# US 7,410,976 B2 · Spirochromanone derivatives

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- Number: US 7,410,976 B2
- Document ID: US7410976B2
- Status: Granted
- Kind: B2
- Application number: 11/487,029
- Filed: 2006-07-14
- Published: 2007-01-25
- Granted: 2008-08-12
- Earliest claimed: 2005-07-19
- Assignees: Merck & Co., Inc.
- Inventors: Takeru Yamakawa; Hideki Jona; Kenji Niiyama; Koji Yamada; Tomoharu Iino; Mitsuru Ohkubo; Hideaki Imamura; Jun Shibata; Jun Kusunoki; Lihu Yang
- Web page: https://patentgrep.com/patent/US7410976B2

## CPC

- C07D 491/10: Spiro-condensed systems
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/12: Antihypertensives
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- C07D 495/10: Spiro-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

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.

## Claims

### Claim 1

A compound of formula (I):
wherein R1 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 -Q1-N(Ra)-Q2-Rb,
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(Rc)Rd, or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R5 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 -Ql-N(Ra)-Q2-Rb, 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(RC)Rd, or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R2, R3 and R4 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—Rk or a group of —N(Re)Rf, or
a lower alkoxy group substituted by the group of —N(Re)Rf, 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;
Q1 and Q2 each independently represent a single bond, or a group of —CO—, —SO2— or —C(Rg)(Rh)—, when Q2 represents the group of —C(Rg)(Rh)—, Ra and Rg, taken together, may represent a group of -Q1-N═C(Rh)—Rb;
Ra and Rb 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(Ri)Rj, 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;
Rc, Rd, Rg, Rh, Ri and Rj each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
Re and Rf 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;
Rk 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.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R1 is a halogen atom, a cyano group, an aralkyloxycarbonyl group or a group of -Q1-N(Ra)-Q2-Rb,
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(Rc)Rd, or a lower alkyl or alkenyl group having the said aryl or heterocyclic group,
and in the group of -Q1-N(Ra)-Q2-Rb,
(i) Q1 and Q2 are a single bond, Ra is a hydrogen atom or a lower alkyl group, and Rb 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) Q1 is a single bond, Q2 is a group of —CO—, Ra is a hydrogen atom or a lower alkyl group, and Rb is a hydrogen atom, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group or a group of —N(Ri)Rj, 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) Q1 is a group of —CO—, Q2 is a single bond, and Ra and Rb each independently are a hydrogen atom or a lower alkyl group,
(iv) Q1 is a group of —CO—, Q2 is a group of —C(Rg)(Rh)—, Ra is a hydrogen atom or a lower alkyl group, and Rb 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) Q1 is a group of —SO2—, Q2 is a single bond, and Ra and Rb each independently are a hydrogen atom or a lower alkyl group; and
R5 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.

### Claim 3 (depends on 1)

The compound of claim 1, wherein the compound is represented by formula (Ia):
wherein R1a 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 -Q1a-N(Ra)-Q2a-Rb, 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(Rc)Rd;
R2a, R3a and R4a 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(Re)Rf, 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;
Q1a and Q2a each independently represent a single bond, or a group of —CO—, —SO2— or —C(Rg) (Rh)—;
Ra and Rb 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(Ri)Rj, 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;
Rc, Rd, Rg, Rh, Ri and Rj each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
Re and Rf 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.

### Claim 4 (depends on 3)

The compound of claim 3, wherein R1a is a cyano group, a lower alkenyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, or a group of -Q1a-N(Ra)-Q2a-Rb,
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(Rc)Rd,
and in the group of -Q1a-N(Ra)-Q2a-Rb,
(i) Q1a and Q2a are a single bond, Ra is a hydrogen atom or a lower alkyl group, and Rb 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) Q1a is a single bond, Q2a is a group of —CO—, Ra is a hydrogen atom or a lower alkyl group, and Rb is a hydrogen atom, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group or a group of —N(Ri)Rj, 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) Q1a is a group of —CO—, Q2a is a single bond, and Ra and Rb each independently are a hydrogen atom or a lower alkyl group,
(iv) Q1a is a group of —CO—, Q2a is a group of —C(Rg)(Rh)—, Ra is a hydrogen atom or a lower alkyl group, and Rb 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) Q1a is a group of —SO2—, Q2a is a single bond, and Ra and Rb 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.

### Claim 5 (depends on 1)

The compound of claim 1, wherein the heterocyclic group for R1 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(Rc)Rd;
or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.

### Claim 6 (depends on 1)

The compound of claim 1, wherein R1 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 R5 is a hydrogen atom; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.

### Claim 7 (depends on 2)

The compound of claim 2, wherein the heteroaromatic group for Rb 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.

### Claim 8 (depends on 1)

The compound of claim 1, wherein the compound is represented by formula (I-1)
wherein Ar1 is selected from a group of formula (aa):
R10 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 -Q1-N(Ra)-Q2-Rb,
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(Rc)Rd, or a lower alkyl or alkenyl group having the said aryl or heterocyclic group,
and in the group of -Q1-N(Ra)-Q2-Rb,
(i) Q1 and Q2 are a single bond, Ra is a hydrogen atom or a lower alkyl group, and Rb 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) Q1 is a single bond, Q2 is a group of —CO—, Ra is a hydrogen atom or a lower alkyl group, and Rb is a hydrogen atom, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group or a group of —N(Ri)Rj, 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) Q1 is a group of —CO—, Q2 is a single bond, and Ra and Rb each independently are a hydrogen atom or a lower alkyl group,
(iv) Q1 is a group of —CO—, Q2 is a group of —C(Rg)(Rh)—, Ra is a hydrogen atom or a lower alkyl group, and Rb 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) Q1 is a group of —SO2—, Q2 is a single bond, and Ra and Rb each independently are a hydrogen atom or a lower alkyl group;
R50 is a hydrogen atom, a halogen atom or a lower alkyl group;
R2, R3 and R4 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—Rk or a group of —N(Re)Rf, or
a lower alkoxy group substituted by the group of —N(Re)Rf, 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;
Rc, Rd, Rg, Rh, Ri and Rj each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
Re and Rf 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;
Rk 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.

### Claim 9 (depends on 8)

The compound of claim 8, wherein R10 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.

### Claim 10 (depends on 8)

The compound of claim 8, wherein R10 is a tetrazolyl group; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.

### Claim 11 (depends on 8)

The compound of claim 8, wherein Ar1 is a group of formula (aa1):
in which R2 and R4 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(Re)Rf; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester of a carboxylic group thereof.

### Claim 12 (depends on 8)

The compound of claim 8, wherein Ar1 is a group of formula (aa1):
in which R2 is a methoxy group, an ethoxy group, a 1-pyrrolidinyl group or a phenyl group, R3 is a hydrogen atom, a fluorine atom, a chlorine atom or a cyano group, and R4 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.

### Claim 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.

### Claim 14 (depends on 1)

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.

### Claim 15 (depends on 1)

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.

### Claim 16 (depends on 1)

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.

### Claim 17 (depends on 1)

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.

### Claim 18 (depends on 1)

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.

### Claim 19 (depends on 1)

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.

### Claim 20 (depends on 1)

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.

### Claim 21 (depends on 1)

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.

### Claim 22 (depends on 1)

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.

### Claim 23

A compound of formula (I):
wherein R1 and R5 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 -Q1-N(Ra)-Q2-Rb,
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(Rc)Rd, or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R2, R3 and R4 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-Rk or a group of -N(Re)Rf, or
a lower alkoxy group substituted by the group of -N(Re)Rf, 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 R2, R3 and R4 is lower alkoxy, hydroxy-lower alkoxy, cyclo-lower alkyl, or aryl substituted with at least one lower alkoxy;
Q1 and Q2 each independently represent a single bond, or a group of -CO-, -SO2- or -C(Rg)(Rh)-, when Q2 represents the group of C(Rg)(Rh)-, Ra and Rg, taken together, may represent a group of-Q1-N=C(Rh)-Rb;
Ra and Rb 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(Ri)Rj, 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;
Rc, Rd, Rg, Rh, Ri and Rj each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
Re and Rf 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;
Rk 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.

### Claim 24 (depends on 23)

The compound of claim 23, wherein the compound is represented by formula (Ia):
wherein R1a 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 -Q1a-N(Ra)-Q2aRb, 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(Rc)Rd;
R2a, R3a and R4a 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(Re)Rf, 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 R2a, R3a and R4a is lower alkoxy, hydroxy-lower alkoxy, cyclo-lower alkyl, or aryl substituted with at least one lower alkoxy;
Q1a and Q2a each independently represent a single bond, or a group of-CO-, -SO2- or C(Rg)(Rh)-;
Ra and Rb 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(Ri)Rj, 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;
Rc, Rd, Rg, Rh, Ri and Rj each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
Re and Rf 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.

### Claim 25 (depends on 23)

The compound of claim 23, wherein the compound is represented by formula (I-1):
wherein Ar1 is selected from a group of formula (aa):
R10 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 -Q1-N(Ra)-Q2-Rb,
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(Rc)Rd, or a lower alkyl or alkenyl group having the said aryl or heterocyclic group,
and in the group of -Q1-N(Ra)-Q2-Rb,
(i) Q1 and Q2 are a single bond, Ra is a hydrogen atom or a lower alkyl group, and Rb 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) Q1 is a single bond, Q2 is a group of -CO-, Ra is a hydrogen atom or a lower alkyl group, and Rb is a hydrogen atom, a lower alkoxy group, a halo-lower alkoxy group, an aralkyloxy group or a group of -N(Ri)Rj, 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) Q1 is a group of -CO-, Q2 is a single bond, and Ra and Rb each independently are a hydrogen atom or a lower alkyl group,
(iv) Q1 is a group of -CO-, Q2 is a group of -C(Rg)(Rh)-, Ra is a hydrogen atom or a lower alkyl group, and Rb 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) Q1 is a group of -SO2-, Q2 is a single bond, and Ra and Rb each independently are a hydrogen atom or a lower alkyl group;
R50 is a hydrogen atom, a halogen atom or a lower alkyl group;
R2, R3 and R4 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-Rk or a group of -N(Re)Rf, or
a lower alkoxy group substituted by the group of -N(Re)Rf, 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 R2, R3 and R4 is lower alkoxy, hydroxy-lower alkoxy, cyclo-lower alkyl, or aryl substituted with at least one lower alkoxy;
Rc, Rd, Rg, Rh, Ri and Rj each independently represent a hydrogen atom, a lower alkyl group, or a halo-lower alkyl group;
Re and Rf 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;
Rk 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.

### Claim 26

A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I):
wherein R1 and R5 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 -Q1-N(Ra)-Q2-Rb,
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(Rc)Rd, or a lower alkyl or alkenyl group having the said aryl or heterocyclic group;
R2, R3 and R4 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-Rk or a group of -N(Re)Rf, or
a lower alkoxy group substituted by the group of -N(Re)Rf, 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;
Q1 and Q2 each independently represent a single bond, or a group of -CO-, -SO2- or -C(Rg)(Rh)-, when Q2 represents the group of -C(Rg)(Rh)-, Ra and Rg, taken together, may represent a group of -Q1-N=C(Rh)-Rb;
Ra and Rb 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(Ri)Rj, 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; Rc, Rd, Rg, Rh, Ri and Rj each independently represent a hydrogen atom, a lower alkyl group, or a halo- lower alkyl group;
Re and Rf 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;
Rk 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.

### Claim 27 (depends on 26)

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.

### Claim 28 (depends on 26)

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.

### Claim 29 (depends on 26)

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.