申请人:——
公开号:US20030004172A1
公开(公告)日:2003-01-02
Selective MMP-13 inhibitors are fused pyrimidinones of the formula
1
or a pharmaceutically acceptable salt thereof, wherein:
W, together with the carbon atoms to which it is attached, form a 5-membered ring diradical
2
X is O, S, SO, SO
2
, NR
5
, or CH
2
;
3
B is O or NR
5
; or
A and B are taken together to form —C≡C—;
R
1
, R
4
, and R
5
are hydrogen, alkyl, alkenyl, alkynyl, (CH
2
)
n
aryl, (CH
2
)
n
cycloalkyl, C
1
-C
6
alkanoyl, or (CH
2
)
n
heteroaryl;
R
2
and R
3
are hydrogen, alkyl, alkenyl, alkynyl CN, NO
2
, NR
4
R
5
, (CH
2
)
n
cycloalkyl, (CH
2
)
n
aryl, or (CH
2
)
n
heteroaryl;
R
2
may further be halo;
n is an integer of from 0 to 5; and
R
4
and R
5
when taken together with a nitrogen to which they are both attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing O, S, or N, and substituted or unsubstituted;
with the proviso that R
1
and R
3
are not both selected from hydrogen and C
1
-C
6
alkyl.
选择性MMP-13抑制剂是具有以下结构的嘧啶酮类化合物或其药用盐:
其中:
W与其连接的碳原子一起形成一个5元环二自由基;
X为O、S、SO、SO2、NR5或CH2;
B为O或NR5;
或A和B结合形成—C≡C—;
R1、R4和R5为氢、烷基、烯基、炔基、(CH2)n芳基、(CH2)n环烷基、C1-C6烷酰基或(CH2)n杂环芳基;
R2和R3为氢、烷基、烯基、炔基、CN、NO2、NR4R5、(CH2)n环烷基、(CH2)n芳基或(CH2)n杂环芳基;R2还可以是卤素;
n为0到5的整数;
R4和R5与它们都连接的氮一起形成含碳原子且可选择含有O、S或N的3-8元环,可以是取代或未取代的;
但要注意R1和R3不同时选择自氢和C1-C6烷基。