# US 10,118,925 B2 · Imidazo[4,5-c] ring compounds containing substituted guanidine groups

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- Number: US 10,118,925 B2
- Document ID: US10118925B2
- Status: Granted
- Kind: B2
- Application number: 15/753,573
- Filed: 2016-08-26
- Published: 2018-08-30
- Granted: 2018-11-06
- Earliest claimed: 2015-08-31
- Assignees: 3M Innovative Properties Company
- Applicants: 3M Innovative Properties Company
- Inventors: George W. Griesgraber
- Web page: https://patentgrep.com/patent/US10118925B2

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Imidazo[4,5-c] ring compounds, (particularly imidzao[4,5-c]quinolines, 6,7,8,9-tetrahydroimidazo[4,5-c]quinolines, imidazo[4,5-c]naphthyridines, and 6,7,8,9-tetrahydroimidazo[4,5-c]naphthyridine compounds) having a substituted guanidine substituent at the 1-position, 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 animals and in the treatment of diseases including viral and neoplastic diseases are also disclosed.

## Claims

### Claim 1

A compound of the Formula (I):
wherein:
R3 and R4 are taken together to form a fused benzene ring, a fused pyridine ring, a fused cyclohexene ring, or a fused tetrahydropyridine ring; wherein the fused benzene ring, fused pyridine ring, fused cyclohexene ring, or fused tetrahydropyridine ring is either unsubstituted or substituted by one or more R groups;
R is selected from the group consisting of halogen, hydroxyl, alkyl, alkoxy, haloalkyl, —C(O)—O-alkyl, —C(O)—O—CH2Ph, —C(O)—O-aryl, amino, alkylamino, and dialkylamino aryl, arylalkylenyl, aryloxyalkylenyl, arylalkyleneoxy, aryloxy, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkyenyl, heteroarylalkyleneoxy, and heteroaryloxy, wherein the alkyl, aryl, arylalkylenyl, aryloxyalkylenyl, arylalkyleneoxy, aryloxy, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkyenyl, heteroaryalkyleneoxy, and heteroaryloxy groups can be unsubstituted or substituted by one or more substituents independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, hydroxyl, hydroxyalkylenyl, alkoxyalkylenyl, arylalkyleneoxy, and nitrile;
R1 is selected from the group consisting of —W—X—N(R7)—C(═N—R5)—N(H)R6, —W—Z—N(R7)—C(═N—R5)—N(H)R6, and
W is selected from the group consisting of a covalent bond, —O—, and NH—;
X is selected from the group consisting of alkylene, alkenylene, and alkynylene, wherein any of the alkylene, alkenylene, and alkynylene groups can be optionally interrupted by one or more —O— groups;
Z is selected from the group consisting of
—X-arylene-X—,
—X-heteroarylene-X—,
—X-arylene-, and
—X-heteroarylene-;
R2 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, —O-alkyl, hydroxyalkylenyl, alkoxyalkylenyl, alkylaminoalkylenyl, hydroxyl, —CH2—NH—O-alkyl, and —CH2NHC(O)-alkyl;
R7 is selected from the group consisting of hydrogen, alkyl, arylalkylenyl, alkoxyalkylenyl, aryloxyalkylenyl, benzyloxyalkylenyl, aryl-(CH2)2-6—O-alkylenyl, and cycloalkylalkylenyl; wherein any of the alkyl, arylalkylenyl, alkoxyalkylenyl, aryloxyalkylenyl, benzyloxyalkylenyl, aryl-(CH2)2-6—O-alkylenyl, and cycloalkylalkylenyl groups can be either unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, hydroxyl, alkyl, alkoxy, haloalkyl, and nitrile;
R5 and R6 are independently selected from the group consisting of hydrogen, —C(O)—O-alkyl, alkyl, cycloalkyl, aryl, arylalkylenyl, aryloxyalkylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, cycloalkylalkylenyl, aryl-(CH2)2-6—O-alkylenyl, and benzyloxyalkylenyl; wherein any of the alkyl, cycloalkyl, aryl, arylalkylenyl, aryloxyalkylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, cycloalkylalkylenyl, aryl-(CH2)2-6—O-alkylenyl, and benzyloxyalkylenyl groups can be either unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogen, hydroxyl, alkoxy, alkyl, haloalkyl, cycloalkyl, nitrile, aryl, heteroaryl, and dialkylamino; with the proviso that R5 and R6 are not both hydrogen;
Q is selected from the group consisting of a covalent bond, —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2CH2CH2CH2—, —CH2CH2CH2CH2CH2—, —CH2—O—CH2—, and —OCH2—;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound or salt of claim 1, wherein R7 is hydrogen.

### Claim 3 (depends on 1)

The compound or salt of claim 1, wherein W is a covalent bond or —O—.

### Claim 4 (depends on 1)

The compound or salt of claim 1, wherein X is alkylene optionally interrupted by one or more —O— groups.

### Claim 5 (depends on 1)

The compound or salt of claim 1, wherein Z is —C1-5alkylene-arylene-C1-5alkylene- or —C1-5alkylene-heteroarylene-C1-5alkylene-.

### Claim 6 (depends on 1)

The compound or salt of claim 1, wherein R2 is selected from the group consisting hydrogen, alkyl, alkoxyalkylenyl, alkylaminoalkylenyl, and hydroxyalkylenyl.

### Claim 7 (depends on 1)

The compound or salt of claim 1, wherein R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, phenyl, and phenylalkylenyl, and wherein R5 and R6 are not both hydrogen.

### Claim 8

A compound of the Formula XIII:
wherein:
R1B is selected from the group consisting of —XB—N(R7B)—C(═N—R5B)—N(H)R6B, and —ZB—N(R7B)—C(═N—R5B)—N(H)R6B, and
XB is selected from the group consisting of alkylene, alkenylene, and alkynylene, wherein the alkylene, alkenylene, and alkynylene groups can be optionally interrupted by one or more —O— groups;
ZB is selected from the group consisting of
—XB-arylene-XB—,
—XB-heteroarylene-XB—,
—XB-arylene-, and
—XB-heteroarylene-;
R2B is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, —O-alkyl, hydroxyalkylenyl, alkoxyalkylenyl, alkylaminoalkylenyl, hydroxyl, —CH2—NH—O-alkyl, and —CH2NHC(O)-alkyl;
R7B is selected from the group consisting of hydrogen, alkyl, arylalkylenyl, alkoxyalkylenyl, aryloxyalkylenyl, benzyloxyalkylenyl, aryl-(CH2)2-6—O-alkylenyl, and cycloalkylalkylenyl; wherein any of the alkyl, arylalkylenyl, alkoxyalkylenyl, aryloxyalkylenyl, benzyloxyalkylenyl, aryl-(CH2)2-6—O-alkylenyl, and cycloalkylalkylenyl groups can be either unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, hydroxyl, alkyl, alkoxy, haloalkyl, and nitrile;
R5B and R6B are independently selected from the group consisting of hydrogen, —C(O)—O-alkyl, alkyl, cycloalkyl, aryl, arylalkylenyl, aryloxyalkylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, cycloalkylalkylenyl, aryl-(CH2)2-6—O-alkylenyl, and benzyloxyalkylenyl; wherein any of the, cycloalkyl, aryl, arylalkylenyl, aryloxyalkylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, cycloalkylalkylenyl, aryl-(CH2)2-6—O-alkylenyl, and benzyloxyalkylenyl groups can be either unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogen, hydroxyl, alkoxy, alkyl, haloalkyl, cycloalkyl, nitrile, aryl, heteroaryl, and dialkylamino; with the proviso that R5B and R6B are not both hydrogen;
QB is selected from the group consisting of a covalent bond, —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2CH2CH2CH2—, —CH2CH2CH2CH2CH2—, —CH2—O—CH2—, and —OCH2—;
or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 8)

The compound or salt of claim 8, wherein R7B is hydrogen.

### Claim 10 (depends on 8)

The compound or salt of claim 8, wherein XB is alkylene optionally interrupted by one or more —O— groups.

### Claim 11 (depends on 8)

The compound or salt of claim 8, wherein XB is selected from the group consisting of CH2CH2—, —CH2CH2CH2—, —CH2CH2CH2CH2—, —CH2CH2CH2CH2CH2—, —CH2CH2CH2CH2CH2CH2—, —CH2CH2CH2CH2CH2CH2CH2—, —CH2CH2CH2CH2CH2CH2CH2CH2—, —CH2C(CH3)2—, —CH2C(CH3)2CH2—, —CH2CH2—O—CH2CH2—, —CH2CH2—O—CH2CH2—O—CH2CH2—, —(CH2)2-4—(OCH2CH2-)1-5, and —(CH2)2-6—(OCH2CH2-)1-4.

### Claim 12 (depends on 8)

The compound or salt of claim 8, wherein ZB is —C1-5alkylene-arylene-C1-5alkylene- or —C1-5alkylene-heteroarylene-C1-5alkylene-.

### Claim 13 (depends on 8)

The compound or salt of claim 8, wherein ZB is —CH2-phenylene-CH2—.

### Claim 14 (depends on 8)

The compound or salt of claim 8, wherein R2B is selected from the group consisting hydrogen, alkyl, alkoxyalkylenyl, alkylaminoalkylenyl, and hydroxyalkylenyl.

### Claim 15 (depends on 8)

The compound or salt of claim 8, wherein R2B is selected from the group consisting of hydrogen, —CH3, —CH2CH3, —CH2CH2CH3, —CH2CH2CH2CH3, —CH2OCH3, —CH2OCH2CH3, and —CH2CH2OCH3.

### Claim 16 (depends on 8)

The compound or salt of claim 8, wherein R5B and R6B are independently selected from the group consisting of hydrogen, alkyl, phenyl, phenylalkylenyl; and wherein R5B and R6B are not both hydrogen.

### Claim 17 (depends on 8)

The compound or salt of claim 8, wherein R5B and R6B are independently selected from the group consisting of alkyl, phenyl, and phenylalkylenyl.

### Claim 18 (depends on 8)

The compound or salt of claim 8, wherein R5B is alkyl and R6B is alkyl.

### Claim 19 (depends on 1)

A method of inducing biosynthesis of IFN-alpha in an animal comprising administering an effective amount of a compound or salt of claim 1 to the animal.

### Claim 20 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 1 in combination with a pharmaceutically acceptable carrier.