Aryl substituted pyrimidines for use in influenza virus infection
The invention relates to compounds having the structure of formula (I) which can be used for the treatment of or against influenza infections.
1. A compound of formula (I):
or a stereo-isomeric form thereof, or a pharmaceutically acceptable salt, solvate, or polymorph thereof, wherein
X is —CF or N;
Y is N, —CF, —C—Cl, —C—CN or —C—CH 3 ;
R 1 is —H, —CH 3 , —COOH, —CF 3 , -cyclopropyl, —CONH 2 , —CONH(C 1-3 alkyl), or —CON(C 1-3 alkyl) 2 ;
Q is N or O; and
R 2 is a heterocycle optionally substituted by halogen, cyano, C 1-3 alkyl, hydroxyl, amino, methoxy, —COOH, —CF 3 , or cycloalkyl.
2. A pharmaceutical composition comprising a compound of claim 1 and one or more pharmaceutically acceptable excipients, diluents, or carriers.
3. A method of inhibiting replication of influenza virus in a biological sample comprising contacting the biological sample with an effective amount of a compound of claim 1 .
4. The method of claim 3 , comprising contacting the biological sample with an additional therapeutic agent.
5. The method of claim 4 , wherein the additional therapeutic agent is an antiviral agent, an influenza vaccine, or a combination thereof.
6. The compound of claim 1 , wherein X and Y are each CF or X and Y are each N.
7. The compound of claim 1 , wherein R 1 is —H, —CH 3 , or —COOH.
8. The compound of claim 1 , wherein Q is N.
9. The compound of claim 1 , wherein R 2 is optionally substituted pyrimidine, optionally substituted quinazoline, optionally substituted 5,6,7,8-tetrahydroquinazoline, optionally substituted 6,7-dihydro-5H-cyclopenta[d]pyrimidine, optionally substituted thieno[2,3-d]pyrimidine, optionally substituted pyrazine, or optionally substituted 7H-purine.
10. A compound selected from the group consisting of:
10
11
12
13
14
15
16
18
19
20
30
35
36
37
38
39
40
41
42
43
44
45
46
47
54
64
65
and
71
and pharmaceutically acceptable salts thereof.
11. The pharmaceutical composition of claim 2 , wherein the pharmaceutical composition comprises an additional therapeutic agent.
12. The pharmaceutical composition of claim 11 , wherein the additional therapeutic agent is an antiviral agent, an influenza vaccine, or a combination thereof.
13. A method of treating a viral influenza infection in a patient comprising administering to the patient an effective amount of a compound of claim 1 .
14. The method of claim 13 , wherein the viral influenza infection is caused by influenza A virus or influenza B virus.
15. The method of claim 13 , wherein the method comprises co-administering to the subject an additional therapeutic agent.
16. The method of claim 13 , wherein the additional therapeutic agent is an antiviral agent, an influenza vaccine, or a combination thereof.
17. The method of claim 13 , wherein the additional therapeutic agent is an antiviral agent.