N-1 branched cycloalkyl substituted imidazo[4,5-c]quinoline compounds, compositions, and methods
Imidazo[4,5-c]quinoline compounds of Formula (I) having a substituent that is attached at the N−1 position by a branched group, single enantiomers of the compounds, pharmaceutical compositions containing the compounds, and methods of making the compounds are disclosed. Methods of use of the compounds as immune response modifiers, for inducing cytokine biosynthesis in humans and animals, and in the treatment of diseases including infectious and neoplastic diseases are also disclosed.
1. A compound of Formula (II), or salt thereof:
wherein:
n is an integer of 0 or 1;
R is selected from the group consisting of halogen, hydroxy, alkyl, alkoxy, and —C(O)—O— alkyl;
R 1 is alkyl;
R 2 is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, n-butyl, —CH 2 OCH 3 , —CH 2 OCH 2 CH 3 , and —CH 2 CH 2 OCH 3 ; and
Z is a bond, —CH 2 —, —CH 2 CH 2 —, —CH 2 OCH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —C═C—.
2. The compound or salt of claim 1 , wherein R is selected from the group consisting of halogen, hydroxy, —C 1-7 alkyl, —C 1-7 alkoxy, and —C(O)—O—C 1-5 alkyl.
3. The compound or salt of claim 1 , wherein n is 0.
4. The compound or salt of claim 1 , wherein R 1 is —C 1-4 alkyl.
5. The compound or salt of claim 1 , wherein R 2 is selected from the group consisting of hydrogen, methyl, and ethyl.
6. The compound or salt of claim 1 , wherein Z is a —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, or —C═C—.
7. The compound or salt of claim 1 , wherein R 1 is —CH 3 or —CH 2 CH 3 ; R 2 is selected from the group consisting of hydrogen, methyl, and ethyl; Z is —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, or —C═C—; and n is 0.
8. The compound or salt of claim 7 , wherein the compound is 1-[(1R)-1-(4-aminoimidazo[4,5-c]quinolin-1-yl)ethyl]cyclopentanol.
9. The compound or salt of claim 7 , wherein the compound is 1-[(1R)-1-(4-aminoimidazo[4,5-c]quinolin-1-yl)propyl]cyclopentanol.
10. The compound or salt of claim 7 , wherein the compound is 1-[(1R)-1-(4-aminoimidazo[4,5-c]quinolin-1-yl)ethyl]cyclopent-3-en-ol.
11. The compound or salt of claim 7 , wherein the compound is 1-[(1R)-1-(4-aminoimidazo[4,5-c]quinolin-1-yl)propyl]cyclohexanol.
12. A pharmaceutical composition comprising an effective amount of a compound or salt of claim 1 in combination with a pharmaceutically acceptable carrier.
13. The pharmaceutical composition of claim 12 , further comprising an antigen.
14. The pharmaceutical composition of claim 12 for use in treating an infectious disease in a human or animal.
15. A method of inducing cytokine biosynthesis in a human or animal comprising administering an effective amount of a compound or salt of claim 1 to the human or animal.