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US 6,756,382 B2Granted
Amide substituted imidazoquinolines
Assignee3M Innovative Properties Company
InventorsPatrick L. Coleman, Stephen L. Crooks, George W. Griesgraber, Kyle J. Lindstrom, Bryon A. Merrill, Michael J. Rice
Life of this patent
Estimating the term…
Abstract
Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain amide 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.
Claims23
A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula (I):
- wherein
- R1 is —C2-4 alkyl-NR3—CO—R4 wherein R4 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, or alkyl;
- R2 is selected from the group consisting of:
- -hydrogen;
- -alkyl;
- -alkenyl;
- -aryl;
- -(substituted aryl);
- -heteroaryl;
- -(substituted heteroaryl);
- -heterocyclyl;
- -(substituted heterocyclyl);
- -alkyl-O-aryl;
- -alkyl —O-alkyl;
- -alkyl-O-alkenyl;
- and
- -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
- —OH;
- -halogen;
- —N(R3)2;
- —CO—N(R3)2;
- —CO—C1-10 alkyl;
- —CO—O—C1-10 alkyl;
- —N3;
- -aryl;
- -(substituted aryl);
- -heteroaryl;
- -(substituted heteroaryl);
- -heterocyclyl;
- -(substituted heterocyclyl);
- —CO-aryl;
- and
- —CO-heteroaryl;
- each R3 is independently selected from the group consisting of hydrogen;
- C1-10 alkyl-heteroaryl;
- C1-10 alkyl-(substituted heteroaryl);
- C1-10 alkyl-aryl;
- C1-10 alkyl-(substituted aryl) and C1-10 alkyl;
- n is 0 to 4;
- and each R present is independently selected from the group consisting of C1-10 alkyl, C1-10 alkoxy, halogen and trifluoromethyl,
- wherein the substituent(s) of the substituted aryl are indenendently selected from the groun consisting of alkyl, alkoxy, alkythio, hydroxy, halogen, haloalkyl, haloalkylcarbonyl, haloalkoxy, nitro, alkylcarbonyl, alkenylcarbonyl, arylcarbonyl, heteroarvicarbonyl, aryl, arvialkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocycloalkyl, nitrile, alkoxycarbonyl, alkanoyloxy, and alkanovithi;
- or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
39 more elements
A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula (Ib):
- wherein
- R1 is C2-4 alkyl-NR3-CO—R4 wherein R4 is heterocyclyl or substituted heterocyclyl;
- R2 is selected from the group consisting of:
- -hydrogen;
- -alkyl;
- -alkenyl;
- -aryl;
- -(substituted aryl);
- -heteroaryl;
- -(substituted heteroaryl);
- -heterocyclyl;
- -(substituted heterocyclyl);
- -alkyl-O-aryl;
- -alkyl —O-alkyl;
- -alkyl-O-alkenyl;
- and
- -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
- —OH;
- -halogen;
- —N(R3)2;
- —CO—N(R3)2;
- —CO—C1-10 alkyl;
- —CO—O—C1-10 alkyl;
- —N3;
- -aryl;
- -(substituted aryl);
- -heteroaryl;
- -(substituted heteroaryl);
- -heterocyclyl;
- -(substituted heterocyclyl);
- —CO-aryl;
- and
- —CO-heteroaryl;
- each R3 is independently selected from the group consisting of hydrogen;
- C1-10 alkyl-heteroaryl;
- C1-10 alkyl-(substituted heteroaryl);
- C1-10 alkyl-aryl;
- C1-10 alkyl-(substituted aryl) and C1-10 alkyl;
- n is 0 to 4;
- and each R present is independently selected from the group consisting of C1-10 alkyl, C1-10 alkoxy, halogen and trifluoromethyl, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
37 more elements
A compound of the formula (Id):
- wherein
- R1 is —C2-4 alkyl-NR3—CO—R4 wherein R4 is heteroaryl or substituted heteroaryl;
- R2 is selected from the group consisting of:
- -hydrogen;
- -alkyl;
- -alkenyl;
- -aryl;
- -(substituted aryl);
- -heteroaryl;
- -(substituted heteroaryl);
- -heterocyclyl;
- -(substituted heterocyclyl);
- -alkyl-O-aryl;
- -alkyl —O-alkyl;
- -alkyl-O-alkenyl;
- and
- -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
- —OH;
- -halogen;
- —N(R3)2;
- —CO—N(R3)2;
- —CO—C1-10 alkyl;
- —CO—O—C1-10 alkyl;
- —N3;
- -aryl;
- -(substituted aryl);
- -heteroaryl;
- -(substituted heteroaryl);
- -heterocyclyl;
- -(substituted heterocyclyl);
- —CO-aryl;
- and
- —CO-heteroaryl;
- each R3 is independently selected from the group consisting of hydrogen;
- C1-10 alkyl-heteroaryl;
- C1-10 alkyl-(substituted heteroaryl);
- C1-10 alkyl-aryl;
- C1-10 alkyl-(substituted aryl) and C1-10 alkyl;
- n is 0 to 4;
- and each R present is independently selected from the group consisting of C1-10 alkyl, C1-10 alkoxy, halogen and trifluoromethyl, or a pharmaceutically acceptable salt thereof.
37 more elements
A compound of the formula (Ie):
- wherein
- R1 is —C2-4 alkyl-NR3—CO—C1-8 alkyl;
- R2 is selected from the group consisting of:
- -hydrogen;
- -alkyl;
- -alkenyl;
- -aryl;
- -(substituted aryl);
- -heteroaryl;
- -(substituted heteroaryl);
- -heterocyclyl;
- -(substituted heterocyclyl);
- -alkyl-O-aryl;
- -alkyl —O-alkyl;
- -alkyl-O-alkenyl;
- and
- -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
- —OH;
- -halogen;
- —N(R3)2;
- —CO—N(R3)2;
- —CO—C1-10 alkyl;
- —N3;
- -aryl;
- -(substituted aryl);
- -heteroaryl;
- -(substituted heteroaryl);
- -heterocyclyl;
- -(substituted heterocyclyl);
- —CO-aryl;
- and
- —CO-heteroaryl;
- each R3 is independently selected from the group consisting of hydrogen;
- C1-10 alkyl-heteroaryl;
- C1-10 alkyl-(substituted heteroaryl);
- C1-10 alkyl-aryl;
- C1-10 alkyl-(substituted aryl) and C1-10 alkyl;
- n is 0 to 4;
- and each R present is independently selected from the group consisting of C1-10 alkyl, C1-10 alkoxy, halogen and trifluoromethyl, or a pharmaceutically acceptable salt thereof.
36 more elements
A pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the group consisting of:
- (2S,3S)-N-{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-1-methyl-5-oxo-2-pyridin-3-ylpyrrolidine-3-carboxamide;
- N-{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl)}-1-[(4-tert-butylphenyl)sulfonyl]-L-prolinamide;
- N-[8-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)octyl]benzamide;
- N-{8-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]octyl}benzamide;
- N-[3-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]benzamide;
- N-{3-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2,2-dimethylpropyl}benzamide;
- N-[8-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)octyl]benzamide;
- N-{3-[4-amino-2-(3-phenoxypropyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}-4-bromobenzamide;
- N-{3-[4-amino-2-(3-phenoxypropyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}benzamide;
- N-{3-[4-amino-2-(2-methoxyethyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl]propyl}benzamide;
- and
- N-{3-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}benzamide;
- or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable carrier.
10 more elements
A compound selected from the group consisting of:
- N-{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}isoquinoline-3-carboxamide;
- N-{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}quinoline-3-carboxamide;
- N-{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}quinoxaline-2-carboxamide;
- N-[3-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]isoquinoline-3-carboxamide;
- N-{3-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}isoquinoline-3-carboxamide;
- N-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]cyclopentanecarboxamide;
- N-[4-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]cyclohexanecarboxamide;
- N-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-methylpropanamide;
- N-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]butanamide;
- N-[4-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]cyclopentanecarboxamide;
- N-[4-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-methylpropanamide;
- N-[4-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]butanamide;
- N-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]cyclohexanecarboxamide;
- N-[3-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]cyclohexanecarboxamide;
- N-[3-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]cyclopentanecarboxamide;
- N-[3-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]-2-methylpropanamide;
- N-[3-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]butanamide;
- and
- N-{2-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethyl}-2-ethoxyacetamide;
- or a pharmaceutically acceptable salt thereof.
17 more elements
Dependencies are inferred from the claim text.