Gamma secretase inhibitors

摘要

Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts 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.;

主权项

1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein
R is —(C1-C6)alkylNR2R3, —(C1-C6)alkyl R4;R1 is independently selected from the group consisting halogen, (C1-C6)alkyl, —CN, —CF3, —O—(C1-C6)alkyl, —O-(halo(C1-C6)alkyl), —C(O)—O—(C1-C6)—OH-substituted (C1-C4)alkyl, halo (C1-C6)alkyl, —(C1-C4)alkoxy-OH, —(C1-C4)alkoxy(C1-C4)alkoxy and —S(O)2(C1-C6)alkyl;n is 0, 1, 2, 3;R2 is H or (C1-C6)alkyl;R3 is H, alkyl, halo(C1-C6)alkyl, —(C3-C6)cycloalkyl, —(C1-C3)alkyl-(C3-C6)cycloalkyl optionally substituted with 1 or 2 L1 groups or —C(O)—(C1-C6)alkyl;R4 is —CN, —OH-substituted halo(C1-C6)alkyl, —(C3-C6)cycloalkyl optionally substituted with 1 or 2 L1 groups, —(C3-C5)heterocycloalkyl containing 1-2 heteroatoms selected from N and O optionally substituted with 1 or 2 L1 groups, —C(O)NH2, —C(S)NH2, —C(O)NH—(C1-C4)alkyl, —C(O)NH—(C3-C5)heterocycloalkyl containing 1-2 heteroatoms selected from N and O, —C(O)—NH—(C3-C6)cycloalkyl, —C(O)—(C3-C5)heterocycloalkyl containing 1-2 heteroatoms selected from N and O, —N((C1-C4)alkyl)-C(O)—(C1-C3)alkyl, —N((C1-C4)haloalkyl)-C(O)(C1-C3)alkyl), —S(O)2—(C1-C3)alkyl and —P(O)—((C1-C3)alkoxy)2;L1 is independently selected from the group consisting of —CH3, —NH2, —OH, —C(O)—CH3, ═O and —C(O)—NH2;Ar is selected from the group consisting of phenyl optionally substituted with 1 or 2 L2 groups, and pyridyl optionally substituted with 1 or 2 L2 groups; andL2 is independently selected from the group consisting of: halogen, (C1-C6)alkyl, —CN, —CF3, —O—(C1-C6)alkyl —O-(halo(C1-C6)alkyl), —C(O)—O—(C1-C6)alkyl, —OH— substituted(C1-C6)alkyl, halo(C1-C6)alkyl, —OH-substituted (C1-C4)alkoxy, —(C1-C4)alkoxy(C1-C4)alkoxy and —S(O)2(C1-C6)alkyl.