Urea substituted imidazoquinolines
View Patent ↗Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain urea, thiourea, acylurea, or sulfonylurea functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases.
1. A compound of the formula:
wherein
bonds represented by the dashed lines are present or absent;
R 1 is —C 2-6 alkyl-NR 3 —CY—NR 5 —R 4 ;
Y is ═O;
R 3 is hydrogen;
R 4 is C 1-10 to alkyl, and R 5 is hydrogen, or R 4 and R 5 combine to form a morpholine ring;
and
R 2 is selected from the group consisting of C 1-4 alkyl and C 1-4 alkyl-O—C 1-4 alkyl;
or a pharmaceutically acceptable salt thereof.
2. The compound or salt of claim 1 wherein the bonds represented by the dashed lines are absent, and R 4 and R 5 combine to form a morpholine ring.
3. The compound or salt of claim 2 wherein the compound is N-[4-(4-amino-2-methyl-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl)butyl]morpholine-4-carboxamide.
4. The compound or salt of claim 1 wherein bonds represented by the dashed lines are present; R 4 is ethyl, 1-methylethyl, or n-propyl; and R 2 is C 1-4 alkyl, ethoxymethyl, or methoxyethyl.
5. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 1 in combination with a pharmaceutically acceptable carrier.
6. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 2 in combination with a pharmaceutically acceptable carrier.
7. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 3 in combination with a pharmaceutically acceptable carrier.
8. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 4 in combination with a pharmaceutically acceptable carrier.
9. A method of inducing cytokine biosynthesis in an animal comprising administering a therapeutically effective amount of a compound or salt of claim 1 to the animal wherein the cytokine is interferon α and/or tumors necrosis factors α.
10. A method of inducing cytokine biosynthesis in an animal comprising administering a therapeutically effective amount of a compound or salt of claim 2 to the animal wherein the cytokine is interferon α and/or tumors necrosis factors α.
11. A method of inducing cytokine biosynthesis in an animal comprising administering a therapeutically effective amount of a compound or salt of claim 3 to the animal wherein the cytokine is interferon α and/or tumors necrosis factors α.
12. A method of inducing cytokine biosynthesis in an animal comprising administering a therapeutically effective amount of a compound or salt of claim 4 to the animal wherein the cytokine is interferon α and/or tumors necrosis factors α.