3H-phenoxazine derivatives suitable as near-infrared imaging agents, preparation an use thereof
申请人：Auberson Yves
公开号：US20070031336A1
公开（公告）日：2007-02-08
The present invention provides compounds of formula (I) wherein X and Y represent CH, CH
2
or a divalent or trivalent heteroatom under the proviso that X and Y are not simultaneously CH or CH
2
; m and o represent independently of each other 0 or 1, with the proviso that if m is 0 then the dotted line between Y and the neighboring C atom represents a bond and Y is CH or a trivalent heteroatom, if m is 1 then the dotted line between Y and the neighboring C atom is absent and Y is CH
2
or a divalent heteroatom, if o is 0 then the dotted line between X and the neighboring C atom represents a bond and X is CH or a trivalent heteroatom, if o is 1 then the dotted line between X and the neighboring C atom is absent and X is CH
2
or a divalent heteroatom; A represents (CH
3
CR
4
)
p
and Q represents (CR
9
R
10
)
n
; n and p represent independently of each other 0 or 1; R
6
, R
7
, R
13
and R
14
denote independently of each other hydrogen, halogen, (C
1-4
)alkyl, (C
1-4
)alkylSO
2
, SO
3
H, carboxy, (C
1-4
)alkoxy carbonyl, (C
1-4
)alkoxy, OH or NR
15
R
16
; R
1
, R
2
, R
3
, R
4
, R
9
, R
10
, R
11
and R
12
denote independently of each other hydrogen, (C
1-4
)alkyl, carboxy, (C
1-4
)alkoxy carbonyl or (C
1-4
)alkoxy, or, when X is CH or CH
2
then R
1
and R
2
can also be OH or NR
15
R
16
, or when Y is CH or CH
2
then R
11
, R
12
can also be OH or NR
15
R
16
; R
5
, R
8
, R
15
and R
16
are independently of each other hydrogen, (C
1-4
)alkyl, (C
1-4
)alkoxy, R
17
O—C(O)—(C
1-4
)alkyl or (reactive group)-(C
1-4
)alkyl; and R
17
represents hydrogen or (C
1-4
)alkyl; compositions comprising such compounds, a process for the production of such compounds of formula (I), a method of labeling target structures, especially amyloid plaques, in the brain, a method for identifying Alzheimer's disease, use of a compound of formula I as a near-infrared imaging agent and a conjugate comprising a compound of formula (I) covalently linked to a biomolecule through a reactive group.
本发明提供了公式（I）化合物，其中X和Y分别代表CH，CH2或二价或三价杂原子，前提是X和Y不同时为CH或CH2; m和o独立地表示0或1，前提是如果m为0，则Y与相邻的C原子之间的虚线表示一条键，并且Y为CH或三价杂原子，如果m为1，则Y与相邻的C原子之间的虚线不存在，并且Y为CH2或二价杂原子，如果o为0，则X与相邻的C原子之间的虚线表示一条键，并且X为CH或三价杂原子，如果o为1，则X与相邻的C原子之间的虚线不存在，并且X为CH2或二价杂原子; A表示（CH3CR4）p，Q表示（CR9R10）n; n和p独立地表示0或1; R6、R7、R13和R14独立地表示氢、卤、（C1-4）烷基、（C1-4）烷基SO2、SO3H、羧基、（C1-4）烷氧基羰基、（C1-4）烷氧基、OH或NR15R16; R1、R2、R3、R4、R9、R10、R11和R12独立地表示氢、（C1-4）烷基、羧基、（C1-4）烷氧基羰基或（C1-4）烷氧基，或者当X为CH或CH2时，R1和R2也可以是OH或NR15R16，或者当Y为CH或CH2时，R11、R12也可以是OH或NR15R16; R5、R8、R15和R16独立地表示氢、（C1-4）烷基、（C1-4）烷氧基、R17O-C（O）-（C1-4）烷基或（反应基）-（C1-4）烷基; R17表示氢或（C1-4）烷基; 包括这种化合物的组合物，制备这种化合物的方法，标记靶结构（特别是脑中的淀粉样斑块）的方法，识别阿尔茨海默病的方法，将公式I的化合物用作近红外成像剂的用途以及包括通过反应基共价连接到生物分子的公式（I）化合物的共轭物。
