Substituted imidazo ring systems and methods

Patent metadata

Field	Value
Publication number	US-9765071-B2
Application number	US-201615068892-A
Country	US
Kind code	B2
Filing date	Mar 14, 2016
Priority date	Nov 25, 2003
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

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.

First claim

What is claimed is:

1. 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;
R 1-1 is alkyl;
R is fluoro;
R 2 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.

2. The compound or salt of claim 1 wherein n is 0.

3. The compound or salt of claim 1 wherein X is C 1-6 alkylene.

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

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

6. The compound or salt of claim 1 wherein R 2 is selected from the group consisting of hydrogen, hydroxymethyl, methyl, ethyl, n-propyl, n-butyl, ethoxymethyl, 2-methoxyethyl, and 2-hydroxyethyl.

7. The compound or salt of claim 1 wherein R 1-1 is C 1-8 alkyl.

8. The compound or salt of claim 1 wherein R 1-1 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.

9. 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.

10. A compound of the Formula (I-1):

wherein:
X is alkylene optionally interrupted by one or more —O— groups;
Z is —C(O)—;
R 1-1 is selected from the group consisting of:
hydrogen,
alkyl,
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;

R 2 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;

R A and R B 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 R a groups;
R is selected from the group consisting of:
fluoro,
alkyl,
haloalkyl,
alkoxy, and
N(R 9 ) 2 ; and

R a is selected from the group consisting of:
halogen,
hydroxy,
alkyl,
alkenyl,
haloalkyl,
alkoxy,
alkylthio, and
—N(R 9 ) 2 ;

R 9 is selected from the group consisting of hydrogen and alkyl;
Y is selected from the group consisting of —O— and —S(O) 0-2 ;
or a pharmaceutically acceptable salt thereof.

11. The compound or salt of claim 10 wherein R 1-1 is alkyl; and R 2 is selected from the group consisting of alkyl, alkylene-Y-alkyl, and alkyl substituted by hydroxyl.

12. The compound or salt of claim 10 wherein Y is —O—.

13. The compound or salt of claim 10 wherein:
R 2 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;
R A and R B are taken together to form either a fused aryl ring that is unsubstituted, or a fused 5 to 7 membered saturated ring that is unsubstituted.

14. The compound or salt of claim 13 wherein R 1-1 is selected from the group consisting of alkyl, aryl, and alkylene-aryl.

15. The compound or salt of claim 13 wherein R 1-1 is alkyl.

16. The compound or salt of claim 13 wherein R 1-1 is C 1-8 alkyl.

17. The compound or salt of claim 13 wherein R 1-1 is —(CH 2 ) 1-7 CH 3 .

18. A compound 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;
1-[4-Amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butan-2-one;
or a pharmaceutically acceptable salt thereof.

Assignees

• 3M Innovative Properties Co

Inventors

• Krepski Larry R
• Dellaria Jr Joseph F
• Duffy Daniel E
• Radmer Matthew R
• Amos David T

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P39/02

  Antidotes · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/04

  Immunostimulants · CPC title