US2004157874A1PendingUtilityA1
Amido ether substituted imidazoquinolines
Est. expiryDec 8, 2020(expired)· nominal 20-yr term from priority
A61P 37/02A61P 31/12C07D 471/04
51
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Claims
Abstract
Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain ether and 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.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of the formula (I):
wherein: X is —CHR 5 —, —CHR 5 -alkyl-, or —CHR 5 -alkenyl-;
R 1 is selected from the group consisting of:
—R 4 —CR 3 —Z-R 6 -alkyl;
—R 4 —CR 3 —Z-R 6 -alkenyl;
—R 4 —CR 3 —Z-R 6 -aryl;
—R 4 —CR 3 —Z-R 6 -heteroaryl;
—R 4 —CR 3 —Z-R 6 -heterocyclyl;
—R 4 —CR 3 —Z-H;
—R 4 —NR 7 —CR 3 —R 6 -alkyl;
—R 4 —NR 7 —CR 3 —R 6 -alkenyl;
—R 4 —NR 7 —CR 3 —R 6 -aryl;
—R 4 —NR 7 —CR 3 —R 6 -heteroaryl;
—R 4 —NR 7 —CR 3 —R 6 -heterocyclyl; and
—R 4 —NR 7 —CR 3 —R 8 ;
each Z is independently —NR 5 —, —O—, or —S—;
R 2 is selected from the group consisting of:
-hydrogen;
-alkyl;
-alkenyl;
-aryl;
-heteroaryl;
-heterocyclyl;
-alkyl-Y-alkyl;
-alkyl-Y-alkenyl;
-alkyl-Y-aryl; and
-alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
—OH;
-halogen;
—N(R 5 ) 2 ;
—CO—N(R 5 ) 2 ;
—CO—C 1-10 alkyl;
—CO—O—C 1-10 alkyl;
—N 3 ;
-aryl;
-heteroaryl;
-heterocyclyl;
—CO-aryl; and
—CO-heteroaryl;
each R 3 is ═O or ═S;
each R 4 is independently alkyl or alkenyl, which may be interrupted by one or more —O— groups;
each R 5 is independently H or C 1-10 alkyl;
R 6 is a bond, alkyl, or alkenyl, which may be interrupted by one or more —O— groups;
R 7 is H, C 1-10 alkyl, or arylalkyl; or R 4 and R 7 can join together to form a ring;
R 8 is H or C 1-10 alkyl; or R 7 and R 8 can join together to form a ring;
each Y is independently —O— or —S(O) 0-2 —;
n is 0 to 4; and
each R present is independently selected from the group consisting of C 1-10 alkyl, C 1-10 alkoxy, hydroxy, halogen and trifluoromethyl;
or a pharmaceutically acceptable salt thereof.
2 . A compound or salt of claim 1 wherein the heteroaryl is selected from the group consisting of 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-thiazolyl, and 4-pyrazolyl.
3 . A compound or salt of claim 1 wherein X is —CH(alkyl)(alkyl)- wherein the alkyl groups can be the same or different.
4 . A compound or salt of claim 1 wherein X is —CH 2 —CH 2 —.
5 . A compound or salt of claim 1 wherein X is —CH(C 2 H 5 )(CH 2 )—.
6 . A compound or salt of claim 1 wherein R 2 is H.
7 . A compound or salt of claim 1 wherein R 2 is alkyl.
8 . A compound or salt of claim 1 wherein R 2 is -alkyl-O-alkyl.
9 . A compound of the formula (II)
wherein: X is —CHR 5 —, —CHR 5 -alkyl-, or —CHR 5 -alkenyl-;
R 1 is selected from the group consisting of:
—R 4 —CR 3 —Z-R 6 -alkyl;
—R 4 —CR 3 —Z-R 6 -alkenyl;
—R 4 —CR 3 —Z-R 6 -aryl;
—R 4 —CR 3 —Z-R 6 -heteroaryl;
—R 4 —CR 3 —Z-R 6 -heterocyclyl;
—R 4 —CR 3 —Z-H;
—R 4 —NR 7 —CR 3 —R 6 -alkyl;
—R 4 —NR 7 —CR 3 —R 6 -alkenyl;
—R 4 —NR 7 —CR 3 —R 6 -aryl;
—R 4 —NR 7 —CR 3 —R 6 -heteroaryl;
—R 4 —NR 7 —CR 3 —R 6 -heterocyclyl; and
—R 4 —NR 7 —CR 3 —R 8 ;
each Z is independently —NR 5 —, —O—, or —S—;
R 2 is selected from the group consisting of:
-hydrogen;
-alkyl;
-alkenyl;
-aryl;
-heteroaryl;
-heterocyclyl;
-alkyl-Y-alkyl;
-alkyl-Y-alkenyl;
-alkyl-Y-aryl; and
-alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
—OH;
-halogen;
—N(R 5 ) 2 ;
—CO—N(R 5 ) 2 ;
—CO—C 1-10 alkyl;
—CO—O—C 1-10 alkyl;
—N 3 ;
-aryl;
-heteroaryl;
-heterocyclyl;
—CO-aryl; and
—CO-heteroaryl;
each R 3 is ═O or ═S;
each R 4 is independently alkyl or alkenyl, which may be interrupted by one or more —O— groups;
each R 5 is independently H or C 1-10 alkyl;
R 6 is a bond, alkyl, or alkenyl, which may be interrupted by one or more —O— groups;
R 7 is H, C 1-10 alkyl, arylalkyl; or R 4 and R 7 can join together to form a ring;
R 8 is H or C 1-10 alkyl; or R 7 and R 8 can join together to form a ring;
each Y is independently —O— or —S(O) 0-2 —;
n is 0 to 4; and
each R present is independently selected from the group consisting of C 1-10 alkyl, C 1-10 alkoxy, hydroxy, halogen, and trifluoromethyl;
or a pharmaceutically acceptable salt thereof.
10 . A compound or salt of claim 9 wherein R 2 is H or alkyl.
11 . A compound or salt of claim 9 wherein R 2 is -alkyl-O-alkyl.
12 . A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 1 and a pharmaceutically acceptable carrier.
13 . 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.
14 . The method of claim 13 wherein the cytokine is IFN-α.
15 . A method of treating a viral disease in an animal comprising administering a therapeutically effective amount of a compound or salt of claim 1 to the animal.
16 . A method of treating a neoplastic disease in an animal comprising administering a therapeutically effective amount of a compound or salt of claim 1 to the animal.
17 . A compound of the formula (III):
wherein: X is —CHR 5 —, —CHR 5 -alkyl-, or —CHR 5 -alkenyl-;
R 1 is selected from the group consisting of:
—R 4 —CR 3 —Z-R 6 -alkyl;
—R 4 —CR 3 —Z-R 6 -alkenyl;
—R 4 —CR 3 —Z-R 6 -aryl;
—R 4 —CR 3 —Z-R 6 -heteroaryl;
—R 4 —CR 3 —Z-R 6 -heterocyclyl;
—R 4 —CR 3 —Z-H;
—R 4 —NR 7 —CR 3 —R 6 -alkyl;
—R 4 —NR 7 —CR 3 —R 6 -alkenyl;
—R 4 —NR 7 —CR 3 —R 6 -aryl;
—R 4 —NR 7 —CR 3 —R 6 -heteroaryl;
—R 4 —NR 7 CR 3 —R 6 -heterocyclyl; and —R 4 —NR 7 —CR 3 —R 8 ;
each Z is independently —NR 5 —, —O— or —S—;
R 2 is selected from the group consisting of:
-hydrogen;
-alkyl;
-alkenyl;
-aryl;
-heteroaryl;
-heterocyclyl;
-alkyl-Y-alkyl;
-alkyl-Y-alkenyl;
-alkyl-Y-aryl; and
-alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
—OH;
-halogen;
—N(R 5 ) 2 ;
—CO—N(R 5 ) 2 ;
—CO—C 1-10 alkyl;
—CO—O—C 1-10 alkyl;
—N 3 ;
-aryl;
-heteroaryl;
-heterocyclyl;
—CO-aryl; and
—CO-heteroaryl;
each R 3 is ═O or ═S;
each R 4 is independently alkyl or alkenyl, which may be interrupted by one or more —O— groups;
each R 5 is independently H or C 1-10 alkyl;
R 6 is a bond, or is alkyl, or alkenyl, which may be interrupted by one or more —O— groups;
R 7 is H, C 1-10 alkyl, or arylalkyl; or R 4 and R 7 can join to form a ring;
R 8 is H or C 1-10 alkyl; or R 7 and R 8 can join to form a each Y is independently —O— or —S(O) 0-2 —;
n is 0 to 4; and
each R present is independently selected from the group consisting of C 1-10 alkyl, C 1-10 alkoxy, hydroxy, halogen and trifluoromethyl;
or a pharmaceutically acceptable salt thereof.
18 . A compound of the formula (IV):
wherein X is —CHR 5 —, —CHR 5 -alkyl-, or —CHR 5 -alkenyl-;
R 1 is selected from the group consisting of:
—R 4 —CR 3 Q-R 6 -alkyl;
—R 4 —CR 3 -Q-R 6 -alkenyl;
—R 4 —CR 3 -Q-R 6 -aryl;
—R 4 —CR 3 -Q-R 6 -heteroaryl;
—R 4 —CR 3 -Q-R 6 -heterocyclyl;
—R 4 —CR 3 -Q-H;
—R 4 —NR 5 —CR 3 —R 6 -alkyl;
—R 4 —NR 5 —CR 3 —R 6 -alkenyl;
—R 4 —NR 7 —CR 3 —R 6 -aryl;
—R 4 —NR 7 —CR 3 —R 6 -heteroaryl;
—R 4 —NR 7 —CR 3 —R 6 -heterocyclyl; and
—R 4 —NR 7 —CR 3 —R 8 ;
each Q is independently —NR 5 — or —O—:
each R 3 is ═O or ═S;
each R 4 is independently alkyl or alkenyl, which may be interrupted by one or more —O— groups;
each R 5 is independently H or C 1-10 alkyl;
R 6 is a bond, alkyl, or alkenyl, which may be interrupted by one or more —O— groups;
R 7 is H, C 1-10 alkyl, or arylalkyl; or R 4 and R 7 can join to form a ring;
R 8 is H or C 1-10 alkyl; or R 7 and R 8 can join to form a ring;
n is 0 to 4; and
each R present is independently selected from the group consisting of C 1-10 alkyl, C 1-10 alkoxy, halogen and trifluoromethyl;
or a pharmaceutically acceptable salt thereof.
19 . A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 9 and a pharmaceutically acceptable carrier.
20 . A method of inducing cytokine biosynthesis in an animal comprising administering a therapeutically effective amount of a compound or salt of claim 9 to the animal.
21 . The method of claim 20 wherein the cytokine is IFN-α.
22 . A method of treating a viral disease in an animal comprising administering a therapeutically effective amount of a compound or salt of claim 9 to the animal.
23 . A method of treating a neoplastic disease in an animal comprising administering a therapeutically effective amount of a compound or salt of claim 9 to the animal.
24 . A compound of the formula (V):
wherein: X is —CHR 5 —, —CHR 5 -alkyl-, or —CHR 5 -alkenyl-;
R 2 is selected from the group consisting of:
-hydrogen;
-alkyl;
-alkenyl;
-aryl;
-heteroaryl;
-heterocyclyl;
-alkyl-Y-alkyl;
-alkyl-Y-alkenyl;
-alkyl-Y-aryl; and
-alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
—OH;
-halogen;
—N(R 5 ) 2 ;
—CO—N(R 5 ) 2 ;
—CO—C 1-10 alkyl;
—CO—O—C 1-10 alkyl;
—N 3 ;
-aryl;
-heteroaryl;
-heterocyclyl;
—CO-aryl; and
—CO-heteroaryl;
each R 4 is independently alkyl or alkenyl, which may be interrupted by one or more —O— groups;
R 7 is H, C 1-10 alkyl, or arylalkyl; or R 4 and R 7 can join to form a ring;
each Y is independently —O— or —S(O) 0-2 —;
n is 0 to 4; and
each R present is independently selected from the group consisting of C 1-10 alkyl, C 1-10 alkoxy, hydroxy, halogen and trifluoromethyl;
or a pharmaceutically acceptable salt thereof.Join the waitlist — get patent alerts
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