| 摘要 |
The present invention relates to novel 5,6-dihydroimidazo[1,5-a]pyrazinyl derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, in particular BACE1 and/or BACE2 (wherein BACE1, is also known as Asp2, or memapsin2 and BACE2 is also known as Asp1, Memapsin 1 or DRAP). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, dementia of the Alzheimer's type, dementia associated with beta-amyloid, age-related macular degeneration, type 2 diabetes and other metabolic disorders. |
| 主权项 |
1. A compound of Formula (I)or a stereoisomeric form thereof, wherein:
R is selected from the group consisting of hydrogen; halo; —CN; C1-4alkyl optionally substituted with one or more substituents each independently selected from halo, —CN and C1-4alkyloxy; C1-4alkyloxy optionally substituted with one or more substituents each independently selected from halo and C1-4alkyloxy; and —(CH2)m—NRx(C═O)Ry, wherein m is an integer selected from the group consisting of 0, 1, 2, and 3, Rx is selected from H and C1-4alkyl, and Ry is C1-4alkyl; R1 is selected from the group consisting of hydrogen; halo; C1-4alkyl optionally substituted with one or more halo substituents; —C1-4alkyl(C3-7cycloalkyl); and C3-7cycloalkyl; R2 is selected from the group consisting of C1-4alkyl optionally substituted with one or more substituents each independently selected from fluoro, and C1-4alkyloxy; and C3-7cycloalkyl; R3 is in each instance an independently selected halo substituent; n is an integer selected from 1 and 2; R4 is selected from (a) and (b): wherein R5 and R6 are each independently selected from the group consisting of aryl and heteroaryl, each of which may be optionally substituted with one or more substituents each independently selected from the group consisting of halo, —CN, C1-4alkyl optionally substituted with one or more halo substituents, and C1-4alkyloxy optionally substituted with one or more halo substituents; wherein aryl is phenyl; wherein heteroaryl is a 5-membered aromatic heterocycle selected from the group consisting of oxazole and pyrazole; or is a 6-membered aromatic heterocycle selected from the group consisting of pyridinyl, pyrimidinyl and pyrazinyl; or a pharmaceutically acceptable addition salt or a solvate thereof. |
