公开(公告)号：US20170305922A1

公开(公告)日：2017-10-26

申请号：US15511503

申请日：2015-09-17

申请人： Epizyme, Inc.

发明人： Richard Chesworth ,  Oscar Miguel Moradei ,  Gideon Shapiro ,  Lei JIn ,  Robert E. Babine

IPC分类号： C07D487/10 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04

CPC分类号： C07D487/10 ,  C07D239/42 ,  C07D401/04 ,  C07D401/14 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D471/08 ,  C07D471/10 ,  C07D487/04 ,  C07D487/14 ,  C07D491/107 ,  C07D491/113 ,  C07D493/04 ,  C07D498/04 ,  C07D498/08 ,  C07D513/04

摘要： Provided herein are compounds of Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, wherein R1, R2a, R2b, R3 and Ring B are as defined herein, and Ring A is a group of Formula (A-i), (A-ii), or (A-iii): wherein R, R, R, R, and R are as defined herein. Compounds of the present invention are useful for inhibiting CARM1 activity. Methods of using the compounds for treating CARM1-mediated disorders are also described.

公开(公告)号：US09777008B2

公开(公告)日：2017-10-03

申请号：US15177056

申请日：2016-06-08

申请人： Epizyme, Inc.

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

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

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：US20170253601A1

公开(公告)日：2017-09-07

申请号：US15510602

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 ,  Darren Martin HARVEY

IPC分类号： C07D487/04 ,  C07D413/14 ,  C07D413/12

CPC分类号： C07D487/04 ,  A61P35/00 ,  C07D413/12 ,  C07D413/14

摘要： The present disclosure provides substituted pyrrolidine compounds having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein R1, B, 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：US09738651B2

公开(公告)日：2017-08-22

申请号：US14775766

申请日：2014-03-14

申请人： Epizyme, Inc.

发明人： Richard Chesworth ,  Oscar Miguel Moradei ,  Gideon Shapiro ,  Lei Jin ,  Robert E. Babine

IPC分类号： C07D471/04 ,  C07D405/14 ,  C07D405/12 ,  C07D239/48 ,  C07D239/42 ,  C07D403/04 ,  C07D401/04 ,  C07D413/04 ,  C07D405/04 ,  C07D487/10 ,  C07D403/12 ,  C07D413/14 ,  C07D409/14 ,  C07D413/12 ,  C07D417/14 ,  C07D471/10 ,  C07D487/08 ,  C07D493/04 ,  C07D493/10 ,  C07D495/04 ,  C07D498/04 ,  C07D498/10 ,  C07D487/04

CPC分类号： C07D487/10 ,  C07D239/42 ,  C07D401/04 ,  C07D403/04 ,  C07D403/12 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D487/08 ,  C07D493/04 ,  C07D493/10 ,  C07D495/04 ,  C07D498/04 ,  C07D498/10

摘要： Provided herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X, R1, R1a, R2a, R2b, R2c, R2d, are as defined herein, and Ring HET is a 6-membered monocyclic heteroaryl ring system of Formula (II) wherein L2, R13, G8, G10, G11, and G12 are as defined herein. Compounds of the present invention are useful for inhibiting CARM1 activity. Methods of using the compounds for treating CARM1-mediated disorders are also described.

公开(公告)号：US20170224685A1

公开(公告)日：2017-08-10

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 Munchhof ,  Lei Jin ,  Elayne Penebre ,  Olena I. Barbash

IPC分类号： A61K31/506 ,  A61K31/4725 ,  G01N33/574

CPC分类号： A61K31/506 ,  A61K31/4725 ,  A61K31/513 ,  A61K45/06 ,  A61P35/00 ,  G01N33/57496 ,  G01N2333/4748 ,  A61K31/4545 ,  A61K2300/00

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：US09718816B2

公开(公告)日：2017-08-01

申请号：US14775197

申请日：2014-03-14

申请人： Epizyme, Inc.

发明人： Richard Chesworth ,  Oscar Miguel Moradei ,  Gideon Shapiro ,  Kenneth W. Duncan ,  Lorna Helen Mitchell ,  Lei Jin ,  Robert E. Babine

IPC分类号： C07D471/04 ,  C07D498/08 ,  C07D487/04

CPC分类号： C07D471/04 ,  C07D487/04 ,  C07D498/08

摘要： Provided herein are compounds of Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X, R1, R2a, R2b, R2c, R2d, are as defined herein, and Ring HET is an optionally substituted 6,5-bicyclic heteroaryl ring system comprising 2 to 5 nitrogen atoms, inclusive, wherein the point of attachment is provided on the 6-membered ring of the 6,5-bicyclic heteroaryl ring system, and wherein the 6-membered ring is further substituted with a group of formula -L1-R3, wherein L1 and R3 are as defined herein. Compounds of the present invention are useful for inhibiting CARM1 activity. Methods of using the compounds for treating CARM1-mediated disorders are also described.

公开(公告)号：US20170198006A1

公开(公告)日：2017-07-13

申请号：US15321280

申请日：2015-06-25

申请人： Epizyme, Inc.

发明人： Kenneth W. Duncan ,  Richard Chesworth ,  Gideon Shapiro ,  Edward James Olhava ,  Michael A. Patane ,  Michael John Munchhof ,  Kevin Wayne Kuntz ,  Lei Jin

IPC分类号： C07H19/16 ,  C07D405/06 ,  C07D401/12 ,  C07D403/04 ,  C07C311/41 ,  C07D233/64 ,  C07D207/14

CPC分类号： C07H19/16 ,  A61P3/00 ,  A61P3/10 ,  A61P7/00 ,  A61P35/00 ,  C07C311/41 ,  C07D205/04 ,  C07D207/14 ,  C07D207/273 ,  C07D211/28 ,  C07D231/12 ,  C07D233/64 ,  C07D233/88 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D417/12 ,  C07D487/04 ,  C07D513/04 ,  C07H19/167

摘要： Described herein are compounds of Formula (I)-(XIII), 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：US09637472B2

公开(公告)日：2017-05-02

申请号：US14536162

申请日：2014-11-07

申请人： Epizyme, Inc.

发明人： Kevin Wayne Kuntz ,  Edward James Olhava ,  Richard Chesworth ,  Kenneth William Duncan

IPC分类号： C07D401/12 ,  C07D471/04 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14

CPC分类号： C07D401/12 ,  A61P35/00 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D471/04

摘要： The present invention relates to substituted 6,5-fused bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof.

公开(公告)号：US09630961B2

公开(公告)日：2017-04-25

申请号：US14808270

申请日：2015-07-24

申请人： Epizyme, Inc.

发明人： Richard Chesworth ,  Lorna Helen Mitchell ,  Gideon Shapiro ,  Oscar Miguel Moradei

IPC分类号： C07D471/04 ,  C07D409/04 ,  C07D403/04 ,  C07D413/04 ,  C07D231/12 ,  C07D407/04 ,  C07D411/04 ,  C07D405/04 ,  C07D417/04 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/428 ,  A61K31/437 ,  A61K31/42

CPC分类号： C07D471/04 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/42 ,  A61K31/428 ,  A61K31/437 ,  C07D231/12 ,  C07D403/04 ,  C07D405/04 ,  C07D407/04 ,  C07D409/04 ,  C07D411/04 ,  C07D413/04 ,  C07D417/04

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

公开(公告)号：US09604930B2

公开(公告)日：2017-03-28

申请号：US14654253

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 ,  Lei Jin

IPC分类号： A61K31/00 ,  C07D217/04 ,  C07D401/14 ,  C07D217/12 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  C07D413/12

CPC分类号： A61K31/506 ,  C07D217/04 ,  C07D217/12 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D413/12 ,  C12N9/1007

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.