Polyamine transport selective therapeutic agents with enhanced stability

Patent metadata

Field	Value
Publication number	US-9346741-B2
Application number	US-201314388856-A
Country	US
Kind code	B2
Filing date	Mar 14, 2013
Priority date	Mar 28, 2012
Publication date	May 24, 2016
Grant date	May 24, 2016

Abstract

Disclosed herein are di-substituted aryl polyamine compounds and methods of making and using the same. The di-substituted polyamine compounds act as PTS targeting agents, which selectively target the polyamine transport system (PTS) with high efficacy and have improved stability in the presence of amine oxidases.

First claim

What is claimed is:

1. A compound of the following the formula:
R′HN—(CH 2 ) x —NH—(CH 2 ) y —NH—CH 2 —R—CH 2 —NH—(CH 2 ) xx —NH—(CH 2 ) yy —NHR″  (I)

wherein R is selected from the group consisting of anthracene, naphthalene, and benzene;
wherein x, xx, y, and yy are independently selected from the group consisting of 3 and 4;
or a pharmaceutically acceptable salt thereof; wherein R′ and R″ are independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, and butyl.

2. The compound of claim 1 , wherein R′ and R″ are each methyl.

3. The compound of claim 1 , wherein x, xx, y, and yy are each 4.

4. The compound of claim 1 , wherein x, xx, y, and yy are each 3.

5. The compound of claim 1 , wherein R′ and R″=methyl, wherein x, xx, y, and yy are each 4, and wherein R=anthracene.

6. The compound of claim 1 , wherein R′ and R″=methyl, wherein x, xx, y, and yy are each 4, and wherein R=naphthalene.

7. The compound of claim 1 , wherein R′ and R″=methyl, wherein x, xx, y, and yy are each 4, and wherein R=benzene.

8. A compound of the following the formula:

wherein R is selected from the group consisting of anthracene, naphthalene, and benzene; and
or a pharmaceutically acceptable salt thereof; wherein each R′ is independently selected from the group consisting of methyl, ethyl, propyl, isopropyl and butyl.

9. The compound of claim 8 , wherein each R′ is methyl.

10. The compound of claim 8 , wherein R=anthracene.

11. The compound of claim 8 , wherein R=naphthalene.

12. The compound of claim 8 , wherein R=benzene.

13. A compound of the following the formula:

wherein R is selected from the group consisting of anthracene (6b), naphthalene (7b), and benzene (8b); and
wherein R′ is methyl;
or a pharmaceutically acceptable salt thereof.

14. The compound of claim 13 , wherein R=naphthalene.

15. The compound of claim 13 , wherein R=anthracene.

16. The compound of claim 13 , wherein R=benzene.

17. A method for treating a disorder characterized by unrestrained cell proliferation and/or differentiation, wherein the method comprises administering to a subject a composition comprising a compound of claim 1 in an amount effective to reduce an amount of cell proliferation or differentiation, wherein the disorder is breast cancer, leukemia or melanoma.

Assignees

• Phanstiel Iv Otto
• Muth Aaron
• Univ Central Florida Res Found

Inventors

• Phanstiel Iv Otto
• Muth Aaron

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/138

  Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377) · CPC title

• C07C211/30

  the six-membered aromatic ring being part of a condensed ring system formed by two rings · CPC title

• A61K31/785 Primary

  Polymers containing nitrogen · CPC title

• A61K31/137

  Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} · CPC title