β-Cyclodextrin derivatives

• US 7,851,457 B2
• Filed: 01/28/2005
• Issued: 12/14/2010
• Est. Priority Date: 01/29/2004
• Status: Expired due to Fees

• Current Assignee: Innovative Biologics, Inc.
• Original Assignee: Innovative Biologics, Inc.
• Inventors: Karginov, Vladimir, Fahmi, Noureddine, Hecht, Sidney
• Primary Examiner(s): Zeman; Robert A
• Application Number:
  US11/045,423
• Publication Number:
  US 20060247208A1
• Time in Patent Office: 2,146 Days
• Field of Search: None
• US Class Current: 514/58
• CPC Class Codes: A61K 31/724 Cyclodextrins
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: C08B 37/0012 Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof

Abstract

The invention provides low molecular weight compounds that block the pore formed by protective antigen and inhibit anthrax toxin action. Structures of the compounds are derivatives of β-cyclodextrin. Per-substituted alkylamino derivates displayed inhibitory activity, and they were protective against anthrax lethal toxin action at low micromolar concentrations. Also, the addition of one of the alkylamino derivatives to the bilayer lipid membrane with multiple PA channels caused a significant decrease in membrane conductance. Thus, the invention also provides methods for protection against anthrax toxicity.

Claims

1. A compound according to the formula

2. The compound according to claim 1, wherein R₆ is NH₂, SCH₂CH₂NH₂, SCH₂CH₂CH₂NH₂, or SCH₂CH₂CH₂CH₂NH₂.

3. The compound according to claim 1, wherein R₆ is NH₂, N₃ or aminoalkyl.

4. The compound according to claim 1, wherein R₆ is SH, S-alkylguanidyl or S-aminoalkyl.

5. The compound according to claim 1, wherein R₆ is O-alkylguanidyl, O-aminoalkyl or OSO₃Na.

6. The compound according to claim 1, wherein R₆ is lower alkyl, aralkyl, aryl or heterocyclic ring(s).

7. The compound according to claim 1, wherein R₆ is I.

8. A compound according to the formula

9. The compound according to claim 8, wherein R₆ is aminoalkyl.

10. The compound according to claim 8, wherein R₆ is SH, lower alkyl, S-alkylguanidyl or S-aminoalkyl.

11. The compound according to claim 8, wherein R₆ is O-alkylguanidyl, or O-aminoalkyl.

12. The compound according to claim 8, wherein R₆ is lower alkyl, aralkyl, aryl or heterocyclic ring(s).

13. The compound according to claim 8, wherein R₆ is SCH₂CH₂NH₂, SCH₂CH₂CH₂NH₂, or SCH₂CH₂CH₂CH₂NH₂.

14. The compound according to claim 8, wherein R₆ is I.