Quinoline derivatives and their use as 5-HT
Disclosed are quinoline compounds having affinity for the 5-HT 6 receptor and having the formula: where R 1 , R 2 , R 3 , R 4 , R 5 , n, m, p and A are defined herein, and salts thereof, compositions containing these compounds and salts and processes for making and using the same.
1. A compound of formula (I):
wherein:
R 1 and R 2 independently represent hydrogen or C 1-6 alkyl or R 1 is linked to R 2 to form a group (CH 2 ) 2 , (CH 2 ) 3 or (CH 2 ) 4 ;
R 3 , R 4 and R 5 independently represent hydrogen, halogen, cyano, —CF 3 , —CF 3 O, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkanoyl or a group —CONR 6 R 7 , wherein R 6 and R 7 independently represent hydrogen or C 1-6 alkyl;
m represents an integer from 1 to 4,
or m is an integer greater than 1, and two R 2 groups are linked to form a CH 2 , (CH 2 ) 2 or (CH 2 ) 3 group;
n represents an integer from 1 to 3;
p represents 1 or 2;
A represents an aryl group wherein said aryl is optionally substituted by 1, 2 or 3 substituents which may be the same or different, and which are selected from the group consisting of halogen, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, trifluoromethanesulfonyloxy, pentafluoroethyl, C 1-6 alkoxy, arylC 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkoxyC 1-6 alkyl, C 3-7 cycloalkylC 1-6 alkoxy, C 1-6 alkanoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyloxy, C 1-6 alkylsulfonylC 1-6 alkyl, arylsulfonyl, arylsulfonyloxy, arylsulfonylC 1-6 alkyl, C 1-6 alkylsulfonamido, C 1-6 alkylamido, C 1-6 alkylsulfonamidoC 1-6 alkyl, C 1-6 alkylamidoC 1-6 alkyl, arylsulfonamido, arylcarboxamido, arylsulfonamidoC 1-6 alkyl, arylcarboxamidoC 1-6 alkyl, aroyl, aroylC 1-6 alkyl, arylC 1-6 alkanoyl, and a group CONR 8 R 9 or SO 2 NR 8 R 9 , wherein R 8 and R 9 independently represent hydrogen or C 1-6 alkyl;
or a pharmaceutically acceptable salt thereof.
2. The compound or salt according to claim 1 , wherein R 1 represents hydrogen, methyl, ethyl, isopropyl, isobutyl or 2,2-dimethylpropyl.
3. The compound or salt according to claim 1 , wherein R 1 represents hydrogen or methyl.
4. The compound or salt according to claim 1 , wherein R 2 represents hydrogen, methyl.
5. The compound or salt according to claim 1 , wherein m is 1 and R 2 represents 3-methyl or 2-methyl, or m is 2 and R 2 represents 3,3-dimethyl or 2,5-dimethyl.
6. The compound or salt according to claim 1 , wherein R 2 is linked to R 1 to form a (CH 2 ) 3 group.
7. The compound or salt according to claim 1 , wherein R 2 represents hydrogen or methyl.
8. The compound or salt according to claim 1 , wherein R 3 represents hydrogen, methyl or halogen.
9. The compound or salt according to claim 1 , wherein R 3 represents hydrogen.
10. The compound or salt according to claim 1 , wherein R 4 and R 5 independently represent hydrogen or methyl.
11. The compound or salt according to claim 1 , wherein n represents 1.
12. The compound or salt according to claim 1 , wherein m and p independently represent 1 or 2.
13. The compound or salt according to claim 1 , wherein m and p both represent 1.
14. The compound or salt according to claim 1 , wherein m represents 2 and both R 2 groups are linked to form a CH 2 group linking C-2 and C-5 of the piperazine ring.
15. The compound or salt according to claim 1 , wherein A represents an optionally substituted phenyl.
16. The compound or salt according to claim 15 , wherein A represents a phenyl optionally substituted with halogen, cyano, trifluoromethyl or trifluoromethoxy.
17. The compound or salt according to claim 15 , wherein A is unsubstituted phenyl.
18. The compound or salt according to claim 1 , wherein A represents a phenyl substituted by halogen, C 1-6 alkyl, C 1-6 alkoxy, trifluoromethyl or trifluoromethoxy.