Methods for treatment of renal failure

• US 20070082958A1
• Filed: 10/06/2005
• Published: 04/12/2007
• Est. Priority Date: 10/06/2005
• Status: Active Grant

• Current Assignee: Rappaport Family Institute, TECHNION RESEARCH AND DEVELOPMENT FOUNDATION, LTD.
• Original Assignee: Rappaport Family Institute, TECHNION RESEARCH AND DEVELOPMENT FOUNDATION, LTD.
• Inventors: Abassi, Zaid, Binah, Ofer, Youdim, Moussa
• Granted Patent: US 8,263,655 B2
• Time in Patent Office: Days
• US Class Current: 514/657
• CPC Class Codes: A61K 31/131 acyclic
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61P 13/12 of the kidneys

Abstract

Propargylamine, propargylamine derivatives including N-propargyl-1-aminoindan and analogs thereof, and pharmaceutically acceptable salts thereof, are useful for prevention or treatment of renal failure.

Claims

1. A method for treatment of a subject susceptible to or suffering from renal failure which comprises administering to the subject an amount of an active agent selected from the group consisting of propargylamine, a propargylamine derivative, and a pharmaceutically acceptable salt thereof, effective to treat the subject.

2. A method according to claim 1 wherein the renal failure is acute renal failure (ARF).

3. A method according to claim 1 wherein the renal failure is chronic renal failure (CRF).

4. A method according to claim 1 wherein said active agent is selected from the group consisting of N-propargyl-1-aminoindan, an enantiomer thereof, an analog thereof, and a pharmaceutically acceptable salt of the aforesaid.

5. A method according to claim 4 wherein said active agent is racemic N-propargyl-1-aminoindan.

6. A method according to claim 4 wherein said active agent is the enantiomer R(+)-N-propargyl-1-aminoindan.

7. A method according to claim 4 wherein said active agent is the enantiomer S-(−

)-N-propargyl-1-aminoindan.

8. A method according to claim 4 wherein said active agent is a pharmaceutically acceptable salt of R(+)-N-propargyl-1-aminoindan or S-(−

)-N-propargyl-1-aminoindan.

9. A method according to claim 8 wherein said pharmaceutically acceptable salt is selected from the group consisting of the mesylate salt;

the esylate salt;

the sulfate salt; and

the hydrochloride salt of R(+)-N-propargyl-1-aminoindan or S-(−

)-N-propargyl-1-aminoindan.

10. A method according to claim 4 wherein said analog of N-propargyl-1-aminoindan is selected from the group consisting of 4-fluoro-N-propargyl-1-aminoindan, 5-fluoro-N-propargyl-1-aminoindan, 6-fluoro-N-propargyl-1-aminoindan, an enantiomer thereof and pharmaceutically acceptable addition salts thereof.

11. A method according to claim 4 wherein said analog of N-propargyl-1-aminoindan is selected from the group consisting of:

(rac)-3-(N-methyl,N-propyl-carbamyloxy)-α

-methyl-N′

-propargyl phenethylamine HCl;

(rac)-3-(N,N-dimethyl-carbamyloxy)-α

-methyl-N′

-methyl,N′

-propargyl phenethylamine HCl;

(rac)-3-(N-methyl,N-hexyl-carbamyloxy)-α

-methyl-N′

-methyl,N′

-propargyl phenethylamine mesylate;

(rac)-3-(N-methyl,N-cyclohexyl-carbamyloxy)-α

-methyl-N′

-methyl,N′

-propargyl phenethylamine HCl; and

(S)-3-(N-methyl,N-hexyl-carbamyloxy)-α

-methyl-N′

-methyl,N′

-propargyl phenethylamine ethanesulfonate.

12. A method according to claim 4 wherein said analog of N-propargyl-1-aminoindan is selected from the group consisting of:

(rac) 6-(N-methyl,N-ethyl-carbamyloxy)-N′

-propargyl-1-aminoindan HCl;

(rac) 6-(N,N-dimethyl,carbamyloxy)-N′

-methyl-N′

-propargyl-1-aminoindan HCl;

(rac) 6-(N-methyl,N-ethyl-carbamyloxy-N′

-propargyl-1-aminotetralin HCl;

(rac) 6-(N,N-dimethyl-thiocarbamyloxy)-1-aminoindan HCl;

(rac) 6-(N-propyl-carbamyloxy-N′

-propargyl-1-aminoindan HCl;

(rac) 5-chloro-6-(N-methyl,N-propyl-carbamyloxy)-N′

-propargyl-1-aminoindan HCl;

(S)-6-(N-methyl),N-propyl-carbamyloxy)-N′

-propargyl-1-aminoindan HCl; and

(R)-6-(N-methyl,N-ethyl-carbamyloxy)-N′

-propargyl-1-aminoindan hemi-(L)-tartrate. 6 and 6-(N-methyl,N-ethyl-carbamyloxy)-N′

-methyl,N′

-propargyl-1-aminoindan.

13. A method according to claim 1 wherein said active agent is propargylamine or an aliphatic propargylamine.

14. A method according to claim 13 wherein said aliphatic propargylamine is selected from the group consisting of the compounds N-(1-heptyl)propargylamine or a propargylamine;

N-(1-octyl)propargylamine;

N-(1-nonyl)propargylamine;

N-(1-decyl)propargyl-amine;

N-(1-undecyl)propargylamine;

N-(1-dodecyl)propgyl-amine;

R—

N-(2-butyl)propargylamine;

R—

N-(2-pentyl)propargylamine;

R—

N-(2-hexyl)propargylamine;

R—

N-(2-heptyl)propargylamine;

R—

N-(2-octyl)propargyl-amine;

R—

N-(2-nonyl)propargylamine;

R—

N-(2-decyl)propargylamine, R—

N-(2-undecyl)propargylamine;

R—

N-(2-dodecyl)propargylamine;

N-(1-butyl)-N-methyl-propargyl-amine;

N-(2-butyl)-N-methylpropargylamine;

N-(2-pentyl)-N-methyl-propargyl-amine;

N-(1-pentyl)-N-methylpropargylamine;

N-(2-hexyl)-N-methyl-propargyl-amine;

N-(2-heptyl)-N-methylpropargylamine;

N-(2-decyl)-N-methyl-propargyl-amine;

N-(2-dodecyl)-N-methylpropargylamine;

R(−

)-N-(2-butyl)-N-methyl-propargylamine;

or a pharmaceutically acceptable salt thereof.

15. A method according to claim 1 wherein said active agent is selected from the group consisting of selegiline, desmethylselegiline, pargyline, chlorgyline, and (N-methyl-N-propargyl-10-aminomethyl-dibenzo[b,f]oxepin.

16. A method for treatment of a subject susceptible to or suffering from renal failure caused by congestive heart failure which comprises administering to the subject an amount of an active agent selected from the group consisting of propargylamine, a propargylamine derivative, and a pharmaceutically acceptable salt thereof, effective to treat the subject.

17. The method according to claim 16 wherein said agent is R(+)-N-propargyl-1-aminoindan, S-(−

)-N-propargyl-1-aminoindan or a pharmaceutically acceptable salt thereof.

18. An article of manufacture comprising packaging material and a pharmaceutical composition contained within the packaging material, said pharmaceutical composition comprising an active agent selected from propargylamine, a propargylamine derivative or a pharmaceutically acceptable salt thereof, and said packaging material includes a label that indicates that said agent is therapeutically effective for treating renal failure.