Aminocarbonylcarbamate compounds

Patent metadata

Field	Value
Publication number	US-9833432-B2
Application number	US-201615195326-A
Country	US
Kind code	B2
Filing date	Jun 28, 2016
Priority date	Feb 28, 2014
Publication date	Dec 5, 2017
Grant date	Dec 5, 2017

Abstract

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.

First claim

What is claimed is:

1. A method for inhibiting dopamine reuptake, comprising:
administering a therapeutically effective amount of a compound of Formula I or pharmaceutically acceptable salt thereof to a mammal in need 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 method according to claim 1 , which is for the treatment of central nervous system disease.

3. The method according to claim 1 , which is for the treatment of attention deficit hyperactivity disorder (ADHD).

4. The method according to claim 1 , wherein the compound is administered with at least one pharmaceutically-acceptable carrier.

5. The method according to claim 4 , wherein the carrier is lactose, dibasic calcium phosphate, corn starch or a mixture thereof.

6. The method according to claim 1 , wherein the compound is administered orally.

7. The method according to claim 1 , further comprising one or more additional therapeutic agents.

8. The method according to claim 7 , wherein the one or more additional therapeutic agents are independently selected from the group consisting of amphetamine, methylphenidate, dextroamphetamine, dexmethylphenidate, and lisdexamfetamine.

9. The method according to claim 1 , wherein the mammal is a human subject.

10. The method according to claim 1 , wherein the compound is a compound of Formula (II) or 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; and
R 4 is H— or aryl,
wherein at least one of R 1 , R 2 and R 4 is not H—.

11. The method according to claim 10 , wherein the compound is selected from the group consisting of:
2-(isopropylamino)-3-phenylpropyl (aminocarbonyl)carbamate;
2-(dimethylamino)-3-phenylpropyl (aminocarbonyl)carbamate;
2-(methylamino)-3-phenylpropyl (aminocarbonyl)carbamate; and
2-amino-3-phenylpropyl (anilinocarbonyl)carbamate.

12. The method according to claim 10 , wherein the compound is selected from the group consisting of:
(2R)-2-(isopropylamino)-3-phenylpropyl (aminocarbonyl)carbamate;
(2R)-2-(dimethylamino)-3-phenylpropyl (aminocarbonyl)carbamate;
(2R)-2-(methylamino)-3-phenylpropyl (aminocarbonyl)carbamate; and
(2R)-2-amino-3-phenylpropyl (anilinocarbonyl)carbamate.

13. The method according to claim 10 , wherein the salt is hydrochloride.

14. The method according to claim 1 , wherein the compound is a compound of Formula (III) or 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; 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 method according to claim 14 , wherein the compound 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.

16. The method according to claim 14 , wherein the compound 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.

17. The method according to claim 14 , wherein the salt is hydrochloride.

Assignees

• Sk Biopharmaceuticals Co Ltd

Inventors

• Kang Young-Soon
• Chung Jin-Yong
• Maeng Cheol-Young
• Yi Han-Ju
• Lee Ki-Ho
• Heo Joon
• Chae Eun-Hee
• Shin Yu-Jin

Classifications

• A61K9/0053 Primary

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K31/27 Primary

  of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/325 Primary

  Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof (thiurams A61K31/145) · CPC title

• C07C275/60 Primary

  Y being an oxygen atom, e.g. allophanic acids · CPC title