# US 2014/0194628 A1 · Substituted imidazo ring systems and methods

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- Number: US 2014/0194628 A1
- Document ID: US20140194628A1
- Status: Published application
- Kind: A1
- Application number: 14/205,114
- Filed: 2014-03-11
- Published: 2014-07-10
- Earliest claimed: 2003-11-25
- Assignees: 3M Innovative Properties Company
- Applicants: 3M Innovative Properties Company
- Inventors: Larry R. Krepski; Joseph F. Dellaria, Jr.; Daniel E. Duffy; Matthew R. Radmer; David T. Amos
- Web page: https://patentgrep.com/patent/US20140194628A1

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- A61P 11/08: Bronchodilators
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/14: for baldness or alopecia
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 31/04: Antibacterial agents
- A61P 31/06: for tuberculosis
- A61P 31/10: Antimycotics
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/16: for influenza or rhinoviruses
- A61P 31/18: for HIV
- A61P 31/22: for herpes viruses
- A61P 33/02: Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P 33/06: Antimalarials
- A61P 33/10: Anthelmintics
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 39/02: Antidotes
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 213/74: Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- C07D 255/02: not condensed with other rings
- C07D 471/14: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Imidazo ring systems substituted at the 1-position, pharmaceutical compositions containing the compounds, intermediates, methods of making the compounds, and methods of use of these compounds as immunomodulators, for inducing cytokine biosynthesis in animals and in the treatment of diseases including viral and neoplastic diseases are disclosed.

## Claims

### Claim 1

A compound of the Formula (I-1):
wherein:
X is alkylene optionally interrupted by one or more —O— groups;
Z is —C(O)—;
R1-1 is selected from the group consisting of:
hydrogen,
alkyl,
aryl,
alkylene-aryl,
heteroaryl,
alkylene-heteroaryl, and
alkyl, aryl, alkylene-aryl, heteroaryl, or alkylene-heteroaryl substituted by one or more substituents selected from the group consisting of:
halogen,
cyano,
nitro,
alkoxy,
dialkylamino,
alkylthio,
haloalkyl,
haloalkoxy, and
alkyl;
R2 is selected from the group consisting of:
hydrogen,
alkyl,
alkenyl,
alkylene-Y-alkyl,
alkyene-Y-alkenyl, and
alkyl or alkenyl substituted by one or more substituents selected from the group consisting of hydroxyl and halogen;
RA and RB are each independently selected from the group consisting of:
hydrogen,
alkyl,
alkenyl,
alkoxy, and
alkylthio;
or RA and RB are taken together to form either a fused aryl ring that is unsubstituted or substituted by one or more R groups, or a fused 5 to 7 membered saturated ring that is unsubstituted or substituted by one or more Ra groups;
R is selected from the group consisting of:
fluoro,
alkyl,
haloalkyl,
alkoxy, and
—N(R9)2; and
Ra is selected from the group consisting of:
halogen,
hydroxy,
alkyl,
alkenyl,
haloalkyl,
alkoxy,
alkylthio, and
—N(R9)2;
Y is selected from the group consisting of —O— and —S(O)0-2—; and
R9 is selected from the group consisting of hydrogen and alkyl;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound or salt of claim 1 wherein R1-1 is alkyl; and R2 is selected from the group consisting of alkyl, alkylene-Y-alkyl, and alkyl substituted by hydroxyl.

### Claim 3 (depends on 1)

The compound or salt of claim 1 wherein Y is —O—.

### Claim 4 (depends on 1)

The compound or salt of claim 1 wherein:
R2 is selected from the group consisting of hydrogen, alkyl, alkylene-O-alkyl, and alkyl substituted by one or more substituents selected from the group consisting of hydroxyl and halogen;
RA and RB are taken together to form either a fused aryl ring that is unsubstituted or substituted by one or more R groups, or a fused 5 to 7 membered saturated ring that is unsubstituted or substituted by one or more Ra groups.

### Claim 5 (depends on 4)

The compound or salt of claim 4 wherein R1-1 is selected from the group consisting of alkyl, aryl, and alkylene-aryl.

### Claim 6 (depends on 4)

The compound or salt of claim 4 wherein R1-1 is alkyl.

### Claim 7 (depends on 4)

The compound or salt of claim 4 wherein R1-1 is C1-8 alkyl.

### Claim 8 (depends on 4)

The compound or salt of claim 4 wherein R1-1 is —(CH2)1-7CH3.

### Claim 9

A compound of the Formula (Ia):
wherein:
X is alkylene optionally interrupted by one or more —O— groups;
n is an integer from 0 to 1;
R1-1 is alkyl;
R is fluoro;
R2 is selected from the group consisting of:
hydrogen,
alkyl,
alkylene-O-alkyl, and
alkyl substituted by one or more substituents selected from the group consisting of hydroxyl and halogen;
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 9)

The compound or salt of claim 9 wherein n is 0.

### Claim 11 (depends on 9)

The compound or salt of claim 9 wherein X is C1-6 alkylene.

### Claim 12 (depends on 9)

The compound or salt of claim 9 wherein X is —(CH2)2-4—O—(CH2)1-3—.

### Claim 13 (depends on 9)

The compound or salt of claim 9 wherein X is selected from the group consisting of —(CH2)1-6—, —CH2—C(CH3)2—, —(CH2)2—O—CH2—, —(CH2)3—O—CH2—, and —CH2—C(CH3)2—CH2—.

### Claim 14 (depends on 9)

The compound or salt of claim 9 wherein R2 is selected from the group consisting of hydrogen, hydroxymethyl, methyl, ethyl, n-propyl, n-butyl, ethoxymethyl, 2-methoxyethyl, and 2-hydroxyethyl.

### Claim 15 (depends on 9)

The compound or salt of claim 9 wherein R1-1 is C1-8 alkyl.

### Claim 16 (depends on 9)

The compound or salt of claim 9 wherein R1-1 is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, cyclopentyl, n-hexyl, cyclohexyl, n-hexyl, and n-octyl.

### Claim 17 (depends on 1)

The compound or salt of claim 1 selected from the group consisting of:
4-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)-1-phenylbutan-1-one;
5-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one;
4-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)-1-phenylbutan-1-one;
6-(4-Amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)-1-phenylhexan-1-one;
6-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)-1-phenylhexan-1-one;
5-(4-Amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one;
5-(4-Amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one;
5-(4-Amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one;
5-(4-Amino-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)pentan-2-one;
7-(4-Amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)heptan-2-one;
12-(4-Amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)-1-phenyldodecan-1-one;
1-(4-Amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)-6-methylheptan-4-one;
1-(4-Amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)decan-4-one;
5-(4-Amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)-4,4-dimethylpentan-2-one;
5-(4-Amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)-4,4-dimethylpentan-2-one;
5-(4-Amino-1H-imidazo[4,5-c]quinolin-1-yl)-4,4-dimethylpentan-2-one;
5-(4-Amino-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-1-yl)pentan-2-one;
1-[4-Amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butan-2-one.

### Claim 18

The compound 5-(4-Amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)-4,4-dimethylpentan-2-one; or a pharmaceutically acceptable salt thereof.