Adenosine A2a receptor antagonists
View Patent ↗Disclosed herein are compounds having the structural formula A including pharmaceutically acceptable salts or solvates of said compound, wherein X, Y, Q and R are as defined in the specification; pharmaceutical compositions thereof; methods of treating central nervous system diseases by administering the compound of the present invention to a patient in need of such treatment, and processes for preparing the compound of this invention.
1. A compound having the structural formula A
or a pharmaceutically acceptable salt of said compound, wherein:
R is selected from the group consisting of R 1 -furanyl-, R 1 -thienyl-, R 1 -pyridyl-, R 1 -oxazolyl-, R 1 -pyrrolyl- and R 2 -aryl-;
X is —(CH 2 ) n —;
Y is a pyrrolidinyl or azepanyl group with an aryl or heteroaryl moiety fused to two adjacent carbon atoms on Y, Y is a piperidinyl group with a pyridyl, pyrimidyl or pyrido[4,3-b]pyridyl group fused to two adjacent carbon atoms on Y, or Y is a piperidinyl group with a phenyl moiety fused to two adjacent carbon atoms on Y, wherein the piperidinyl group fused to a phenyl moiety has a substituent Q other than hydrogen, wherein X is attached to the N atom of the piperidinyl, pyrrolidinyl or azepanyl group;
Q is 1-4 substituents, which can be the same or different, and are independently selected from the group consisting of hydrogen, cycloalkyl, amino, aryl, aralkyl, heteroaryl, alkyl, CF 3 , CN, halogen, NO 2 , alkoxy, alkoxyalkoxy, cycloalkylalkoxy, alkylamino, alkylsulfonamino, alkylaminosulfonyl, dialkylaminosulfonyl, NH 2 SO 2 and hydroxy;
n is 1 to 4;
R 1 is 1-3 substituents, which may be the same or different, and are independently selected from the group consisting of hydrogen, alkyl, CF 3 , halogen and NO 2 ; and
R 2 is 1-3 substituents, which may be the same or different, and are independently selected from the group consisting of hydrogen, alkyl, CF 3 , halogen, NO 2 , alkoxy, alkylamino, alkylsulfonamido, alkylaminosulfonyl, dialkylaminosulfonyl, aminosulfonyl, and hydroxyl.
2. A compound selected from the group consisting of
COMPOUND #
STRUCTURE
1
2
3
4
5
6
7
8
9
10
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
55
56
57
58
AND
59
3. A compound according to claim 2 selected from the group consisting of:
COMPOUND #
STRUCTURE
1
3
5
6
7
8
9
10
20
21
23
27
28
29
30
31
33
35
36
37
38
41
42
44
47
48
49
54
55
56
57
58
AND
59
4. A compound according to claim 3 selected from the group consisting of:
COMPOUND #
STRUCTURE
3
7
28
29
31
35
36
37
42
47
48
49
56
AND
57
5. A compound according to claim 4 selected from the group of:
COMPOUND #
STRUCTURE
3
29
47
49
56
AND
57
6. A pharmaceutical composition comprising one or more compounds of claim 1 and a pharmaceutically acceptable carrier.
7. The pharmaceutical composition according to claim 6 , wherein the amount of compound or compounds of claim 1 is a therapeutically acceptable amount.
8. A method of treating psychoses, comprising administering one or more compounds of claim 1 to a patient in need of such treatment.
9. A compound having the structural formula A
or a pharmaceutically acceptable salt thereof, wherein:
R is furanyl;
X is —(CH 2 ) 2 —;
Y is a pyrrolidinyl or azepanyl group with a phenyl moiety fused to two adjacent carbon atoms on Y; Y is a piperidinyl group with a pyridyl or pyrido[4,3-b]pyridyl group fused to two adjacent carbon atoms on Y; or Y is a piperidinyl group with a phenyl moiety fused to two adjacent carbon atoms on Y, wherein the piperidinyl group fused to the phenyl moiety has a substituent Q other than hydrogen; wherein X is attached to the N atom of the piperidinyl, pyrrolidinyl or azepanyl group; and
Q is 1-4 substituents independently selected from the group consisting of hydrogen, cycloalkyl, aralkyl, alkyl, halogen, NO 2 , alkoxy and alkoxyalkoxy.