Substituted benzoxazole, benzimidazole, oxazolopyridine and imidazopyridine derivatives as gamma secretase modulators

A compound of formula (I)

• or a stereoisomeric form thereof, wherein
• R1 is hydrogen, cyano, CF3, halo, or C1-4alkyl optionally substituted with one or more substituents each independently selected from the group consisting of hydroxyl and C1-4alkyloxy;
• R2 is hydrogen, C1-4alkyl or halo;
• X is CR5 or N;
• R5 is hydrogen or halo;
• A1 is CR6 or N;
• R6 is hydrogen, halo or C1-4alkyloxy;
• A2, A3 and A4 each independently are CH, CF or N;
• provided that no more than two of A1, A2, A3 and A4 are N;
• Y1 is CH
• Y2 is CR4;
• Y3 is CH;
• R4 is hydrogen, halo, C1-4alkyloxy, cyano, cycloC3-7alkyl, C2-4alkenyl, or C1-4alkyl optionally substituted with one or more substituents each independently selected from the group consisting of halo and C1-4alkyloxy;
• R3 is C2-6alkyl substituted with one or more halo substituents;
• C1-6alkyl optionally substituted with one or more substituents each independently selected from the group consisting of piperidinyl, morpholinyl, pyrrolidinyl, Ar, C1-6alkyloxy, tetrahydropyranyl, cycloC3-7alkyloxy and cycloC3-7alkyl;
• cycloC3-7alkyl substituted with one or more phenyl substituents optionally substituted with one or more halo substituents;
• cycloC3-7alkyl;
• piperidinyl;
• morpholinyl;
• pyrrolidinyl;
• tetrahydropyranyl;
• O—Ar;
• NR7R8;
• C1-6alkyloxy;
• C1-6alkylthio;
• Ar;
• CH2—O—Ar;
• S—Ar;
• NCH3—Ar;
• NH—Ar;
• or 1,6-dihydro-1-methyl-6-oxo-3-pyridinyl;
• wherein each piperidinyl, morpholinyl and pyrrolidinyl may be substituted with one or more substituents each independently selected from the group consisting of C1-4alkyl, C2-6alkenyl, C1-4alkylcarbonyl, halo and C1-4alkyloxycarbonyl;
• wherein each Ar independently is
• phenyl optionally substituted with one or more substituents each independently selected from the group consisting of halo, C1-4alkyloxy, cyano, NR7R8, morpholinyl, C1-4alkyl, C1-4alkyloxy substituted with one or more halo substituents, and C1-4alkyl substituted with one or more halo substituents;
• or
• a 5- or 6-membered heteroaryl selected from the group consisting of pyridinyl, pyrimidinyl, oxazolyl, furanyl, thiophenyl, pyrazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxadiazolyl, pyridazinyl and pyrazinyl;
• wherein said 5- or 6-membered heteroaryl is optionally substituted with one or more substituents each independently selected from the group consisting of halo, C1-4alkyloxy, cyano, C1-4alkyl, C1-4alkyloxy substituted with one or more halo substituents, and C1-4alkyl substituted with one or more halo substituents;
• each R7 is selected independently from hydrogen or C1-4alkyl;
• each R8 is selected independently from hydrogen, C1-4alkyl or C1-4alkylcarbonyl;
• Z is NR9;
• R9 is hydrogen, or C1-6alkyl optionally substituted with one or more substituents each independently selected from the group consisting of halo, cyano, phenyl, cycloC3-7alkyl and C1-4alkyloxy;
• or a pharmaceutically acceptable addition salt thereof.