公开(公告)号：US09546178B2

公开(公告)日：2017-01-17

申请号：US14930929

申请日：2015-11-03

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: C07D491/044 ,  C07D498/04 ,  C07D498/14 ,  C07D519/00 ,  A61K31/553 ,  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: 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：US20160200739A1

公开(公告)日：2016-07-14

申请号：US15074100

申请日：2016-03-18

Applicant: Genentech, Inc.

Inventor： Nicole Blaquiere ,  Georgette Castanedo ,  Jianwen A. Feng ,  Baihua Hu ,  Steven Staben ,  Po-wai Yuen ,  Guosheng Wu ,  Jason Burch

IPC: C07D513/04 ,  C07D401/14 ,  C07D413/14 ,  C07D471/04 ,  C07D413/10 ,  C07D401/10 ,  C07D403/10 ,  C07D491/052

CPC classification number: C07D513/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/10 ,  C07D403/14 ,  C07D413/10 ,  C07D413/14 ,  C07D417/10 ,  C07D471/04 ,  C07D487/04 ,  C07D491/048 ,  C07D491/052 ,  C07D495/04

Abstract: The invention relates to compounds of Formula (0): wherein Q, A1-A8, R4 and R5 and each has the meaning as described herein. Compounds of Formula (0) and pharmaceutical compositions thereof are useful in the treatment of diseases and disorders in which undesired or over-activation of NF-kB signaling is observed.

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：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：US11666581B2

公开(公告)日：2023-06-06

申请号：US16194897

申请日：2018-11-19

Applicant: Genentech, Inc.

Inventor： Thomas Pillow ,  Jack Sadowsky ,  Leanna Staben ,  Steven Staben ,  Binqing Wei ,  Ingrid Wertz ,  Pragya Adhikari ,  Nicole Blaquiere ,  Peter Dragovich ,  Wayne Fairbrother

IPC: A61K31/551 ,  A61K47/54 ,  A61K47/68 ,  A61K47/65 ,  A61P37/06 ,  A61P35/00 ,  C07K16/28 ,  C07K16/32 ,  C12N9/00

CPC classification number: A61K31/551 ,  A61K47/545 ,  A61K47/65 ,  A61K47/68 ,  A61P35/00 ,  A61P37/06 ,  C07K16/2827 ,  C07K16/32 ,  C12N9/93 ,  C12Y203/02007

Abstract: The subject matter described herein is directed to antibody-PROTAC conjugates (PACs), to pharmaceutical compositions containing them, and to their use in treating diseases and conditions where targeted protein degradation is beneficial.

公开(公告)号：US20190175612A1

公开(公告)日：2019-06-13

申请号：US16194897

申请日：2018-11-19

Applicant: Genentech, Inc.

Inventor： Thomas Pillow ,  Jack Sadowsky ,  Leanna Staben ,  Steven Staben ,  Binqing Wei ,  Ingrid Wertz ,  Pragya Adhikari ,  Nicole Blaquiere ,  Peter Dragovich ,  Wayne Fairbrother

IPC: A61K31/551 ,  A61P35/00 ,  A61P37/06 ,  A61K47/65 ,  C12N9/00 ,  C07K16/32 ,  C07K16/28

Abstract: The subject matter described herein is directed to antibody-PROTAC conjugates (PACs), to pharmaceutical compositions containing them, and to their use in treating diseases and conditions where targeted protein degradation is beneficial.

公开(公告)号：US09309265B2

公开(公告)日：2016-04-12

申请号：US14446154

申请日：2014-07-29

Applicant: Genentech, Inc. ,  F. HOFFMANN—LA ROCHE AG

Inventor： Steven Do ,  Richard Goldsmith ,  Tim Heffron ,  Aleksandr Kolesnikov ,  Steven Staben ,  Alan G. Olivero ,  Michael Siu ,  Daniel P. Sutherlin ,  Bing-Yan Zhu ,  Paul Goldsmith ,  Tracy Bayliss ,  Adrian Folkes ,  Neil Pegg

IPC: A01N37/00 ,  C07D333/00 ,  C07F5/02 ,  C07D495/04 ,  C07D495/14 ,  C07D513/14 ,  A61K31/381 ,  A61K31/4155 ,  A61K31/4196 ,  A61K31/4245 ,  A61K31/427 ,  A61K31/429 ,  A61K31/4365 ,  A61K31/4436 ,  A61K31/496 ,  A61K31/53

CPC classification number: C07F5/02 ,  A61K31/381 ,  A61K31/4155 ,  A61K31/4196 ,  A61K31/4245 ,  A61K31/427 ,  A61K31/429 ,  A61K31/4365 ,  A61K31/4436 ,  A61K31/496 ,  A61K31/53 ,  C07D495/04 ,  C07D495/14 ,  C07D513/14

Abstract: Benzopyran and benzoxepin compounds of Formulas I and II, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, 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 Formulas I and II 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和II的苯并吡喃和苯并辛菌素化合物，包括立体异构体，几何异构体，互变异构体，溶剂合物，代谢物和药学上可接受的盐，可用于抑制脂质激酶，包括p110α和PI3K的其他同种型，并用于治疗疾病如癌症 由脂质激酶介导。 公开了使用式I和II的化合物在体外，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：US20160052933A1

公开(公告)日：2016-02-25

申请号：US14930929

申请日：2015-11-03

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: C07D491/044 ,  C07D498/04 ,  C07D519/00 ,  C07D498/14

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：US20150166569A1

公开(公告)日：2015-06-18

申请号：US14622446

申请日：2015-02-13

Applicant: Genentech, Inc.

Inventor： Steven Staben ,  Georgette Castanedo ,  Christian A.G.N. Montalbetti ,  Jianwen Feng

IPC: C07D498/04 ,  C07D513/04 ,  C07D519/00 ,  C07D487/04

CPC classification number: C07D498/04 ,  C07D487/04 ,  C07D498/00 ,  C07D498/12 ,  C07D513/04 ,  C07D519/00

Abstract: The invention relates to novel compounds of Formula I: wherein A1, A2, A3, A4, A5, A6, R2, R4, R5, R6, R7, R8 and subscripts m and n each has the meaning as described herein. Compounds of Formula I and pharmaceutical compositions thereof are useful in the treatment of disease and disorders in which undesired or over-activation of NF-kB signaling is observed.

Abstract translation: 本发明涉及式I的新化合物：其中A1，A2，A3，A4，A5，A6，R2，R4，R5，R6，R7，R8和下标m和n各自具有本文所述的含义。 式I化合物及其药物组合物可用于治疗观察到NF-kB信号传导的不期望或过度活化的疾病和病症。

公开(公告)号：US20150065482A1

公开(公告)日：2015-03-05

申请号：US14466153

申请日：2014-08-22

Applicant: Genentech, Inc.

Inventor： Nicole Blaquiere ,  Georgette Castanedo ,  Jianwen A. Feng ,  Baihua Hu ,  Steven Staben ,  Po-wai Yuen ,  Guosheng Wu ,  Jason Burch

IPC: C07D513/04 ,  C07D471/04 ,  C07D403/10 ,  C07D401/14 ,  C07D413/10 ,  C07D491/052 ,  C07D487/04 ,  C07D401/10

CPC classification number: C07D513/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/10 ,  C07D403/14 ,  C07D413/10 ,  C07D413/14 ,  C07D417/10 ,  C07D471/04 ,  C07D487/04 ,  C07D491/048 ,  C07D491/052 ,  C07D495/04

Abstract: The invention relates to compounds of Formula (0): wherein Q, A1-A8, R4 and R5 and each has the meaning as described herein. Compounds of Formula (0) and pharmaceutical compositions thereof are useful in the treatment of diseases and disorders in which undesired or over-activation of NF-kB signaling is observed.

Abstract translation: 本发明涉及式（O）的化合物：其中Q，A1-A8，R4和R5各自具有如本文所述的含义。 式（0）的化合物及其药物组合物可用于治疗其中观察到NF-kB信号传导的不期望或过度活化的疾病和病症。