Piperidine and piperazine derivatives
View Patent ↗Compounds of general formula (Ia): in which R 1 , A 1 , m, X, n, Y and R 3 have any of the meanings given in the specification, have affinity for sigma receptors and are useful in the treatment of disorders of the central nervous system.
1. A compound of general formula (Ia)
in which:
R 1 represents a phenyl group that is substituted by one, two, or three substituents selected independently from a halogen atom, a cyano group, a halo(1-4C) alkyl group, a (1-6C)alkoxy group, and a halo(1-4C)alkoxy group;
A 1 represents (CH 2 ) m ;
m is 3;
X is CH or N;
n is 2;
Y is O, NR 2 , or S;
R 2 is hydrogen, (1-4C)alkyl or phenyl(1-4C)alkyl, or is as defined for R 3 ; and
R 3 represents a phenyl group that is substituted by one, two, or three substituents selected independently from a halogen atom, a cyano group, a halo(1-4C) alkyl group, a (1-4C)alkoxy group, and a halo(1-4C)alkoxy group;
or a pharmaceutically acceptable salt thereof.
2. A compound as claimed in claim 1 , in which X is N.
3. A compound as claimed in claim 2 , in which Y is O or NR 2 .
4. A compound as claimed in claim 3 , in which Y is NR 2 and R 2 is hydrogen.
5. A compound as claimed in claim 3 , in which Y is O.
6. A compound as claimed in claim 1 , in which R 3 represents 2-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 4-chlorophenyl, 4-cyanophenyl, or 2-trifluoromethylphenyl.
7. A compound as claimed in claim 6 , in which R 3 represents a 4-fluorophenyl group.
8. A compound as claimed in claim 1 , which is 1-[2-(2-Fluorophenoxy)ethyl]-4-[3-(4-trifluoromethoxyphenyl)propyl]piperazine, 1-[2-(2-Fluorophenoxy)ethyl]-4-[3-(3,4,5-trimethoxyphenyl)propyl]piperazine, 1-[2-(4-Fluorophenoxy)ethyl]-4-[3-(3,4,5-trimethoxyphenyl)propyl]piperazine, 1-[2-(4-Fluorophenoxy)ethyl]-4-[3-(4-isopropoxyphenyl)propyl]piperazine, or 1-[2-(4-Fluorophenoxy)ethyl]-4-[3-(4-methoxyphenyl)propyl]piperazine, or a pharmaceutically acceptable salt thereof.
9. A compound which is 1-[2-(2-Fluorophenoxy)ethyl]-4-[3-(4-trifluoromethoxyphenyl)propyl]piperazine or a pharmaceutically acceptable salt thereof.
10. A compound which is 1-[2-(2-Fluorophenoxy)ethyl]-4-[3-(4-trifluoromethoxyphenyl)propyl]piperazine dihydrochloride.
11. A compound as claimed in claim 1 , in which R 1 is selected from 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4-difluorophenyl, 3-chlorophenyl, 3-methylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-isopropoxyphenyl, 3,4-dimethoxyphenyl, 2,3,4-trimethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-fluoro-3,4-dimethoxyphenyl, 3-chloro-4-methoxyphenyl, 4-chloro-3-methoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, or 4-trifluoromethoxyphenyl.
12. A compound as claimed in claim 11 , in which R 1 is selected from 4-trifluoromethoxyphenyl, 3,4,5-trimethoxyphenyl, 4-methoxyphenyl, or 4-isopropoxyphenyl.