Gamma secretase modulators
Disclosed herein are compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein each of the substituents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing the compound of Formula (I) and use of the compound in the treatment of neurodegenerative diseases or conditions such as Alzheimer's disease.
1. A compound of the Formula (I):
or a pharmaceutically acceptable salt thereof,
wherein:
X is a bond, —S—, —S(O) 2 —, —NH—, —O—, —CH 2 —, —C(O) or —CHOH;
R is halogen;
R 1 is hydrogen, —OH or C1-C3 alkyl optionally substituted with 1 to 3 halogen;
n is 0-3;
W is alkyl or alkoxy, wherein the alkyl and alkoxy are optionally substituted with 1 to 3 halogen; and
Y is
wherein V is —C—or —N—, and Z is halo, alkyl or alkoxy wherein the alkyl or alkoxy is optionally substituted with 1 to 3 halogen.
2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein n is 2.
3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R is fluoro.
4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Y is:
5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Y is selected from the group consisting of:
6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Y is:
7. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein the R groups that are bound to the phenyl moiety are as shown in Formula (II):
8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:
9. The compound of claim 1 or a pharmaceutically acceptable salt thereof, which is:
10. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
11. A pharmaceutical composition comprising the compound of claim 9 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
12. A method of treating Alzheimer's disease comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.