Substituted imidazoquinolines

1. A method for treating a disease sensitive to TLR7 activation, or a method for treating a cancer sensitive to the activation of TLR7, or a method for treating a viral or neoplastic disease, or a method for activating TLR7,

comprising administering to a subject in need thereof an effective amount of a compound of formula I

wherein

R 1 is selected from the group consisting of:

alkyl, alkynyl, aryl, alkoxy, heterocyclyl and heteroaryl,

which alkyl, alkynyl, aryl, alkoxy, heterocyclyl or heteroaryl is unsubstituted or substituted by one or more substituents;

A is C 1 -C 6 alkyl;

B is —N(R 2 )(R 3 );

R 2 is H or —(CO)—R 5 ;

R 5 is selected from the group consisting of:

alkyl, cycloalkyl, alkynyl, and heterocyclyl,

each of which is unsubstituted or substituted by one or more substituents;

R 3 is heterocyclyl,

which heterocyclyl is unsubstituted or substituted by one or more substituents;

or a pharmaceutically acceptable solvate, salt, N-oxide or stereoisomer thereof,

wherein at least one of the following conditions i to iv is satisfied:

i) R 2 is —(CO)—R 5 ;

ii) A is not propyl;

iii) R 1 is not butyl;

iv) R 3 does not encompass substituted piperidyl.

2. A method according to claim 1 , which is for treating a disease sensitive to TLR7 activation.

3. A method according to claim 1 , which is for treating a cancer sensitive to the activation of TLR7.

4. A method according to claim 1 , which is for treating a viral or neoplastic disease.

5. A method according to claim 1 , which is for activating TLR7.

6. A method for treating a disease sensitive to TLR7 activation, or a method for treating a cancer sensitive to the activation of TLR7, or a method for treating a viral or neoplastic disease, or a method for activating TLR7,

comprising administering to a subject in need thereof an effective amount of one of the following compounds

N-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N-(1,1-dioxidotetrahydro-3-thienyl)acetamide,

N-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N-(1-methyl-1-oxidopiperidin-4-yl)acetamide,

3-{acetyl[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]amino}-2,5-anhydro-1,3,4-trideoxypentitol,

N-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N-(1-benzyl-2-methyl-1-oxidopyrrolidin-3-yl)acetamide,

2-ethyl-1-[4-(tetrahydro-2H-pyran-4-ylamino)butyl]-1H-imidazo[4,5-c]quinolin-4-amine,

1-[4-(1-azabicyclo[2.2.2]oct-3-ylamino)butyl]-2-ethyl-1H-imidazo[4,5-c]quinolin-4-amine or

1-{4-[(1,1-dioxido-3,4-dihydro-2H-thiochromen-4-yl)amino]butyl}-2-ethyl-1H-imidazo[4,5-c]quinolin-4-amine,

or a pharmaceutically acceptable solvate, salt, N-oxide or stereoisomer thereof.

7. A method according to claim 1 , wherein a compound of formula I or a pharmaceutically acceptable solvate, salt, N-oxide or stereoisomer thereof is administered, wherein, in the compound of formula I,

R 1 is selected from the group consisting of:

alkyl, alkynyl, aryl, alkoxy, heterocyclyl and heteroaryl,

which alkyl, alkynyl, aryl, alkoxy, heterocyclyl or heteroaryl is unsubstituted or substituted by one or more substituents selected from the group consisting of: —H, —OH, halogen, —CO—N(R 4 ) 2 , —N(R 4 ) 2 , —CO—C 1-10 alkyl, —CO—O—C 1-10 alkyl, —N 3 , optionally substituted aryl, heterocyclyl and —CO-aryl,

wherein each R 4 is independently —H, —C 1-10 alkyl, —C 1-10 alkyl-aryl, or aryl;

A is C 1 -C 6 alkyl;

B is —N(R 2 )(R 3 );

R 2 is H or —(CO)—R 5 ;

R 5 is selected from the group consisting of:

alkyl, cycloalkyl, alkynyl, and heterocyclyl,

each of which is unsubstituted or substituted by one or more substituents selected from the group consisting of: —H, —OH, halogen, —CN, —NO 2 , —COOH, —SH, —CO—C 1-6 alkyl, —CO—O—C 1-6 alkyl, —N 3 , optionally substituted aryl, heterocyclyl, —CO-aryl and —CO-heterocyclyl;

R 3 is

heterocyclyl,

which heterocyclyl is unsubstituted or substituted by one or more substituents selected from group consisting of: —H, alkyl, alkenyl, alkoxy, halogen, —OH, —N 3 , trifluromethyl, -alkyl-aryl, —O-alkyl-aryl, —CO-aryl, aryl, heterocyclyl, heteroaryl, CO-heteroaryl, —CO-substituted aryl, CO-substituted heteroaryl, —CO—O-alkyl, —CO—N-alkyl, and —CO—N-aryl;

wherein at least one of the following conditions i to iv is satisfied:

i) R 2 is —(CO)—R 5 ;

ii) A is not propyl;

iii) R 1 is not butyl;

iv) R 3 is not substituted piperidyl.

8. A method according to claim 6 , wherein one of the following compounds is administered

N-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N-(1,1-dioxidotetrahydro-3-thienyl)acetamide,

N-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N-(1-methyl-1-oxidopiperidin-4-yl)acetamide,

3-{acetyl[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]amino}-2,5-anhydro-1,3,4-trideoxypentitol,

N-[4-(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N-(1-benzyl-2-methyl-1-oxidopyrrolidin-3-yl)acetamide,

2-ethyl-1-[4-(tetrahydro-2H-pyran-4-ylamino)butyl]-1H-imidazo[4,5-c]quinolin-4-amine,

1-[4-(1-azabicyclo[2.2.2]oct-3-ylamino)butyl]-2-ethyl-1H-imidazo[4,5-c]quinolin-4-amine or

1-{4-[(1,1-dioxido-3,4-dihydro-2H-thiochromen-4-yl)amino]butyl}-2-ethyl-1H-imidazo[4,5-c]quinolin-4-amine,

or a pharmaceutically acceptable salt thereof.

9. A method according to claim 1 , wherein a compound of formula I or a pharmaceutically acceptable salt thereof is administered.

10. A method according to claim 1 , wherein a compound of formula I or a pharmaceutically acceptable salt thereof is administered, wherein, in the compound of formula I,

R 1 is selected from the group consisting of:

alkyl, alkynyl, aryl, alkoxy, heterocyclyl and heteroaryl,

which alkyl, alkynyl, aryl, alkoxy, heterocyclyl or heteroaryl is unsubstituted or substituted by one or more substituents selected from the group consisting of: —H, —OH, halogen, —CO—N(R 4 ) 2 , —N(R 4 ) 2 , —CO—C 1-10 alkyl, —CO—O—C 1-10 alkyl, —N 3 , optionally substituted aryl, heterocyclyl and —CO-aryl,

wherein each R 4 is independently —H, —C 1-10 alkyl, —C 1 -10 alkyl-aryl, or aryl;

A is C 1 -C 6 alkyl;

B is —N(R 2 )(R 3 );

R 2 is H or —(CO)—R 5 ;

R 5 is selected from the group consisting of:

alkyl, cycloalkyl, alkynyl, and heterocyclyl,

each of which is unsubstituted or substituted by one or more substituents selected from the group consisting of: —H, —OH, halogen, —CN, —NO 2 , —COOH, —SH, —CO—C 1-6 alkyl, —CO—O—C 1-6 alkyl, —N 3 , optionally substituted aryl, heterocyclyl, —CO-aryl and —CO-heterocyclyl;

R 3 is

heterocyclyl,

which heterocyclyl is unsubstituted or substituted by one or more substituents selected from group consisting of: —H, alkyl, alkenyl, alkoxy, halogen, —OH, —N 3 , trifluromethyl, -alkyl-aryl, —O-alkyl-aryl, —CO-aryl, aryl, heterocyclyl, heteroaryl, CO-heteroaryl, —CO-substituted aryl, CO-substituted heteroaryl, —CO—O-alkyl, —CO—N-alkyl, and —CO—N-aryl;

wherein at least one of the following conditions i to iv is satisfied:

i) R 2 is —(CO)—R 5 ;

ii) A is not propyl;

iii) R 1 is not butyl;

iv) R 3 is not substituted piperidyl.

11. A method according to claim 1 , wherein a compound of formula I or a pharmaceutically acceptable solvate, salt, N-oxide or stereoisomer thereof is administered, wherein, in the compound of formula I,

R 3 is heterocyclyl, which is unsubstituted or substituted by one or more substituents which are selected from group consisting of: —H, alkyl, alkenyl, halogen and —OH.

12. A method according to claim 1 , wherein a compound of formula I or a pharmaceutically acceptable solvate, salt, N-oxide or stereoisomer thereof is administered, wherein, in the compound of formula I,

R 3 is selected from the group consisting of: dioxo-tetrahydrothiophenyl, tetrahydrofuranyl, tetrahydropyranyl and azabicyclooctanyl, each of which is optionally substituted by one or more substituents which are selected from group consisting of: —H, alkyl, alkenyl, halogen and —OH.

13. A method according to claim 1 , wherein a compound of formula I or a pharmaceutically acceptable solvate, salt, N-oxide or stereoisomer thereof is administered, wherein, in the compound of formula I,

R 1 is alkyl and R 5 is alkyl.

14. A method according to claim 1 , wherein a compound of formula I or a pharmaceutically acceptable solvate, salt, N-oxide or stereoisomer thereof is administered, wherein, in the compound of formula I,

R 2 is H.

15. A method according to claim 1 , wherein a compound of formula I or a pharmaceutically acceptable solvate, salt, N-oxide or stereoisomer thereof is administered, wherein, in the compound of formula I, only condition i) is satisfied.

16. A method according to claim 1 , wherein a compound of formula I or a pharmaceutically acceptable solvate, salt, N-oxide or stereoisomer thereof is administered, wherein, in the compound of formula I, only condition ii) is satisfied.

17. A method according to claim 1 , wherein a compound of formula I or a pharmaceutically acceptable solvate, salt, N-oxide or stereoisomer thereof is administered, wherein, in the compound of formula I, only condition iii) is satisfied.

18. A method according to claim 1 , wherein a compound of formula I or a pharmaceutically acceptable solvate, salt, N-oxide or stereoisomer thereof is administered, wherein, in the compound of formula I, only condition iv) is satisfied.

19. A method for treating a disease sensitive to TLR7 activation, or a method for treating a cancer sensitive to the activation of TLR7, or a method for treating a viral or neoplastic disease, or a method for activating TLR7,

comprising administering to a subject in need thereof an effective amount a compound of formula I

wherein

R 1 is selected from the group consisting of:

H, alkyl, alkynyl, aryl, alkoxy, heterocyclyl and heteroaryl,

which alkyl, alkynyl, aryl, alkoxy, heterocyclyl or heteroaryl is unsubstituted or substituted by one or more substituents;

A is C 1 -C 6 alkyl;

B is —N(R 2 )(R 3 );

R 2 is H or —(CO)—R 5 ;

R 5 is selected from the group consisting of:

alkyl, cycloalkyl, alkynyl, aryl, heterocyclyl and heteroaryl,

each of which is unsubstituted or substituted by one or more substituents;

R 3 is selected from the group consisting of:

—H, alkyl, alkenyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl,

which alkyl, alkenyl, aryl, heteroaryls, cycloalkyl or heterocyclyl is unsubstituted or substituted by one or more substituents;

or a pharmaceutically acceptable solvate, salt, N-oxide or stereoisomer thereof.

20. A method according to claim 1 , wherein a compound of formula I or a pharmaceutically acceptable solvate, salt, N-oxide or stereoisomer thereof is administered, wherein, in the compound of formula I,

R 2 is —(CO)—R 5 .