PRMT5 inhibitors
View Patent ↗The present invention provides a compound of Formula (I) or the pharmaceutically acceptable salts thereof, which are PRMT5 inhibitors.
1. A compound of formula I,
or a pharmaceutically acceptable salt thereof, wherein
R 1 is hydrogen or C 1-4 alkyl, and
R 2 is hydrogen or C 1-4 alkyl, or
R 1 and R 2 , together with the atom to which they are attached, form a C 3-6 cycloalkyl ring;
R 3 is halogen or —NHR 4 ;
R 4 is a 5- or 6-membered saturated heterocycle, unsubstituted or substituted with one, two, or three moieties independently selected from the group consisting of C(O)R 5 and halogen;
R 5 is C 1-4 alkyl; and
R 6 , R 7 , R 8 , and R 9 , are independently selected from hydrogen, halogen and C 1-4 alkyl.
2. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein
R 1 is hydrogen or C 1-4 alkyl, and
R 2 is hydrogen or C 1-4 alkyl, or
R 1 and R 2 , together with the atom to which they are attached, form a C 3-6 cycloalkyl ring;
R 3 is halogen or —NHR 4 ;
R 4 is a 5- or 6-membered saturated heterocycle containing 1 N atom, wherein the heterocycle is unsubstituted or substituted with one, two, or three moieties independently selected from the group consisting of C(O)R 5 and halogen;
R 5 is C 1-4 alkyl; and
R 6 , R 7 , R 8 , and R 9 are independently selected from hydrogen, halogen and C 1-4 alkyl.
3. A compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein
R 1 is hydrogen or C 1-4 alkyl;
R 2 is hydrogen or C 1-4 alkyl;
R 3 is halogen or —NHR 4 ;
R 4 is a 6-membered saturated heterocycle containing 1 N atom, wherein the heterocycle is unsubstituted or substituted with C(O)R 5 ; and
R 5 is C 1-4 alkyl.
4. A compound of claim 3 , or a pharmaceutically acceptable salt thereof, where R 1 is hydrogen, CH 3 or CH 2 CH 3 .
5. A compound of claim 3 , or a pharmaceutically acceptable salt thereof, where R 2 is hydrogen or CH 3 .
6. A compound of claim 3 , or a pharmaceutically acceptable salt thereof, where R 3 is
Cl, or
7. A compound of claim 2 ,
which is
or a pharmaceutically acceptable salt thereof.
8. A composition for treating cancer comprising a compound of claim 2 and a pharmaceutically acceptable carrier.
9. A method for treating cancer comprising administering to a patient in need there of a composition of claim 8 .