abstract: Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-ffuorophenyl)cyclopropane-1,1-dicarboxamide.