IP Library › Granted Patent US 7,563,788

Granted Patent B2

US 7,563,788 · App. 10/598,841 · Granted Jul 21, 2009

Substituted Imidazo[1,2-a]pyridines as Antibacterial Agents

Assignee: Pfizer Inc.

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Quick Facts

Patent No.: US 7,563,788
App. No.: 10/598,841
Granted: Jul 21, 2009
Kind: B2

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Abstract

Compounds of formula I and methods for their preparation are disclosed. Further disclosed are methods of making biologically active compounds of formula I as well as pharmaceutically acceptable compositions comprising compounds of formula I. Compounds of formula I as disclosed herein can be used in a variety of applications including use as antibacterial agents.

Claims (155)

1. A compound of the formula

or a pharmaceutically acceptable salt thereof, wherein:

X 1 is CH 2 , NH, or O;

X 2 is absent, or is

(CH 2 ) x′ , NH, O, or

wherein “ ” are points of attachment, or

is a tether 2, 3 or 4 atoms in length, selected from

wherein R is H or (C 1 -C 6 )alkyl, and

wherein “ ” are points of attachment and x′ is an integer from 1 to 3;

Y is C—H, C—F, or C—OMe;

R 1 is H or halo;

R 2 is (C 3 -C 6 )cycloalkyl,

(CH 2 ) x -aryl,

(CH 2 ) x -heterocyclyl, or

(CH 2 ) x -heteroaryl,

wherein x is 0, 1, or 2;

R 3 is H,

(C 1 -C 6 )alkyl,

(C 3 -C 6 )cycloalkyl,

aryl,

heterocyclyl,

heteroaryl,

C(O)NR a R b ,

C(O)R a ,

CO 2 R a ,

C(O)C(O)NR a R b ,

NO 2 ,

SO 2 R a ,

SO 2 NR a R b ,

C(R c )═NOR a ,

C(R c )═NR a ,

wherein “ ” indicates the point of attachment,

and wherein

R a is H,

(C 1 -C 6 )alkyl,

(C 3 -C 6 )cycloalkyl,

(CH 2 ) y -aryl,

(CH 2 ) y -heterocycyl, or

(CH 2 ) y -heteroaryl,

wherein y is 0, 1, or 2;

R b is H,

(C 1 -C 6 )alkyl,

(C 3 -C 6 )cycloalkyl,

aryl,

heterocyclyl, or

heteroaryl;

R c is H,

(C 1 -C 6 )alkyl,

(C 3 -C 6 )cycloalkyl,

aryl,

heterocyclyl, or

heteroaryl; and

R 4 is (C 1 -C 6 )alkyl, (C 1 -C 6 alkyl)-O—(C 1 -C 6 alkyl), cyclopropyl, CH 2 -cyclopropyl, or cyclobutyl.

2. A compound according to claim 1 in which Y is C—H or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 1 in which X 1 is NH,

X 2 is absent, or is (CH 2 ) x′ , NH, or O;

R 1 is H;

R 2 is

(CH 2 ) x -heteroaryl,

wherein x is 0, 1, or 2;

R 3 is

aryl,

heterocyclyl,

heteroaryl,

C(O)NR a R b ,

C(O)R a , or

CO 2 R a ,

and,

R 4 is (C 1 -C 6 )alkyl, cyclopropyl, CH 2 -cyclopropyl or cyclobutyl, or a pharmaceutically acceptable salt thereof.

4. A compound according to claim 1 in which R 2 is heteroaryl or a pharmaceutically acceptable salt thereof.

5. A compound according to claim 1 in which R 2 is heteroaryl and is selected from the group consisting of pyridine, and pyrimidine, either of which may be optionally substituted, or a pharmaceutically acceptable salt thereof.

6. A compound according to claim 1 in which X 2 is absent and R 3 is hydrogen, heteroaryl, C(O)NR a R b , C(O)R a , or CO 2 R a , or a pharmaceutically acceptable salt thereof.

7. A compound according to claim 1 in which R 4 is ethyl or cyclobutyl, or a pharmaceutically acceptable salt thereof.

8. A compound selected from the group consisting of:

(7-pyridin-3-yl-imidazo[1,2-a]pyridin-2-yl)-carbamic acid ethyl ester;

1-ethyl-3-(7-pyridin-3-yl-imidazo[1,2-a]pyridin-2-yl)-urea;

[7-(2-dimethylamino-pyrimidin-5-yl)-imidazo[1,2-a]pyridin-2-yl]-carbamic acid ethyl ester;

1-[7-(2-dimethylamino-pyrimidin-5-yl)-imidazo[1,2-a]pyridin-2-yl]-3-ethyl-urea;

[7-(6-methoxy-pyridin-3-yl)-imidazo[1,2-a]pyridin-2-yl]-carbamic acid ethyl ester;

1-ethyl-3-[7-(6-methoxy-pyridin-3-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

1-ethyl-3-[7-(2-methoxy-pyrimidin-5-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

1-ethyl-3-{7-[6-(2-morpholin-4-yl-ethoxy)-pyridin-3-yl]-imidazo[1,2-a]pyridin-2-yl}-urea;

1-ethyl-3-(5-hydroxymethyl-7-pyridin-3-yl-imidazo[1,2-a]pyridin-2-yl)-urea;

1-ethyl-3-(5-formyl-7-pyridin-3-yl-imidazo[1,2-a]pyridin-2-yl)-urea;

2-(3-ethyl-ureido)-7-pyridin-3-yl-imidazo[1,2-a]pyridine-5-carboxylic acid methyl ester;

1-ethyl-3-(7-pyrimidin-5-yl-imidazo[1,2-a]pyridin-2-yl)-urea;

1-[7-(3,5-dimethyl-isoxazol-4-yl)-imidazo[1,2-a]pyridin-2-yl]-3-ethyl-urea;

1-[7-(1-benzyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridin-2-yl]-3-ethyl-urea;

1-ethyl-3-{7-[6-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-imidazo[1,2-a]pyridin-2-yl}-urea;

1-ethyl-3-[7-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

1-[7-(2,4-dimethoxy-pyrimidin-5-yl)-imidazo[1,2-a]pyridin-2-yl]-3-ethyl-urea;

4-[2-(3-ethyl-ureido)-imidazo[1,2-a]pyridin-7-yl]-3,5-dimethyl-pyrazole-1-carboxylic acid tert-butyl ester;

1-ethyl-3-[7-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

1-(3-chloro-7-pyridin-3-yl-imidazo[1,2-a]pyridin-2-yl)-3-ethyl-urea;

1-[3-chloro-7-(2-dimethylamino-pyrimidin-5-yl)-imidazo[1,2-a]pyridin-2-yl]-3-ethyl-urea;

2-(3-ethyl-ureido)-imidazo[1,2-a]pyridine-7-carboxylic acid methyl ester;

2-(3-ethyl-ureido)-imidazo[1,2-a]pyridine-7-carboxylic acid amide;

1-ethyl-3-[7-(5-methyl-2H-[1,2,4]triazol-3-yl)-Imidazo[1,2-a]pyridin-2-yl]-urea;

1-[7-(1,5-dimethyl-1H-[1,2,4]triazol-3-yl)-imidazo[1,2-a]pyridin-2-yl]-3-ethyl-urea;

1-[7-(2,5-dimethyl-2H-[1,2,4]triazol-3-yl)-imidazo[1,2-a]pyridin-2-yl]-3-ethyl-urea;

1-ethyl-3-[7-(5-methyl-[1,2,4]oxadiazol-3-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

1-ethyl-3-[5-(1-methyl-1H-pyrazol-4-yl)-7-pyridin-3-yl-imidazo[1,2-a]pyridin-2-yl]-urea;

2-(3-ethyl-ureido)-imidazo[1,2-a]pyridine-7-carboxylic acid;

1-[7-(3,5-dimethyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridin-2-yl]-3-ethyl-urea;

1-ethyl-3-[7-(piperidine-1-carbonyl)-imidazo[1,2-a]pyridin-2-yl]-urea;

1-cyclopropyl-3-(7-pyrimidin-5-yl-imidazo[1,2-a]pyridin-2-yl)-urea;

1-cyclopropylmethyl-3-(7-pyrimidin-5-yl-imidazo[1,2-a]pyridin-2-yl)-urea;

1-propyl-3-(7-pyrimidin-5-yl-imidazo[1,2-a]pyridin-2-yl)-urea;

1-isopropyl-3-(7-pyrimidin-5-yl-imidazo[1,2-a]pyridin-2-yl)-urea;

1-(7-pyrimidin-5-yl-imidazo[1,2-a]pyridin-2-yl)-3-(2,2,2-trifluoro-ethyl)-urea;

1-(2-methoxy-ethyl)-3-(7-pyrimidin-5-yl-imidazo[1,2-a]pyridin-2-yl)-urea;

1-cyclobutyl-3-(7-pyrimidin-5-yl-imidazo[1,2-a]pyridin-2-yl)-urea;

1-[7-(6-amino-pyridin-3-yl)-imidazo[1,2-a]pyridin-2-yl]-3-ethyl-urea;

N-(7-acetylimidazo[1,2-a]pyridin-2-yl)-N′-ethylurea;

1-ethyl-3-[7-(5-methyl-[1,3,4]oxadiazol-2-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

{4-[2-(3-ethyl-ureido)-imidazo[1,2-a]pyridin-7-yl]-pyridin-2-yl}-carbamic acid tert-butyl ester;

1-ethyl-3-[7-(2H-pyrazol-3-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

1-ethyl-3-(7-[1,2,3]thiadiazol-4-yl-imidazo[1,2-a]pyridin-2-yl)-urea;

1-ethyl-3-[7-(5-isopropyl-[1,2,4]oxadiazol-3-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

1-ethyl-3-[7-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

{4-[2-(3-ethyl-ureido)-imidazo[1,2-a]pyridin-7-yl]-pyridin-2-yl}-carbamic acid tert-butyl ester;

1-[7-(2-amino-pyridin-4-yl)-imidazo[1,2-a]pyridin-2-yl]-3-ethyl-urea;

1-ethyl-3-[7-morpholinyl-4-carbonyl)-imidazo[1,2-a]pyridin-2-yl]-urea;

1-ethyl-3-[7-(2-methoxy-pyridin-4-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

1-ethyl-3-[5-(3-methyl-[1,2,4]oxadiazol-5-yl)-7-pyridin-3-yl-imidazo[1,2-a]pyridin-2-yl]-urea;

1-ethyl-3-[7-(6-fluoro-pyridin-3-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

1-ethyl-3-[7-(1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

1-ethyl-3-[7-(6-methyl-pyridin-3-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

1-ethyl-3-[7-(1-methyl-2-oxo-1,2-dihydro-pyridin-4-yl)-imidazo[1,2-a]pyridin-2-yl]-urea;

7-(2-dimethylamino-pyrimidin-5-yl)-2-(3-ethyl-ureido)-imidazo[1,2-a]pyridine-5-carboxylic acid ethylamide, and

1-[7-(2-dimethylamino-pyrimidin-5-yl)-5-pyrimidin-2-yl-imidazo[1,2-a]pyridin-2-yl]-3-ethyl-urea, or

a pharmaceutically acceptable salt thereof.

9. A compound selected from the group consisting of: