Lipidated imidazoquinoline derivatives
The compounds of the subject invention are adjuvant molecules that comprise a imidazoquinoline molecule covalently linked to a phospho- or phosphonolipid group. The compounds of the invention have been shown to be inducers of interferon-a, IL-12 and other immunostimulatory cytokines and possess an improved activity profile in comparison to known cytokine inducers when used as adjuvants for vaccine antigens.
1. A compound comprising Formula I
wherein
R 1 ═H, C 1-6 alkyl, C 1-3 alkoxyC 1-3 alkyl, C 3-6 cycloalkylC 1-3 alkoxy, C 3-6 cycloalkylC 1-3 alkyl
Z═C 2 -C 6 alkyl or alkenyl, unsubstituted or terminally substituted by —(O—C 2 -C 6 alkyl) 1-6 -
Y═O, NH
X═O, CH 2 , CF 2
W═O or S
m=1-2,
wherein
R 2 ═H or straight/branched/unsaturated C 4 -C 24 alkyl or acyl
R 3 =straight/branched/unsaturated C 4 -C 24 alkyl or acyl
R 4 , R 5 =independently H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, or trifluoromethyl; or taken together alternatively form a 6-membered aryl, heteroaryl containing one nitrogen atom, cycloalkyl, or heterocycloalkyl ring containing one nitrogen atom; unsubstituted or substituted by one or more of C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, or trifluoromethyl, or pharmaceutically acceptable salts thereof.
2. A compound having Formula II
wherein
R 1 ═H, C 1-6 alkyl, C 1-3 alkoxyC 1-3 alkyl, C 3-6 cycloalkylC 1-3 alkoxy, C 3-6 cycloalkylC 1-3 alkyl
n=1-6
X═O, CH 2 , CF 2
Y═O, NH
W═O or S
m=1-2,
R 2 ═H or straight/branched/unsaturated C 4 -C 24 alkyl or acyl
R 3 =straight/branched/unsaturated C 4 -C 24 alkyl or acyl.