公开(公告)号：US20190185447A1

公开(公告)日：2019-06-20

申请号：US16271215

申请日：2019-02-08

Applicant: Exelixis, Inc. ,  Genentech, Inc.

Inventor： Sriram Naganathan ,  Nathan Guz ,  Matthew Pfeiffer ,  C. Gregory Sowell ,  Tracy Bostick ,  Jason Yang ,  Amit Srivastava ,  Neel Kumar Anand

IPC: C07D401/04 ,  C07D498/04

Abstract: Disclosed herein is a process of making a compound of formula I The compound of formula I is an inhibitor of MEK and thus can be used to treat cancer.

公开(公告)号：US20190218182A1

公开(公告)日：2019-07-18

申请号：US16362863

申请日：2019-03-25

Applicant: Exelixis, Inc.

Inventor： Dana T. Aftab ,  Sriram Naganathan ,  Wei Xu ,  Steven Lacy ,  Linh Nguyen

IPC: C07D215/22 ,  G01N33/487 ,  C07C233/60 ,  C07C305/24 ,  C07D215/60

CPC classification number: C07D215/22 ,  C07C233/60 ,  C07C305/24 ,  C07C2601/02 ,  C07D215/60 ,  G01N33/487 ,  G01N2570/00

Abstract: The invention relates to metabolites of cabozantinib (I) as well as uses thereof.

公开(公告)号：US20140256938A1

公开(公告)日：2014-09-11

申请号：US14353251

申请日：2012-10-22

Applicant: Exelixis, Inc.

Inventor： Jo Ann Wilson ,  Sriram Naganathan ,  Neil G. Andersen ,  Matthew Pfeiffer

IPC: C07D215/233 ,  C07C231/02

CPC classification number: C07D215/233 ,  C07C231/02 ,  C07C233/58 ,  C07C233/59 ,  C07D215/00 ,  C07D239/90

Abstract: A process for preparing a compound of Formula I is disclosed, comprising the steps: wherein: R1 is halo; R2 is halo; R3 is (C1-C6)alkyl or (C1-C6)alkyl optionally substituted with heterocycloalkyl; R4 is (C1-C6)alkyl; and Q is CH or N; comprising: (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent; (b) adding and a tertiary amine base to the mixture of step (a) to form a compound of Formula A; and (c) coupling a compound of Formula A with an amine of Formula B to form a compound of Formula I.

Abstract translation: 公开了制备式I化合物的方法，包括以下步骤：其中：R1为卤素; R2是卤素; R 3是（C 1 -C 6）烷基或任选被杂环烷基取代的（C 1 -C 6）烷基; R4是（C1-C6）烷基; Q为CH或N; 包括：（a）在极性非质子溶剂中将1,1-环丙烷二羧酸与亚硫酰氯接触; （b）向步骤（a）的混合物中加入叔胺碱，形成式A的化合物; 和（c）将式A的化合物与式B的胺偶联以形成式I的化合物。

公开(公告)号：US10793541B2

公开(公告)日：2020-10-06

申请号：US16271215

申请日：2019-02-08

Applicant: Exelixis, Inc. ,  Genentech, Inc.

Inventor： Sriram Naganathan ,  Nathan Guz ,  Matthew Pfeiffer ,  C. Gregory Sowell ,  Tracy Bostick ,  Jason Yang ,  Amit Srivastava ,  Neel Kumar Anand

IPC: C07D471/04 ,  C07D401/04 ,  C07D498/04

Abstract: Disclosed herein is a process of making a compound of formula I The compound of formula I is an inhibitor of MEK and thus can be used to treat cancer.

公开(公告)号：US10159666B2

公开(公告)日：2018-12-25

申请号：US15126767

申请日：2015-03-17

Applicant: Exelixis, Inc.

Inventor： Dana T. Aftab ,  Sriram Naganathan ,  Wei Xu ,  Steven Lacy

IPC: A61K31/47 ,  A61K9/20 ,  A61K9/00

Abstract: The invention relates to administration of various pharmaceutical formulations of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, (cabozantinib) a c-Met inhibitor, and its metabolites, to achieve desirable pharmacokinetic and pharmacodynamic effects.

公开(公告)号：US09969692B2

公开(公告)日：2018-05-15

申请号：US15133708

申请日：2016-04-20

Applicant: Exelixis, Inc.

Inventor： Jo Ann Wilson ,  Sriram Naganathan ,  Neil G. Andersen ,  Matthew Pfeiffer

IPC: C07D215/00 ,  C07D215/233 ,  C07D239/90 ,  C07C231/02

CPC classification number: C07D215/233 ,  C07C231/02 ,  C07C233/58 ,  C07C233/59 ,  C07D215/00 ,  C07D239/90

Abstract: A process for preparing a compound of Formula I is disclosed, comprising the steps: wherein: R1 is halo; R2 is halo; R3 is (C1-C6)alkyl or (C1-C6)alkyl optionally substituted with heterocycloalkyl; R4 is (C1-C6)alkyl; and Q is CH or N; comprising: (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent; (b) adding and a tertiary amine base to the mixture of step (a) to form a compound of Formula A; and (c) coupling a compound of Formula A with an amine of Formula B to form a compound of Formula I.

公开(公告)号：US20170087143A1

公开(公告)日：2017-03-30

申请号：US15126767

申请日：2015-03-17

Applicant: Exelixis, Inc.

Inventor： Dana T. Aftab ,  Sriram Naganathan ,  Wei Xu ,  Steven Lacy

IPC: A61K31/47 ,  A61K9/00

CPC classification number: A61K31/47 ,  A61K9/0053 ,  A61K9/2054

Abstract: The invention relates to administration of various pharmaceutical formulations of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, (cabozantinib) a c-Met inhibitor, and its metabolites, to achieve desirable pharmacokinetic and pharmacodynamic effects.

公开(公告)号：US20160229805A1

公开(公告)日：2016-08-11

申请号：US15133708

申请日：2016-04-20

Applicant: Exelixis, Inc.

Inventor： Jo Ann Wilson ,  Sriram Naganathan ,  Neil G. Andersen ,  Matthew Pfeiffer

IPC: C07D215/233 ,  C07C231/02

CPC classification number: C07D215/233 ,  C07C231/02 ,  C07C233/58 ,  C07C233/59 ,  C07D215/00 ,  C07D239/90

Abstract: A process for preparing a compound of Formula I is disclosed, comprising the steps: wherein: R1 is halo; R2 is halo; R3 is (C1-C6)alkyl or (C1-C6)alkyl optionally substituted with heterocycloalkyl; R4 is (C1-C6)alkyl; and Q is CH or N; comprising: (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent; (b) adding and a tertiary amine base to the mixture of step (a) to form a compound of Formula A; and (c) coupling a compound of Formula A with an amine of Formula B to form a compound of Formula 1.

Abstract translation: 公开了制备式I化合物的方法，包括以下步骤：其中：R1为卤素; R2是卤素; R 3是（C 1 -C 6）烷基或任选被杂环烷基取代的（C 1 -C 6）烷基; R4是（C1-C6）烷基; Q为CH或N; 包括：（a）在极性非质子溶剂中将1,1-环丙烷二羧酸与亚硫酰氯接触; （b）向步骤（a）的混合物中加入叔胺碱，形成式A的化合物; 和（c）将式A的化合物与式B的胺偶联以形成式1的化合物。

公开(公告)号：US09365516B2

公开(公告)日：2016-06-14

申请号：US14353251

申请日：2012-10-22

Applicant: Exelixis, Inc.

Inventor： Jo Ann Wilson ,  Sriram Naganathan ,  Neil G. Andersen ,  Matthew Pfeiffer

IPC: C07D239/72 ,  C07D215/00 ,  C07D215/233 ,  C07D239/90 ,  C07C231/02

CPC classification number: C07D215/233 ,  C07C231/02 ,  C07C233/58 ,  C07C233/59 ,  C07D215/00 ,  C07D239/90

Abstract: A process for preparing a compound of Formula I is disclosed: wherein: R1 is halo; R2 is halo; R3 is (C1-C6)alkyl or (C1-C6)alkyl optionally substituted with heterocycloalkyl; R4 is (C1-C6)alkyl; and Q is CH or N; comprising: (a) contacting 1,1-cyclopropane dicarboxylic acid with thionyl chloride in a polar aprotic solvent; (b) adding and a tertiary amine base to the mixture of step (a) to form a compound of Formula A; and (c) coupling a compound of Formula A with an amine of Formula B to form a compound of Formula I.

Abstract translation: 公开了制备式I化合物的方法：其中：R1为卤素; R2是卤素; R 3是（C 1 -C 6）烷基或任选被杂环烷基取代的（C 1 -C 6）烷基; R4是（C1-C6）烷基; Q为CH或N; 包括：（a）在极性非质子溶剂中将1,1-环丙烷二羧酸与亚硫酰氯接触; （b）向步骤（a）的混合物中加入叔胺碱，形成式A的化合物; 和（c）将式A的化合物与式B的胺偶联以形成式I的化合物。

公开(公告)号：US11414396B2

公开(公告)日：2022-08-16

申请号：US17003570

申请日：2020-08-26

Applicant: Exelixis, Inc. ,  Genentech, Inc.

Inventor： Sriram Naganathan ,  Nathan Guz ,  Matthew Pfeiffer ,  C. Gregory Sowell ,  Tracy Bostick ,  Jason Yang ,  Amit Srivastava ,  Neel Kumar Anand

IPC: C07D401/04 ,  C07D498/04

Abstract: Disclosed herein is a process of making a compound of formula I The compound of formula I is an inhibitor of MEK and thus can be used to treat cancer.