Tetrahydroquinoline derivatives
View Patent ↗The present invention relates to tetrahydroquinoline derivatives having general formula I: or a pharmaceutically acceptable salt thereof, wherein R1 is formyl, (1-6C)alkylcarbonyl or (1-6C)alkylsulfonyl; R2 and R3 are H or (1-4C)alkyl; R4 is phenyl; R5 is (1-4C)alkyl; Y—X is C(O)—O, S(O)2-O, NHC(O)—O, NHC(S)—O, OC(O)—O, bond-O, C(O)—NH, S(O)2-NH, NHC(O)—NH, NHC(S)—NH, OC(O)—NH, bond-NH, NH—C(O), O—C(O), NH—S(O)2, or O—S(O)2 or Y—X is a bond; R6 is H, trifluoromethyl, (1-6C)alkyl, 1- or 2-adamantyl(1-4C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (3-9C)heteroaryl, (3-6C)cycloalkyl, (2-6C)heterocycloalkyl, (1-4C)alkylthio(1-4C)alkyl, (6-10C)aryl(1-4C)alkyl, (3-9C)heteroaryl(1-4C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl, (2-6C)heterocycloalkyl(1-4C)alkyl, R8,R9-aminocarbonyl(1-4C)alkyl, R8,R9-amino(1-4C)alkyl, R8-oxycarbonyl(1-4C)alkyl, R8-oxy(1-4C)alkyl, R8-carbonyl(1-4C)alkyl or (6-10C)aryl; R7 is H, (1-4C)alkyl, (1-4C)alkoxy, halogen, trifluoromethyl, cyano, nitro, hydroxyl; and R8 and/or R9 is H, (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (6-10C)aryl, (3-9C)heteroaryl, (6-10C)aryl(1-4C)alkyl, (3-9C)heteroaryl(1-4C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl, (2-6C)heterocycloalkyl(1-4C)alkyl, (1-4C)(di)alkylamino(1-4C)alkyl, (1-4C)alkoxy(1-4C)alkyl, (1-4C)alkylthio(1-4C)alkyl, (1-4C)alkylcarbonylamino(1-4C)alkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, (1-4C)alkoxycarbonylamino(1-4C)alkyl, (3-6C)cycloalkyl, (2-6C)heterocycloalkyl, or R8 and R9 may be joined in a (2-6C)heterocycloalkyl ring. The present invention also relates to pharmaceutical compositions comprising said derivatives and the use of these derivatives to control fertility.
1. A tetrahydroquinoline compound of Formula I,
or a pharmaceutically acceptable salt thereof, wherein
R 1 is (1-6C)alkylcarbonyl;
R 2 and R 3 are (1-4C)alkyl;
R 4 is phenyl, optionally substituted with one or more substituents selected from the group hydroxy, halogen, (1-4C)alkyl, and (1-4C)alkoxy;
R 5 is (1-4C)alkyl;
Y—X is C(O)—O, C(O)—NH, or OC(O)—NH;
R 6 is (1-6C)alkyl, 1- or 2-adamantyl(1-4C)alkyl, heteroaryl selected from imidazolyl, thiadiazolyl, pyridyl, (benz)thienyl, (benzo)furyl, quinolyl, tetrahydroquinolyl, quinoxalyl, indolyl, thienyl and furyl, phenyl(1-4C)alkyl, (1-4C)alkyl heteroaryl, wherein the heteroaryl is selected from imidazolyl, thiadiazolyl, pyridyl, (benz)thienyl, (benzo)furyl, quinolyl, tetrahydroquinolyl, quinoxalyl, indolyl, thienyl and furyl, heterocycloalkyl(1-4C)alkyl, wherein the heterocycloalkyl is selected from piperidine, morpholine and pyrrolidine, R 8 ,R 9 -aminocarbonyl(1-4C)alkyl, R 8 ,R 9 -amino(1-4C)alkyl, R 8 -oxycarbonyl(1-4C)alkyl, R 8 -oxy(1-4C)alkyl or phenyl, wherein phenyl is optionally substituted with nitro, trifluoromethyl, chlorophenyl, pyridyl, morpholinocarbonyloxy, isoxazolecarbonyloxy, oxazolidinoneoxycarbonyl, (1-4C)alkoxycarbonyl(1-4C)alkylcarbonyloxy, (1-4C)alkylsulfonyloxy, dimethylisoxazolesulfonyloxy, and (di)phenylamino, or one or more of halogens, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)(di)alkylamino, phenyl, and (1-4C)(di)alkylcarbamoyl;
R 7 is H, (1-4C)alkyl, or (1-4C)alkoxy;
R 8 is (1-4C)alkyl, phenyl(1-4C)alkyl, heteroaryl(1-4C)alkyl, wherein the heteroaryl is selected from imidazolyl, thiadiazolyl, pyridyl, (benz)thienyl, (benzo)furyl, quinolyl, tetrahydroquinolyl, quinoxalyl, indolyl, thienyl and furyl, (3-6C)cycloalkyl(1-4C)alkyl, heterocycloalkyl(1-4C)alkyl, wherein the heterocycloalkyl is selected from piperidine, morpholine and pyrrolidine, (1-4C)alkoxy(1-4C)alkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, t-butylcarbamoyl, benzyl optionally substituted with (1-4C)alkoxy or one or more halogens, or R 8 together with R 9 may form a heterocycloalkyl selected from azetidine, pyrrolidine, piperidine, piperazine, thiomorpholine and morpholine, wherein the heterocycloalkyl ring is optionally substituted with phenyl, and
R 9 is H, or (1-4C)alkyl,
wherein the compound is not 1-acetyl-6-benzoylamino-4-(4-methylphenyl)-1,2,3,4-tetrahydro-2,2,4-trimethylquinoline.
2. The tetrahydroquinoline compound of claim 1 , wherein the tetrahydroquinoline compound of formula I, Y—X is C(O)—NH.
3. The tetrahydroquinoline compound of claim 1 , wherein R 6 is heteroaryl selected from imidazolyl, thiadiazolyl, pyridyl, (benz)thienyl, (benzo)furyl, quinolyl, tetrahydroquinolyl, quinoxalyl, indolyl, thienyl and furyl, phenyl(1-4C)alkyl, (1-4C)alkylheteroaryl, wherein the heteroaryl is selected from imidazolyl, thiadiazolyl, pyridyl, (benz)thienyl, (benzo)furyl, quinolyl, tetrahydroquinolyl, quinoxalyl, indolyl, thienyl and furyl, or phenyl optionally substituted with nitro, trifluoromethyl, chlorophenyl, pyridyl, morpholinocarbonyloxy, isoxazolecarbonyloxy, oxazolidinoneoxycarbonyl, (1-4C)alkoxycarbonyl(1-4C)alkylcarbonyloxy, (1-4C)alkylsulfonyloxy, (1-4C)alkylsulfonyloxy, dimethylisoxazolesulfonyloxy, or (di)phenylamino, or one or more of halogens, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)(di)alkylamino, phenyl, and (1-4C)(di)alkylcarbamoyl.