Novel condensed imidazole derivatives

1 . A compound represented by the following formula, or a salt or hydrate thereof,

wherein,

T 1 represents a monocyclic or bicyclic 4- to 12-membered heterocyclic group containing one or two nitrogen atoms in the ring, that may have one or more substituents;

X represents a C 1-6 alkyl group which may have one or more substituents, a C 2-6 alkenyl group which may have one or more substituents, a C 2-6 alkynyl group which may have one or more substituents, a C 6-10 aryl group which may have one or more substituents, a 5 to 10-membered heteroaryl group which may have one or more substituents, a C 6-10 aryl C 1-6 alkyl group which may have one or more substituents, or a 5 to 10-membered heteroaryl C 1-6 alkyl group which may have one or more substituents;

Z 1 and Z 2 each independently represent a nitrogen atom or a group represented by the formula —CR 2 ═;

R 1 and R 2 each independently represent a group according to the formula -A 0 -A 1 -A 2

(wherein A 0 represents a single bond or a C 1-6 alkylene group which may have 1 to 3 substituents selected from group B consisting of the substituents described below;

A 1 represents a single bond, an oxygen atom, a sulfur atom, a sulfinyl group, a sulfonyl group, a carbonyl group, a group represented by the formula —O—CO—, a group represented by the formula —CO—O—, a group represented by the formula —NR A —, a group represented by the formula —CO—NR A —, a group represented by the formula —NR A —CO—, a group represented by the formula —SO 2 —NR A —, or a group represented by the formula —NR A —SO 2 —;

A 2 and R A each independently represent a hydrogen atom, a halogen atom, a cyano group, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, C 6-10 aryl group, a 5 to 1 0-membered heteroaryl group, a 4 to 8-membered heterocyclic group, a 5 to 10-membered heteroaryl C 1-6 alkyl group, a C 6-10 aryl C 1-6 alkyl group, or a C 2-7 alkylcarbonyl group;

however, A 2 and R A each independently may have 1 to 3 substituents selected from the substituent group B described below:

when Z 2 is a group represented by the formula —CR 2 ═, R 1 , and R 2 may in combination form a 5 to 7-membered ring;

except in cases where: [1] R 1 is a hydrogen atom; Z 1 is a nitrogen atom; and Z 2 is —CH═; and [2] Z 1 is a nitrogen atom; and Z 2 is —C(OH)═;

<Substituent Group B>

Substituent group B represents the group consisting of: a hydroxyl group, a mercapto group, a cyano group, a nitro group, a halogen atom, a trifluoromethyl group, a C 1-6 alkyl group which may have one or more substituents, a C 3-8 cycloalkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 6-10 aryl group, a 5 to 10-membered heteroaryl group, a 4 to 8-membered heterocyclic group, a C 1-6 alkoxy group, a C 1-6 alkylthio group, a group represented by the formula —SO 2 —NR B1 —R B2 , a group represented by the formula —NR B1 —CO—R B2 , a group represented by the formula —NR B1 -R B2 (where R B1 and R B2 each independently represent a hydrogen atom or a C 1-6 alkyl group), a group represented by the formula —CO-R B3 (where R B3 represents a 4 to 8-membered heterocyclic group), a group represented by the formula —CO—R B4 —R B5 and a group represented by the formula —CH 2 —CO—R B4 —R B5 (where R B4 represents a single bond, an oxygen atom, or a group represented by the formula —NR B6 —; R B5 and R B6 each independently represent a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 6-10 aryl group, a 5 to 10-membered heteroaryl group, a 4 to 8-membered heterocyclic C 1-6 alkyl group, a C 6-10 aryl C 1-6 alkyl group, or a 5 to 10-membered heteroaryl C 1-6 alkyl group)).

2 . The compound according to claim 1 , or a salt or hydrate thereof, wherein T 1 is,

a group represented by the following formula:

(wherein, n and m each independently represent 0 or 1) which may have one or more substituents;

an azetidin-1-yl group which may have one or more substituents;

a pyrrolidin-1-yl group which may have one or more substituents;

a piperidin-1-yl group which may have one or more substituents; or

an azepan-1-yl group which may have one or more substituents.

3 . The compound according to claim 1 , or a salt or hydrate thereof, wherein T 1 is,

a group represented by the following formula:

(where n and m each independently represent 0 or 1);

an azetidin-1-yl group which may have an amino group;

a pyrrolidin-1-yl group which may have an amino group;

a piperidin-1-yl group which may have an amino group; or

an azepan-1-yl group which may have an amino group.

4 . The compound according to claim 1 , or a salt or hydrate thereof, wherein T 1 is a piperazin-1-yl group or a 3-aminopiperidin-1-yl group.

5 . The compound according to claim 1 , or a salt or hydrate thereof, wherein T 1 is a piperazin-1-yl group.

6 . The compound according to claim 1 , or a salt or hydrate thereof, wherein X is a group represented by the formula —X 1 —X 2 (where X 1 represents a single bond or a methylene group which may have one or more substituents; X 2 represents a C 2-6 alkenyl group which may have one or more substituents, a C 2-6 alkynyl group may have one or more substituents, or a phenyl group which may have one or more substituents).

7 . The compound according to claim 1 , or a salt or hydrate thereof, wherein X is a group represented by the formula —X 11 —X 12 (where X 11 represents a single bond or a methylene group; X 12 represents a C 2-6 alkenyl group, a C 2-6 alkynyl group, or a phenyl group which may have one or more substituents).

8 . The compound according to claim 6 , or a salt or hydrate thereof, wherein the phenyl group that may have one or more substituents is a phenyl group which may have at the 2-position a substituent selected from the group consisting of a hydroxyl group, a fluorine atom, a chlorine atom, a methyl group, an ethyl group, a fluoromethyl group, a vinyl group, a methoxy group, an ethoxy group, an acetyl group, a cyano group, a formyl group, and a C 2-7 alkoxycarbonyl group.

9 . The compound according to claim 1 , or a salt or hydrate thereof, wherein X is a 3-methyl-2-buten-1-yl group, a 2-butyn-1-yl group, a benzyl group, or a 2-chlorophenyl group.

10 . The compound according to claim 1 , or a salt or hydrate thereof, wherein X is a 2-butyn-1-yl group.

11 . The compound according to claim 1 , or a salt or hydrate thereof, wherein either the Z 1 or Z 2 is a nitrogen atom.

12 . The compound according to claim 1 , or a salt or hydrate thereof, wherein,

Z 1 is a nitrogen atom; and

Z 2 is a group represented by the formula —CR 2 ═

(where R 2 is as defined above in claim 1) .

13 . The compound according to claim 1 , or a salt or a hydrate thereof, wherein,

Z 2 is a nitrogen atom; and

Z 1 is a group represented by the formula —CR 2 ═

(where R 2 is as defined above in claim 1) .

14 . The compound according to claim 1 , or a salt or hydrate thereof,

wherein R 1 represents a hydrogen atom, or a group represented by the formula -A 10 -A 11 -A 12

(where A 10 represents a C 1-6 alkylene group which may have 1 to 3 substituents selected from the substituent group C described below;

A 11 represents a single bond, an oxygen atom, a sulfur atom or a carbonyl group;

A 12 represents a hydrogen atom, a C 6-10 aryl group which may have 1 to 3 substituents selected from the substituent group C described below, a 5 to 10-membered heteroaryl group which may have 1 to 3 substituents selected from the substituent group C described below, a 5 to 10-membered heteroaryl C 1-6 alkyl group which may have 1 to 3 substituents selected from the substituent group C described below, or a C 6-10 aryl C 1-6 alkyl group which may have 1 to 3 substituents selected from the substituent group C described below:

<Substituent Group C>

Substituent group C represents the group consisting of: a hydroxyl group, a nitro group, a cyano group, a halogen atom, a C 1-6 alkyl group, a C 1-6 alkoxy group, a C 1-6 alkylthio group, a trifluoromethyl group, a group represented by the formula —NR C1 —R C2 (where each of R C1 and R C2 independently represent a hydrogen atom or C 1-6 alkyl group), a group represented by the formula —CO—R C3 —R C4 and a group represented by the formula —CH 2 —CO—R C3 —R C4 (where R C3 represents a single bond, an oxygen atom, or a group represented by the formula —NR C5 —; R C4 and R C5 each independently represent a hydrogen atom or a C 1-6 alkyl group).

15 . The compound according to claim 1 , or a salt or hydrate thereof,

wherein R 1 is a hydrogen atom, a C 1-6 alkyl group which may have 1 to 3 substituents selected from the substituent group C described below, a 5 to 10-membered heteroaryl C 1-6 alkyl group which may have 1 to 3 substituents selected from the substituent group C described below, or a C 6-10 aryl C 1-6 alkyl group which may have 1 to 3 substituents selected from the substituent group C described below:

<Substituent Group C>

Substituent group C represents the group consisting of: a hydroxyl group, a nitro group, a cyano group, a halogen atom, a C 1-6 alkyl group, a C 1-6 alkoxy group, a C 1-6 alkylthio group, a trifluoromethyl group, a group represented by the formula —NR C1 —R C2 (where each of R C1 and R C2 independently represent a hydrogen atom or a C 1-6 alkyl group), a group represented by the formula —CO—R C3 —R C4 and a group represented by the formula —CH 2 —CO—R —C3 R C4 (where R C3 represents a single bond, an oxygen atom, or a group represented by the formula —NR C5 —; R C4 and R C5 each independently represent a hydrogen atom or a C 1-6 alkyl group);

16 . The compound according to claim 14 , or a salt or hydrate thereof, wherein the substituent group C is a group consisting of a cyano group, a C 1-6 alkoxy group, a C 2-7 alkoxycarbonyl group, and a halogen atom.

17 . The compound according to claim 1 , or a salt or hydrate thereof, wherein R 1 is a methyl group, a cyanobenzyl group, a fluorocyanobenzyl group, a phenethyl group, a 2-methoxyethyl group, or a 4-methoxycarbonylpyridin-2-yl group.

18 . The compound according to claim 1 , or a salt or hydrate thereof, wherein R 1 is a methyl group or a 2-cyanobenzyl group.

19 . The compound according to claim 1 , or a salt or hydrate thereof,

wherein R 2 is a hydrogen atom, a cyano group, or a group represented by the formula -A 21 -A 22

(where A 21 represents a single bond, an oxygen atom, a sulfur atom, a sulfinyl group, a sulfonyl group, a carbonyl group, a group represented by the formula —O—CO—, a group represented by the formula —CO—O—, a group represented by the formula —NR A2 —, a group represented by the formula —CO—NR A2 —, or a group represented by the formula —NR A2 —CO—;

A 22 and R A2 each independently represent a hydrogen atom, a cyano group, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 6-10 group, a 5- to 10-membered heteroaryl group, a 4- to 8-membered heterocyclic group, a 5- to 10-membered heteroaryl C 1-6 alkyl group, or a C 6-10 aryl C 1-6 alkyl group;

however, A 22 and R A2 each may independently have 1- to 3 substituents selected from the substituent group D described below:

<Substituent Group D>

Substituent group D represents the group consisting of: a hydroxyl group, a cyano group, a nitro group, a halogen atom, a C 1-6 alkyl group, a C 1-6 alkoxy group, a C 1-6 alkylthio group, a trifluoromethyl group, a group represented by the formula —NR D1 —R D2 (where R D1 and R D2 each independently represent a hydrogen atom or a C 1-6 alkyl group), a group represented by the formula —CO—R D3 (where R D3 represents a 4 to 8-membered heterocyclic group), and a group represented by the formula —CO—R D4 —R D5 (where R D4 represents a single bond, an oxygen atom, or a group represented by the formula —NR D6 —; R D5 and R D6 each independently represent a hydrogen atom, a C 3-8 cycloalkyl group, or a C 1-6 alkyl group)).

20 . The compound according to claim 1 , or a salt or hydrate thereof,

wherein R 2 represents a hydrogen atom, a cyano group, a carboxy group, a C 2-7 alkoxycarbonyl group, a C 1-6 alkyl group, a group represented by the formula —CONR D7 R D8 (where R D7 and R D8 each independently represent a hydrogen atom or a C 1-6 alkyl group), or a group represented by the formula -A 23 -A 24

(where A 23 represents an oxygen atom, a sulfur atom or a group represented by the formula —NR A3 ;

A 24 and R A3 each independently represent a hydrogen atom, a C 1-6 alkyl group which may have a substituent selected from the substituent group D1 described below, a C 3 -8 cycloalkyl group which may have a substituent selected from the substituent group D1 described below, a C 2-6 alkenyl group which may have a substituent selected from the substituent group D1 described below, a C 2-6 alkynyl group which may have a substituent selected from the substituent group D1 described below, a phenyl group which may have a substituent selected from the substituent group D1 described below, or a 5 to 10-membered heteroaryl group which may have a substituent selected from the substituent group D1 described below:

<Substituent Group D1>

Substituent group D1 represents the group consisting of: a carboxy group, a C 2-7 alkoxycarbonyl group, a C 1-6 alkyl group, a group represented by the formula —CONR D7 R D8 (where R D7 and R D8 each independently represent a hydrogen atom or C 1-6 alkyl group), a pyrrolidin-1-ylcarbonyl group, a C 1-6 alkyl group, and a C 1-6 alkoxy group).

21 . The compound according to claim 1 , or a salt or hydrate thereof,

wherein R 2 represents a hydrogen atom, a cyano group, a C 1-6 alkoxy group, or a group represented by the formula -A 25 -A 26

(where A 25 represents an oxygen atom, a sulfur atom, or a group represented by the formula —NR A4 —;

A26 and R A4 each independently represent a hydrogen atom, a C 1-6 alkyl group having a substituent selected from the substituent group D1 described below, a C 3-8 cycloalkyl group having a substituent selected from the substituent group D1 described below, or a phenyl group having a substituent selected from the substituent group D1 described below:

<Substituent Group D1>

Substituent group D1 represents the group consisting of: a carboxy group, a C 2-7 alkoxycarbonyl group, a C 1-6 alkyl group, a group represented by the formula —CONR D7 R D8 (where R D7 and R D8 each independently represent a hydrogen atom or a C 1-6 alkyl group), pyrrolidin-1-ylcarbonyl group, a C 1-6 alkyl group, and a C 1-6 alkoxy group).

22 . The compound according to claim 1 , or a salt or hydrate thereof,

wherein R 2 is a hydrogen atom, a cyano group, a methoxy group, a carbamoylphenyloxy group, or a group represented by the following formula:

(where A 27 represents an oxygen atom, a sulfur atom, or —NH—;

A 28 and A 29 each independently represent a hydrogen atom or a C 1-6 alkyl group).

23 . The compound according to claim 1 , or a salt or hydrate thereof, wherein R 2 is a hydrogen atom, a cyano group, or a 2-carbamoylphenyloxy group.

24 . The compound according to claim 1 , or a salt or hydrate thereof, wherein the compound of formula (I) indicated above is any one selected from the group consisting of:

7-(2-butynyl)-2-cyano-1-methyl-8-(piperazin-1-yl)-1,7-dihydropurin-6-one,

3-(2-butynyl)-5-methyl-2-(piperazin-1-yl)-3,5-dihydroimidazo[4,5-d]pyridazin-4-one,

2-(3-aminopiperidin-1-yl)-3-(2-butynyl)-5-methyl-3,5-dihydroimidazo[4,5-d]pyridazin-4-one,

2-[7-(2-butynyl)-1-methyl-6-oxo-8-(piperazin-1-yl)-6,7-dihydro-1H-purin-2-yloxy]benzamide,

7-(2-butynyl)-1-(2-cyanobenzyl)-6-oxo-8-(piperazin-1-yl)-6,7-dihydro-1H-purine-2-carbonitrile, and

2-[3-(2-butynyl)-4-oxo-2-(piperazin-1-yl)-3,4-dihydroimidazo[4,5-d]pyridazin-5-ylmethyl]benzonitrile.

25 . A pharmaceutical agent comprising a compound of claim 1 .

26 . A dipeptidyl peptidase IV inhibitor comprising a compound of claim 1 .

27 . A pharmaceutical composition comprising a compound of claim 1 and an adjuvant useful for formulation.

28 . A preventive or a therapeutic agent for diabetes mellitus, which comprises a compound of claim 1 .

29 . A preventive or therapeutic agent, which comprises a compound of claim 1 , for diabetes mellitus, obesity, hyperlipidemia, AIDS, osteoporosis, a gastrointestinal disorder, angiogenesis, infertility, an inflammatory disease, an allergic disease, or cancer.

30 . An immunomodulator, a hormone modulator, or an anti-rheumatic drug, which comprises a compound of claim 1 .

31 . A therapeutic or preventive method for a disease in which the inhibition of dipeptidyl peptidase IV is effective, wherein the method comprises administering to a patient a compound of claim 1 , or a salt or hydrate thereof, in a pharmaceutically effective amount.

32 . The use of a compound of claim 1 , or a salt or hydrate thereof, in producing a pharmaceutical agent.

33 . The use of a compound of claim 1 , or a salt or hydrate thereof, in producing a therapeutic or preventive agent for a disease in which the inhibition of dipeptidyl peptidase IV is effective.