Glutarimides for medical treatment
The present invention provides selected glutarimides 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 compound of the formula:
or a pharmaceutically acceptable salt thereof
wherein
R 2 is hydrogen or C 1 -C 6 alkyl;
R 1 is 2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl; and
n is 0 or 1.
2. The compound of claim 1 , wherein R 2 is hydrogen.
3. The compound of claim 1 , wherein R 2 is methyl.
4. The compound of claim 1 wherein n is 0.
5. The compound of claim 1 , wherein n is 1.
6. The compound of claim 1 of the formula:
or a pharmaceutically acceptable salt thereof.
7. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof of claim 1 optionally in a pharmaceutically acceptable carrier.
8. The compound of claim 6 of the formula:
or a pharmaceutically acceptable salt thereof.
9. The compound of claim 6 of the formula:
or a pharmaceutically acceptable salt thereof.