Quinoline-based proteasome inhibitors and uses thereof
Described herein are quinoline compounds useful for, among other things, inhibition of the proteasome and for treatment of cancer and inflammation.
1. A compound of the formula III:
wherein:
R 6 is hydrogen or alkyl;
R 8 is hydrogen or alkyl;
R 9 is hydrogen or alkyl; and
R 10 is hydrogen or alkyl;
wherein:
R 6 , and R 8 -R 10 are not all simultaneously H; and
R 6 , R 8 , and R 10 are not simultaneously CH 3 .
2. The compound of claim 1 , wherein R 6 is hydrogen or lower alkyl.
3. The compound of claim 2 , wherein R 6 is methyl or ethyl.
4. The compound of claim 1 , wherein R 9 is methyl, isopropyl or butyl.
5. A compound of the formula:
wherein:
R 1
R 2
R 3
R 4
R 5
CH 2 CH 3
CH 3
H
CH 3
H
CH 3
H
CH 3
CH 3
H
H
H
CH 3
H
CH 3
H
CH 3
H
(CH 2 )CH 3
H
CH 3
H
CH(CH 3 ) 2
H.
6. A pharmaceutical composition comprising one or more compounds of claim 1 and one or more pharmaceutically acceptable excipients.
7. A method for treating multiple myeloma comprising administering a therapeutically effective amount of at least one compound of claim 1 to a subject in need thereof.
8. A method for inhibiting proteasome function comprising administering a therapeutically effective amount of at least one compound of claim 1 to a subject in need thereof.
9. The method of claim 8 , wherein the proteasome function is decreased by 5% to 100%.