Sigma receptor inhibitors
The invention relates to compounds of formula (I) having pharmacological activity towards the sigma receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use for the treatment and or prophylaxis of a disease in which the sigma receptor is involved.
1. A compound of the formula I:
wherein
R 1 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted heterocyclylalkyl, —COR 8 , —C(O)OR 8 , —C(O)NR 8 R 9 , —CH═NR 8 , —CN, —OR 8 , —OC(O)R 8 , —NR 8 R 9 , —NR 8 C(O)R 9 , —NO 2 , —N═CR 8 R 9 , and halogen;
R 2 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, —COR 8 , —C(O)OR 8 , —CH═NR 8 , —CN, —OR 8 , —OC(O)R 8 , —S(O) t —R 8 , —NR 8 R 9 , —NR 8 C(O)R 9 , —NO 2 , —N═CR 8 R 9 , and halogen;
R 3 and R 4 are independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, —COR 8 , —C(O)OR 8 , —C(O)NR 8 R 9 , —CH═NR 8 , —CN, —OR 8 , —OC(O)R 8 , —S(O) t —R 8 , —NR 8 R 9 , —NR 8 C(O)R 9 , —NO 2 , —N═CR 8 R 9 , and halogen, or together they form a fused ring system,
R 5 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, —COR 8 , —C(O)OR 8 , —C(O)NR 8 R 9 , —CH═NR 8 , —CN, —OR 8 , —OC(O)R 8 , —S(O) t —R 8 , —NR 8 R 9 , —NR 8 C(O)R 9 , —NO 2 , —N═CR 8 R 9 , and halogen;
R 6 is selected from the group consisting of hydrogen, substituted or unsubstituted ethyl, n-propyl, i-propyl, n-butyl, t-butyl or n-pentyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, —COR 8 , —C(O)OR 8 , —C(O)NR 8 R 9 , —CH═NR 8 , —CN, —OR 8 , —OC(O)R 8 , —S(O) t —R 8 , —NR 8 R 9 , —NR 8 C(O)R 9 , —NO 2 , —N═CR 8 R 9 , and halogen;
n is 1 or 2;
t is 1 or 2;
R 8 and R 9 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryloxy, and halogen;
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 wherein R 1 is H, —COR 8 , or substituted or unsubstituted alkyl.
3. The compound according to claim 1 wherein R 1 is H, methyl or acetyl.
4. The compound according to claim 1 wherein R 1 is hydrogen.
5. The compound according to claim 1 wherein R 2 is H or alkyl.
6. The compound according to claim 1 wherein R 2 is methyl or H.
7. The compound according to claim 1 wherein R 3 and R 4 are situated in the meta and para positions of the phenyl group.
8. The compound according to claim 1 wherein R 3 and R 4 are independently selected from the group consisting of halogen, and substituted or unsubstituted alkyl.
9. The compound according to claim 1 wherein R 3 and R 4 are independently selected from the group consisting of halogen and haloalkyl.
10. The compound according to claim 1 wherein n is 2.
11. A compound according to claim 1 which is selected from the group consisting of:
2-[1-(3,4-Dichlorophenyl)-5-methyl-1H-pyrazol-3-yloxy]-N,N-diethylethanamine;
2-[1-(3,4-Dichlorophenyl)-5-isopropyl-1H-pyrazol-3-yloxy]-N,N-diethylethanamine;
2-[1-(3,4-dichlorophenyl)-1H-pyrazol-3-yloxy]-N,N-diethylethanamine;
2-[1-(3,4-Dichlorophenyl)-4,5-dimethyl-1H-pyrazol-3-yloxy]-N,N-diethylethanamine;
1-{1-(3,4-dichlorophenyl)-3-[2-(diethylamino)ethoxy]-5-methyl-1H-pyrazol-4-yl}ethanone; and
N,N-Diethyl-2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethanamine
or a pharmaceutically acceptable salt thereof.
12. A pharmaceutical composition comprising the compound as defined in claim 1 and a pharmaceutically acceptable carrier, adjuvant or vehicle.
13. The compound according to claim 1 wherein R 5 and R 6 are both ethyl.
14. The compound according to claim 1 wherein R 5 is methyl and R 6 is benzyl.