Imidazoquinolyl compounds having anti-inflammatory, antifungal, antiparasitic, and anticancer activity
Amine compounds having activity against inflammation, fungi, unicellular parasitic microorganisms, and cancer are described. The compounds contain a monocyclic, bicyclic, or tricyclic aromatic ring having one, two, or three ring nitrogen atoms.
1. A compound represented by Formula IC or a pharmaceutically acceptable salt thereof
wherein
R 1 is hydrogen, OH, NH 2 , or N(CH 3 ) 2 ;
R 2 is selected from the group consisting of hydrogen, halo, methyl, and perfluoromethyl;
R 8 is hydrogen, or alkyl having from 1 to 15 carbon atoms unsubstituted or substituted by alkoxy having 1 or 2 carbon atoms or acetoxy; and
R 9 is a branched or unbranched alkyl having from 2 to 16 carbon atoms substituted by alkoxy having from 1 to 12 carbon atom;
and wherein the compound is not 1-(8-Butoxyoctyl)-1H-imidazo[4,5-c]quinoline, 1-(10-Butoxydecyl)-1H-imidazo[4,5-c]quinoline, 1-Octyl-1H-imidazo[4,5-c]quinoline, or 1-Hexadecyl-1H-imidazo[4,5-c]quinolin-4-amine.
2. The compound or salt of claim 1 , wherein R 2 is hydrogen.
3. The compound or salt of claim 2 , wherein the compound is selected from the group consisting of:
1-{5-[3-(Hexyloxy)propoxy]pentyl}-1H-imidazo[4,5-c]quinoline and
1-{3-[3-(Hexyloxy)phenoxy]propyl}-1H-imidazo[4,5-c]quinoline.
4. The compound or salt of claim 2 , wherein R 9 is an unbranched alkyl having from 2 to 10 carbon atoms, substituted by alkoxy having from 1 to 12 carbon atoms.
5. The compound or salt of claim 4 , wherein the compound is selected from the group consisting of:
1-[2-(Dodecyloxy)ethyl]-1H-imidazo[4,5-c]quinoline,
1-[2-(Dodecyloxy)ethyl]-N,N-dimethyl-1H-imidazo[4,5-c]quinolin-4-amine,
1-[6-(Octyloxy)hexyl]-1H-imidazo[4,5-c]quinoline,
1-(8-Ethoxyoctyl)-1H-imidazo[4,5-c]quinoline,
1-(8-Methoxyoctyl)-1H-imidazo[4,5-c]quinoline,
1-[9-(Hexyloxy)nonyl]-1H-imidazo[4,5-c]quinoline,
1-[3-(Decyloxy)propyl]-1H-imidazo[4,5-c]quinoline,
1-[4-(Decyloxy)butyl]-1H-imidazo[4,5-c]quinoline,
1-[8-(Hexyloxy)octyl]-1H-imidazo[4,5-c]quinoline.
6. A pharmaceutical composition comprising an effective amount of the compound or pharmaceutically acceptable salt of claim 1 and a pharmaceutically acceptable carrier.
7. A method for treating a fungal infection in a subject comprising administering to the subject an effective amount of the compound or pharmaceutically acceptable salt of claim 1 .
8. The method of claim 7 , wherein the subject is a human subject.
9. The method of claim 7 , wherein the fungal infection is from a fungus selected from the group consisting of Candida, Saccharomyces, Trichophyton, Cryptococcus, Aspergillus , and Rhizopus.
10. The method of claim 9 , wherein the Candida is Candida albicans or Candida glabrata.
11. The method of claim 9 , wherein the Saccharomyces is Saccharomyces cerevisiae.
12. The method of claim 9 , wherein the Trichophyton is Trichophyton rubrum.
13. The method of claim 9 , wherein the Cryptococcus is Cryptococcus neoformans.
14. The method of claim 13 , wherein the Cryptococcus neoformans is Cryptococcus neoformans serotype D or Cryptococcus neoformans serotype A.
15. The method of claim 9 , wherein the Aspergillus is Aspergillus fumigatus.
16. The method of claim 7 , wherein the compound or pharmaceutically acceptable salt is administered topically to the subject.
17. The method of claim 7 , wherein the compound or pharmaceutically acceptable salt is administered systemically to the subject.
18. The method of claim 17 , wherein the compound or pharmaceutically acceptable salt is administered orally, rectally, parenterally, or nasally.
19. The method of claim 17 , wherein the compound is administered in a dose sufficient to achieve peak concentrations in infected tissues greater than 10 micromolar.