Pyrido[4,3-b]indoles containing rigid moieties
View Patent ↗This disclosure is directed to pyrido[4,3-b]indoles having rigid moieties. The compounds in one embodiment are pyrido[4,3-b]indoles having an unsaturated hydrocarbon moiety. The compounds in another embodiment are pyrido[4,3-b]indoles having a cycloalkyl, cycloalkenyl or heterocyclyl moiety. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.
1. A method of treating a disorder selected from the group consisting of schizophrenia and Parkinson's disease in an individual comprising administering to an individual in need thereof an effective amount of a compound of the formula (J-1):
wherein:
R 1 is substituted or unsubstituted C 1 -C 8 alkyl or perhaloalkyl;
R 4 is halo, trifluoromethyl, C 1 -C 8 unsubstituted alkyl or substituted amino;
R 12 is halo, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C 1 -C 8 perhaloalkyl, C 1 -C 8 alkoxy; the bond indicates the presence of either an E or Z double bond configuration; and
Q is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein R 1 is methyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, or 3-hydroxy-3-methyl-but-1-yl; R 4 is CF 3 , CH 3 , F or Cl; R 12 is F, CH 3 , ethyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tert-butyl, CF 3 , phenyl, pyridin-4-yl, —CH 2 CO 2 H, —CH 2 CONHCH 3 , or methoxy; and Q is 4-fluorophenyl, 4-methoxyphenyl, 3-fluoro-4-methoxyphenyl, pyridin-3-yl, pyridin-4-yl, 6-methylpyridin-3-yl, 6-trifluoromethylpyridin-3-yl, or pyrimidin-4-yl.
3. The method of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein R 1 is substituted or unsubstituted C 1 -C 8 alkyl.
5. The method of claim 3 , wherein and Q is substituted or unsubstituted heteroaryl.
6. The method of claim 1 , wherein the disorder is schizophrenia.
7. The method of claim 1 , wherein the disorder is Parkinson's disease.
8. The method of claim 1 , wherein the compound is of the formula (J-1a):
or a pharmaceutically acceptable salt thereof.
9. The method of claim 1 , wherein the compound is of the formula (J-1b):
or a pharmaceutically acceptable salt thereof.
10. The method of claim 8 , wherein R 1 is unsubstituted C 1 -C 8 alkyl.
11. The method of claim 10 , wherein R 1 is methyl.
12. The method of claim 8 , wherein R 4 is methyl or chloro.
13. The method of claim 12 , wherein R 4 is methyl.
14. The method of claim 8 , wherein R 12 is unsubstituted C 1 -C 8 alkyl.
15. The method of claim 14 , wherein R 12 is methyl.
16. The method of claim 8 , wherein Q is substituted or unsubstituted pyridyl.
17. The method of claim 16 , wherein Q is 3-pyridyl.
18. The method of claim 16 , wherein Q is 4-pyridyl.
19. The method of claim 16 , wherein Q is 6-methyl-3-pyridyl.