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:
R 1 (L 1 ) n L 2 -B-Het-R 5
wherein B has the structure:
Het is
n is 0 or 1;
o is 0, 1, or 2;
p and r are, independently, 0 or 1;
X 1 is N or CR 6 ;
X 2 is N;
L 1 is —O—;
L 2 is CR 2 R 3 ;
R 1 is optionally substituted phenyl, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted C 3 -C 7 cycloalkyl C 1 -C 6 alkyl, or C 2 -C 9 heterocycle optionally substituted with C 1 -C 6 alkyl or C 1 -C 6 heteroalkyl;
R 2 and R 3 are each, independently, hydrogen or R 2 and R 3 combine with the carbon to which they are attached to form a carbonyl;
each R 4 is, independently, halogen, hydroxyl, optionally substituted C 1 -C 6 alkyl, or two R 4 combine with the carbon to which they are attached to form a carbonyl;
R 5 is a bicyclic heteroaryl comprising a 6-membered ring, wherein R 5 is unsubstituted or is substituted with 1 to 4 substituents selected from the group consisting of C 1 -C 6 alkyl and C 2 -C 9 heterocyclyl; and
each R 6 is, independently, hydrogen, halogen, or optionally substituted C 1 -C 6 alkyl,
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein B has the structure:
3. The compound of claim 2 , wherein B has the structure:
4. The compound of claim 2 , wherein B has the structure:
5. The compound of claim 1 , wherein R 1 is C 2 -C 9 heterocycle optionally substituted with C 1 -C 6 alkyl or C 1 -C 6 heteroalkyl.
6. The compound of claim 5 , wherein C 2 -C 9 heterocycle optionally substituted with C 1 -C 6 alkyl or C 1 -C 6 heteroalkyl is
7. The compound of claim 2 , having the structure:
wherein
R 2 and R 3 are each, independently, hydrogen or R 2 and R 3 combine with the carbon to which they are attached to form a carbonyl;
each R 4 is, independently, fluoro, methyl, or two R 4 combine with the carbon to which they are attached to form a carbonyl;
R 5 is C 2 -C 9 bicyclic heteroaryl comprising a 6-membered ring, wherein R 5 is substituted with 1 to 4 substituents selected from the group consisting of C 1 -C 6 alkyl, and C 2 -C 9 heterocyclyl; and
each R 6 is, independently, hydrogen or methyl.
8. The compound of claim 1 , wherein R 5 is an indazole having the structure:
wherein
R 5a is hydrogen or optionally substituted C 1 -C 6 alkyl, and
R 5b is C 1 -C 6 alkyl; or C 2 -C 9 heterocyclyl.
9. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable excipient.
10. The compound of claim 8 , wherein R 5b is methyl or iso-propyl.
11. The compound of claim 8 , wherein R 5b is oxetane.
12. The compound of claim 1 , wherein the compound is selected from the group consisting of:
and pharmaceutically acceptable salts thereof.