| 摘要 |
Disclosed are compounds of the formula;
or a pharmaceutically acceptable salt or solvate thereof, wherein
R1 is;R is —C(O)—N(R27)(R28) or;
and the remaining variables are as defined in the specification.
;Also disclosed are pharmaceutical compositions comprising the compounds of formula I.;Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease.;Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody. |
| 主权项 |
1. A compound having the structural formula:or a pharmaceutically acceptable salt thereof, wherein:
R19 is H, alkyl, optionally substituted benzyl, benzoyl, —SO2alkyl; —SO2 (optionally substituted phenyl), —SO2N(alkyl)2; phenyl, —C(O)alkyl, —C(O)-heteroaryl, —C(O)—NH (optionally substituted phenyl), —C(O)—O-benzyl, —C(O)—CH2—O-alkyl, —SO2— (optionally substituted heteroaryl), —C(O)-morpholinyl or cycloalkylalkyl, wherein the optional substituents on said phenyl and said benzyl are from 1 to 4 independently selected R32 groups, and wherein each said heteroaryl is selected from the group consisting of pyridyl, oxazolyl, pyrazinyl, thienyl and imidazolyl and the optional substituents on said heteroaryl are selected from alkyl and halo; wherein each R32 is selected from the group consisting of halo, alkyl, alkoxy, cyano and phenyl; R1 is R is —C(O)—N(R27)(R28); R2 is difluorobenzyl; R3 is H or alkyl; R4 is H or alkyl; R5 is H or alkyl; R14 is 1 to 4 substituents independently selected from the group consisting of H, alkyl, halo, —CN, and haloalkyl; and R27 and R28 are independently selected from alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, hydroxyalkyl, and alkoxyalkyl; or R27 and R28 together with the nitrogen to which they are attached, form an unsubstituted 3-7 membered heterocycloalkyl ring, or a 3-7 membered heterocycloalkyl ring substituted by 1-3 substituents independently selected from the group consisting of alkyl, and alkoxyalkyl. |
