NOVEL SUBSTITUTED BICYCLIC HETEROCYCLIC COMPOUNDS AS GAMMA SECRETASE MODULATORS

摘要

The present invention is concerned with substituted bicyclic heterocyclic compounds of Formula (I);;wherein Het1, Het2, A1, A2, A3 and A4 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

主权项

1. A compound of formula (I) or a stereoisomeric form thereof, wherein Het1 is a 5-membered or 6-membered aromatic heterocycle, having formula (a-1), (a-2), (a-3), (a-4) or (a-5): R0 is H or C1-4alkyl; R1 is H, C1-4alkyl or C1-4alkyloxyC1-4alkyl; R2 is C1-4alkyl; X is O or S; G1 is CH or N; G2 is CH, N or C substituted with C1-4alkyl; provided that G1 and G2 are not simultaneously N; G3 is CH or N; R10a and R10b each independently are hydrogen or C1-4alkyl; A1 is CR3 or N; wherein R3 is H, halo or C1-4alkyloxy; A2, A3 and A4 each independently are CH, CF or N; provided that maximum two of A1, A2, A3 and A4 are N; Het2 is a 9-membered bicyclic aromatic heterocycle, having formula (b-2): Y1 is N; Y2 is CR4b; Y3 is CH; R4b is H; H halo; C1-4alkyloxy; cyano; cycloC3-7alkyl; or C1-4alkyl optionally substituted with one or more substituents each independently selected from the group consisting of halo and amino; R6b 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, Ar, C1-6alkyloxy, tetrahydropyranyl, cycloC3-7alkyloxy, and cycloC3-7alkyl; cycloC3-7alkyl; cycloC3-7alkyl substituted with one or more phenyl substituents optionally substituted with one or more halo substituents; piperidinyl; morpholinyl; pyrrolidinyl; NR8R9; tetrahydropyranyl; O—Ar; C1-6alkyloxy; C1-6alkylthio; Ar; CH2—O—Ar; S—Ar; NCH3—Ar; or NH—Ar; wherein each piperidinyl, morpholinyl, and pyrrolidinyl may optionally 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, NR8R9, morpholinyl, C1-4alkyl, and C1-4alkyl substituted with one or more halo substituents; pyridinyl optionally substituted with one or more substituents each independently selected from the group consisting of halo, C1-4alkyloxy, cyano, C1-4alkyl, and C1-4alkyl substituted with one or more halo substituents; oxazolyl optionally substituted with one or more C1-4alkyl substituents; or thienyl optionally substituted with one or more halo substituents; each R8 independently is H or C1-4alkyl; each R9 independently is H or C1-4alkyl; R7 is H, C1-6alkyl optionally substituted with one or more substituents each independently selected from the group consisting of halo, phenyl, and C1-4alkyloxy; or a pharmaceutically acceptable addition salt or a solvate thereof.