Tetrahydroquinoline derivatives and their use as FSH receptor modulators
View Patent ↗The present invention relates to tetrahydroquinoline derivatives having general formula (I) or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are H, Me; R 3 is (2-6C)heterocycloalkyl(1-4C)alkyl, (2-5C)heteroaryl(1-4C)alkyl, (6C)aryl (1-4C)alkyl, (1-4C)(di)alkylaminocarbonylamino(2-4C)alkyl, (2-6C) heterocycloalkylcarbonylamino(2-4C)alkyl, R 5 -(2-4C)alkyl or R 5 -carbonyl(1-4C)alkyl; R 4 is (2-5C)heteroaryl, (6C)aryl, (3-8C)cycloalkyl, (2-6C)heterocycloalkyl or (1-6C) alkyl and R 5 is (di)(1-4C)alkylamino, (1-4C)alkoxy, amino, hydroxy, (6C)arylamino, (di)(3-4C)alkenylamino, (2-5C)heteroaryl(1-4C)alkylamino, (6C)aryl(1-4C) alkylamino, (di)[(1-4C)alkoxy(2-4C)alkyl]amino, (di)[(1-4C)alkylamino(2-4C) alkyl]amino, (di)[amino(2-4C)alkyl]amino or (di)[hydroxy(2-4C)alkyl]amino. 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 R 1 and R 2 are Me;
R 3 is (2-6C)heterocycloalkyl(1-4C)alkyl, (2-5C)heteroaryl(1-4C)alkyl, (6C)aryl(1-4C) alkyl, (1-4C)(di)alkylaminocarbonylamino(2-4C)alkyl, (2-6C)heterocycloalkylcarbonylamino(2-4C)alkyl, R 5 -(2-4C)alkyl or R 5 -carbonyl(1-4C)alkyl;
R 4 is (2-5C)heteroaryl, (6C)aryl, (3-8C)cycloalkyl, (2-6C)heterocycloalkyl or (1-6C)alkyl; and
R 5 is (di)(1-4C)alkylamino, (1-4C)alkoxy, amino, hydroxy, (6C)arylamino, (di)(3-4C)alkenylamino, (2-5C)heteroaryl(1-4C)alkylamino, (6C)aryl( 1-4C)alkylamino, (di)[(1-4C)alkoxy(2-4C)alkyl]amino, (di)[(1-4C)alkylamino(2-4C)alkyl]amino, (di)[amino(2-4C)alkyl]amino or (di)[hydroxy(2-4C)alkyl]amino.
2. The derivative according to claim 1 wherein R 3 is (2-6C)heterocycloalkyl(1-4C)alkyl, (2-5C)heteroaryl(1-4C)alkyl, (2-6C)heterocycloalkylcarbonylamino(2-4C)alkyl, R 5 -(2-4C)alkyl or R 5 -carbonyl(1-4C)alkyl.
3. The derivative according to claim 2 wherein R 5 is (di)(1-4C)alkylamino, amino, (di)(3-4C)alkenylamino, (2-5C)heteroaryl(1-4C)alkylamino or (6C)aryl(1-4C)alkylamino.
4. The derivative according to claim 3 wherein R 5 is (di)(1-4C)alkylamino or amino.
5. The derivative according to claim 4 wherein R 5 is (di)(1-4C)alkylamino.
6. The derivative according to claim 1 wherein R 4 is (6C)aryl.
7. The derivative according to claim 6 wherein R 3 is (2-6C)heterocycloalkyl(1-4C)alkyl, (2-5C)heteroaryl(1-4C)alkyl or R 5 -(2-4C)alkyl.
8. A pharmaceutical composition comprising the tetrahydroquinoline derivative of claim 1 and at least one pharmaceutically suitable auxiliary.
9. A method of fertility regulation comprising administering an FSH receptor activity modulating amount of the pharmaceutical composition of claim 8 to a patient in need thereof, wherein the fertility regulation is contraception in a female.