ZA200502564B

ZA200502564B - N-substituted-2-oxodihydropyridine derivatives

Info

Publication number: ZA200502564B
Application number: ZA200502564A
Authority: ZA
Inventors: Nagaaki Sato; Makoto Ando; Shiho Ishikawa; Tsuyoshi Nagase; Keita Nagai; Akio Kanatani
Original assignee: Banyu Pharma Co Ltd
Priority date: 2002-09-30
Filing date: 2005-03-30
Publication date: 2006-06-28

Description

N-SUBSTITUTED-2-OXODIHYDROPYRIDINE DERIVATIVES

Technical Field

The present invention is useful in medical fields. In more detail, N-substituted-2-oxodihydropyridinederivatives of the present invention have an effect as neuropeptide Y receptor : antagonists and are useful as agents for the treatment of various kinds of cardiovascular disorders, nervous system disorders, metabolic diseases, genital or reproductive disorders, gastro-intestinal disorders, respiratory disorders, inflammatory diseases or glaucoma, and the like.

Background Art

Neuropeptide Y (hereinafter referred toasNPY), apeptide consisting of 36 amino acids, was first isolated from porcine brain by Tatemoto et al in 1982 (NATURE, vol. 296, p. 659(1982)).

NPY is widely distributed in central nervous system and peripheral nervous system, and plays various roles as one of ’ the most abundant peptides in the nervous system. That is, NPY acts as an orexigenic substance in the central nervous system and markedly promotes fat accumulation via the mediation of secretion of various hormones or the action of the nervous system.

It is known that continuous intracerebroventricular administration of NPY induces obesity and insulin resistance due to these actions (INTERNATIONAL JOURNAL OF OBESITY, vol.19,

P.517(1995); Endocrinology, vol.133, p.1753(1993)). Itisalso known that NPY has central actions such as depression, anxiety,

schizophrenia, pain, dementia, circadian rhythm control and the like (DRUGS, vol.52, p.371(1996); THE JOURNAL OF NEUROSCIENCE, vol.18, p.3014(1998)). Furthermore, in the periphery, NPY coexists withnorepinephrine in sympathetic-nerve terminals and is related to the tonicity of the sympathetic nervous system.

It is known that peripheral administration of NPY causes vasoconstriction and enhances the activities of other vasoconstrictive substances such as norepinephrine (BRITISH

JOURNAL OF PHARMACOLOGY, vol.95, p.419(1988)). It is also reported that NPY could participate in the development of cardiac hypertrophy as a result of the sympathetic stimulation (PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED

STATES OF AMERICA, vol.97, p. 1595(2000)) .

On the other hand, it is reported that NPY is also involved in the secretory function of sexual hormones and growth hormone, sexual behavior and reproductive function, gastro-intestinal motility, bronchoconstriction, inflammation and alcohol preference (LIFE SCIENCE, vol.55, p.551(1994); THE JOURNAL OF

ALLERGY AND CLINICAL IMMUNOLOGY, vol.101, p.S345(1998) ; NATURE, ’ 20 vo0l.396, p.366(1998)). ) To

NPY has a variety of pharmacological effects resulting . from NPY binding to some NPY receptors to which peptide YY and pancreatic polypeptide, which are the analogs of NPY, also bind.

It is known that these pharmacological effects of NPY aremediated by the action of at least five receptors with or without synergistic interactions (TRENDS IN NEUROSCIENCES, vol.20, p.294(1997)).

It is reported that the central effects mediated by NPY

Y1l receptor include remarkable orexigenic effect (ENDOCRINOLOGY,

vol.137, p.3177(1996); ENDOCRINOLOGY, vol.141, p.1011(2000)).

Further, NPY Y1 receptor is reported to be involved in anxiety and pain (NATURE, vol. 259, p.528(1993); BRAINRESEARCH, vol.859, pP.361(2000). In addition, the pressor effect mediated by the strong vasoconstrictor action in the periphery is also reported (FEBS LETTERS, vol.362, p.192(1995); NATURE MEDICINE, vol.4, p.722(1998)).

It is known that the effects mediated by NPY ¥2 receptor include an inhibitory effect on the release of various neurotransmitters in the sympathetic nerve endings (BRITISH

JOURNAL OF PHARMACOLOGY, vol.102, p.41(1991); SYNAPSE, vol.2,

P.299(1988)). In periphery, NPY Y2 causes constriction of blood vessel or vas deferens directly or via the control of release of various neurotransmitters (THE JOURNAL OF PHARMACOLOGY AND

EXPERIMENTAL THERAPEUTICS, vol.261, p.863(1992); BRITISH

JOURNAL OF PHARMACOLOGY, vol.100, p.190(1990)). Inhibition of lipolysis in adipose tissues is also known (ENDOCRINOLOGY, vol.131l, p.1970(1992)). Further, inhibition of ion secretion in the gastro-intestinal tract is reported (BRITISH JOURNAL OF

PHARMACOLOGY, vol.101, p.247(1990)). On the other hand, the effects on the central nervous system functions such as memory, anxiety and the like are also known (BRAIN RESEARCH, vol.503, p.73(1989);: PEPTIDES, vol.19, p.359(1998)).

It is reported that NPY ¥3 receptor exists mainly in brainstem and heart, and is related to the regulation of blood pressure and heart rate (THE JOURNAL OF PHARMACOLOGY AND

EXPERIMENTAL THERAPEUTICS, vol.258, p.633(1991); PEPTIDES, vol.ll, p.545(1990)). It is also known that NPY ¥3 is involved in the control of catecholamine secretion in adrenal gland (THE

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 244, p.468(1988); LIFE SCIENCE, vol.50, p.PL7(1992)).

NPY Y4 receptor has high affinity for pancreatic i . polypeptide in particular. As for the pharmacological effects of NPY Y4, inhibition of pancreatic exocrine secretion and gastro-intestinal motility is reported (GASTROENTEROLOGY, vol.85, p.1411(1983)). Further, it is reported that NPY enhances the secretion of sexual hormones in the central nervous system (ENDOCRINOLOGY, vol.140, p.5171(1999)).

As for the effects mediated by NPY ¥Y5 receptor, fat accumulation effects including orexigenic effect are prominent (NATURE, vol. 382, p.168(1996); AMERICAN JOURNAL OF PHYSIOLOGY, vol.277, p.R1428(1999)). It is also reported that the NPY ¥5 receptormediates some CNS effects, such as seizure and epilepsy, or pain and morphine withdrawal symptoms, and the control of circadian rhythm (NATURE MEDICINE, vol.3, p.761(1997);

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED

STATES OF AMERICA, vol.96, p.13518(1999); THE JOURNAL OF

PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol.284, "20 p.633(1998); THE JOURNAL OF NEUROSCIENCE, vol.21, p.5367(2001 ).

In addition, diuretic effect and hypoglicemic effect in the periphery are reported (BRITISH JOURNAL OF PHARMACOLOGY, vol. 120, p.1335(1998) ; ENDOCRINOLOGY, v0l.139, p.3018(1998)). NPY is also reported to enhance cardiac hypertrophy as a result of the sympathetic accentuation (PROCEEDINGS OF THE NATIONAL

ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol.97, p.1595 (2000)).

The effects of NPY are expressed when NPY binds to the

NPY receptors in the central or peripheral nervous system.

~

Therefore, the action of NPY can be prevented by blocking its ’ binding to NPY receptors. For this reason, it is expected that substances antagonize NPY binding to NPY receptors may be useful for the prophylaxis or treatment of various diseases related 5 to NPY, for example cardiovascular disorders such as angina, acute or congestive heart failure, myocardial infarction, hypertension, nephropathy, electrolyte abnormality, vasospasm, etc., central nervous system disorders such as bulimia, depression, anxiety, seizure, epilepsy, dementia, pain, alcoholism, drug withdrawal, circadian rhythm disorders, schizophrenia, memory impairment, sleep disorders, cognitive impairment, etc., metabolic diseases such as obesity, diabetes, hormone abnormality, gout, fatty liver, etc., genital or reproductive disorders such as infertility, preterm labor, sexual dysfunction, etc., gastro-intestinal disorders, respiratory disorders, inflammatory diseases or glaucoma, and the like. (TRENDS IN PHARMACOLOGICAL SCIENCES, vol.l15, p.153(1994); LIFE SCIENCE, vol.55, p.551(1994); DRUGS, vol.52, p.371(1996); THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vo0l.101, p.S345(1998); NATURE, vol.396, p.366(1998); THE

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 284, p.633(1998); TRENDS IN PHARMACOLOGICAL SCIENCES, vol.20, p.104(1999); PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES

OF THE UNITED STATES OF AMERICA, vo0l.97, p. 1595(2000); THE ) 25 JOURNAL OF NEUROSCIENCE, vol. 21, p.5367(2001); PHARMACOLOGY

A & THERAPEUTICS, vol.65, p.397(1995); ENDOCRINOLOGY, vol.140, p.4046(1999); AMERICAN JOUNARL OF PHYSIOLOGY, vol.280, p.R1061(2001); AMERICAN JOUNARL OF PHYSIOLOGY, vol.278,

P.R1627(2000); CURRENT OPINION IN CLINICAL NUTRITION AND

METABOLIC CARE, vol.2, p.425(1999); CURRENT RHEUMATOLOGY . REPORTS, vol.3, p.101(2001), AMERICAN JOURNAL OF RESPIRATORY

AND CRITICAL CARE MEDICINE, vol.165, p.1217(2002).

It was recently found that, as a result of the study by the present inventors, certain NPY receptor antagonists are useful for the prophylaxis or treatment of hypercholesterolemia, hyperlipidemia andarteriosclerosis (International application publication W099/27965).

International application publication WO01/62738 discloses a variety of imidazoline derivatives, and mentions that the derivatives have excellent NPY receptor antagonistic actions and also show excellent pharmacokinetics such as transport into brain or transport to cerebrospinal fluid, etc.

However, the said literature does not describe the compounds of the present invention.

Disclosure of Invention

The object of the present invention is to provide novel medicines which have NPY antagonistic actions.

The present inventors have discovered that the compounds of the formula (I):

R2

SN

2 NH . A =\ 0 ) 2 NNT

A RY EN

~~ Oo

R* R® (wherein Ar! and Ar? are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected from the group consisting of cyano, halogen, nitro, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl) -lower alkyl, lower alkenyl, lower alkylamino, di-lower alkylamino, lower alkanoylamino, lower alkylsuifonylamino, arylsulfonylamino, hydroxy, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio, carboxyl, formyl, lower alkanoyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl, lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl;

R'andR’are independently lower alkyl, cyclo-loweralkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl;

R®, R* and R® are independently hydrogen, cyano, halogen or hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a = substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl) have NPY antagonistic actions especially on NPY Y5 receptors, show excellent pharmacokinetics such as transport into brain or transport to cerebrospinal fluid, etc., and are also very safe, thereby completed the present invention.

The compounds of the present invention (I) have NPY antagonistic actions especially on NPY Y5 receptors, show

) excellent pharmacokinetics such as transport into brain or transport to cerebrospinal fluid, etc., and are very safe, thus they are useful as agents for the treatment of various diseases related to NPY, for example, cardiovascular disorders such as angina, acute or congestiveheart failure, myocardial infarction, hypertension, nephropathy, electrolyte abnormality, vasospasm, arteriosclerosis, etc., central nervous system disorders such as bulimia, depression, anxiety, seizure, epilepsy, dementia,

pain, alcoholism, drug withdrawal, circadian rhythm disorders, schizophrenia, memory impairment, sleep disorders, cognitive impairment, etc., metabolic diseases such as obesity, diabetes, hormone abnormality, hypercholesterolemia, hyperlipidemia,

gout, fatty liver, etc., genital or reproductive disorders such as infertility, preterm labor, sexual dysfunction, etc., gastro-intestinal disorders, respiratory disorders, inflammatory diseases or glaucoma, and the like, also for example, atherosclerosis, hypogonadism, hyperandrogenism, polycystic ovary syndrome, hirsutism, gastro-intestinal motility disorder,

obesity-related gastro-esophageal reflux, obesity hypoventilation (Pickwickian syndrome) , sleep apnea, inflammation, systemic inflammation of the vasculature, osteoarthritis, insulin resistance, bronchoconstriction, alcohol preference, metabolic syndrome, Alzheimer's disease,

cardiac hypertrophy, left ventricular hypertrophy, . hypertriglyceridemia, low HDL cholesterol, cardiovascular disorders such as coronary heart disease (CHD), cerebrovascular disease, stroke, peripheral vascular disease, suddendeath, etc., gallbladder diseases, cancer (breast, endometrial, colon),

breathlessness, hyperuricemia, impaired fertility, low back ; pain, or increased anesthetic risk, and the like.

The compounds of the present invention (I) are particularly useful as agents for the treatment of bulimia, obesity, diabetes and the like.

The present invention relates to the compounds of the formula (I), or the salts or esters thereof, and the production methods and the use thereof.

The present invention further relates to the intermediate for the production of the compound of the formula (I), namely a compound of the formula (III-1):

HO lo) Z “N” RY? \ o (n-1)

RP

(wherein R' is lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl) -lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected £rom the group consisting of halogen, di-lower alkylamino, lower alkoxy, formyl, lower ) alkoxycarbonyl, di-lower alkylcarbamoyl, optionally protected lower alkylamino, optionally protected lower alkanoylamino, optionally protected hydroxy and optionally protected lower alkylcarbamoyl:

R® is hydrogen, cyano, halogen or optionally protected . hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, di-lower 256 alkylamino, lower alkoxy, formyl, lower alkoxycarbonyl,

di-lower alkylcarbamoyl, optionally protected lower alkylamino, : optionally protected lower alkanoylamino, optionally protected hydroxy and optionally protected lower alkylcarbamoyl, provided that the compound of the formula (III-1) wherein R' is methyl and R® is hydrogen, ethyl or methoxy is excluded) and the like.

The means of terms used in the present specification are defined, and more detailed description of this invention is described below. "Halogen" refers to fluorine, chlorine, bromine and iodine. : "Lower alkyl” refers to a straight- or branched-chain alkyl group of Cl to C6, and its examples are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, isohexyl and the like. "Halo-lower alkyl” refers to said lower alkyl substituted with identically or differently one, two or more, preferably one to three said halogen at the substitutable, arbitrary position(s), andits examples are fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 1,2-4difluoroethyl, ~ 20 chloromethyl, 2-chloroethyl, 1,2-dichloroethyl, bromomethyl, iodomethyl and the like. "Hydroxy-lower alkyl” refers to said lower alkyl substituted with one, two or more, preferably one or two hydroxy at the substitutable, arbitrary position(s), and its examples are hydroxymethyl, 2-hydroxyethyl, l-hydroxy-1l-methylethyl, s 1,2-dihydroxyethyl, 3-hydroxypropyl and the like. "Cyclo-lower alkyl” refers to a cycloalkyl group of C3 toCé6, andits examples arecyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like. -

"Cyclo(lower alkyl)-lower alkyl” refers to said lower : alkyl substituted with one, two or more, preferably one said cyclo-lower alkyl at the substitutable, arbitrary position(s), and its examples are cyclopropylmethyl, 2-cyclopropylethyl, 3-cyclopropylpropyl., cyclobutylmethyl, 2-~cyclobutylethyl, 3-cyclobutylpropyl, cyclopentylmethyl, 2-cyclopentylethyl, 3-cyclopentylpropyl, cyclohexylmethyl, 2-cyclohexylethyl, 3-cyclohexylpropyl and the like.

"Lower alkenyl” refers to a straight- or branched-chain alkenyl group of C2 to C6, and its examples are vinyl, 1-propenyl , 2-propenyl, isopropenyl, 3-butenyl, 2-butenyl, 1l-butenyl, l-methyl-2-propenyl, l-methyl-l-propenyl, l-ethyl-l-ethenyl, 2-methyl-2-propenyl, 2-methyl-1l-propenyl, 3-methyl-2-butenyl, 4-pentenyl and the like.

"Lower alkylamino” refers to an amino group mono-substituted with said lower alkyl, and its examples are methylamino, ethylamino, propylamino, isopropylamino, butylamino, sec-butylamino, tert-butylamino, and the like.

"Di-lower alkylamino” refers to an amino group di-substitutedwithidenticallyordifferentlysaidloweralkyl, and its examples are dimethylamino, diethylamino, ethylmethylamino, dipropylamino, methylpropylamino, diisopropylamino and the like.

"Lower alkanoyl” refers to an alkanoyl group containing

256 said lower alkyl, that is, an alkanoyl group of C2 to C7, and

. its examples areacetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl and the like.

"Lower alkanoylamino” refers to an amino group mono-substituted with said lower alkanoyl, and its examples are acetylamino, propionylamino, butyrylamino, isobutyrylamino, ) valerylamino, isovalerylamino, pivaloylamino and the like. "Lower alkylsulfonyl” refers to an alkylsulfonyl group containingsaidloweralkyl, andits examples aremethylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, and the like. "Lower alkylsulfonylamino” refers to an amino group mono-substitutedwithsaidloweralkylsulfonyl, andits examples are methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, isopropylsulfonylamino, butylsulfonylamino, sec-butylsulfonylamino, tert-butylsulfonylamino and the like. "Aryl" refers to phenyl, naphthyl and the like. "Arylsulfonyl” refers to an arylsulfonyl group containing said aryl, and its examples are phenylsulfonyl, l-naphthylsulfonyl, 2-naphthylsulfonyl and the like. "Arylsulfonylamino” refers to an amino group mono-substituted with said arylsulfonyl, and its examples are phenylsulfonylamino, ] 1-naphthylsulfonylamino, i 2-naphthylsulfonylamino and the like. "Lower alkoxy" refers to a straight- or branched-chain alkoxy group of Cl to C6, and its examples are methoxy, ethoxy,

Propoxy, isopropoxy, butoxy, sec-butoxy ’ isobutoxy, tert-butoxy, pentyloxy, isopentyloxy, hexyloxy, isohexyloxy, : and the like. "Halo-lower alkoxy” refers to said lower alkoxy substituted with identically or differently one, two or more, preferably one to three said halogen at the substitutable,

arbitrary position(s), and its examples are fluoromethoxy, ’ difluoromethoxy, trifluoromethoxy, 2-fluoroethoxy, 1,2-difluoroethoxy, chloromethoxy., 2-chloroethoxy, 1l,2-dichloroethoxy, bromomethoxy, iodomethoxy and the like. “"Aryloxy" refers to aryloxy containing said aryl, and itsexamples are, phenoxy, 1-naphthoxy, 2-naphthoxy andthe like. "Lower alkylthio” refers to a straight- or branched-chain alkylthio group of Cl to C6, and its examples are methylthio, ethylthio, propylthio, isopropylthio, butylthio, sec-butylthio, isobutylthio, tert-butylthio, pentylthio, isopentylthio, hexylthio, isohexylthio and the like. "Lower alkoxycarbonyl” refers to an alkoxycarbonyl group containing said lower alkoxy, that is, an alkoxycarbonyl group of C2to C7, and its examples are methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl., isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl and the like. "Lower alkylcarbamoyl” refers to a carbamoyl group 200 'mono-substituted with said lower alkyl, and its examples are methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, sec~butylcarbamoyl, tert-butylcarbamoyl and the like. "Di-lower alkylcarbamoyl” refers to a carbamoyl group di-substituted with said lower alkyl, and its examples are , dimethylcarbamoyl, diethylcarbamoyl, ethylmethylcarbamoyl, dipropylcarbamoyl, methylpropylcarbamoyl, diisopropylcarbamoyl and the like. "Heteroaryl” refers to 5- or 6-membered monocyclic heteroaromatic group which contains one, two or more, preferably ) one to three hetero atom(s) identically or differently selected from the group consisting of oxygen, nitrogen and sulfur; or condensed cyclic heteroaromatic group, where said monocyclic heteroaromatic group is condensed with said aryl group or condensed each other with the same or different said monocyclic heteroaromatic group, and its examples are pyrrolyl, furyl, thienyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, indolyl, benzofuranyl, benzothienyl, benzoimidazolyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, indazolyl, purinyl, quinolyl, isoquinolyl, phthalazinyl, naphthylidinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 1,5~-naphthyridinyl and the like. “"Heteroaryloxy” refers to a heteroaryloxy group containing said heteroaryl, and its examples are 2-thienyloxy, 3-thienyloxy, 2-pyridyloxy, 3-pyridyloxy, 4-pyridyloxy, 3-indolyloxy, 4-indolyloxy, 5-indolyloxy, 6-indolyloxy and the like.

The salts of the compounds of the formula (I) refer to the pharmaceutically acceptable, common salts, and examples thereof are base addition salt to said carboxyl group or hydroxy \ when the compound has a carboxyl group or a hydroxy, or acid addition salt to said amino or basic heterocyclyl when the compound has an amino or a basic heterocyclyl group and the like.

Said base addition salts include salts with alkali metals

(e.g. sodium, potassium); saltswith alkaline earthmetals (e.g. ) calcium, magnesium); ammonium salts; salts with organic amines (e.g. trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, procaine,

N,N'-dibenzylethylenediamine) and the like.

Said acid addition salts include salts with inorganic acids (e.g. hydrochloric acid, sulfuric acid, nitric acid, phosphoricacid, perchloricacid), saltswithorganicacids (e.g. maleic acid, fumaric acid, tartaric acid, citric acid, ascorbic acid, trifluoroacetic acid), salts with sulfonic acids (e.g. methanesulfonic acid, isethionic acid, benzenesulfonic acid, p-toluenesulfonic acid) and the like.

The esters of the compounds of the formula (I) refer to, for example, the pharmaceutically acceptable, common esters of said carboxyl group when the compound has a carboxyl group, and examples thereof are esters with lower alkyl (e.g. methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, cyclopropyl, cyclobutyl, cyclopentyl), esters with aralkyl (e.g. benzyl, phenethyl), esters with lower alkenyl (e.g. allyl, 2-butenyl), esters ‘with lower-alkoxy-lower-alkyl (e.g. methoxymethyl, 2-methoxyethyl, 2-ethoxyethyl), esters with lower-alkanoyloxy-lower-alkyl (e.g. acetoxymethyl, pivaloyloxymethyl, l1-pivaloyloxyethyl), esters with lower-alkoxycarbonyl-lower-alkyl (e.g. ) 25 methoxycarbonylmethyl, isopropoxycarbonylmethyl), esterswith « carboxy-lower alkyl (e.g. carboxymethyl), esters with lower-alkoxycarbonyloxy-lower-alkyl (e.g. 1-(ethoxycarbonyloxy)ethyl, 1-(cyclohexyloxycarbonyloxy)ethyl), esters with carbamoyloxy-lower alkyl (e.g. carbamoyloxymethyl), esters : with phthalidyl, esters with (5-substituted-2-0xo0-1,3-dioxol-4-yl)methyl (e.g. (5-methyl-2-o0x0-1,3-dioxol-4-yl)methyl) and the like. "An agent for treatment” refers to a medicament which is employed for the treatment and/or prophylaxis of various diseases.

Inorder todisclose the aforesaid compounds of the formula (I) of the present invention more specifically, the various symbols used in the formula (I) are explained in more detail by presenting preferred embodiments. . Ar! and Ar? are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected from the group consisting of cyano, halogen, nitro, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl) -lower alkyl, lower alkenyl, lower alkylamino, di-lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, arylsulfonylamino, hydroxy, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio, ~~ 20 carboxyl, formyl, lower alkanoyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl, lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl. "Aryl or heteroaryl, any of which is optionally substituted by a substituent selected from the group consisting ) 25 of cyano, halogen, nitro, lower alkyl, halo-lower alkyl,

A hydroxy-lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl) -lower alkyl, lower alkenyl, lower alkylamino, di-lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, arylsulfonylamino, hydroxy, lower alkoxy, halo-lower alkoxy,

aryloxy, heteroaryloxy, lower alkylthio, carboxyl, formyl, : lower alkanoyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl, lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl” refers to unsubstituted said aryl or said heteroaryl, or said aryl or said heteroaryl, the last two groups having substituent(s) at the substitutable, arbitrary position(s) wherein said substituent(s) may be one, two or more, preferably one or two member(s) identically or differently selected fromthe group consistingof cyano, halogen, nitro, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl, lower alkenyl, lower alkylamino, di-lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, arylsulfonylamino, hydroxy, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio, carboxyl, formyl, lower alkanoyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl, lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl.

Halogen as said substituent includes preferably fluorine, chlorine, bromine and the like, more preferably fluorine and the like.

Lower alkyl as said substituent preferably includes methyl, ethyl, propyl, isopropyl and the like.

Halo-lower alkyl as said substituent preferably includes difluoromethyl, trifluoromethyl and the like. ) Hydroxy-lower alkyl as said substituent preferably includes hydroxymethyl, 2-hydroxyethyl, l-hydroxy-l-methylethyl and the like.

Cyclo-lower alkyl as said substituent preferably includes cyclopropyl and the like. : Cyclo(lower alkyl)-lower alkyl as said substituent preferably includes cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and the like.

Lower alkenyl as said substituent preferably includes vinyl, l-propenyl, 2-methyl-l-propenyl and the like.

Lower alkylamino as said substituent preferably includes methylamino, ethylamino and the like.

Di-lower alkylamino as said substituent preferably includes dimethylamino, diethylamino and the like.

Lower alkanoylamino as said substituent preferably includes acetylamino, propionylamino and the like.

Lower alkylsulfonylamino as said substituent preferably includes methylsulfonylamino, ethylsulfonylamino and the like.

Arylsulfonylamino as said substituent preferably includes phenylsulfonylamino and the like.

Lower alkoxy as said substituent preferably includes methoxy, ethoxy and the like.

Halo-lower alkoxy as said substituent preferably includes fluoromethoxy, difluoromethoxy, trifluoromethoxy and the like.

Aryloxy as said substituent preferably includes phenoxy and the like.

Heteroaryloxy as said substituent preferably includes 2-pyridyloxy, 3-pyridyloxy, 4-pyridyloxy and the like. ) Lower alkylthio as said substituent preferably includes methylthio, ethylthio and the like.

Lower alkanoyl as said substituent preferably includes formyl, acetyl, propionyl and the like.

Lower alkoxycarbonyl as sald substituent preferably ’ includes methoxycarbonyl, ethoxycarbonyl and the like.

Lower alkylcarbamoyl as said substituent preferably includes methylcarbamoyl, ethylcarbamoyl and the like. : Di-lower alkylcarbamoyl as said substituent preferably includes dimethylcarbamoyl, diethylcarbamoyl and the like.

Lower alkylsulfonyl as said substituent preferably includes methylsulfonyl, ethylsulfonyl and the like.

Arylsulfonyl as said substituent preferably includes phenylsulfonyl and the like.

Aryl as said substituent preferably includes phenyl and the like.

Heteroaryl as said substituent preferably includes thienyl, thiazolyl, isothiazolyl, pyridyl, pyrazinyl and the like.

The substituents of Ar’ or Ar’ preferably include halogen, halo-lower alkyl and the like.

Aryl as Ar’ or Ar? preferably includes phenyl and the like, and heteroaryl as Ar' or Ar? preferably includes pyridyl and the like. oo

More specifically, Ar'orAr’includes, forexample, phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 3-bromo-4-fluorophenyl, 4 -bromophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, . 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-hydroxymethylphenyl, 3-hydroxymethylphenyl, 4 -hydroxymethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl,

2-difluoromethoxyphenyl, 3-difluoromethoxyphenyl,

: 4-difluoromethoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-formylphenyl, 3-formylphenyl, 4-formylphenyl, 2-thienyl,

4-chloro-2-thienyl, 5-chloro-2-thienyl, 4-bromo-2-thienyl, 5-bromo-2-thienyl, 4-methyl-2-thienyl, 5-methyl-2-thienyl,

4 -methoxy-2-thienyl, 5-methoxy-2-thienyl, 3-thienyl, 5-chloro-3-thienyl, 5-methyl-3-thienyl, 5-methoxy-3-thienyl, 2-pyridyl, 4-methyl-2-pyridyl, 5-methyl-2-pyridyl, 4-methoxy-2-pyridyl, 5-methoxy-2-pyridyl, 4-chloro-2-pyridyl, 5-chloro-2-pyridyl, 3-pyridyl, 4-methyl-3-pyridyl, 5-methyl-3-pyridyl, 4-methoxy-3-pyridyl, 5-methoxy-3-pyridyl, 6-fluoro-3-pyridyl, 4-chloro-3-pyridyl, 5-chloro-3-pyridyl, 6-difluoromethyl-3-pyridyl, 6-trifluoromethyl-3-pyridyl,

6-cyclopropyl-3-pyridyl, 4-pyridyl, 2-fluoro-4-pyridyl, 2-chloro-4-pyridyl, 3-chloro-4-pyridyl, 2-methyl-4-pyridyl, 3-methyl-4-pyridyl, 2-methoxy-4-pyridyl, 3-methoxy-4-pyridyl ,

etc.

Among the above, the preferable examples are 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl,

2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-bromophenyl, 3-bromo-4-fluorophenyl, 4-bromophenyl, 3-methylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 3-difluoromethoxyphenyl,

4-difluoromethoxyphenyl, 2-thienyl, 4-chloro-2-thienyl, . 5-chloro-2-thienyl, 4-bromo-2-thienyl, 5-bromo-2-thienyl, 3-pyridyl, 4-methoxy-3-pyridyl, 5-methoxy-3-pyridyl, 6-fluoro-3-pyridyl, 4-chloro-3-pyridyl, 5-chloro-3-pyridyl, 6-difluoromethyl-3-pyridyl, 6-trifluoromethyl-3-pyridyl,

6-cyclopropyl-3-pyridyl, 2-fluoro-4-pyridyl, etc., and the - particularly preferable examples are 4-fluorophenyl, 4-chlorophenyl, 3-bromo-4-fluorophenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 6-fluoro-3-pyridyl, 6-difluoromethyl-3-pyridyl, 6~trifluoromethyl-3-pyridyl, 2-fluoro-4-pyridyl, etc.

The preferred embodiment of Ar' and Ar? includes, for example, the case where one of them is aryl which is substituted by a substituent selected from the group consisting of halogen and halo-lower alkyl, and the other is heteroaryl which is substituted by a substituent selected from the group consisting of halogen and halo-lower alkyl. The particularly preferable embodiment of Ar! and Ar? includes, for example, the case where one of them is -4-fluorophenyl, 4-chlorophenyl, 3-trifluoromethylphenyl or 4-trifluoromethylphenyl, and the other is 6-fluoro-3-pyridyl; the case where one of them is 4-fluorophenyl, 4-chlorophenyl, 3-trifluoromethylphenyl or 4-trifluoromethylphenyl, and the other is 2-fluoro-4-pyridyl; the case where one of them is 4-fluorophenyl, 4-chlorophenyl, 3-trifluoromethylphenyl or 4-trifluoromethylphenyl, and the ) other is 6-trifluoromethyl-3-pyridyl; the case where one of them is 4-fluorophenyl or 4-chlorophenyl, and the other is 6-difluoromethyl-3-pyridyl.

R'andR2?are independently loweralkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which . is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl. i "Lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl” refers to unsubstituted said lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, or said lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl) -lower alkyl or lower alkoxy, the last four groups having substituent(s) at the substitutable, arbitrary position(s) wherein said substituent(s) may be one, two or more, preferably one or two member(s) identically or differently selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl.

Halogen as said substituent preferably includes fluorine and the like.

Lower alkanoylamino as said substituent preferably . includes acetylamino, propionylamino and the like.

Lower alkoxycarbonyl as said substituent preferably includes methoxycarbonyl, ethoxycarbonyl and the like. i Lower alkylcarbamoyl as said substituent preferably includes methylcarbamoyl, ethylcarbamoyl and the like.

Di-lower alkylcarbamoyl as said substituent preferably includes dimethylcarbamoyl, diethylcarbamoyl and the like.

The substituent of lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl) -lower alkyl or lower alkoxy as R* preferably includes halogen and the like.

Lower alkyl as R' preferably includes methyl, ethyl, propyl, isopropyl, isobutyl and the like.

Cyclo-lower alkyl as R! preferably includes cyclopropyl, cyclobutyl and the like.

Cyclo(lower alkyl) -lower alkyl as R' preferably includes cyclopropylmethyl, 2-cyclopropylethyl, cyclobutylmethyl and the like.

Lower alkoxy as R! preferably includes methoxy, ethoxy, propoxy, isopropoxy, isobutoxy and the like.

R* preferably includes lower alkyl, cyclo-lower alkyl or lower alkoxy, any of which is optionally substituted by said "20 substituent(s). oo

More specifically, R! includes, for example, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, | ethyl, cyclopropyl, cyclobutyl, 2-fluoroethyl, 2,2-difluoroethyl, propyl, isopropyl, isobutyl, methoxy, difluoromethoxy, ethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, propoxy, isopropoxy, . isobutoxy and the like, preferably methyl, difluoromethyl, ethyl, 2,2-difluoroethyl, propyl, isopropyl, cyclopropyl, methoxy, ethoxy and the like. : The substituent of lower alkyl, cyclo-lower alkyl,

cyclo(lower alkyl) -lower alkyl or lower alkoxy as R? preferably v includes halogen, lower alkylamino, di-lower alkylamino, hydroxy, lower alkoxy and the like.

Lower alkyl as R? includes preferably methyl, ethyl, propyl, isopropyl, isobutyl and the like, more preferably methyl and the like.

Cyclo-lower alkyl as R? preferably includes cyclopropyl, cyclobutyl and the like.

Cyclo(lower alkyl) -lower alkyl as R? preferably includes cyclopropylmethyl, 2-cyclopropylethyl, cyclobutylmethyl and the like.

Lower alkoxy as R? includes preferably methoxy, ethoxy,

Propoxy, isopropoxy, isobutoxy and the like, more preferably methoxy and the like.

R? includes preferably lower alkyl which is optionally substituted by said substituent and the like, more preferably methyl and the like.

R®, R? and R® are independently hydrogen, cyano, halogen or hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, ‘the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl.

Halogen as R?, R® or R® includes, for example, preferably fluorine, chlorine, bromine and the like, more preferably fluorine, chlorine and the like. "Lower alkyl, lower alkoxy or lower alkylthio, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower i alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl” refers to unsubstituted said lower alkyl, lower alkoxy or lower alkylthio, or said lower alkyl, lower alkoxy or lower alkylthio, the last three groups having substituent (s) ) at the substitutable, arbitrary position(s) wherein said substituent(s) may be one, two or more, preferably one or two member(s) identically or differently selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl.

Halogen as said substituent preferably includes fluorine and the like.

Di-lower alkylamino as said substituent preferably includes dimethylamino, diethylamino and the like. “20 Lower alkanoylamino as said substituent preferably includes acetylamino, propionylamino and the like.

Lower alkoxycarbonyl as said substituent preferably includes methoxycarbonyl, ethoxycarbonyl and the like. . Lower alkylcarbamoyl as said substituent preferably includes methylcarbamoyl, ethylcarbamoyl and the like.

The substituent of lower alkyl, lower alkoxy or lower : alkylthio as R?®, R*! or R® preferably includes halogen and the like.

Lower alkyl being optionally substituted by said substituent as R?®, R* or R® includes methyl, fluoromethyl, difluoromethyl, trifluoromethyl, ethyl, 2-fluoroethyl, 2,2-difluoroethyl, propyl, isopropyl, isobutyl and the like, among which the preferred are methyl, ethyl and the like. Lower alkoxy being optionally substituted by said substituent as R?,

R* or R® includes methoxy, difluoromethoxy, ethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, propoxy, isopropoxy, isobutoxy and the like, among which the preferred is methoxy and the like. Lower alkylthio being optionally substituted by said substituent as R?, R* or R® includes methylthio, ethylthio, propylthio, isopropylthio, isobutylthio and the like, among which the preferred is methylthio and the like.

The preferable examples of R?}, R* or R® are hydrogen, halogen, hydroxy, lower alkyl optionally having said substituent(s) and the like, and among which, for example, the © 20 case where R® is hydrogen, halogen or hydroxy or lower alkyl optionally having said substituent(s), and both R*! and R® are hydrogen is more preferable.

In the formula (I), the group represented by the formula (a): ’ R2 : : SN

NH a

AP \ ={ (a) . BR’, R* and R® each can be present at the substitutable, arbitrary position(s) on N-substituted-2-oxodihvdropyridine ring : represented by the formula (b): (b)

X 0) .

Among the compounds of the formula (I), the compound of the formula (I-1):

R2 we 1

Ar® NZ ~~ Nh (11)

N o

RS

(wherein Art, Ar?, R', R? and R® have each the same meaning as defined above) and the like are preferable.

Among the compounds of the formula (I) or formula (I-1), the preferable compounds is, for example, the compound in which one of Ar! and Ar® is aryl, more preferably phenyl, substituted by a substituent selected from the group consisting of halogen

To and halo-lower alkyl, and the other is heteroaryl, more preferably 3-pyridyl or 4-pyridyl, substituted by a substituent selected from the group consisting of halogen and halo-lower alkyl; R! is lower alkyl, cyclo-lower alkyl or lower alkoxy, any of which is optionally substituted by said substituent(s);

R? is lower alkyl, preferably methyl, optionally substituted . by said substituent(s); and R® is hydrogen, halogen or hydroxy, or lower alkyl optionally having said substituent(s). Among the compound of the formula (I), in addition to the above embodiment, the compound in which both R* and R® are hydrogen is preferable. : The compounds of the present invention may include stereoisomers such as optical isomers, diastereoisomers and geometrical isomers, or tautomers depending upon the mode of substituents. The compounds of the present invention include all the stereoisomers, tautomers and their mixtures.

Also included within the scope of the invention are polymorphs, hydrates and solvates of the compounds of the present invention.

The present invention also includes prodrugs of the compounds of the present inventionwithinits scope. Ingeneral, such prodrugs are functional derivatives of the compounds of the present invention which can be readily converted in vivo into the required compound. Thus, in the treatment methods for various diseases according to the present invention, the term "administering" shall encompass not only administration of the compound specified in this disclosure but also administration of a compound which is converted in vivo into the specified compound when it is administered to a patient. Conventional ’ 20 procedures for selection and preparation of suitable prodrug derivatives are described, for example, in "Design of Prodrugs," ed. H. Bundgaard, Elsevier (1985), which are referred and entirely incorporated in this specification. The metabolites of these compounds include active compounds which are produced upon introduction of compounds of the present invention into . the biological milieu, and they are encompassed in the scope of the present invention.

The specific compounds of the formula (I) are, forexample, 5-[(4S,5S)~-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5-

methyl-2-imidazolin-2-yl]l-1-methyl-2-pyridone, : 1-difluoromethyl-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro- 3-pyridyl)-5-methyl-2-imidazolin-2-yll-2-pyridone, l-ethyl-5-[(4S,55)-4-(4-fluorophenyl)-4-(6-£fluoro-3-

pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, 1-difluoromethyl-5-[(4R,5S)-4-(4-fluorophenyl)-4-~(2-fluoro- 4-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, 1-(2,2-difluoroethyl)-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6- fluoro-3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone,

5-[ (4S,5S)-4-(4-fluorophenyl)-4- (6-£luoro-3-pyridyl)-5- methyl-2-imidazolin-2-yl]-1-propyl-2-pyridone, 5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5- methyl-2-imidazolin-2-yl]-1-isopropyl-2-pyridone, l1-difluoromethyl-5-[(4R,5S)-4~(4-fluorophenyl)-5-methyl-

4-(6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl1}-2- pyridone, l-difluoromethyl-5-[(4S,5S)-4-(4-fluorophenyl)-5-methyl- 4-(6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2- pyridone,

"20° 1l-ethyl-5-[(4R,5S)-4-(4-fluorophenyl)-5-methyl-4-(6- trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2-pyridone, l-ethyl-5-[(4S,5S5)-4-(4-fluorophenyl)-5-methyl-4-(6- trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2-pyridone, 5-[(4R,5S)-4-(4-fluorophenyl)-5-methyl-4-(6-trifluoro-

methyl-3-pyridyl)-2-imidazolin-2-yl]-1-propyl-2-pyridone,

] 5-[(4S,5S8)-4-(4-fluorophenyl)-5-methyl-4-(6-trifluoro- methyl-3-pyridyl)-2-imidazolin-2-yl]-1-propyl-2-pyridone, 1-(2,2-difluorcethyl)-5-[(4R,5S)-4-(4-fluorophenyl)-5- methyl-4-(6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-

2-pyridone,

’ 1-(2,2-difluorocethyl)-5-[(4S,58)-4~-(4-fluorophenyl)-5-

methyl-4-(6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]- 2-pyridone,

3-chloro-1l-ethyl-5-[(4R,5S)-4-(4~fluorophenyl)-5-methyl- 4-(6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2- pyridone, 3-chloro-l-ethyl-5-[(4S,5S)-4~-(4-fluorophenyl)-5-methyl- 4-(6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl1]-2-

pyridone, ; | | oo 5-[(4S,58)-4-(3-bromo-4-fluorophenyl)-4-(6-fluoro-3- pyridyl)-5-methyl-2-imidazolin-2-yl]-1-difluoromethyl-2- pyridone, 1-difluoromethyl-5-[(4S,5S8)-4-(4-fluorophenyl)-4-(2-fluoro-

4-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, l-ethyl-5-[(4S,58)-4-(4-fluorophenyl)}-4-(2-fluoro-4- pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, 1-(2,2-difluoroethyl)-5-[(4S,58)-4-(4-fluorophenyl)-4-(2- fluoro-4-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone,

1-difluoromethyl-5-[(4R,5S)-4-(2-fluoro-4-pyridyl)-5- methyl-4-(4-trifluorophenyl)-2-imidazolin~-2-yl]-2-pyridone, 1-difluoromethyl-5-~[(48,5S)-4-(2-fluoro-4-pyridyl)-5- methyl-4-(4-trifluorophenyl)-2-imidazolin-2-yl]-2-pyridone, l-ethyl-5-[(4R,55)-4-(4-fluorophenyl)-4-(2-fluoro-4-

pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone,

, 3-chloro-l-ethyl-5-[(4S,5S)-4~-(4-fluorophenyl)-4-(6-fluoro- 3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, 5-[(4R,58)-4-(4-fluorophenyl)-5-methyl-4-(6-trifluoro- methyl-3-pyridyl)-2-imidazolin-2-yl]-1-methyl-2-pyridone,

Claims

} 1. A compound of the formula (I): R2 e 2 NH ’ = R' (1 2 a . RL WA ~~ (0 R* R° (wherein Ar' and Ar’ are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected from the group consisting of cyano, halogen, nitro, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl) -lower alkyl, lower alkenyl, lower alkylamino, di-lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, arylsulfonylamino, hydroxy, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio, carboxyl, formyl, lower alkanoyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl,’ lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl; R!'andR?are independently lower alkyl, cyclo-loweralkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower . 20 alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl; R®, R* and R® are independently hydrogen, cyano, halogen or hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, ) the last three groups being optionally substituted by a } substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl), or a salt or ester thereof.

2. The compound, or a salt or ester thereof, as claimed in claim 1, wherein both R* and R® are hydrogen.

3. The compound of the formula (I-1) , or a salt or ester thereof, as claimed in claim 1: R2 ~= R! 7’ NS oO RS wherein Ar! and Ar? are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected from the group consisting of cyano, halogen, nitro, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl, lower alkenyl, lower alkylamino, di-lower alkylamino, lower alkanoylamino, lower " alkylsulfonylamino, arylsulfonylamino, hydroxy. lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio, carboxyl, formyl, lower alkanoyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl,

lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl; ’ R'andR%are independently lower alkyl, cyclo-loweralkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl; R® is hydrogen, cyano, halogen or hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl.

4. The compound, or a salt thereof, as claimed in claim 1, 2 or 3, wherein one of Ar! and Ar? is aryl which is substituted by a substituent selected from the group consisting of halogen and halo-lower alkyl, and one of the remainder is heteroaryl which is substituted by a substituent selected from the group consisting of halogen and halo-lower alkyl.

5. The compound, or a salt or ester thereof, as claimed in claim 1, 2 or 3, wherein R! is lower alkyl, cyclo-lower alkyl or lower “ alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl. . 6. The compound, or a salt or ester thereof, as claimed in claim 1, 2or 3, whereinR?is lower alkyl whichis optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl.

7. The compound, or a salt or ester thereof, as claimed in claim 2 or 3, wherein R? is hydrogen, halogen or hydroxy, or lower alkyl which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl.

8. The compound, or a salt thereof, as claimed in claim 2 or 3, wherein one of Ar! and Ar? is aryl which is substituted by 90 a substituent selected from the group consisting of halogen and halo-lower alkyl, and one of the remainder is heteroaryl which is substituted by a substituent selected from the group consisting of halogen and halo-lower alkyl; ) R! is lower alkyl, cyclo-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected i from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl;

R? is lower alkyl which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl; and R? is hydrogen, halogen or hydroxy, or lower alkyl which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl. 9 A The compound, or a salt thereof, as claimed in claim 1, wherein the compound is selected from the group consisting of 5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5- methyl-2-imidazolin-2-yl]-1-methyl-2-pyridone, 1-difluoromethyl-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro- 3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, l-ethyl-5-[(45,5S)-4-(4~-fluorophenyl)-4-(6-fluoro-3-

pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, 7 l1-difluoromethyl-5-[(4R,55)-4-~(4-fluorophenyl)-~-4-(2-fluoro- 4-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, 1-(2,2-difluoroethyl)-5-[(4S,58)~-4-(4-fluorophenyl)-4-(6-

fluoro-3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone,

5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5-

5 methyl-2-imidazolin-2-~yl]-1-propyl-2-pyridone, 5-[(4S,55)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5- methyl-2-imidazolin-2-yl]-l-isopropyl-2-pyridone, 1-difluoromethyl-5-[(4R,55)-4-(4-fluorophenyl)-5-methyl-4-

(6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2- ’ pyridone, 1-difluoromethyl-5-[(4S,5S)-4-(4-fluorophenyl)-5-methyl-4- (6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2- pyridone, l-ethyl-5-[(4R,5S)-4-(4-fluorophenyl)-5-methyl-4-(6-tri- fluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2-pyridone, l-ethyl-5-[(4S,5S)-4-(4-fluorophenyl)-5-methyl-4-(6-tri- fluoromethyl-3-pyridyl)-2-imidazolin-2-yl]l-2-pyridone, 5-[(4R,58)~4-(4-fluorophenyl)-5-methyl-4-(6-trifluoro- methyl-3-pyridyl)-2-imidazolin-2-yl]-1-propyl-2-pyridone, 5-1(4S,58)-4-(4-fluorophenyl)-5-methyl-4-(6-trifluoro- methyl-3-pyridyl)-2-imidazolin-2-yl}-1-propyl-2-pyridone, 1-(2,2-difluoroethyl)-5-[(4R,5S)-4-(4-fluorophenyl)-5- methyl-4-(6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl1]- 2-pyridone, 1-(2,2-difluoroethyl)-5-[(4S,5S)-4-(4-fluorophenyl)-5- methyl-4-(6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]- 2-pyridone, 3-chloro-l-ethyl-5-[(4R,5S)-4-(4-fluorophenyl)-5-methyl-4- (6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2- pyridone, 3-chloro-1-ethyl-5-[(4S,5S8)-4-(4-fluorophenyl)-5-methyl-4- (6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2- pyridone,

. 5-[(4S,55)-4-(3-bromo-4-fluorophenyl)-4-(6-fluoro-3- Pyridyl)-5-methyl-2-imidazolin-2-yl]-1-difluoromethyl-2- pyridone, 1-difluoromethyl-5-[(4S,5S)~-4-(4-fluorophenyl)-4-(2-fluoro-

4-pyridyl)-5-methyl-2-imidazolin-2-yl]}-2-pyridone, l-ethyl-5-[(4S,5S)-4-(4-fluorophenyl)-4-(2-£fluoro-4-

pyridyl) -5-methyl-2-imidazolin-2-yl]-2-pyridone, } 1-(2,2-difluoroethyl)-5-[(4S,58)-4-(4-fluorophenyl)-4-(2-

fluoro-4-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, l-difluoromethyl-5-~[(4R,5S)-4-(2-fluoro-4-pyridyl)-5- methyl-4-(4-trifluorophenyl)-2-imidazolin-2~yl]l-2-pyridone, 1-difluoromethyl-5-[(4S,5S)-4-(2~-fluoro-4-pyridyl)-5- methyl-4-(4-trifluorophenyl)-2-imidazolin-2-yl]-2-pyridone,

l-ethyl-5-[(4R,5S)-4-(4-fluorophenyl)-4-(2-fluoro-4- pyridyl) -5-methyl-2-imidazolin-2-yl]-2-pyridone, 3-chloro-l-ethyl-5-[(45,5S8)-4-(4-fluorophenyl)-4-(6-fluoro- 3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, 5-[(4R,58)-4~(4-fluorophenyl)-5-methyl-4-(6-trifluoro-

methyl-3-pyridyl)-2-imidazolin-2-yl]-1-methyl-2-pyridone, 5-[(4S,58)-4-(4-fluorophenyl)-5-methyl-4-(6-trifluoro- methyl-3-pyridyl)-2-imidazolin-2-yl]-1-methyl-2-pyridone, l-difluoromethyl-5-[(4R,5S)-4-(4-fluorophenyl)-4-(6-fluoro- 3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone,

1-difluoromethyl-5-[ (4R,5S)-4- (4-chlorophenyl)-4-(2-£1luoro- 4-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, l-difluoromethyl-5-[(4S,58)-4-(4-chlorophenyl)-4-(2-fluoro- 4-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone,

l-ethyl-5-[(4R,5S)-4-(2-fluoro-4-pyridyl)-5-methyl-4-(4-

trifluoromethylphenyl)-2-imidazolin-2-yl]-2-pyridone,

: l-ethyl-5-[(4S,58)-4~(2-fluoro-4-pyridyl)-5-methyl-4-(4- trifluoromethylphenyl)-2-imidazolin-2-yl]-2-pyridone, l-ethyl-5-[(4R,5S8)-4-(4-chlorophenyl)-4-(2-fluoro-4- pyridyl) -5-methyl-2-imidazolin-2-yl]-2~pyridone,

l-ethyl-5-{(4S,58)-4-(4-chlorophenyl)-4-(2~fluoro-4- pyridyl) -5-methyl-2-imidazolin-2-yl]-2-pyridone, . 3-chloro-l-ethyl-5-[(4R,5S)-4-(4-fluorophenyl)-4-(2-fluoro- 4-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone,

1-ethyl-3-fluoro-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-£fluoro- 3-pyridyl)-5-methyl-2-imidazolin-2-yl}-2-pyridone, 3-chloro-5-[(4S,58)-4-(4-fluorophenyl)-4-(6-£fluoro-3- pyridyl) -5-methyl-2-imidazolin-2-yl]-1-methyl-2-pyridone, l-ethyl-5-[(4S,5S)~-4-(4-fluorophenyl)-4-(6-£fluoro-3-

pyridyl)-5-methyl-2-imidazolin-2-yl]l-3-methyl-2-pyridone, 3-chloro-5-[(4R,5S)-4-(4-fluorophenyl)-5-methyl-4-(6- trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]l-1-methyl-2- pyridone, 3-chloro-5-[(4S,5S)-4-(4-fluorophenyl)-5-methyl-4-(6-

trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-1-methyl-2- pyridone, l-ethyl-3-fluoro-5-[(4R,5S)-4-(4-fluorophenyl)-5-methyl-4- (6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2- pyridone,

1-ethyl-3-fluoro-5-[(4S,5S)-4-(4-fluorophenyl)-5-methyl- 4-(6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2- pyridone, l1-ethyl-5-[(4R,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3-

pyridyl) -5-methyl-2-imidazolin-2-yl]-2-pyridone,

1-(2,2-difluoroethyl)-5-[ (4R,5S)-4-(4-fluorophenyl)-4-(6-

; fluoro-3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, 5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5- methyl-2-imidazolin-2-yl]-1,3-dimethyl-2-pyridone, 3-chloro-5-[(4R,58)-4-(4-fluorophenyl)-4-(6-fluoro-3-

pyridyl)-5-methyl-2-imidazolin-2-yl]-1-methyl-2-pyridone, ’ 3-chloro-1l-ethyl-5-[(4R,5S)-4-(4-fluorophenyl)-4-(6-fluoro- 3-pyridyl)-5-methyl-2-imidazolin-2-yl]l-2-pyridone, l-ethyl-3-fluoro-5-[(4R,5S)-4-(4-fluorophenyl)-4-(6-fluoro- 3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, 1-difluoromethyl-5-[(4R,55)-4-(6-difluoromethyl-3-pyridyl)- 4-(4-fluorophenyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, l1-difluoromethyl-5-[(4S,5S)~4-(6-difluoromethyl-3-pyridyl)- 4-(4-fluorophenyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, 5-[(4R,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5- methyl-2-imidazolin-2-yl]-1-methyl-2-pyridone, l-ethyl-3-fluoro-5-[(4R,5S)-4-(4-chlorophenyl)-4-(2-fluoro- 4-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, l-ethyl-3-fluoro-5-[(4S,5S)-4-(4-chlorophenyl)-4-(2-fluoro- 4-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, 3-ethyl-5-[ (4S,5S)-4-(4-fluorophenyl) -4-(6-£luoro-3- pyridyl)-5-methyl-2-imidazolin-2-yl]-1-methyl-2-pyridone, 3-ethyl-5-[(4R,5S)-4-(4-fluorophenyl)-4-(2-fluoro-4- pyridyl)-5-methyl-2-imidazolin-2-yl]-1-methyl-2-pyridone, © 20 3-ethyl-5-[(4R,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3- ) Co pyridyl) -5-methyl-2-imidazolin-2-yl]-1-methyl-2-pyridone, l-ethyl-5-[(4S,55)-4-(4-fluorophenyl)-4-(6-fluoro-3- pyridyl)}-5-methyl-2-imidazolin-2-yl]-3-methoxy-2-pyridone, 1-difluoromethyl-~-5-[(4R,5S)-4-(6-difluoromethyl-3-pyridyl)- 4-(4-fluorophenyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, . 1-difluoromethyl-5-{(45,5S8)-4-(6-difluoromethyl-3-pyridyl)- 4-(4-fluorophenyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, 5-[(4R,58)-4-(6-difluoromethyl-3-pyridyl)-4-(4-fluoro- phenyl)-5-methyl-2-imidazolin-2-yl]-1-ethyl-2-pyridone,

5-[(4S,58)-4-(6-difluoromethyl-3-pyridyl)-4-(4-fluoro- ’ phenyl) -5-methyl-2-imidazolin-2-yl]-1-ethyl-2-pyridone, 5-[(4R,5S)-4-(6-difluoromethyl-3-pyridyl)-4-(4-fluoro- phenyl)-5-methyl-2-imidazolin-2-yl]-1l-ethyl-3-fluoro-2-

pyridone, 5-[(45,5S)-4-(6-difluoromethyl-3-pyridyl)-4-(4-fluoro- phenyl) -~-5-methyl-2-imidazolin-2-yl]-1l-ethyl-3-fluoro-2-

pyridone, 5-[(4S,5S)~4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5-

methyl-2-imidazolin-2-yl]-l-methoxy-2-pyridone, 5-1(4R,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5- methyl-2-imidazolin-2-yl]-1-methoxy-2-pyridone, l-ethoxy-5-[(4R,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3- pyridyl) -5-methyl-2-imidazolin-2-yl]-2-pyridone,

1-cyclopropyl-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3- pyridyl) -5-methyl-2-imidazolin-2-yl]-2-pyridone, l-cyclopropyl-5-[(4R,5S)-4-(4-fluorophenyl)-5-methyl-4-(6- trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2-pyridone, 5-[(4S,58)-4-(4-fluorophenyl)-4-(2-fluoro-4-pyridyl)-5-

methyl-2-imidazolin-2-yl]-1l-methoxy-2-pyridone, 5-[(4R,5S)-4-(4-fluorophenyl)-5-methyl-4-(6-trifluoro- methyl-3-pyridyl)-2-imidazolin-2-yl]-1-methoxy-2-pyridone,

~~ 5-[(4R,5S)-4-(4-chlorophenyl)-4-(2-fluoro-4-pyridyl)-5- methyl-2-imidazolin-2-yl}]-1l-methoxy-2-pyridone, 1-difluoromethyl-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro- s 3-pyridyl)-5-methyl-2-imidazolin-2-yl]-3-methyl-2-pyridone, l-difluoromethyl-5~[(4R,5S)-4-(4-fluorophenyl)-4-(6-fluoro- 3-pyridyl)-5-methyl-2-imidazolin-2-yl]-3-methyl-2-pyridone, l1-difluoromethyl-5-[(4S,5S)~4~(4-fluorophenyl)-4-(6-£fluoro-

3-pyridyl)~-5-methyl-2-imidazolin-2-yl]-3-methoxy-2- ’ pyridone, ) l1-difluoromethyl-5-[(4R,5S)-4-(4-fluorophenyl)-4-(6-fluoro- 3-pyridyl)-5-methyl-2-imidazolin-2-yl]-3-methoxy-2- pyridone, 5-[1(5S)-4,4-bis(4-fluorophenyl)-5-methyl-2-imidazolin-2-yl] -l-methoxy-2-pyridone, l1-difluoromethyl-5-[(4S,5S)-4-(6-cyclopropyl-3-pyridyl)-4- (4-fluorophenyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, 5-[(4S,5S)-4-(6-cyclopropyl-3-pyridyl)-4-(4-fluorophenyl)- 5-methyl-2-imidazolin-2-yl]-1l-ethyl-2-pyridone, 5-[(4S,5S)-4-(4-chlorophenyl)-4-(6-fluoro-3-pyridyl)-5- methyl-2-imidazolin-2-yll-1-methoxy-2-pyridone, 5-[(4S,58)-4-(6-fluoro-3-pyridyl)-5-methyl-4-(4-trifluoro- methylphenyl)-2-imidazolin-2-yl]-1l-methoxy-2-pyridone, 5-[(4R,5S)-4-(4-fluorophenyl)-4-(2-fluoro-4-pyridyl)-5- methyl-2-imidazolin-2-yl]-1-methoxy-2-pyridone, l-cyclopropyl-5-[(4R,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3- pyridyl) -5-methyl-2-imidazolin-2-yl]-2-pyridone, "20 1l-cyclopropyl-5-[(4R,5S)-4-(4-fluorophenyl)-4-(2-filuoro-4- pyridyl) -5-methyl-2-imidazolin-2-yl]-2-pyridone, l-ethyl-5-[(5S)-4,4-bis(6-fluoro-3-pyridyl)-5-methyl-2- imidazolin-2-yl]l-2-pyridone, 5-[(5S)-4,4-bis(6-fluoro-3-pyridyl)-5-methyl-2-imidazolin- 256 2-yl]-1-difluoromethyl-2-pyridone,

. l-cyclopropyl-5-[(4S,5S)-4-(4-fluorophenyl)-4-(2-fluoro-4- pyridyl) -5-methyl-2-imidazolin-2-yl]-2-pyridone, l-difluoromethyl-3-ethyl-5-[(4S,5S)-4-(4~-fluorophenyl)- 4-(6-fluoro-3-pyridyl)-5-methyl-2-imidazolin-2-y1]1-2-

pyridone, l-difluoromethyl-3-ethyl-5~[(4R,5S)~-4-(4-fluorophenyl)- 4-(6-fluoro-3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2- pyridone,

l1-difluoromethoxy-5-[(4S,5S)-4~-(4-fluorophenyl)-4-(6- fluoro-3-pyridyl)-5-methyl-~2-imidazolin-2-yl]-2-pyridone, 5-[(4R,55)-4-(6-difluoromethyl-3-pyridyl)-4-(4-fluoro- phenyl) -5-methyl-2-imidazolin-2-yl]-1-methoxy-2-pyridone, 5-[(4S,58)-4-(6-difluoromethyl-3-pyridyl)-4-(4-fluoro-

phenyl)-5-methyl-2-imidazolin-2-yl]-1-methoxy-2-pyridone, 1-difluoromethoxy-5-[(4R,5S8)-4-(4-fluorophenyl)-4-(6- fluoro-3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone, l1-difluoromethyl-3-ethyl-5-[(4R,5S)~4-(4~-fluorophenyl)- 4-(2-fluoro-4-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-

pyridone, 1-difluoromethyl-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro- 3-pyridyl)-5-methyl-2-imidazolin-2-yl]-3-hydroxy-2- pyridone, 1-difluoromethyl-5-[(4S,5S)-4-(4-fluoro-3-hydroxyphenyl) -

4-(6-fluoro-3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2- pyridone, and 1-difluoromethyl-5-[(4S,5R)-4-(4-fluorophenyl)-4-(6- fluoro-3-pyridyl)-5-hydroxymethyl-2-imidazolin-2-y1]-2-

pyridone.

; 10. The compound, or a salt thereof, asclaimedinclaiml, wherein the compound is 1-difluoromethyl-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro- 3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone.

) 1i. The compound, or asalt thereof, asclaimedinclaiml, wherein . the compound is l-ethyl-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3- pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone.

12. The compound, orasalt thereof, asclaimedinclaiml, wherein the compound is 5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5- methyl-2-imidazolin-2-yl]-l-propyl-2-pyridone.

13. The compound, orasalt thereof, asclaimedinclaiml, wherein the compound is 5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5- methyl-2-imidazolin-2-yl]-l-isopropyl-2-pyridone.

14. The compound, orasalt thereof, asclaimedinclaiml, wherein the compound is 1-difluoromethyl-5-[(4R,5S)-4-(4-fluorophenyl)-5-methyl-4- (6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2- pyridone.

15. The compound, or asalt thereof, asclaimedinclaiml, wherein the compound is 1-difluoromethyl-5-[(4S,5S)-4-(4-fluorophenyl)-5-methyl-4- . (6-trifluoromethyl-3-pyridyl) -2-imidazolin-2-yl] -2- pyridone.

16. The compound, or asalt thereof, asclaimedinclaiml, wherein the compound is . l-ethyl-5-[(4R,5S)-4-(4-fluorophenyl)-5-methyl-4-(6- . trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2-pyridone.

17. The compound, orasalt thereof, as claimedinclaiml, wherein the compound is l-ethyl-5-[(4S,5S)-4-(4-fluorophenyl)-5-methyl-4-(6- trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2-pyridone.

18. The compound, or asalt thereof, as claimed inclaiml, wherein the compound is 5-[(4R,5S8)-4-(4-fluorophenyl)-5-methyl-4-(6~-trifluoro- methyl-3-pyridyl)-2-imidazolin-2-yl]l-1-propyl-2-pyridone.

19. The compound, or asalt thereof, as claimed in claiml, wherein the compound is 5-[(4S,5S8)-4-(4-fluorophenyl)-5-methyl-4-(6-trifluoro- methyl-3-pyridyl)-2-imidazolin-2-yl}-1-propyl-2-pyridone. "20 20. The compound, or a salt thereof, as claimed inclaiml, wherein the compound is 3-chloro-l-ethyl-5-[(4R,5S)-4-(4-fluorophenyl)-5-methyl- 4-(6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-y1l]-2- ) pyridone.

. 21. The compound, or a salt thereof, as claimedinclaiml, wherein the compound is 3-chloro-l-ethyl-5-[(4S,5S)-4-(4-fluorophenyl)-5-methyl-4- (6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]}-2-

pyridone. : ) 22. The compound, or asalt thereof, asclaimedinclaiml, wherein the compound is 1-difluoromethyl-5-[(4R,5S)-4-(4-fluorophenyl)-4-(6-fluoro- 3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone.

23. The compound, or a salt thereof, asclaimedinclaiml, wherein the compound is 1-difluoromethyl-5-[(4R,5S)-4-(4-chlorophenyl)-4-(2-fluoro- 4-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone.

24. The compound, orasalt thereof, as claimedinclaiml, wherein the compound is l-difluoromethyl-5-[(4S,5S)-4-(4-chlorophenyl)-4-(2-fluoro- 4-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone.

25. The compound, or a salt thereof, as claimed inclaiml, wherein the compound is 1l-ethyl-5-[(4R,5S)-4-(4-chlorophenyl)-4-(2-fluoro-4- pyridyl) -5-methyl-2-imidazolin-2-yl]-2-pyridone.

26. The compound, or a salt thereof, asclaimedinclaiml, wherein the compound is l-ethyl-5-[(4S,5S)-4-(4-chlorophenyl)-4-(2-fluoro-4- . pyridyl) -5-methyl-2-imidazolin-2-yl]-2-pyridone.

27. The compound, or a salt thereof, asclaimedinclaiml, wherein the compound is l-ethyl-3-fluoro-5-[ (4S,5S)-4-(4-fluorophenyl)-4- (6-fluoro- } 3-pyridyl)-5-methyl-2-imidazolin-2-yll-2-pyridone.

28. The compound, or a salt thereof, as claimed inclaiml, wherein the compound is l-ethyl-3-fluoro-5-[(4R,5S)-4-(4-fluorophenyl)-5-methyl- 4-(6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2- pyridone.

29. The compound, or asalt thereof, as claimed inclaim 1, wherein the compound is . l-ethyl-3-fluoro-5-[(4S,55)-4-(4-fluorophenyl)-5-methyl- 4-(6-trifluoromethyl-3-pyridyl)-2-imidazolin-2-yl]-2- pyridone.

30. The compound, or asalt thereof, as claimed inclaiml, wherein the compound is 3-ethyl-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoro-3- : pyridyl) -5-methyl-2-imidazolin-2-yl]-1-methyl-2-pyridone. oo

31. The compound, orasalt thereof, as claimedinclaiml, wherein the compound is . 1-difluoromethyl-5-[(4R,5S)-4-(6-difluoromethyl-3-pyridyl)- 4-(4-fluorophenyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone. ‘ 32. The compound, or asalt thereof, asclaimedinclaiml, wherein the compound is l1-difluoromethyl-5-[(4S,55)-4-(6-difluoromethyl-3-pyridyl)- 4-(4-fluorophenyl)-5-methyl-2-imidazolin-2-yl]-2-pyridone.

i 33. The compound, or a salt thereof, asclaimedinclaiml, wherein the compound is 5-[(4R,5S)-4-(6-difluoromethyl-3-pyridyl)-4-(4-fluoro- phenyl)-5-methyl-2-imidazolin-2-yl]-1-ethyl-3-fluoro-2- pyridone.

34. The compound, or a salt thereof, asclaimedinclaiml, wherein the compound is 5-[(4S,58)-4-(6-difluoromethyl-3-pyridyl)-4-(4-fluoro- phenyl) -5-methyl-2-imidazolin-2-yl]}-l-ethyl-3-fluoro-2- pyridone.

35. The compound, or asalt thereof, asclaimedinclaiml, wherein the compound is 5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-£luoro-3-pyridyl)-5- methyl-2-imidazolin-2-yl]-1-methoxy-2-pyridone.

36. The compound, or a salt thereof, asclaimedinclaiml, wherein the compound is Co N 5-[(4R,5S)-4-(4~-fluorophenyl)-5-methyl-4-(6-trifluoro- methyl-3-pyridyl)-2-imidazolin-2-yl]-1-methoxy-2-pyridone.

37. The compound, or asalt thereof, asclaimedinclaiml, wherein the compound is . l-difluoromethyl-3-ethyl-5-[(4S,5S)-4~(4-fluorophenyl)- 4-(6-fluoro-3-pyridyl)-5-methyl-2-imidazolin-2-yl]-2-~ pyridone.

38. A process for preparing a compound of the formula (I): } R2 PSN 2 NH ’ = R! (1 P NT RL WA ~ 0 R* R° (wherein Ar! and Ar? are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected from the group consisting of cyano, halogen, nitro, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl, lower alkenyl, lower alkylamino, di-lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, arylsulfonylamino, hydroxy, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio, carboxyl, formyl, lower alkanoyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl, lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl; R'andR’are independently lower alkyl, cyclo- lower alkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, ) lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower ) 20 alkylcarbamoyl; R’, R* and R® are independently hydrogen, cyano, halogen or hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl), or a salt or ester thereof, which comprises reacting a compound of the formula (II): R?® wi A NH, (n) Ar?P NH, (wherein Ar'® and Ar®® are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected fromthe group consisting of cyano, halogen, nitro, lower alkyl, halo-lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl) -lower alkyl, lower alkenyl, di-lower alkylamino, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio, formyl, lower alkanoyl, lower alkoxycarbonyl, di-lower alkylcarbamoyl, lower alkylsulfonyl, arylsulfonyl, aryl, heteroaryl, optionally protected hydroxy-lower alkyl, optionally protected lower alkylamino, optionally protected lower alkanoylamino, optionally protected lower alkylsulfonylamino, optionally protected arylsulfonylamino, optionally protected hydroxy, optionally protected carboxyl, optionally protected carbamoyl and optionally protected lower alkylcarbamoyl; R?® is lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl) -lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, di-lower alkylamino, lower alkoxy, formyl, lower alkoxycarbonyl, di-lower alkylcarbamoyl, optionally protected lower alkylamino, optionally protected lower alkanoylamino, optionally protected hydroxy and optionally protected lower alkylcarbamoyl) with a compound of the formula (III): OH oO ~~ ~R° - N sek, ~~ o RP RSP (wherein R'® is lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, di-lower alkylamino, lower alkoxy, formyl, lower alkoxycarbonyl, di-lower alkylcarbamoyl, optionally protected lower alkylamino, optionally protected lower alkanoylamino, optionally protected hydroxy and optionally protected lower alkylcarbamoyl;

R’®, R*? and R°? are independently hydrogen, cyano, halogen or optionally protected hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, di-lower alkylamino, lower alkoxy, formyl, lower alkoxycarbonyl, di-lower alkylcarbamoyl, optionally protected lower alkylamino, optionally protected lower alkanoylamino, optionally protected hydroxy and optionally protected lower alkylcarbamoyl),

subjecting the resulting compound of the formula (IV): a2 , SN NH Ar?P NH, ’ (IV) 0) RP RP oy A S (0) R* RP (wherein Ar'P, Ar®®, R', R?", R%, R% and R°® have each the same meaning as defined above) to intramolecular ring closure condensation to give a compound of the formula (V): RP Ar'P 2 NH Ar-P —_— N 1p (V) ~~, h ~ N RPG, A 3 (0) RAP RSP (wherein Ar'?, Ar?, RP, R?, R%, R*’ and R’® have each the same meaningas defined above), andoptionally removing the protecting group(s) from the compound (V).

39. A process for preparing a compound of the formula (I):

R2 . Ar AP? NH =\ R' (1) ° NN * SN ~ oO R* R° (wherein Ar! and Ar? are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected from the group consisting of cyano, halogen, nitro, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl, lower alkenyl, lower alkylamino, di-lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, arylsulfonylamino, hydroxy, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio, carboxyl, formyl, lower alkanoyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl, lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl; R'andR’are independently loweralkyl, cyclo-loweralkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl; . 20 R?, R* and R® are independently hydrogen, cyano, halogen or hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, ' lower alkoxy , formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl), or a salt or ester thereof, which comprises reacting a compound of the formula (II): R2P wi A NH, (mn) Ar? NH, (wherein Ar'® and Ar®® are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected from the group consisting of cyano, halogen, nitro, lower alkyl, halo-lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl, lower alkenyl, di-lower alkylamino, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio, formyl, lower alkanoyl, lower alkoxycarbonyl, di-lower alkylcarbamoyl, lower alkylsulfonyl, arylsulfonyl, aryl, heteroaryl, optionally protected hydroxy-lower alkyl, optionally protected lower alkylamino, optionally protected lower alkanoylamino, optionally protected lower alkylsulfonylamino, optionally protected arylsulfonylamino, optionally protected hydroxy, optionally protected carboxyl, optionally protected carbamoyl and optionally protected lower alkylcarbamoyl: R® is lower alkyl, cyclo-lower alkyl, cyclo(lower “ alkyl) -lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, di-lower alkylamino, lower alkoxy, formyl, lower alkoxycarbonyl, di-lower alkylcarbamoyl, optionally protected lower alkylamino, optionally protected lower alkanoylamino, ’ optionally protected hydroxy and optionally protected lower alkylcarbamoyl) with an acid addition salt of a compound of the formula (VI): RS "= ip 2 ~~ "Se ~~ 0 RP RP (wherein R® is amino or lower alkoxy:

R® is lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, di-lower alkylamino, lower alkoxy, formyl, lower alkoxycarbonyl, di-lower alkylcarbamoyl, optionally protected lower alkylamino, optionally protected lower alkanoylamino, optionally protected hydroxy and optionally protected lower alkylcarbamoyl;

R%®, R*? and R*® are independently hydrogen, cyano, halogen or optionally protected hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, di-lower alkylamino, lower alkoxy, formyl, lower alkoxycarbonyl, di-lower alkylcarbamoyl, optionally protected - lower alkylamino, optionally protected lower alkanoylamino, optionally protected hydroxy and optionally protected lower alkylcarbamoyl) to give a compound of the formula (V):

. R2P “A APP NH =\ R'P (Vv) ¢ x gle ~ oO R* R°P (wherein Ar'®?, Ar?®, R', R?®, R%, R* and R°® have each the same meaningas definedabove), andoptionally removing the protecting group(s) from the compound (V).

40. A neuropeptide Y receptor antagonist agent comprising a compound of the formula (I): R2 SN Ar? NH = R' (1 PF SN ~ oO R* R° (wherein Ar! and Ar? are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected : from the group consisting of cyano, halogen, nitro, lower alkyl, : halo-lower alkyl, hydroxy-lower alkyl, cyclo-lower alkyl, “ cyclo(lower alkyl) -lower alkyl, lower alkenyl, lower alkylamino, di-lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, arylsulfonylamino, hydroxy, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio,

carboxyl, formyl, lower alkanoyl, lower alkoxycarbonyl, ’ carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl, , lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl; R'andR?are independently lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl; R?®, R* and R® are independently hydrogen, cyano, halogen or hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl), or a salt or ester thereof as an active ingredient.

41. An agent for the treatment of bulimia, obesity or diabetes, comprising a compound of the formula (I): R2 SA A NH = R’ (n } ° SN RCL AN ~~ Oo R* R® (wherein Ar! and Ar? are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected from the group consisting of cyano, halogen, nitro, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl) -lower alkyl, lower alkenyl, lower alkylamino, ~~ H di-lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, arylsulfonylamino, hydroxy, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio, carboxyl, formyl, lower alkanoyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl, lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl; R'andR’are independently loweralkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl; R®, R* and R® are independently hydrogen, cyano, halogen or hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl), or a salt or ester thereof as an active ingredient.

42. A compound of the formula (III-1):

HO o) ZZ >N” Re NN o (M-1) RP wherein R' is lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl) -lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, di-lower alkylamino, lower alkoxy, formyl, lower alkoxycarbonyl, di-lower alkylcarbamoyl, optionally protected : lower alkylamino, optionally protected lower alkanoylamino, optionally protected hydroxy and optionally protected lower alkylcarbamoyl: R’® is hydrogen, cyano, halogen or optionally protected hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, di-lower alkylamino, lower alkoxy, formyl, lower alkoxycarbonyl, di-lower alkylcarbamoyl, optionally protected lower alkylamino, optionally protected lower alkanoylamino, optionally protected hydroxy and optionally protected lower alkylcarbamoyl, provided that the compound of the formula (III-1) wherein RP is methyl and RP is hydrogen, ethyl or methoxy is excluded.

43. The compound as claimed in claim 42, which is selected from : the group consisting of l-ethyl-2-pyridone-5-carboxylic acid, l1-difluoromethyl-2-pyridone-5-carboxylic acid, 1l-propyl-2-pyridone-5-carboxylic acid,

1-isopropyl-2-pyridone-5-carboxylic acid, 1-(2.2-difluoroethyl)-2-pyridone-5-carboxylic acid, 3-chloro-1-methyl-2-pyridone-5-carboxylic acid, 3-chloro-1l-ethyl-2-pyridone-5-carboxylic acid, 1-ethyl-3-fluoro-2-pyridone-5-carboxylic acid,

1.3-dimethyl-2-pyridone-5-carboxylic acid, 1-ethyl-3-methyl-2-pyridone-5-carboxylic acid, 1-ethyl-3-methoxy-2-pyridone-5-carboxylic acid, 1-difluoromethyl-3-methyl-2-pyridone-5-carboxylic acid, 1-difluoromethyl-3-ethyl-2-pyridone-5-carboxylic acid, 1-methoxy-2-pyridone-5-carboxylic acid, 1-ethoxy-2-pyridone-5-carboxylic acid, 1-difluoromethoxy-2-pyridone-5-carboxylic acid, 1-difluoromethyl-3-methoxy-2-pyridone-5-carboxylic acid, and 1-cyclopropyl-2-pyridone-5-carboxylic acid.

44. A compound of the formula (I): R2 “SN NH Ar’ = R! AN "THN ~~ fo) R* RS (I) (wherein Ar! and Ar? are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected Amended sheet: 11 May 2006 from the group consisting of cyano, halogen, nitro, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl, lower alkenyl, lower alkylamino, di-lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, arylsulfonylamino, hydroxy, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio, carboxyl, formyl, lower alkanoyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl, lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl; R! and R? are independently lower alkyl, cyclo- loweralkyl, cyclo{lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl; R}, R? and R® are independently hydrogen, cyano, halogen or hydroxyl, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl), or a salt or ester thereof , for use in a method for the treatment of bulimia, obesity or diabetes, which comprises administering to a patient in need of such treatment a therapeutically effective amount of the compound.

45. Use of a compound of the formula (I): Amended sheet: 11 May 2006

R2 SN 2 NH ’ = R' (1) P Nn SESE hd (0 R* R° (wherein Ar' and Ar? are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected from the group consisting of cyano, halogen, nitro, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl) -lower alkyl, lower alkenyl, lower alkylamino, di-lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, arylsulfonylamino, hydroxy, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio,

carboxyl, formyl, lower alkanoyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl, lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl;

R'andR?are independently loweralkyl, cyclo-loweralkyl, ~ cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl;

R?}, R* and R® are independently hydrogen, cyano, halogen or hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl), or a salt or ester thereof for manufacturing a medicament for the treatment of bulimia, obesity or diabetes.