公开(公告)号：US09198918B2

公开(公告)日：2015-12-01

申请号：US14297142

申请日：2014-06-05

Applicant: Genentech, Inc.

Inventor： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

IPC: A61K31/553 ,  C07D498/04 ,  C07D498/14 ,  C07D519/00 ,  A61K45/06

CPC classification number: C07D498/04 ,  A61K31/553 ,  A61K45/06 ,  C07D491/044 ,  C07D498/14 ,  C07D519/00

Abstract: Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Abstract translation: 式I的苯并氧氮杂化合物，包括立体异构体，几何异构体，互变异构体，溶剂合物，代谢物及其药学上可接受的盐，其中：Z1是CR1或N; Z2为CR2或N; Z3为CR3或N; Z4是CR4或N; B是与苯并氧杂环环稠合的吡唑基，咪唑基或三唑基环，可用于抑制脂质激酶，包括p110α和PI3K的其他同种型，并用于治疗由脂质激酶介导的癌症等疾病。 公开了使用式I化合物在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

公开(公告)号：US20140343036A1

公开(公告)日：2014-11-20

申请号：US14448941

申请日：2014-07-31

Applicant: Genentech, Inc.

Inventor： Huifen Chen ,  Terry Crawford ,  Steven R. Magnuson ,  Chudi Ndubaku ,  Lan Wang

IPC: C07D471/04 ,  C07D401/12 ,  C07D413/12

CPC classification number: C07D471/04 ,  C07D217/22 ,  C07D217/26 ,  C07D401/04 ,  C07D401/12 ,  C07D413/04 ,  C07D413/12

Abstract: The invention provides novel compounds having the general formula: wherein A, R1 and R2 are as described herein, compositions including the compounds and methods of using the compounds.

Abstract translation: 本发明提供具有以下通式的新化合物：其中A，R 1和R 2如本文所述，包括该化合物的组合物和使用该化合物的方法。

公开(公告)号：US20130324516A1

公开(公告)日：2013-12-05

申请号：US13906626

申请日：2013-05-31

Applicant: Genentech, Inc

Inventor： Huifen Chen ,  Terry Crawford ,  Seth F. Harris ,  Steven R. Magnuson ,  Chudi Ndubaku ,  Lan Wang

IPC: C07D471/04 ,  C07D239/94

CPC classification number: A61K31/519 ,  A61K31/5377 ,  A61K31/551 ,  A61K31/553 ,  C07D239/94 ,  C07D239/95 ,  C07D401/04 ,  C07D401/06 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D471/04

Abstract: The invention provides novel compounds having the general formula: wherein A, R1, R2 and R3 are as defined herein, compositions including the compounds and methods of using the compounds.

Abstract translation: 本发明提供具有以下通式的新化合物：其中A，R 1，R 2和R 3如本文所定义，包括该化合物的组合物和使用该化合物的方法。

公开(公告)号：US20190330235A1

公开(公告)日：2019-10-31

申请号：US16507523

申请日：2019-07-10

Applicant: Genentech, Inc.

Inventor： Jennafer Dotson ,  Robert Andrew Heald ,  Timothy Heffron ,  Graham Elgin Jones ,  Sussie Lerche Krintel ,  Neville James McLean ,  Chudi Ndubaku ,  Alan G. Olivero ,  Laurent Salphati ,  Lan Wang ,  BinQing Wei

IPC: C07D498/22 ,  C07D498/20 ,  A61K31/5377 ,  C07D471/14 ,  C07D498/14 ,  A61K31/5383 ,  A61K31/5386 ,  A61K39/395 ,  C07D491/147 ,  C07D495/14 ,  C07D491/14 ,  C07D487/14 ,  C07K16/22

Abstract: Tricyclic PI3k inhibitor compounds of Formula I with anti-cancer activity, anti-inflammatory activity, or immunoregulatory properties, and more specifically with PI3 kinase modulating or inhibitory activity are described. Methods are described for using the tricyclic PI3K inhibitor compounds of Formula I for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, organisms, or associated pathological conditions. Formula I compounds include stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof. The dashed lines indicate an optional double bond, and at least one dashed line is a double bond. The substituents are as described.

公开(公告)号：US20170081341A1

公开(公告)日：2017-03-23

申请号：US15368937

申请日：2016-12-05

Applicant: Genentech, Inc.

Inventor： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

IPC: C07D498/04

CPC classification number: C07D498/04 ,  A61K31/553 ,  A61K45/06 ,  C07D491/044 ,  C07D498/14 ,  C07D519/00

Abstract: Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

公开(公告)号：US20140058098A1

公开(公告)日：2014-02-27

申请号：US14047206

申请日：2013-10-07

Applicant: Genentech, Inc.

Inventor： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

IPC: C07D498/04

CPC classification number: C07D498/04 ,  A61K31/553 ,  A61K45/06 ,  C07D491/044 ,  C07D498/14 ,  C07D519/00

Abstract: Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

公开(公告)号：US20130079331A1

公开(公告)日：2013-03-28

申请号：US13681763

申请日：2012-11-20

Applicant: GENENTECH, INC.

Inventor： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

IPC: C07D498/04

CPC classification number: C07D498/04 ,  A61K31/553 ,  A61K45/06 ,  C07D491/044 ,  C07D498/14 ,  C07D519/00

Abstract: Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Abstract translation: 式I的苯并氧氮杂化合物，包括立体异构体，几何异构体，互变异构体，溶剂合物，代谢物及其药学上可接受的盐，其中：Z1是CR1或N; Z2为CR2或N; Z3为CR3或N; Z4是CR4或N; B是与苯并氧杂环环稠合的吡唑基，咪唑基或三唑基环，可用于抑制脂质激酶，包括p110α和PI3K的其他同种型，并用于治疗由脂质激酶介导的癌症等疾病。 公开了使用式I化合物在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

公开(公告)号：US11236046B2

公开(公告)日：2022-02-01

申请号：US16657102

申请日：2019-10-18

Applicant: Genentech, Inc.

Inventor： Huifen Chen ,  Yanyan Chu ,  Steven Do ,  Anthony Estrada ,  Baihua Hu ,  Aleksandr Kolesnikov ,  Xingyu Lin ,  Joseph P. Lyssikatos ,  Daniel Shore ,  Vishal Verma ,  Lan Wang ,  Guosheng Wu ,  Po-wai Yuen

IPC: C07D207/48 ,  C07D403/12 ,  C07D401/14 ,  C07D401/12 ,  C07D403/14 ,  C07D417/12 ,  C07D451/02 ,  C07D491/048 ,  C07D405/14

Abstract: The invention is concerned with the compounds of formula I or II: and salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I or II as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

公开(公告)号：US20180118680A1

公开(公告)日：2018-05-03

申请号：US15851322

申请日：2017-12-21

Applicant: Genentech, Inc.

Inventor： Huifen Chen ,  Yanyan Chu ,  Steven Do ,  Anthony Estrada ,  Baihua Hu ,  Aleksandr Kolesnikov ,  Xingyu Lin ,  Joseph P. Lyssikatos ,  Daniel Shore ,  Vishal Verma ,  Lan Wang ,  Guosheng Wu ,  Po-wai Yuen

IPC: C07D207/48 ,  C07D403/14 ,  C07D417/12 ,  C07D403/12 ,  C07D451/02 ,  C07D405/14 ,  C07D401/14 ,  C07D491/048 ,  C07D401/12

Abstract: The invention is concerned with the compounds of formula I or II: and salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I or II as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

公开(公告)号：US09855269B2

公开(公告)日：2018-01-02

申请号：US15454793

申请日：2017-03-09

Applicant: Genentech, Inc.

Inventor： Huifen Chen ,  Terry Crawford ,  Seth F. Harris ,  Steven R. Magnuson ,  Chudi Nbdubaku ,  Lan Wang

IPC: A61K31/519 ,  A61K31/5377 ,  A61K31/551 ,  A61K31/553

CPC classification number: A61K31/519 ,  A61K31/5377 ,  A61K31/551 ,  A61K31/553 ,  C07D239/94 ,  C07D239/95 ,  C07D401/04 ,  C07D401/06 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D471/04

Abstract: The invention provides a method of inhibiting angiogenesis in a patient by administering a compound of formula (I): wherein R1 R2 and R3 are as defined herein, compositions including the compounds and methods of using the compounds.