Dihydrobenzimidazolones for medical treatment
The present invention provides selected dihydrobenzimidazolones 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.
1. A method for the treatment of a cancer in a human responsive to a cereblon-binding drug therapy comprising administering an effective amount of a compound or a pharmaceutically acceptable salt thereof to a human patient wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
5. The method of claim 1 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
6. The method of claim 1 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
7. The method of claim 1 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
8. The method of claim 1 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
9. A method for the treatment of a cancer in a human responsive to a cereblon-binding drug therapy comprising administering an effective amount of a compound or a pharmaceutically acceptable salt thereof to a human patient wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
10. The method of claim 9 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
11. The method of claim 9 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
12. The method of claim 9 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
13. The method of claim 9 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
14. A method for the treatment of a cancer in a human responsive to a cereblon-binding drug therapy comprising administering an effective amount of a compound or a pharmaceutically acceptable salt thereof to a human patient wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
15. The method of claim 14 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
16. The method of claim 14 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
17. The method of claim 14 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
18. The method of claim 14 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
19. The method of claim 14 , wherein the compound is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.