| 摘要 |
The present invention is concerned with novel substituted 3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione derivatives of Formula (I) wherein R1, R2, R3, R4, R5, Z and X 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) a tautomer or a stereoisomeric form thereof, wherein R1 is hydrogen, C1-4alkyl or Ar;
provided however that R1 is C1-4alkyl or Ar when L is a covalent bond; R2 is hydrogen, phenyl, cycloC3-7alkyl, tetrahydro-2H-pyranyl, tetrahydro-2H-thiopyranyl, piperidinyl, or C1-4alkyl optionally substituted with one or more substituents each independently selected from the group consisting of halo, hydroxyl, C1-4alkyloxy and NR7R8; Z is methylene or 1,2-ethanediyl, wherein methylene or 1,2-ethanediyl is optionally substituted with one or two C1-4alkyl substituents; L is a covalent bond, —(CH2)m-n—Y—(CH2)n—, 1,2-cyclopropanediyl, C1-6alkanediyl optionally substituted with one or more substituents selected from the group consisting of tetrahydro-2H-pyranyl, phenyl and C1-4alkyloxyC1-4alkyl, or C1-6alkanediyl wherein two geminal hydrogen atoms are replaced by C2-6alkanediyl; m represents 3, 4, 5, 6 or 7; n represents 1, 2 or 3; Y is O or NH; Ar is a ring system selected from the group consisting of phenyl, indolyl, oxazolyl, benzo[b]thienyl, 1,3-benzodioxolyl, 1,4-benzodioxanyl, 3,4-dihydro-2H-1,5-benzodioxepinyl, pyridyl, indanyl, 1,2,3,4-tetrahydro-1-naphthalenyl, and naphthalenyl;
wherein said ring system is optionally substituted with one or more substituents each independently selected from the group consisting of halo, Ar2, R0,C1-4alkyl optionally substituted with one or more substituents each independently selected from the group consisting of halo, C1-4alkyloxy and cycloC3-7alkyl, andC1-4alkyloxy optionally substituted with one or more substituents each independently selected from the group consisting of halo and cycloC3-7alkyl; Ar2 is phenyl optionally substituted with one or more substituents each independently selected from the group consisting of halo and C1-4alkyl optionally substituted with one or more halo substituents; R3 is hydrogen, halo or C1-4alkyl; R4 is hydrogen, halo or C1-4alkyl; R5 is hydrogen or C1-4alkyl; X is CR6 or N; R6 is hydrogen or C1-4alkyl; R7 is hydrogen or C1-4alkyl; R8 is hydrogen or C1-4alkyl; R0 is a ring system selected from the group consisting of piperidinyl, morpholinyl, cycloC3-7alkyl, pyrazolyl and pyrrolidinyl; wherein said ring system is optionally substituted with one or more substituents each independently selected from the group consisting of halo or C1-4alkyl optionally substituted with one or more halo atoms; or a pharmaceutically acceptable addition salt or a solvate thereof. |
