公开(公告)号：US11566003B2

公开(公告)日：2023-01-31

申请号：US16921297

申请日：2020-07-06

申请人： Genentech, Inc.

发明人： 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分类号： 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

摘要： 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

申请人： Genentech, Inc.

发明人： 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分类号： C07D487/04 ,  C07D403/04 ,  C07D401/04 ,  C07D405/14 ,  C07D237/28 ,  C07D401/14 ,  C07D417/04

摘要： 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

申请人： Genentech, Inc.

发明人： Marian C. Bryan ,  Bryan Chan ,  Francois Diederich ,  Jennafer Dotson ,  Emily Hanan ,  Timothy Heffron ,  Michael Lainchbury

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

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

摘要： 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.

摘要翻译： 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

申请人： Genentech, Inc.

发明人： 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分类号： A61K31/553 ,  C07D498/04 ,  C07D498/14 ,  C07D519/00 ,  A61K45/06

CPC分类号： C07D498/04 ,  A61K31/553 ,  A61K45/06 ,  C07D491/044 ,  C07D498/14 ,  C07D519/00

摘要： 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.

摘要翻译： 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

申请人： Genentech, Inc.

发明人： 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分类号： 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分类号： 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

摘要： 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.

摘要翻译： 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：US09670228B2

公开(公告)日：2017-06-06

申请号：US15368937

申请日：2016-12-05

申请人： Genentech, Inc.

发明人： 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分类号： C07D498/04

CPC分类号： C07D498/04 ,  A61K31/553 ,  A61K45/06 ,  C07D491/044 ,  C07D498/14 ,  C07D519/00

摘要： 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：US09546182B2

公开(公告)日：2017-01-17

申请号：US14524204

申请日：2014-10-27

申请人： Genentech, Inc.

发明人： 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分类号： C07D471/14 ,  C07D471/22 ,  C07D487/14 ,  C07D498/14 ,  C07D491/14 ,  C07D495/14 ,  A61K31/5377 ,  A61K31/5383 ,  A61K31/5386 ,  A61K39/395 ,  C07D491/147 ,  C07D498/20 ,  A61K39/00

CPC分类号： 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

摘要： 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.

摘要翻译： 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：US09546178B2

公开(公告)日：2017-01-17

申请号：US14930929

申请日：2015-11-03

申请人： Genentech, Inc.

发明人： 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分类号： C07D491/044 ,  C07D498/04 ,  C07D498/14 ,  C07D519/00 ,  A61K31/553 ,  A61K45/06

CPC分类号： C07D498/04 ,  A61K31/553 ,  A61K45/06 ,  C07D491/044 ,  C07D498/14 ,  C07D519/00

摘要： 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.

摘要翻译： 本发明涉及式I的苯并氧氮杂化合物，其包括立体异构体，几何异构体，互变异构体或其药学上可接受的盐，其中：Z 1为CR 1或N; Z 2为CR 2或N; Z 3为CR 3或N; Z 4为CR 4或N; 并且B是吡唑基，咪唑基或三唑基环，该化合物具有抗癌活性，更具体地，抑制PI3激酶活性。

公开(公告)号：US20150094347A1

公开(公告)日：2015-04-02

申请号：US14565669

申请日：2014-12-10

申请人： Genentech, Inc.

发明人： 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分类号： C07D495/04

CPC分类号： 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

摘要： 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.

摘要翻译： 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

申请人： Genentech, Inc.

发明人： 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分类号： C07D498/14 ,  A61K31/5377 ,  A61K31/5386 ,  A61K31/5383 ,  C07D498/20 ,  C07D491/147 ,  A61K39/395

CPC分类号： 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

摘要： 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.

摘要翻译： 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。