Synthesis and antimicrobial activity of novel dicationic “reversed amidines”
The present invention relates to novel 2,5-bis{[alkyl (or aryl) imino]aminophenyl}furans and thiophenes of the general formula in which R 1 , R 2 , R 3 and R 4 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, and alkylhalide groups; R 5 is H, alkyl or aryl; R 6 is H, alkyl, aryl, or NR 7 R 8 , in which R 7 and R 8 are each independently selected from the group consisting of H, alkyl and aryl; and X is O, S or NR 9 , in which R 9 is H or alkyl, and to the use of such compounds.
1. A compound according to Formula I:
wherein:
R 1 , R 2 , R 3 and R 4 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, and alkylhalide groups;
R 5 is H, alkyl or aryl;
R 6 is H, alkyl, aryl, or NR 7 R 8 , wherein R 7 and R 8 are each independently selected from the group consisting of H, alkyl and aryl; and
X is S or NR 9 , wherein R 9 is H or alkyl.
2. The compound according to claim 1 , wherein R 1 and R 2 are each an H.
3. The compound according to claim 1 , wherein R 1 and R 2 are each an H and R 3 and R 4 are each lower alkyls.
4. The compound according to claim 1 , wherein R 3 and R 4 are each a halide.
5. The compound according to claim 1 , wherein R 3 and R 4 are each alkoxy.
6. The compound according to claim 1 , wherein R 3 and R 4 are each alkyl halides.
7. The compound according to claim 1 , wherein R 5 is an H, R 6 is a NR 7 R 8, and R 7 and R 8 are each an H.
8. The compound according to claim 1 , wherein R 6 is a pyridyl.
9. The compound according to claim 1 , wherein R 6 is a substituted pyridyl.
10. The compound according to claim 1 , wherein R 6 is a quinolinyl.
11. A pharmaceutical composition comprising a compound according to Formula I:
wherein:
R 1 , R 2 , R 3 and R 4 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, and alkylhalide groups;
R 5 is H, alkyl or aryl;
R 6 is H, alkyl, aryl, or NR 7 R 8, wherein R 7 and R 8 are each independently selected from the group consisting of H, alkyl and aryl; and
X is S or NR 9 , wherein R 9 is H or alkyl; in a pharmaceutically acceptable carrier.
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.
15. A process for preparing a pharmaceutical composition comprising admixing the compound of Formula (I) according to claim 1 and optionally a pharmaceutically utilizable carrier.
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 an effective amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof:
wherein:
wherein R 1 , R 2 , R 3 and R 4 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, and alkylhalide groups;
R 5 is H, alkyl or aryl;
R 6 is H, alkyl, aryl, or NR 7 R 8 , wherein R 7 and R 8 are each independently selected from the group consisting of H, alkyl and aryl; and
X is S or NR 9 , wherein R 9 is H or alkyl.
17. 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 lambila, Plasmodium spp., Pneumocystis carinii, Toxoplasma pondii, Fusarium solani , and Cryptococcus neoformans , said method comprising administering to the subject an effective amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof:
wherein:
wherein R 1 , R 2 , R 3 and R 4 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, and alkylhalide groups:
R 5 is H, alkyl or aryl:
R 6 is H, alkyl, aryl, or NR 7 R 8 , wherein R 7 and R 8 are each independently selected from the group consisting of H, alkyl and aryl: and
X is S or NR 9 , wherein R 9 is H or alkyl,
wherein the compound is administered parenterally.
18. 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 an effective amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof:
wherein:
wherein R 1 , R 2 , R 3 and R4 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, and alkylhalide groups:
R 5 is H, alkyl or aryl:
R 6 is H, alkyl, aryl, or NR 7 R 8 , wherein R 7 and R 8 are each independently selected from the group consisting of H, alkyl and aryl; and
X is S or NR 9 , wherein R 9 is H or alkyl,
wherein the compound is administered orally.
19. 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 an effective amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof:
wherein:
wherein R 1 , R 2 , R 3 and R4 are each independently selected from the group consisting of H, alkyl, alkoxy, halide, and alkylhalide groups:
R 5 is H, alkyl or aryl:
R 6 is H, alkyl, aryl, or NR 7 R 8 , wherein R 7 and R 8 are each independently selected from the group consisting of H, alkyl and aryl; and
X is S or NR 9 , wherein R 9 is H or alkyl,
wherein the compound is administered topically.