Synthesis and antimicrobial activity of novel dicationic ''reversed amidines''

• US 20080058372A1
• Filed: 07/09/2007
• Published: 03/06/2008
• Est. Priority Date: 11/06/2000
• Status: Active Grant

• Current Assignee: Duke University, Georgia State University Research Foundation, Inc., University of North Carolina At Chapel Hill (University of North Carolina System)
• Original Assignee: Duke University, Georgia State University Research Foundation, Inc., University of North Carolina At Chapel Hill (University of North Carolina System)
• Inventors: Stephens, Chad, Wilson, W., Tidwell, Richard, Boykin, David, Perfect, John
• Granted Patent: US 7,745,456 B2
• Time in Patent Office: Days
• US Class Current: 514/314
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07D 307/10 with substituted hydrocarbon radicals attached to ring carbon atoms
• CPC Class Codes: C07D 307/14 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 307/52 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 333/20 by nitrogen atoms nitro, nitroso radicals C07D333/12
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to novel 2,5-bis{[alkyl(or aryl)imino]aminophenyl}furans and thiophenes of the general formula
in which R₁, R₂, R₃ and R₄ are each independently selected from the group consisting of H, alkyl, alkoxy, halide, and alkylhalide groups; R₅ is H, alkyl or aryl; R₆ is H, alkyl, aryl, or NR₇R₈, in which R₇ and R₈ are each independently selected from the group consisting of H, alkyl and aryl; and X is O, S or NR₉, in which R₉ is H or alkyl, and to the use of such compounds.

Claims

1. A compound according to Formula I:

2. The compound according to claim 1, wherein R₁ and R₂ are each an H.

3. The compound according to claim 1, wherein R₁ and R₂ are each an H and R₃ and R₄ are each lower alkyls.

4. The compound according to claim 1, wherein R₃ and R₄ are each a halide.

5. The compound according to claim 1, wherein R₃ and R₄ are each alkoxy.

6. The compound according to claim 1, wherein R₃ and R₄ are each alkyl halides.

7. The compound according to claim 1, wherein R₅ is an H, R₆ is a NR₇R₈, and R₇ and R₈ are each an H.

8. The compound according to claim 1, wherein R₆ is a pyridyl.

9. The compound according to claim 1, wherein R₆ is a substituted pyridyl.

10. The compound according to claim 1, wherein R₆ is a quinolinyl.

15. A process for preparing a pharmaceutical composition comprising formulating the compound of the formula (I) according to claim 1 and optionally a pharmaceutically utilizable carrier.

11. A pharmaceutical composition comprising a compound according to Formula I:

12. The pharmaceutical composition of claim 11, wherein the composition is formulated for parenteral administration.

13. The pharmaceutical composition of claim 11, wherein the composition is formulated for oral administration.

14. The pharmaceutical composition of claim 11, wherein the composition is formulated for topical administration.

16. A method of treating an microbial infection in a subject in need of such treatment, wherein the microbial infection is caused by a microorganism selected from the group consisting of Mycobacterium tuberculosis, Trypanosoma spp., Candida albicans, Aspergillus spp., Cryptosporidium parvum, Giardia lamblia, Plasmodium spp., Pneumocystis carinii, Toxoplasma gondii, Fusarium solani, and Cryptococcus neoformans, said method comprising administering to the subject a compound according to Formula I or a pharmaceutically acceptable salt thereof:

17. The method according to claim 16, wherein the compound is administered parenterally.

18. The method according to claim 16, wherein the compound is administered orally.

19. The method according to claim 16, wherein the compound is administered topically.