公开(公告)号：US08846762B2

公开(公告)日：2014-09-30

申请号：US13738846

申请日：2013-01-10

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 ,  A61K31/4365 ,  A61K31/4196 ,  A61K31/53 ,  C07D495/04 ,  A61K31/496 ,  A61K31/427 ,  A61K31/429 ,  A61K31/4155 ,  C07D495/14 ,  A61K31/4245 ,  A61K31/4436 ,  C07D513/14 ,  A61K31/381

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, tautomer 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的苯并吡喃和苯并氧杂环己酮化合物，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介导 通过脂质激酶。 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：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：US20170210724A1

公开(公告)日：2017-07-27

申请号：US15481852

申请日：2017-04-07

Applicant: Genentech, Inc.

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

IPC: C07D401/10 ,  C07D401/14 ,  C07D491/107 ,  C07D409/14 ,  C07D405/14 ,  C07D495/04 ,  C07D495/06 ,  C07D471/04 ,  C07D487/04 ,  C07D413/10 ,  C07D403/10 ,  C07D405/10 ,  C07D417/14 ,  C07D491/048 ,  C07D413/14

CPC classification number: C07D401/10 ,  A61K31/395 ,  C07D401/14 ,  C07D403/10 ,  C07D403/14 ,  C07D405/10 ,  C07D405/14 ,  C07D409/14 ,  C07D413/10 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D491/048 ,  C07D491/107 ,  C07D495/04 ,  C07D495/06

Abstract: The invention relates to compounds of Formula (0): wherein A1-A8, R4 and R5 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：US20170145034A1

公开(公告)日：2017-05-25

申请号：US15425698

申请日：2017-02-06

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 ,  C07D491/052 ,  C07D471/04 ,  C07D413/10 ,  C07D491/048 ,  C07D403/14 ,  C07D413/14 ,  C07D495/04 ,  C07D487/04 ,  C07D417/10 ,  C07D403/10 ,  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.

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：US20160096850A9

公开(公告)日：2016-04-07

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.

公开(公告)号：US08993563B2

公开(公告)日：2015-03-31

申请号：US13738829

申请日：2013-01-10

Applicant: Genentech, Inc. ,  F. Hoffmann-la Roche AG

Inventor： Tracy Bayliss ,  Irina Chuckowree ,  Adrian Folkes ,  Sally Oxenford ,  Nan Chi Wan ,  Georgette Castanedo ,  Richard Goldsmith ,  Janet Gunzner ,  Tim Heffron ,  Simon Mathieu ,  Alan Olivero ,  Steven Staben ,  Daniel P. Sutherlin ,  Bing-Yan Zhu

IPC: A61K31/519 ,  C07D495/04 ,  C07D413/14 ,  A61K31/5377 ,  C07D491/04

CPC classification number: A61K31/5377 ,  A61K31/519 ,  C07D413/14 ,  C07D491/04 ,  C07D495/04

Abstract: Compounds of Formulas Ia-d where X is S or O, mor is a morpholine group, and R3 is a monocyclic heteroaryl group, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for modulating the activity of lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia-d 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Ia-d的化合物，其中X是S或O，mor是吗啉基团，R3是单环杂芳基，并且包括立体异构体，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调节 脂质激酶（包括PI3K）的活性，以及​​用于治疗脂质激酶介导的疾病如癌症。 公开了使用式Ia-d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：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：US20150038460A1

公开(公告)日：2015-02-05

申请号：US14515742

申请日：2014-10-16

Applicant: Genentech, Inc.

Inventor： Steven Staben ,  Jianwen Feng ,  Pui Leng Loke ,  Christian A.G.N. Montalbetti

IPC: C07F7/08 ,  C07D491/107 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D403/04 ,  C07D487/04 ,  C07D491/08 ,  C07D401/14 ,  C07D417/14

CPC classification number: C07F7/0805 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D487/04 ,  C07D491/08 ,  C07D491/10 ,  C07D491/107

Abstract: The invention relates to novel compounds of Formula I: wherein A, Y, R1, R2 and the subscript b each has the meaning as described herein and compounds of Formula I, and stereoisomers, geometric isomers, tautomers, solvates, metabolites, isotopes, pharmaceutically acceptable salts, or prodrugs thereof. 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A，Y，R 1，R 2和下标b各自具有本文所述的含义，式I化合物和立体异构体，几何异构体，互变异构体，溶剂合物，代谢物，同位素，药学上 其可接受的盐或前药。 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：US20140336154A1

公开(公告)日：2014-11-13

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: C07F5/02 ,  C07D495/14

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。