公开(公告)号：US11566003B2

公开(公告)日：2023-01-31

申请号：US16921297

申请日：2020-07-06

Applicant: Genentech, Inc.

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

IPC: C07D217/22 ,  A61K31/549 ,  A61P35/00 ,  A61K45/06 ,  C07D401/04 ,  A61K31/4725 ,  A61K31/506 ,  A61K31/501 ,  C07D471/04 ,  C07D413/04 ,  C07D413/14 ,  A61K31/5377 ,  C07D417/04 ,  A61K31/4985 ,  C07D401/14 ,  C07D487/04 ,  A61K31/551 ,  C07D498/04 ,  A61K31/5383 ,  C07D405/14 ,  C07D519/00 ,  C07D498/14 ,  C07D513/04 ,  A61K31/554 ,  A61K31/55 ,  A61K31/472 ,  C07D409/14 ,  C07D491/04 ,  C07D487/14

Abstract: Isoquinoline compounds 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：US20220073520A1

公开(公告)日：2022-03-10

申请号：US17213362

申请日：2021-03-26

Applicant: Genentech, Inc.

Inventor： Sushant Malhotra ,  Michael Siu ,  Weiru Wang ,  BinQing Wei ,  Aihe Zhou ,  Bryan K. Chan ,  Lewis J. Gazzard ,  Timothy Heffron ,  Michael Lainchbury ,  Andrew Madin ,  Eileen Mary Seward ,  Matthew W. Cartwright ,  Emanuela Gancia ,  David Favor ,  Kin Chiu Fong ,  Andrew Good ,  Yonghan Hu

IPC: C07D487/04 ,  C07D403/04 ,  C07D401/04 ,  C07D405/14 ,  C07D237/28 ,  C07D401/14 ,  C07D417/04

Abstract: Cinnoline 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 cinnoline compounds.

公开(公告)号：US20160257682A1

公开(公告)日：2016-09-08

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

IPC: C07D471/04 ,  A61K31/517 ,  A61K31/5386 ,  C07D519/00 ,  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.

Abstract translation: 本发明涉及作为含有EGFR突变体的T790M抑制剂的新化合物，含有它们的药物组合物，其制备方法及其在治疗中用于预防或治疗癌症的新化合物。

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：US09175009B2

公开(公告)日：2015-11-03

申请号：US14565669

申请日：2014-12-10

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: A61K31/41 ,  C07D249/14 ,  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.

Abstract translation: 式I的苯并氧杂环己烯化合物，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; 并且其中（i）X1为N且X2为S，（ii）X1为S且X2为N，（iii）X1为CR7，X2为S，（iv）X1为S且X2为CR7; （ⅴ）X1为NR8，X2为N，（vi）X1为N，X2为NR8，i X1为CR7，X2为O，（ii）X1为O，X2为CR7，ix为CR7 X2为C（R7）2，（x）X1为C（R7）2，X2为CR7; （xi）X1是N，X2是O，或（xii）X1是O，X2是N，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：US11944606B2

公开(公告)日：2024-04-02

申请号：US17178021

申请日：2021-02-17

Applicant: Genentech, Inc.

Inventor： Timothy Heffron ,  Sushant Malhotra ,  BinQing Wei ,  Bryan Chan ,  Lewis Gazzard ,  Emanuela Gancia ,  Michael Lainchbury ,  Andrew Madin ,  Eileen Seward ,  Yonghan Hu

IPC: A61K31/437 ,  A61K31/444 ,  A61K31/506 ,  A61K31/513 ,  A61K31/5377 ,  C07D471/04

CPC classification number: A61K31/437 ,  A61K31/444 ,  A61K31/506 ,  A61K31/513 ,  A61K31/5377 ,  C07D471/04

Abstract: Azaindole 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 azaindole compounds.

公开(公告)号：US20220370420A1

公开(公告)日：2022-11-24

申请号：US17204089

申请日：2021-03-17

Applicant: Genentech, Inc.

Inventor： Sushant Malhotra ,  Craig Stivala ,  BinQing Wei ,  Bryan K. Chan ,  Timothy Heffron ,  Michael Lainchbury ,  Andrew Madin ,  Terry Aaron Panchal ,  Eileen Mary Seward ,  Toby Blench ,  Matthew W. Cartwright ,  Elsa Amandine Dechaux ,  Richard Elliott ,  Emanuela Gancia

IPC: A61K31/437 ,  A61K45/06 ,  C07D471/10 ,  C07D491/20 ,  C07D519/00 ,  C07D487/20 ,  C07D471/20 ,  A61K31/5377 ,  A61K31/444 ,  A61K31/496 ,  A61K31/513 ,  A61K31/4985

Abstract: Spirocyclic 2,3-dihydro-7-azaindole 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 spirocyclic 2,3-dihydro-7-azaindole compounds.

公开(公告)号：US20210332064A1

公开(公告)日：2021-10-28

申请号：US17220307

申请日：2021-04-01

Applicant: Genentech, Inc.

Inventor： Jun Liang ,  Rohan V. Mendonca ,  Michael Siu ,  John Tellis ,  Weiru Wang ,  BinQing Wei ,  Bryan Chan ,  Edna F. Choo ,  Joy Drobnick ,  Lewis J. Gazzard ,  Timothy Heffron

IPC: C07D498/04 ,  C07D401/04 ,  C07D401/14 ,  C07D519/00

Abstract: 3-Carbonylaminoisoquinoline 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 3-carbonylaminoisoquinoline compounds.

公开(公告)号：US11034692B1

公开(公告)日：2021-06-15

申请号：US16542129

申请日：2019-08-15

Applicant: Genentech, Inc.

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

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

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：US10952995B2

公开(公告)日：2021-03-23

申请号：US16568459

申请日：2019-09-12

Applicant: Genentech, Inc.

Inventor： Timothy Heffron ,  Sushant Malhotra ,  BinQing Wei ,  Bryan Chan ,  Lewis Gazzard ,  Emanuela Gancia ,  Michael Lainchbury ,  Andrew Madin ,  Eileen Seward ,  Yonghan Hu

IPC: A61K31/437 ,  A61K31/444 ,  A61K31/506 ,  A61K31/513 ,  A61K31/5377 ,  C07D471/04

Abstract: Azaindole 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 azaindole compounds.