申请人:Scopes David Ian Carter
公开号:US20100298325A1
公开(公告)日:2010-11-25
a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof: wherein X and Y are independently NR
5
or O; W and Z are independently a bond or (CH2)mCH(R7)(CH2)n; m=0-1, n=0-2; R is hydrogen or halogen; R
1
and R
2
are independently selected from hydrogen halogen, CF
3
, CN, OR
8
, NR
9
R
10
, NR
9
COR
11
, NR
9
SO
2
R
11
or C
1-6
alkyl optionally substituted by hydroxyl, C
1-6
alkoxy or NR
9
R
10
; R
3
is hydrogen, halogen, CF
3
, CN, OR
8
, SR
8
or SO
2
R
11
; R
4
is hydrogen, halogen, CF
3
, OR
9
, NR
9
R
10
, NR
9
COR
11
, NR
9
SO
2
R
11
or C
1-6
alkyl optionally substituted by hydroxyl, C
1-6
alkoxy or NR
9
R
10
; R
5
is hydrogen or C
1-6
alkyl optionally substituted by hydroxyl, C
1-6
alkoxy or NR
9
R
10
; R6 is hydrogen, fluorine, C1-6 alkyl, or C1-6 alkoxy; R
6
is hydrogen, fluorine, C
1-6
alkyl, or C
1-6
alkoxy; R
7
is hydrogen, C
1-6
alkyl, phenyl or C
1-3
alkylphenyl wherein said phenyl groups are optionally substituted by one or more substituents selected from halogen, C
1-6
alkyl, CF
3
, OCF
3 or
OR
9
; R
8
is hydrogen or C
1-6
alkyl optionally substituted by fluorine, C
1-6
alkoxy or NR
9
R
10
, R
9
is hydrogen, C
1-6
alkyl or C
1-3
alkylphenyl wherein said phenyl group is optionally substituted by one or more substituents selected from halogen, C
1-6
alkyl, CF
3
, OR
8
, NR
9
R
10
Or OCF
3
; R
10
is hydrogen, C
1-6
alkyl, C
1-6
alkenyl, phenyl or C
1-3
alkylphenyl wherein said phenyl groups are optionally substituted by one or more substituents selected from halogen, C
1-6
alkyl, CF
3
, OR
8
or OCF
3
; or the groups R
9
and R
10
when they are attached to a nitrogen atom may together form a 5- or 6-membered ring which optionally contains one further heteroatom selected from NR
9
, S and O; and R
11
is C
1-6
alkyl or a phenyl group optionally substituted by one or more substituents selected from halogen, C
1-6
alkyl, CF
3
, OCF
3
or OR
8
is provided. The compounds are useful in treating amyloid related diseases.
该化合物的结构式(I)或其药用可接受的盐或前药:其中X和Y分别独立为NR5或O;W和Z分别独立为键或(CH2)mCH(R7)(CH2)n;m=0-1,n=0-2;R为氢或卤素;R1和R2分别选自氢卤素,CF3,CN,OR8,NR9R10,NR9COR11,NR9SO2R11或C1-6烷基,可选择地被羟基,C1-6烷氧基或NR9R10取代;R3为氢,卤素,CF3,CN,OR8,SR8或SO2R11;R4为氢,卤素,CF3,OR9,NR9R10,NR9COR11,NR9SO2R11或C1-6烷基,可选择地被羟基,C1-6烷氧基或NR9R10取代;R5为氢或C1-6烷基,可选择地被羟基,C1-6烷氧基或NR9R10取代;R6为氢,氟,C1-6烷基或C1-6烷氧基;R7为氢,C1-6烷基,苯基或C1-3烷基苯基,其中所述苯基可选择地被一个或多个取代基取代,所述取代基选自卤素,C1-6烷基,CF3,OCF3或OR9;R8为氢或C1-6烷基,可选择地被氟,C1-6烷氧基或NR9R10取代;R9为氢,C1-6烷基或C1-3烷基苯基,其中所述苯基可选择地被一个或多个取代基取代,所述取代基选自卤素,C1-6烷基,CF3,OR8,NR9R10或OCF3;R10为氢,C1-6烷基,C1-6烯基,苯基或C1-3烷基苯基,其中所述苯基可选择地被一个或多个取代基取代,所述取代基选自卤素,C1-6烷基,CF3,OR8或OCF3;或当连接到氮原子时,R9和R10组合可形成一个可选择地含有来自NR9,S和O的进一步杂原子的5-或6-成员环;R11为C1-6烷基或一个苯基,可选择地被一个或多个取代基取代,所述取代基选自卤素,C1-6烷基,CF3,OCF3或OR8。这些化合物在治疗与淀粉样蛋白相关的疾病中很有用。