LRRK2 inhibitors and methods of making and using the same

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:

R X is

is

each R 4 is independently unsubstituted or substituted C 1 -C 6 alkyl;

n is 0, 1, 2, 3, 4, 5, or 6;

R 31 is H;

each R 32 is independently H, halogen, or NR 81 R 82 ;

R 81 is H or unsubstituted or substituted C 1 -C 6 alkyl;

R 82 is C(O)R 83 ;

R 83 is unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 2 -C 6 alkenyl, or unsubstituted or substituted C 2 -C 6 alkynyl;

R N is H;

each R 1 is independently unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkoxy, or halogen;

m is 1, 2, or 3;

R 2 is H, C 1 -C 6 alkyl, halogen, NR N1 R N2 , or OR N3 ;

R N1 and R N2 are each independently H, unsubstituted C 1 -C 6 alkyl, unsubstituted or substituted C 2 -C 6 alkenyl, (CH 2 ) 1-3 —O—C 1 -C 6 alkyl, or (CH 2 ) 0-3 —R 91 , or R N1 and R N2 , together with the nitrogen atom to which they are bonded, form a 5- or 6-membered heterocycle optionally comprising 1 or 2 additional heteroatoms selected from N and O;

R N3 is (CH 2 ) 0-3 —R 92 ;

R 91 is unsubstituted or substituted C 3 -C 8 cycloalkyl, unsubstituted or substituted 5- or 6-membered heterocycle comprising 1-3 heteroatoms selected from N, O, and S, or phenyl substituted with S(O) 2 R 10 , NHC(O)R 11 , C(O)R 12 , or C(O)NHR 13 ;

R 92 is substituted C 3 -C 8 cycloalkyl, unsubstituted or substituted 5- or 6-membered heterocycle comprising 1-3 heteroatoms selected from N, O, and S, or phenyl substituted with NO 2 , S(O) 2 R 10 , NHC(O)R 11 , C(O)R 12 , or C(O)NHR 13 ; and

R 10 , R 11 , R 12 , and R 13 are each independently unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 2 -C 6 alkenyl, NH—C 1 -C 6 alkyl, unsubstituted or substituted 5- or 6-membered heterocycle comprising 1-3 heteroatoms selected from N, O, and S, or unsubstituted or substituted phenyl.

2. The compound of claim 1 , wherein

3. The compound of claim 1 , wherein

4. The compound of claim 1 , wherein

5. The compound of claim 1 , wherein n is 0 or 1.

6. The compound of claim 1 , wherein R 32 is halogen.

7. The compound of claim 6 , wherein R 32 is chlorine or fluorine.

8. The compound of claim 1 , wherein R 1 is C 1 -C 6 alkoxy selected from methoxy, ethoxy, propoxy, i-propoxy, butoxy, i-butoxy, t-butoxy, pentoxy, and hexyloxy, each of which is optionally substituted.

9. The compound of claim 1 , wherein R 2 is NR N1 R N2 .

10. The compound of claim 9 , wherein one of R N1 and R N2 is H, and the other is unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 2 -C 6 alkenyl, (CH 2 ) 1-3 —O—C 1 -C 6 alkyl, or (CH 2 ) 0-3 —R 91 .

11. The compound of claim 1 , having formula Ib1:

or a pharmaceutically acceptable salt thereof, wherein R O is unsubstituted or substituted methyl and m is 1, 2, or 3.

12. The compound of claim 1 , wherein R 2 is OR N3 .

13. A compound selected from:

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 13 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

16. A method of treating Parkinson's disease in a subject, comprising administering to the subject an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

17. A compound selected from:

or a pharmaceutically acceptable salt thereof.

18. A compound selected from:

or a pharmaceutically acceptable salt thereof.

19. A compound selected from:

or a pharmaceutically acceptable salt thereof.

20. A pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof of claim 13 , and a pharmaceutically acceptable carrier.

21. A method of treating Parkinson's disease in a subject, comprising administering to the subject an effective amount of the compound or a pharmaceutically acceptable salt thereof of claim 13 .