N-1 branched alkyl ether substituted imidazo[4,5-c]quinoline compounds, compositions, and methods
Imidazo[4,5-c]quinoline compounds 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 method of treating an infection in a human or animal, the method comprising administering an effective amount of a compound represented by Formula (II), or a salt thereof to the human or animal,
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 —X—O—Y where X is a C 1-3 alkylene and Y is a C 1-3 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 ;
R 3 is a C 1-4 alkyl,
R 4 is a C 1-4 alkyl, or
R 3 and R 4 are combined to form a ring of 3-7 carbon atoms optionally having one oxygen atom in the ring; and
R 5 is —H, —CH 3 , —F, or —OH.
2 . The method of claim 1 , wherein the infection is by an adenovirus, a herpes virus, a poxvirus, a picornavirus, an orthomyxovirus, a paramyxovirus, a coronavirus, a papovavirus, a hepadnavirus, a flavivirus, or a retrovirus, or an ebola virus.
3 . The method of claim 1 , wherein the infection is by a herpes virus selected from HSV-I, HSV-II, CMV, and VZV.
4 . The method of claim 1 , wherein the infection is by an variola, vaccinia, or molluscum contagiosum.
5 . The method of claim 1 , wherein the infection is by a rhinovirus or enterovirus.
6 . The method of claim 1 , wherein the infection is by an influenza virus or an avian influenza.
7 . The method of claim 1 , wherein the infection is by a parainfluenza virus, a mumps virus, a measles virus, or a respiratory syncytial virus.
8 . The method of claim 1 , wherein the infection is by a coronavirus selected from SARS.
9 . The method of claim 1 , wherein the infection is by a papillomavirus that causes genital warts, common warts, or plantar warts.
10 . The method of claim 1 , wherein the infection is by hepatitis B virus.
11 . The method of claim 1 , wherein the infection is by hepatitis C virus or Dengue virus.
12 . The method of claim 1 , wherein the infection is by a lentivirus selected from HIV.
13 . The method of claim 1 , wherein the infection is by malaria, leishmaniasis, cryptosporidiosis, toxopolasmosis, or a trypanosome infection.
14 . The method of claim 1 , wherein R is selected from the group consisting of halogen, hydroxy, —C 1-12 alkyl, —C 1-12 alkoxy, and —C(O)—O—C 1-10 alkyl.
15 . The method of claim 1 , wherein n is 0.
16 . The method of claim 1 , wherein X is —CH 2 —, —CH 2 CH 2 —, or —CH(CH 3 )—.
17 . The method of claim 1 , wherein R 3 is a C 1-4 alkyl, R 4 is a C 1-4 alkyl, or both R 3 and R 4 are a C 1-4 alkyl.
18 . The method of claim 1 , wherein R 3 and R 4 are combined to form a ring of 3-7 carbon atoms optionally having one oxygen atom in the ring.
19 . The method of claim 1 , wherein X is-CH 2 — or —CH(CH 3 )—, Y is —CH 3 or —CH 2 CH 3 ; R 2 is selected from the group consisting of hydrogen, methyl, and ethyl; R 3 is a C 1-4 alkyl; R 4 is a C 1-4 alkyl; R 5 is —H, —CH 3 , or —OH; and n is 0.
20 . The method of claim 1 , wherein the compound is selected from:
(3R)-3-(4-aminoimidazo [4,5-c]quinolin-1-yl)-4-ethoxy-2-methyl-butan-2-ol,
(3R)-3-(4-amino-2-methyl-imidazo [4,5-c]quinolin-1-yl)-4-ethoxy-2-methyl-butan-2-ol,
(3R)-3-(4-amino-2-ethyl-imidazo [4,5-c]quinolin-1-yl)-4-ethoxy-2-methyl-butan-2-ol,
1-[(1S)-1-(ethoxymethyl)-2,2-dimethyl-propyl] imidazo [4,5-c]quinolin-4-amine,
1-[(1S)-1-(methoxymethyl)-2,2-dimethyl-propyl] imidazo [4,5-c]quinolin-4-amine,
(2R)-2-(4-aminoimidazo [4,5-c]quinolin-1-yl)-1-ethoxy-3-ethyl-pentan-3-ol,
(3R,4S)-3-(4-aminoimidazo [4,5-c]quinolin-1-yl)-4-ethoxy-2-methyl-pentan-2-ol, and
1-[(1R)-1-(4-aminoimidazo [4,5-c]quinolin-1-yl)-2-ethoxy-ethyl]cyclopentanol.