Azaquinazolinediones chymase inhibitors
Disclosed are small molecule inhibitors of the formula (I), which are useful in treating various diseases and conditions involving chymase.
1. A compound of the formula (I):
wherein
X 1 , X 2 , X 3 and X 4 are each independently —CH— or nitrogen, with the proviso that at least one of them is nitrogen;
E is —COOH or —COOR wherein R is C 1 -C 5 alkyl;
G is C 1 -C 2 alkyl;
J is a heteroaryl group optionally substituted with 1-3 substituents chosen from halogen, C 1 -C 3 alkyl and C 1 -C 3 alkoxy;
M is C 1 -C 5 alkyl optionally substituted with 1-3 substitutents chosen from C 1 -C 5 alkyl and C 3 -C 6 carbocycle;
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 and wherein:
E is —COOH or —COOR wherein R is C 1 -C 3 alkyl;
G is —CH 2 —;
J is a heteroaryl group chosen from indolyl, benzothiazolyl and benzoisothiazolyl each optionally substituted with 1-3 C 1 -C 3 alkyl groups;
M is C 1 -C 3 alkyl optionally substituted with 1-3 substitutents chosen from C 1 -C 5 alkyl, phenyl and cyclopropyl.
3. The compound according to claim 2 and wherein:
E is —COOH;
J is a heteroaryl group chosen from indolyl and benzoisothiazolyl each optionally substituted with 1-3 methyl groups;
M is C 1 -C 2 alkyl optionally substituted with 1-3 substitutents chosen from C 1 -C 5 alkyl, phenyl and cyclopropyl.
4. The compound according to claim 3 and wherein:
J is a heteroaryl group chosen from indolyl or benzoisothiazolyl each optionally substituted with 2-3 methyl groups;
M is C 1 -C 2 alkyl optionally substituted with 1 substitutent chosen from C 1 -C 5 alkyl, phenyl and cyclopropyl.
5. The compound according to claim 4 and wherein:
6. The compound according to claim 5 and wherein:
7. A compound chosen from
or a pharmaceutically acceptable salt thereof.
8. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and one or more pharmaceutically acceptable carries and/or adjuvants.