Compounds and uses thereof
The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.
1. A compound having the structure of Formula I:
wherein
R 1 is H, halo, CN, NO 2 , hydroxyl, optionally substituted amino, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 1 -C 6 alkenyl, optionally substituted C 1 -C 6 heteroalkenyl, optionally substituted C 3 -C 10 carbocyclyl, optionally substituted C 2 -C 9 heterocyclyl, optionally substituted C 6 -C 10 aryl, or optionally substituted C 2 -C 9 heteroaryl,
R 2 is H or optionally substituted C 1 -C 6 alkyl, or
R 1 and R 2 , together with the atoms to which each is attached, combine to form an optionally substituted C 3 -C 10 carbocyclylene, optionally substituted C 2 -C 9 heterocyclylene, optionally substituted C 6 -C 10 arylene, or optionally substituted C 2 -C 9 heteroarylene;
L 1 is optionally substituted C 1 -C 6 alkylene or optionally substituted C 1 -C 6 heteroalkylene; and
R 3 is optionally substituted C 2 -C 9 heteroaryl,
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 3 is a heteroaryl having the structure of Formula Ia:
wherein
each of X 1 , X 2 , X 3 , and X 4 is, independently, O, NR 4 , or CR 5 ,
wherein
each R 4 is, independently, H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, optionally substituted C 2 -C 9 heterocyclyl, optionally substituted C 6 -C 10 aryl, or optionally substituted C 2 -C 9 heteroaryl,
each R 5 is, independently, H, CN, optionally substituted C 1 -C 6 alkyl, or optionally substituted C 1 -C 6 heteroalkyl, and
if one of X 1 , X 2 , X 3 , or X 4 is O, then the adjacent atoms are N or CR 5 ; and
X 5 is N or C, wherein 1, 2, or 3 of X 1 , X 2 , X 3 , X 4 , or X 5 is O or N.
3. The compound of claim 1 , wherein R 3 is
4. The compound of claim 1 , wherein each of R 5 is, independently, H, CN, or optionally substituted C 1 -C 6 alkyl.
5. The compound of claim 1 , wherein R 4 is H.
6. The compound of claim 1 , wherein R 4 is optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 3 -C 10 carbocyclyl, optionally substituted C 2 -C 9 heterocyclyl, optionally substituted C 6 -C 10 aryl, or optionally substituted C 2 -C 9 heteroaryl.
7. The compound of claim 1 , wherein R 2 is H or optionally substituted C 1 -C 6 alkyl.
8. The compound of claim 1 , wherein R 1 is H, halo, CN, NO 2 , hydroxyl, optionally substituted amino, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 1 -C 6 alkenyl, optionally substituted C 1 -C 6 heteroalkenyl, optionally substituted C 3 -C 10 carbocyclyl, optionally substituted C 2 -C 9 heterocyclyl, optionally substituted C 6 -C 10 aryl, or optionally substituted C 2 -C 9 heteroaryl.
9. The compound of claim 8 , wherein R 1 is is F, Cl, Br, I, CN, NO 2 , NH 2 ,
10. The compound of claim 1 , wherein R 1 and R 2 , together with the atoms to which each is attached, combine to form an optionally substituted C 3 -C 10 carbocyclylene, optionally substituted C 2 -C 9 heterocyclylene, optionally substituted C 6 -C 10 arylene, or optionally substituted C 2 -C 9 heteroarylene.
11. The compound of claim 1 , wherein L 1 is optionally substituted C 1 -C 6 heteroalkylene.
12. A compound selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
13. A pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt thereof, of claim 1 , and a pharmaceutically acceptable excipient.
14. A method of inhibiting toxicity in a cell related to a protein, the method comprising administering an effective amount of a compound of claim 1 .
15. A method of inhibiting SCD5, the method comprising contacting a cell with an effective amount of a compound of claim 1 .
16. A method of inhibiting SCD1, the method comprising contacting a cell with an effective amount of a compound of claim 1 .