公开(公告)号：US20240343733A1

公开(公告)日：2024-10-17

申请号：US18576940

申请日：2022-07-07

Applicant: BIOGEN MA INC. ,  C4 THRAPEUTICS, INC.

Inventor： Kevin M. Guckian ,  Emily Anne Peterson ,  Fang Gao ,  Ryan Evans ,  Eric Stefan ,  Jeremy L. Yap ,  Corey Don Anderson ,  Morgan Welzel O'Shea ,  Jae Young M. Ahn ,  Christopher G. Nasveschuk ,  James A. Henderson

IPC: C07D487/04 ,  A61K31/4545 ,  A61K31/513 ,  A61K31/519 ,  C07D401/14 ,  C07D471/04 ,  C07D487/10 ,  C07D519/00

CPC classification number: C07D487/04 ,  A61K31/4545 ,  A61K31/513 ,  A61K31/519 ,  C07D401/14 ,  C07D471/04 ,  C07D487/10 ,  C07D519/00

Abstract: This disclosure relates to compounds of Formula (A): IRAK-L-DSM (A), or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches IRAK to DSM; and IRAK is an IRAK4 binding moiety represented by Formula (I) that is covalently attached to linker L; in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of IRAK4 proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of IRAK4 proteins. The present disclosure also provides methods of treating disorders responsive to modulation of IRAK4 activity and/or degradation of IRAK4 with at least one compound described herein.

公开(公告)号：US20230087118A1

公开(公告)日：2023-03-23

申请号：US17623181

申请日：2020-06-24

Applicant: BIOGEN MA INC.

Inventor： Emily Anne Peterson ,  Ryan Evans ,  Fang Gao ,  Philippe Bolduc ,  Magnus Pfaffenbach ,  Zhili Xin ,  Tricia May-Dracka

IPC: C07D471/04 ,  C07D487/04 ,  A61K31/437 ,  A61K31/4985 ,  A61K45/06 ,  C07D519/00 ,  A61K31/519

Abstract: This invention relates to Imidazo[1,2-a]pyridinyl Derivatives of formula (I′), or pharmaceutically acceptable salts thereof, in which all of the variables are as defined in the specification, capable of modulating the activity of IRAK4. The invention further provides a method of manufacturing compounds of the invention, and methods for their therapeutic use. The invention further provides methods to their preparation, to their medical use, in particular to their use in the treatment and management of diseases or disorders including inflammatory disease, autoimmune disease, cancer, cardiovascular disease, a disease of the central nervous system, disease of the skin, an ophthalmic disease and condition, and a bone disease.

公开(公告)号：US20220089592A1

公开(公告)日：2022-03-24

申请号：US17421348

申请日：2020-01-17

Applicant: BIOGEN MA INC.

Inventor： Brian T. Hopkins ,  Magnus Pfaffenbach ,  Tricia May-dracka ,  Ryan Evans ,  Fang Gao ,  Istvan Enyedy ,  Zhili Xin ,  Philippe Bolduc ,  Emily Anne Peterson

IPC: C07D471/04 ,  C07D519/00 ,  C07D487/04

Abstract: This invention relates to Imidazo[1,2-a]pyridinyl Derivatives of formula (I′), or pharmaceutically acceptable salts thereof, in which all of the variables are as defined in the specification, capable of modulating the activity of IRAK4. The invention further provides a method of manufacturing compounds of the invention, and methods for their therapeutic use. The invention further provides methods to their preparation, to their medical use, in particular to their use in the treatment and management of diseases or disorders including inflammatory disease, autoimmune disease, cancer, cardiovascular disease, a disease of the central nervous system, disease of the skin, an ophthalmic disease and condition, and a bone disease.

公开(公告)号：US20240116922A1

公开(公告)日：2024-04-11

申请号：US18269073

申请日：2021-12-21

Applicant: BIOGEN MA INC.

Inventor： Emily Anne Peterson ,  Magnus Pfaffenbach ,  Fang Gao ,  Philippe Bolduc ,  Zhili Xin ,  Ryan Evans

IPC: C07D471/04 ,  A61K45/06 ,  C07D487/04

CPC classification number: C07D471/04 ,  A61K45/06 ,  C07D487/04

Abstract: This disclosure relates to imidazo[1,2-a]pyridinyl derivatives of formula (I), or pharmaceutically acceptable salts thereof, Formula (I) in which all of the variables are as defined in the specification, capable of modulating the activity of IRAK4. The disclosure further provides methods to their preparation, to their medical use, in particular to their use in the treatment and management of diseases or disorders including inflammatory disease, autoimmune disease, cancer, cardiovascular disease, a disease of the central nervous system, disease of the skin, an ophthalmic disease and condition, and a bone disease.

公开(公告)号：US20230002361A1

公开(公告)日：2023-01-05

申请号：US17623182

申请日：2020-06-24

Applicant: BIOGEN MA INC.

Inventor： Emily Anne Peterson ,  Ryan Evans ,  Fang Gao ,  Philippe Bolduc ,  Magnus Pfaffenbach ,  Zhili Xin

IPC: C07D405/14 ,  C07D471/04 ,  C07D401/12 ,  C07D487/04 ,  C07D519/00

Abstract: This invention relates to 2H-indazole Derivatives of formula (I′), or pharmaceutically acceptable salts thereof, in which all of the variables are as defined in the specification, capable of modulating the activity of IRAK4. The invention further provides a method of manufacturing compounds of the invention, and methods for their therapeutic use. The invention further provides methods to their preparation, to their medical use, in particular to their use in the treatment and management of diseases or disorders including inflammatory disease, autoimmune disease, cancer, cardiovascular disease, a disease of the central nervous system, disease of the skin, an ophthalmic disease and condition, and a bone disease.

公开(公告)号：US20250018046A1

公开(公告)日：2025-01-16

申请号：US18576933

申请日：2022-07-07

Applicant: BIOGEN MA INC ,  C4 THERAPEUTICS, INC.

Inventor： Kevin M. Guckian ,  Emily Anne Peterson ,  Fang Gao ,  Ryan Evans ,  Eric Stefan ,  Jeremy L. Yap ,  Corey Don Anderson ,  Morgan Weizel O'Shea ,  Jae Young M. Ahn ,  Christopher G. Nasveschuk ,  James A. Henderson

IPC: A61K47/55 ,  A61K47/54

Abstract: This disclosure relates to compounds of Formula (A): Formula (A), or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches IRAK to DSM; and IRAK is an IRAK4 binding moiety represented by Formula (I) that is covalently attached to linker L; Formula (I) in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of IRAK4 proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of IRAK4 proteins. The present disclosure also provides methods of treating disorders responsive to modulation of IRAK4 activity and/or degradation of IRAK4 with at least one compound described herein.