Tetrahydroquinoline derivatives
View Patent ↗The present invention relates to tetrahydroquinoline derivatives having gene formula (I) or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are H or Me; R 3 is H, hydroxy, (1-4C)alkoxy, (di)(1-4C)alkylamino(2-4C)alkoxy or (2-6)heterocycloakl(2-4C)alkoxy; R 4 is H, OH, (1-4C)alkoxy or R 7 ; R 5 is H, OH, (1-4C)alkoxy or R 7 , with the proviso that if R 4 is H, R 5 is not H, OH or (1-4C)alkoxy and that if R 5 is H, R 4 is not H, OH or (1-4C)alkoxy; R 6 is (2-5C)heteroaryl, (6C)aryl, (3-8C)cycloalkyl, (2 6C)heterocycloalkyl or (1-6C)alkyl; R 7 is amino, (di)(1-4C)alkylamino, (6C)arylcarbonylamino, (6C)arylcarbonyloxy, (2-5C) heteroarylcarbonylamino, (2-5C)heteroarylcarbonyloxy, R 8 -(2-4C)alkylamino, R 8 -(2-4C)alkoxy, R 9 -methylamino or R 9 -methoxy; R 8 is hydroxy, amino, (-14C)alkoxy, (di)(1-4C)alkylamino, (2-6C)heterocycloalkyl, (2-6C) heterocycloalkylcarbonylamino, (di)(1-4C)alkylaminocarbonylamino, (1-4C)alkoxycarbonylamino and R 9 is aminocarbonyl, (di)(1-4C)alkylaminocarbonyl, (2-5C)heteroaryl or (6C)aryl. The present invention also relates to pharmaceutical compositions comprising said derivatives and the use of these derivatives to regulate fertility.
1. A tetrahydroquinoline derivative according to Formula 1,
or a pharmaceutically acceptable salt thereof, wherein
R 1 and R 2 are H or Me
R 3 is H, hydroxy, (1-4C)alkoxy,
R 4 is H, OH, or (1-4C)alkoxy,
R 5 is OH, (1-4C)alkoxy or R 7 ,
with the proviso that if R 4 is H, R 5 is not OH or (1-4C)alkoxy
R 6 is (2-5C)heteroaryl, (6C)aryl, (3-8C)cycloalkyl, or (1-6C)alkyl, wherein the (2-5C)heteroaryl and the (6C)aryl are optionally substituted with one or more substituents selected from hydroxyl, amino, halogen, phenyl, (1-4C)alkyl, (1-4C)alkoxy, or (1-4C)(di)alkylamino,
R 7 is amino, (di)(1-4C)alkylamino, (2-5C)heteroarylcarbonylamino, (2-5C)heteroarylcarbonyloxy, R 8 -(2-4C)alkoxy, R 9 -methylamino or R 9 -methoxy
R 8 is amino, (di)(1-4C)alkylamino, (2-6C)heterocycloalkyl, (2-6C)heterocycloalkylcarbonylamino, or (1-4C)alkoxycarbonylamino and
R 9 is aminocarbonyl, (di)(1-4C)alkylaminocarbonyl, (2-5C)heteroaryl, optionally substituted with one or more (1-4C)alkyl substituents, or (6C)aryl.
2. The tetrahydroquinoline derivative of claim 1 wherein R 8 is amino, (di)(1-4C)alkylamino, (2-6C)heterocycloalkyl or (2-6C)heterocycloalkylcarbonylamino.
3. The tetrahydroquinoline derivative of claim 1 wherein R 7 is (di)(1-4C)alkylamino, R 8 -(2-4C)alkoxy, R 9 -methylamino or R 9 -methoxy.
4. The tetrahydroquinoline derivative of claim 3 wherein R 8 is amino, (di)(1-4C)alkylamino or (2-6C)heterocycloalkyl.
5. The tetrahydroquinoline derivative of claim 4 wherein R 8 is (di)(1-4C)alkylamino or (2-6C)heterocycloalkyl.
6. The tetrahydroquinoline derivative of claim 3 wherein R 6 is (2-5C)heteroaryl or (6C)aryl.
7. The tetrahydroquinoline derivative of claim 1 wherein R 6 is (4-5C)heteroaryl or (6C)aryl and R9 is aminocarbonyl, (di)(1-4C)alkylaminocarbonyl, (3-5C)heteroaryl or (6C)aryl.
8. The tetrahydroquinoline derivative of claim 1 wherein R 7 is (di)(1-4C)alkylamino, R 8 -ethoxy, R 9 -methylamino or R 9 -methoxy and R 9 is aminocarbonyl, (di)(1-4C)alkylaminocarbonyl, (3-5C)heteroaryl or (6C)aryl.
9. The tetrahydroquinoline derivative of claim 1 wherein R 8 is (di)(1-4C)alkylamino or (4-5C)heterocycloalkyl and R 9 is aminocarbonyl, (di)(1-4C)alkylaminocarbonyl, (3-5C)heteroaryl or (6C)aryl.
10. A pharmaceutical composition comprising the tetrahydroquinoline derivative of claim 1 and at least one pharmaceutically suitable auxiliary.