公开(公告)号：US20200048195A1

公开(公告)日：2020-02-13

申请号：US16423618

申请日：2019-05-28

Applicant: EPIZYME, INC.

Inventor： Megan Alene Cloonan Foley ,  Kevin Wayne KUNTZ ,  Lorna Helen MITCHELL ,  Michael John MUNCHHOF ,  Darren Martin HARVEY

IPC: C07D207/14 ,  C07D403/12 ,  C07D401/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  A61P35/00

Abstract: The present disclosure provides pyrrolidine carboxamide compounds having Formula I and the pharmaceutically acceptable salts and solvates thereof, wherein A, B, X, Y, 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：US20170253601A1

公开(公告)日：2017-09-07

申请号：US15510602

申请日：2015-09-09

Applicant: EPIZYME, INC.

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

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

CPC classification number: C07D487/04 ,  A61P35/00 ,  C07D413/12 ,  C07D413/14

Abstract: 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：US20210137936A1

公开(公告)日：2021-05-13

申请号：US17032432

申请日：2020-09-25

Applicant: Epizyme, Inc. ,  Eisai R&D Management Co., Ltd.

Inventor： Kevin Wayne KUNTZ ,  Kuan-Chun HUANG ,  Hyeong Wook CHOI ,  Kristen SANDERS ,  Steven MATHIEU ,  Arani CHANDA ,  Francis FANG

IPC: A61K31/5377 ,  C07D405/12

Abstract: Provided herein is N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide hydrobromide. Also provided herein is a particular polymorph form of this compound.

公开(公告)号：US20210017163A1

公开(公告)日：2021-01-21

申请号：US16891427

申请日：2020-06-03

Applicant: Epizyme, Inc. ,  Eisai R&D Management Co., Ltd.

Inventor： Kevin Wayne KUNTZ ,  Hyeong Wook CHOI ,  Steven MATHIEU ,  Kristen SANDERS ,  Arani CHANDA

IPC: C07D405/12 ,  A61K31/5377 ,  C07D413/12

Abstract: Provided herein are novel solid forms of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide hydrochloride, and related compositions and methods.

公开(公告)号：US20200148650A1

公开(公告)日：2020-05-14

申请号：US16588209

申请日：2019-09-30

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

Abstract: The present disclosure provides substituted isoxazole carboxamide compounds having Formula (1) 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：US20200016162A1

公开(公告)日：2020-01-16

申请号：US16453501

申请日：2019-06-26

Applicant: Epizyme, Inc.

Inventor： Kevin Wayne KUNTZ ,  Sarah Kathleen KNUTSON ,  Timothy James Nelson WIGLE ,  Robert A. COPELAND ,  Victoria M. RICHON ,  Margaret D. SCOTT ,  Christopher J. SNEERINGER ,  Roy M. POLLOCK

IPC: A61K31/5377 ,  C07D473/34 ,  C12Q1/48 ,  G01N33/50 ,  G01N33/574 ,  A61K31/711 ,  A61K38/17 ,  C07D405/12 ,  C12Q1/68 ,  A61K31/4412 ,  A61K31/4427 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/497 ,  A61K31/551 ,  A61K31/7076

Abstract: The invention relates to inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono- through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.

公开(公告)号：US20170280720A1

公开(公告)日：2017-10-05

申请号：US15511514

申请日：2015-09-17

Applicant: EPIZYME, INC.

Inventor： Richard CHESWORTH ,  Lorna Helen MITCHELL ,  Gideon SHAPIRO ,  Oscar Miguel MORADEI ,  Kevin Wayne KUNTZ ,  Kenneth W. DUNCAN ,  Lei JIN

IPC: A01N47/10 ,  C07D277/20 ,  C07D233/54 ,  C07D209/10 ,  C07D241/02

CPC classification number: A01N47/10 ,  A61K38/45 ,  C07D209/10 ,  C07D233/54 ,  C07D241/02 ,  C07D277/20 ,  C07D471/04 ,  C07D487/04

Abstract: 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：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：US20230140327A1

公开(公告)日：2023-05-04

申请号：US17936555

申请日：2022-09-29

Applicant: Epizyme, Inc. ,  Eisai R&D Management Co., Ltd.

Inventor： Kevin Wayne KUNTZ ,  Kuan-Chun Huang ,  Hyeong Wook Choi ,  Kristen Sanders ,  Steven Mathieu ,  Arani Chanda ,  Francis Fang

IPC: A61K31/5377 ,  C07D405/12

Abstract: Provided herein is N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide hydrobromide. Also provided herein is a particular polymorph form of this compound.

公开(公告)号：US20210053948A1

公开(公告)日：2021-02-25

申请号：US16985404

申请日：2020-08-05

Applicant: Epizyme, Inc.

Inventor： Heike KEILHACK ,  Sarah Kathleen KNUTSON ,  Kevin Wayne KUNTZ

IPC: C07D405/12 ,  A61K45/06 ,  A61K31/436 ,  A61K31/53 ,  A61K31/573 ,  A61K31/704 ,  A61K31/7068 ,  C07D213/64 ,  A61K31/4412 ,  A61K31/5377 ,  A61K31/4439 ,  C07D413/14 ,  A61K31/444 ,  A61P35/00 ,  A61K31/4745 ,  A61K31/675

Abstract: The present invention relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and one or more other therapeutic agents, particularly anticancer agents such as prednisone, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.