LRRK2 inhibitors
The present invention is directed to compounds of formula I The compounds are considered useful for the treatment of diseases associated with LRRK2 such as Parkinson's disease.
1. A compound of formula I, or a pharmaceutically acceptable salt thereof, wherein:
R 1 is CH 2 R 4 or R 4 ;
R 2 is a C 1 -C 3 alkyl, an isotopically labelled C 1 -C 3 alkyl, a C 3 -C 6 cycloalkyl, or a C 1 -C 3 haloalkyl;
R 3 is halogen, cyano, a O—C 1 -C 3 haloalkyl, a C 1 -C 3 haloalkyl, a C 3 -C 6 cycloalkyl, or a C 1 -C 3 alkyl;
R 4 is a 4- to 7-membered heterocycle having 1-2 heteroatoms independently selected from oxygen and nitrogen; a C 1 -C 3 alkyl, a C 1 -C 3 cyanoalkyl, a C 1 -C 3 haloalkyl, or a C 3 -C 6 cycloalkyl;
or R 4 is a bicyclic 8-membered heterocycle having 1-2 heteroatoms independently selected from oxygen and nitrogen;
wherein each heterocycle or cycloalkyl is unsubstituted or substituted with 1, 2, or 3 groups independently selected from the group consisting of cyano, deuterium, halogen, C 1 -C 3 alkyl, an isotopically labelled C 1 -C 3 alkyl, a O—C 1 -C 3 haloalkyl, a O—C 1 -C 3 alkyl, or a C 1 -C 3 haloalkyl.
2. The compound of claim 1 , wherein the compound is a compound of formula Ia, or a pharmaceutically acceptable salt thereof:
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from a C 1 -C 3 alkyl, an isotopically labelled C 1 -C 3 alkyl or a C 3 -C 6 cycloalkyl.
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from —CH 3 , —CH 2 CH 3 , —CD 3 or cyclopropyl.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is an isotopically labelled C 1 -C 3 alkyl.
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is —CD 3 .
7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is chloro.
8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is a 4- to 6-membered heterocycle having one oxygen atom, wherein the 4- to 6-membered heterocycle is unsubstituted or substituted with one group selected from the list consisting of cyano, deuterium, halogen, C 1 -C 3 alkyl, an isotopically labelled C 1 -C 3 alkyl or C 1 -C 3 haloalkyl.
9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is a 4- to 6-membered heterocycle having one oxygen atom, wherein the 4- to 6-membered heterocycle is unsubstituted or substituted with two groups independently selected from the list consisting of cyano, deuterium, halogen, C 1 -C 3 alkyl, an isotopically labelled C 1 -C 3 alkyl or C 1 -C 3 haloalkyl.
10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is unsubstituted tetrahydro-2H-pyran-4-yl.
11. The compound of claim 1 selected from the list of:
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , wherein the compound is
13. The compound of claim 1 , wherein the compound is
14. The compound of claim 1 , wherein the compound is
15. The compound of claim 1 , wherein the compound is
16. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
17. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
18. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
19. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.