Preparation of condensed triazepine derivatives and their use as BET inhibitors
The invention relates to compounds of the formula: and pharmaceutically acceptable salts thereof. These compounds are useful in the treatment of inflammatory diseases, fibtrotic diseases and neoplastic diseases.
1. A compound having the following formula (I),
or a pharmaceutically acceptable salt thereof,
wherein:
R 1 and R 2 are each independently selected from the group consisting of hydrogen, halogen, and (C 1 -C 6 ) alkyl;
R 3 is selected from the group consisting of (C 1 -C 6 ) alkyl, —OH, and halogen;
R 4 is selected from the group consisting of (C 1 -C 4 ) alkyl and
R 5 is selected from the group consisting of an aryl, a heteroaryl, a benzodioxolane and a benzodioxane, wherein said aryl, heteroaryl, benzodioxolane or benzodioxane is optionally substituted with a halogen or a (C 1 -C 4 )alkoxy group;
R 7 is (C 1 -C 6 ) alkyl.
2. A compound according to claim 1 , or a pharmaceutical salt thereof, wherein R 4 is (C 1 -C 4 ) alkyl.
3. A compound according to claim 1 , or a
pharmaceutical salt thereof, wherein R 4 is
4. A compound according to claim 1 , or a pharmaceutical salt thereof, wherein R 7 is (C 1 -C 4 ) alkyl.
5. A compound according to claim 1 , or a pharmaceutical salt thereof, wherein R 5 is selected from the group of
wherein W is a halogen.
6. A compound according to claim 1 , or a pharmaceutical salt thereof, wherein R 5 is phenyl substituted with a halogen.
7. A compound according to claim 1 , which is a compound of Formula (IIa):
wherein W is a halogen,
or a pharmaceutically acceptable salt thereof.
8. A compound according to claim 1 , or a pharmaceutical salt thereof, wherein R 1 and R 2 are each independently selected from (C 1 -C 6 ) alkyl.
9. A compound according to claim 1 , or a pharmaceutical salt thereof, wherein R 3 is (C 1 -C 6 ) alkyl.
10. A compound according to claim 1 , or a pharmaceutical salt thereof, wherein R 4 is
and R 7 is ethyl.
11. A compound according to claim 1 , or a pharmaceutical salt thereof, wherein
R 4 is
R 7 is ethyl; and
R 1 , R 2 and R 3 are each methyl.
12. A compound according to claim 1 , wherein the compound is selected from the group consisting of
or a pharmaceutical salt of any of the foregoing compounds.
13. A compound according to claim 1 , wherein the compound is
or a pharmaceutical salt thereof.
14. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers or excipients.
15. A compound according to claim 1 , or a pharmaceutical salt thereof, wherein R 5 is phenyl substituted with chlorine.
16. A compound according to claim 7 , or a pharmaceutical salt thereof wherein W is chloro.
17. A compound according to claim 1 , or a pharmaceutical salt thereof, wherein le and le are each independently selected from (C 1 -C 3 ) alkyl.
18. A compound according to claim 1 , or a pharmaceutical salt thereof, wherein le and le are methyl.
19. A compound according to claim 1 , or a pharmaceutical salt thereof, wherein R 3 is (C 1 -C 3 ) alkyl.
20. A compound according to claim 1 , or a pharmaceutical salt thereof, wherein R 3 is methyl.
21. A compound according to claim 1 , wherein the compound is selected from the group consisting of
22. A compound according to claim 1 , wherein the compound is