Aminocarbonylcarbamate compounds
The present disclosure provides a compound represented by Formula (I) and a pharmaceutically acceptable salt which are effective as a dopamine reuptake inhibitor and a method of using the compound: wherein X is independently halo, alkyl, alkoxy or nitro; m is 0, 1, 2, 3 or 4; n is 1 or 2; R 1 and R 2 are independently H— or alkyl; R 3 is H—, alkyl or aralkyl; and R 4 is H— or aryl.
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein
X is independently halo, alkyl, alkoxy or nitro;
m is 0, 1, 2, 3 or 4
n is 1 or 2;
R 1 and R 2 are independently H— or alkyl;
R 3 is H—, alkyl or aralkyl; and
R 4 is H— or aryl,
wherein at least one of R 1 , R 2 , R 3 and R 4 is not H—.
2. The compound or pharmaceutically acceptable salt of claim 1 , wherein X is halo, C 1 -C 4 alkyl, C 1 -C 4 alkoxy or nitro; R 1 and R 2 are independently H—or C 1 -C 4 alkyl; R 3 is C 1 -C 4 alkyl or C 6 -C 10 aryl-C 1 -C 4 alkyl; and R 4 is H— or C 6 -C 10 aryl.
3. The compound or pharmaceutically acceptable salt of claim 1 , which is a compound of Formula (II):
wherein
X is independently halo, alkyl, alkoxy or nitro;
m is 0, 1, 2, 3 or 4;
n is 1 or 2;
R 1 and R 2 are independently H— or alkyl; and
R 4 is H— or aryl,
wherein at least one of R 1 , R 2 and R 4 is not H—.
4. The compound or pharmaceutically acceptable salt according to claim 3 , wherein X is H—, halo, C 1 -C 4 alkyl, C 1 -C 4 alkoxy or nitro; R 1 and R 2 are independently H— or C 1 -C 4 alkyl; and R 4 is H— or C 6 -C 10 aryl.
5. The compound or pharmaceutically acceptable salt according to claim 3 , wherein m is 1, 2, 3 or 4 and each X is independently halo, methyl, tent-butyl, ethoxy or nitro.
6. The compound or pharmaceutically acceptable salt according to claim 3 , wherein R 1 and R 2 are independently H—, methyl or isopropyl.
7. The compound or pharmaceutically acceptable salt according to claim 3 , wherein R 4 is H— or phenyl.
8. The compound or pharmaceutically acceptable salt according to claim 3 , wherein R 4 is H—.
9. The compound or pharmaceutically acceptable salt according to claim 3 , wherein n is 1, and R 4 is H—.
10. The compound or pharmaceutically acceptable salt according to claim 3 , which is selected from the group consisting of:
2-(isopropylamino)-3-phenylpropyl (aminocarbonyl)carbamate;
2-(dimethylamino)-3-phenylpropyl (aminocarbonyl)carbamate;
2-amino-3-(2-chlorophenyl)propyl (aminocarbonyl)carbamate;
2-amino-3-(2,4-dichlorophenyl)propyl (aminocarbonyl)carbamate;
2-amino-3-(3,4-dichlorophenyl)propyl (aminocarbonyl)carbamate;
2-amino-3-(4-chlorophenyl)propyl (aminocarbonyl)carbamate;
2-amino-3-(3-chlorophenyl)propyl (aminocarbonyl)carbamate;
2-amino-3-(4-nitrophenyl)propyl (aminocarbonyl)carbamate;
2-amino-3-(4-tert-butylphenyl)propyl (aminocarbonyl)carbamate;
2-amino-3-(2-fluorophenyl)propyl (aminocarbonyl)carbamate;
2-(methylamino)-3-phenylpropyl (aminocarbonyl)carbamate; and
2-amino-3-phenylpropyl (anilinocarbonyl)carbamate.
11. The compound or pharmaceutically acceptable salt according to claim 3 , wherein the compound is a substantially pure stereoisomer.
12. The compound or pharmaceutically acceptable salt according to claim 11 , which is selected from the group consisting of:
(2R)-2-(isopropylamino)-3-phenylpropyl (aminocarbonyl)carbamate;
(2R)-2-(dimethylamino)-3-phenylpropyl (aminocarbonyl)carbamate;
(2R)-2-amino-3-(2-chlorophenyl)propyl (aminocarbonyl)carbamate;
(2R)-2-amino-3-(2,4-dichlorophenyl)propyl (aminocarbonyl)carbamate;
(2R)-2-amino-3-(3,4-dichlorophenyl)propyl (aminocarbonyl)carbamate;
(2R)-2-(methylamino)-3-phenylpropyl (aminocarbonyl)carbamate; and
(2R)-2-amino-3-phenylpropyl (anilinocarbonyl)carbamate.
13. The compound or pharmaceutically acceptable salt according to claim 1 , wherein the salt is hydrochloride.
14. The compound or pharmaceutically acceptable salt of claim 1 , which is a compound of Formula (III):
wherein
X is independently halo, alkyl, alkoxy or nitro;
m is 0, 1, 2, 3 or 4;
n is 1 or 2;
R 1 and R 2 are independently H— or alkyl; and
R 3 is H—, alkyl or aralkyl,
wherein at least one of R 1 , R 2 and R 3 is not H—.
15. The compound or pharmaceutically acceptable salt according to claim 14 , wherein X is H—, halo, C 1 -C 4 alkyl, C 1 -C 4 alkoxy or nitro; and R 1 and R 2 are independently H— or C 1 -C 4 alkyl.
16. The compound or pharmaceutically acceptable salt according to claim 14 , wherein m is 1, 2, 3 or 4 and each X is independently halo, methyl, tert-butyl, ethoxy or nitro.
17. The compound or pharmaceutically acceptable salt according to claim 14 , wherein R 1 and R 2 are independently H—, methyl or isopropyl.
18. The compound or pharmaceutically acceptable salt according to claim 14 , wherein R 3 is C 1 -C 4 alkyl or C 6 -C 10 aryl-C 1 -C 4 alkyl.
19. The compound or pharmaceutically acceptable salt according to claim 14 , wherein R 3 is methyl, ethyl or benzyl.
20. The compound or pharmaceutically acceptable salt according to claim 14 , wherein n is 1 and R 3 is H—.
21. The compound or pharmaceutically acceptable salt according to claim 14 , which is selected from the group consisting of:
2-amino-3-phenylpropyl (aminocarbonyl)methylcarbamate;
2-(dimethylamino)-3-phenylpropyl (aminocarbonyl)methylcarbamate;
2-amino-3-phenylpropyl (aminocarbonyl)benzylcarbamate;
2-amino-3-phenylpropyl (aminocarbonyl)ethylcarbamate;
2-amino-3-(2-chlorophenyl)propyl (aminocarbonyl)methylcarbamate;
2-amino-3-(4-fluorophenyl)propyl (aminocarbonyl)methylcarbamate;
2-amino-3-(4-chlorophenyl)propyl (aminocarbonyl)methylcarbamate;
2-amino-3-(2,4-dichlorophenyl)propyl (aminocarbonyl)methylcarbamate;
2-amino-3-(3,4-dichlorophenyl)propyl (aminocarbonyl)methylcarbamate;
2-amino-3-(4-nitrophenyl)propyl (aminocarbonyl)methylcarbamate;
2-amino-3-(4-methylphenyl)propyl (aminocarbonyl)methylcarbamate;
2-amino-3-(4-ethoxyphenyl)propyl (aminocarbonyl)methylcarbamate; and
2-amino-4-phenylbutyl (aminocarbonyl)methylcarbamate.
22. The compound or pharmaceutically acceptable salt according to claim 14 , wherein the compound is a substantially pure stereoisomer.
23. The compound or pharmaceutically acceptable salt according to claim 22 , which is selected from the group consisting of:
(2R)-2-amino-3-phenylpropyl (aminocarbonyl)methylcarbamate;
(2R)-2-(dimethylamino)-3-phenylpropyl (aminocarbonyl)methylcarbamate;
(2R)-2-amino-3-phenylpropyl (aminocarbonyl)benzylcarbamate;
(2R)-2-amino-3-phenylpropyl (aminocarbonyl)ethylcarbamate;
(2R)-2-amino-3-(2-chlorophenyl)propyl (aminocarbonyl)methylcarbamate;
(2R)-2-amino-3-(4-chlorophenyl)propyl (aminocarbonyl)methylcarbamate;
(2R)-2-amino-3-(2,4-dichlorophenyl)propyl (aminocarbonyl)methylcarbamate;
(2R)-2-amino-3-(3,4-dichlorophenyl)propyl (aminocarbonyl)methylcarbamate;
(2S)-2-amino-3-phenylpropyl (aminocarbonyl)methylcarbamate;
(2R)-2-amino-3-(4-nitrophenyl)propyl (aminocarbonyl)methylcarbamate;
(2R)-2-amino-3-(4-methylphenyl)propyl (aminocarbonyl)methylcarbamate;
(2R)-2-amino-3-(4-ethoxyphenyl)propyl (aminocarbonyl)methylcarbamate; and
(2R)-2-amino-4-phenylbutyl (aminocarbonyl)methylcarbamate.
24. The compound or pharmaceutically acceptable salt according to claim 14 , wherein the salt is hydrochloride.
25. A pharmaceutical composition comprising a therapeutically effective amount of the compound or pharmaceutically acceptable salt of claim 1 and a pharmaceutically acceptable carrier.
26. The pharmaceutical composition of claim 25 , which is an oral formulation.
27. The pharmaceutical composition of claim 25 , further comprising an active ingredient which is effective to treat ADHD.
28. The compound or pharmaceutically acceptable salt according to claim 1 , wherein m is 0.
29. The compound or pharmaceutically acceptable salt according to claim 14 , wherein m is 0.