4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives as medicaments for the treatment of infertility
View Patent ↗The present invention relates to 2-methyl-4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives having the general Formula (I) wherein the substituents are defined as in the description, or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said derivatives, as well as to the use of these 2-methyl-4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives in therapy, more specifically for the treatment of fertility disorders.
1. A 2-methyl-4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to Formula 1,
wherein
R 1 is (1-6C)alkyl, (2-6C)alkenyl or (2-6C)alkynyl;
R 2 is halogen;
R 3 is SO 2 NR 5 R 6 or (1-4C)alkoxy, optionally substituted with one of more fluorine atoms;
X is O or NR 7 ;
R 4 is R 8 —(2-8C)alkyl, R 8 —(3-8C)alkenyl, R 8 —(3-8C)alkynyl or R 8 —(2-4C)alkoxy-(2-4C)alkyl;
Z is CN or NO 2 ;
R 5 and R 6 are independently H or (1-4C)alkyl; or
R 5 together with R 6 and the N to which they are bonded form a 3-8 membered saturated ring optionally containing a further heteroatom selected from O and S;
R 8 is OH, (1-4C)alkoxy, NH 2 ; NR 9 C(O)R 11 , NR 9 SO 2 R 11 or C(O)NR 9 R 10 ;
R 7 and R 9 are independently H or (1-4C)alkyl;
R 10 is (1-4C)alkyl, (1-4C)alkoxy(1-4C)alkyl, or phenyl(1-4C)alkyl or
(2-5C)heteroaryl(1-4C)alkyl, both optionally substituted on the (hetero)aromatic ring with one or more substituents selected from OH, NH 2 , halogen, NO 2 , CF 3 , CN, (1-4C)alkyl, (1-4C)alkoxy and (di)(1-4C)alkylamino;
R 11 is (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkoxy(1-4C)alkyl, (3-6C)-cycloalkyl, (1-4C)alkoxy, (di)(1-4C)alkylamino, or phenyl or (2-5C)heteroaryl, both optionally substituted on the (hetero)aromatic ring with one or more substituents selected from OH, NH 2 , halogen, NO 2 , CF 3 , CN, (1-4C)alkyl, (1-4C)alkoxy and (di)(1-4C)alkylamino; or a pharmaceutically acceptable salt thereof.
2. The 2-methyl-4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative of claim 1 , wherein X is O.
3. The 2-methyl-4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative of claim 1 , wherein R 1 is (1-6C)alkyl.
4. The 2-methyl-4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative of claim 1 , wherein R 2 is Cl, Br or I.
5. The 2-methyl-4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative of claim 1 , wherein Z is CN.
6. The 2-methyl-4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative of claim 1 , wherein R 3 is SO 2 NR 5 R 6 .
7. A pharmaceutical composition comprising a 2-methyl-4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative of claim 1 or a pharmaceutically acceptable salt thereof, and pharmaceutically suitable auxiliaries.