2-AMINO-QUINOLINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE)

摘要

Disclosed is a compound of formula (I) wherein a is an integer from 0 to 4; R1 is selected from the group consisting of halogen, C1-4alkyl, C1-4alkoxy, halogenated C1-4alkyl and halogenated C1-4alkoxy; A is selected from the group consisting of aryl and heteroaryl; R2 is selected from the group consisting of hydrogen and C1-4alkoxy; R3 is selected from the group consisting of hydrogen, C1-8alkyl, hydroxyl substituted C2-8alkyl, NRARB substituted C2-8alkyl, -C1-4alkyl-O-C1-4alkyl, cycloalkyl, -(C1-4alkyl)-cycloalkyl, heterocycloalkyl and -(C1-4alkyl)heterocycloalkyl; wherein RA and RB are each independently selected from the group consisting of hydrogen and C1-4alkyl; A1 is selected from the group consisting of -(CH2)b-; wherein b is an integer from 2 to 4; L1 is selected from the group consisting of-NRc- and -C(O)-NRc-; wherein RC is selected from the group consisting of hydrogen, C1-8alkyl, hydroxy substituted C1-4alkyl, -C1-4alkyl-O-C1-4alkyl and C5-7cycloalkyl; R4 is selected from the group consisting of C1-8alkyl, C2-12alkenyl, -C1-4alkyl-O-C1-4alkyl, -C1-4alkyl-NRDRE, -C1-4alkyl-OH, cycloalkyl, -C1-4alkylcycloalkyl, partially unsaturated carbocyclyl, -C1-4alkyl-(partially unsaturated carbocyclyl), aryl, aralkyl, heteroaryl, -C1-4alkyl-heteroaryl, heterocycloalkyl and -C1-4alkyl-heterocycloalkyl; wherein RD and RE are each independently selected from the group consisting of hydrogen and C1-4alkyl; and wherein the cycloalkyl, partially unsaturated carbocyclyl, aryl, heteroaryl or heterocycloalkyl, whether alone or as part of a substituent group, is optionally substituted with one or more substituents independently selected from the group consisting of fluoro, C1-4alkyl, -C1-4alkyl-O-C1-4alkyl, carboxy, -C(O)O-C1-4alkyl and aralkyl; alternatively, L1 is -NRc- and RC and R4 are taken together with the nitrogen atom to which they are attached to form a ring structure selected from the group consisting of 1-pyrazolyl, 1-imidazolyl and 1-(1 ,2,3-triazolyl); wherein the 1-pyrazolyl, 1-imidazolyl or 1-(1,2,3-triazolyl) is optionally substituted with a substituent selected from the group consisting of C1-6alkyl; or a pharmaceutically acceptable salt thereof.