Spirochromanone derivatives
View Patent ↗The invention relates to a compound of a formula (I): or a pharmaceutically acceptable salt or ester thereof, useful as a therapeutic agent for various ACC-related disorders.
1. A compound of formula (I):
wherein R 1 represents a halogen atom, a cyano group, a lower alkenyl group, a lower alkoxy group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-lower alkoxy group, a carboxy-lower alkenyl group, or a group of -Q 1 -N(R a )-Q 2 -R b ,
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group,
an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of —CO—N(R c )R d , or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R 5 represents a hydrogen atom, a halogen atom, a cyano group, a lower alkenyl group, a lower alkoxy group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-lower alkoxy group, a carboxy-lower alkenyl group, or a group of -Q l -N(R a )-Q 2 -R b , a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group, an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of -CO-N(R C )R d , or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R 2 , R 3 and R 4 each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, a hydroxy-lower alkoxy group, a lower alkoxy-lower alkoxy group, a cyclo-lower alkyloxy group, a cyclo-lower alkyl-lower alkoxy group, a lower alkylthio group, a group of —O—R k or a group of —N(R e )R f , or
a lower alkoxy group substituted by the group of —N(R e )R f , or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group and a cyclo-lower alkyl group, or
an aryl or heteroaromatic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a nitro group, a hydroxyl group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group and a lower alkylthio group;
Q 1 and Q 2 each independently represent a single bond, or a group of —CO—, —SO 2 — or —C(R g )(R h )—, when Q 2 represents the group of —C(R g )(R h )—, R a and R g , taken together, may represent a group of -Q 1 -N═C(R h )—R b ;
R a and R b each independently represent a hydrogen atom, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group, a carbamoyl group, a lower alkoxycarbonyl group or a group of —N(R i )R j , or
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or
a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group;
R c , R d , R g , R h , R i and R j each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
R e and R f each independently represent a hydrogen atom, a lower alkyl group or a halo-lower alkyl group, or taken together, they may form a lower alkylene group optionally interrupted by an oxygen atom, a sulfur atom or an imino group;
R k represents a pyrrolidinyl, tetrahydrofuranyl, piperidyl group optionally substituted by a lower alkyl group or a halo-lower alkyl group;
T, U, W and Y each independently represent a nitrogen atom or a methine group; and
V represents an oxygen atom or a sulfur atom;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
2. The compound of claim 1 , wherein R 1 is a halogen atom, a cyano group, an aralkyloxycarbonyl group or a group of -Q 1 -N(R a )-Q 2 -R b ,
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group,
an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of —CO—N(R c )R d , or a lower alkyl or alkenyl group having the said aryl or heterocyclic group,
and in the group of -Q 1 -N(R a )-Q 2 -R b ,
(i) Q 1 and Q 2 are a single bond, R a is a hydrogen atom or a lower alkyl group, and R b is a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group,
(ii) Q 1 is a single bond, Q 2 is a group of —CO—, R a is a hydrogen atom or a lower alkyl group, and R b is a hydrogen atom, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group or a group of —N(R i )R j , or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group,
(iii) Q 1 is a group of —CO—, Q 2 is a single bond, and R a and R b each independently are a hydrogen atom or a lower alkyl group,
(iv) Q 1 is a group of —CO—, Q 2 is a group of —C(R g )(R h )—, R a is a hydrogen atom or a lower alkyl group, and R b is a carbamoyl group, or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or
(v) Q 1 is a group of —SO 2 —, Q 2 is a single bond, and R a and R b each independently are a hydrogen atom or a lower alkyl group; and
R 5 is a hydrogen atom, a halogen atom or a lower alkyl group;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
3. The compound of claim 1 , wherein the compound is represented by formula (Ia):
wherein R 1a represents a halogen atom, a cyano group, a lower alkenyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, or a group of -Q 1a -N(R a )-Q 2a -R b , or
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group, or
an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of —CO—N(R c )R d ;
R 2a , R 3a and R 4a each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, a cyclo-lower alkyloxy group, a cyclo-lower alkyl-lower alkoxy group, a lower alkylthio group, or a group of —N(R e )R f , or
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group and a cyclo-lower alkyl group, or
an aryl or heteroaromatic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a nitro group, a hydroxyl group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group and a lower alkylthio group;
Q 1a and Q 2a each independently represent a single bond, or a group of —CO—, —SO 2 — or —C(R g ) (R h )—;
R a and R b each independently represent a hydrogen atom, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group, a carbamoyl group, a lower alkoxycarbonyl group or a group of —N(R i )R j , or
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group; or
a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group;
R c , R d , R g , R h , R i and R j each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
R e and R f each independently represent a hydrogen atom, a lower alkyl group or a halo-lower alkyl group, or taken together, they may form a lower alkylene group optionally interrupted by an oxygen atom, a sulfur atom or an imino group;
T, U, W and Y each independently represent a nitrogen atom or a methine group; and
V represents an oxygen atom or a sulfur atom;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
4. The compound of claim 3 , wherein R 1a is a cyano group, a lower alkenyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, or a group of -Q 1a -N(R a )-Q 2a -R b ,
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group, or
an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of —CO—N(R c )R d ,
and in the group of -Q 1a -N(R a )-Q 2a -R b ,
(i) Q 1a and Q 2a are a single bond, R a is a hydrogen atom or a lower alkyl group, and R b is a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group,
(ii) Q 1a is a single bond, Q 2a is a group of —CO—, R a is a hydrogen atom or a lower alkyl group, and R b is a hydrogen atom, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group or a group of —N(R i )R j , or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group,
(iii) Q 1a is a group of —CO—, Q 2a is a single bond, and R a and R b each independently are a hydrogen atom or a lower alkyl group,
(iv) Q 1a is a group of —CO—, Q 2a is a group of —C(R g )(R h )—, R a is a hydrogen atom or a lower alkyl group, and R b is a carbamoyl group, or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or
(v) Q 1a is a group of —SO 2 —, Q 2a is a single bond, and R a and R b each independently are a hydrogen atom or a lower alkyl group;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
5. The compound of claim 1 , wherein the heterocyclic group for R 1 is a pyrrolyl group, an imidazolyl group, a pyrazolyl group, a 1,2,4-triazolyl group, a tetrazolyl group, a pyridyl group, a pyrimidinyl group, a pyrrolidinyl group, a dihydro-1,2,4-triazolyl group, a dihydro-1,2,4-oxadiazolyl group, a dihydro-1,3,4-oxadiazolyl group, a dihydro-1,2,4-thiadiazolyl group, a dihydro-1,2,3,5-oxathiadiazolyl group, a piperidyl group, a piperazinyl group, a morpholinyl group or a thiomorpholinyl group, which may have a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of —CO—N(R c )R d ;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
6. The compound of claim 1 , wherein R 1 is an acetylamino group, a methoxycarbonylamino group, a carbamoylamino group, a 2-methyl-3-pyrazolylamino group, a 2-ethyl-3-pyrazolylamino group, a 1,2,4-triazol-3-ylamino group, a (carbamoylmethyl)carbamoyl group, an aminosulfonyl group, a methylaminosulfonyl group, a 1-carboxy-1-methylethyl group, a tert-butyl group, a 3-carboxyphenyl group, a 4-pyrazolyl group, a 1-methyl-4-pyrazolyl group, a 1,2,4-triazol-3-yl group, a 5-carbamoyl-1,2,4-triazol-3-yl group, a 5-tetrazolyl group, a 1-methyl-5-tetrazolyl group, a 2-methyl-5-tetrazolyl group, a 1-pivaloyloxymethyl-5-tetrazolyl group, a 2-pivaloyloxymethyl-5-tetrazolyl group, a 3-pyridyl group, a 4-carboxy-2-pyridyl group, a 5-carboxy-3-pyridyl group, a 5-carbamoyl-2-pyridyl group, a 5-carbamoyl-3-pyridyl group, a 2-pyrimidinyl group, a 5-oxo-4,5-dihydro-1,2,4-triazol-3-yl group, a 5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl group, a 5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl group, a 3-oxo-1-piperazinyl group, a 4-acetyl-1-piperazinyl group, a 4-carbamoyl-1-piperazinyl group, a 4-methylsulfonyl-1-piperazinyl group or a 1,1-dioxido-4-thiomorpholinyl group, and R 5 is a hydrogen atom; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
7. The compound of claim 2 , wherein the heteroaromatic group for R b is a pyrrolyl group, a pyrazolyl group, a 1,2,4-triazolyl group or a pyrimidinyl group, which may be substituted by a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
8. The compound of claim 1 , wherein the compound is represented by formula (I-1)
wherein Ar 1 is selected from a group of formula (aa):
R 10 is a halogen atom, a cyano group, a lower alkenyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-lower alkoxy group, a carboxy-lower alkenyl group, or a group of -Q 1 -N(R a )-Q 2 -R b ,
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group,
an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of —CO—N(R c )R d , or a lower alkyl or alkenyl group having the said aryl or heterocyclic group,
and in the group of -Q 1 -N(R a )-Q 2 -R b ,
(i) Q 1 and Q 2 are a single bond, R a is a hydrogen atom or a lower alkyl group, and R b is a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group,
(ii) Q 1 is a single bond, Q 2 is a group of —CO—, R a is a hydrogen atom or a lower alkyl group, and R b is a hydrogen atom, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group or a group of —N(R i )R j , or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group,
(iii) Q 1 is a group of —CO—, Q 2 is a single bond, and R a and R b each independently are a hydrogen atom or a lower alkyl group,
(iv) Q 1 is a group of —CO—, Q 2 is a group of —C(R g )(R h )—, R a is a hydrogen atom or a lower alkyl group, and R b is a carbamoyl group, or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or
(v) Q 1 is a group of —SO 2 —, Q 2 is a single bond, and R a and R b each independently are a hydrogen atom or a lower alkyl group;
R 50 is a hydrogen atom, a halogen atom or a lower alkyl group;
R 2 , R 3 and R 4 each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, a hydroxy-lower alkoxy group, a lower alkoxy-lower alkoxy group, a cyclo-lower alkyloxy group, a cyclo-lower alkyl-lower alkoxy group, a lower alkylthio group, a group of —O—R k or a group of —N(R e )R f , or
a lower alkoxy group substituted by the group of —N(R e )R f , or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group and a cyclo-lower alkyl group, or
an aryl or heteroaromatic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a nitro group, a hydroxyl group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group and a lower alkylthio group;
R c , R d , R g , R h , R i and R j each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
R e and R f each independently represent a hydrogen atom, a lower alkyl group or a halo-lower alkyl group, or taken together, they may form a lower alkylene group optionally interrupted by an oxygen atom, a sulfur atom or an imino group;
R k represents a pyrrolidinyl, tetrahydrofuranyl, piperidyl group optionally substituted by a lower alkyl group or a halo-lower alkyl group; and
U and Y each independently represent a nitrogen atom or a methine group; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
9. The compound of claim 8 , wherein R 10 is a tetrazolyl group or a 5-carboxy-3-pyridyl group; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
10. The compound of claim 8 , wherein R 10 is a tetrazolyl group; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
11. The compound of claim 8 , wherein Ar 1 is a group of formula (aa1):
in which R 2 and R 4 each are independently a hydrogen atom, a halogen atom, a cyclo-lower alkyl group, a lower alkoxy group, a phenyl group, a pyridyl group or a group of —N(R e )R f ; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
12. The compound of claim 8 , wherein Ar 1 is a group of formula (aa1):
in which R 2 is a methoxy group, an ethoxy group, a 1-pyrrolidinyl group or a phenyl group, R 3 is a hydrogen atom, a fluorine atom, a chlorine atom or a cyano group, and R 4 is a fluorine atom, a chlorine atom, a methoxy group or a cyclopropyl group; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
13. A compound selected from the group consisting of:
(1) N-{1′-[(4-methoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}acetamide,
(2) N-{1′-[(4-methoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}acetamide hydrochloride,
(3) N-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}acetamide,
(4) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-spiro[chroman-2,4′-piperidin]-4-one,
(5) 6-amino-1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-spiro[chroman-2,4′-piperidin]-4-one,
(6) N-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}urea,
(7) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidine]-6-sulfonamide,
(8) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-N-methyl-4-oxospiro[chroman-2,4′-piperidine]-6-sulfonamide,
(9) 6-bromo-1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-spiro[chroman-2,4′-piperidin]-4-one,
(10) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-[(1-methyl-1H-pyrazol-5-yl)amino]spiro[chroman-2,4′-piperidin]-4-one,
(11) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-[(1-ethyl-1H-pyrazol-5-yl)amino]spiro[chroman-2,4′-piperidin]-4-one,
(12) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-pyrimidin-2-yl-spiro[chroman-2,4′-piperidin]-4-one,
(13) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-pyridin-3-yl-spiro[chroman-2,4′-piperidin]-4-one,
(14) 5-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinamide,
(15) 6-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinamide,
(16) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidine]-6-carbonitrile,
(17) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(18) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one sodium salt,
(19) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1-methyltetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(20) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(2-methyltetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(21) (5-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}-2H-tetrazol-2-yl)-methyl pivalate,
(22) (5-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}-2H-tetrazol-1-yl)-methyl pivalate,
(23) 1′-[(8-cyclopropyl-4-ethoxy-1,7-naphthyridin-2-yl)-carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(24) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)spiro[chroman-2,4′-piperidin]-4-one,
(25) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)spiro[chroman-2,4′-piperidin]-4-one,
(26) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(benzyloxycarbonyl)spiro[chroman-2,4′-piperidin]-4-one,
(27) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(carboxy)spiro[chroman-2,4′-piperidin]-4-one,
(28) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)spiro[chroman-2,4′-piperidin]-4-one,
(29) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1H-1,2,4-triazol-3-yl)spiro[chroman-2,4′-piperidin]-4-one,
(30) 3-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}-1H-1,2,4-triazole-5-carboxamide,
(31) 6-(4-acetylpiperazin-1-yl)-1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-spiro[chroman-2,4′-piperidin]-4-one,
(32) 6-(4-acetylpiperazin-1-yl)-1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]spiro[chroman-2,4′-piperidin]-4-one,
(33) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-[4-(methylsulfonyl)piperazin-1-yl]spiro[chroman-2,4′-piperidin]-4-one,
(34) sodium 3-{1′-[(1-cyclopropyl-5-methoxyisoquinolin-7-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}-5-oxo-1,2,4-oxadiazol-4-ide,
(35) 1′-[4-(2-hydroxyethoxy)-8-methoxy-2-naphthoyl]-6-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)spiro[chroman-2,4′-piperidin]-4-one,
(36) 1′-[8-methoxy-4-(1H-tetrazol-5-yl)-2-naphthoyl]-6-(1-methyl-1H-pyrazol-4-yl)spiro[chroman-2,4′-piperidin]-4-one,
(37) 3-1′-[(8-cyclopropyl-4-methoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}-1H-1,2,4-triazole-5-carboxamide,
(38) 5-{1′-[(8-cyclopropyl-4-methoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinic acid,
(39) N-(2-amino-2-oxoethyl)-1′-{[1-cyclopropyl-5-(2-hydroxyethoxy)isoquinolin-7-yl]carbonyl}-4-oxospiro[chroman-2,4′-piperidine]-6-carboxamide,
(40) 5-(1′-{[8-cyclopropyl-4-(2-hydroxyethoxy)-1,7-naphthyridin-2-yl]carbonyl}-4-oxospiro[chroman-2,4′-piperidin]-6-yl)nicotinamide,
(41) 5-{1′-[(1-cyclopropyl-5-methoxyisoquinolin-7-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinic acid sodium salt,
(42) 3-{1′-[(1-cyclopropyl-5-methoxyisoquinolin-7-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}benzoic acid,
(43) 1′-(4,8-dimethoxy-2-naphthoyl)-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(44) 1′-(8-methoxy-4-morpholin-4-yl-2-naphthoyl)-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(45) 1′-[(8-methoxy-4-phenylquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(46) 1′-[(8-cyclopropyl-4-methoxyquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(47) 1′-[(4-ethoxy-8-ethylquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(48) 1′-[(4-ethoxy-8-ethylquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(49) 1′-[(5,8-dichloro-4-ethoxyquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(50) 1′-[(1,5-dimethoxyisoquinolin-7-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(51) 1′-[(1-cyclopropyl-5-ethoxyisoquinolin-7-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(52) sodium 5-{1′-[(1-cyclopropyl-5-ethoxyisoquinolin-7-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}tetrazol-1-ide,
(53) 1′-{[1-cyclopropyl-5-(2-hydroxyethoxy)isoquinolin-7-yl]carbonyl}-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(54) 1′-[(4-cyclopropyl-8-ethoxyisoquinolin-6-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(55) 1′-[(4-cyclopropyl-8-methoxyquinolin-6-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(56) sodium 5-{1′-[(1-cyclopropyl-5-ethoxyisoquinolin-7-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinate,
(57) sodium 5-{1′-[(8-cyclopropyl-4-methoxy-quinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinate,
(58) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1H-pyrazol-4-yl)spiro[chroman-2,4′-piperidin]-4-one,
(59) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1-methyl-1H-pyrazol-4-yl)spiro[chroman-2,4′-piperidin]-4-one,
(60) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1,1-dioxidothiomorpholin-4-yl)spiro[chroman-2,4′-piperidin]-4-one,
(61) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(3-oxopiperazin-1-yl)spiro[chroman-2,4′-piperidin]-4-one,
(62) 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(4H-1,2,4-triazol-3-ylamino)spiro[chroman-2,4′-piperidin]-4-one,
(63) 1′-[(4-hydroxy-8-methoxyquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(64) 1′-[(8-hydroxy-4-methoxyquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one,
(65) 1-[(8-cyclopropyl-4-methoxyquinolin-2-yl)carbonyl]-6′-(1H-tetrazol-5-yl)spiro[piperidine-4,2′-thiochroman]-4′-one,
(66) 6′-tert-butyl-1-[(4,8-dimethoxyquinolin-2-yl)carbonyl]spiro[piperidine-4,2′-pyrano[2,3-c]pyridin]-4′(3′H)-one,
(67) sodium 5-{1′-[(8-cyclopropyl-4-ethoxy-1,7-naphthyridin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinate,
(68) sodium 2-{1′-[(1-cyclopropyl-5-methoxyisoquinolin-7-yl)carbonyl]-4-oxo-spiro[chroman-2,4′-piperidin]-6-yl}isonicotinate,
(69) sodium 2-{1′-[(1-cyclopropyl-5-ethoxyisoquinolin-7-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}isonicotinate,
(70) 4,8-dimethoxy-2-({6-[(methoxycarbonyl)amino]-4-oxospiro[chroman-2,4′-piperidin]-1′-yl}carbonyl)quinoline hydrochloride,
(71) 2-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}-2-methylpropanoic acid, and
(72) 1′-[(1,5-dimethoxyisoquinolin-3-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
14. The compound of claim 1 , which is 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one; or a pharmaceutically acceptable salt thereof.
15. The compound of claim 1 , which is (5-{1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}-2H-tetrazol-2-yl)methyl pivalate; or a pharmaceutically acceptable salt thereof.
16. The compound of claim 1 , which is 5-{1′-[(8-cyclopropyl-4-methoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinic acid; or a pharmaceutically acceptable salt or ester thereof.
17. The compound of claim 1 , which is 1′-(8-methoxy-4-morpholin-4-yl-2-naphthoyl)-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one; or a pharmaceutically acceptable salt thereof.
18. The compound of claim 1 , which is 1′-[(4-ethoxy-8-ethylquinolin-2-yl)carbonyl]-6-(1H-tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one; or a pharmaceutically acceptable salt thereof.
19. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I) of claim 1 , or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof, and a pharmaceutically acceptable additive.
20. A method for the treatment of diabetes in a subject in need thereof which comprises administering to said subject a therapeutically effective amount of a compound of formula (I), of claim 1 , or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
21. A method for the treatment of obesity in a subject in need thereof which comprises administering to said subject a therapeutically effective amount of a compound of formula (I), of claim 1 , or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of carboxylic group thereof.
22. A method for the treatment of non-alcoholic fatty liver disease in a subject in need thereof which comprises administering to said subject a therapeutically effective amount of a compound of formula (I), of claim 1 , or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
23. A compound of formula (I):
wherein R 1 and R 5 each independently represent a hydrogen atom, a halogen atom, a cyano group, a lower alkenyl group, a lower alkoxy group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-lower alkoxy group, a carboxy-lower alkenyl group, or a group of -Q 1 -N(R a )-Q 2 -R b ,
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group,
an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of -CO-N(R c )R d , or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R 2 , R 3 and R 4 each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, a hydroxy-lower alkoxy group, a lower alkoxy-lower alkoxy group, a cyclo-lower alkyloxy group, a cyclo-lower alkyl-lower alkoxy group, a lower alkylthio group, a group of -O-R k or a group of -N(R e )R f , or
a lower alkoxy group substituted by the group of -N(R e )R f , or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group and a cyclo-lower alkyl group, or
an aryl or heteroaromatic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a nitro group, a hydroxyl group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group and a lower alkylthio group, provided that at least one of R 2 , R 3 and R 4 is lower alkoxy, hydroxy-lower alkoxy, cyclo-lower alkyl, or aryl substituted with at least one lower alkoxy;
Q 1 and Q 2 each independently represent a single bond, or a group of -CO-, -SO 2 - or -C(R g )(R h )-, when Q 2 represents the group of C(R g )(R h )-, R a and R g , taken together, may represent a group of-Q 1 -N=C(R h )-R b ;
R a and R b each independently represent a hydrogen atom, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group, a carbamoyl group, a lower alkoxycarbonyl group or a group of -N(R i )R j , or
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group;
R c , R d , R g , R h , R i and R j each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
R e and R f each independently represent a hydrogen atom, a lower alkyl group or a halo-lower alkyl group, or taken together, they may form a lower alkylene group optionally interrupted by an oxygen atom, a sulfur atom or an imino group;
R k represents a pyrrolidinyl, tetrahydrofuranyl, piperidyl group optionally substituted by a lower alkyl group or a halo-lower alkyl group;
T, U, W and Y each independently represent a nitrogen atom or a methine group; and V represents an oxygen atom or a sulfur atom;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
24. The compound of claim 23 , wherein the compound is represented by formula (Ia):
wherein R 1a represents a hydrogen atom, a halogen atom, a cyano group, a lower alkenyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, or a group of -Q 1a -N(R a )-Q 2a R b , or
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group, or
an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of -CO-N(R c )R d ;
R 2a , R 3a and R 4a each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, a cyclo-lower alkyloxy group, a cyclo-lower alkyl-lower alkoxy group, a lower alkylthio group, or a group of -N(R e )R f , or
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group and a cyclo-lower alkyl group, or
an aryl or heteroaromatic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a nitro group, a hydroxyl group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group and a lower alkylthio group;
provided that at least one of R 2a , R 3a and R 4a is lower alkoxy, hydroxy-lower alkoxy, cyclo-lower alkyl, or aryl substituted with at least one lower alkoxy;
Q 1a and Q 2a each independently represent a single bond, or a group of-CO-, -SO 2 - or C(R g )(R h )-;
R a and R b each independently represent a hydrogen atom, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group, a carbamoyl group, a lower alkoxycarbonyl group or a group of-N(R i )R j , or
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group; or
a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group;
R c , R d , R g , R h , R i and R j each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
R e and R f each independently represent a hydrogen atom, a lower alkyl group or a halo-lower alkyl group, or taken together, they may form a lower alkylene group optionally interrupted by an oxygen atom, a sulfur atom or an imino group;
T, U, W and Y each independently represent a nitrogen atom or a methine group; and V represents an oxygen atom or a sulfur atom;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
25. The compound of claim 23 , wherein the compound is represented by formula (I- 1 ):
wherein Ar 1 is selected from a group of formula (aa):
R 10 is a hydrogen atom, a halogen atom, a cyano group, a lower alkenyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-lower alkoxy group, a carboxy-lower alkenyl group, or a group of -Q 1 -N(R a )-Q 2 -R b,
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group,
an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of -CO-N(R c )R d , or a lower alkyl or alkenyl group having the said aryl or heterocyclic group,
and in the group of -Q 1 -N(R a )-Q 2 -R b,
(i) Q 1 and Q 2 are a single bond, R a is a hydrogen atom or a lower alkyl group, and R b is a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group,
(ii) Q 1 is a single bond, Q 2 is a group of -CO-, R a is a hydrogen atom or a lower alkyl group, and R b is a hydrogen atom, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group or a group of -N(R i )R j , or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group,
(iii) Q 1 is a group of -CO-, Q 2 is a single bond, and R a and R b each independently are a hydrogen atom or a lower alkyl group,
(iv) Q 1 is a group of -CO-, Q 2 is a group of -C(R g )(R h )-, R a is a hydrogen atom or a lower alkyl group, and R b is a carbamoyl group, or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or
(v) Q 1 is a group of -SO 2 -, Q 2 is a single bond, and R a and R b each independently are a hydrogen atom or a lower alkyl group;
R 50 is a hydrogen atom, a halogen atom or a lower alkyl group;
R 2, R 3 and R 4 each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, a hydroxy-lower alkoxy group, a lower alkoxy-lower alkoxy group, a cyclo-lower alkyloxy group, a cyclo-lower alkyl-lower alkoxy group, a lower alkylthio group, a group of -O-R k or a group of -N(R e )R f , or
a lower alkoxy group substituted by the group of -N(R e )R f , or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group and a cyclo-lower alkyl group, or
an aryl or heteroaromatic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a nitro group, a hydroxyl group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group and a lower alkylthio group,
provided that at least one of R 2 , R 3 and R 4 is lower alkoxy, hydroxy-lower alkoxy, cyclo-lower alkyl, or aryl substituted with at least one lower alkoxy;
R c , R d , R g , R h , R i and R j each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
R e and R f each independently represent a hydrogen atom, a lower alkyl group or a halo-lower alkyl group, or taken together, they may form a lower alkylene group optionally interrupted by an oxygen atom, a sulfur atom or an imino group;
R k represents a pyrrolidinyl, tetrahydrofuranyl, piperidyl group optionally substituted by a lower alkyl group or a halo-lower alkyl group; and
U and Y each independently represent a nitrogen atom or a methine group;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
26. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I):
wherein R 1 and R 5 each independently represent a hydrogen atom, a halogen atom, a cyano group, a lower alkenyl group, a lower alkoxy group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-lower alkoxy group, a carboxy-lower alkenyl group, or a group of -Q 1 -N(R a )-Q 2 -R b,
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an azido group, a lower alkoxy group, a halo-lower alkoxy group, a lower alkylthio group, a lower alkanoyloxy group, a carboxyl group, a carbamoyl group, a lower alkoxycarbonyl group and a lower alkylsulfonyl group,
an aryl or heterocyclic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group, an oxo group, a thioxo group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a lower alkanoyloxy-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a formyl group, a carboxyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkylsulfonyl group and a group of -CO-N(R c )R d , or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R 2 , R 3 and R 4 each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, a hydroxy-lower alkoxy group, a lower alkoxy-lower alkoxy group, a cyclo-lower alkyloxy group, a cyclo-lower alkyl-lower alkoxy group, a lower alkylthio group, a group of -O-R k or a group of -N(R e )R f , or
a lower alkoxy group substituted by the group of -N(R e )R f , or a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a hydroxyl group and a cyclo-lower alkyl group, or
an aryl or heteroaromatic group optionally substituted by a substituent selected from a group consisting of a halogen atom, a nitro group, a hydroxyl group, a lower alkyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group, a cyclo-lower alkyl group, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group and a lower alkylthio group;
Q 1 and Q 2 each independently represent a single bond, or a group of -CO-, -SO 2 - or -C(R g )(R h )-, when Q 2 represents the group of -C(R g )(R h )-, R a and R g , taken together, may represent a group of -Q 1 -N=C(R h )-R b;
R a and R b each independently represent a hydrogen atom, a lower alkenyl group, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group, a carbamoyl group, a lower alkoxycarbonyl group or a group of -N(R i )R j , or
a lower alkyl group optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group, or
a heteroaromatic group optionally substituted by a lower alkyl group that is optionally substituted by a substituent selected from a group consisting of a halogen atom, a lower alkoxy group, a carbamoyl group and a lower alkoxycarbonyl group; R c , R d , R g , R h , R i and R j each independently represent a hydrogen atom, a lower alkyl group, or a halo- lower alkyl group;
R e and R f each independently represent a hydrogen atom, a lower alkyl group or a halo-lower alkyl group, or taken together, they may form a lower alkylene group optionally interrupted by an oxygen atom, a sulfur atom or an imino group;
R k represents a pyrrolidinyl, tetrahydrofuranyl, piperidyl group optionally substituted by a lower alkyl group or a halo-lower alkyl group;
T, U, W and Y each independently represent a nitrogen atom or a methine group; and
V represents an oxygen atom or a sulfur atom;
or a pharmaceutically acceptable salt thereof; or a pharmaceutically acceptable ester of a carboxylic group thereof,
and a pharmaceutically acceptable additive.
27. A method for the treatment of diabetes in a subject in need thereof which comprises administering to said subject a therapeutically effective amount of a compound of formula (I) of claim 26 , or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
28. A method for the treatment of obesity in a subject in need thereof which comprises administering to said subject a therapeutically effective amount of a compound of formula (I) of claim 26 , or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.
29. A method for the treatment of non-alcoholic fatty liver disease in a subject in need thereof which comprises administering to said subject a therapeutically effective amount of a compound of formula (I) of claim 26 , or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.