COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF BRUTON'S TYROSINE KINASE

The present disclosure relates to bifunctional compounds that serve as degraders (and/or inhibitors) of Bruton's tyrosine kinase (BTK). In the present disclosure, the bifunctional compounds, which contain a target protein (BTK) binding moiety and a E3 ubiquitin ligase (CRBN) binding moiety, are...

Full description

Saved in:
Bibliographic Details
Main Authors Kang, Borui, Kim, HongJoong, Peng, Xianyou, Wang, Guangdi
Format Patent
LanguageEnglish
Published 04.05.2023
Subjects
CHEMISTRY
HETEROCYCLIC COMPOUNDS
METALLURGY
ORGANIC CHEMISTRY
Online AccessGet full text

Cover

More Information
Summary:The present disclosure relates to bifunctional compounds that serve as degraders (and/or inhibitors) of Bruton's tyrosine kinase (BTK). In the present disclosure, the bifunctional compounds, which contain a target protein (BTK) binding moiety and a E3 ubiquitin ligase (CRBN) binding moiety, are directed to bind to both the BTK and CRBN, such that the BTK is placed in close proximity to the E3 ligase to mediate ubiquitylation of the target protein followed by degradation of the target protein by the proteasome. The present disclosure provides methods for synthesizing the herein disclosed bifunctional compounds, and their pharmacological activities associated with degradation or inhibition of the target protein. Further, the present disclosure teaches the utilization of such compounds in a treatment for proliferative diseases and autoimmune disorders, including hematological cancers and rheumatoid arthritis, particularly non-Hodgkin lymphoma, and especially chronic lymphocytic leukemia (CLL) and mantle cell lymphoma.
Bibliography:Application Number: US202217820312