公开(公告)号：US20150094347A1

公开(公告)日：2015-04-02

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: C07D495/04

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：US20150079081A1

公开(公告)日：2015-03-19

申请号：US14524204

申请日：2014-10-27

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 ,  BinQuing Wei

IPC: C07D498/14 ,  A61K31/5377 ,  A61K31/5386 ,  A61K31/5383 ,  C07D498/20 ,  C07D491/147 ,  A61K39/395

CPC classification number: C07D498/22 ,  A61K31/5377 ,  A61K31/5383 ,  A61K31/5386 ,  A61K39/3955 ,  A61K2039/505 ,  C07D471/14 ,  C07D471/22 ,  C07D487/14 ,  C07D491/14 ,  C07D491/147 ,  C07D495/14 ,  C07D498/14 ,  C07D498/20 ,  C07K16/22 ,  C07K2317/24

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.

Abstract translation: 描述了具有抗癌活性，抗炎活性或免疫调节特性，更具体地与PI3激酶调节或抑制活性的式I的三环PI3k抑制剂化合物。 描述了使用式I的三环PI3K抑制剂化合物用于体外，原位和体内诊断或治疗哺乳动物细胞，生物体或相关病理条件的方法。 式I化合物包括立体异构体，几何异构体，互变异构体及其药学上可接受的盐。 虚线表示可选的双键，至少一条虚线是双键。 取代基如所述。

公开(公告)号：US20150051201A1

公开(公告)日：2015-02-19

申请号：US14531349

申请日：2014-11-03

Applicant: Genentech, Inc.

Inventor： Charles Baker-Glenn ,  Bryan K. Chan ,  Jennafer Dotson ,  Anthony Estrada ,  Timothy Heffron ,  Joseph Lyssikatos ,  Zachary Sweeney

IPC: C07D487/04 ,  C07D498/04 ,  C07D498/20 ,  C07D471/04

CPC classification number: C07D487/04 ,  A61K31/506 ,  C07D403/12 ,  C07D471/04 ,  C07D491/04 ,  C07D491/048 ,  C07D498/04 ,  C07D498/20

Abstract: Compounds of formula I: or pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3 and A are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

Abstract translation: 式I化合物或其药学上可接受的盐，其中X，R 1，R 2，R 3和A如本文所定义。 还公开了制备化合物和使用该化合物治疗与LRRK2受体（例如帕金森病）相关的疾病的方法。

公开(公告)号：US20140135308A1

公开(公告)日：2014-05-15

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: C07D495/04 ,  C07D495/14 ,  A61K45/06 ,  A61K31/429 ,  A61K31/541 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/4545 ,  A61K31/4439 ,  A61K31/4365 ,  A61K31/4196 ,  A61K31/506 ,  A61K31/4985 ,  A61K31/551 ,  C07D513/04

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：US12297210B2

公开(公告)日：2025-05-13

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 ,  A61P37/04 ,  C07D471/04

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：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.