Fused heterocyclic compounds as phosphodiesterases (PDES) inhibitors

1. A compound represented by the formula (I):

wherein

ring A represents an optionally substituted 6-membered ring,

Z 1 represents —N═, and Z 2 , Z 3 and Z 4 represent —CH═;

the nitrogen atom of —N═ for Z 1 may be oxidized;

Y represents an oxygen atom, a sulfur atom, an optionally substituted methylene group or —NR c —;

R c represents a hydrogen atom, or a substituent; and

R represents

(1) a group represented by the formula:

wherein

R 1 represents a phenyl group substituted with at least one substituent selected from the group consisting of (a) an optionally substituted esterified carboxy group, (b) an optionally substituted alkyl group, (c) an optionally substituted C 6-14 aryl group, and (d) an optionally substituted alkyl-carbonyl group, or a 5- to 10-membered heterocyclic group, which is optionally substituted;

L represents a sulfur atom, an oxygen atom, an optionally substituted methylene group, —CO—,

—NR a —, —CH 2 O—, —OCH 2 —, —NR a COO—, —OCONR a —, —NR a CONR b —, —NR a COCH 2 —, —CH 2 CONR a —,

—NR a CO—, —CONR a —,

R a and R b are the same or different and each represents a hydrogen atom, or an optionally substituted C 1-6 alkyl group, or

L and R 1 in combination optionally form an optionally substituted bi- or tri-cyclic fused heterocyclic group; and

ring B 1 represents a benzene ring, a pyridine ring, a pyrimidine ring, a pyrazine ring or a pyridazine ring, each of which is optionally substituted; or

(2) a group represented by the formula:

wherein

R 2 represents a phenyl group or a 5- to 10-membered heterocyclic group, each of which is optionally substituted;

ring B 2 represents a benzene ring, a pyridine ring, a pyrimidine ring, a pyrazine ring or a pyridazine ring, each of which is optionally substituted; and

ring D represents an optionally further substituted 5- or 6-membered ring;

provided that

3,3′-benzene-1,4-diylbis(1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one),

1-cyclohexyl-3-(4-{[4-(methylsulfonyl)piperazin-1-yl]methyl}phenyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one,

and

3-[8-(4-methylpiperazin-1-yl)naphthalen-2-yl]-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

are excluded;

or a salt thereof.

2. The compound according to claim 1 , wherein L is an oxygen atom, or —NR a — wherein R a represents a hydrogen atom or an optionally substituted C 1-6 alkyl group, or

L and R 1 in combination optionally form an optionally substituted bi- or tri-cyclic fused heterocyclic group,

or a salt thereof.

3. The compound according to claim 1 , wherein the partial structure of formula (I):

is a group represented by the formula:

wherein

R 3 ′″ represents a hydrogen atom, a halogen atom, an optionally substituted C 1-4 alkyl group, or an optionally substituted C 1-4 alkoxy group,

Y 1 represents an optionally substituted methylene group or —NR c —, and

R c represents a hydrogen atom, or a substituent,

or a salt thereof.

4. The compound according to claim 1 , wherein the partial structure of formula (I):

is a group represented by the formula:

wherein

R 3a and R 3b are the same or different and each represents a hydrogen atom, a halogen atom, cyano, an optionally substituted C 1-4 alkyl group or an optionally substituted C 1-4 alkoxy group, and

R 4 represents an optionally substituted C 1-4 alkyl group,

provided that when one of R 3a and R 3b is a hydrogen atom, the other is not a hydrogen atom,

or a salt thereof.

5. The compound according to claim 1 , wherein ring B 1 is an optionally substituted benzene ring, or a salt thereof.

6. The compound according to claim 1 , wherein R 1 is a 5- to 10-membered heterocyclic group which may be substituted, or a salt thereof.

7. The compound according to claim 6 , wherein the 5- to 10-membered heterocyclic group which may be substituted is a group represented by the formula:

wherein R x represents a hydrogen atom or an optionally substituted C 1-6 alkyl group, or a salt thereof.

8. 1-Ethyl-6-methyl-3-{4-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, or a salt thereof.

9. 1-Ethyl-6-methoxy-3-{4-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, or a salt thereof.

10. 6-Methyl-1-(1-methylethyl)-3-{4-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, or a salt thereof.

11. 1-Ethyl-6-fluoro-3-{4-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, or a salt thereof.

12. 1,7-Dimethyl-3-{4-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, or a salt thereof.

13. 1-Ethyl-7-(hydroxymethyl)-3-{4-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, or a salt thereof.

14. A pharmaceutical composition comprising the compound according to claim 1 , or a salt thereof, and a pharmaceutically acceptable carrier.

15. The pharmaceutical composition according to claim 14 , which is a phosphodiesterase 10 A inhibitor.

16. The pharmaceutical composition according to claim 14 , which is an agent for treating schizophrenia, Alzheimer's disease, or bipolar disorders.

17. A method for treating schizophrenia, Alzheimer's disease, or bipolar disorders in a mammal, which comprises administering an effective amount of a compound represented by the formula (I):

wherein

ring A represents an optionally substituted 6-membered ring,

Z 1 represents —N═, and Z 2 , Z 3 and Z 4 represent —CH═;

the nitrogen atom of —N═ for Z 1 may be oxidized;

Y represents an oxygen atom, a sulfur atom, an optionally substituted methylene group or —NR c —;

R c represents a hydrogen atom, or a substituent; and

R represents

(1) a group represented by the formula:

wherein

R 1 represents a phenyl group substituted with at least one substituent selected from the group consisting of (a) an optionally substituted esterified carboxy group, (b) an optionally substituted alkyl group, (c) an optionally substituted C 6-14 aryl group, and (d) an optionally substituted alkyl-carbonyl group, or a 5- to 10-membered heterocyclic group, which is optionally substituted;

L represents a sulfur atom, an oxygen atom, an optionally substituted methylene group, —CO—,

—NR a —, —CH 2 O—, —OCH 2 —, —NR a COO—, —OCONR a —, —NR a CONR b —, —NR a COCH 2 —, —CH 2 CONR a —,

—NR a CO—, —CONR a —,

R a and R b are the same or different and each represents a hydrogen atom, or an optionally substituted C 1-6 alkyl group, or

L and R 1 in combination optionally form an optionally substituted bi- or tri-cyclic fused heterocyclic group; and

ring B 1 represents a benzene ring, a pyridine ring, a pyrimidine ring, a pyrazine ring or a pyridazine ring, each of which is optionally substituted; or

(2) a group represented by the formula:

wherein

R 2 represents a phenyl group or a 5- to 10-membered heterocyclic group, each of which is optionally substituted;

ring B 2 represents a benzene ring, a pyridine ring, a pyrimidine ring, a pyrazine ring or a pyridazine ring, each of which is optionally substituted; and

ring D represents an optionally further substituted 5- or 6-membered ring, or a salt thereof, to a mammal.