Dihydroquinolinones for medical treatment

Patent metadata

Field	Value
Publication number	US-2025084055-A1
Application number	US-202418806363-A
Country	US
Kind code	A1
Filing date	Aug 15, 2024
Priority date	Sep 4, 2017
Publication date	Mar 13, 2025
Grant date	—

Abstract

The present invention provides dihydroquinolinone compounds which bind to the ubiquitously expressed E3 ligase protein cereblon (CRBN) and alter the substrate specificity of the CRBN E3 ubiquitin ligase complex, resulting in breakdown of intrinsic downstream proteins. The disclosed compounds are useful for the treatment of cancer.

First claim

We claim:

1 . A compound of formula:

or a pharmaceutically acceptable salt thereof,
wherein
X is CH or N,
R 1 is —C(O)—R 6 ,
R 2 is H,
or R 1 and R 2 together with the nitrogen they are attached to form a heteroaryl, which can be substituted by 1 or 2 substituents selected from R 3 ,
R 3 is selected from the group consisting of
i) —(CH 2 ) 0-1 -aryl substituted by 1-2 substituents selected from R 4
ii) —(CH 2 ) 0-1 -aryl,
iii) —C(═O)N(R 3a ,R 3b ),
iv) —C(═O)O—C 1-6 alkyl,
v) —C(C 3-7 cycloalkyl)-aryl
vi) C 1-6 alkyl,
vii) —C 3-7 cycloalkyl
viii) —CH 2 —O—(CH 2 ) 0-1 -aryl,
ix) heteroaryl substituted by 1-2 substituents selected from R 4 ,
x) hydroxy-C 1-6 alkyl, and
xi) unsubstituted heteroaryl,

R 3a is selected from the group consisting of H and C 1-6 alkyl,
R 3b is selected from the group consisting of H, C 1-6 alkyl, and —C 3-7 cycloalkyl,
or R 3a and R 3b form together with the nitrogen they are attached to a heterocycloalkyl,
R 4 is selected from the group consisting of unsubstituted heteroaryl, heteroaryl substituted by 1-2 substituents selected from R 5 , and C 1-6 alkoxy,
R 5 is C 1-6 alkyl,
R 6 is selected from the group consisting of unsubstituted heteroaryl and heteroaryl substituted by 1-2 substituents selected from R 7 ,
R 7 is selected from the group consisting of unsubstituted heteroaryl and heteroaryl substituted by 1-2 substituents selected from R 8 ,
R 8 is C 1-6 alkyl,

with the proviso that 6-imidazol-1-yl-3,4-dihydro-1H-quinolin-2-one is excluded.

Assignees

• C4 Therapeutics Inc

Inventors

• Norcross Roger
• Britschgi Adrian
• Dey Fabian
• Goergler Annick
• Kusznir Eric Andre
• Wichert Moreno Attilio

Classifications

• C07D495/14

  Ortho-condensed systems · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/4375

  the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine · CPC title

• A61K47/55

  the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug · CPC title