申请人：——
公开号：US20030229067A1
公开（公告）日：2003-12-11
The subject invention provides compounds having the structure:
1
wherein,
R
1
is a substituted or unsubstituted alkyl, wherein the substituent is hydroxyl, dihydroxy, carboxyl, —C(═O)NR
a
R
b
, —NR
a
R
b
, —NR
a
C(═O)NR
a
R
b
, —NR
a
C(═O)OR
a
, —OC(═O)NR
a
R
b
, or —NHC(═O)R
a
;
R
2
is hydrogen or a substituted or unsubstituted alkyl, wherein the substituent is hydroxyl, dihydroxy, carboxyl, —C(═O)NR
a
R
b
, —NR
a
R
b
, —NR
a
C(═O)NR
a
R
b
, —NR
a
C(═O)OR
a
, —OC(═O)NR
a
R
b
, or —NHC(═O)R
a
, or
R
1
, R
2
and N together form a substituted piperazine, substituted azetidine ring, or a pyrrolidine ring substituted with —(CH
2
)
2
OH or —CH
2
C(═O)OH;
R
3
is a substituted or unsubstituted phenyl or a 5-6 membered heteroaryl ring, wherein the substituent is halogen, hydroxyl, cyano, (C
1
-C
15
)alkyl, (C
1
-C
15
)alkoxy, or —NR
a
R
b
;
R
4
is hydrogen or substituted or unsubstituted (C
1
-C
15
)alkyl;
R
5
is —(CH
2
)
m
OR
6
, —CHNOR
7
, —C(═O)NR
8
R
9
, —(CH
2
)
m
C(═O)OR
10
, —(CH
2
)
k
C(═O)NR
11
R
12
;
wherein R
6
is a substituted or unsubstituted (C
1
-C
30
)alkyl, (C
3
-C
10
)cycloalkyl, or an aryl, heteroaryl or 4-8 membered heterocyclic ring;
R
7
is hydrogen, or a substituted or unsubstituted (C
1
-C
30
)alkyl, (C
1
-C
30
)alkylaryl;
R
8
and R
9
are each independently hydrogen, or a substituted or unsubstituted (C
1
-C
30
)alkyl, (C
1
-C
30
)alkylaryl, (C
1
-C
30
)alkylamino, (C
1
-C
30
)alkoxy, or a saturated or unsaturated, monocyclic or bicyclic, carbocyclic or heterocyclic ring, or
R
8
, N, and R
9
together form a substituted or unsubstituted 4-8 membered heterocyclic ring;
R
10
is hydrogen or a substituted or unsubstituted (C
1
-C
30
)alkyl, (C
3
-C
10
)cycloalkyl, or an aryl, heteroaryl or heterocyclic ring;
R
11
, N and R
12
together form a 4-8 membered heterocyclic ring;
R
a
and R
b
are each independently hydrogen or alkyl;
m is 0, 1, 2 or 3; and
k is 1, 2 or 3,
or a specific enantiomer thereof, or a specific tautomer thereof, or a pharmaceutically acceptable salt thereof, and a method for treating a disease associated with the A
2b
adenosine receptor in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of the compounds of the invention.
该主题发明提供具有以下结构的化合物：
1
其中，
R
1
是取代或未取代的烷基，其中取代基是羟基、二羟基、羧基、—C(═O)NR
a
R
b
、—NR
a
R
b
、—NR
a
C(═O)NR
a
R
b
、—NR
a
C(═O)OR
a
、—OC(═O)NR
a
R
b
或—NHC(═O)R
a
；
R
2
是氢或取代或未取代的烷基，其中取代基是羟基、二羟基、羧基、—C(═O)NR
a
R
b
、—NR
a
R
b
、—NR
a
C(═O)NR
a
R
b
、—NR
a
C(═O)OR
a
、—OC(═O)NR
a
R
b
或—NHC(═O)R
a
，或
R
1
、R
2
和N共同形成取代哌嗪、取代氮杂环丙烷环或取代的—(CH
2
)
2
OH或—CH
2
C(═O)OH的吡咯烷环；
R
3
是取代或未取代的苯基或5-6成员杂芳环，其中取代基是卤素、羟基、氰基、(C
1
-C
15
)烷基、(C
1
-C
15
)烷氧基或—NR
a
R
b
；
R
4
是氢或取代或未取代的(C
1
-C
15
)烷基；
R
5
是—(CH
2
)
m
OR
6
、—CHNOR
7
、—C(═O)NR
8
R
9
、—(CH
2
)
m
C(═O)OR
10
、—(CH
2)
k
C(═O)NR
11
R
12
；
其中R
6
是取代或未取代的(C
1
-C
30
)烷基、(C
3
-C
10
)环烷基或芳基、杂芳基或4-8成员杂环环；
R
7
是氢或取代或未取代的(C
1
-C
30
)烷基、(C
1
-C
30
)烷基芳基；
R
8
和R
9
各自独立地是氢或取代或未取代的(C
1
-C
30
)烷基、(C
1
-C
30
)烷基芳基、(C
1
-C
30
)烷基氨基、(C
1
-C
30
)烷氧基或饱和或不饱和的、单环或双环的、碳环或杂环环，或
R
8
、N和R
9
共同形成取代或未取代的4-8成员杂环环；
R
10
是氢或取代或未取代的(C
1
-C
30
)烷基、(C
3
-C
10
)环烷基或芳基、杂芳基或杂环环；
R
11
、N和R
12
共同形成4-8成员杂环环；
R
a
和R
b
各自独立地是氢或烷基；
m为0、1、2或3；和
k为1、2或3，
或其特定对映体，或其特定互变异构体，或其药学上可接受的盐，以及一种治疗与需要此类治疗的受试者相关的A
2b
腺苷受体相关疾病的方法，包括向受试者施用该发明化合物的治疗有效量。
