Heterocyclic substituted 2-amino quinazoline derivatives for the treatment of viral infections
This invention relates to heterocyclic substituted 2-amino-quinazoline derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.
1. A method of stimulating the innate immune system of a subject through activation of TLR7 and/or TLR8 of said subject, said method comprising administering to said subject an effective amount of a compound of formula (I)
or a pharmaceutically acceptable salt, tautomer(s), stereo-isomeric forms or polymorph thereof, wherein
R 1 is selected from the group consisting of:
R 2 is selected from the group consisting of hydrogen, —O—(C 1-3 )-alkyl, halogen, (C 1-3 )-alkyl, —O—(C 1-3 )-alkyl-O—(C 1-3 )-alkyl and CH 2 OH;
R 3 is selected from the group consisting of hydrogen, —O—(C 1-3 )-alkyl, halogen, (C 1-3 )-alkyl and —C(═O)—R 7 , wherein R 7 is selected from the group consisting of —O—(C 1-3 )-alkyl, NH 2 , NH(CH 3 ), N(CH 3 ) 2 , N(CH 3 )(C 1-3 )-alkyl, N((C 1-3 )-alkyl) 2 and pyrolidine;
R 4 is hydrogen or fluorine;
R 5 is selected from the group consisting of (C 1-3 )-alkyl, (C 1-3 )-fluoro-alkyl and CH 2 OH;
R 8 , R 9 , R 10 , R 11 and R 12 are each independently selected from the group consisting of hydrogen, (C 1-3 )-alkyl, —O—(C 1-3 )-alkyl and halogen; and
R 13 is selected from the group consisting of hydrogen, (C 1-3 )-alkyl and (C 1-3 )-fluoro-alkyl.
2. The method of claim 1 , wherein R 5 is CH 3 , and R 9 and R 11 are each independently H or CH 3 .
3. The method of claim 1 , wherein R 13 is H, CH 3 or CH 2 CH 3 .
4. The method of claim 1 , wherein R 1 is
5. The method of claim 4 , wherein R 9 is CH 3 .
6. The method of claim 4 , wherein R 2 is OCH 3 or —O—C 2 H 4 —O—CH 3 .
7. The method of claim 4 , wherein
R 3 , R 4 , R 13 and R 8 are each H;
R 9 is CH 3 ; and
R 2 is —O—(C 1-3 )-alkyl-O—(C 1-3 )-alkyl.
8. The method of claim 4 , wherein
R 3 , R 4 , R 13 and R 8 are each H;
R 9 is CH 3 , and
R 2 is OCH 3 .
9. The method of claim 1 , wherein R 1 is
10. The method of claim 9 , wherein
R 5 is CH 3 , and
R 8 , R 9 , R 10 and R 11 are each H.
11. The method of claim 1 , wherein R 1 is
12. The method of claim 11 , wherein
R 5 is CH 3 or CH 2 OH.
13. The method of claim 1 , wherein R 1 is
14. The method of claim 13 , wherein
R 5 is CH 3 , and
R 8 and R 9 are each H.
15. The method of claim 1 , wherein R 1 is
16. The method of claim 15 , wherein
each R 5 is CH 3 , and
R 8 and R 9 are each H.
17. The method of claim 4 , wherein R 1 is
18. The method of claim 17 , wherein each R 13 is (C 1-3 )-alkyl.
19. The method of claim 1 , wherein R 1 is
20. The method of claim 19 , wherein each R 13 is (C 1-3 )-alkyl.
21. The method of claim 1 , wherein the compound is selected from the group consisting of
22. The method of claim 1 , wherein the compound is together with one or more pharmaceutically acceptable excipients, diluents or carriers in a pharmaceutical composition.