公开(公告)号：US20220356174A1

公开(公告)日：2022-11-10

申请号：US17262395

申请日：2019-07-24

申请人： Epizyme, Inc.

发明人： Oscar Moradei ,  John W. Lampe ,  Darren Martin Harvey ,  John Emmerson Campbell ,  Kenneth William Duncan ,  Michael John Munchhof

IPC分类号： C07D409/12 ,  A61P35/00 ,  C07D401/12 ,  C07D405/12 ,  C07D417/12 ,  C07D413/12 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D401/14 ,  C07D491/056 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04 ,  C07D213/75 ,  C07D495/04 ,  C07D498/04

摘要： This disclosure generally relates to pyridine-2-one compounds of formula (I) and methods of using them in the treatment of a disorder, such as cancer or a SMARCA2-associated disorder, including as antagonists (e.g., inhibitors) of SMARCA2. The present disclosure provides treatment modalities, e.g., strategies, treatment methods, patient stratification methods, compounds, combinations, and compositions that are useful for the treatment of disorders, e.g., proliferative disorders, such as certain cancers. Some aspects of this disclosure provide treatment modalities, methods, strategies, compounds, compositions, combinations, and dosage forms for the treatment of cell proliferative disorders, e.g., cancers with decreased activity or function, or loss of function, of SMARCA4 with a SMARCA2 antagonist.

公开(公告)号：US10391089B2

公开(公告)日：2019-08-27

申请号：US15844097

申请日：2017-12-15

申请人： Epizyme, Inc.

发明人： Kenneth W. Duncan ,  Richard Chesworth ,  Paula Ann Boriack-Sjodin ,  Michael John Munchhof ,  Lei Jin

IPC分类号： C07D401/14 ,  A61K31/4725 ,  C07D217/12 ,  C07D401/12 ,  C07D405/12 ,  C07D217/04 ,  C07D405/14 ,  C07D413/12 ,  A61K31/506 ,  C12N9/10 ,  A61P7/06 ,  A61P3/04 ,  A61P3/10 ,  A61P35/00 ,  A61K31/496 ,  A61K31/498 ,  A61K31/5377 ,  A61K31/538

摘要： Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

公开(公告)号：US10106510B2

公开(公告)日：2018-10-23

申请号：US15510605

申请日：2015-09-09

申请人： EPIZYME, INC.

发明人： Megan Alene Cloonan Foley ,  Kevin Wayne Kuntz ,  Lorna Helen Mitchell ,  Michael John Munchhof

IPC分类号： A61K31/42 ,  C07D261/18 ,  C07D261/08

摘要： The present disclosure provides substituted cyclohexylamine compounds having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2a, R2b, R3a, R3b, R4, R5, and R7 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.

公开(公告)号：US09732072B2

公开(公告)日：2017-08-15

申请号：US14882638

申请日：2015-10-14

申请人： Epizyme, Inc.

发明人： Kenneth W. Duncan ,  Richard Chesworth ,  Paula Ann Boriack-Sjodin ,  Michael John Munchhof

IPC分类号： C07D413/12 ,  C07D403/12 ,  C07D401/12 ,  C07D407/12 ,  C07D209/44 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D403/14

CPC分类号： C07D413/12 ,  C07D209/44 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12

摘要： Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

公开(公告)号：US20170088541A1

公开(公告)日：2017-03-30

申请号：US15150759

申请日：2016-05-10

申请人： Epizyme, Inc.

发明人： Kenneth W. Duncan ,  Richard Chesworth ,  Michael John Munchhof

IPC分类号： C07D401/06 ,  C07D413/06 ,  C07D401/14

CPC分类号： C07D405/14 ,  C07D401/06 ,  C07D401/14 ,  C07D413/06 ,  C07D413/14

摘要： Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

公开(公告)号：US09388173B2

公开(公告)日：2016-07-12

申请号：US14515154

申请日：2014-10-15

申请人： Epizyme, Inc.

发明人： Kenneth W. Duncan ,  Richard Chesworth ,  Michael John Munchhof ,  Lei Jin

IPC分类号： C07D217/00 ,  C07D413/12 ,  C07D401/14 ,  C07D405/14 ,  C07D217/02 ,  C07D401/12 ,  C07D405/12 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D217/04

CPC分类号： C07D487/04 ,  C07D217/02 ,  C07D217/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04

摘要： Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

公开(公告)号：US10653693B2

公开(公告)日：2020-05-19

申请号：US15501550

申请日：2015-08-04

申请人： Epizyme, Inc. ,  Glaxosmithkline Intellectual Property Development Limited

发明人： Kenneth W. Duncan ,  Richard Chesworth ,  Paula Ann Boriack-Sjodin ,  Michael John Munchhof ,  Lei Jin ,  Elayne Penebre ,  Olena I. Barbash

IPC分类号： A61K31/506 ,  A61K31/4725 ,  A61K31/513 ,  A61P35/00 ,  A61K45/06 ,  G01N33/574

摘要： Described herein are methods of treating cancer using one or more PRMT5 inhibitors, for example using one or more compounds of Formulae (1-5) or (A-F), pharmaceutically acceptable salts thereof, and/or pharmaceutical compositions thereof. Described herein are methods of treating cancer using one or more PRMT5 inhibitors, for example using one or more compounds of Formulae (1-5) or (A-F), pharmaceutically acceptable salts thereof, and/or pharmaceutical compositions thereof.

公开(公告)号：US10428029B2

公开(公告)日：2019-10-01

申请号：US15510593

申请日：2015-09-09

申请人： EPIZYME, INC.

发明人： Megan Alene Cloonan Foley ,  Kevin Wayne Kuntz ,  James Edward John Mills ,  Lorna Helen Mitchell ,  Michael John Munchhof ,  Darren Martin Harvey

IPC分类号： C07D261/18 ,  C07D413/14 ,  C07D413/12

摘要： The present disclosure provides substituted isoxazole carboxamide compounds having Formula (I) and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, A, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.

公开(公告)号：US10150758B2

公开(公告)日：2018-12-11

申请号：US15150759

申请日：2016-05-10

申请人： Epizyme, Inc.

发明人： Kenneth W. Duncan ,  Richard Chesworth ,  Michael John Munchhof

IPC分类号： C07D401/06 ,  C07D405/14 ,  A61K31/4725 ,  C07D401/14 ,  C07D413/14 ,  C07D413/06

摘要： Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

公开(公告)号：US10118918B2

公开(公告)日：2018-11-06

申请号：US14654161

申请日：2013-12-20

申请人： Epizyme, Inc.

发明人： Kenneth W. Duncan ,  Richard Chesworth ,  Paula Ann Boriack-Sjodin ,  Michael John Munchhof

IPC分类号： C07D413/12 ,  C07D403/12 ,  C07D401/12 ,  C07D407/12 ,  C07D209/44 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D403/14

摘要： Described herein are compounds of formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.