# US 6,723,735 B1 · Imidazo-pyridine derivatives as ligands for GABA receptors

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- Number: US 6,723,735 B1
- Document ID: US6723735B1
- Status: Granted
- Kind: B1
- Application number: 10/070,026
- Filed: 2002-02-25
- Granted: 2004-04-20
- Earliest claimed: 1999-09-07
- Assignees: Merck Sharp & Dohme Corp.
- Inventors: David James Hallett; Michael Rowley
- Web page: https://patentgrep.com/patent/US6723735B1

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/22: Anxiolytics
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention is directed to 3-phenylimidazol[4,5-b]pyridine derivatives, that are selective ligands for GABAA receptors. These compounds are useful in the treatment and prevention of disorders of the central nervous system, including anxiety and convulsions.

## Claims

### Claim 1

A compound of formula I, or a pharmaceutically acceptable salt or a prodrug thereof:
wherein
Y represents a chemical bond, or a methylene (CH2), carbonyl (C═O), thiocarbonyl (C═S) or amide (CONH or NHCO) linkage;
Z represents an optionally substituted phenyl, heteroaryl or heteroaryl(C1-6)alkyl group, wherein heteroaryl is selected from the group consisting of pyridine, pyrrolidine, imidazole and thiophene, or a group of formula —NR1R2;
R1 and R2 independently represent hydrogen, hydrocarbon or a heterocyclic group wherein the heterocyclic group is selected from the group consisting of pyridine, pyrrolidine, imidazole and thiophene; or R1 and R2, together with the intervening nitrogen atom, represent an optionally substituted heterocyclic ring selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl; and
R3 represents phenyl or furanyl, which groups may be optionally substituted.

### Claim 2 (depends on 1)

The compound of claim 1 represented by formula II, or a pharmaceutically acceptable salt or a prodrug thereof:
wherein
Z1 represents an optionally substituted aryl or heteroaryl group, wherein heteroaryl is selected from the group consisting of pyridine, pyrrolidine, imidazole and thiophene; and
R13 represents phenyl or furanyl.

### Claim 3 (depends on 2)

The compound of claim 2 wherein Z1 represents cyanophenyl, formylphenyl, acetylphenyl, pyridinyl, cyano-thienyl or imidazolyl.

### Claim 4 (depends on 2)

A compound of claim 2 wherein R13 represents phenyl or furanyl.

### Claim 5

A compound which is selected from:
6-(furan-3-yl)-3-[3-(pyridin-3-yl)phenyl]-3H-imidazo[4,5-b]pyridine;
1-[3-(6-(furan-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)phenyl]pyrrolidin-2-one;
6-(furan-3-yl)-3-[3-(imidazol-1-yl)phenyl]-3H-imidazo[4,5-b]pyridine;
6-phenyl-3-[3-(pyridin-3-yl)phenyl]-3H-imidazo[4,5-b]pyridine;
or a pharmaceutically acceptable salt or a prodrug thereof.

### Claim 6

A compound which is selected from:
1-[3′-(6-(furan-3-yl)imidazo[4,5-b]pyridin-3-yl)biphenyl-2-yl]ethanone;
3′-[6-(furan-3-yl)imidazo[4,5-b]pyridin-3-yl]biphenyl-2-carbaldehyde;
3′-[6-(furan-3-yl)imidazo[4,5-b]pyridin-3-yl]biphenyl-2-carbonitrile;
3-[3-(6-(furan-3-yl)imidazo[4,5-b]pyridin-3-yl)phenyl]thiophene-2-carbonitrile;
or a pharmaceutically acceptable salt or a prodrug thereof.

### Claim 7 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt or a prodrug thereof and a pharmaceutically acceptable carrier.

### Claim 8 (depends on 1)

A process for the preparation of the compound of claim 1, which comprises:
(A) reacting a compound of formula III:
wherein Y, Z and R3 are as defined in claim 1; with formic acid; or
(B) reacting a compound of formula VI with a compound of formula VII:
wherein Z and R3 are as defined in claim 1, L2 represents a suitable leaving group, and M1 represents a boronic acid moiety —B(OH)2 or a cyclic ester thereof formed with an organic diol; in the presence of a transition metal catalyst; or
(C) reacting a compound of formula VIII with a compound of formula IX:
wherein Z and R3 are as defined in claim 1, and L3 represents a suitable leaving group; in the presence of a transition metal catalyst; or
(D) reacting a compound of formula X with a compound of formula XI:
wherein Y, Z and R3 are as defined in claim 1, and L4 represents a suitable leaving group; in the presence of a transition metal catalyst.

### Claim 9 (depends on 1)

A method for the treatment of anxiety which comprises administering to a patient in need of such treatment an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt or a prodrug thereof.

### Claim 10 (depends on 1)

A method for the prevention of anxiety which comprises administering to a patient in need of such prevention an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt or a prodrug thereof.