公开(公告)号：US09738679B2

公开(公告)日：2017-08-22

申请号：US14777317

申请日：2014-03-14

Applicant: Epizyme, Inc.

Inventor： Edward James Olhava

IPC: C07H19/167 ,  C07H19/173 ,  C07H19/16 ,  A61K31/7076 ,  A61K31/4184 ,  C07D235/12 ,  C07H19/06 ,  C07H19/067

CPC classification number: C07H19/16 ,  A61K31/4184 ,  A61K31/7076 ,  C07B2200/13 ,  C07D235/12 ,  C07H1/06 ,  C07H19/06 ,  C07H19/067 ,  C07H19/167 ,  Y02A50/401 ,  Y02A50/409 ,  Y02A50/411

Abstract: The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning calorimetry profile, as well as a unique crystalline structure.

公开(公告)号：US20170232030A1

公开(公告)日：2017-08-17

申请号：US15503542

申请日：2015-08-12

Applicant: Epizyme, Inc. ,  Celgene Corporation

Inventor： Christine Klaus ,  Maria Alejandra Raimondi ,  Scott Richard Daigle ,  Roy MacFarlane Pollock ,  Vivek Chopra

IPC: A61K31/7064 ,  A61K31/7068 ,  A61K31/519 ,  A61K45/06 ,  A61K31/706

CPC classification number: A61K31/7064 ,  A61K31/135 ,  A61K31/136 ,  A61K31/4045 ,  A61K31/4745 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/704 ,  A61K31/706 ,  A61K31/7068 ,  A61K31/7076 ,  A61K45/06 ,  A61P35/00 ,  A61K2300/00

Abstract: The disclosure relates to combinations comprising inhibitors of human histone methyltransferase DOT1L and one or more therapeutic agents, particularly anticancer agents, and methods of combination therapy for administering to subjects in need thereof for the treatment of 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

Applicant: Epizyme, Inc.

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

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

CPC classification number: C07D413/12 ,  C07D209/44 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12

Abstract: 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：US20170190676A1

公开(公告)日：2017-07-06

申请号：US15510593

申请日：2015-09-09

Applicant: EPIZYME, INC.

Inventor： Megan Alene Cloonan FOLEY ,  Kevin Wayne KUNTZ ,  James Edward John MILLS ,  Lorna Helen MITCHELL ,  Michael John MUNCHHOF ,  Darren Martin HARVEY

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

CPC classification number: C07D261/18 ,  C07D413/12 ,  C07D413/14

Abstract: 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：US20170119735A1

公开(公告)日：2017-05-04

申请号：US15178696

申请日：2016-06-10

Applicant: Epizyme, Inc.

Inventor： Richard Chesworth ,  Lorna Helen Mitchell ,  Gideon Shapiro ,  Kevin Wayne Kuntz

IPC: A61K31/416 ,  A61K31/4439

CPC classification number: C07D231/56 ,  A61K31/416 ,  A61K31/4439 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/04 ,  C07D405/12

Abstract: Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention 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：US09624205B2

公开(公告)日：2017-04-18

申请号：US14904803

申请日：2014-07-18

Applicant: Epizyme, Inc.

Inventor： John Emmerson Campbell

IPC: A61K31/522 ,  C07D405/14 ,  C07D401/14 ,  C07D405/12

CPC classification number: C07D405/14 ,  C07D401/14 ,  C07D405/12

Abstract: The present invention relates to substituted 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. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

公开(公告)号：US20170088541A1

公开(公告)日：2017-03-30

申请号：US15150759

申请日：2016-05-10

Applicant: Epizyme, Inc.

Inventor： Kenneth W. Duncan ,  Richard Chesworth ,  Michael John Munchhof

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

CPC classification number: C07D405/14 ,  C07D401/06 ,  C07D401/14 ,  C07D413/06 ,  C07D413/14

Abstract: 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：US20170080010A1

公开(公告)日：2017-03-23

申请号：US15248080

申请日：2016-08-26

Applicant: Epizyme, Inc.

Inventor： Christine Klaus ,  Maria Alejandra Raimondi ,  Scott R. Daigle ,  Roy MacFarlane Pollock

IPC: A61K31/7076 ,  A61K31/706 ,  A61K31/635 ,  A61K31/4745 ,  A61K31/7068 ,  A61K31/135 ,  A61K31/704 ,  A61K31/136

Abstract: The present invention relates to compositions comprising inhibitors of human histone methyltransferase DOT1L and one or more therapeutic agents, particularly anticancer agents, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.

公开(公告)号：US20170056409A1

公开(公告)日：2017-03-02

申请号：US15092903

申请日：2016-04-07

Applicant: Epizyme, Inc.

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

IPC: A61K31/5377 ,  A61K31/506

CPC classification number: A61K31/5377 ,  A61K31/506 ,  C07D239/42 ,  C07D239/48 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D413/04 ,  C07D471/04

Abstract: 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 a 6-membered monocyclic heteroaryl ring system of formula: 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.

Abstract translation: 其中L2，R13，G8，G10，G11和G12如本文所定义。 本发明的化合物可用于抑制CARM1活性。 还描述了使用该化合物治疗CARM1介导的病症的方法。

公开(公告)号：US20160332969A1

公开(公告)日：2016-11-17

申请号：US15162453

申请日：2016-05-23

Applicant: Epizyme, Inc.

Inventor： Kevin W. Kuntz ,  Richard Chesworth ,  Kenneth W. Duncan ,  Heike Keilhack ,  Natalie Warholic ,  Christine Klaus ,  Sarah K. Knutson ,  Timothy J. N. Wigle ,  Masashi Seki

IPC: C07D213/64 ,  C07D405/12 ,  C07D491/113 ,  C07D491/048 ,  C07D405/14 ,  C07D409/12 ,  C07D491/08 ,  C07D401/12 ,  C07D401/14

Abstract: The present invention relates to substituted benzene 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. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.