Ether substituted imidazopyridines
View Patent ↗Imidazopyridine compounds that contain an ether or thioether 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. Methods of preparing the compounds and intermediates useful in the preparation of the compounds are also disclosed.
1. A compound of the formula (I-6):
wherein:
X is —CH(R 5 )—, —CH(R 5 )-alkylene-, —CH(R 5 )-alkenylene-, or CH(R 5 )-alkylene-Y-alkylene-;
R 1-6 is selected from the group consisting of:
-alkyl;
-aryl;
-heteroaryl;
-heterocyclyl;
-alkenyl;
-R 6 -aryl;
-R 6 -heteroaryl;
-R 6 -heterocyclyl;
R 2 is selected from the group consisting of:
-hydrogen;
-alkyl;
-alkenyl;
-aryl;
-heteroaryl;
-heterocyclyl;
-alkylene-Y-alkyl;
-alkylene-Y-alkenyl;
-alkylene-Y-aryl; and
-alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
—OH;
-halogen;
N(R 5 ) 2 ;
—C(O)—C 1-10 alkyl;
—C(O)—O—C 1-10 alkyl;
—N 3 ;
-aryl;
-heteroaryl;
-heterocyclyl;
—C(O)-aryl; and
—C(O)-heteroaryl;
Y is —O— or —S(O) 0-2 —;
R 3 and R 4 are independently selected from the group consisting of hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, C 1-10 alkylthio, amino, alkylamino, dialkylamino, halogen, and nitro;
each R 5 is independently hydrogen, C 1-10 alkyl, or C 2-10 alkenyl; and
R 6 is alkylene, alkenylene, or alkynylene, which may be interrupted by one or more —O— atoms;
or a pharmaceutically acceptable salt thereof.
2. A compound or salt of claim 1 wherein —S(O) 0-2 — is —S—.
3. A compound or salt of claim 1 wherein —S(O) 0-2 — is —SO—.
4. A compound or salt of claim 1 wherein —S(O) 0-2 — is —S(O) 2 —.
5. A compound or salt of claim 1 wherein R 3 and R 4 are independently hydrogen, alkyl, halogen, or nitro.
6. A compound or salt of claim 1 wherein R 3 and R 4 are both methyl.
7. A compound or salt of claim 1 wherein R 2 is hydrogen.
8. A compound or salt of claim 1 wherein R 2 is -alkyl.
9. A compound or salt of claim 1 wherein R 2 is -alkylene-O-alkyl.
10. A compound or salt of claim 1 wherein R 1-6 is alkyl.
11. A compound or salt of claim 1 wherein R 1-6 is aryl.
12. A compound or salt of claim 1 wherein R 1-6 is substituted aryl.
13. A compound or salt of claim 1 wherein R 1-6 is heteroaryl.
14. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable carrier.
15. A method of inducing cytokine biosynthesis in an animal comprising administering an effective amount of a compound of claim 1 to the animal wherein the cytokine is interferon α and/or tumor necrosis factor α.