Compounds for delivering amino acids or peptides with antioxidant activity into mitochondria and use thereof

• US 7,585,846 B2
• Filed: 11/26/2004
• Issued: 09/08/2009
• Est. Priority Date: 11/25/2003
• Status: Expired due to Fees

• Current Assignee: University of Rochester
• Original Assignee: University of Rochester
• Inventors: Xu, Lin, Sharma, Virendra K., Anders, Marion W., Sheu, Shey-Shing
• Primary Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US10/580,803
• Publication Number:
  US 20070099845A1
• Time in Patent Office: 1,747 Days
• Field of Search: None
• US Class Current: 514/1.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 5/0215 containing natural amino acids, forming a peptide bond via their side chain functional group, e.g. epsilon-Lys, gamma-Glu

Abstract

Disclosed are hydrophilic choline/N-heterocycle ester compounds containing single amino acids, peptides, or derivatives thereof which have the potential to express anti-oxidant activity capable of reducing reactive oxygen species in cells. These compounds may be used to inhibit oxidative stress-induced cell injury or death both in vivo and ex vivo. In addition, methods for the synthesis of these compounds are disclosed.

Claims

1. A compound having the structural formula (I) or (II)

2. The compound according to claim 1 wherein Z¹ is a direct link and Z² is an aliphatic or non-aliphatic C1 to C10 hydrocarbon group.

3. The compound according to claim 1 wherein Z¹ is a direct link and Z² is an aliphatic or non-aromatic cyclic group.

4. The compound according to claim 1 wherein Z¹ is an aliphatic or non-aliphatic C1 to C10 hydrocarbon group and Z² is an aliphatic or non-aliphatic C1 to C10 hydrocarbon group.

5. The compound according to claim 1 wherein Z¹ is an aliphatic or non-aliphatic C1 to C10 hydrocarbon group and Z² is an aliphatic or non-aromatic cyclic group.

6. The compound according to claim 1 wherein Z¹ is a single, fused or multi-ring aromatic group and Z² is an aliphatic or non-aliphatic C1 to C10 hydrocarbon group.

7. The compound according to claim 1 wherein Z¹ is a single, fused or multi-ring aromatic group and Z² is an aliphatic or non-aromatic cyclic group.

8. The compound according to claim 1 wherein Z¹ is an aliphatic or non-aromatic cyclic group and Z² is an aliphatic or non-aliphatic C1 to C10 hydrocarbon group.

9. The compound according to claim 1 wherein Z¹ is an aliphatic or non-aromatic cyclic group and Z² is an aliphatic or non-aliphatic cyclic group.

10. The compound according to claim 1 having a structure according to formula (I).

11. The compound according to claim 10 wherein Q¹, Q², and Q³ are independently aliphatic C1 to C5 hydrocarbon group.

12. The compound according to claim 10 wherein Q² and Q³ together form an aliphatic N-heterocycle group.

13. The compound according to claim 1 having a structure according to formula (II).

14. The compound according to claim 13 wherein Q² is present, and the N-heterocyclic possessing a quaternary nitrogen is, pyrrolidinyl, morpholinyl, or piperidinyl.

15. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to claim 1.