公开(公告)号：US08785626B2

公开(公告)日：2014-07-22

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.

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：US20210277024A1

公开(公告)日：2021-09-09

申请号：US17156384

申请日：2021-01-22

Applicant: Genentech, Inc.

Inventor： Terry Kellar ,  Jun Liang ,  Sushant Malhotra ,  Rohan V. Mendonca ,  Michael Siu ,  Craig Stivala ,  John C. Tellis ,  BinQing Wei ,  Bryan K. Chan ,  Lewis J. Gazzard ,  Timothy Heffron ,  Graham Jones ,  Michael Lainchbury ,  Andrew Madin ,  Eileen Mary Seward ,  Matthew W. Cartwright ,  Emanuela Gancia ,  David Favor ,  Kin Chiu Fong ,  Andrew Good ,  Yonghan Hu

IPC: C07D519/00 ,  C07D471/04 ,  A61P37/04

Abstract: Naphthyridine compounds of formula (I). variations thereof, and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the naphthyridine compounds.

公开(公告)号：US20210253580A1

公开(公告)日：2021-08-19

申请号：US17156387

申请日：2021-01-22

Applicant: Genentech, Inc.

Inventor： Jun Liang ,  Sushant Malhotra ,  Rohan V. Mendonca ,  Naomi Rajapaksa ,  Michael Siu ,  Craig Stivala ,  John C. Tellis ,  BinQing Wei ,  Bryan K. Chan ,  Joy Alison Drobnick ,  Lewis J. Gazzard ,  Timothy Heffron ,  Graham Jones ,  Michael Lainchbury ,  Andrew Madin ,  Eileen Mary Seward ,  Matthew W. Cartwright ,  Emanuela Gancia ,  David Favor ,  Kin Chiu Fong ,  Andrew Good ,  Yonghan Hu

IPC: C07D487/04 ,  C07D513/04 ,  C07D519/00 ,  C07D487/14 ,  C07D498/14 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D498/04 ,  A61P37/04

Abstract: Isoquinoline compounds of formula (I): variations thereof, and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the isoquinoline compounds.

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：US10407424B2

公开(公告)日：2019-09-10

申请号：US15942321

申请日：2018-03-30

Applicant: Genentech, Inc.

Inventor： Bryan Chan ,  Naomi Rajapaksa ,  Michael Siu ,  Craig Stivala ,  John Tellis ,  Weiru Wang ,  BinQing Wei ,  Aihe Zhou ,  Matthew W. Cartwright ,  Emanuela Gancia ,  Graham Jones ,  Blake Daniels ,  Michael Lainchbury ,  Andrew Madin ,  Eileen Seward ,  David Favor ,  Kin Chiu Fong ,  Andrew Good ,  Yonghan Hu ,  Baihua Hu ,  Aijun Lu ,  Joy Drobnick ,  Lewis Gazzard ,  Timothy Heffron ,  Malcolm Huestis ,  Jun Liang ,  Sushant Malhotra ,  Rohan Mendonca

IPC: C07D471/04 ,  A61K31/55 ,  A61P35/00 ,  A61K31/444 ,  A61K31/4375 ,  A61K31/506 ,  C07D519/00 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/5383 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/5025 ,  A61K31/551 ,  A61K45/06

Abstract: Naphthyridine compounds and their use as inhibitors of HPK1 are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the naphthyridine compounds.

公开(公告)号：US09951064B2

公开(公告)日：2018-04-24

申请号：US15152947

申请日：2016-05-12

Applicant: Genentech, Inc.

Inventor： Marian C. Bryan ,  Bryan Chan ,  Francois Diederich ,  Jennafer Dotson ,  Emily Hanan ,  Timothy Heffron ,  Michael Lainchbury ,  Robert Heald ,  Eileen M. Seward

IPC: C07D471/04 ,  C07D519/00 ,  A61K31/517 ,  A61K31/5386 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  A61K31/541

CPC classification number: C07D471/04 ,  A61K31/506 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/5386 ,  A61K31/541 ,  A61K45/06 ,  C07D519/00

Abstract: This invention relates to novel compounds which are inhibitors of T790M containing EGFR mutants, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the prevention or treatment of cancer.

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：US08952043B2

公开(公告)日：2015-02-10

申请号：US14162520

申请日：2014-01-23

Applicant: Genentech, Inc.

Inventor： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Richard Goldsmith ,  Robert Heald ,  Timothy Heffron ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  BinQing Wei

IPC: C07D249/14 ,  A61K31/41 ,  C07D495/04 ,  A61K31/381 ,  A61K31/4245 ,  A61K31/429 ,  A61K31/4365 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  C07D495/14 ,  C07D513/04 ,  C07D513/14 ,  A61K31/4196 ,  A61K31/4545 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/541 ,  A61K31/551 ,  A61K45/06

CPC classification number: C07D495/04 ,  A61K31/381 ,  A61K31/41 ,  A61K31/4196 ,  A61K31/4245 ,  A61K31/429 ,  A61K31/4365 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/551 ,  A61K45/06 ,  C07D249/14 ,  C07D495/14 ,  C07D513/04 ,  C07D513/14

Abstract: Benzoxepin compounds of Formula I, and 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 where (i) X1 is N and X2 is S, (ii) X1 is S and X2 is N, (iii) X1 is CR7 and X2 is S, (iv) X1 is S and X2 is CR7; (v) X1 is NR8 and X2 is N, (vi) X1 is N and X2 is NR8, (vii) X1 is CR7 and X2 is O, (viii) X1 is O and X2 is CR7, (ix) X1 is CR7 and X2 is C(R7)2, (x) X1 is C(R7)2 and X2 is CR7; (xi) X1 is N and X2 is O, or (xii) X1 is O and X2 is N, 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。