Spiropyrrolidine beta-secretase inhibitors for the treatment of alzheimer'S disease
View Patent ↗The present invention is directed to spiropyrrolidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.
1. A compound of formula (I)
wherein:
R 1 is selected from the group consisting of
(1) hydrogen
(2) C 1-6 alkyl,
(3) C 3-9 cycloalkyl, and
(4) phenyl,
wherein said alkyl, cycloalkyl or phenyl R 1 moiety is optionally substituted with one or more
(a) halo,
(b) —OH,
(c) —CN,
(d) —C 1-6 alkyl
(e) —C 3-6 cycloalkyl, or
(f) —O—C 1-6 alkyl;
R 2 is hydrogen;
R 3 is selected from the group consisting of:
(1) hydrogen,
(2) C 6-10 aryl (for example, phenyl), and
(3) heteroaryl,
wherein said aryl or heteroaryl R 3 moiety is optionally substituted with one or more
(a) halo,
(b) —C 1-6 alkyl, wherein said alkyl is optionally substituted with one or more halogen, and
(c) —O—C 1-6 alkyl;
R 11 is selected from the group consisting of
(1) hydrogen
(2) C 1-6 alkyl,
(3) C 3-6 cycloalkyl, and
(4) phenyl,
wherein said alkyl, cycloalkyl or phenyl R 11 moiety is optionally substituted with one or more
(a) halo,
(b) —OH,
(c) —CN,
(d) —C 1-6 alkyl
(e) —C 3-6 cycloalkyl, or
(f) —O—C 1-6 alkyl.
2. A compound of claim 1 , wherein R 1 is selected from the group consisting of: hydrogen, phenyl (optionally substituted with halogen), and cyclohexyl.
3. A compound of claim 2 , wherein R 3 is hydrogen or unsubstituted phenyl.
4. A compound, or a pharmaceutically acceptable salt thereof, said compound having a structure:
Structure
and
5. A compound, or a pharmaceutically acceptable salt thereof, said compound having a structure:
Structure
and
6. A pharmaceutical composition, comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
7. A pharmaceutical composition, comprising a compound of claim 5 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
8. A pharmaceutical composition, comprising a compound of claim 4 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.