WO1999027965A1

WO1999027965A1 - Antihyperlipemic agents

Info

Publication number: WO1999027965A1
Application number: PCT/JP1998/005358
Authority: WO
Inventors: Takehiro Fukami; Kuroda Takahiro F; Akio Kanatani; Masaki Ihara
Original assignee: Banyu Pharmaceutical Co., Ltd.
Priority date: 1997-11-28
Filing date: 1998-11-27
Publication date: 1999-06-10
Also published as: AU1262199A

Abstract

Remedies for hypercholesterolemia, hyperlipemia and arteriosclerosis containing as the active ingredient neuropeptide Y Y5 receptor antagonists typified by, for example, a compound represented by formula [I-f-1].

Description

Meiyo Antihyperlipidemic agent

Technical field

The present invention is useful in the field of medicine. More specifically, the present invention relates to a novel agent for treating hypercholesterolemia, hyperlipidemia and arteriosclerosis, which comprises a nerve peptide 5 receptor antagonist as an active ingredient. Background technology

In recent years, due to the aging of the population and changes in eating habits, it has been pointed out that arteriosclerosis and the accompanying frequency of various coronary and cerebral artery diseases have increased. Although various factors are thought to contribute to the occurrence of arteriosclerosis, elevation of blood cholesterol is one of the most important risk factors, and lowering of blood cholesterol is necessary for treatment and prevention of arteriosclerosis. Agents Used to Treat Hyperlipidemia, Drug Evaluations 6th. Edition, 903 Drugs are known to be effective [Ajazin 'Used' Two 'Treats' Hyper Revidea, Drug Evaluate Sections' Sixth Edition. -926 (1986)]. In particular, it is known that non-HDL (high-density lipoprotein) cholesterol such as LDL (low-density lipoprotein) cholesterol is typically important as a risk factor for the above diseases. [Journal of the American Medical Association, Vol. 251, 351 (1984)].

Examples of the cholesterol lowering agent include clofibrate-based preparations, probucol, lovastatin, simvastatin, pranostatin, pravastatin, fluvastatin, and the like. Nature;), 343, 425 (1990)], etc., are known. However, there is a need for safer and more effective cholesterol lowering agents. Neuropeptide Y (hereinafter referred to as NPY) is a peptide consisting of 36 amino acids and was first isolated from pig brain by Tatsumoto et al. In 1982 [Nature, 296, 659 (1982)]. . NPY is widely distributed in the central nervous system and the peripheral nervous system, and as one of the most abundant peptides in the nervous system, controls various functions in living organisms. That is, NPY acts centrally as an appetite-stimulating substance and remarkably promotes fat accumulation through secretion of various hormones or the action of the nervous system. Continuous intraventricular administration of NPY is known to induce obesity and insulin resistance based on these effects. It is also related to the control of emotions and the function of the central autonomic nervous system. Furthermore, in the periphery, NPY coexists with norepinephrine at sympathetic nerve endings and is associated with sympathetic tone. It is known that peripheral administration of NPY causes vasoconstriction and enhances the action of other vasoconstrictors such as norepinephrine [International jounal of obesity] 19, 517 (1995); Endocrinology. 133, 1753 (1993); Pretty 'Journal' Obb. Pharmacology, 95 , 419 (1988)].

The function of NPY is expressed by binding to NPY receptors present in the central or peripheral nervous system, but NPY receptors have so far been classified into six subtypes, Yl, Υ2, Υ3, Υ4, Υ5, and Υ6. The type is known [Annual Reports in Medicinal Chemistry, 32, 21 (1997)]. The NPY Y5 receptor was cloned in 1996 and is thought to be involved in the appetite-inducing action of ΝΡΥ [Nature, 382, 168 (1996)] ]. In fact, it has been reported that intracerebral administration of the Y5 receptor antisense deoxyribonucleotide significantly suppresses fasting-induced appetite in rats [Diabetes. 46, 1792 ( 1997), and certain Y5 receptor antagonists have been reported to suppress appetite induced by centrally administered NPY or fasting-induced appetite in rats [International Public WO97Z No. 19682; International Publication WO97Z20820; International Publication W097 20821; International Publication WO97 / 20822; International Publication WO97Z20823]. However, the involvement of the NPY in the physiological actions other than appetite of NPY has not been elucidated, and in particular, it has never been shown that Y5 receptor antagonists have a blood cholesterol-lowering effect. unknown. Disclosure of the invention

An object of the present invention is to provide a safer and more effective agent for treating hypercholesterolemia, hyperlipidemia and arteriosclerosis.

The present inventors have reported that NPY Y5 receptor antagonists have an effect of lowering blood cholesterol, particularly non-HDL cholesterol, in vivo, and as a result, hypercholesterolemia, hyperlipidemia and arteriosclerosis The present invention was found to be effective as a therapeutic agent for the present invention, and the present invention was completed.

The present invention relates to a therapeutic agent for hypercholesterolemia, hyperlipidemia and arteriosclerosis, which comprises an NPY Y5 receptor antagonist as an active ingredient.

The symbols and terms described in this specification will be described.

The “neuropeptide Y Y5 receptor antagonist” is not particularly limited as long as it has the action and is a pharmaceutically acceptable drug. For example, the general formula [I-a]

[I-a]

Wherein A is a nitrogen atom or a group represented by C—R ⁵ ; Ar ¹ is an aryl which may have a substituent selected from the group consisting of a halogen atom, a lower alkyl group and a halo-lower alkyl group. Ar ² comprises a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group and an aryl group An aryl group or a heteroaromatic group which may have a substituent selected from the group; R ¹ is a hydrogen atom or a lower alkyl group or a bond linked to R ⁵ ; R ² is a hydrogen atom or a lower alkyl group; R ³ and R ⁴ are the same or different and are a hydrogen atom or a lower alkyl group, or R ³ and R ⁴ are linked to each other to form an alkylene group having 2 to 4 carbon atoms which may have a lower alkyl group; R ⁵ is a hydrogen atom, a hydroxyl group, a lower alkyl group or a lower alkoxy group; Or a bond in connection with R ¹ ] and a salt thereof,

General formula [I-b]

Wherein ring A and ring B are ortho-fused with each other, ring A is an aromatic carbon or heterocyclic ring; ring B is a 4- to 7-membered aliphatic carbon or nitrogen-containing heterocyclic ring, and the nitrogen atom Is a ring that can be present only at the condensed site with ring A; Ar is a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower group An aromatic carbon or a heterocyclic group which may have a substituent selected from the group consisting of an alkylamino group and an aromatic carbocyclic group; R is a halogen atom, a nitrogen atom, a lower alkyl group, A substituent or a hydrogen atom selected from the group consisting of a lower alkoxy group, an aromatic carbocyclic group, and a carbonyl group having an aromatic carbocyclic group.

The group represented by the formula

In the case of the group represented by, Ar does not mean a phenyl group or a 4-chlorophenyl group)), a compound represented by the formula:

General formula [I-Ic] [I-i-c]

[Wherein, Ar ¹ represents an aryl group which may have a substituent selected from the group consisting of a halogen atom, a lower alkyl group and a halo-lower alkyl group; Ar ² is a halogen atom, a lower alkyl group, a lower alkyl group; An aryl group which may have a substituent selected from the group consisting of an alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group and an aryl group; R ¹ and R ² are the same or different and are a hydrogen atom or a lower alkyl group; R ³ and R ⁴ are the same or different and are a hydrogen atom or a lower alkyl group, or R ³ and R ^And R ⁴ represents a hydrogen atom, a lower alkyl group or a lower alkoxy group, wherein both of ⁴ are linked to each other to form an alkylene group having 2 to 4 carbon atoms which may have a lower alkyl group; And a salt thereof represented by the general formula [I-d]

[I-d]

[Wherein, Ar ¹ is a group consisting of a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, an acyl group and an aryl group. Ar ² is a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, which may have a substituent selected from the group consisting of an aryl group and a heteroaromatic ring group. A lower alkylamino group, a di-lower alkylamino group and an aryl group, which may have a substituent selected from the group consisting of an aryl group and a heteroaromatic ring group; n is 0, 1 or 2; R ¹ and R ² are the same or different and each represent a hydrogen atom or a lower alkyl group] and a salt thereof; -General formula [I-e]

Ar-Y

[Wherein, Ar is a halogen atom, a nitro group, an amino group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, a lower alkanoyl group, and aryl. An aryl group or a heteroaromatic group, which may have a substituent selected from the group consisting of: R ¹ and R ² are the same or different, and a lower alkyl group or both R ¹ and R ² are R ³ represents an amino group, a lower alkyl group or a lower alkylamino group which may be connected to each other via an oxygen atom or a sulfur atom; Y represents an ethylene group, a trimethylene group, a vinylene group, a propenylene group; Or a group represented by 1—CH ₂ —, 1 S—CH ₂ — or —C¾—NH—] and a salt thereof,

General formula [I-I f]

[In the formula, R ¹ represents a hydrogen atom or a lower alkyl group, or a lower alkylene group which may be interposed with R ² to interpose an oxygen atom; R ² represents a lower alkyl group Or together with R ¹ has the meaning described above; R ³ and R ⁴ together represent a hydrogen atom, or together form a single bond; R ⁵ and R ⁶ represents a hydrogen atom at the same time, or a lower alkylidene group which may be joined together and intervened by an oxygen atom; R ⁷ and R ⁸ independently represent a hydrogen atom, a halogen atom, a nitro group; Group, hydroxyl group, lower alkyl group, lower alkoxy group, aryl group, aralkyloxy group, di-lower alkylamino group, lower alkoxycarbonylamino group or arylcarbonylamino group, or both A lower alkylene group or a benzene ring ortho-condensed with an adjacent ring; X represents an oxygen atom or a sulfur atom; and Y represents a methine group or a nitrogen atom. (However, 9-1 (2-hydroxy-1,4-dimethyl-6-oxo-1-1-cyclohexene-1-inole)) 1,5-methoxy-1,3,3-dimethyl-1,2,3,4,9- Trahydro-1H-xanthene-1-one and 9-1 (2-hydroxy-14-methyl-16-oxo-1-cyclohexene-1-yl) -3-3-methyl-2,3,4,9-tetrahydro-1H —Xanthene—except for 1-one) and its salts,

General formula [I-g]

0

Ar— S— NH— L— K— W [i-g]

0

Where Ar is the formula

B is 1 or 2; j is an integer of 0 to 3; K is —CH ₂ —NR ⁸ —CHR ^5- (CH ₂ ) j-, -CH ₂ -NR ⁸ -CO- (CH ₂₎ "or one _{CH 2 - NH - CO - NH} - a (CH ₂₎ j- group represented by; L is a pentamethylene group, hepta 'group or the formula

— (C¾) (CH ₂ )

P is an integer of 0 to 2; Q is a nitrogen atom, an oxygen atom, a sulfur atom or a group represented by —NR ⁷ — or —C (R ⁴ ) ₂ —; RR ² and R ³ Is Independently a hydrogen atom, a halogen atom, a nitro group, a hydroxyl group, a lower alkoxy group, a hydroxy lower alkyl group, a halo lower alkyl group or a group represented by —N (R ⁴ ) ₂ ; R ⁴ is independently a lower group; An alkyl group; R ⁵ is independently a hydrogen atom, a hydroxymethyl group or a lower alkoxymethyl group; R ⁶ is a hydrogen atom, a halogen atom, a nitro group, a hydroxyl group, an oxo group, a lower alkyl group, a lower alkoxy group, Xy-lower alkyl group, methoxy-lower alkyl group, halo-lower alkyl group or one N (R ⁴ ) ₂ — NHCOR ⁴ — N (COR ⁴ ) ₂ — NHC0 ₂ R ⁴ -NHCONHR \-NHSO ₂ R ⁴ , one N ( S0 ₂ R ⁴ ) ₂ — C〇 ₂ R ⁴ -CON (R ⁴ ) ₂ or a group represented by S 0 ₂ N (R ⁴ ) ₂ ; R ⁷ independently represents a hydrogen atom or a lower alkyl group; R ⁸ is independently a hydrogen atom or a lower alkyl group; V is a nitrogen atom, an oxygen atom, A sulfur atom or a group represented by —NR ⁴ —;

A compound represented by the formula:

General formula [I-I h]

Wherein alk represents a single bond or a lower alkylene group; n represents 0 or 1; Means (i) a hydrogen atom, a halogen atom, a nitro group, a cyano group, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group, A nitrogen atom, a hydroxyl group, a lower alkoxy group, an amino group, a substituted amino group, a propyloxy group, a lower alkoxycarbonyl group, an (aryl or heteroaryl) lower alkoxycarbonyl group, a carbamoyl group or N-substituted (Ii) an amino group or a substituted amino group; (iii) a hydroxyl group, a lower alkoxy group, a lower alkenyloxy group, a lower alkynyloxy group, or a hydroxy lower group. Alkoxy group, lower alkoxy lower alkoxy group, (aryl Or a lower alkoxy group, a lower alkoxycarbonyloxy group, a (aryl or heteroaryl) lower alkoxycarbonyloxy group, an aminocarbonyloxy group or an N-substituted aminocarboxy group; (Iv) a carboxy group, a lower alkoxycarbonyl group, a lower alkoxy lower alkoxycarbonyl group or a (aryl or heteroaryl) lower alkoxycarbonyl group; (V) a carbamoyl group or an N-substituted rubamoyl group; (Vi)-CH (OH) — R, — CO— R, one NR ⁰¹ — CO-0-R, —NR ⁰¹ — CO— R, — NR ⁰¹ — CO-NR ⁰¹ — R,-NR ⁰¹ — SO _{^{2 - R, - NR 01 -}} SO 2 - NR 01 - R, one _{_{S0 2 - R, - S0 2}} - NR 01 - R or single S0 ₂ - NR ⁰¹ - CO- group [wherein represented by R, R And R ^fll have the meanings ^given below, Or - N (R) group represented by (R ⁰¹⁾ refers to disubstituted Amino group by lower § alkylene group {said lower alkylene group is an oxygen atom or S (0) _n or a group represented by NR ° Or may be condensed with a benzene ring at two adjacent carbon atoms.]] Or a group represented by (vii)-X ¹ (X ² ) (X ³ ) ; wherein, (a) if the X ¹ gar CH- group represented by, X ² and X ³ taken ^{together, -X 4 - (CO) p} - (CH 2). One one _{_{^{(CH 2) q - X 4}}} - (CO) p - (CH 2) r - or _{_{- (CH 2) S - X}} 4 - CO- (CH 2) t - a group represented by; or ( b) When X ¹ is a nitrogen atom, X ² and X ³ together represent a group represented by —CO— (C¾) _u — [X ⁴ is — CH ₂ — or — N (R ⁰¹ ) a group represented by 1 or an oxygen atom; 0 is an integer of 3 to 5; p is 0 or 1; q is 1 or 2; r is 1; s is 1 or 2; t is 1 or 2; u represents an integer of 3 to 5 (however, when p is 0, X ⁴ does not represent a group represented by —CH ₂ —)]; R ² and R ³ are each independently i) a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group; or (ii) a halogen atom, a hydroxyl group, a lower alkoxy group Hydroxy lower alkoxy group, lower alkoxy lower alkoxy group, amino group, substituted amino group, carboquine group, lower alkoxycarbonyl group, lower alkoxy lower alkoxycarbonyl group, (aryl or heteroaryl) lower alkoxycarbonyl group, force A substituent selected from the group consisting of a rubamoyl group, an N-substituent rubamoyl group, and a group represented by —S (O) n-R R ² and R ³ together represent a lower alkylene group {the lower alkylene group is represented by an oxygen atom or S (0) ^} or NRQ X may be condensed with a benzene ring at two adjacent carbon atoms}; X represents a nitrogen atom or a methine group; in the above definition, all aromatic ring moieties And benzo ring A, respectively, means that they are unsubstituted or substituted by one or more substituents selected from the group consisting of (i) to (vi) shown below. (I) halogen atoms, lower alkyl groups, lower alkenyl groups, lower alkynyl groups, aryl groups, heteroaryl groups, lower alkoxy groups, lower alkenyloxy groups, lower alkynyloxy groups, hydroxyl groups, lower alkanoyloxy groups (Aryl or heteroaryl) lower alkanoyloxy group, lower alkanol group, (aryl or heteroaryl) lower alkanol group, (aryl or heteroaryl) carbonyl group, nitro group, cyano group; (ii) halogen atom, hydroxyl group , Lower alkoxy group, (aryl or heteroaryl) oxy group, aryl group, heteroaryl group, amino group, substituted amino group, carboxy group, lower alkoxycarbonyl group, lower alkoxy lower alkoxycarbonyl group, (aryl Or heteroaryl) a lower alkoxy group, a lower alkyl group substituted by a nitromoyl group or an N-substituted carnomoyl group; (iii) a halogen atom, a hydroxyl group, a lower alkoxy group, (aryl or hetero) Rinore) Okishi group, Ariru group, hetero Ariru group, an amino group, a substituted Amino group, a carboxy group, a lower alkoxy (Iv) amibonyl group, lower alkoxy lower alkoxycarbonyl group, (aryl or heteroaryl) lower alkoxycarbonyl group, lower alkoxy group substituted by rubamoyl group or N-substituting rubamoizole group; (V) carboxy group, lower alkoxycarbonyl group, lower alkoxy lower alkoxycarbonyl group, (aryl or heteroaryl) lower alkoxycarbonyl group; (vi) carbamoyl group and N— Substituted rubamoyl groups; substituted amino groups, N-substituted rubamoyl groups and substituted amino groups of N-substituted aminocarbonyloxy groups include (i) lower alkyl groups, aryl groups, and heteroaryl groups. Or (aryl or heteroaryl) mono-substituted by lower alkyl group That properly it may be disubstituted independently of one another; (ii) {said lower alkylene group to be disubstituted by lower alkylene group bonded through an oxygen atom or S (0) _n or a group represented by NR ° Or may be condensed with a benzene ring at two adjacent carbon atoms}; or (iii) monosubstituted by a group represented by —CO— (O) _v —R or V means 0 or 1; n means 0, 1 or 2; R ⁰ is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, an aryl group, Heteroari Ichiru group, (§ Li one Norre or to Teroari one Honoré) lower alk kill group, a lower Arukanoinore group, (Arinore or Heteroarinore) carbonylation Le group or single S0 ₂ - or means a group represented by R, or halogen R represents a hydrogen atom or a lower alkyl group; R represents a hydrogen atom, a lower alkyl group, an aryl group, a heteroaryl group or ( Or a heteroaryl group), a compound having a power meaning a lower alkyl group, or a lower alkyl group substituted by a halogen atom, a hydroxyl group or a lower alkoxy group] and a salt thereof,

General formula [I-i] "T-one; Ί

alk ² ,

[Wherein, alk ¹ and alk ² independently represent a single bond or a lower alkylene group; R ¹ represents a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group; R ² represents an alkyl group, lower alkoxy lower alkyl group, aryl group, heteroaryl group or (aryl or heteroaryl) lower alkyl group; R ² represents (i) a hydrogen atom, a halogen atom, Group, cyano group, lower alkyl group, lower alkenyl group, lower alkynyl group, aryl group, heteroaryl group or (aryl or heteroaryl) lower alkyl group, or halogen atom, hydroxyl group, lower alkoxy group, amino group, Substituted amino, carboxy, lower alkoxycarbonyl, (aryl or heteroaryl (Ii) a lower alkyl group substituted by a lower alkoxycarbonyl group, a carbamoyl group or an N-substituent rubamoyl group; (ii) an amino group or a substituted amino group; (iii) a hydroxyl group, a lower alkoxy group, Lower alkenyloxy, lower alkynyloxy, hydroxy lower alkoxy, lower alkoxy lower alkoxy, (aryl or heteroaryl) lower alkoxy, lower alkoxycarbonyloxy, (aryl or heteroaryl) ) A lower alkoxycarbonyloxy group, an aminocarbonyloxy group or an N-substituted aminocarboxy group; (iv) a carboxy group, a lower alkoxycarbonyl group, a lower alkoxylower alkoxycarbonyl group, or an (arino or heteroaryl) lower group; (V) a carbamoyl group or an N-substituted rubamoyl group;

(vi) ― CH (OH) one R, — CO— R, one NR ¹ — CO— O -R,-NR ¹ — CO — R, — NR ¹ — CO— NR] — R, — NR ¹ — S0 ₂ - R, one ^{_{^{NR 1 - S0 2 - NR 1}}} - R, - S0 2 - R, - S0 2 - NR 1 - R or single S0 ₂ - NR ¹ group represented one CO one R [wherein, R Has the meaning given below, and R ¹ has the meaning given above, or the group represented by —N (R) (R ¹ ) is disubstituted by a lower alkylene group. (The lower alkylene group may be via an oxygen atom or a group represented by S (O) n or NR °, and may be fused to a benzene ring at two adjacent carbon atoms. Or a group represented by (vii) -X ¹ (X ² ) (X ³ ); wherein (a) X ¹ is a group represented by —CH— When X ² and X ³ together, —X ⁴ — (CO) p-(CH ₂ ). —, One (CH ₂ ) _q — X ⁴ — (CO) p-(CH ₂ ) _r — or — (CH ₂ ) _S — X ⁴ — CO— (CH ₂ ) _t — b) When X ¹ is a nitrogen atom, X ² and X ³ together represent a group represented by one CO-(CH ₂ ) _U- [X ⁴ is — CH ₂ — or — N (R ¹ ) — a group or oxygen atom represented by —; 0 is an integer of 3 to 5; p is 0 or 1; q is 1 or 2; r is 1; s is 1 or 2; Represents 1 or 2; u represents an integer of 3 to 5 (however, when p is 0, X ⁴ does not represent a group represented by one CH ₂ —)]; R ³ and R ⁴ represent Independently of one another: (i) a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group; or (Ii) a halogen atom, a hydroxyl group, a lower alkoxy group, Droxy lower alkoxy group, lower alkoxy lower alkoxy group, amino group, substituted amino group, carboxy group, lower alkoxycarbonyl group, lower alkoxy lower alkoxycarbonyl group, (aryl or heteroaryl) lower alkoxycarbonyl group, Le group, N- substituted force Rubamoiru group and - S (0) _n - or means a lower alkyl group substituted with a substituent selected from the group consisting of groups represented by R; R ³及beauty R ⁴ is together, such connexion, benzene ring a lower alkylene group means a {said lower alkylene group is an acid atom or S (0) "or may be bonded through a group represented by NR ^Q, also contact adjacent two carbon atoms X may be a single bond, a 1,2-ethenylene group, a 1,2-ethynylene group, an oxygen atom, a carbonyl group, one S (0) _n — Or a group represented by C (〇R ′) ₂ —, an arylene group or a heteroarylene group; one of R ′ represents a hydrogen atom, or two R ′ are each a lower alkyl group Or together means a lower alkylene group; in the above definitions, all the aromatic ring moieties and the benzo ring A are each unsubstituted or (i) to ( vi) means substituted with one or more substituents selected from the group consisting of: ω halogen atom, lower alkyl Group, lower alkenyl group, lower alkynyl group, aryl group, heteroaryl group, lower alkoxy group, lower alkenyloxy group, lower alkynyloxy group, hydroxyl group, lower alkanoyloxy group, aryl or heteroaryl ) Lower alkanoyloxy group, lower alkanoyl group, (aryl or heteroaryl) lower alkanoyl group, (aryl or heteroaryl) carbonyl group, nitro group, cyano group; (ii) halogen atom, hydroxyl group, lower alkoxy group, (Aryl or heteroaryl) oxy group, aryl group, heteroaryl group, amino group, substituted amino group, carboxy group, lower alkoxycarbonyl group, lower alkoxy lower alkoxycarbonyl group, (aryl or heteroaryl) lower A lower alkyl group substituted by a alkoxycarbonyl group, a rubamoyl group or an N-substituting rubamoyl group; (iii) a halogen atom, a hydroxyl group, a lower alkoxy group, an (aryl or heteroaryl) oxy group, an aryl group, a heteroaryl group, or amino Group, substituted amino group, carboxyl group, lower alkoxycarbonyl group, lower alkoxy lower alkoxycarbonyl group, (aryl or heteroaryl) lower alkoxycarbonyl group, phenolic moyl group or N-substituted rubamoyl group (Iv) amino group, substituted amino group; (V) carboxy group, lower alkoxycarbonyl group, lower alkoxy lower alkoxycarbonyl group, (aryl or heteroaryl) lower alkoxy A carbonyl group; (vi) a substituted rubamoyl group and an N-substituted rubamoyl group; a substituted amino group, an N-substituted carbamoyl group and a substituted amino group of an N-substituted aminocarbonyloxy group are represented by (i) A lower alkyl group, aryl group, heteroaryl group or (aryl or heteroaryl) lower alkyl group being mono-substituted or independently di-substituted with each other; (ii) a lower alkylene group Disubstituted {the lower alkylene group is an oxygen atom or S (0) _n or NR. Or may be condensed with a benzene ring at two adjacent carbon atoms}; or (iii) monosubstituted by a group represented by —CO— (0) _V —R Or independently of one another; V means 0 or 1; n means 0, 1 or 2; Represents a hydrogen atom, lower alkyl group, lower alkenyl group, lower alkynyl group, aryl group, heteroaryl group, (aryl or heteroaryl Reel) a lower alkyl group, a lower Arukanoiru group, (§ Li one Norre or Heteroa reel) carbonyl group or single S0 ₂ - or means a group represented by R, or Roh, mouth Gen atom, a hydroxyl group or a lower alkoxy group R represents a hydrogen atom, a lower alkyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group, or a halogen atom, a hydroxyl group or a lower alkoxy group; And a salt thereof, and a general formula [i-j]

[I-! ]

[Where X ¹ is C ₃ —. ₈ cycloalkylene group, C ₃ - C ₈ Shikuroaruke two alkylene groups, C ₃ one C _e cycloalkylidene group, c ₃ - c ₈ Shikuroaruke two alkylidene group, Okiso c ₃ - c ₈ cycloalkylene group, Okiso C ₃ - C ₈ Shikuroaruke two lens groups, Okiso C ₃ - C ₈ cycloalkylidene group or Okiso C ₃ - C ₈ Shikuroaruke two isopropylidene group; X ² represents an oxygen atom or - S (0) _n - or single n (R ⁴⁾ - in formula A compound represented by the formula: alk ² , R ′, R ² , R ³ , R ⁴ and benzo ring A have the same meaning as defined in the above general formula [I-i]. And one or more drugs selected from the group consisting of and salts thereof.

“Treatment agent” means a drug that is provided for the purpose of treatment and / or prevention of various diseases.

“Halogen atom” means a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

The term "lower alkyl group" means a linear, branched or cyclic alkyl group having 1 to 7 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and the like. sec-butynole group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, tert-pentyl group, 1-methylbutyl group, 2-methylbutyl group, 1,2-dimethylpropyl group, 1-ethylpropyl group, Hexyl group, isohexyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 2,2-dimethylbutyl group, 1-ethylbutyl Group, 1,1,2-trimethylpropyl group, 1,2,2-trimethylpropyl group, 1-ethyl-2-methylpropyl group, 1-ethyl-1 monomethylpropyl group, cyclopropyl group, cyclobutyl group, cyclopentyl Group, cyclohexyl group, cycloheptyl group, cyclopropylmethyl group, 1-cyclopropylethyl group, 2-cyclopropylethyl group, 1-cyclopropylpropyl group, 2-cyclopropylpropyl group, 3 —Cyclopropylpropyl group, cyclopentylmethyl group, 2-cyclopentylethynole group, cyclohexylmethyl group and the like.

The “halo lower alkyl group” means the lower alkyl group having the halogen atom, and examples thereof include a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a 1-fluoroethyl group, a 2-fluoroethyl group, and a 2,2,2-trifluoroalkyl group. And a chloroethyl group, a pentafluoroethyl group, a chloromethyl group, a dichloromethyl group, a trichloromethyl group, a 1-chloroethyl group, and a 2-chloroethyl group.

"Aryl group" means a phenyl group, a naphthyl group or an anthryl group, and a phenyl group and a naphthyl group are preferred.

“Lower alkenyl group” means a straight-chain or branched alkenyl group having 2 to 7 carbon atoms, such as vinyl group, 2-propenyl group, isopropenyl group, 3-butenyl group, 2- Butenyl group, 1-butenyl group, 1-methyl-2-propenyl group, 1-methyl-1-propenyl group, 1-ethyl-1-ethenyl group, 2-methyl-2-propenyl group, 2-methyl-1-propenyl Group, 3-methyl-2-butenyl group, 4-pentenyl group and the like.

The term "lower alkoxy group" means an alkoxy group having a lower alkyl group, that is, an alkoxy group having 1 to 7 carbon atoms or an alkylene dioxy group having 1 to 3 carbon atoms, such as a methoxy group and an ethoxy group. Group, propyloxy group, isopropyloxy group, butoxy group, isoptyloxy group, tert-butoxy group, pentylokine group, cyclopropyloxy group, cyclobutyloxy group, cyclopentyloxy group, cyclohexyloxy group, cycloheptyloxy group, Shi Chloropropylmethyloxy, 1-cyclopropylethyloxy, 2-cyclopropylpropyloxy, 1-cyclopropylpropyloxy, 2-cyclopropylpropyloxy, 3-cyclo Examples include a propylpropyloxy group, a cyclopentylmethyloxy group, a 2-cyclopentylethyloxy group, a cyclohexylmethyloxy group, a methylenedioxy group, an ethylenedioxy group, and a trimethylenedioxy group.

“Lower alkylthio group” means an alkylthio group having a lower alkyl group, that is, an alkylthio group having 1 to 7 carbon atoms, for example, a methylthio group, an ethylthio group, a propylthio group, an isopropylthio group, a butylthio group, an isobutylthio group. Group, tert-butylthio group, pentylthio group, cyclopropylthio group, cyclobutylthio group, cyclopentylthio group, cyclohexylthio group, cycloheptylthio group, cyclopropylmethylthio group, 1-cyclopropylethylthio group, 2 —Cyclopropylethylthio, 1-cyclopropylpropylthio, 2-cyclopropylpropylthio, 3-cyclopropylpropylthio, cyclopentylmethylthio, 2-cyclopentylethylthio, cyclohexylmethylthio Etc. .

The term "lower alkylamino group" means an amino group mono-substituted by the lower alkyl group, for example, methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, sec-butylamino group, tert-butylamino. And the like.

The “di-lower alkylamino group” means an amino group di-substituted by the lower alkyl group, for example, a dimethylamino group, a getylamino group, an ethylmethylamino group, a dipropylamino group, a methylpropylamino group, a diisopropylamino group and the like. No.

"Heteroaromatic group" means a 5- or 6-membered group containing one or more, preferably 1 to 3, complex atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom, which are the same or different. A condensed ring in which the monocyclic aromatic heterocyclic group or the monocyclic aromatic heterocyclic group is condensed with the aryl group, or in which the same or different monocyclic aromatic heterocyclic groups are condensed with each other Means an aromatic heterocyclic group of the formula, for example, a piperyl group, a furyl group, a cyenyl group, an imidazolyl group, a virazolyl group, Thiazolinole group, isothiazolyl group, oxazolinole group, isoxazolyl group, triazolyl group, oxadiazolyl group, thiadiazolyl group, pyridyl group, virazinyl group, pyrimidinyl group, pyridazinyl group, indolinole group, benzofuranyl group, benzocenyl Midazolyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzothiazolinole, indazolinole, purinyl, quinolyl, isoquinolyl, phthalazinyl, naphthyridinyl Group, quinoxalinyl group, quinazolinyl group, cinnolinyl group, pteridinyl group and the like.

The “alkylene group having 2 to 4 carbon atoms” in the general formula [Ia] or [Ic] means a linear alkylene group, that is, an ethylene group, a trimethylene group, or a tetramethylene group.

“Aromatic carbon ring” means a benzene ring, a naphthalene ring or an anthracene ring.

“Aromatic heterocyclic ring” refers to a 5- or 6-membered member containing one or more, preferably one to three, atoms which are the same or different and are selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom. Or a fused aromatic heterocyclic ring in which the monocyclic aromatic heterocyclic ring is fused with the aromatic carbocyclic ring or in which the same or different monocyclic aromatic heterocyclic rings are fused with each other Means, for example, a pyrrole ring, a furan ring, a thiophene ring, an imidazole ring, a pyrazole ring, a thiazole ring, an isothiazole ring, an oxazole ring, an isoxazole ring, a triazole ring, an oxaziazole ring, a thiaziazole ring, pyridine Ring, virazine ring, pyrimidine ring, pyridazine ring, indole ring, benzofuran ring, benzothiophene ring, benzimidazo Ring, benzoxazolyl ring, benzoisoxazolyl ring, benzothiazole ring, benzoisothiazole ring, indazole ring, purine ring, quinoline ring, isoquinoline ring, phthalazine ring, naphthyridine ring, quinoxaline ring, quinazoline ring, cinnoline And a pteridine ring.

“Aliphatic carbocycle” means a carbocycle in which the bonds between the ring atoms except for the fused site are saturated, for example, a cyclobutane ring, a cyclobutene ring, a cyclopentane ring, a cyclopentene ring, a cyclohexane ring Ring, cyclohexyl A sen ring, a cycloheptane ring, a cycloheptene ring and the like are mentioned.

The term "aliphatic nitrogen-containing heterocyclic ring" means a nitrogen-containing heterocyclic ring containing one nitrogen atom and having at least a saturated bond between the ring atoms excluding the condensed site. For example, an azetidine ring, A lysine ring, piperidine ring, perhydroazepine ring and the like can be mentioned.

“Aromatic carbocyclic group” means a group formed from the aromatic carbocyclic ring, and means a phenyl group, a naphthyl group or an anthryl group.

“Aromatic heterocyclic group” means a group formed from the aromatic heterocyclic ring, for example, a pyrrolyl group, a furyl group, a cyenyl group, an imidazolyl group, a virazolinole group, a thiazolyl group, an isothiazolyl group, an oxazolyl group , Isoxazolyl, triazolyl, oxaziazolyl, thiadiazolyl, pyridyl, vilazinyl, pyrimidininole, pyridazinyl, indolyl, benzofuranyl, benzochenyl, benzoimidazolyl, benzoxoxa Zolyl, benzoisoxazolyl, benzothiazolyl, benzothiazolyl, indazolinole, purinyl, quinolyl, isoquinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl Group, pteridinyl group, etc. It is.

The term “acyl group” means a lower alkanoyl group, a lower alkenoyl group, a lower alkynyl group or an aroyl group, and among them, a lower alkanoyl group, an aroyl group and the like are preferable.

The term "lower alkanoyl group" means an alkanoyl group having 1 to 7 carbon atoms, for example, formyl group, acetyl group, propionyl group, butyryl group, isobutylyl group, valeryl group, isopararyl group, pinoyl group and the like. No.

The term "lower alkenoyl group" means an alkenoyl group having 3 to 7 carbon atoms, and examples thereof include an acryloyl group, a methacryloyl group, and a crotonyl group.

The term "lower alkynyl group" means an alkinoinole group having 3 to 7 carbon atoms, and examples thereof include a propioyl group.

The term "aroyl group" means an arylonyl group having 7 to 11 carbon atoms, and examples thereof include a benzoyl group, a naphthoyl group and a 2-naphthoyl group.

In general formula [I-e], “may be via an oxygen atom or a sulfur atom The `` alkylene group '' means an alkylene group having 2 or 6 carbon atoms which may be interposed through an oxygen atom or a sulfur atom, and the alkylene group together with an adjacent nitrogen atom is, for example, a pyrrolidinyl group, an oxazolidinyl group, an isoxoxa group. It forms a zolidinyl group, a thiazolidinyl group, an isothiazolidinyl group, a piperidino group, a morpholino group, a thiomorpholino group, a hexahydro-1H-azepinyl group and the like.

The “lower alkylene group” in the general formula [I-f] means a linear or branched alkylene group having 2 to 6 carbon atoms, for example, an ethylene group, a trimethylene group, a tetramethylene group, a pentamethylene group, Hexamethylene group and the like.

The “lower alkylene group optionally interposed with an oxygen atom” in the general formula [If] means a group in which any one methylene group of the lower alkylene group or the alkylene group is replaced by an oxygen atom. For example, ethylene group, trimethylene group, tetramethylene group, pentamethylene group, hexamethylene group, 2-oxatrimethylene group, 2-oxatetramethylene group, 2-oxapentamethylene group, 3-oxapentamethylene And a 2-oxahexamethylene group, and a 3-oxahexamethylene group. The group is, together with an adjacent ring carbon, for example, a cyclopropane ring, a cyclobutane ring, a cyclopentane ring, a cyclohexane ring, a cycloheptane A ring, an oxetane ring, an oxolane ring, an oxane ring, an oxepane ring, etc.

The “lower alkylidene group optionally interposed with an oxygen atom” in the general formula [If] is a straight-chain, branched or cyclic alkylidene group having 2 to 6 carbon atoms or any one of the alkylidene groups. A methylene group is a group in which an oxygen atom has been replaced by an oxygen atom.For example, ethylidene, isopropylidene, 1-ethylpropylidene, cyclopropylidene, cyclobutylidene, cyclopentylidene, cyclohexylidene, tetrahydropyran 4 and the like.

“Hydroxy lower alkyl group” means the lower alkyl group having a hydroxyl group, that is, a hydroxyalkyl group having 1 to 7 carbon atoms, such as a hydroxymethyl group, a 1-hydroxyethyl group, a 2-hydroxyethyl group. , 1-hydroxypropyl, 2-hydroxypropyl, 3-hydroxypropyl, 1- Examples include a hydroxybutyl group, a 2-hydroxybutyl group, a 3-hydroxybutyl group, and a 4-hydroxybutyl group.

“Methoxy lower alkyl group” means the lower alkyl group having a methoxy group, that is, a methoxyalkyl group having 2 to 8 carbon atoms, such as a methoxymethyl group, a 1-methoxyl group, Methoxytyl group, 1-methoxypropyl group, 2-methoxypropyl group, 3-methoxypropyl group, 1-methoxybutyl group, 2-methoxybutyl group, 3-methoxybutyl group, 4-methoxybutyl group, etc. Is mentioned.

The “lower alkylene group” of alk, alk ¹ or alk ² means a linear or branched alkylene group having 1 to 7 carbon atoms, such as a methylene group, an ethylene group, a propylene group, a butylene group, Examples include a 2-propylene group, a 2-methyl-1,3-propylene group, a 3-methyl-1,5-pentylene group, and a 2,2-dimethyl-1,3-propylene group.

“Lower alkynyl group” means a straight or branched alkynyl group having 2 to 7 carbon atoms, such as ethynyl group, 2-propynyl group, 1-methyl-2-propynyl group, 2-butynyl group. , 1-methyl-2-butynyl group, 2-pentynyl group and the like.

The “heteroaryl group” has the same meaning as the above-mentioned heteroaromatic ring group.

"Aryl lower alkyl group" means the lower alkyl group having the aryl group, for example, benzyl group, 1-phenylethyl group, 2-phenylethylenol group, 1-phenylpropyl group, 3-phenylpropyl group. , 1-phenylbutyl, 4-phenylbutyl, 1-naphthylmethyl, 2-naphthylmethyl, 1- (1-naphthyl) ethyl, 2- (1-naphthyl) ethyl, 1- (2-na And a 2- (2-naphthyl) ethyl group.

The “heteroaryl lower alkyl group” means the lower alkyl group having the heteroaryl group, for example, a 2-pyridylmethinole group, a 3-pyridylmethyl group, a 4-pyridylmethyl group, a 1- (2-pyridyl group. ) Ethyl, 1- (3-pyridyl) ethyl, 1- (4-pyridyl) ethyl, 2- (2-pyridyl) ethyl, 2- (3-pyridyl) ethyl, 2- (4-1 Pyridyl) ethyl group, 1- (2-pyridyl) propyl group, 3- (2-pyridyl) propyl group, 1- (2-pyridyl) And a 4- (2-pyridyl) butyl group.

The “lower alkoxycarbonyl group” means an alkoxycarbonyl group having a lower alkoxy group, that is, an alkoxycarbonyl group having 2 to 8 carbon atoms, for example, a methoxycarbonyl group, an ethoxycarbonyl group, a propyloxy group. Cyclocarbonyl group, isopropyloxycarbonyl group, butoxycarbonyl group, isobutyloxycarbonyl group, tert-butoxycarbonyl group, pentyloxycarbonyl group, cyclopropyloxycarbonyl group, cyclobutyloxycarbonyl group, cyclopentyloxycarbonyl group , Cyclohexyloxycarbonyl, cycloheptyloxycarbonyl, cyclopropylmethyloxycarbonyl, 1-cyclopropylethyloxycarbonyl, 2-cyclopropylethyloxycarbonyl 1-cyclopropylpropyloxycarbonyl group, 2-cyclopropylpropyloxycarbonyl group, 3-cyclopropylpropyloxycarbonyl group, cyclopentylmethyloxycarbonyl group, 2-cyclopentylethyloxycarbonyl group And cyclohexylmethyloxycarbonyl group.

The term "lower alkoxycarbonylamino group" means an alkoxycarbonylamino group having the lower alkoxycarbonyl group, such as a methoxycarbonylamino group, an ethoxycarbonylamino group, a propoxycarbonylamino group, A propoxycarbonylamino group, a butoxycarbonylamino group, a tert-butoxycarbonylamino group and the like.

"Aryl lower alkoxycarbonyl group" means the above-mentioned lower alkoxycarbonyl group having the aforementioned aryl group, for example, benzyloxycarbonyl, 1-phenylethyloxycarbonyl, 2-phenyl Ethyloxycarbonyl, 3-phenylpropyloxycarbonyl, 1-naphthylmethyloxycarbonyl, 2-naphthylmethyloxycarbonyl, 1- (1-naphthyl) ethyloxycarbonyl 1- (2-naphthyl) ethyloxycarbonyl group, 2- (1-naphthyl) ethyloxycarbonyl group, 2- (2-naphthyl) ethyloxycarbonyl group, 3- (1— A naphthyl) propyloxycarbonyl group; a 3- (2-naphthyl) propyloxycarbonyl group; “Heteroarylene lower alkoxycarbonyl group” refers to the aforementioned heteroaryl The lower alkoxycarbonyl group having a group, for example, 2-pyridylmethyloxycarbonyl group, 4-pyridylmethyloxycarbonyl group, 2- (2-pyridyl) ethyloxycarbonyl group, 2-( Examples thereof include a 4-pyridyl) ethyloxycarbonyl group, a 3- (2-pyridinole) propyloxycarbinole group, and a 3- (4-pyridyl) propyloxycarbonyl group.

“Lower alkenyloxy group” means an alkenyloxy group having a lower alkenyl group, that is, an alkenyloxy group having 2 to 7 carbon atoms, for example, a vinyloxy group, a 2-propenyloxy group, an isopropenyloxy group. Group, 3-butenyloxy group, 2-butenyloxy group, 1-butenyloxy group, 1-methyl-12-propenyloxy group, 1-methyl-1--1-propenyloxy group, 1-ethyl-1-ethenyloxy group And 2-methyl-2-propenyloxy group, 2-methyl-1-propenyloxy group, 3-methyl-2-butenyloxy group, and 4-pentenyloxy group.

"Lower alkynyloxy group" means an alkynyloxy group having a lower alkynyl group, that is, an alkynyloxy group having 2 to 7 carbon atoms, such as an ethynyloxy group, a 2-propynyloxy group, and a monomethyl group. —2-propynyloxy group, 2-butynyloxy group, 1-methyl-2-butynyloxy group, 2-pentynyloxy group and the like.

“Hydroxy lower alkoxy group” means a hydroxyalkoxy group having the hydroxy lower alkyl group.

The “lower alkoxy lower alkoxy group” means an alkoxyalkoxy group having the lower alkoxy group, for example, a methoxymethyloxy group, an ethoxymethyloxy group, a 1-methoxyshetyloxy group, a 1-ethoxyshetyl. Methoxy group, 2-methoxyloxy group, 2-ethoxyloxyl group, 1-methoxypropyloxy group, 2-methoxypropyloxy group, 3-methoxypropyloxy group, and the like. .

The “aralkyloxy group” or the “aryl lower alkoxy group” means the lower alkoxy group having the aryl group, for example, a benzyloxy group,

1-phenylethyloxy group, 2-phenylethyloxy group, 3-phenylpyroxy group, 1-naphthylmethyloxy group, 2-naphthylmethyloxy group, 1- (1-naphthyl) ethyloxy group, 1- (2-naphthyl) ethyloxy group,

2- (1-naphthyl) ethyloxy group, 2- (2-naphthyl) ethyloxy group,

And 3- (1-naphthyl) propyloxy group, 3- (2-naphthyl) propyloxy group and the like.

The “heteroaryl lower alkoxy group” means the lower alkoxy group having the heteroaryl group, for example, a 2-pyridylmethyloxy group, a 4-pyridylmethyloxy group, a 2- (2-pyridyl) ethyloxy group. And 2- (4-pyridyl) ethyloxy, 3- (2-pyridinole) propyloxy, and 3- (4-pyridyl) propyloxy.

The “lower alkoxycarbonyloxy group” means an alkoxycarboxy group having the lower alkoxycarbonyl group.

“Aryl lower alkoxycarbonyloxy group” means an aryl alkoxycarboxy group having the above aryl lower alkoxycarbonyl group.

The term "heteroaryl lower alkoxycarbonyloxy group" means a heteroarylalkoxycarbonyloxy group having the above-mentioned heteroaryl lower alkoxycarbonyl group.

“Lower alkoxy lower alkoxycarbonyl group” means an alkoxyalkoxyl alkoxyl group having the lower alkoxy lower alkoxy group. As the “amino group di-substituted by a lower alkylene group”, for example, a 1-azetidino group, a 1-pyrrolidino group, a 1-piperidino group and the like are preferable.

Examples of the “lower alkylene group optionally interposed through an oxygen atom or a group represented by S (0) _n or NR °” include a morpholino group, a thiomorpholino group, a thiomorpholino S-oxide group, Morpholino S, S-dioxide group, 4-R. — A piperazino group and the like are preferred.

“Lower alkanoyloxy group” means an alkanoyloxy group having the lower alkanoyl group.

"Aryl lower alkyl group" means the lower alkanoyl group having the aryl group, for example, phenylacetyl group, 3-phenylpropionyl group, 4-phenylbutyryl group, 1 One naphthyl acetyl group, 2-naphthyl acetyl Butyl, 3- (1-naphthyl) propionyl, 3- (2-naphthyl) propionyl, 4- (1-naphthyl) butylinole, and 4- (2-naphthyl) butylyl.

“Heteroaryl lower alkynyl group” means the lower alkynyl group having the heteroaryl group, for example, 2-pyridylacetyl, 4-pyridylacetyl, 3- (2-pyridinoleyl). A) propionyl group, 3- (4-pyridinole) propionyl group, 4- (2-pyridinole) butylinole group, and 4- (4-pyridinole) butyryl group.

“Aryl lower alkanoyloxy group” means an aryl alkanoyloxy group having the above aryl lower alkanoyl group.

"Heteroaryl lower alkanoyloxy group" means a heteroaryl lower alkanoyloxy group having the above heteroaryl lower alkanoyloxy group.

The “arylcarbonyl group” means an arylcarbinyl group having the aryl group, and examples thereof include a benzoyl group, a 1-naphthoyl group, and a 2-naphthoyl group.

The term "arylcarbonylamino group" means an arylcarbonylamino group having the arylcarbonyl group, and examples thereof include a benzoylamino group, a 1-naphthoylamino group, and a 2-naphthoylamino group.

"Heteroarylcarbonyl group" means a heteroarylcarbonyl group having a heteroaryl group, such as a 2-furoyl group, a 3-furoyl group, a 2-tenoinole group, and a 3-tenoinole group. , 2-pyridinole, 3-pyridinole, 4-pyridyl and the like.

The “aryloxy group” means an aryloxy group having the above aryl group, and examples thereof include a phenyloxy group, a 1-naphthoxy group, and a 2-naphthoxy group.

The term "heteroaryloxy group" means a heteroaryloxy group having the above-mentioned heteroaryl group. Examples thereof include a 2-furyloxy group, a 3-furyloxy group, a 2-phenyloxy group, a 3-phenyloxy group, and a 2-phenyloxy group. Examples include a pyridyloxy group and a 3-pyridyloxy group. “Arylene group” means an arylene group in which the aryl group has become a divalent group, for example, 1,2-phenylene group, 1,3-phenylene group, 1,4-phenylene group. And 1,2-naphthylene, 1,3-naphthylene, 1,4-naphthylene, 2,4-naphthylene, 1,5-naphthylene, and 2,7-naphthylene. The “heteroarylene group” means a heteroarylene group in which the heteroaryl group has become a divalent group, for example, 2,3-furylene group, 2,4-furylene group, 3,4-monofurylene group, Examples thereof include a 2,3-Chenylene group, a 2,4-Chenylene group, a 3,4-Chenylene group, a 2,3-pyridylene group, and a 2,4-pyridylene group.

“C ₃ -C ₈ cycloalkylene group” means a cycloalkylene group having 3 to 8 carbon atoms, such as 1,3-cyclopentylene group, 1,3-cyclohexylene group, 1,4-cyclohexane group. Xylene groups and the like can be mentioned.

The “C ₃ -C ₈ cycloalkenylene group” means a cycloalkenylene group having 3 to 8 carbon atoms, for example, 1,3-cyclopenter-2-enylene group, 1,3-cyclohexene. Examples include a phenylene group and a 1,4-cyclohexyl 2-phenylene group.

“C ₃ -C ₈ cycloalkylidene group” means a cycloalkylidene group having 3 to 8 carbon atoms, such as cyclopropylidene group, cyclobutylidene group, cyclopentylidene group, cyclohexylidene group, etc. .

The - "Ji ₈ cycloalkenylene isopropylidene group C _3" carbon number of 3 means Shikuroaruke two isopropylidene groups 8, for example 1, 1 Shikuropenta - 2 Eniriden group, 1, 1 Kisa 2 Eniriden group to Shikuro , 1,1-cyclohexa-3-enylidene group and the like.

"Okiso C ₃ - Ji ₈ cycloalkylene group" and the C ₃ having Okiso group - means a C ₈ cycloalkylene group, such as 2-Okiso one 1, 3-cyclopentylene group, 2-Okiso one 1 2,3-cyclohexylene group, 2-oxo-1,4-cyclohexylene group, 3-oxo-1,3-cyclohexylene group, 3-oxo-1,4-cyclohexylene group, etc. Can be

"Okiso C ₃ - 0 ₈ cycloalkenylene group" and the C ₃ having Okiso group - mean C ₈ Shikuroaruke two alkylene groups, such as 2-Okiso one 1, 3-cyclopenta-5 Eniren group, 2- Oxo-1,3-cyclohexa-1-enylene group, 2- Oxo-1,4-cyclohexa 5-enylene group, 3-oxo-1,4-cyclohexa 5-enylene group and the like.

The - "Okiso C _3. ₈ cycloalkylidene group", said C ₃ having Okiso group - means a C ₈ cycloalkylidene group, for example, 2-year old Kiso cyclopropylidene group, 2-O ROCEPHIN black butylidene group, 2 — Oxocyclopentylidene group, 2-oxo hexylidene group and the like.

The “oxo C ₃ —c ₈ cycloalkenylidene group” means the above-mentioned c ₃ -C ₈ cycloalkenylidene group having an oxo group, for example, a 2-oxo-1,1-cyclobenzene-3-enylidene group, —Oxo-1,5-cyclohexyl-5-enylidene group, 3-oxo-1,1-cyclohexyl 5-enylidene group, and the like. General formulas [I-a], [I-b], [Ic], [I-d], [I-e], [I-f], [I-g], [I-h], [I-a] The “salt” of the compound represented by [I-i] or [I-j] means a pharmaceutically acceptable conventional one, for example, a basic group such as a basic heterocyclic group or an amino substituent. And salts of a base addition salt at the carboxyl group in the case of having a carboxyl group.

The acid addition salts include, for example, inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate, perchlorate; for example, maleate, fumarate, tartrate, citrate, ascorbate, Organic acid salts such as trifluoroacetate; sulfonates such as methanesulfonate, isethionate, benzenesulfonate and P-toluenesulfonate.

Examples of the base addition salt include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; for example, ammonium salt; for example, trimethylamine salt, triethylamine salt; And organic amine salts such as dicyclohexylamine salt, ethanolamine salt, diethanolamine salt, triethanolamine salt, procaine salt, and Ν, Ν ′ dibenzylethylenediamine salt.

The “neuropeptide Υ5 receptor antagonist other than cholesterol lowering agent” is not particularly limited as long as it has the action and is a pharmaceutically acceptable drug. For example, hydroxymethyl dalaryl CoA reductase Inhibitors are preferred, among which, for example, Nature, 343, 425 (1990) Preferred are lovastatin, simvastatin, pravastatin, fluvastatin and the like described in (1).

Each compound according to the present invention will be described in more detail with reference to preferred specific examples.

Hereinafter, the compound represented by the general formula [I-a] will be described.

A represents a group represented by a nitrogen atom or C one R ^5.

A is preferably a nitrogen atom.

Ar ¹ represents an aryl group which may have a substituent selected from the group consisting of a halogen atom, a lower alkyl group and a halo-lower alkyl group.

"An aryl group which may have a substituent selected from the group consisting of a halogen atom, a lower alkyl group and a halo-lower alkyl group" refers to the unsubstituted aryl group or any substitutable position. Means the aryl group having a substituent, and the substituent is the same or different from the group consisting of a halogen atom, a lower alkyl group and a halo-lower alkyl group, and one or more, preferably one or two, are selected. be able to.

As the halogen atom for the substituent, for example, a chlorine atom, a bromine atom and the like are preferable.

As the lower alkyl group for the substituent, for example, a methyl group, an ethyl group, a propanol group, an isopropyl group, a cyclopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group and the like are more preferable. Is preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, a cyclopropyl group or the like. The halo-lower alkyl group for the substituent is, for example, preferably a trifluoromethyl group.

As the substituent, a halogen atom and the like are preferable.

As the aryl group for Ar ¹ , for example, a phenyl group is suitable.

Therefore, examples of Ar ¹ include a phenyl group and a 3-chlorophenyl group, and among them, a 3-chlorophenyl group and the like are preferable.

Ar ² is a substituent selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkenyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group and an aryl group. With Represents an aryl group or a heteroaromatic ring group.

A substituent selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group and an aryl group; An aryl group or a heteroaromatic ring group, which may have an unsubstituted aryl group or a heteroaromatic ring group, or the aryl group having a substituent at any substitutable position. And the substituent is a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group. And one or two or more, preferably one or two, identical or different from the group consisting of

The lower alkyl group for the substituent is, for example, preferably a methyl group, an ethyl group.

Examples of the lower alkenyl group for the substituent include a vinyl group, a 2-propenyl group, an isopropyl group, a 2-butenyl group, a 3-methyl-2-butenyl group, and more preferably a vinyl group, Propenyl groups and the like are preferred.

The halo-lower alkyl group for the substituent is, for example, preferably a fluoromethyl group, a trifluoromethyl group.

The lower alkoxy group for the substituent is, for example, preferably a methoxy group, an ethoxy group, a propyloxy group, a methylenedioxy group, and the like, and more preferably a methoxy group, a methylenedioxy group, and the like.

The lower alkylthio group for the substituent is, for example, preferably a methylthio group, an ethylthio group, a propylthio group, and more preferably a methylthio group. The lower alkylamino group of the substituent is, for example, preferably a methylamino group.

As the di-lower alkylamino group for the substituent, for example, a dimethylamino group is preferred.

The aryl group of the substituent is, for example, preferably a phenyl group. As the substituent, a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a di-lower alkylamino group and the like are preferable.

The aryl group of Ar ² is preferably, for example, a phenyl group, and the heteroaromatic group is, for example, a pyridyl group.

Therefore, as Ar ² , for example, a phenyl group, a 1-naphthyl group, a 2-naphthyl group, a 2-pyridinole group, a 3-pyridinole group, a 4-pyridyl group, a 2-chlorophenyl group, a 3-chlorophenyl group , 4-chlorophenyl, 3,4-dichlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 5-chloro-3-pyridyl, 5-bromo-3-pyridyl, 2 —Methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-propylphenyl, 5-methyl-2-pyridyl, 6-methyl-3-pyridyl, 6- Ethyl-3-pyridyl, 2-methyl-4-pyridyl, 2-ethyl-4-pyridyl, 2-propyl-14-pyridyl, 2-butyl-4-pyridyl, 3-methyl 4-pyridyl group, 3-vinylvinyl group, 4-vinylphenyl group, 4- (2-propenyl) phenyl group, 5-vinyl-3-pyridyl group, 3-trifluoronorelomethylphenyl group, -trifluoro Romethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 4-ethoxyphenyl group, 4-isopropyloxyphenyl group, 3,4-dimethoxyphenyl group, 3,4 4-Methylenedioxyphenyl, 6-methoxy-3-pyridyl, 2-methoxy-4-pyridyl, 3-dimethylaminophenyl, 4-dimethylaminophenyl, 4-methoxy-3-dimethylamino Phenyl, 2-methylthiophenyl, 3-methylthiophenyl, 4-methylthiophenyl, 2-methylthio-4-pyridyl, 3-biphenylyl , 4-biphenylyl group and the like. Among them, 4-pyridyl group, 2-methyl-4-pyridyl group, 2-ethyl-4-pyridinole group, 2-propyl-4-pyridyl group, 2-butyl-4-pyridyl group, 3- Black phenyl group, 4-Monophenyl group, 3,4-Dichlorophenyl group, 3-Bromophenyl group, 4-Bromophenyl group, 2-Methylphenyl group, 3-Methylphenyl group, 4-Methylphenyl group, 4 —Ethylphenyl group, 3-methyl-4-pyridyl group, 3-ethyl-4-pyridyl group, 4-vinylphenyl group, 4- (2-propenyl) Phenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 3,4-dimethoxyphenyl, 3,4-methylenedioxyphenyl, 3-methoxy-14-pyridyl, A 4-methylthiophenyl group, a 3-methylthio-4-pyridyl group and the like are preferred.

R ¹ represents a bond connected to a hydrogen atom or a lower alkyl group or R ⁵ .

As the lower alkyl group for R ¹ , for example, a methyl group, an ethyl group, and the like are preferable. By "means a bond linked to R ⁵ ', when the group A is represented by C-R ^5, a double bond with an existing bond linked both R ¹ and R ⁵ together form To do.

It is preferable that R ¹ represents a bond in connection with a hydrogen atom or R ⁵ .

R ² represents a hydrogen atom or a lower alkyl group.

As the lower alkyl group for R ² , for example, a methyl group, an ethyl group and the like are preferable.

As R ² , a hydrogen atom is preferable.

R ³ and R ⁴ may be the same or different and each may be a hydrogen atom or a lower alkyl group, or both R ³ and R ⁴ may be linked to each other to have a lower alkyl group; Means an alkylene group.

As the lower alkyl group for R ³ and R ⁴ , for example, a methyl group, an ethyl group and the like are preferable.

The `` alkylene group having 2 to 4 carbon atoms which may have a lower alkyl group '' is the unsubstituted alkylene group or the same or different 1 or 2 or more lower alkyl groups at any substitutable position. And the unsubstituted alkylene group is preferable.

The lower alkyl group as a substituent is, for example, preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, etc., and more preferably a methyl group.

As R ³ and R ⁴ , R ³ and R ⁴ are the same or different and are a lower alkyl group, or a carbon which may have a lower alkyl group by linking both R ³ and R ⁴ to each other. A C 2-4 alkylene group, particularly a C 2 alkylene group, is preferred.

R ⁵ represents a bond in connection with a hydrogen atom, a hydroxyl group, a lower alkyl group or a lower alkoxy group, or R ¹ . As the lower alkyl group for R ⁵ , for example, a methyl group, an ethyl group, and the like are preferable. As the lower alkoxy group for R ⁵ , for example, a methoxy group, an ethoxyquin group, a propyloxy group and the like are preferable.

The rR ¹ connected to means coupled with ", when the group A is represented by C one R ^5, both R ¹ and R ⁵ each other, a double bond with an existing bond linked to To form.

It is preferable that R ⁵ represents a bond in connection with a hydrogen atom or a hydroxyl group or R ¹ .

Hereinafter, the compound represented by the general formula [I-b] will be described.

Ring A and ring B are ortho-fused with each other; ring A is an aromatic carbon or heterocycle; ring B is a 4- to 7-membered aliphatic carbon or nitrogen-containing heterocycle, wherein the nitrogen atom is Means a ring that can only exist at the fused site of

Preferred examples of the aromatic carbon ring A include a benzene ring and a naphthalene ring, and examples of the aromatic heterocycle include an indole ring, a benzofuran ring, a benzothiophene ring, and a quinoline ring.

As the 4- to 7-membered aliphatic carbocyclic ring of the B ring, for example, a cyclopentane ring, a cyclopentene ring, a cyclohexane ring, a cyclohexene ring and the like are preferable.

As the 4- to 7-membered aliphatic nitrogen-containing heterocyclic ring of the B ring, for example, a pyrrolidine ring and the like are preferable.

Therefore, the expression

(Where R represents a substituent or a hydrogen atom selected from the group consisting of a halogen atom, a nitro group, a lower alkyl group, a lower alkoxy group, an aromatic carbocyclic group and a carbonyl group having an aromatic carbocyclic group. The group represented by

Wherein R has the meaning described above, and the like.

Group represented by the formula

Group or formula represented by

It is preferred, such as a group represented by ₍

formula

The bond between the group represented by and the carbonyl group adjacent thereto is preferably a case where the group is bonded to the carbon atom of the carbonyl group on the ring atom of the ring B excluding the condensed site with the ring A.

R represents a hydrogen atom or a substituent selected from the group consisting of a halogen atom, a nitro group, a lower alkyl group, a lower alkoxy group, an aromatic carbocyclic group, and a hydrocarbon group having an aromatic carbocyclic group.

The substituent is the same or different from one or more of the group consisting of a halogen atom, a nitro group, a lower alkyl group, a lower alkoxy group, an aromatic carbocyclic group and a functional group having an aromatic carbocyclic group, Preferably 1 or 2 can be selected and the formula

(Wherein ring A and ring B have the above-mentioned meanings).

The lower alkoxy group for the substituent is, for example, preferably a methoxy group, an ethoxyquin group, a propyloxy group, an isopropyloxy group, a methylenedioxy group, and more preferably a methoxy group, a methylenedioxy group.

As the aromatic carbocyclic group for the substituent, for example, a phenyl group is suitable. As the carbonyl group having an aromatic carbocyclic group as the substituent, for example, a benzyl group or the like is suitable.

As R, a substituent such as a halogen atom or a lower alkyl group in addition to a hydrogen atom is preferable.

Ar is a halogen atom, lower alkyl group, lower alkenyl group, halo-lower alkyl Or a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group and an aromatic carbocyclic group, which may have an aromatic carbon or heterocyclic group. Means

A substituent selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, and an aromatic carbocyclic group; An aromatic carbon or heterocyclic group which may have an unsubstituted aromatic carbocyclic group or an aromatic heterocyclic group, or the aromatic having a substituent at any substitutable position. Means a carbocyclic group or the aromatic heterocyclic group, and the substituent is a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower group. One or more, preferably one or two, preferably the same or different from the group consisting of an alkylamino group and an aromatic carbocyclic group can be selected. Kill.

Suitable examples of the halogen atom for the substituent include a chlorine atom and a bromine atom.

The lower alkyl group for the substituent is, for example, preferably a methyl group, an ethyl group, a propyl group, a butyl group.

The lower alkenyl group for the substituent includes, for example, a vinyl group, a 2-propenyl group, an isopropyl group, a 2-butenyl group, a 3-methyl-2-butenyl group, and more preferably a vinyl group, a 2-propyl group A benzyl group and the like are preferred.

The lower alkoxy group for the substituent is, for example, preferably a methoxy group, an ethoxy group, a propyloxy group, an isopropyloxy group, a methylenedioxy group, and more preferably a methoxy group, a methylenedioxy group.

The lower alkylthio group for the substituent is, for example, preferably a methylthio group, an ethylthio group, a propylthio group, and more preferably a methylthio group. As the lower alkylamino group for the substituent, for example, a methylamino group and the like are preferable.

Examples of the di-lower alkylamino group for the substituent include a dimethylamino group and the like. Is preferred.

As the aromatic carbocyclic group for the substituent, for example, a phenyl group is suitable. As the substituent, a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a di-lower alkylamino group and the like are preferable.

As the aromatic carbocyclic group for Ar, for example, a funyl group, a naphthyl group and the like are preferable, and as the aromatic heterocyclic group, for example, a pyridyl group and the like are preferable.

Therefore, as Ar, for example, a phenyl group, a 1-naphthyl group, a 2-naphthyl group, a 2-pyridyl group, a 3-pyridyl group, a 4-pyridyl group, a 2-chlorophenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group , 3,4-dichlorophenyl group, 2-bromophenyl group, 3-bromophenyl group, 4-bromophenyl group, 5-chloro-3-pyridyl group, 5-bromo-3-pyridyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-propylphenyl, 5-methyl-2-pyridyl, 6-methyl-3-pyridyl, 6-ethyl-3-pyridyl, 2-methyl-4-pyridyl Group, 2-ethyl-4,4-pyridyl group, 2-propyl-1,4-pyridinole group, 2-butyl-4-pyridyl group, 3-methyl-4,1 Pyridyl group, 3-vinylvinyl group, 4-vinylphenyl group, 4- (2-propenyl) phenyl group, 5-vinyl-3-pyridyl group, 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group Group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 4-ethoxyphenyl group, 4-isopropyloxyphenyl group, 3,4-dimethoxyphenyl group, 3,4-methylenediene Methoxyphenyl, 6-methoxy-3-pyridyl, 2-methoxy-1-pyridyl, 3-dimethylaminophenyl, 4-dimethylaminophenyl, 4-methoxy

3-dimethylaminophenyl, 2-methylthiophenyl, 3-methylthiophenyl, 4-methylthiophenyl, 2-methylthio-4-pyridyl, 3

-Biphenylinole group, 4-biphenylinole group and the like. Among them, 4-pyridinole group, 2-methyl-4-1-pyridyl group, 2-ethyl-4-pyridyl group, 2-propyl-1 group

4-pyridyl, 2-butyl-1-pyridyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 3-bromophenyl, 4-bromophenyl, 2-methylphenyl, 3-methylphenyl Methylphenyl group, 4-methyl Phenyl, 4-ethylphenyl, 3-methyl-4-pyridyl, 3-ethyl-4-pyridyl, 4-vinylphenyl, 4- (2-propenyl) phenyl, 3-methoxyphenyl , 4-methoxyphenyl, 4-ethoxyphenyl, 3,4-dimethoxyphenyl, 3,4-methylenedioxyphenyl, 3-methoxy-4-pyridyl, 4-methylthiophenyl , 3-Methylthio-14-pyridyl groups and the like are preferred.

Note that the expression

The group represented by the formula

Wherein Ar is a phenyl group, and a compound represented by the formula:

The group represented by the formula

And a compound in which Ar is a 4-chlorophenyl group is excluded from the present invention.

The compound represented by the general formula [I-c] will be described below.

"An aryl group which may have a substituent selected from the group consisting of a halogen atom, a lower alkyl group and a halo-lower alkyl group" is the unsubstituted aryl group or any substitutable aryl group. The aryl group having a substituent at the position, wherein the substituent is the same or different from the group consisting of a halogen atom, a lower alkyl group and a halo-lower alkyl group; Can choose it can.

As the lower alkyl group for the substituent, for example, a methyl group, an ethyl group, a propanol group, an isopropyl group, a cyclopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group and the like are more preferable. Is preferably a methyl group, an ethylene group, a propyl group, an isopropyl group, a cyclopropyl group or the like. The halo-lower alkyl group for the substituent is, for example, preferably a trifluoromethyl group.

As the substituent, a halogen atom and the like are preferable.

As the aryl group for Ar ¹ , for example, a phenyl group is suitable.

Ar ² is a substituent selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group and an aryl group. It means an aryl group or a heteroaromatic group which may be present.

It has a substituent selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group and an aryl group. The aryl group or the heteroaromatic group which may be substituted or unsubstituted, the aryl group or the heteroaromatic ring group, or the aryl group or the heteroaromatic group having a substituent at any substitutable position. A cyclic group, wherein the substituent is a group consisting of a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, and an aryl group. Thus, the same or different one or more, preferably one or two can be selected.

The lower alkyl group for the substituent is, for example, preferably a methyl group, an ethyl group. It is.

Examples of the lower alkenyl group for the substituent include a vinyl group, a 2-propenyl group, an isopropyl group, a 2-butenyl group, a 3-methyl-2-butenyl group, and more preferably a vinyl group, a 2-propyl group. A benzyl group and the like are preferred.

The di-lower alkylamino group for the substituent is, for example, preferably a dimethylamino group.

The aryl group of the substituent is, for example, preferably a phenyl group.

As the substituent, a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a di-lower alkylamino group and the like are preferable.

Accordingly, Ar ² includes, for example, phenyl, 1-naphthyl, 2-naphthyl, 2-pyridinole, 3-pyridyl, 4-pyridyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, Monochlorophenyl, 3,4-dichlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 5-chloro-3-pyridyl, 5-bromo-3-pyridyl Group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 3-ethylphenyl group, 4-ethylphenyl group, 4-propylphenyl group, 5-methyl-2-pyridyl group, 6-methyl-3-pyridyl group 6-ethyl-3-pyridyl group, 2-methyl-4 monopyridyl group, 2-ethyl-4-pyridyl group, 2-propyl-14-pyridyl group, 2-propyl-4-pyridyl group, 3-methyl-4 Pyridyl group, 3- Vinylphenyl, 4-vinylphenyl, 4- (2-propenyl) phenyl, 5-vinyl-3-pyridyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-methyl Toxylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-isopropyloxyphenyl, 3,4-dimethoxyphenyl, 3,4-methylenedioxyphenyl, 6-methyl Toxi-3-pyridyl group, 2-methoxy-4-pyridyl group, 3-dimethylaminophenyl group, 4-dimethylaminophenyl group, 4-methoxy-3-dimethylaminophenyl group, 2-methylthio Phenyl, 3-methylthiophenyl, 4-methylthiophenyl, 2-methylthio-4-pyridyl, 3-biphenylyl, 4-biphenylyl Among which, among others, 4-pyridinole, 2-methyl-4-pyridyl, 2-ethyl-4-pyridyl, 2-propyl-4-pyridyl, 2-butyl-4-pyridyl, and 3-chlorophenyl Group, 4-chlorophenyl group, 3,4-dichlorophenyl group, 3-bromophenyl group, 4-bromophenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 4-ethylphenyl group, 3-methyl 1-4-pyridyl group, 3-ethyl-4-pyridyl group, 4-vinylphenyl group, 4- (2-propenyl) phenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 4-ethoxy Thiphenyl group, 3,4-dimethoxyphenyl group, 3,4-methylenedioxyphenyl group, 3-methoxy-4-pyridyl group, 4-methylthiophenyl group, 3-methylthio-1-41 Lysyl group and the like.

R ¹ and R ² are the same or different and each represents a hydrogen atom or a lower alkyl group. As the lower alkyl group for R ¹ and R ² , for example, a methyl group, an ethyl group and the like are preferable.

As R ¹ and R ² , both are preferably hydrogen atoms.

R ³ and R ⁴ are the same or different and each may be a hydrogen atom or a lower alkyl group, or both R ³ and R ⁴ may be linked to each other to form a lower alkyl group; Means a group.

"C2-C4 alkylene group optionally having lower alkyl group" and Represents an unsubstituted alkylene group or an alkylene group having one or more lower alkyl groups which are the same or different at any substitutable position, and the unsubstituted alkylene group is preferable.

As R ³ and R ⁴ , even if R ³ and R ⁴ are the same or different and are a lower alkyl group, or both R ³ and R ⁴ are linked to each other to have a lower alkyl group Preferred are alkylene groups having 2 to 4 carbon atoms, particularly alkylene groups having 2 carbon atoms.

R ⁵ represents a hydrogen atom, a lower alkyl group or a lower alkoxy group.

As the lower alkyl group for R ⁵ , for example, a methyl group, an ethyl group, and the like are preferable.

Lower alkoxy as R ^5, alkoxy groups of from 1 to 7 carbon atoms, i.e., for example, main butoxy group, an ethoxy group, etc. Puropiruokishi group, more preferably a suitable main preparative alkoxy group.

The R ^5, are preferable a hydrogen atom.

Hereinafter, the compound represented by the general formula [Id] will be described.

Ar ¹ is selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, an acyl group and an aryl group. It means an aryl group or a heteroaromatic ring group which may have a substituent.

A substituent selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, an acyl group and an aryl group. The aryl group or the heteroaromatic ring group '' may be the unsubstituted aryl group or the heteroaromatic ring group, or the aryl group having the substituent at any substitutable position or the aryl group A heteroaromatic group, wherein the substituent is a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkynoleamino group, or an acyl group; And one or more, preferably one or two, identical or different from the group consisting of Can be

As the halogen atom for the substituent, for example, a chlorine atom, a bromine atom and the like are preferable. M

Examples of the lower alkenyl group for the substituent include a vinyl group, a 2-propenyl group, an isopropenyl group, a 2-butenyl group, a 3-methyl-2-butenyl group, and more preferably a vinyl group, Propenyl groups and the like are preferred.

The lower alkylthio group for the substituent is, for example, preferably a methylthio group, an ethylthio group, a propylthio group, and more preferably a methylthio group. The lower alkylamino group for the substituent is, for example, preferably a methylamino group.

As the acyl group for the substituent, for example, a formyl group, an acetyl group, a benzoyl group and the like, and more preferably a benzoyl group and the like are suitable.

The aryl group of the substituent is, for example, preferably a phenyl group.

As the substituent, a halogen atom, a lower alkyl group, an acyl group and the like are preferable.

The aryl group of Ar ¹ is preferably, for example, a phenyl group or a naphthyl group, and the heteroaromatic group is, for example, a pyridyl group or a benzoxazolyl group. Therefore, Ar ¹ is, for example, phenyl, 1-naphthinole, 2-naphthyl, 2-pyridinole, 3-pyridinole, 4-pyridyl, 2-benzoxazolyl, 4-isobutylphenyl Group, 3-benzoylphenyl group, 2-funololol 4-biphenylyl group and the like, and among them, 111-naphthyl group, 2-naphthinolene group, 3-benzoylphenyl group and the like are preferable. is there.

Ar ² is a halogen atom, lower alkyl group, lower alkenyl group, halo-lower alkyl Aryl, heteroalkyl, lower alkylthio, lower alkylamino, di-lower alkylamino, and aryl, which may have a substituent selected from the group consisting of aryl and heteroaryl. It means an aromatic ring group.

Having a substituent selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group and an aryl group. The aryl group or the heteroaromatic ring group which may be substituted '' is the unsubstituted aryl group or the heteroaromatic ring group, or the aryl group or the heteroaryl group having a substituent at any substitutable position. And the substituent is a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, and aryl. One or two or more, preferably one or two, identical or different groups can be selected from the group consisting of one group.

The lower alkoxy group for the substituent is, for example, preferably a methoxy group, an ethoxyquin group, a propyloxy group, a methylenedioxy group, and the like, and more preferably a methoxy group, a methylenedioxy group, and the like.

The aryl group of the substituent is, for example, preferably a phenyl group.

The aryl group of Ar ² is preferably, for example, a phenyl group, and the heteroaromatic ring group is, for example, a pyridyl group.

Therefore, as Ar ² , for example, phenyl, 1-naphthyl, 2-naphthyl, 2-pyridyl, 3-pyridyl, 4-pyridinole, 2-chlorophenyl, 3-chloro Phenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 5-chloro-3-pyridyl, 5-bromo-3-pyridyl Group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 3-ethylphenyl group, 4-ethylphenyl group, 4-propylphenyl group, 5-methyl-12-pyridyl group, 6-methyl-3 —Pyridyl, 6-ethyl-3-pyridyl, 2-methyl-4-pyridyl, 2-ethyl-4-pyridyl, 2-propyl-4-pyridyl, 2-butyl-4-pyridyl, 3— Methyl 4-pyridyl, 3-vinylphenyl, 4-vinylphenyl, 4- (2-propenyl) phenyl, 5-vinyl-3-pyridyl, 3-trifluoromethylphenyl, 4-trifluoromethyl Phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-isopropyloxyphenyl, 3,4-dimethoxyphenyl, 3,4-methylenedioxyphenyl, 6-methoxy-3-pyridyl group, 2-methoxy-4-pyridyl group, 3-dimethylaminophenyl group, 4-dimethylaminophenyl group, 4-methoxy-13-dimethylaminophenyl group , 2-methylthiophenoyl, 3-methylthiophenyl, 4-methylthiophenyl, 2-methylthio-4-pyridyl, 3-biphenyl Group, 4-pyridinyl group, 2-methyl-4-cyclopyridyl group, 2-ethyl-4-pyridyl group, 2-propyl-4-pyridyl group, 2-butyl-4-pyridyl group. Group, 3-chlorophenyl group, 4-chlorophenyl group, 3,4-dichlorophenyl group, 3-bromophenyl group, 4-bromophenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 4-methylphenyl group, 3-methyl-4-pyridyl group, 3-ethyl-4-pyridyl group, 4-vinylphenyl group, 4- (2-propeninole) phenyl group, 3-methoxyphenyl Binole group, 4-methoxyphenyl group, 4-ethoxyphenyl group, 3,4-dimethoxyphenyl group, 3,4-methylenedioxyphenyl group, 3-methoxy-4-pyridyl group , 4-methylthiophenyl, 3-methylthio-4-pyridyl and the like are preferred.

n means 0, 1 or 2.

As n, 0 or 1 is preferable.

As R ¹ and R ² , both are preferably hydrogen atoms.

In the present specification, in order to avoid unnecessary confusion in the nomenclature of compounds, they are represented by the general formula [I-a], [I-b], [I-c] or [I-d]. The naming of the compound and other explanations shall be described, assuming that the position number of the pyrazole ring part in the compound is as shown in the following general formula [Γ].

Hereinafter, the compound represented by the general formula [I-e] will be described.

Ar is selected from the group consisting of a halogen atom, a nitro group, an amino group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, a lower alkanoyl group and an aryl group. Or an aryl group or a heteroaromatic group which may have a substituent.

From halogen atom, nitro group, amino group, lower alkyl group, halo-lower alkyl group, lower alkoxy group, lower alkylthio group, lower alkylamino group, di-lower alkylamino group, lower alkanol group and aryl group An aryl group or a heteroaromatic group, which may have a substituent selected from the group consisting of The substituted aryl group or the heteroaromatic ring group, or the aryl group or the heteroaromatic ring group having a substituent at any substitutable position, wherein the substituent is a halogen atom, a nitro group, The same or different from the group consisting of: an amino group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, a lower alkanol group and an aryl group. Two or more, preferably one or two can be selected.

Preferred examples of the halogen atom for the substituent include a chlorine atom and a bromine atom.

As the lower alkanoyl group for the substituent, for example, an acetyl group is not preferred.

The aryl group of the substituent is, for example, preferably a phenyl group. As the substituent, a halogen atom, a nitro group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkanoyl group and the like are preferable.

Examples of the aryl group of Ar include a phenyl group and a naphthyl group, and examples of the heteroaromatic ring group include a pyridyl group, an indolinole group, a benzoimidazolyl group and a benzyl group. Nzoxazolyl groups and the like are preferred.

Accordingly, as Ar, for example, phenyl, 1-naphthyl, 2-naphthinole, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-indolinole, 3-indolyl, 2-benzoyl Midazolyl group, 2-benzoxazolyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 3,4-dichlorophenyl group, 2-bromophenyl group, 3-bromophenyl group, 4-bromophenyl group , 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-aminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3,5-dimethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl group, 3,5-bis (trifluoromethyl) phenyl group, 2-methoxy Phenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-isopropyloxyphenyl, 3,4-dimethoxyphenyl, 2,3-methylenedioxyphenyl, 3, 4- Methylenedioxyphenyl group, 1-methyl-12-indolinole group, 1-methoxy-2-indolinole group, 5-methoxy-2-indolinole group, 3-dimethylaminophenyl group, 4-dimethylaminophenyl Benzyl, 2-methylthiophenyl, 3-methylthiophenyl, 4-methylthiophenyl, 3-methyl-4-methylthiophenyl, 4-acetylphenyl, 2-biphenyl, 3-biphenyl Examples include a biphenyl group and a 4-biphenyl group, among which a phenyl group, a 1-naphthyl group, a 3-pyridinole group, a 2-indolinole group, and a 4-bromophenyl group. 4-, 4-nitrophenyl, 3,5-dimethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2,3-methylenedioxyphenyl, 3,4-methylenedioxy Preferred are an enyl group, a 5-methoxy-12-indolinole group, a 3-methyl-4-methylthiophenyl group, a 4-acetylphenyl group, and the like.

R ¹ and R ² are the same or different and each represents a lower alkyl group or an alkylene group in which both R ¹ and R ² may be linked to each other and may be via an oxygen atom or a sulfur atom.

As the lower alkyl group for R ¹ and R ² , for example, a methyl group, an ethyl group and the like are preferable. As the “alkylene group optionally interposed through an oxygen atom or a sulfur atom”, more preferably, for example, a pyrrolidinyl group, a thiazolidinyl group, a piperidino group, a monorefolino group, a hexahydro-1H-azepinyl group, etc. together with an adjacent nitrogen atom. Is preferably a group forming a pyrrolidinyl group or a piperidino group.

As R ¹ and R ² , an alkylene group in which both R ¹ and R ² may be connected to each other via an oxygen atom or a sulfur atom is preferable.

R ³ represents an amino group, a lower alkyl group or a lower alkylamino group. As the lower alkyl group for R ³ , for example, a methyl group, an ethyl group, a propyl group, an isopropyl group and the like are preferable.

As the lower alkylamino group for R ³ , for example, a methylamino group, an ethylamino group and the like are preferable.

R ³ is preferably a lower alkyl group or a lower alkylamino group. Y is an ethylene group, a trimethylene group, a vinylene group, a probenylene group or

CH ₂ —, — S— CH ₂ — or — CH ₂ — NH—

As Y, a group represented by an ethylene group, a vinylene group, a propenylene group, or 1 O—CH ₂ — is preferable.

Hereinafter, the compound represented by the general formula [If] will be described.

In the present specification, the position number of the xanthene skeleton is expressed in principle by the position number given to the skeleton in the general formula [If], or, if necessary, by adding a braille to the position number.

R ¹ represents a hydrogen atom or a lower alkyl group, or a lower alkylene group together with R ² even if an oxygen atom is interposed.

As the lower alkyl group for R ¹ , for example, a methyl group, an ethyl group, and the like are preferable.

As the “lower alkylene group optionally interposed with an oxygen atom”, which R ¹ and R ² together mean, for example, a trimethylene group, a tetramethylene group, a pentamethylene group and the like are preferable.

R ² represents a lower alkyl group or, together with R ¹ , has the meaning described above.

As the lower alkyl group for R ² , for example, a methyl group, an ethyl group and the like are preferable. R ³ and R ⁴ represent a hydrogen atom at the same time, or both are a single bond Means

It is preferable that R ³ and R ⁴ be a single bond when they are taken together.

R ⁵ and R ⁶ represent a hydrogen atom at the same time, or a lower alkylidene group which may be taken together to intervene with an oxygen atom.

It is preferred that R ⁵ and R ⁶ be a lower alkylidene group, even if both are joined together and an oxygen atom is interposed. As the lower alkylidene group, for example, an isopropylidene group, an ethylpyridene pyridene group, a cyclobutylidene group, a cyclopentylidene group, a cyclohexylidene group and the like are preferable.

Preferred embodiments of RR ² , R ⁵ and R ⁶ include, for example, R ¹ and R ² are both a lower alkyl group, and R ⁵ and R ⁶ are taken together to form a linear or branched lower alkylidene. When R ¹ and R ² are together, an oxygen atom may be intervened, or when R ¹ and R ² are a lower alkylene group, and R ⁵ and R ⁶ are together, an oxygen atom may be intervened. And when it is a cyclic lower alkylidene group.

R ⁷ and R ⁸ are independently a hydrogen atom, a halogen atom, a nitro group, a hydroxyl group, a lower alkyl group, a lower alkoxy group, an aryl group, an aralkyloxy group, a di-lower alkylamino group, a lower alkoxycarbonylamino group or Aryl means a luponylamino group, or a combination of both, a lower alkylene group, or a benzene ring which is ortho-condensed with an adjacent ring.

As the halogen atom for R ⁷ or R ⁸ , for example, a fluorine atom, a chlorine atom, a bromine atom and the like, more preferably a fluorine atom and the like are suitable.

As the lower alkyl group for R ⁷ or R ⁸ , for example, a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, and the like, and more preferably a methyl group, an ethyl group, and the like are preferable.

As the lower alkoxy group for R ⁷ or R ⁸ , for example, a methoxy group, an ethoxyquin group, a propoxy group and the like, and more preferably a methoxy group and the like are preferred.

As the aryl group for R ⁷ or R ⁸ , for example, a phenyl group is suitable. As the aralkyloxy group for R ⁷ or R ⁸ , for example, a benzyloxy group or the like can be obtained in a good time.

Examples of the di-lower alkylamino group for R ⁷ or R ⁸ include a dimethylamino group, Getylamino groups and the like are preferred.

As the lower alkoxycarbonylamino group for R ⁷ or R ⁸ , for example, an isopropoxycarbonylamino group is suitable.

The § reel carbonyl § amino group R ⁷ or R ^8, for example, base Nzoiruami amino group and the like.

As the “lower alkylene group” that R ⁷ and R ⁸ together mean, for example, a trimethylene group, a tetramethylene group, and the like are suitable, and both ends of the group are compounds represented by a general formula [If]. It is more preferable to bind to the 5- and 6-positions of the above.

When R ⁷ and R ⁸ together represent a benzene ring which is ortho-fused to an adjacent ring, the benzene ring is fused to the 5- and 6-positions of the compound represented by the general formula [If]. Is preferred.

It is preferred that R ⁷ and R ⁸ are each present at the 5- or 6-position, and independently represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group.

X represents an oxygen atom or a sulfur atom, and an oxygen atom is preferred.

Y means a methine group or a nitrogen atom, with a methine group being preferred.

The compound according to the present invention may have stereoisomers or tautomers such as optical isomers, diastereoisomers, and geometric isomers, depending on the mode of the substituent. It also includes stereoisomers and tautomers and mixtures thereof.

The general formulas [I-a], [I-b], [I-c], [I-d], [I-e], [I-f], [I-g], [I-h], Specific examples of the compound represented by [I-i] or [Ij] or a salt thereof include, for example,

5- (4-methoxyphenyl) -3- (4-phenylbiperazinyl) carboxy luminopyrazole,

5- (4-chlorophenyl) -1-3- (4-phenylbiperazinyl) carbonylaminopyrazolyl,

5- (2-methylphenyl) -1-3- (4-phenylbiperazinyl) carbonylaminopyrazole, 5- (3-methylphenyl) -1-3- (4-phenylbiperazinyl) carbonylaminovirazole,

5-(4-methylphenyl) 1-3 (4-phenylbiperazinyl) carbonyl aminopyrazole,

5- (2-Methoxyethoxy)-3-(4-Ferbirubiperazinyl) carboni Laminopyrazole,

5-(3,4 dichloromouth phenyl) —3— (4-phenylbiperazinyl) carbonylaminopyrazol,

5- (4-bromophenyl) -3- (4-phenylbiperazinyl) carbonylaminovirazole,

5- (3-chlorophenyl) -1-3- (4-phenylbiperazinyl) carbonylaminopyrazole,

5—Phenyl-3— (4-Phenylbiperazinyl) carbonylamino villazole,

5- (4-dimethylaminophenyl) -1- (4-phenylbiperazinyl) power rubonylaminovirazole,

5- (3-dimethylaminophenyl) 1-3- (4-phenylbiperazinyl) power rubonylaminovirazole,

5-(3,4-Dimethoxyphenyl) -1-3- (4-phenylbiperazinyl) carbonylamyl virazole,

5-(4-Isopropoxyphenyl)-3-(4-Ipylbiperazinyl) force Luponylaminopyrazole,

5-(4-Ethoxyphenyl) 1 3- (4-Phenylbiperazinyl) carboxy luminopyrazole

5- (3-bromophenyl) -1- (4-phenylbiperazinyl) carbonylaminopyrazole,

3- [4- (3-chlorophenyl) piperazinyl] carbonylamino-5- (4-methoxyphenyl) pyrazole,

3- [4- (3-chlorophenyl) piperazinyl] carbonylamino-5- (3,4-dimethoxyphenyl) virazole, 5- (2-chlorophenyl) -3- (4-phenylpiperazinyl) carbonylaminopyrazole,

5-(4-Methylthiophenyl) -3- (4-phenylbiperazinyl) carbonylaminovirazole,

5-(3,4-methylenedioxyphenyl) -1-3- (4-phenylbiperazinyl) carbonylaminopyrazole,

3- (4-monophenylbiperazinyl) carbonylamino-5- (4-pyridyl) pyrazole,

5- (4-Methoxyphenyl) 1-3-methyl [2- (methylphenylamino) ethyl] aminocarbonylaminopyrazole,

5-(3-Methoxyphenyl) -3- (4-Phenylbiperazinyl) carboniluminaminopyrazole,

5— (4-Methoxyphenyl) 1 3— (2-Methyl 4-phenylbiperazinyl) carbonylaminobiazole,

5- (4-Methoxyphenyl)-3- [2- (phenylamino) ethyl] aminocarbonylaminovirazole,

5- (4-biphenylinole) i 3- (4-phenylpiperazinyl) carbonylaminopyrazole,

5- (3-dimethylamino-4-methoxyphenyl)-3- (4-phenylbiperazinyl) carbonylaminopyrazole,

3- (4-hydroxy-14-phenylbiperidino) carbonylamino-5- (4-methoxyphenyl) pyrazole,

5- (4-methoxyphenyl) -1- (4-phenyl-1,2,3,6-tetrahydropyridine-1yl)

5- (4-methoxyphenyl) 1-3- (4-vinylbiperidino) carbonylaminopyrazole,

5- (4-methoxyphenyl) -1- (4-phenylhomopiperazinyl) carbonylnyaminopyrazole,

3- (2-Indanyl) carbonylamino-5- (4-methylphenyl) villazol, 3- (2-Indanyl) carbonylamino-5- (3-methylphenyl) virazole,

3- (2-Indanyl) carbonylamino-5- (2-methylphenyl) virazole,

5- (4-chlorophenyl) -1-3- (1-indanyl) carbonylaminoviazole,

3- (2-indanyl) carbonylamino-5- (3-methoxyphenyl) pyrazole,

5- (3-chlorophenyl) —3- (2-indanyl) carbonylaminovirazole,

5- (3,4-dichlorophenyl) — 3- (2-indanyl) carbonylamino pyrazole,

3- (2-Indanyl) carbonylamino-5- (4-Methoxyphenyl) pyrazole,

3- (2-Indanyl) Power Luponylamine 5- (2-Pyridyl) pyrazole, 3- (2-Indanyl) carbonylamino-5- (4-pyridyl) pyrazole, 3- (2-Indanyl) carbonylamino-5- ( 2—Methoxy phenol)

5- (4-chlorophenyl) -1-3- (1,2,3,4-tetrahydro-1-naphthinole) carbonylaminopyrazole,

5— (2-chlorophenyl) —3— (2-indanyl) carbonylaminovinylsol,

3- (2-Indanyl) Carbonylamine 5— (3-Pyridyl) pyrazole, 3- (2-Indanyl) Power Luponylamine 5— (1-Naphthyl) Virazol, 3- (2-Indanyl) Power Rubynonamine 5— (2-naphthyl) virazole, 5- (4-dimethylaminophenyl) 1-3- (2-indanyl) carbonylaminopyrazole,

5- (3-dimethylaminophenyl) -3- (2-indanyl) carbonylaminopyrazole,

5- (3,4-dimethoxyphenyl) -1-3- (2-indanyl) carbonylamido Nopyrazole,

3- (2-indanyl) carbonylamino-5- (4-isopropoxyphene) pyrazole,

5— (4-Ethoxyphenyl) —3— (2-Indanyl) carbonylaminovirazole,

3- (2-indanyl) carbonylamino-5- (4-trifluoromethylphenyl) pyrazole,

3- (2-Indanyl) carbonylamino-5- (3-Trifluoromethylphenyl) pyrazole,

3- (2-Indanyl) carbonylamine 5— (4-Methylthiophenidyl) pyrazole,

3- (2-Indanyl) carbonylamino 5- (3,4-Methylenedioxyphenyl) pyrazole,

5- (3-dimethylamino-4-methoxyphenyl) 1-3- (2-indanyl) carbonylaminopyrazole,

3- (2,3-dihydro-1H-cyclopenta [b] naphthalene-1-yl) force rubonylamino 5- (4-pyridyl) pyrazole,

5- (3,4-dimethoxyphenyl) -1-3- (1,2,3,4-tetrahydro-1-naphthyl) carbonylaminopyrazole,

3- (2,3-dihydro-1-H-cyclopenta [a] naphthalene-1-yl) carbonylamino 5- (3,4-dimethoxyphenyl) pyrazol,

3- (2,3-dihydro-1H-cyclopenta [b] naphthalene-1-yl) power rubonylamino 5- (3,4-dimethoxyphenyl) pyrazole,

5- (4-bromophenyl) -1-3- (2-indanyl) carbonylaminobirazole,

5- (3-bromophenyl) -1-3- (2-indanyl) carbonylaminovinylsol,

3- (2-Indanyl) carbonylamino-5- (4-vinylphenyl) virazole,

3- (2-Indanyl) carbonylamino-5- (3-vinylphenyl) villa Zol,

3- (2-Indanyl) carbonylamino-5- {4- (2-Prodenyl) phenyl} pyrazole,

5— (4—biphenylinole) 1—3— (2—indanyl) Riponylaminovirazole,

5- (3-biphenylinole) -1- (2-indanyl) carbonylaminobiazole,

5-(4-ethylfurnyl) 1- 3-(2- indanyl) carbonyl aminovirazole,

5-(3-ethylfurinyl)-3-(2- indanyl) carbonylaminovirazole,

3- (2-Indanyl) carbonylamino-5- (4-propylpheninole) pyrazole,

5- (4-Methoxyphenyl) —3- (2-Methyl-2-indanyl) carbonylaminovirazole,

3-(2,3-dihydro 1H-cyclopenta [a] naphthalene-2-yl) carbonylamino 5- (4-pyridyl) villazol,

(+)-3-(2,3-dihydro-1H-cyclopenta [a] naphthalene-12-inole) carbonylamine 5- (4-pyridyl) pyrazole,

(1)-3-(2,3-dihydro-1H-cyclopentene [a] naphthalene-1 2-inole) Riponylamino 5- (4-pyridyl) pyrazole,

3- (5, 6-dichroic indane-2-yl) carbonylamino 5- (4-methoxyethoxy) pyrazole,

3— (5—Mouth indane-1—2-inole) Carbonylamino 5— (4—Methoxy phenyl) pyrazole,

3- (5,6-dichloroindan-1-yl) carbonylamino 5- (4-pyridyl) pyrazol,

3- (4-bromoindane-1-yl) carbonylamino-5- (4-methoxyphenyl) pyrazole,

3- (2,3-dihydro-1-H-cyclopenta [b] naphthalene-2-yl) force Rubonylamino-5- (2-ethylpyridine-1-41) pyrazole,

3- (5-bromoindane-2-yl) carbonylamino-5- (4-methoxyphenyl) pyrazole,

5- (4-Methoxyphenyl) 1-3- (4-Phenylindane-2-yl) Power rubonylaminopyrazole,

3- (4-phenylindan-2-yl) carbonylamino-5- (4-pyridyl) pyrazole,

3- (2,3-dihydro 1H-cyclopenta [a] naphthalene-1-yl) carbonylylamino-5- (2-ethylpyridine-1-yl) virazole,

(+)-3-(2,3-dihydro 1H-cyclopenta [a] naphthalene-1-yl) carbonylamino-5- (2-ethylpyridin-4-yl) pyrazole, (-) -3 ( 2,3-dihydro-1H-cyclopentyl [a] naphthalene-1-yl) carbonylamino-5- (2-ethylpyridine-14-yl) pyrazole, 3- (2,3-dihydro-1H-cyclopentane) [a] naphthalene-1-2-yl) carbonylamino-5- (2-methylpyridine-1-4-inole)

3-(2,3-dihydro-1H-cyclopenta [a] naphthalene-1-yl) carbonylamino-5- (2-propylpyridine-4-yl) pyrazole, 5- (2-butylpyridine-1 4 1- (2,3-dihydro 1H-cyclopenta [a] naphthalene-1-yl) carbonylaminovirazole, 3- (bicyclo [4.2.O.] octa 1 (6), 2, 4-triene 7-inole) Carbonylamino-5— (3,4 dimethoxyphenyl) pyrazol,

5- (4-methoxyphenyl) -1-3- (5-nitroindane-2-yl) carbonylaminopyrazole,

5-(4-methoxyphenyl)-3-(4-12 troindane-2-yl) carbonylylaminovirazole,

5— (3,4 dimethoxy phenyl) —3— (1,2,3,4-tetrahydro-2-vinyl)

3- (5-benzoylindane-2-yl) carbonylamino-5- (4-methoxyphenyl) pyrazole,

3- (5-benzoylindane-2-yl) carbonylamino-5- (4-pi Lysyl) pyrazole,

5- (3,4-dimethoxyphenyl) -1- (1,2,3,4-tetrahydrodibenzo [b, d] furan-3-yl)

5- (3,4-dimethoxyphenyl) -3- (9-methyl-1,2,3,4-tetrahydrocarbazole-2-yl)

3-(2,3-dihydro 1H-pyrro [1,2-a] indole-1-2-inole) Luponylamine 5- (3,4-dimethoxyphenyl) pyrazole,

3- (2,3-dihydro-1H-cyclopenta [b] indole-12-yl) -1-5- (4-methoxyphenyl) carbonylamino benzoyl,

3-(7,8-dihydro 6H-cyclopenta [g] quinoline-7-yl) carbonylylamino-5- (4-methoxyphenyl) pyrazol,

5-(2-Ethylpyridine-1-4-inole)-3-(2,3-Dihydro-1H-pyrro [1, 2-a] Indole-1-2-yl) Carbonylaminobiazole, 5- (3,4-Dimethoxyphenyl) -1-3- (1,2,3,4-tetrahydrodibenzo [b, d] thiophene-3-yl)

5- (4-Methoxyphenyl) 1-3- (4-Methyl-2,3-dihydro 1H-Cyclopenta [b] indole-2-yl) Carbonylaminovirazole, 5- (4-Methoxyphenyl)- 3-(5-phenylindan-2-yl) force rubonylaminovirazole

5-(4 monophenyl phenyl)-3-(1 monophenylbiperidine-4-yl)

5- (4-methoxyphenyl) -1- (1-phenylbiperidine-14-yl) power rubonylaminopyrazole,

5-(3,4 diphenyl mouth phenyl)-3-(1-phenylbiperidine-1-4-yl)

3- [1— (3-chlorophenyl) piperidin-1-yl] carbonylamino-5- (4-methoxyphenyl) pyrazole,

5—Phenyl-3— (3-Phenylpropionyl) aminovirazole,

5- (4-chlorophenyl) -1-3- (3-phenylpropionyl) aminopyrazole, oo

5- (4-chlorophenyl) -1-3-phenylacetylaminopyrazole, 3- (1,3-benzoxazole-2-ylacetyl) amino-5- (4-chlorophenyl) pyrazole,

5— (4—Chlorophenyl) — 3— (2—Naphthylacetyl) aminovirazole,

5- (3,4-dimethoxyphenyl) 1-3- (2-naphthylacetyl) aminobiazole,

5- (4-dimethylaminophenyl) -1- (2-naphthylacetyl) aminopyrazole,

3- [3- (1,3-benzoxazole-2-yl) propionyl] amino— 5-(4-chlorophenyl) pyrazole,

3- (2-naphthylacetyl) amino-5- (4-pyridyl) birazol, 5- (4-methoxyphenyl) -1-3- [3- (2-naphthyl) propionyl] aminopyrazole,

5- (4-methoxyphenyl) -1-3- [3- (1-naphthyl) propionyl] aminopyrazole,

5— (3-dimethylamino-1-methoxyphenyl)-3- (2-naphthylacetyl) aminopyrazole,

5- (5-Methyl-2-pyridyl) -1- (2-naphthylacetyl) aminovirazole,

5— (6-methyl—3-pyridyl) — 3— (2-naphthylacetyl) aminobi lazone

5-(4-Methoxyethoxy) 1 3-[2-methyl-1 2-(2- naphthyl) propionyl] aminopyrazole,

3- [2- (3-benzoylphenyl) propionyl] amino-5- (3,4-dimethoxyphenyl) pyrazol,

5— (4—Phenyl phenyl) 1-3— (3—Pyridyl acetyl) aminopyrazole,

5-(3,4-Dimethoxyphenyl) — 3 -— [2- (2-Fluoro-4-biphenylyl) propionyl] aminopyrazole, 5- (4-chlorophenyl) 1-3- (4-pyridylacetyl) aminovirazole,

5- (3,4-Dimethoxyphenyl) 1-3- [2- (4-isobutylphenyl) pulpionyl] aminopyrazole,

5— (6-Methyl-2-pyridyl) —3— (2-Naphthylacetyl) aminovirazole,

5- (4-methoxyphenyl) -3- [2- (2-naphthyl) propionyl] aminopyrazole,

5- (5-bromo-3-pyridyl) -1- (2-naphthylacetyl) aminobilasone,

3- (2-naphthylacetyl) amino-5- (5-vinyl-3-pyridyl) pyrazole,

5- (5-Ethyl-3-pyridyl) -1-3- (2-naphthylacetyl) aminobiazole, (E) -6-methyl-2--2- [2- (1-naphthyl) vinyl] —4-piperidi Nopyridine,

(Z) 1 6-methyl-2- [2- (1-naphthyl) vinyl] -4-piperidinopyridine,

6-Methyl-2- [2- (1-naphthyl) ethyl] 1-4-piperidinopyridine, (E) —2-methyl-6- [2- (1-naphthyl) vinyl] 1-4-pyrrolidinopyridine

(E) 1-Methyl-1-6- (2-phenylvinyl) -4-pyrrolidinopyridine, (E) -2- [2- (2-benzozoxazolyl) vinyl] -6-methyl-4-pi Lysinopyridine,

(E) —2— [2- (2-indolinole) vinyl] —6-methyl-4-pyrrolidino pyridine,

(E) -2- [2- [2- (5-Methoxyindolinole)] vinyl] —6-methyl—4-pyrrolidinopyridine,

(E) —2-Methyl-6— (2-phenylvinyl) -1-piperidinopyridine, (E) -2- [2- (2-benzoxazolyl) vinyl] -1-6-methyl-4-pi Peridinopyridine, (E) — 2— [2- (2-biphenylinole) vinyl] — 6-methyl-1-4-piperidinopyridine,

(E) -2- [2- (3-biphenylyl) vinyl] -1-6-methyl-4-piperidinopyridine,

(E) —4—Homopiberidino 2-methyl-6— (2-phenylvinyl) pyridinine,

(E) 1-4-Homopiberidino 2-methyl-6- [2- (1-naphthyl) vinyl] pyridine,

(E) —2-Methyl-4-morpholinol 6— [2- (1-Naphthyl) vinyl] pyridine,

(E) —2-Methyl-1-4-pyrrolidino-1-6- [2- (3-trifluoromethylphenyl) vinyl] pyridine,

(E) 1-Methyl-6- [2- [2- (N-methylindolyl)] vinyl] 1-4-pyrrolidinopyridine,

(E) — 2-Methyl-4-1-pyrrolidinol 6— [2- (3,5-Pistrifluormetylphenyl) vinyl] pyridine,

(E) 1 2— [2— [2— (N—methoxyindolyl)] vinyl]

(E) —2-Methyl-1-4-pyrrolidino-1-6- [2- (2-pyridyl) vinyl] pyridine,

(E) —2-Methyl-1-4-pyrrolidino-1-6- [2- (3-pyridyl) vinyl] pyridine,

(E) — 2-Methyl-4-pyrrolidinol 6— [2- (4-pyridyl) vinyl] pyridine,

(E) —2 -— [2- (2-Indolyl) vinyl] -6-methyl-4-piperidinopyridine,

(E) —2— [2- (3-indolyl) vinyl] —6-methyl-4-piperidino pyridine,

(E) -2-[[2- (3,5-dimethylphenyl) vinyl] -6-methyl-4-piperidinopyridine, (E) —2-Methyl-1 4-piberidino 6— [2- (3-trifluoromethylphenyl) vinyl] pyridine,

(E) 1-Methyl-6- [2- (4-trotropinyl) vinyl] 1-4-piperidinopyridine,

(E) -2- (2-benzylvinyl) -1-6-methyl-4-piperidinopyridine, (E) —2-methyl-6- [2- (2,3-methylenedioxyphenyl) vinyl] One 4-piperidinopyridine,

(E) —2-Methyl-1 6— [2- (3,4-methylenedioxyphenyl) vinyl] -4-piperidinopyridine,

2-Methyl-6- (1-naphthyl) oxymethyl-4-pyrrolidinopyridine, 2-methyl-6- (2-naphthyl) oxymethyl- 4-pyrrolidinopyridine, 2-methyl-6- (4-1-2trophenyl) oxymethyl 4-pyrrolidinopyridine,

2-methyl-6- (3-ditrophenyl) oxymethyl-4-pyrrolidinopyridine,

2- (4-acetylphenyl) oxymethyl-1-6-methyl-4-pyrrolidinoviridine,

2- (3,5-dimethylphenyl) oxymethyl-6-methyl-4-pyrrolidino pyridine,

2-methyl-6- (3,4-methylenedioxyphenyl) oxymethyl-4-pipiridinopyridine,

2- (2-indolinole) thiomethyl-1-6-methyl-4-pyrrolidinopyridine, 2-methyl-6- (4-nitrophenyl) thiomethyl-4-pyrrolidinopyridin,

2- (3,5-dimethylphenyl) thiomethyl-1-methyl-4-pyrrolidinoviridine,

2-methyl-6- (2-naphthyloxymethyl) -4-piperidinopyridine, 2-methyl-6-phenoxymethyl-4-piperidinopyridine,

2-Methyl-6- (1-naphthyl) oxymethyl-4-piperidinopyridine, 2- (3,5-dimethylphenyl) oxymethyl-6-methyl-4-piperidino Pyridine,

2-methyl-6- (4-methylthiophenyl) oxymethyl-4-piperidinopyridine,

2-methyl-1-piperidino 6- (3-trifluoromethylphenyl) oxymethyl pyridine,

2-methyl-1-piperidino 6- (4-trifluoromethylphenyl) oxymethyl pyridine,

2- (4-bromophenyl) oxymethyl-1-6-methyl-4-piberidinoviridine,

2-methyl-6- (3-methyl-4-methylthiophenyl) oxymethyl-4-piperidinopyridine,

2- (2-indolinole) thiomethyl-6-methyl-4-piperidinopyridine, 2-methyl-6- (1-naphthyl) thiomethyl-4-piperidinopyridine, 2-methyl-6- (2-naphthyl) thiomethyl-1- Piperidinopyridine, 2- (2-benzimidazolyl) thiomethyl-6-methyl-4-piperidinopyridine,

2-methyl-6-phenylthiomethyl-4-piperidinopyridine,

4—Homopyberidino 2— (2-Indolyl) thiomethyl—6—Methylpyridin,

2- (2-indolinole) thiomethyl-6-methyl-4 morpholinopyridine, 2-methyl-6- (4-nitrophenyl) oxymethyl-4- 4-4-thiazolidinylpyridine,

(Ε) —2-Amino-6- (2-phenylvinyl) -1-4-piperidinopyridine, (Ε) —2-Amino-4-morpholino-6- (2-phenylvinyl) pyridine, (Ε ) —2-amino-4 _ morpholinol 6— [2- (2-pyridyl) vinyl] pyridine,

2-Methyl-6- (1-naphthylmethyl) amino 4-piperidinopyridine, 2-methyl-6- [2- (1-naphthyl) ethyl] 1-41-pyrrolidinopyridine, (Ε) -2-isopropyl 6— (2-phenylenyl) —4-piberidinoviridine 2-methyl-6- (3-phenylpropyl) -1-piperidinopyridine, 2-amino-6- (4-nitrophenyl) oxymethyl-4-piperidinopyridine,

2-amino-6- (3,5-dimethylphenyl) oxymethyl-4-piperidinopyridine,

2-amino-6- (3,4-methylenedioxyphenyl) oxymethyl-1 4-piperidinopyridine,

2-methylamino-6- (4-nitrophenyl) oxymethyl-4-piberidinopyridine,

2-ethylamino-6- (4-ditrophenyl) oxymethyl-4-piberidinopyridine,

(Ε) — 2-ethylamino— 6— (2-phenylvinyl) — 4-piridinopyridine,

(Ε) 1-methylamino 6- (2-phenylvinyl) 1-4-piridinopyridine,

(Ε) —2-Methylamino—4 morpholino— 6— (2-phenylvinyl) pyridine,

(Ε) -2-Methylamino-1 4-pyrrolidino-1 6- [2- (3-Trifluorometylphenyl) vinyl] pyridine,

(Ε) — 2-Methylamino-4-piperidino-1 6— [2- (3-trifluoromethylphenyl) vinyl] pyridine,

(Ε) —2-Methylamino-6— [2- (1-naphthyl) vinyl] —4-pyrrolidinopyridine,

(Ε) One 2-ethyl-6- (2-phenylvinyl) —4-piperidinopyridine, (Ε) — 2- (2-phenylvinyl) — 6-propyl—4-piridinopyridine, (Ε) -2-[2- (4-aminophenyl) vinyl] -6-methyl-4-piperidinopyridine,

3,3-Dimethyl-9- (4,4-dimethyl-2,6-dioxocyclohexyl) 1-l-oxo-l, 2,3,4-tetrahydroxanthene (tautomerism of the compound of formula [I-l-l-l]) Body), 9- (2-Hydroxy-4,4-dimethyl-6-oxo-1-cyclohexenyl) -6-methoxy-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthenoneone,

9- (2-Hydroxy-1,4-dimethyl-6-oxo-1-cyclohexenyl) — 7-methoxy-1,3,3-dimethyl-2,3,4,9-tetrahydro 1H—xanthene 1— On,

9— (2-Hydroxy-4,4-dimethyl-6-oxo-1-cyclohexenyl) —8-methoxy-1,3,3-dimethyl-2,3,4,9—tetrahydro-1H—xanthene-1— On,

9- (2-Hydroxy-1,4-dimethyl-6-oxo-1-cyclohexenyl) -3,3-dimethyl-7-nitro-2,3,4,9-tetrahydro 1H-xanthen-1-one,

6-Jetylamino-1 9- (2-Hydroxy-1,4,4-dimethyl-1 6-oxo-1 1-Cyclohexenyl) -1,3,3-dimethyl-2,3,4,9-Tetrahydro-1H-Xanthen-1 On,

7-Bromo-9-1 (2-hydroxy-4,4-dimethyl-6-oxo-1-cyclohexyl) —3,3-dimethyl-2,3,4,9-tetrahydro 1H-xanthen-1-one ,

5-Fluoro-9- (2-hydroxy-4,4-dimethyl-6-oxo-1 1-cyclohexenyl) -1,3,3-dimethyl-2,3,4,9-tetrahydro 1H-xanthenone 1 One,

5-hydroxy-9- (2-hydroxy-1,4,1-dimethyl-6-oxo1-1-cyclohexenyl) -1,3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1one,

6-hydroxyl-1- (2-hydroxy-4,4-dimethyl-6-oxo-1-cyclohexenyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one,

6-ethoxy 9- (2-hydroxy-1,4,4-dimethyl-6-oxo-1-cyclohexenyl) -1,3,3-dimethyl-2,3,4,9-tetrahydro 1H-xanthen-11-year-old , -(2-hydroxy-4,4-dimethyl-6-oxo-1-cyclohexenyl) -3,3-dimethyl-6-propoxy-2,3,4,9-tetrahydro 1H-xanthenoneone,

6-benzyloxy 9- (2-hydroxy-1,4,4-dimethyl-6-oxo-1-cyclohexenyl) -1,3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-11one,

7-chloro-1- (2-hydroquin-1,4-dimethyl-6-oxo-1-cyclohexyl) -3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthene-1 — ON,

5-chloro-9- (2-hydroxy-1,4-dimethyl-6-oxo-1-cyclohexenyl) -1,3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthene-1 One on,

6-Chloro-9- (2-hydroxy-1,4-dimethyl-6-oxo-1-six-hexyl) 1,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthene On,

8-Chloro-9-1 (2-hydroxy-1,4-dimethyl-6-oxo-1-cyclohexyl) —3,3-dimethyl-1,2,3,4,9-tetrahydro-1H-xanthen-1-one ,

5,7-Dichloro mouth 9- (2-Hydroxy-1,4,1-dimethyl-6-oxo-1-cyclohexenyl) -1,3,3-Dimethyl 2,3,4,9-tetrahydro 1H-Xanthen-1 One on,

7-Fluoro-9-1 (2-hydroxy-4,4-dimethyl-6-oxo-11-cyclohexenyl) -1,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one,

6-Fluoro-9- (2-hydroxy-4,4-dimethyl-6-oxo-1-cyclohexenyl) —3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthenoneone,

5,6-difluoro-9- (2-hydroxy-4,4-dimethyl-6-oxo-1-1-cyclohexenyl) -1,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthene-1one , 9- (2-hydroxy-1,4,1-dimethyl-6-oxo-1-cyclohexenyl) -3,3,6-trimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one,

9- (2-Hydroxy-1,4,1-dimethyl-6-oxo-1-cyclohexeninole) -1,3,3,5-trimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one,

6-Ethyl-9-1 (2-hydroxy-4,4-dimethyl-6-oxo-1-cyclohexenyl) -1,3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthene-1 One on,

9- (2-Hydroxy-1,4-dimethyl-6-oxo-1-cyclohexenyl) -1-6-isopropyl-1,3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-11 On,

6-tert-butyl-1-9-1 (2-hydroxy-4,4-dimethyl-6-oxo-11-cyclohexenyl) -1,3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthene-1 One on,

7- (2-Hydroxy-1,4,1-dimethyl-6-oxo-1-cyclohexenyl) -10,10-dimethyl-1,2,3,4,7,9,10,11-octahydro-1H-benzo [c] xanthene 8-one,

7- (2-Hydroxy-4,4-dimethyl-6-oxo-1-cyclohexenyl) -10,10-dimethyl-7,9,10,11-tetrahydro8H-benzo [c] xanthen-1-one,

9-(4,4-I-ethyl-2 -hydroxy-6-oxo-1 -cyclohexenyl)-3,3 -Jetyl-2,3,4,9-tetrahydro-1H-xanthen-11one, 9 '-( 5-Hydroxy-1- 7-oxospiro [2.5] Doctor 5-en-6-inole) 1-oxo-1 Γ, 2 ', 4', 9 '—Tetrahydrospiro [cyclopropane-1,3' — 3Ή-xanthene] ,

9 '— (6-Hydroxy-1-8-oxospiro [3.5] Nona 6-en-1 7-inole) 1 Γ —Oxo Γ, 2', 4 ', 9' —Tetrahydrospiro [cyclobutane-1,3'1 3Ή—xanthene],

9'-1 (7-Hydroxy 9-year-old xospiro [4.5] Big one 7-One eight-yl) 1-oxo, 2 ', 4', 9'-tetrahydrospiro [cyclopentane-1, '13'-xanthene],

9 '-(8-Hydroxy 10-oxospiro [5.5] Pendoca 8-en-one 9-yl) 1-oxo-II, 2', 4 ', 9'-Tetrahydrospiro [cyclohexane-1 3, '— 3Ή—xanthene],

9 '1 (8-hydroxy-10-oxo 3- 3-year-old spiraspiro [5.5] panda 1-8-en 1 9-yl) 1 -1 oxo 1, 2', 4 ', 9' -tetrahydrospiro [Tetrahi-Dropyran 1-4, 3'-1 3'-xanthene],

9 '-(6-Hydroxy-1 8-oxospiro [3.5] Nona 6-en 7-inole) — 6' —Methoxy 1 Γ 1-year-old oxo 1, 2 4 ', 9'-Tetrahydroxy-spiro [cyclobutane 1 1 , 3 '—3Ή—xanthene],

6'-Ethyl- 9'-I (6-hydroxy-8-year-old spirospirate [3.5] Nona-I-6-en-7-yl) I-Oxo-I 1 ', 2', 4 ', 9'-Tetrahydrospiro [cyclobutane-1 1, 3 '— 3Ή—xanthene],

9 '-(6-Hydroxy-8-oxospiro [3.5] Nona-6-en-1-7-inole)-6'-Methyl-Γ-oxo-1Γ, 2', 4 ', 9'-tetrahydrospiro [cyclobutane-1 1, 3 '— 3'Η—xanthene],

5 '—Fluoro 9' — (6-Hydroxy 8—Kiso Spiro [3.5] Nona _ 6—Nen 7—Innole) 1 Γ —Oxo Γ, 2 ', 4', 9 '—Tetrahydrospiro [cyclobutane 1 1 , 3 '— 3Ή—xanthene],

9- (4,4-Getyl-1-hydroxy-6-oxo-1-cyclohexenyl) -3,3-Gethyl-6-methyl-2,3,4,9-tetrahydro 1H-xanthen-1-one,

9-(4,4-I-ethyl-2-hydroxy-1-6-oxo-1-cyclohexenyl)-3,3-Jethyl-5-fluoro-2,3,4,9-tetrahydro 1H-xanthene ,

9-1 (4,4-Jetyl-2-hydroxy-1-6-oxo-1-1-cyclohexenyl) 1,3,3-Jetyl-6-methoxy-2,3,4,9-tetrahydro-1H-xanthene-11 On,

9-1- (2-hydroxy-1,4-dimethyl-6-oxo-1-cyclohexenyl) -3,3-dimethyl-6-two-row 2,3,4,9-tetrahydro-1H-xanthen-1-one,

1- (2-Hydroxy-4,4-dimethyl-1-6-oxo-1-cyclohexenyl) -6-isopropoxycarbonylamino-3,3-dimethyl-2,3,4,9-tetrahydro 1H-xanthene 1 One,

6-benzoylamino-9-1 (2-hydroxy-1,4-dimethyl-6-oxo-11-cyclohexenyl) -1,3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one ,

6-bromo-9- (2-hydroxy-4,4-dimethyl-6-oxo-1-six-hexyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthene-one ,

9-1- (2-hydroxy-4,4-dimethyl-6-oxo-1-cyclohexenyl) -3,3-dimethyl-6-phenyl 2,3,4,9-tetrahydro-1H-xanthenoneone,

9-1- (2-hydroxy-4,4-dimethyl-6-oxo-1-cyclohexenyl) -1,3,3-dimethyl-2,3,4,9-tetrahydro 1H-8-azaxanthen-1-one,

9-1- (1-acetyl-2-hydroxypropyl) -3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one,

9-1- (2-hydroxy-4,4-dimethyl-6-oxo-1-cyclohexenyl) -3,3-dimethyl-2,3,4,9-tetrahydro 1H-10-thiaanthracene 1-one,

(4aS *, 9S *, 9aS *) 1-9-1 (2-hydroxy-1,4,4-dimethyl-1-6-oxo-1-cyclohexenyl) 1,3,3-dimethyl-2,3,4,4a, 9,9a —Hexahydr 1H—Xanthen—1-one,

(4aS *, 9R *. 9aR *) 1 9- (2-hydroxy-1,4,4-dimethyl-6-oxo-1-cyclohexenyl) 1,3,3-dimethyl-2,3,4,4a, 9 9a—Hexahi Draw 1H—Xanthene

N- [trans-4-[(1,2,3,4-tetrahydro-2-naphthylmethyl) aminomethyl "1 cyclohexylmethyl] 1-naphthalene 1 1-sulfonamide, N- [trans—4-1-[[1- (4-cyclohexyl) 1-2-hydroxyhexyl] aminomethyl] cyclohexylmethyl] 1-naphthalene-1-sulfonamide, N— [trans-4-[(2-naphthyl Methyl) aminomethyl] cyclohexylmethyl] — 2-nitro-benzenesulfonamide,

2-nitro-N— [trans-4-[(1,2,3,4-tetrahydro-1-naphthylmethyl) aminomethyl] cyclohexylmethyl] -benzenesulfonamide, 2-amino-N— [trans- 4-[(1,2,3,4-tetrahydro 2-naphthylmethyl) aminomethyl] cyclohexylmethyl] benzenesulfonamide, N-[trans-4-[(1,2,3,4-tetrahydro) 2-naphthylmethyl) aminomethyl] cyclohexylmethyl] -naphthalene-2-sulfonamide,

N- [trans-4-[(1,2,3,4-tetrahydro-2-naphthylmethyl) aminomethyl] cyclohexylmethyl] -2-trifluoromethylbenzenesulfonamide,

N- [trans—4 — [(2-naphthylmethyl) aminomethyl] cyclohexylmethyl] 1-2—trifluoromethylbenzenesulfonamide,

N- [trans-4-[(1-naphthylmethyl) aminomethyl] cyclohexylmethyl] —2—trifluoromethylbenzenesulfonamide,

2-nitro-N- [trans-4-[(1,2,3,4-tetrahydro-1-3-quinolylmethyl) aminomethyl] cyclohexylmethyl] monobenzenesulfonamide, 2-nitro-N— [ trans— 4-— [(2-quinolylmethyl) aminomethyl] hexylhexylmethyl] benzenesulfonamide,

2-nitro-N— [trans-4-[(4-quinolylmethyl) aminomethyl] cyclohexylmethyl] benzenesulfonamide,

N— [trans-4-[(3,4-ethylenedioxybenzyl) aminomethyl] cyclohexylmethyl] —2-nitrobenzenesulfonamide,

N- [6- (2-naphthylmethyl) aminohexyl] —2—trifluoromethylbenzenesulfonamide,

2-amino-N- [8- (1,2,3,4-tetrahydro-2-naphthylmethyl) aminooctyl] -benzenesulfonamide,

2—two-row N— [6-(1, 2, 3, 4-tetrahydro 2-naphthylcarbone Lamino) hexyl] —benzenesulfonamide,

N- [6- (1-naphthylaminocarbonyl) aminohexyl] 1-naphthalene 1-1-sulfonamide,

Naphthalene-1-sulfonic acid {2 -— (1- (4-aminoquinazoline-1-2-inole) piperidine-14-yl] ethyl} amide,

Naphthalene 1-sulfonic acid [1- (4-aminoquinazoline-1-inole) piperidine-41-methyl] amide,

Naphthalene-1-sulfonic acid {2-[4- (4-aminoquinazoline-2-inole) piperazine-1-yl] ethyl}

2-[4-(Naphthalene 1 -sulfonyl) piperazine-1 -yl] quinazoline-4-ylamine,

Naphthalene 1-sulfonic acid [7- (4-aminoquinazoline-2-ylamino) heptyl] amide hydrochloride,

Naphthalene-1-sulfonic acid [8- (4-aminoquinazoline-2-ylamino) octyl] amide,

Naphthalene-1-sulfonic acid [6- (4-aminoquinazoline-2-ylamino) hexyl] amide,

Naphthalene-1-sulfonic acid [6- (4-aminoquinazoline-12-ylamino) hexyl] amide,

Naphthalene-1-sulfonic acid [8- (4-aminoquinazoline-12-ylamino) octyl] amide hydrochloride,

Naphthalene-2-sulfonic acid [7- (4-aminoquinazoline-12-inoleamino) heptyl] amide hydrochloride,

Naphthalene-1-sulfonic acid [5- (4-aminoquinazoline-2-inoleamino) —3,3-dimethylpentyl] amide,

Naphthalene-1-sulfonic acid {3-- {1- [3- (4-aminoquinazoline-2-ylamino) propyl] cyclopentyl} propyl} amide,

Naphthalene-1-sulfonic acid {5 -— [1- (4-aminoquinazoline-2-ylamino) cyclopentyl] pentyl} amide,

Naphthalene-1-sulfonic acid [6- (4-aminoquinazoline-2-inoleamino) —6-Methylheptyl] amide,

trans-naphthalene-1-sulfonic acid [6- (4-aminoquinazoline-1-ylamino) -hexa-3-enyl] amide,

cis-naphthalene-1-sulfonic acid [6- (4-aminoquinazoline-2-ylamino) -hexa-3-enyl] amide,

Naphthalene-1-sulfonic acid [6- (4-aminoquinazoline-12-ylamino) -hexa-3-ynyl] amide,

Naphthalene-1-sulfonic acid [6- (4-aminoquinazoline-2-inoleamino) -5-methoxyhexyl] amide,

Naphthalene-1-sulfonic acid [6- (4-aminoquinazoline 2-inoleamino) -17-methoxyheptyl] amide,

Naphthalene-1-sulfonic acid [5- (4-aminoquinazoline 2-inoleamino) -1,3-dimethylpentyl] amide,

Naphthalene-1-sulfonic acid [6- (4-aminoquinazoline-2-ylamino) -6-methylheptyl] amide,

Naphthalene-1-sulfonic acid [7- (4-aminoquinazoline-2-ylamino) -4,4-dimethylheptyl] amide,

trans-naphthalene-1-sulfonic acid [8- (4-aminoquinazoline-l-ylamino) -octa-l-phenyl] amide,

Benzenesulfonic acid [6- (4-aminoquinazoline-2-ylamino) hexanol] amide,

N— [6 -— (4-aminoquinazoline-1-ylamino) hexyl] (N, N—dimethylamino) sulfonamide,

N— [6- (4-aminoquinazoline-1-ylamino) hexyl] (piperidin-1-yl) sulfonamide,

N— [6- (4-aminoquinazoline—2-ylamino) hexyl] (4-methylpyperazine-1-yl) sulfonamide,

N— [6- (4-aminoquinazoline-2-ylamino) hexyl] -1- (N-methylamino) sulfonamide,

Naphthalene-1-sulfonic acid [6- (4-amino-8-methoxyquinazoline 2—ylamino) hexyl] amide,

Naphthalene-1-sulfonic acid [6- (4-amino-8-methoxyquinazoline-12-ylamino) hexyl] amide,

N- [6- (4-amino-8-methoxyquinazoline-12-ylamino) hexanol]-(N, N-dimethylamino) sulfonamide,

N— [6 -— (4-amino-8-methoxyquinazoline-1-ylamino) hexyl] -1- (piperidine-11-yl) sulfonamide,

Naphthalene-1-sulfonic acid {6 -— [4- (2-methoxyhexylamino) quinazoline-2-ylamino] hexyl} amide,

Naphthalene-1-sulfonic acid {6 -— [4- (2-dimethylaminoethylamino) quinazoline-1-ylamino] hexyl} amide,

Naphthalene-1-sulfonic acid [6- (4-methylaminoquinazoline-2-ylamino) hexyl] amide,

Naphthalene-1-sulfonic acid [6- (4-dimethylaminoquinazoline-12-ylamino) hexyl] amide,

Naphthalene-1-sulfonic acid [6- (4-methylamino-8-methoxyquinazoline-1-inoinamino) hexyl] amide,

Naphthalene-1-sulfonic acid {6 -— [4- (2-dimethylaminoethylamino) -18-methoxyquinazoline-12-ylamino] hexyl} amide, naphthalene-2-sulfonic acid [6 -— (4-a Minoquinazoline—2-ylamino) hexyl] methylamide,

Naphthalene-1-sulfonic acid {6-[(4-methylaminoquinazoline-2-yl) methylamino] hexyl} amide,

Naphthalene-1-sulfonic acid {6 -— ((4-methynoleamino-18-methoxyquinazoline-12-inole) methylamino) hexyl} amide,

Naphthalene-1-sulfonic acid {6- [4- (3-dimethylaminopropylamino) quinazoline-2-ylamino] hexyl} amide hydrochloride,

Naphthalene-1-sulfonic acid [6- (4-amino-6-bromoquinazoline-2-ylamino) hexyl] amide hydrochloride,

N- (3-{2- [4- (cyclopropylmethylamino) quinazoline-1- L-amino] ethoxy} propyl) 4-fluorobenzenesulfonamide, 4- (4-chlorophenylamino) —2- [3- (N-pyro mouth) propyl-1 1-amino] —8-me Toxiquinazoline hydrochloride,

4-(4-phenylamino) 1 2-[3-(N-imidazo) propyl-1-amino] quinazoline hydrochloride,

N (4)-(4-chlorophenylamino) 1 N (2) — (2-cyclohexylaminoethyl) quinazoline — 2, 4-diamine dihydrochloride,

4- (4-chlorophenylamino) -2- [3- (N-pyrrolidino) propyl

— 1-amino] quinazoline hydrochloride,

4-cyclohexylamino-2- [3- (N-pyro mouth) propyl-1-amino] quinazoline hydrochloride,

[3- (4-cyclohexylaminoquinazoline-l- 2-ylamino) propyl] force rubamide acid tert-butyl ester,

[3- (4-benzylaminoquinazoline-2-ylamino) propyl] carbamide acid tert-butylester,

4-benzylamino-2- (3-aminopropylamino) quinazoline,

4- (4-chlorophenyl) amino 2- [3- (N-pyromethyl) propyl-1-amino] quinazoline hydrochloride,

4- (4-phenylamino) 1 2- [2- (N-pyromethyl) ethyl-1-amino] quinazoline hydrochloride,

4- (4-chlorophenylamino) 2- (2- (N-imidazo) ethyl-1amino) quinazoline hydrochloride,

4- (4-phenylamino) -2- (2- (N-pyrrolidino) ethyl-1-amino) quinazoline hydrochloride,

4-(4-phenylamino) 4- 2- [3- (N-imidazo) propyl-1-amino]-8-methoxyquinazoline hydrochloride,

4- (4-chlorophenylamino) —2— [4- (N-imidazo) butyl-1-amino] quinazoline hydrochloride,

4-cyclohexylamino-2- [3- (N-pyromethyl) propyl-1-amino] -18-methoxyquinazoline hydrochloride, 4-cyclohexylamino-2- [3- (N-imidazo mouth) propyl-1-amino] quinazoline hydrochloride,

4-cyclohexylamino-2- [3- (N-pyrrolidino) propyl-1-amino] quinazoline hydrochloride,

4-cyclohexylamino-2- [2- (N-pyromethyl) ethyl-1-amino] quinazoline hydrochloride,

4-cyclohexylamino—2— [2— (N—imidazo mouth) ethyl-1-amino] quinazoline hydrochloride,

4-cyclohexylamino-2- [2- (N-pyrrolidino) ethyl-1-amino] quinazoline hydrochloride,

4-cyclohexylamino-2- [3- (N-imidazo) propyl-1-amino] -8-methoxyquinazoline hydrochloride,

4-cyclohexylamino—2- [4- (N-imidazo) butyl-1-amino] quinazoline hydrochloride,

2, 4-diphenylaminoquinazoline hydrochloride,

2- (4-Methoxyphenylamino) 4- (4-phenylaminoquinazoline hydrochloride, 2- (4-fluorophenylamino) -4- (phenylaminoquinazoline hydrochloride, 2- (4-phenylamino) Enenylamino) —4-phenylaminoquinazoline hydrochloride, 2- [4- (N, N-dimethylamino) phenylamino] -1-4-phenylaminoquinazoline dihydrochloride,

2- (3,4-dimethoxyphenylamine) -4-phenylaminoquinazoline hydrochloride,

2-[4-(N, N-Jethylamino) phenylamino] 1-phenylamino quinazoline dihydrochloride,

2- [4- (benzyloxy) phenylamino] —4-phenylaminoquinazoline hydrochloride,

2- (4-Aminophenylamino) 1-4-phenylaminoquinazoline dihydrochloride, 2- [3- (N, N-dimethylamino) phenylamino] —4-phenylaminoquinazoline dihydrochloride,

2— [4- (N, N-dipropylamino) phenylamino Ί—4-phenylamino Noquinazoline dihydrochloride,

2— (4-Cyanophenylamino) —4-phenylaminoquinazoline hydrochloride, 2- [4- (2-pyridylamino) phenylamino] 1-4-phenylaminoquinazoline dihydrochloride,

2- [4- (aminomethyl) phenylenamino] 1-4-phenylaminoquinazolinni hydrochloride,

2- [3- (Aminomethyl) phenylamino] —4-phenylaminoquinazoli — {ra acid ^ nt}

2-(4-Hydroxyphenylamino) 1-4-phenylaminoquinazoline hydrochloride ¾,

2— [4- (3-cyclohexylpropyloxy) phenylinamino] —4-phenylaminoquinazoline hydrochloride,

2,4-di- (4-methoxyphenylamino) quinazoline hydrochloride,

2- (4-cyanophenylamino) 1-41 (3-methoxyphenylamino) quinazoline hydrochloride,

2-[4-(Ν, Ν-acetylamino) phenylamino] 1-41 (3-methoxyphenylamino) quinazoline dihydrochloride,

2- (4-cyclohexylphenylamino) 1-41 (3-methoxyphenylamino) quinazoline hydrochloride,

2- (4-Methoxyphenylamino) 1-4- (3-Methoxyphenylamino) quinazoline hydrochloride,

2- [4- (aminomethyl) phenylamino] 1-4- (3-methoxyphenylamino) quinazoline dihydrochloride,

2— [4- (Ν, ジェ —Jethylamino) phenylamino] —4— (4-Methoxyphenylamino) quinazoline dihydrochloride,

2- [4- (Ν, Ν-dipropylamino) phenylamino] -1-4- (4-methoxyphenylamino) quinazoline dihydrochloride,

2- (4-hydroquinphenylamino) 1-4- (4-methoxyphenylamino) quinazoline hydrochloride,

2- [4- (2-Pyridylamino) phenylamino] -1- 4- (4-Methoxyphene Nilamino) quinazoline dihydrochloride,

2— [4- (Ν, Ν-dimethylamino) phenylamino] —4— (4-methoxyphenylamino) quinazoline dihydrochloride,

2- [4- (piperidine-1-inole) phenylamino] —4-phenylaminoquinazoline dihydrochloride,

2- [4- (benzyloxy) phenylamino] -4- (3-methoxyphenylamino) quinazoline hydrochloride,

2- (4-hydroxyphenylamino) 1- (3-methoxyphenylamino) quinazoline hydrochloride,

2-[3-(Ν, Ν-dimethylamino) phenylamino] —4— (3-methoxyphenylamino) quinazoline dihydrochloride,

2-(4-chlorophenylamino) 1-4-phenylaminoquinazoline hydrochloride, 2-(4-methylphenylamino)-4-phenylaminoquinazoline hydrochloride, 2-(3- 4- (4-phenylaminoquinazoline) hydrochloride, 2- (2-methoxyphenylazoline) hydrochloride, 2- (4-nitrophenylamino) hydrochloride, 2- (4-nitrophenylamino) hydrochloride 1-phenylaminoquinazoline hydrochloride, 2,4-di (3-methoxyphenylamino) quinazoline hydrochloride,

2— [4- (benzyloxy) phenylamino] 1-4— (4-methoxyphenolamino) quinazoline hydrochloride,

2- [4- (aminomethyl) phenylenamino] -4- (4-methoxyphenylamino) quinazoline dihydrochloride,

2— [4— (Piperidin-1-yl) phenylamino] 1-41 (3-methoxyphenylamino) quinazoline hydrochloride,

2— [4— (Piperidine-1-inole) phenylamino] —4— (4-Methoxyphenylamino) quinazoline hydrochloride,

4-Methyl- [4- (4-phenylaminoquinazoline-1-ylamino) phenyl] methanesulfonamide hydrochloride,

Ν-2-[4- (4-methylbiperidine-1-1-sulfonylmethyl) phenyl] 1--4-phenylquinazoline-2,4-diamine hydrochloride,

Ν— 2— [4-1 (Ν-methylbiperazine-1-11-sulfonylmethinole) phenyl]- N—4-phenylquinazoline mono 2,4-diamine dihydrochloride,

N-2- [4- (Morpholine-1-41-sulfonylmethyl) phenyl] -N-4-phenylphenylquinazoline-2,4-diamine hydrochloride,

N, N-dimethyl [4- (4-phenylaminoquinazoline-l-2-ylamino) phenyl] methanesulfonamide hydrochloride,

N— (2-Methoxyxetil) — [4- (4-phenylaminoquinazoline-1-2-amino) phenyl] methanesulfonamide hydrochloride,

2-[4- (ethanesulfonylmethyl) phenylamino] —4-phenylaminoquinazoline hydrochloride,

N- {4- [4- (4-methoxyphenylamino) quinazoline-2-ylamino] benzyl} methanesulfonamide hydrochloride,

N- {4— [4 -— (3-Methoxyphenylamino) quinazoline-1-ylamino] benzyl} methanesulfonamide hydrochloride,

N— [4- (4-Phenylaminoquinazoline-1-2-amino) benzyl] methanesulfonamide hydrochloride,

2-(4-cyclohexylphenylamino) 1-4-phenylaminoquinazoline

6-bromo-2,4-di (3-methoxyphenylamino) quinazoline hydrochloride, 2- (3-methoxyphenylamino) -1-6-nitro-4-phenylaminoquinazoline hydrochloride,

6-amino-1 2- (3-methoxyphenylamino) 1-4-phenylaminoquinazoline hydrochloride,

2, 4-diphenylamino-6-phenylquinazoline,

N, N-dimethyl [4- (6-phenyl-4-phenylaminoquinazoline-2-ylamino) phenyl] methanesulfonamide hydrochloride,

N, N-Dimethyl [4- (5-Methoxy-4-phenylaminoquinazoline-1-ylamino) phenyl] methanesulfonamide hydrochloride,

N-methyl-1- [4- (6-methoxy-4-phenylaminoquinazoline-2-inoleamino) phenyl] methanesulfonamide hydrochloride,

6-Methoxy 2— (4-Methoxyphenylamino) 1-4-Phenylamino Nazoline hydrochloride,

2- (4-hydroxyphenylamino) -1-6-methoxy-4-phenylaminoquinazoline hydrochloride,

2- (4-benzyloxyphenylamino) -6-methoxy-4-phenylaminoquinazoline hydrochloride,

N-Methyl- [4- (7-Methoxy-14-phenylaminoquinazoline-12-ylamino) phenyl] methanesulfonamide hydrochloride,

N-methyl- [4- (8-methoxy-4-phenylaminoquinazoline-12-ylamino) phenyl] methanesulfonamide hydrochloride,

N- [4- (8-methoxy-4-phenylaminoquinazoline-2-ylamino) benzyl] methanesulfonamide hydrochloride,

N— {4 -— [8-Methoxy-14- (3-Methoxyphenylamino) quinazoline-12-ylamino] benzyl} methanesulfonamide hydrochloride,

5-(8-Methoxy 4-phenylaminoquinazoline-2-ylamino) naphthalene 1-methylsulfonic acid hydrochloride,

8—Methoxy 2— [4— (Piperidin-1-yl) phenylamino] —4-phenylaminoquinazoline dihydrochloride,

8-Methoxy 2- (4-methoxyphenylamino) 1-4-phenylaminoquinazoline hydrochloride,

2- (4-aminomethylphenylamino) -18-methoxy-1-4-phenylaminoquinquinazoline hydrochloride,

Naphthalene-1-sulfonic acid 4-[(4-aminoquinazoline-12-inoleamino) methyl] benzylamide hydrochloride,

Naphthalene-1-sulfonic acid 3-[(4-aminoquinazoline-12-ylamino) methyl] benzylamide hydrochloride,

2-(N-methyl-1-methoxyphenylamino) -8-methoxy41- (4-cyanophenylamino) quinazoline,

2— [N ¹ —Methyl-4— (acetoaminomethyl) pheninoleamino] 1—8—Methoxy 4— (4—1 cyanophenylamino) quinazoline,

2-[N ¹ -Methyl-1-41 (pyrrolidine-1-ylmethyl) pheninoleamino] -1- 4-phenylaminoquinazoline,

2— [N ¹ —Methyl-41- (pyrrolidine-1-1-methyl) phenylenamino] —8-Methoxy-1-41- (4-cyanophenylamino) quinazoline

4- (4-chlorophenylamino) 1 2 — [(4-pyrrolidine-1-ylmethyl) phenylamino] 1—8- (2-hydroxyethoxy) quinazoline,

1- {4- [4- (4-chlorophenylamino) -1-8- (2-hydroxyxetoxy) quinazoline-2-ylamino] benzyl} 1-2-pyrrolidin-1-one,

2- (2-chloro-4-methoxyphenylamino) -1-8- (2-morpholinoethoxy) -4-1 (2-methylphenylamino) quinazoline,

2- (2-Methoxy-1-amino) 1-4-1 (2-Methylphenylamino) -8-Methoxyquinazoline,

2- (2-Methyl-1-4-methoxyphenylamino) -4-1- (2-Methylphenylenolamino) -18-methoxyquinazoline,

2- (2-methyl-4-methoxyphenylamino) 18- (2-morpholinoethoxy) 4- (2-methylphenylamino) quinazoline,

4- (4-cyclophenylamino) -1-2- (4-[(cyclopropylmethylmethylamino) methyl] -1-2-methylphenylamino} -18-methoxyquinazoline, 2- [4- [acetylamino Methyl) phenylamino] -4- (3-methoxyphenylamino) quinazoline,

2— [4— (Acetylaminomethyl) phenylamino] —8—Methoxy 4- (4—Methoxyphenylamino) quinazoline,

{3- [4- (4-chlorophenylamino) -18-ethylquinazoline-12-ylamino] benzyl} benzamide,

2- [3- (Acetylaminomethyl) phenylamino] —8-Methoxy-1-41- (3-methoxyphenylamino) quinazoline,

2— [4— (N-piperidinylmethyl) phenylamino] —8—Methoxy 41- (4-methoxyphenylamino) quinazoline,

2-{3-[4- (4-chlorophenylamino) 1 8-(2-methoxyethoxy) quinazoline-2-ylamino] phenoxy}-N, N-dimethylacetamide, 4- 1 {4-1-1 [4 — (4—Phenylamino) 1 8— (2-hydroxyethoxy) B) quinazoline-1—ylamino] phenyl} —1,1,1

4- (4-chlorophenylamino) 18-methoxy 2- [4- (propane-2-sulfonylmethyl) phenylamino] quinazoline,

6-N, N-dimethylamino-4- (4-chlorophenylamino) 1-2- [2-methoxymethyl-4-1 (propane-1-sulfonylmethyl) phenylenamino] quinazoline,

2- [2-Methoxymethyl-4-1 (propane-2-sulfonylmethyl) phenylamino] —8-methyl-4-phenylaminoquinazoline,

[4-(6-Chloro-4-phenylaminoquinazoline-1-2-ylamino) -1-3-methoxymethylphenyl] N, N-dimethylmethanesulfonamide, {4— [4— (4-fluorophenyl 1-N-N-dimethylmethanesulfonamide, diphenylamino) -1- (2-hydroxyethoxy) quinazoline-2-ylamino] phenyl

{3- [4- (4-fluorophenylamino) -18-methylquinazoline-12-ylamino] phenyl} -N, N-dimethylmethanesulfonamide,

2 -— {4- [8- (2-dimethylaminoethoxy) 1-41- (4-fluorophenylenoleamino) quinazoline-1-2-ylamino] phenyl} ethanesulfonic acid dimethylamide,

4- (4-chlorophenylamino) 1 2- [2-methoxy 4- (propane-1-sulfonylmethyl) benzylamino] 1-methylquinazoline,

N-Methyl- [4- (8-methyl-4-phenylaminoquinazoline-2-ylamino) phenyl] methanesulfonamide hydrochloride,

N, N-dimethyl- [4- (8-methyl-4-phenylaminoquinazoline-1-ylamino) phenyl] methanesulfonamide hydrochloride,

N, N-dimethyl [4- (8-methyl-4-methylaminoquinazoline-l- 2-inoamino) phenyl] methanesulfonamide hydrochloride,

N, N-Dimethyl- [4- (8-Methoxy-41-phenylaminoquinazoline-1 2

—Illamino) phenyl] methanesulfonamide hydrochloride,

N (6), N (6) -dimethyl-N (2), N (4) diphenylquinazoline- 2, 4, 6-triamide hydrochloride,

N (4) mono (3-chlorophenyl) mono N (6), N (6) monodimethyl N (2) -phenylquinazoline-2,4,6-triamide hydrochloride,

[4- (6-dimethylamino-4-phenylaminoquinazoline-2-ylamino) phenyl] 1-N, N-dimethylmethanesulfonamide hydrochloride,

[4- (8-dimethylaminomethyl-4-phenylaminoquinazoline-1-inoleamino) phenyl] -N, N-dimethylmethanesulfonamide hydrochloride, 8-methoxymethyl-N (2) — (4-me Toxifenyl)-N (4)-phenylquinazoline-2,4-diamine hydrochloride,

N (2)-(4-Ethanesulfonylmethylphenyl) —8-methoxymethyl—N (4) —Phenylquinazoline-1,2,4-diamine hydrochloride,

[4- (8-Methoxymethyl-4-1-phenylaminoquinazoline-2-ylamino) phenyl] —N-methylmethanesulfonamide hydrochloride,

N (2) mono (4-ethanesulfonylmethylphenyl) -8-methoxy-N (4) -phenylquinazoline-1,2,4-diamine hydrochloride,

N (4) -cyclopropyl-N (2)-(4-Ethanesulfonylmethylphenyl) -8-methoxyquinazoline-2,4-diamine hydrochloride,

4-cyclopropylmethylamine 2- (4-ethanesulfonylmethylphenylenamino) quinazoline hydrochloride,

N (2)-(4-Ethanesulfonylmethylphenyl) -N (4) —Methylquinazoline—2,4-Diamine hydrochloride,

N (4)-(2-Dimethylaminoethyl) -N (2)-(4-Ethanesulfonylmethylphenyl) quinazoline- 2,4-diamine hydrochloride,

{4— [4- (3-chlorophenylamino) quinazoline-1-ylamino] phenyl} 1-N, N-dimethylmethanesulfonamide hydrochloride,

[(4-methoxyphenyl) -1- (4-phenylaminoquinazoline-1-yl) amino] ethyl acetate;

[{2-— [4- (2-Methoxyethoxy) phenylamino] quinazoline-1- (4-methoxyphenyl) amino] ethyl acetate;

N (4) -cyclohexyl N (4) —ethyl-N (2)-[4- Toxi) phenyl] quinazoline-2,4-diamine hydrochloride,

[4- (3,4-dihydro-1H-isoquinoline-2-inole) quinazoline-12-yl] [4- (2-methoxyethoxyquin) phenyl] amine hydrochloride,

2- [4- (benzoylaminomethyl) phenylamino] 1-41-phenylaminoquinquinazoline hydrochloride,

2- [4- (aminocarbonyl) phenylamino] -4 phenylaminoquinazoline hydrochloride,

2- [4- (2-hydroxyethyl) phenylamino] 4-phenylaminoquinazoline hydrochloride,

2- [4- (2-Hydroxyethyl) phenylamino] -4-1 (3-methoxyphenylamino) quinazoline hydrochloride,

2- [4- (2-hydroxyethyl) phenylamino] 8-methoxy-4phenylaminoquinazoline hydrochloride,

2- [4- (2-methoxyhexyl) phenylamino] 1-4-phenylaminoquinazoline hydrochloride,

2- [4- (2-Methoxyshethyl) phenylamino] — 4- (4-aminocarbonylphenylamino) quinazoline hydrochloride,

2- [4- (2-Methoxyhexyl) phenylamino] 1-4- (3-Methoxyphenylamino) quinazoline hydrochloride,

2- [4- (3-Hydroquinpropyl) phenylamino] 18-methoxy-14-phenylaminoquinazoline hydrochloride,

2- [4- (3-hydroxypropyl) phenylamino] -4-phenylaminoquinazoline hydrochloride,

2- [4- (3-hydroxypropyl) phenylamino] -4-1 (3-methoxyphenylamino) quinazoline hydrochloride,

2- [4- (3-hydroquinpropyl) phenylamino] -4-1- (4-methoxyphenylamino) quinazoline hydrochloride,

2- [4- (2-Hydroxyethoxy) phenylamino] 1-41-phenylaminoquinazoline hydrochloride,

2— [4— (2-Hydroxyethoxy) phenylamino] -4- (3-Methoxy Phenylamino) quinazoline hydrochloride,

2— [4— (2-Hydroxyethoxy) phenylamino] —4— (4-Methoxyphenylamino) quinazoline hydrochloride,

2- [4- (2-Methoxyxenyl) phenylamino] 1-41 (4-Methoxyphenylamino) quinazoline hydrochloride,

2- [4- (3-ethyl-4-methoxy) pheninoleamino] 1-4-phenylaminoquinazoline hydrochloride,

2- [4- (3-hydroxypropyl) phenylamino] -4-cyclohexylaminoquinazoline hydrochloride,

4- (4-methylphenylamino) 1-2- [4- (Methoxyacetylaminomethyl) phenylamino] 18-methoxyquinazoline hydrochloride,

4- (4-fluorophenylamino) -1-8-methoxy 2- [4- (2-hydroxyshetyl) phenylamino] quinazoline hydrochloride,

2- [4- (3-Hydroxypropyl) phenylamino] —4- (3-methoxyphenylamino) quinazoline hydrochloride,

2- [4- (3-Hydroxypropyl) phenylinamino] -4- (3-hydroxyphenylamino) quinazoline hydrochloride,

6-chloro-1-cyclohexylamino-2- [4- (3-hydroxypropyl) phenylamino] quinazoline hydrochloride,

6-chloro-1-amino-4-cyclohexylamino 2- [4- (2-hydroxyethoxy) phenylamino] quinazoline hydrochloride,

2- [4- (3-ethoxypropoxy) phenylamino] -4-phenylaminoquinazoline hydrochloride,

6-Fluoro-2- [4- (3-hydroxypropyl) phenylamino] -4- (3-methylphenylamino) quinazoline hydrochloride,

2- [4- (3-benzyloxypropoxy) phenylamino] -4-phenylaminoquinazoline hydrochloride,

2— [4- (3-benzyloxypropoxy) phenylamino] —4- (3-methoxyphenylamino) quinazoline hydrochloride,

2— [4— (2-Methoxyethoxy) phenylamino] —4— (4-Methoxyethoxy Enylamino) quinazoline hydrochloride,

4-cyclohexylamino-2- [4- (3-benzyloxypropoxy) phenylamino] quinazoline hydrochloride,

2— [4- (2-methoxyphenoxy) phenylamino] 1-4— (3-hydroxyphenylamino) quinazoline hydrochloride,

2- [4- (2-methoxyphenoxy) phenylamino] —4- (3-methoxyphenylamino) quinazoline hydrochloride,

4-cyclohexylamino-2- [4- (3-hydroxypropoxy) phenylinoleamino] quinazoline hydrochloride,

4-cyclohexylamino 2- (4-hydroxyphenylamino) quinazolic acid

4-cyclohexylamino-2- [4- (2-methoxetoxy) phenylamino] -8-methoxyquinazoline hydrochloride,

4- (4-chlorophenylamino) -1-2- [4- (2-methoxyethoxy) phenylamino] -18-methoxyquinazoline hydrochloride,

4- (4-fluorophenylamino) 1-2- [4- (2-methoxyphenoxy) phenylamino] -18-methoxyquinazoline hydrochloride,

4-cyclohexylamino-2- [4- (2-methoxyethoxy) phenylamino] quinazoline hydrochloride,

4-1-ethylcyclohexylamino-2- [4- (2-methoxetoxy) phenylamino] 18-methoxyquinazoline hydrochloride,

4- (4-Methyl phenylamino) 2- [4- (2-Methoxyacetylaminomethyl) phenylamino] 8-Methoxyquinazoline hydrochloride,

4-cyclohexylamino-8-methoxy-2- (4-phenylamino) quinazoline hydrochloride,

2,4-di- (4-chlorophenylamino) quinazoline hydrochloride,

2- [4- (2-Methoxyacetylaminomethyl) phenylamino] 1-8-Methoxy-4-phenylaminoquinazoline hydrochloride,

4-cyclohexylamino-2- [4- (2-hydroxyshethyl) phenylamino] quinazoline hydrochloride, 2- [4- (2-aminoethyl) phenylamino] —4- (4-chlorophenylamino) -1-8-methoxyquinazoline hydrochloride,

2- [4- (3-Hydroxypropoxy) phenylamino] —4- (3-methylphenylamino) quinazoline hydrochloride,

4-cyclohexylamino-2- (3,4-methylenedioxyphenylamino) -18-methoxyquinazoline hydrochloride,

2- (3,4-methylenedioxyphenylamino) 18-methoxy-14-phenylaminoquinazoline hydrochloride,

4- (4-fluorophenylamino) 1-2- (3,4-methylenedioxyphenylamino) —8-methoxyquinazoline hydrochloride,

4- (3-hydroxyphenylamino) -1- [4- (piperidine-1-yl) phenylamino] quinazoline hydrochloride,

4-(3-Methylphenylamino) —2— [4- (3-benzyloxypropoxy) phenylamino] quinazoline hydrochloride,

2-[4- (2-acetoxicetyl) phenylamino] 1-phenylamino quinazoline hydrochloride,

4- [6-1 (H) 1-indazoleamino] 1- 2- (4-methoxyphenylamino) quinazoline hydrochloride,

4-cyclohexylamino-2- [4- (2-acetoxitytyl) phenylamino] quinazoline hydrochloride,

4-cyclohexylamino-2- [4- (3-bivaloyloxypropoxy) phenylamino] quinazoline hydrochloride,

(S) —2— (4-Methoxyphenylamino) 4- (1-Phenylethylamino) quinazoline hydrochloride,

4- (4-phenylamino) 4-([2-hydroxyethoxy) phenylamino] 1-8-methoxyquinazoline hydrochloride,

8-Acetoxy 41- (4-chlorophenylamino) 1-2-[(2-Methoxyxethoxy) phenylamino] quinazoline hydrochloride,

4-cyclohexylamino-2- (4-chloro-1--3-methoxyphenylamino) —8-methoxyquinazoline hydrochloride, 4- (4-Methoxy-1-amino) -2- (4-Methoxyphenylamino) quinazoline hydrochloride,

2-cyclohexylamino-4-phenylaminoquinazoline hydrochloride, cis / trans-2- (4-piperidine-11-ylcyclohexylamino) -4-4-1phenylaminoquinazoline dihydrochloride,

2-cyclohexylamino-8-methoxy-4-phenylaminoquinazoline hydrochloride,

trans-2- (4-acetoxycyclohexylamino) 1-41-phenylamino quinazoline hydrochloride,

trans-naphthalene-1-sulfonic acid [4- (4-phenylaminoquinazoline-2-ylamino) cyclohexylmethyl] amide hydrochloride,

trans-naphthalene-1-sulfonic acid [4- (4-aminoquinazoline-12-ylamino) cyclohexylmethyl] amide hydrochloride,

trans— [4- (4-Phenylaminoquinazoline-1-ylamino) cyclohexylmethyl] carbamic acid tert-butyl ester hydrochloride,

trans-4- (Aminomethylcyclohexylamino) -4-phenylaminoquinazoline dihydrochloride,

trans— [4- (4-Phenylaminoquinazoline-1-2-ylamino) cyclohexylmethyl] methanesulfonamide hydrochloride,

trans— 4-Methyl-N— [4- (4-Phenylaminoquinazoline—2-ylamino) cyclohexylmethyl] benzenesulfonamide hydrochloride, trans—N— {4 -— ((4-aminoquinazoline 1-2-Inoleamino) methyl] cyclohexylmethyl} 4-Methoxybenzenesulfonamide hydrochloride, trans-3-{{4-[(4-aminoquinazoline-2-ylamino) methyl] cyclohexylmethyl} Sulfamoyl} methyl 4-benzoate methyl ester hydrochloride,

trans-N- {4 — [(4-aminoquinazoline-1-2-ylamino) methyl] cyclohexylmethyl} —2,5-dimethoxybenzenesulfonamide hydrochloride, trans-N- {4 — [(4- Aminoquinazoline-2-ylamino) methyl] cyclohexylmethyl} benzenesulfonamide hydrochloride, trans-naphthalene-12-sulfonic acid {4-[(4-aminoquinazoline-12-inoleamino) methinole] cyclohexylmethyl} amide hydrochloride,

trans-N- {4-[(4-aminoquinazoline-2-ylamino) methyl] cyclohexylmethyl} methanesulfonamide hydrochloride

trans—N— {4-[(4-aminoquinazoline-1-2-ylamino) methyl] cyclohexylmethyl} phenylmethanesulfonamide hydrochloride,

trans-N- {4 — [(4-aminoquinazoline-1-2-ylamino) methyl] cyclohexylmethynole} 1- (4-tert-butylbenzenesulfonamide hydrochloride, trans—N— {4-((4- Aminoquinazoline- 1-2-ylamino) methyl] cyclohexylmethyl} 1,2,4,6-trimethylbenzenesulfonamide hydrochloride, trans-N- {4-[(4-aminoquinazoline-12-ylamino) methyl] Hexylmethyl} —4-methylbenzenesulfonamide hydrochloride, trans-N- {4-[(4-aminoquinazoline-1-ylamino) methyl] hexylhexylmethyl} benzamide hydrochloride,

trans-N- {4-[(4-aminoquinazoline-1-ylamino) methyl] cyclohexylmethyl} 12-phenylacetamide hydrochloride,

trans—N, N-dimethylaminosulfonic acid {4 -— ((4-aminoquinazoline-1-ylamino) methyl] cyclohexylmethyl} amide hydrochloride, trans-naphthalene-1-sulfonic acid {4--1-[( 4-Aminoquinazoline-2-ylamino) methyl] hexylmethyl} amide hydrochloride,

trans-naphthalene-11-sulfonic acid {4-[(4-amino-8-methoxyquinazoline-2-ylamino) methyl] cyclohexylmethyl} cyclohexyl hydrochloride, trans-naphthalene-11-sulfonic acid {4— [( 4-Amino-6-bromoquinazoline-2-ylamino) methyl] cyclohexylmethyl} amide, trans-naphthalene-2-sulfonic acid {4 — [(4-amino-8-methoxyquinazolin-2-ylamino) methyl] cyclo Xylmethyl} amide hydrochloride, trans-naphthalene-1-sulfonic acid {4-[(4-oxo-1,3,4-dihydroxyquinazoline-1-ylamino) methyl] cyclohexylmethyl} amide, trans-naphthalene-1 Monosulfonic acid {4-[(4-phenylaminoquinazoline-l-2-ylamino) methyl] cyclohexylmethyl} amide, trans-naphthalene-11-sulfonic acid {4-[(4-tert-butylaminoquinazoline-1-ylamino) methyl] cyclohexylmethyl} amide,

(R, S) — cis-naphthalene-1-sulfonic acid {3 -— ((4-aminoquinazoline-1-ylamino) methyl] cyclohexylmethyl} thiomid hydrochloride, trans-naphthalene-1-sulfonic acid [4- (4-aminoquinazoline-2-ylamino) cyclohexylethyl] amide hydrochloride,

Naphthalene-1-sulfonic acid {4— {[4- (2-Methoxyxylamino) quinazoline-1-ylamino] methyl} cyclohexylmethyl} amide, naphthalene-1-sulfonic acid {4-1-1 {[4 -(2-Hydroxyshetylamino) quinazoline-1-2-ylamino] methyl} cyclohexylmethyl} amide, naphthalene-1-sulfonic acid {4-{{4- (2-dimethylaminoethylamino) quinazoline 1- 2-ylamino] methyl} cyclohexylmethyl} amide, naphthalene1-1-sulfonic acid {4-1 {{4- [2- (2-hydroxyhexyl) ethylamino] quinazoline-1-2-ylamino} methyl} cyclohexylmethyl } Amid,

Naphthalene-1-sulfonic acid {4-{{4- [2- (morpholine-1-yl) ethylamino] quinazoline-1-ylamino} methyl} cyclohexylmethyl} amide,

Naphthalene-1-sulfonic acid {4 -— {{4- [1,1-di (hydroxymethyl) methylamino] quinazoline-12-ylamino} methyl} cyclohexylmethyl} amide,

Naphthalene-1-sulfonic acid {4-{{4- (3-Methoxypropylamino) quinazoline-1-ylamino] methyl} cyclohexylmethyl} amide, naphthalene-1-sulfonic acid {4--1-[(4-methyl Aminoquinazoline-2-ylamino) methyl] cyclohexylmethynole} amide,

Naphthalene-1-sulfonic acid {4-{{4- (N, N-dimethylamino) quinazoline-12-ylamino] methyl} cyclohexylmethyl} amide, naphthalene-1-sulfonic acid {4 -— ((4-aminoquinazoline -2-ylmethylamino) methyl] cyclohexylmethinole} amide,

Naphthalene-1-sulfonic acid {4-[(4-aminoquinazoline-1-ylamino) Methyl] cyclohexylmethyl} methylamide,

cis-naphthalene-1-sulfonic acid {4-[(4-aminoquinazoline-2-ylamino) methyl] cyclohexylmethyl} amide,

N- {4-[(4-aminoquinazoline-l-2-ylamino) methyl] cyclohexylmethyl} —4- (acetylamino) benzenesulfonamide,

N— {4 — [(4-aminoquinazoline-1-ylamino) methyl] cyclohexylmethyl} —2-trifluoromethylbenzenesulfonamide,

N— {4-[(4-aminoquinazoline-1-ylamino) methyl] cyclohexylmethyl} —2-nitrobenzenesulfonamide,

Quinoline-8-sulfonic acid {4-[(4-aminoquinazoline-1-ylamino) methyl] cyclohexylmethyl} amide,

N- {4-[(4-aminoquinazoline-2-ylamino) methyl] cyclohexylmethyl} 1-fluorobenzenesulfonamide

Cyclohexanesulfonic acid {4-[(4-aminoquinazoline-12-ylamino) methyl] cyclohexylmethyl} amide,

Propane-2-sulfonate {4-[(4-aminoquinazoline-12-ylamino) methyl] cyclohexylmethyl} amide,

2-Methoxyethanesulfonic acid {4-[(4-aminoquinazoline-1-ylamino) methyl] cyclohexylmethyl} amide,

Morpholine-1-sulfonic acid {4-[(4-aminoquinazoline-12-inorenamino) methyl] cyclohexylmethyl} amide,

Piperidine-1-sulfonic acid {4-[(4-aminoquinazoline-2-inorenamino) methyl] cyclohexylmethyl} amide,

4-Methylbiperazine-1-sulfonic acid {4-[(4-aminoquinazoline-2-ylamino) methyl] cyclohexylmethyl} amide,

N, N-dimethylaminosulfonic acid {4-[(4-amino-18-methoxyquinazoline-12-inoleamino) methyl] cyclohexylmethyl} amide,

N-methylaminosulfonic acid {4-[(4-amino-8-methoxyquinazoline-12-ylamino) methyl] cyclohexylmethyl} amide,

Naphthalene-1-sulfonic acid {4— [(4-amino-8-methoxethoxyquina Zoline-2-ylamino) methyl] cyclohexylmethyl} amide, naphthalene-1-sulfonic acid {4-{{4-amino-8- (N, N-dimethylaminoaminoethoxy) quinazoline-1-ylamino] methyl} cyclohexylmethyl ) Amido,

Naphthalene 1-sulfonic acid {4-{{4-amino-8- (morpholine-4-ylethoxy) quinazoline-2-ylamino] methyl} cyclohexylmethyl} amide,

Naphthalene-1-sulfonic acid {4 -— ((4-amino-8-ethylquinazoline-2—ylamino) methyl] cyclohexylmethyl} amide,

Naphthalene-1-sulfonic acid {4 -— ((4-amino-16-methoxhetoxyquinazoline-2-ylamino) methyl] cyclohexylmethyl} amide, naphthalene-1-sulfonic acid {4-1 — ((4-amino-5 8-Dimethoxyquinazoline-2-ylamino) methyl] cyclohexylmethyl} amide, piperidine-11-Snolephonic acid {3-[(4-amino-18-methoxyquinazoline-12-ylamino) methyl] cyclohexylmethyl} amido Do

Naphthalene-1-sulfonic acid {3 -— ((4-aminoquinazoline-12-inoleamino) methyl] cyclohexylmethyl} amide,

N— {3 — [(4-amino-8-methoxyquinazoline-1-2-inoleamino) methyl] cyclohexylmethyl}-(N, N-dimethylamino) sulfonamide, 8-methoxy-1-2- [4--naphthalene 1-ylmethanesulfonylmethyl) cyclohexylmethyl] quinazoline-1,2,4-diamine,

4- (4-phenylamino) 18-Methoxy 2- (4-pyrrolidine-1-ylmethylcyclohexylamino) quinazoline,

4-methyl-2-phenyl-2-methyl-4- (4-pyrrolidine-1-methylcyclohexyl) quinazoline-1,2,4-diamine,

1- {4- [4- (4-chlorophenyl) -8-methoxyquinazoline-2-ylamino] cyclohexylmethyl} pyrrolidine-1-one,

{4- [4- (4-chlorophenyl) -1-6-dimethylaminoquinazoline-2-ylamino] cyclohexylmethyl} —N-methylacetamide,

2-{4- (4-chlorophenylamino) 1-2-[4-(propane 1-2-sulfo Nylmethyl) cyclohexylamino] quinazoline-1-yloxyethanol

2— {6-Chloro-41- (4-chlorophenylamino) -1-2- [4- (propane—2-sulfonylmethyl) cyclohexylamino] quinazoline-18-yloxy} ethanol,

6—Black mouth 4— (4-Chlorophenyl) -18— (2-Methoxyethoxy) 1-2— {4- [2- (Propane-2-sulfonyl) ethyl] cyclohexyl} quinazoline 2,4 —Jamine,

2-{4- [8- (2-dimethylaminoethoxy) -14- (4-fluorophenylenamino) quinazoline- 1-ylamino] cyclohexyl} ethanesulfonic acid dimethylamide,

N, N-dimethylaminosulfonic acid 4- [4- (4-chlorophenylamino) -18-methoxyquinazoline-12-ylamino] cyclohexylmethyl} amide,

3- {4- [4- (4-chlorophenylamino) -8- (2-hydroxyethoxy) quinazoline-1-2-ylamino] cyclohexyl} -1-(4-methylpyrazine-1 1 Le) one-one propane,

trans-propane-2-sulfonic acid {4 -— ((4-aminoquinazoline-1-ylamino) methyl] cyclohexylmethyl} amide hydrochloride,

trans-N- {4 — [(4-aminoquinazoline-1-2-ylamino) methyl] cyclohexylmethyl} —4-fluorobenzenesulfonamide hydrochloride, trans-N- {4 — [(4- Aminoquinazoline—2-ylamino) methyl] cyclohexylmethyl} —2-nitrobenzenesulfonamide hydrochloride, trans-piperidine-11-sulfonic acid {4 -— ((4-aminoquinazoline-12-inoleamino) methyl] cyclo Hexylmethyl} amide hydrochloride,

trans-morpholine-1-monosulfonic acid {4 -— ((4-aminoquinazoline-2-ylamino) methyl] cyclohexylmethyl} amide hydrochloride

trans-naphthalene-1-sulfonic acid {4-{{4- (2-methoxyhexylamino) quinazoline-12-ylamino] methyl} cyclohexylmethyl} amide, trans-naphthalene-12-sulfonic acid {4— {[4 I- (2-Methoxyxethylamino) quinazoline-l- 2-ylamino] methyl} cyclohexylmethyl} amide, trans-naphthalene-1 1-sulfonic acid {4— {[4- (2-hydroxyxylamino) quinazoline-1-2-ylamino] methyl} cyclohexylmethyl} amide, trans-naphthalene1-1—sulfonic acid {4— {[ 4- (2-hydroxy 1-hydroxymethylethylamino) quinazoline-1-ylamino] methyl} cyclohexylmethyl} amide,

trans-naphthalene-1-sulfonic acid {4-1 {[4- (3-methoxypropylamino) quinazoline-1-2-inoleamino] methyl} cyclohexylmethyl} amide, trans-naphthalene-1-sulfonic acid {4- { {4- [2- (2-hydroxyethoxy) ethylamino] quinazoline-2-ylamino} methyl} cyclohexylmethyl} amide,

trans-naphthalene-1-sulfonic acid {4— [(4-methylaminoquinazoline

2—ylamino) methyl] cyclohexylmethyl} amide,

trans-naphthalene1-1-sulfonic acid {4-1-1 [(4-dimethylaminoquinazoline

—2—ylamino) methyl] cyclohexylmethynole} amide,

trans-naphthalene-1-sulfonic acid {4-[(4-morpholine-141-ylquinazoline-2-ylamino) methyl] cyclohexylmethyl} amide, trans-naphthalene-1-sulfonic acid {4 -— [[4- (4- Methylbiperazine-1 -inole) quinazoline-1 -ylamino] methyl} cyclohexylmethyl} amide

trans—N, N-dimethyl—2— {2-{{4 -— ((naphthalene-1-1-sulfonylamino) methyl] cyclohexylmethyl} amino} quinazoline-14-ylamino} acetamide

trans—N, N—dimethyl-2 -— {2-{{4-[(naphthalene-2-sulfonylamino) methyl] cyclohexylmethyl} amino) quinazoline-1- 4-aminoaminoacetamide,

trans-naphthalene-1—sulfonic acid {4 -— {[4- (2-piperidine-1-1-leutylamino) quinazoline-2-ylamino] methyl} cyclohexylmethyl} amide,

trans-naphthalene-1-sulfonic acid {4 -— [[4- (2-morpholine-4-yl letylamino) quinazoline-l-2-ylamino] methyl} cyclohexylmethy No.

trans-naphthalene-1-sulfonic acid {4-{[4- (3-dimethylaminopropylamino) quinazoline-1-ylamino] methyl} cyclohexylmethyl} amide hydrochloride,

trans-naphthalene-1-sulfonic acid {4 -— [[4- (2-dimethylaminoethylamino) quinazoline-12-ylamino] methyl} cyclohexylmethyl} amide ',

trans-naphthalene-1-sulfonic acid {4-{{4- (2-dimethylaminoethylamino) quinazoline-1-ylamino] methyl} cyclohexylmethyl}

trans-naphthalene-1-sulfonic acid {4-{{4- (2-Jetylaminoethylamino) quinazoline-12-ylamino] methyl} cyclohexylmethyl} amide,

trans-naphthalene-1-sulfonic acid {4-{{4- (2-dimethylamino-1,1,1-dimethylethylamino) quinazoline-12-ylamino] methyl} cyclohexylmethyl} amide,

trans-naphthalene-1-sulfonic acid {4-{{4- [2- (4-methylpiperazine-111-ethyl) ethylamino] quinazoline-1-ylamino} methyl} cyclohexylmethyl} amide,

trans-naphthalene-1-sulfonic acid {4-{[4- (3-dimethylaminopropylamino) quinazoline-1-ylamino] methyl} cyclohexylmethyl} amide,

trans-propane-1-sulfonic acid {4-{{4- (3-dimethylaminopropylamino) quinazoline-12-ylamino] methyl} cyclohexylmethyl} atom

trans-4-Methylbiperazine-1-sulfonic acid {4-{[4 (3-Jetylaminopropylamino) quinazoline-2-ylamino] methyl} cyclohexylmethyl} amide,

trans— N— {4-{[4- (3-Jethylaminopropylamino) quinazoline —2-ylamino] methyl} cyclohexylmethyl} —C-phenylmethanes Lehonamide,

trans-naphthalene-1-sulfonic acid {4-{{4- (3-dimethylaminopropynoleamino) quinazoline-12-ylamino] methyl} cyclohexylmethyl} amide,

trans-N— {4 -— {[4- (3-dimethylaminopropylamino) quinazoline—2-ylamino] methyl} cyclohexanemethylinole} —4-fluorobenzenesulfonamide,

trans—N (4)-(3-dimethylaminopropyl) -1-N (2) — {4-[(2-Methoxybenzylamino) methyl] cyclohexylmethyl} quinazoline-1 2,4-diamine,

trans- {2-{2-{{4-([naphthalene-1-sulfonylamino) methyl] cyclohexylmethyl} amino} quinazoline-4-ylamino} ethyl} tert-butylester carnomicidate,

trans-naphthalene-1-sulfonic acid {4— {[4- (2-aminoethylamino) quinazoline-l-2-ylamino] methyl} cyclohexylmethyl} amide, trans-4-{2-{2-{{4 -[(Naphthalene-1-sulfonylamino) methyl] cyclohexylmethyl} amino} quinazoline-4-ylamino) ethyl} piperazine-one-butane tert-butyl ester

trans-naphthalene-1-sulfonic acid {4 -— [[4- (2-piperazine-11-ylletylamino) quinazoline-12-ylamino] methyl} cyclohexylmethyl} amide,

trans-naphthalene-11-sulfonic acid {4-{[4-[(2-dimethylaminoethyl) methylamino] quinazoline-12-inorenamino] methyl} cyclohexylmethyl} amide,

trans-naphthalene-1-sulfonic acid {4-{[4-aminoquinazoline-12-yl] methylamino} methyl} cyclohexylmethyl} amide hydrochloride, trans-naphthalene-1-sulfonic acid {4— [( 4-Amino-6-fluoroquinazoline-2-ylamino) methyl] cyclohexylmethyl} amide, trans-naphthalene-11-sulfonic acid {4-1 [(4-amino-16-methoxyquinazoline-2-ylamino) methyl] cyclohexylmethyl} Amide hydrochloride, trans-naphthalene-1-sulfonic acid {4 -— ((4-amino-5-methoxyquinazolin-2-ylamino) methyl] cyclohexylmethyl} amide hydrochloride, trans-naphthalene-1-sulfonic acid {4--1-{[4- (2-dimethylaminoethylamino) -1-8-methoxyquinazoline-2-ylamino] methyl} cyclohexylmethyl} amide,

trans-naphthalene-1-sulfonic acid {4-{{4-1 (2- (ethylaminoethylamino) -18-methoxyquinazoline-12-ylamino] methyl} cyclohexylmethyl} amide,

trans-naphthalene-1-sulfonic acid {4-{{4- (3- (ethylpyraminopropynoleamino) -18-methoxyquinazoline-12-ylamino] methyl} cyclohexylmethyl} amide hydrochloride

trans-naphthalene-1-sulfonic acid {4-[(4-aminoquinazoline-2-ylamino) methyl] cyclohexylmethyl} methylamide hydrochloride, trans-naphthalene-1-methyl sulfonate {4-[(4-phenyl Aminoquinazoline-2-ylamino) methyl] cyclohexylmethyl} amide hydrochloride, trans-naphthalene-11-methylsulfonate {4-1 [1- (4-aminoquinazolin-2-ylamino) -1-methylethyl] cyclohexylmethyl} Amide hydrochloride,

trans-naphthalene-1-methyl sulfonate {4- [1-methyl-1- (4-phenylaminoquinazoline-1-ylamino) ethynole] cyclohexylmethyl} amide hydrochloride,

trans-naphthalene-2-sulfonic acid {4-[(4-aminoquinazoline-2-inoleamino) methyl] cyclohexyl} amide hydrochloride

trans-naphthalene-2-sulfonic acid {4 -— [[4- (4-chlorophenylamino) quinazoline-l-2-ylamino] methyl} cyclohexyl} amide hydrochloride, trans-naphthalene-11-sulfonic acid {4— [(4-aminoquinazoline-2-ylamino) methyl] cyclohexyl) amide,

trans-naphthalene-1-sulfonic acid {4-[(4-amino-8-methoxyquinazolin-2-ylamino) methyl] cyclohexyl} amide,

trans-naphthalene-1-sulfonic acid {4--1 {[4- (4 G) quinazoline-l- 2-ylamino] methyl} cyclohexyl} amide, trans-naphthalene-l-l-sulfonic acid {4-[(4-amino-8-methoxyquinazolin-l- 2-ylamino) methyl] cyclohexynole} ami Hydrochloride, trans-naphthalene-1-sulfonic acid {4-{[4- (2-dimethylaminoethylamino) quinazoline-1-ylamino] methyl} cyclohexynole} amide, trans-naphthalene-1-sulfonic acid { 4-{[4- (2-Dimethylaminoethylamino) quinazoline-1-ylamino] methyl} cyclohexynole} amide, trans-N- {4- (4-phenylaminoquinazoline-1-ylamino) cycl Methylhexylmethyl} 1- (N, N-dimethylamino) sulfonamide hydrochloride, trans-N- {4-1-1 {[4- (4-chlorophenyl) amino] quinazoline 1-2-ylami } Cyclohexylmethyl cyclohex} one (N, N-Jimechiruamino) sulfone Ryomi de hydrochloride,

trans—N— {4-{[4- (4-fluorophenyl) amino] -18-methoxyquinazoline-2-ylamino} cyclohexylmethyl} — (N, N-dimethylamino) sulfonamide hydrochloride,

trans-N- {4 -— [4- (cyclopropylmethylamino) quinazoline—2-ylamino] cyclohexylmethyl} methanesulfonamide hydrochloride, trans- {4-—4- (4-one-phenylamine) quinazoline — 2-ylamino] cyclohexylmethyl} carbamide acid tert-butyl ester, trans- {4- [4- (cyclopropylamino) -18-methoxyquinazoline-l-2-ylamino] cyclohexylmethyl} carbamide acid tert-butyl ester,

trans- {4 -— [4- (4-chlorophenylamino) quinazoline-1-ylamino] cyclohexylmethyl} acetamide hydrochloride,

trans- {4- [4- (4-chlorophenylamino) quinazoline-1-ylamino] cyclohexylmethyl} benzamide hydrochloride,

trans- {4 -— [4- (4-chlorophenylamino) quinazoline-12-ylamino] cyclohexylmethyl} -12-methoxybenzamide hydrochloride,

N—trans— {4 -— [4- (cyclopropylmethylamino) quinazoline—2-ylamino] cyclohexylmethyl} —2-methoxybenzamide hydrochloride, trans-4-(4-methylphenylamino) 2- (4-methylaminomethylhexyl) quinazoline-2,4-diamine,

trans— {4- [4- (4-chlorophenylamino) quinazoline-1-ylamino] cyclohexylmethyl} —N-methylacetamide

trans— {4- [4 -— (4-chlorophenylamino) quinazoline—2-ylamino] cyclohexylmethyl} —N-methylbenzamide,

trans—2-Methoxy [4- (4-phenylaminoquinazoline-2-ylamino) cyclohexylmethyl] acetamide,

trans— 2-Methoxy [4- (8-Methoxy-14-phenylaminoquinazolin-12-ylamino) cyclohexylmethyl] acetamide hydrochloride, trans- [4-I (8-Methoxy-4- Phenylaminoquinazoline-l- 2-ylamino) cyclohexylmethyl] carbamide acid tert-butyl ester hydrochloride, trans-[4- (8- methoxy-4- phenylaminoquinazoline-l- 2-ylamino) cyclo Hexylmethyl] methanesulfonamide hydrochloride,

trans-[4- (8-Methoxy-4-phenylaminoquinazoline-1-ylamino) cyclohexylmethyl]-(N, N-dimethylamino) sulfonamide trans-4- (cyclopropylmethyl) -2- (4-piperidine-1-ylmethylcyclohexyl) quinazoline-2,4-diamine dihydrochloride,

trans-4- (4-Phenyl phenyl) -1- (4-piperidine-1-ylmethyl cyclohexyl) quinazoline-2,4-diaminedihydrochloride,

4-(3-chlorophenyl) -l-cyclohexylquinazoline-l, 4-diamine hydrochloride,

2- (N-methylcyclohexylamino) -4-phenylaminoquinazoline hydrochloride,

2- (N-methylcyclohexylamino) -18-hydroxy-4-1-phenylaminoquinazoline hydrochloride,

2- (N-methylcyclohexylamino) -1-8-methoxy-4-phenylamino-quinazoline hydrochloride,

2— (N-methylcyclohexylamino) —8— (Methoxycarbonylmethoxy 1) 4-4-phenylaminoquinazoline hydrochloride,

2- (N-methylcyclohexylamino) -8- (2-hydroxyxetoxy) -1-4-phenylaminoquinazoline hydrochloride,

2- (N-methylcyclohexylamino) 18-hydroxy 4- (4-fluorophenylamino) quinazoline hydrochloride,

2- (N-ethylcyclohexylamino) 18-hydroxyl 4- (4-chlorophenylamino) quinazoline hydrochloride,

trans-2- (4-Benzyloxycyclohexylamino) 1-4-phenylaminoquinazoline hydrochloride,

trans-2- (4-acetoxycyclohexylamino) 1-41 (4-methoxyphenylamino) quinazoline hydrochloride,

N (2)-(trans-4-dimethylaminocyclohexylmethyl) 1 N (4) -methyl-6-p-tolylquinazoline-2,4-diamine,

1 1 {trans 1 4 1 [(4-Methylamino 6-p-tolylquinazoline-2-ylamino) methyl] cyclohexyl} pentane-1 1-ol

1 {trans-4-4-[(4-Methylamino-6-p-tolylquinazoline-1-2-ylamino) methyl] cyclohexyl} pentane

{trans—4 -— [(4-Methylamino-6-p-tolylquinazoline-2-ylamino) methyl] cyclohexyl} phenylmethanol

1 {trans-4-[(4-Methylamino 6-p-tolylquinazoline-2-ylamino) methyl] cyclohexyl} —2-phenylethanone,

N (2) — (trans—4-ethanesulfonylmethylcyclohexylmethyl) mono N (4) —methyl-6—p—tolylquinazoline—2,4-diamine,

N (2)-(trans-4-benzenebenzenesulfonylmethylcyclohexylmethyl) -N (4) -methyl-6-p-tolylquinazoline-2,4-diamine,

1 1 {trans— 4 1 {[4 1 (3-Jetylaminopropylamino) 1, 6,8-Dimethylquinazoline-1 2-ylamino] methyl} Cyclohexyl} Pentane 1 1

1- {trans—4 -— {[4- (3-Jethylaminopropylamino) -1,6,8-dimethylquinazoline-1-ylamino] methyl} cyclohexyl} pentane-1 One on,

1— {trans-4 — {[4- (3- (ethylpyraminopropylamino) —6,8-dimethylquinazoline-1-ylamino] methyl} cyclohexyl} 1-2-phenyluetanone,

{trans-1-41 {[4-1- (3-ethylpyraminopropylamino) -1,6,8-dimethylquinazoline-12-ylamino] methyl} cyclohexyl} phenylmethanone.

The compounds represented by the general formulas [I-a], [I-b], [I-c], [I-d], [I-e], or [I-f] are represented by And the compounds described in the international applications PCT / JP97 04399, PCT / JP97 04567, PCT / JP97 / 0457U PCT / JP97 / 04569, PCT / JP98 / 01015, PCT / JP98Z01855, and PCTZJP98 / 04314, etc. And has NPY Y5 receptor antagonism. The compounds represented by the general formulas [I-g], [I-h], [I-i], and [I-j] are described in International Publication Nos. W097Z19682, WO97 / 20820, WO97Z20821, and W097, respectively. No. 20822, WO97Z20823 and the like, and have NPY Y5 receptor antagonistic activity.

Next, a method for producing the compound according to the present invention will be described.

The compound represented by the general formula [I-a] can be produced, for example, by the following Production Method 1 or the method shown in Production Examples.

Manufacturing method 1

General formula [II-a]

Wherein Ar ² has the meaning as defined in the general formula [I-a], and a compound represented by the general formula [III-a] O

X— C— OAr ³ [III-a]

Wherein Ar ³ is a halogen atom or a phenyl group which may be substituted with a nitro group; X represents a halogen atom, and a compound represented by the general formula [IV-a]

[Wherein, Ar ² and Ar ³ have the same meanings as above], and then the compound [IV-a] and a general formula [V-a]

R ¹ R

Ar ¹ — AH [V-a]

R ³ R ⁴

[Wherein A, Ar RR ² , R ³ and R ⁴ have the meanings as defined in the above general formula [I-a]]. a] can be produced.

The reaction between the compound represented by the general formula [II-a] and the compound represented by the general formula [III-a] is usually performed with respect to 1 mol of the compound represented by the general formula [Π-a]. The reaction is carried out using the compound represented by the general formula [III-a] in an amount of 0.5 mol to excess mol, preferably equimolar or 1.5 mol.

The reaction is usually performed in an inert solvent. Examples of the inert solvent include methylene chloride, chloroform, tetrahydrofuran, ethyl ether, benzene, toluene, dimethylformamide and the like, or a mixed solvent thereof. It is suitable. The above reaction is preferably carried out in the presence of a base. Examples of the base include organic bases such as triethylamine, diisopropylethylamine, pyridine, 4-dimethylaminopyridine, sodium hydroxide, and water. Use inorganic bases such as oxidized lime, sodium carbonate, lium carbonate, sodium hydrogen carbonate Can be

The base is usually preferably used in an equimolar amount or an excess amount relative to 1 mol of the compound represented by the general formula [Π-a]. When the base is a liquid, the base can be used as a solvent and a base.

The reaction temperature is generally -78 ° C to 100 ° C, preferably -20 ° C to 50 ° C. The reaction time is generally 5 minutes to 7 days, preferably 30 minutes to 24 hours. In the reaction between the compound represented by the general formula [IV-a] and the compound represented by the general formula [Va], the compound represented by the general formula [IV-a] obtained by the above reaction is isolated. Without isolation or isolation, the compound represented by the general formula [Va] is usually equimolar to excess mol, preferably equimolar or 1.5 mol per mol of the compound [IV-a]. It is performed using a mole.

The reaction is usually performed in an inert solvent, and as the inert solvent, for example, methylene chloride, chloroform, tetrahydrofuran, dimethylformamide and the like, or a mixed solvent thereof are suitable.

The above reaction is preferably performed in the presence of a base. As the base, for example, triethylamine, diisopropylethylamine, and the like are preferable.

The amount of the base to be used is generally equimolar to excess, preferably 1 to 5 mol, per 1 mol of the compound represented by the general formula [IV-a].

The reaction temperature is usually-30 ° C to 200 ° C, preferably 20 ° C to 100 ° C. The reaction time is generally 5 minutes to 7 days, preferably 30 minutes to 24 hours. The target compound in each of the above steps can be easily isolated and purified by ordinary separation means. Examples of such means include solvent extraction, recrystallization, column chromatography, preparative thin-layer chromatography, and the like.

The compound of the general formula [Ia] can be converted into a pharmaceutically acceptable salt by a conventional method, and conversely, the conversion of the salt into a free compound can be performed by a conventional method.

As the compound represented by the general formula [II-a], a commercially available product can be used, or a method described in the literature [Comprehensive Heterocyclic Chemistry], 5 volumes, AR force tricky (A. RKatritzky), Pergamon Press (1984), etc.] It can be produced by a method or a method described in Reference Examples.

[Wherein R represents a lower alkyl group, and Ar ² and X have the same meanings.] According to the present production method, the compound represented by the general formula (la) and acetonitrile are reacted in the presence of a base group. The compound represented by the general formula [II-a] can be produced by reacting the compound to give a compound represented by the general formula (3a) and then reacting the compound (3a) with hydrazine.

In the reaction of compound (la) with acetonitrile, the reaction conditions vary depending on the type of base used.

When, for example, n-butyllithium, lithium diisopropylamide or the like is used as the base, the reaction is usually carried out in an inert solvent such as tetrahydrofuran or ethyl ether, and the reaction temperature is usually -78 ° C to room temperature. Yes, the reaction time is usually 30 minutes to 6 hours.

When, for example, sodium hydride or the like is used as the base, the reaction is usually performed in an inert solvent such as tetrahydrofuran, ethyl ether, or dimethylformamide, and the reaction temperature is usually from room temperature to 100 ° C. Yes, the reaction time is usually 1 hour to 6 hours.

The reaction of compound (3a) with hydrazine is usually carried out, for example, with ethanol, propanol, isoamyl alcohol, acetic acid, benzene, toluene, xylene or In an inert solvent such as a mixed solvent thereof, hydrazine is used in an amount of 0.5 mol to 10 mol, preferably 1 mol to 1.5 mol, per 1 mol of compound (3a). The reaction temperature is usually from room temperature to the boiling point of the solvent used in the reaction, preferably from 50 ° C to the boiling point of the solvent used in the reaction.

The reaction time is generally 30 minutes to 7 days, preferably 1 hour to 48 hours. The hydrazine used for the reaction may be an anhydride or a hydrate. Further, the compound represented by the general formula (3a) is replaced with a compound represented by the general formula (2a) instead of the compound represented by the general formula (la), and by reacting the compound with cyanide. It can also be manufactured.

The compound represented by the general formula (la) or (2a) can be produced by using a commercially available product, or by appropriately combining a known method or a method analogous thereto as necessary.

The compound represented by the general formula [III-a] or [Va] can be produced by using a commercially available product, or by appropriately combining a known method or a method analogous thereto as necessary.

The compound represented by the general formula [I-b] can be produced, for example, by the following production method 2, 3, 4, or 5 or a method shown in Production Examples.

Manufacturing method 2

General formula [II-b]

[Wherein Ar has the meaning as defined in the above general formula [Ib]], and a general formula [III-b]

[Wherein, A ring, B ring and R have the meanings as defined in the above general formula [I-b]. The compound represented by the general formula [I-b] can be produced by reacting the compound with the carboxylic acid represented by the formula [Ib] or a reactive derivative thereof.

The reaction between the compound represented by the general formula [Π—b] and the carboxylic acid represented by the general formula [III-b] is usually performed with respect to 1 mol of the compound represented by the general formula [Π—b]. The reaction is carried out using a carboxylic acid represented by the general formula [III-b] in an amount of 0.5 mol to excess mol, preferably 1 mol to 1.5 mol.

The reaction is usually carried out in an inert solvent. As the inert solvent, for example, dimethylene chloride, chloroform, tetrahydrofuran, dimethylformamide, pyridine and the like or a mixed solvent thereof are suitable.

The above reaction is preferably carried out in the presence of a condensing agent. Examples of the condensing agent include N, N'-dicyclohexylcarbodiimide, N, N'-diisopropylpyrucarpoimide, and 3- (3-dimethylaminopropyl) -1-3-ethylcarbodiimide, 1-1- (3-dimethylaminopropyl) -13-ethylcarbodiimide hydrochloride, benzotriazo-1-yl-11-ylokistris- (dimethylamino) phosphonium hexane Fluorophosphate, benzotriazole-1-yloxy-tris-pyrrolidinophosphoniumhexafluorophosphate, bromotris- (dimethylamino) phosphonium hexafluorophosphate, diphenylphosphoric azide , 1, Γ-carbonyldiimidazole and the like can be used.

The condensing agent can be used usually in an amount of 1 mol to excess mol, preferably 1 mol to 1.5 mol, per 1 mol of the compound represented by the general formula [Π-b]. The reaction temperature is usually from -50 ° C to 100 ° C, preferably from -20 ° C to 50 ° C. The reaction time is generally 30 minutes to 7 days, preferably 1 hour to 24 hours. By reacting a reactive derivative of the carboxylic acid with a compound represented by the general formula [II-b] instead of the carboxylic acid represented by the general formula [III-b], the compound represented by the general formula [I_b] ] Can also be manufactured.

As the reactive derivative of the carboxylic acid represented by the general formula [III-b], for example, an acid halide, a mixed acid anhydride, an active ester, an active amide and the like are used. The acid halide of the carboxylic acid of the general formula [III-b] can be obtained by reacting the carboxylic acid of the general formula [III-b] with a halogenating agent according to a conventional method. it can. As the halogenating agent, for example, thionyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, phosphorus tribromide, oxalyl chloride, phosgene and the like are used.

The mixed acid anhydride of the carboxylic acid of the general formula [III-b] is obtained by converting the carboxylic acid of the general formula [III-b] to a carboxylic acid according to a conventional method, for example, an alkyl carbonate such as ethyl ethyl carbonate; It can be obtained by reacting with an aromatic carboxylic acid chloride or the like.

The active ester of a carboxylic acid of the general formula [III-b] can be prepared by reacting the carboxylic acid of the general formula [III-b] with N, N'-dicyclohexylcarbodiimide, e.g. Dimethylaminopropyl) In the presence of a condensing agent such as 1-3-ethylcarbodiimide, for example, N-hydroxysuccinimide, N-hydroxyphthalimide, N-hydroxybenzotriazole, etc. —Hydroxy compound; can be obtained by reacting with a phenol compound such as 412 trophenol, 2,4-dinitrophenol, 2,4,5-trichlorophenol, pentachlorophenol, etc. .

The active amide of the carboxylic acid of the general formula [III-b] can be prepared by reacting the carboxylic acid of the general formula [III-b] with 1,1-carbonyldiimidazole, 1,1-carbonylbis (2 —Methylimidazole) and the like.

The reaction between the compound represented by the general formula [II-b] and the reactive derivative of the carboxylic acid represented by the general formula [III-b] is usually carried out by the compound 1 represented by the general formula [Π-b]. The reaction is carried out using a reactive derivative of a carboxylic acid represented by the general formula [III-b] in an amount of 0.5 mol to excess mol, preferably 1 mol to 1.5 mol, per mol.

In addition, the above reaction proceeds even in the absence of a base, but is preferably performed in the presence of a base to promote the reaction more smoothly.

Examples of the base include organic bases such as triethylamine, diisopropylethylamine, pyridine, and 4-dimethylaminopyridine, and sodium hydroxide. Inorganic bases such as sodium hydroxide, sodium hydroxide, sodium carbonate, sodium carbonate, and sodium hydrogencarbonate.

The base is preferably used in an amount of 1 mol or less, relative to 1 mol of the compound represented by the general formula [Π-b]. When the base is a liquid, the base can be used as a solvent and a base.

The reaction temperature is generally-50 ° C to 100 ° C, preferably-20 ° C to 50 ° C. The reaction time is generally 5 minutes to 7 days, preferably 30 minutes to 24 hours. In the reaction of the compound represented by the general formula [III-b] with the carboxylic acid represented by the general formula [III-b] or a reactive derivative thereof, depending on the reaction conditions, the compound represented by the general formula [IV-b] or the general formula [IV-b] Expression [V-b]

[IV-b] [V-b]

[Where Cy is the formula

(Where A ring, B ring and R have the above-mentioned meaning), and Ar has the above-mentioned meaning.] When the compound represented by the following formula is obtained as a by-product There is. These compounds can be converted to the compound represented by the general formula [I-b] by subjecting them to hydrolysis treatment in the presence of sodium hydroxide, potassium hydroxide or the like.

Manufacturing method 3

General formula [VI-b]

[Wherein, Ar ¹ is selected from the group consisting of a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, and an aromatic carbocyclic group X ¹ represents a halogen atom or a trifluoromethanesulfonyloxy group, and A ring, B ring and R have the above-mentioned meanings. And a compound represented by the general formula [VII-b]

R ^a

R ^a — Sn-R ¹ [VII-b]

R ^a

Wherein R ¹ is a lower alkyl group, a lower alkenyl group or an aromatic carbocyclic group; R ^a represents a lower alkyl group] with a compound represented by the following formula: Equation [1— 1— b]

[In the formula, A ring, B ring, ON! ^"1, R and R ¹ are as defined above] can be prepared a compound represented by.

The reaction between the compound represented by the general formula [VI-b] and the compound represented by the general formula [VII-b] is usually performed based on 1 mol of the compound represented by the general formula [VI-b]. The reaction is performed using the compound represented by the general formula [VII-b] in an amount of 0.5 mol to 10 mol, preferably 1 mol to 3 mol.

The reaction is usually performed in an inert solvent, and as the inert solvent, for example, benzene, toluene, tetrahydrofuran, dimethylformamide, N-methylpyrrolidone and the like, or a mixed solvent thereof are suitable.

Examples of the palladium catalyst used in the reaction include tetrakistriphenylphosphine. Sphine palladium, bistriphenylphosphine palladium chloride, palladium acetate, trisdibenzylideneacetone dipalladium and the like can be used.

The palladium catalyst can be used usually in an amount of 0.001 to 1 mol, preferably 0.01 to 0.1 mol, per 1 mol of the compound represented by the general formula [VI-b].

Furthermore, to make the reaction proceed smoothly, triphenylphosphine, tri-

A phosphine ligand such as 2-furylphosphine or lithium chloride can be allowed to coexist.

The reaction temperature is usually from room temperature to 200 ° C, preferably from 60 ° C to 150 ° C. The reaction time is usually 30 minutes to 7 hours, preferably 1 hour to 24 hours. Manufacturing method 4

General formula [I-1 2-b]

[Wherein, Ar ² is selected from the group consisting of a halogen atom, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, and an aromatic carbocyclic group. R ² represents a lower alkenyl group, and A ring, B ring and R have the above-mentioned meanings. By catalytic hydrogenation in the presence of a catalyst, the general formula [I-3-b]

Wherein R ³ represents a lower alkyl group, and A ring, B ring, Ar ² and R have the above-mentioned meanings].

The reaction is usually performed in an inert solvent, and examples of the inert solvent include, for example, Methanol, ethanol, methylene chloride, chloroform, tetrahydrofuran, dimethylformamide, acetic acid and the like, or a mixed solvent thereof are suitable. The catalyst used in the reaction is, for example, preferably a "radium-carbon catalyst". The reaction temperature is usually room temperature.

The hydrogen pressure is usually 1 to 50 atm, preferably 1 to 5 atm. The reaction time is generally 30 minutes to 7 days, preferably 1 hour to 24 hours. Manufacturing method 5

General formula [VIII-b]

Wherein R ⁴ is a substituent selected from the group consisting of a nitro group, a lower alkyl group, a lower alkoxy group, an aromatic carbocyclic group, and a hydrocarbon group having an aromatic carbocyclic group, or a hydrogen atom; A ring, B ring, Ar and X ¹ have the above-mentioned meaning], and a compound represented by the general formula [IX—b]

R ^a

R ^a — Sn- [IX-b] R

[Wherein, R ⁵ represents a lower alkyl group or an aromatic carbocyclic group, and ^Ra has the above-mentioned meaning] with a compound represented by the following formula: [I one 41 b]

[I—41 b]

[Wherein, A ring, B ring, Ar, R ⁴ and R ⁵ have the above-mentioned meanings].

The reaction between the compound represented by the general formula [VIII-b] and the compound represented by the general formula [IX-b] is carried out by reacting the compound represented by the general formula [VI-b] in the production method 2 described above. The reaction can be carried out in the same manner as in the reaction with the compound represented by the general formula [VII-b]. Accordingly, the same conditions can be applied to the reaction conditions and the like.

The compound represented by the general formula [I-b], [I-1-b], [I-3-b] or [I-4-1b] can be easily isolated and purified by ordinary separation means. Examples of such means include solvent extraction, recrystallization, column chromatography, preparative thin-layer chromatography, and the like.

These compounds can be converted into a pharmaceutically acceptable salt by a conventional method, and conversely, the conversion of the salt into a free compound can be performed according to a conventional method. Since the general formula [Π-b] is substantially the same as the general formula [II-a], the compound represented by the general formula can be produced and obtained by the method described above.

As the carboxylic acid represented by the general formula [III-b] used in the present invention, a commercially available product, a known method or a method analogous thereto, or a method described in Reference Examples, etc., may be appropriately combined as necessary. Can be manufactured.

The compound represented by the general formula [VI-b] used in the present invention can be obtained by using a raw material corresponding to a desired compound, a method for producing the compound represented by the general formula [Π-b] and a method according to the production method 2, and It can be produced by appropriately combining known methods as necessary.

The compound represented by the general formula [VII-b] used in the present invention can be produced by using a commercially available product or by appropriately combining a known method or a method analogous thereto as needed.

The compound represented by the general formula [III-b] can be obtained by converting the compound represented by the general formula [III-b] into the general formula [III-b] in the above-mentioned Production Method 2, respectively.

Wherein Ar RR ² , R ³ , R ⁴ and R ⁵ have the same meaning as defined in the general formula [I-c].

The compound represented by the general formula [III-b] is converted to a compound represented by the general formula [III-d] 0

Ar ¹ — (CH ₂ ) _n — C— C— OH [III-d]

R ¹ R ²

[Where,

n, R ¹ and R ² have the same meaning as defined in the above general formula [Id], and the other compounds can be produced in the same manner.

Production methods 3 and 4 can be similarly performed.

The compound represented by the general formula [III-c] or [III-d] can be produced by using a commercially available product, or by appropriately combining a known method or a method analogous thereto as necessary.

The compound represented by the general formula [I-e] can be produced, for example, by the following production methods 6, 7, 8, 9, 10, 11, or 12 or the method shown in Production Examples.

Manufacturing method 6

General formula [II-e]

OHC

In the formula, R ^3P represents a lower alkyl group or an optionally protected amino group or a lower alkylamino group; R ¹ and R ² have the same meanings as defined in the above general formula [I-e]. Having the general formula [III-e]

Ar ^p- (CH ₂ ) _m — T [HI-e]

Wherein, Ar ^p is a halogen atom, a nitro group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a di-lower alkylamino group, have been low-grade Al force Noiru group and Ariru groups and protection An aryl group or a heteroaromatic ring group which may have a substituent selected from the group consisting of an amino group and a lower alkylamino group; m is 1 or 2; T is a triphenylphosphonio group , A dimethoxyphosphoryl group or a methoxyphosphoryl group], and a compound represented by the general formula [IV-e] Ar ^p- (CH ₂ ) _n ― CH

[Wherein, n represents 0 or 1, and Ar ^p , R ′, R ² and R ^3p have the above-mentioned meanings] wherein the protecting group is removed, or By reducing the double bond, the general formula [Ι—1—e]

[I 1 1 e]

Ar

[Wherein, Y ^e represents an ethylene group, a trimethylene group, a vinylene group or a probenylene group, and Ar, RR ² and R ³ have the meanings as defined in the general formula [I-e].] Can be produced.

In the production method 6, a compound of the present invention represented by the general formula [I-e], wherein Y in the formula is an ethylene group, a trimethylene group, a vinylene group or a probenylene group, This is a method for producing a compound represented by the formula:

In the present production method, when an amino group (or imino group) which does not participate in the reaction is present in the reaction substance, the reaction is carried out after protecting the amino group (or imino group) appropriately with a protecting group for the amino group. It is preferable to remove the protecting group after the reaction.

Examples of the protecting group for an amino group include benzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, benzhydryl, and trityl groups. An aralkyl group; for example, a lower alkanoyl group such as a forminole group, an acetyl group, a propionyl group, a butyryl group, a bivaloyl group; an alkenyl group such as a benzoyl group; Lower alkoxycarbonyl groups such as carbonyl group, ethoxycarbonyl group, propyloxycarbonyl group and tert-butoxycarbonyl group; for example, benzyloxycarbonyl group, p-nitrobenzyloxycarbonyl group, phenethyloxy Arabonyl group Lower alkylsilyl groups such as trimethylsilyl group and tert-butyldimethylsilyl group; for example, phthaloyl group; Examples thereof include a alkylidene group and the like, and particularly preferred are an acetyl group, a bivaloyl group, a benzoyl group, an ethoxycarbonyl group, a tert-butynecarbonyl group and the like.

The reaction between the compound represented by the general formula [II-e] and the compound represented by the general formula [III-e] is usually carried out using equimolar amounts of both or a small excess of either, and the reaction is carried out. Usually, the reaction is performed in an inert solvent. Examples of the inert solvent include ethers such as ethyl ether, tetrahydrofuran, and dioxane; aromatic hydrocarbons such as benzene, toluene, benzene, xylene, and the like; Examples include aprotic polar solvents such as formamide, ethyl acetate, and hexamethyl phosphate triamide, and a mixed solvent thereof.

The reaction temperature is usually from −100 ° C. to the boiling point of the solvent used in the reaction, preferably from 70 ° C. to 50 ° C.

The reaction time is generally 5 minutes to 7 days, preferably 10 minutes to 24 hours. The above reaction is preferably performed in the presence of a base. Examples of the base include sodium hydride, n-butyllithium, sodium methoxide, potassium tert-butoxide, sodium hydroxide, and lithium hydroxide. No. The amount of the base to be used is 1 mol to excess mol, preferably 1 to 5 mol, per 1 mol of the compound represented by the general formula [III-e].

Further, in this reaction, a crown ether such as 15-crown-5 may be added in order to promote the reaction smoothly.

After completion of the reaction, a usual treatment is performed to obtain a crude product of the compound represented by the general formula [IV-e]. The thus-obtained compound represented by the general formula [IV-e] is purified by a conventional method or without purification, if necessary, by removing the protecting group of the compound or removing a double bond. The compound of the general formula [I-111] can be produced by appropriately performing the reduction.

The method for removing the protecting group varies depending on the type of the protecting group and the stability of the target compound [I-1-1e]. For example, the method described in the literature [Protective Groups * Protective Groups in Organic Synthesis, TW Greene, see John Wiley & Sons (1981)] or a method analogous thereto, eg, solvolysis using an acid or base, For example, a method in which 0.01 mol to a large excess of an acid, preferably trifluoroacetic acid, formic acid, hydrochloric acid, or the like, or a method in which an equimolar to a large excess of a base, preferably a hydroxylic sphere, calcium hydroxide, or the like is allowed to act; This is carried out by chemical reduction using a catalyst or catalytic reduction using a palladium-carbon catalyst, Raney nickel catalyst or the like.

The reaction for reducing the double bond of the compound represented by the general formula [IV-e] is usually preferably carried out in an inert solvent by catalytic reduction using a palladium-carbon catalyst, a Raney-nickel catalyst, a platinum catalyst, or the like. .

Examples of the inert solvent include alcohols such as methanol, ethanol, and propanol, and acetic acid.

The reaction temperature is usually, - 20 ^e C~100 ° C, a room temperature preferably 0 ° Celsius to. The reaction time is generally 5 minutes to 7 days, preferably 10 minutes to 24 hours. In general, the hydrogen pressure in the catalytic reduction reaction is preferably from normal pressure to 5 atm. The amount of the catalyst used is usually 0.01 to lg, preferably 0.05 to lg of the raw material compound [IV-e] lg. ~ 0.2g.

Manufacturing method 7

General formula [V-e]

Wherein RR ² , R ^3P and T have the above-mentioned meanings, and a compound represented by the general formula [VI-e]

Ar ^p- (CH ₂ ) _n ― CHO [VI-e]

[Wherein Ar ^p and n have the same meanings as above], and a compound represented by the general formula [IV-e]

[Wherein, Ar ^p , n, R \ R ² and R ^3p have the same meaning as above], and if necessary, remove the protecting group or reduce the double bond. By the general formula [I—11 e]

[I-1-1 e]

Ar

[Wherein Ar, R ′, R ² , R ³ and Y ^e have the above-mentioned meanings].

In the production method 7, as in the production method 6, among the compounds of the present invention represented by the general formula [Ie], Y in the formula is an ethylene group, a trimethylene group, a vinylene group or a probenylene group. This is a method for producing a compound.

Production method 7 is equivalent to the reaction in which compound [II-e] and compound [III-e], which are the starting compounds of production method 6, are replaced with compound [V-e] and compound [VI-e], respectively. Therefore, all of the reaction methods and conditions can be carried out according to Production method 6.

Manufacturing method 8

General formula [VII-e]

[Wherein, Z represents a leaving group, and RR ² and R ^3P have the above-mentioned meanings] and a general formula [VIII-e] Ar ^p — W— H [VIII-e]

[Wherein W represents an oxygen atom or a sulfur atom, and Ar ^p has the above-mentioned meaning], and reacted with a compound represented by the general formula [IX-e]

Ar ^p -W- CH ₂

[Wherein, Ar ^p , R \ R ² , R ^3p and W have the above-mentioned meanings], and a protecting group is removed as necessary to obtain a compound represented by the general formula [Ι-2-e]

Ar one γΐ

[Wherein, means a group represented by the formula: 0—CH ₂ — or —S—CH ₂ —, and Ar, R \ R ² and R ³ have the same meaning as above]. Can be manufactured.

Production method 8 is a compound of the present invention represented by the general formula [I-e], wherein Y in the formula is a group represented by —0—CH ₂ — or —S—CH ₂ —, And a method for producing a compound represented by the general formula [I1-2-e].

Examples of the leaving group represented by Z include a halogen atom such as a chlorine atom, a bromine atom or an iodine atom, or an organic sulfo group such as a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, and a p-toluenesulfonyloxy group. And a carbonyl group.

The reaction between the compound represented by the general formula [VII-e] and the compound represented by the general formula [VIII-e] is performed by equimolarly dissolving both the compound [VII-e] and the compound [VIII-e]. It is usually carried out in an inert solvent which does not adversely affect the reaction, using either one in a small molar excess. In addition, this reaction can be performed in the presence of a base to facilitate the reaction.

Examples of the inert solvent include tetrahydrofuran and dioxane. Ethers, for example, halogenated hydrocarbons such as methylene chloride and chloroform, aromatic hydrocarbons such as benzene and toluene, and non-protons such as dimethylformamide, N, N-dimethylacetamide, and acetonitrile A polar solvent is preferred.

Examples of the base include inorganic bases such as sodium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, carbonated lime, sodium bicarbonate and the like, and pyridine, 4-dimethylaminopyridine, triethylamine, diisopyrupyramine and the like. An organic base is preferable, and the base is usually used in an equimolar amount or an excess amount, preferably 1 to 5 mol, relative to compound [VII-e] or compound [VIII-e].

The reaction temperature is usually from —70 to 100 ° C., preferably from −20 to 50. The reaction time is generally 5 minutes to 7 days, preferably 1 to 24 hours.

After the completion of the reaction, if a protecting group is present in the product, after removing the protecting group, or if the product does not have a protecting group, the normal treatment is carried out, and the general formula [I-2-e] Compounds can be prepared.

For the removal of the protecting group and post-treatment, the method described in the above-mentioned Production Method 6 can be applied as it is.

Manufacturing method 9

General formula [X-e]

P ¹

Wherein P ¹ is a hydrogen atom, a lower alkanoyl group, a trifluoroacetyl group or a lower alkoxycarbonyl group; P ² is a hydrogen atom or an amino group-protecting group; Y ^p is an ethylene group, a trimethylene group , A vinylene group, a propenylene group or a group represented by —0—CH ₂ one, one S—CH ₂ — or one CH ₂ — NP ² —, and Ar ^p , R ^1, and R ² are as defined above. And a compound represented by the general formula [XI-e] R ^a -Z [XI-e]

[Wherein, ^Ra represents a lower alkyl group, and Z has the above-mentioned meaning] with a compound represented by the general formula [XII-e]

Ar ^p -Y ^p

[Wherein, Ar ^p , R, R ² , R ^a and Y ^p have the above-mentioned meaning], and a protecting group is removed as necessary to obtain a compound represented by the general formula [I-13 — E]

[I one 3— e]

Ar-Y

Wherein Ar, R ′, R ² , ^Ra and Y have the above-mentioned meanings].

In the production method 9, a compound of the present invention represented by the general formula [I-e], wherein is a lower alkylamino group, that is, a compound represented by the general formula [I-3-e] It is a manufacturing method of.

In the reaction of the compound represented by the general formula [X-e] with the compound represented by the general formula [XI-e], both the compound [X-e] and the compound [XI-e] are equimolar or both. It is usually carried out in an inert solvent which does not adversely affect the reaction, using either one or a small molar excess.

Preferred examples of the inert solvent include ethers such as tetrahydrofuran and dioxane, and aprotic polar solvents such as dimethylformamide, N, N-dimethylacetamide and acetonitrile.

Further, the above reaction is preferably performed in the presence of a base, and as the base, for example, a strong base such as sodium hydride or lithium diisopropylamide is preferable. New

The amount of the base to be used is generally 1 mol to excess mol, preferably 1 to 2 mol, per 1 mol of compound represented by general formula CX-e].

The reaction temperature is generally between 78 ° C and 100 ° C, preferably between 0 ° C and 70 ° C. The reaction time is generally 5 minutes to 7 days, preferably 30 minutes to 24 hours. After completion of the reaction, if a protecting group is present in the product, after removing the protecting group, or if no protecting group is present in the product, the usual treatment is carried out without any treatment.

[I-13—e] can be produced.

When P ′ is a lower alkenyl group, a trifluoroacetyl group or a lower alkoxycarbonyl group, these can be treated according to the protecting group for an amino group.

Manufacturing method 10

General formula [XIII e]

P ¹

[Wherein, R ^3a represents a lower alkyl group, and P \ R ¹ and R ² have the above-mentioned meanings] and a general formula [XIV-e]

[Wherein Ar ^p and Z have the same meanings as above], and a compound represented by the general formula [XV-e]

[Wherein, Ar ^p , PR \ R ² and R ^3a have the same meaning as above], and a protecting group is removed as necessary to obtain a compound represented by the general formula [I-4-1e]

Ar— CH ₂ [I— 41-e]

[Wherein, Ar, R ² and R ^3a have the above-mentioned meanings].

In the production method 10, a compound of the present invention represented by the general formula [I-e], wherein is a lower alkyl group and Y is a group represented by —CH ₂ —NH— That is, it is a method for producing a compound represented by the general formula [I-4-1e].

The reaction between the compound represented by the general formula [XIII-e] and the compound represented by the general formula [XIV-e] is the same as that of the compound represented by the general formula [X-e] in the production method 9. The reaction can be carried out according to the reaction with the compound represented by the general formula [XI-e].

After the completion of the reaction, if a protecting group is present in the product, after removing the protecting group, or if no protecting group is present in the product, the usual treatment is carried out, and the general formula [I-4-e] Compounds can be prepared.

For the removal of the protecting group and post-treatment, the method described in the above-mentioned Production Method 6 is applied as it is.

Manufacturing method 11

General formula [XVI-e]

In the formula, Ar ^p , R, R ² and Y ^p have the above-mentioned meaning], and a compound represented by the general formula [XVII-e]

R ^b — Mg—X [XVII-e], wherein R ^b is a lower alkyl group; X represents a halogen atom] or a general formula [XVIII-e]

R ^b — Li [XVIII-e]

Wherein R ^b has the meaning described above, and a compound represented by the general formula [XIX-e]

[Wherein, Ar ^p , RR ² , R ^b and Y ^p have the above-mentioned meanings]. Then, the hydroxyl group is reductively removed, and if necessary, the protecting group is removed. And the general formula [I-5-e]

[I one 5— e]

Ar-Y

In the formula, Ar, R \ R ² , R ^b and Y have the above-mentioned meanings].

Production method 11 is a compound of the present invention represented by the general formula [I-e], wherein is a group represented by one CH ₂ —R ^b , that is, a compound represented by the general formula [I-5-e] ] This is a method for producing a compound.

In the reaction of the compound represented by the general formula [XVI-e] with the compound represented by the general formula [XVII-e] or the general formula [XVIII-e], usually, both are equimolar or one of them is small. For excess moles, use L in an inert solvent that does not adversely affect the reaction.o

As the inert solvent, for example, ethers such as ethyl ether, tetrahydrofuran, and dioxane are preferable.

The reaction temperature is generally from 1 ° C. to the boiling point of the solvent used in the reaction, preferably from 70 ° C. to 50 ° C.

The reaction time is generally 5 minutes to 7 days, preferably 10 minutes to 24 hours. The removal of the hydroxyl group of compound [XIX-e] can be performed, for example, by reacting methanesulfonyl chloride on compound [XIX-e] in an inert solvent such as ethyl acetate in the presence of a base such as triethylamine to give a corresponding mesylate. Thereafter, the reaction can be carried out by allowing a reducing agent such as lithium aluminum hydride to act in an inert solvent such as tetrahydrofuran.

After the completion of the reaction, if a protecting group is present in the product, after removing the protecting group, or in the case where the protecting group is not present in the product, the usual treatment is carried out, and the general formula [I-5-e] Compounds can be prepared.

For the removal of the protecting group and post-treatment, the method described in the above-mentioned Production Method 6 can be directly applied.

Manufacturing method 12

General formula [XX-e]

[XX-e]

(0 ₂ N) _q- Ar ^ap -Y ^p , R ^3p

[Wherein, Ατ ^ is a halogen atom, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a di-lower alkylamino group, a lower alkanol group and an aryl group, and may be protected. An aryl group which may have a substituent selected from the group consisting of an amino group and a lower alkylamino group; Q represents 1 or 2, and RR ² , R ^3P and Y ^p have the above-mentioned meaning. The nitro group of the compound represented by the formula By removing, the general formula [I-1 6—e]

[Wherein, Ar ³ comprises a halogen atom, an amino group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, a lower alkanol group, and an aryl group. Represents an aryl group or a heteroaromatic ring group which may have a substituent selected from the group, and q, RR ² , R ³ and Y have the above-mentioned meanings] Compounds can be produced.

Production method 12 is a compound of the present invention represented by the general formula [I-e], wherein Ar in the formula has at least one amino group as a substituent, that is, a compound of the general formula [I-e] This is a method for producing the compound represented by the formula:

The reduction of the nitro group of the compound [XX-e] can be performed, for example, by reacting iron powder and ammonium chloride in a solvent such as aqueous methanol, aqueous ethanol, or aqueous dioxane.

The reaction temperature is usually from room temperature to the boiling point of the solvent used in the reaction, preferably from 50 ° C to the boiling point of the solvent used in the reaction.

The reaction time is generally 10 minutes to 24 hours, preferably 30 minutes to 8 hours. After completion of the reaction, if a protecting group is present in the product, after removing the protecting group, or in the case where the protecting group is not present in the product, the ordinary treatment is carried out as it is. ] Can be produced.

The general formulas [I-e], [I-l-e], [I-l2-e], [I-3-e], [I-4-e], [I-l-e] obtained by the above method 5—e] or [I—6—e] compounds can be isolated, for example, by column chromatography using silica gel or an adsorption resin, or by liquid chromatography. This can be achieved by using conventional separation means such as oral chromatography, solvent extraction or recrystallization / reprecipitation alone or in an appropriate combination.

General formulas [I-e], [I-i-e], [I-i-e], [I-i-e], [I-i-e], [I-5-e], or [I The compound 6-e] can be converted into a pharmaceutically acceptable salt by a conventional method, and conversely, the conversion of a salt to a free compound can be performed according to a conventional method.

General formulas [Π-e], [III-e], [V-e], [VI-e], [VII-e], [VIII-e], [X-e], [XI-e], The compound represented by [XIII-e], [XIV-e], [XVI-e], [XVII-e], [XVIII-e] or [XX-e] may be, for example, a commercially available product or a known product. It can be produced by a method, a method equivalent thereto, a method described in Production Examples, or the like.

The compound represented by the general formula [If] can be produced, for example, by the following production method 13, 14, or 15 or a method shown in Production Examples.

Manufacturing method 13

General formula [II-f]

[Wherein RR \ X and Y have the above-mentioned meaning], and a compound represented by the general formula “III-f 1

[Wherein, R ¹ and R ² have the above-mentioned meanings] by reacting with a compound represented by the general formula [I-1-f]

[Wherein, RR ² , R ⁷ , R ^e , X and Y have the above-mentioned meanings].

Production method 13 is a compound of the present invention represented by the general formula [If], wherein R ³ and

R ⁴ together form a single bond, and R ⁵ and R ⁶ together form a general formula [IV—f]

^Rl x ^R2 [IV-f]

[Wherein, R ¹ and R ² have the meanings described above], which are compounds represented by the general formula [I-1-f], which means a lower alkylidene group which may be interposed with an oxygen atom. This is a method for producing a compound.

The reaction between the compound represented by the general formula [II-f] and the compound represented by the general formula [III-f] is usually performed based on 1 mol of the compound represented by the general formula [Π-f]. The reaction is carried out using 1 to 5 mol, preferably 1.5 to 2.5 mol of the compound represented by the general formula [III-f].

The reaction is usually carried out in an inert solvent, and suitable examples of the inert solvent include water, acetic acid, methanol, ethanol, isopropanol and the like, or a mixed solvent thereof.

The above reaction is preferably carried out in the presence of an acidic or basic catalyst. Examples of the acidic catalyst include formic acid, acetic acid, phosphoric acid, hydrochloric acid, sulfuric acid, and paratoluenesulfonic acid. For example, sodium hydroxide, potassium hydroxide, piperidine, triethylamine and the like can be used. The reaction temperature is usually from room temperature to the boiling point of the solvent, preferably 60 ° C to 120 ° C. It is.

The reaction time is generally 10 minutes to 24 hours, preferably 30 minutes to 3 hours.

Manufacturing method 14

General formula [V-f]

[Wherein R ⁵ , R ⁶ , RRX and Y have the above-mentioned meanings] and a general formula [HI-f]

[Wherein, R ¹ and R ² have the same meanings as above], thereby obtaining a compound represented by the general formula [I1-2-f]

[I one 2— f]

[Wherein, R ′, R ² , R ⁵ , R ⁶ , RRX and Y have the above-mentioned meanings]. The production method 14 is a compound of the present invention represented by the general formula [I-f], in which R ³ and R ⁴ in the formula together represent a single bond, that is, a compound represented by the general formula [I-2-] f] is a method for producing the compound represented by the formula:

The reaction between the compound represented by the general formula [Vf] and the compound represented by the general formula [III-f] is usually performed based on 1 mol of the compound represented by the general formula [Vf]. The reaction is carried out using 0.5 to 3 mol, preferably 1 to 1.5 mol of the compound represented by the general formula [III-f].

The above reaction is preferably carried out in the presence of an acidic or basic catalyst. Examples of the acidic catalyst include formic acid, acetic acid, phosphoric acid, hydrochloric acid, sulfuric acid, and paratoluenesulfonic acid. For example, sodium hydroxide, potassium hydroxide, piperidine, triethylamine and the like can be used. The reaction temperature is usually from room temperature to the boiling point of the solvent, preferably from 60 ° C to 120 ° C.

The reaction time is usually 10 minutes to 24 hours, preferably 30 minutes to 3 hours

IH] Yes.

Manufacturing method 15

General formula [I— 2— f]

[Wherein, RR ² , R ⁵ , R ⁶ , RRX and Y have the above-mentioned meanings] by reacting a reducing agent with a compound represented by the general formula [I 1-3-f] [I-1 3— f]

[Wherein, R ′, R ² , R ⁵ , R ⁶ , RRX and Y have the above-mentioned meanings].

Production method 15 is a compound of the present invention represented by the general formula [I-f] in which R ³ and R ⁴ in the formula are both hydrogen atoms, that is, a compound represented by the general formula [I-3-f] This is the method for producing the compound.

Examples of the reducing agent used in the above reaction include diisobutylaluminum hydride.

The above reaction is carried out usually using 1 to 5 mol, preferably 1.5 to 3 mol, of a reducing agent per 1 mol of the compound represented by the general formula [I-2-f].

The reaction is usually performed in an inert solvent, and as the inert solvent, for example, ethyl ether, tetrahydrofuran, toluene, xylene and the like, or a mixed solvent thereof are suitable.

The reaction temperature is usually from −100 ° C. to room temperature, preferably from −80 ° C. to 0 ° C.

The compound represented by the general formula [If], [I1-1-f], [I1-2-f] or [Ι-3-f] can be easily isolated and purified by a usual separation means. Examples of such means include solvent extraction, recrystallization, column chromatography, preparative thin-layer chromatography, and the like.

These compounds can be converted into pharmaceutically acceptable salts by a conventional method. Conversely, the conversion of a salt to a free compound can be carried out according to a conventional method. As the compound represented by the general formula [Π-f], [III-f] or [Vf] used in the present invention, a commercially available product or a known method or a method analogous thereto can be used as appropriate. It can be manufactured by appropriately combining them.

The compounds represented by the general formulas [I-g], [I-h], [I-i], and [I-j] are described in International Publication Nos. W097 / 19682, WO97 / 20820, and WO97 /, respectively. No. 20821, WO97 / 20822, WO97 / 20823, etc., and can be produced and obtained by a method or a method analogous thereto.

The NPY Y5 receptor antagonist according to the present invention can be administered orally or parenterally, and when formulated into a form suitable for such administration, hypercholesterolemia, hyperlipidemia, It can be used as a therapeutic agent for arteriosclerosis. When clinically using the NPY Y5 receptor antagonist according to the present invention, it is possible to add a pharmaceutically acceptable additive to various dosage forms and then administer the same according to the dosage form. As the additives at this time, various additives commonly used in the field of pharmaceutical preparations can be used, for example, gelatin, lactose, sucrose, titanium oxide, starch, crystalline cellulose, hydroxypropylmethylcellulose, carboxymethylcellulose. , Corn starch, microcrystalline wax, white petrolatum, magnesium aluminate metasilicate, anhydrous calcium phosphate, citrate, trisodium citrate, hydroxypropyl cellulose, sorbitol, sorbitan fatty acid ester, polysorbate, sucrose fatty acid Esters, polyoxyethylene, hydrogenated castor oil, polyvinylpyrrolidone, magnesium stearate, light gay anhydride, talc, vegetable oil, benzyl alcohol, gum arabic, propylene glycol , Polyalkylene glycols, cyclodextrin or hydroxypropionic building consequent opening dextrin Bokuri emissions, and the like.

Dosage forms formulated as a mixture with these additives include, for example, solid preparations such as tablets, capsules, granules, powders and suppositories; and liquid preparations such as syrups, elixirs and injections, etc. These can be prepared according to a usual method in the pharmaceutical field. In the case of liquid preparations, they should be dissolved or suspended in water or other appropriate medium before use. Is also good. In particular, in the case of an injection, it may be dissolved or suspended in a physiological saline solution or a glucose solution as necessary, and a buffer or a preservative may be added.

These preparations can contain the NPY Y5 receptor antagonist of the present invention in a proportion of 1.0 to 100% by weight, preferably 1.0 to 60% by weight of the whole drug. These formulations may also contain other therapeutically effective compounds.

When the NPY Y5 receptor antagonist of the present invention is used, for example, in a clinical setting, the dosage and frequency of administration depend on the sex, age, body weight, degree of symptoms, and the type and range of the intended treatment effect of the patient. In general, in the case of oral administration, 0.1 to 100 mgZkg is divided into 1 to several times per adult, and in the case of parenteral administration, 0.001 to 10 mgZkg is divided into 1 to several times. Is preferred.

By using the NPY Y5 receptor antagonist of the present invention in combination with a cholesterol-lowering agent other than the NPY Y5 receptor antagonist, the cholesterol-lowering effect of the drug is additively and synergistically enhanced.

In the above combination, the NPY Y5 receptor antagonist and the cholesterol-lowering agent other than the NPY Y5 receptor antagonist may be administered simultaneously or separately. The composition can be administered after it is formulated as a composition.

A composition of an NPY Y5 receptor antagonist and a cholesterol-lowering agent other than the NPY Y5 receptor antagonist can be formulated in the same manner as when the NPY Y5 receptor antagonist is used alone as described above. The preparation may contain an NPY Y5 receptor antagonist and a cholesterol-lowering agent other than the NPY Y5 receptor antagonist as active ingredients in a proportion of 1.0 to 100% by weight, preferably 1.0 to 60% by weight of the whole drug. .

The weight ratio of the NPY Y5 receptor antagonist to the cholesterol-lowering agent other than the NPY Y5 receptor antagonist may be 0.001: 1 to 1000: 1, but especially the weight ratio is 0.01: 1 to 100: 1. It is preferred that

When a composition of an NPY Y5 receptor antagonist and a cholesterol-lowering agent other than the NPY Y5 receptor antagonist is used, for example, in a clinical setting, the dosage and frequency of administration depend on the sex, age, weight, and symptoms of the patient. Depending on the degree and the type and range of the intended treatment effect, etc., in general, for oral administration, 0.1 to 100 mgZkg per adult is divided into 1 to several doses, and for parenteral administration, 0.001 to 10 mgZkg. It is preferred to administer the kg in one or several divided doses.

As described above, according to the present invention, a therapeutic agent for hypercholesterolemia, hyperlipidemia and arterial sclerosis can be provided. Needless to say, a novel method for treating the disease using these agents is described. Can also be provided. Brief explanation of drawings

FIG. 1 is a graph showing the effect of continuous administration of the compound of Production Example 6 for 2 weeks on total cholesterol in blood of diet-induced obese C57BLZ6j mice.

FIG. 2 is a graph showing the effect of continuous administration of the compound of Production Example 6 for 2 weeks on blood HDL cholesterol of diet-induced obese C57BLZ6j mice.

FIG. 3 is a graph showing the effect of continuous administration of the compound of Production Example 6 for 2 weeks on blood non-HDL cholesterol in diet-induced obese C57BLZ6j mice. BEST MODE FOR CARRYING OUT THE INVENTION

The present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

Example 1

(Formulation Example 1)

97 parts of lactose was added to 3 parts of the compound of Production Example 6, and mixed well to produce 100-fold powder. A kneading solution prepared by adding purified water to 1 part of hydroxypropylcellulose was added to this powder, kneaded and granulated. After sieving through a 20-mesh sieve and drying, the mixture was sieved to a fixed particle size to obtain granules.

Example 2

(Formulation Example 2)

20 parts of lactose and 5 parts of corn starch were added to 2 parts of the compound of Production Example 6, and mixed well. The granules were dried and granulated with ethanol by a conventional method, and 0.5% of magnesium stearate was added to the granules. After mixing, the tablets were made into tablets each containing 10 mg of the compound of Production Example 6 by a conventional method.

Example 3

(Formulation Example 3) 97 parts of lactose was added to 2 parts of the compound of Production Example 6 and 1 part of simpastatin, and mixed well to produce 100-fold powder. A kneading solution prepared by adding purified water to 1 part of hydroxypropylcellulose was added to this powder, kneaded and granulated. After sieving through a 20-mesh sieve and drying, the mixture was sieved to a fixed particle size to obtain granules.

Example 4

(Formulation Example 4)

To 1 part of the compound of Production Example 6 and 1 part of simpastatin, 20 parts of lactose and 5 parts of corn starch were added and mixed well. After granulation, drying and sizing with ethanol by a conventional method, 0.5% of magnesium stearate was added thereto and mixed, and then a tablet containing 10 mg of the compound of Production Example 6 and simpastatin was obtained by a conventional method.

Example 5

(Pharmacological test example 1: NPY binding inhibition test)

The cDNA sequence encoding the human NPY Y5 receptor [see International Patent Application W096Z 16542] was cloned into the expression vectors pcDNA3, pRc / RSV (Invitrogen) and pCI-neo (Promega). The resulting expression vector was converted to a cationic lipid method [Proceedings of the national academy]. • Proceedings of the national academy Transformation into host cells COS-7, CHO and LM (tk—) (American 'type-culture-collection') using the Science of the United States of America, vol. 84, p. 7413 (1987)]. And NPY Y5 receptor expressing cells were obtained.

NPY Y5 membrane sample prepared from cells expressing the receptor with a test compound and 20 ^[125 1] OOOcpm Bae Putaido YY (flax manufactured one sham Co.), Atsuse I buffer (10 mM magnesium chloride, ImM After incubation in 25 mM Tris buffer (pH 7.4) containing phenylmethylsulfonyl fluoride, 0.1% bacitracin and 0.5% BSA at 25 ° C for 2 hours, the mixture was filtered through a glass filter GF / C. After washing with 50 mM Tris buffer containing 0.3% BSA, pH 7.4, the radioactivity on the glass filter was determined using a gamma counter. Non-specific binding was measured in the presence of 1 / M peptide YY and determined for specific peptide YY binding. The 50% inhibitory concentration (ICso value) of the test compound was determined [see Endocrinology, 131, 2090 (1992)]. As a result, IC ₅ of the compound of Production Example 6 was obtained. The value was 27 nM.

As shown above, the compounds of the present invention potently inhibited the binding of peptide YY (NPY and homologous substances) to the NPY Y5 receptor.

Example 6

(Pharmacological test example 2: Blood cholesterol lowering effect)

Male C57BL / 6j mice (21 weeks old at the start of the experiment) are individually bred in plastic cages in a breeding room at a temperature of 23 ± 2 ° C and a humidity of 55 ± 15% under a light / dark cycle of 12 hours / ^ 12 hours. , Solid feed (CE-2, manufactured by CLEA Japan) and water (tap water) were allowed to be ingested freely. Feeding · When the amount of water and body weight are stabilized, the group is divided into three groups consisting of 8 to 9 animals so that the measured values become uniform. Two groups are tasted (medium high-fat diet, oriental yeast) ), One group received a normal diet (CE-2). Table 1 shows a comparison of the composition of the preferred diet and the normal diet. The compound of Production Example 6 (30 mg Zkg) or the vehicle was orally administered once a day for 2 weeks before the start of palatability diet loading. The normal diet group received one dose of vehicle. The vehicle used was a 0.5% aqueous solution of methylcellulose, and the dose was 5 mlZkg. Drug or vehicle administration was given one hour before the start of the dark cycle. Table 1. Favorite food Ingredients and ingredients

Casein 18.2 Normal diet Preference diet Cornstarch 27.8 Protein 25.4 (29.2) 18.2 (15.0) Sucrose 27.8 Carbohydrate 50.3 (59.3) 55.6 (52.4) Cellulose 2.9 Lipid 4.4 (11.5) 15.5 (32.6) No. 4.2 Calorie (Kcal / g ) 3.42 4.41 corn oil 11.3 normal diet: CE - 2 Akirakasa ^_0/0 (heat%) minerals, vitamins, etc. 7.8

After 2 weeks of continuous exposure, animals are fasted overnight and blood is collected in heparinized syringes Was done. Blood was centrifuged (4 ° C, 3000 rpm, 10 minutes), and total cholesterol and HDL-cholesterol in plasma were measured. Total cholesterol is determined by the cholesterol esterase, cholesterol oxidase, and peroxidase methods, HDL cholesterol is calculated by the direct method, and non-HDL cholesterol is calculated by dividing HDL cholesterol from total cholesterol in each individual. I asked for it.

As shown in FIGS. 1 to 3, when C57BLZ6j mice were fed a normal diet or a palatable diet for 2 weeks, the total cholesterol, HDL cholesterol, and non-HDL cholesterol levels in plasma were significantly affected by the palatable diet. Increased. The compound of Production Example 6 suppressed an increase in non-HDL cholesterol due to ingestion of a preferred diet.

Production Example 1

Preparation of 5- (4-methoxyphenyl) -3- (4-phenylbiperazinyl) carbonylaminovirazole

(1) Production of 5- (4-methoxyphenyl) -3-phenoxycarbonylaminovirazole

To a solution of 3-amino-5- (4-methoxyphenyl) pyrazole (1.19 g) in pyridine (lOmL) was added fuunyl carbonate (0.87 mL), and the mixture was stirred at room temperature for 6 hours. The reaction solution was partitioned between ethyl acetate (50 mL) and water (30 mL), and the organic layer was washed with 1N hydrochloric acid (50 mL x 2), saturated aqueous sodium bicarbonate (50 mL) and saturated saline (50 mL), and dried over anhydrous magnesium sulfate. After drying, the solvent was distilled off. The residue was crystallized from ethyl acetate-hexane to give the title compound (0.95 g) as pale-yellow crystals (melting point: 286-291).

(2) Preparation of 5- (4-Methoxyphenyl) -3- (4-Phenylbiperazinyl) carbonylaminopyrazole

5-(4-Methoxyphenyl) A mixture of 1-3-phenoxycarbonylaminovillazone (93 mg), 1-phenylbiperazine (54 mg) and triethylamine (91 mg) in chloroform form (3 mL) The mixture was refluxed for 2 hours. After cooling, ethyl ether (3 mL) was added to the reaction solution, and the precipitated crystals were collected by filtration and dried to give the title compound (103 mg) as colorless crystals (melting point: 235-245 ° C). Production Example 2

Production of 3- (2-indanil) porponylamino 5- (4-methylpheninole) pyrazole

3-Amino-5- (4-methylphenyl) birazol (35mg) and indane-2-carboxylic acid (33mg) are dissolved in pyridine (2mL) and 1- (3-dimethylaminopropyl) -3 —Ethyl carposimid hydrochloride (58 mg) was added, and the mixture was stirred overnight at room temperature. The reaction solution was diluted with ethyl acetate (30 mL), washed with water (30 mL), saturated aqueous sodium bicarbonate (30 mL) and saturated saline (30 mL), dried over anhydrous magnesium sulfate, and the solvent was distilled off. . The crystalline residue was washed with ethyl ether to give the title compound (34 mg) as white crystals (melting point: 220-225 ° C).

Production Example 3

5- (4-Phenyl phenyl) 1-3- (1-phenylbiperidine-14-inole) force Production of luponylaminopyrazole

3-Amino-5- (4-chlorophenyl) pyrazole (23 mg) and 1-phenylbiperidine-1.4-force ribonate hydrochloride (28 mg) were dissolved in pyridine (5 mL), and 1- (3-dimethylamine) was dissolved. (Minopropyl) -13-ethylcarposimid hydrochloride (35 mg) was added and the mixture was stirred at room temperature overnight. The reaction solution was diluted with ethyl acetate (30 mL), washed with water (30 mL), saturated aqueous sodium bicarbonate (30 mL), and saturated saline (30 mL), dried over anhydrous magnesium sulfate, and the solvent was distilled off. did. The residue was crystallized from ethyl ether to give the title compound (20 _mg ) as white crystals (melting point: 209-21 C).

Production Example 4

Preparation of 5-phenyl-3- (3-phenylpropionyl) aminovirazole Dissolve 3-amino-5-phenylvirazole (160 mg) in pyridine (1 mL) and prepare 3-phenylpropionyl chloride ( 0.15 mL), and the mixture was stirred at room temperature for 14 hours and at 50 ° C for 30 minutes. Dilute the reaction solution with ethyl acetate (15 mL), wash with water (15 mL), 10% citric acid (15 mL), aqueous IN sodium hydroxide solution (15 mL) and saturated saline (15 mL), and wash with anhydrous sodium sulfate. And dried. The solvent was distilled off under reduced pressure, and the residue was crystallized from ethanol to give the title compound (139 _mg ). Was obtained as white crystals (melting point: 168-170 ° C).

Production Example 5

(E) Preparation of 1,2-methyl-6- [2- (1-naphthyl) vinyl 1-41-pyrrolidino pyridine

(1) Preparation of 2-ethoxycarboxy 6-methyl-4-pyrrolidinopyridine 2-Thyoxycarbonyl-6-hydroxymethyl-4-pyrrolidinopyridine (24.3 g) was added to a solution of thionyl chloride (8.5 mL) in chloroform (300 mL). mL) was added dropwise under ice-cooling, and the mixture was stirred at 0 ° C for 1 hour. Ice and a 1N aqueous solution of sodium hydroxide were added to the reaction solution to make the solution more viscous, and the mixture was extracted with chloroform. The port-form layer was washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, and then the solvent was distilled off to obtain a crude chloride. To a solution of the crude chloride in methanol (250 mL) was added 10% palladium-carbon (1.3 g), and the mixture was stirred under a hydrogen atmosphere at room temperature for 3 hours. The catalyst was removed by filtration from the reaction solution, and the filtrate was concentrated. To the obtained residue was added a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with chloroform. The port-form layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was evaporated to give the title compound (22.7 g) as a pale-yellow oil.

Ή-NMR (CDCls) δ: 1.43 (3H, t, J = 7.2Hz), 2.01-2.05 (4H, m), 2.52 (3H, s), 3.33-3.96 (4H, m), 4.44 (2H, q , J = 7.2Hz), 6.35 (1H, d, J = 2.3Hz), 7.12 (1H, d, J = 2.3Hz).

(2) Preparation of 2-hydroxymethyl-6-methyl-1-pyrrolidinopyridine

2-Ethoxycarbonyl 6-Hydroxymethyl-4-pyrrolidinopyridine (21.5 g) in tetrahydrofuran (250 mL) under ice-cooling, slowly add aluminum lithium hydride (2.62 g) to 0 ° C. And stirred for 9 hours. Sodium sulfate decahydrate (26.2 g) was slowly added to the reaction solution, and the mixture was stirred at room temperature for 12 hours. Insolubles were removed by filtration from the reaction solution, and the filtrate was dried over anhydrous magnesium sulfate. The solvent was distilled off to obtain a solid. The obtained solid was washed with cooled ethyl acetate to give the title compound (8.8 g) as a colorless solid.

Ή-NMR (CDsOD) δ: 2.00-2.05 (4H, m), 2.34 (3H, s), 3.30-3.35 (4H, m), 4.51 (2H, s), 6.23 (1H, d, J = 2.3Hz), 6.49 (1H, d, J = 2.3Hz). (3) Production of 2-forminole 6-methyl-1-pyrrolidinoviridine

Activated manganese dioxide (475 mg) was added to a solution of 2-hydroxymethyl-1-6-methyl-4-pyrrolidinopyridine (237 mg) in methanol (5 mL), and the mixture was stirred at room temperature.

Stir for 3 days. The reaction mixture was filtered through celite, and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography (hexane-acetone) to give the title compound (78 mg) as a colorless oil.

Ή-NMR (CDC1 ₃ ) δ: 2.03-2.12 (4Η, m), 2.56 (3H, s), 3.35-3.

42 (4H, m), 6.42 (1H, d, J = 2.3Hz), 6.94 (1H, d, J = 2.3Hz), 9.98 (1H, s).

(4) (E) Production of 2-methyl-6- [2- (1-naphthyl) vinyl] 1-p-pyrrolidinopyridine

To a solution of getyl (1-naphthylmethyl) phosphonate (197 mg) in tetrahydrofuran (3 mL) was added, under ice-cooling, 60% sodium hydride-oil (35 _mg ) and 15-one crown-5 (0.02 mL). The mixture was stirred at room temperature for 30 minutes. To this mixed solution was added a solution of 2-formyl-6-methyl-4-pyrrolidinopyridine (112 mg) in tetrahydrofuran (2 mL), and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography (ethyl hexane monoacetate) to give the title compound (96 mg) as a colorless oil.

Ή Ichikaku _{R (CDC1 3) δ: 2.01} - 2.05 (4Η, m), 2.52 (3H, s), 3.34- 3. 38 (4H, m), 6.25 (1H, d, J = 2.2Hz), 6.44 (1H, d, J = 2.2Hz), 7.14 (1H, d, J = 15.6Hz), 7.45-7.54 (3H, m), 7.78-7.87 (3H, m), 8.31-8.37 (1H, m), 8.34 (1H, d, J = 15.6Hz).

Production Example 6

3,3-Dimethyl-91 (4,4-dimethyl-2,6-dioxocyclohexyl) 1-l-oxo-l 1,2,3,4-tetrahydroxanthene (compound of formula [I-f-l]) Mutant)

Salicylaldehyde (1.83 g) and dimedone (4.21 g) were suspended in acetic acid (22.5 ml) and water (30 ml) and stirred at 100 ° C. for 1.5 hours. Bring the reaction mixture to room temperature Allow to cool and filter the precipitated solid to give the title compound as a colorless powder.

5.06 g was obtained.

Melting point 210-212. C

Ή— NMR (CDCla) δ: 0.99 (3H, s), 0.99 (3H, s), 1.03 (3H, s), 1.12 (3H, s), 1.92 (IH, d, J = 16.5 Hz), 2.00 (IH, d, J = 16.5 Hz), 2.33 (2H, s), 2.37 (2H, s), 2.47 (1H, d, J = 17.7 Hz), 2.60 (1H, d, J = 17.7 Hz), 4.67 (IH, s), 7.00-7.04 (3H, m), 7.13-7.19 (IH, m), 10.47 (IH, brs). Production Example 7

9- (2-Hydroxy-4,4-dimethyl-6-oxo-1-1-cyclohexenol) -1-6-methoxy-1,3,3-dimethyl-1,2,3,4,9-tetrahydro-1H-xanthen-11 On manufacture

2-Hydroxy-4-methoxybenzaldehyde (500 mg) and dimedone (921 mg) were suspended in acetic acid (3.3 ml) and water (6.6 ml) and stirred at 100 ° C for 1 hour. The reaction mixture was allowed to cool to room temperature, water was added, and the precipitated solid was collected by filtration and dried to give the title compound (1.05 g) as a colorless powder.

Melting point 196-198 ° C

Ή Single stroke R (CDCla) δ: 0.98 (3Η, s), 0.99 (3H, s), 1.02 (3H, s), 1.12 (3H, s), 1.92 (IH, d, J = 16.0Hz) , 1.99 (IH, d, J = 16.0 Hz), 2.33 (2H, s), 2.34 (1H, d, J = 16.5 Hz), 2.40 (IH, d, J = 16.5 Hz), 2.46 (IH, d, J = 17.5Hz), 2.59 (IH, d, J = 17.5Hz), 3.77 (3H, s), 4.61 (1H, s), 6.56-6.62 (2H, m), 6.89 (1H, m), 10.41 ( IH, brs). Industrial availability

The NPY Y5 receptor antagonist according to the present invention is useful as a therapeutic agent for hypercholesterolemia, hyperlipidemia and arteriosclerosis.

Claims

(1) A therapeutic agent for hypercholesterolemia, hyperlipidemia and arteriosclerosis, comprising a neuropeptide Y Y5 receptor antagonist as an active ingredient.

Two i

(2) Neuropeptide Y Y Blue 5 receptor antagonist has the general formula [I-a]

Of CI-a]

Wherein Α represents a nitrogen atom or a group represented by C—R ⁵ ; Ar ¹ has a substituent selected from the group consisting of a halogen atom, a lower alkyl group, and a lower or lower alkyl group. Ar ² represents a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group and an aryl group. An aryl group or a heteroaromatic ring group which may have a substituent selected from the group consisting of: R ¹ is a hydrogen atom or a lower alkyl group or a bond connected to R ⁵ ; R ² is a hydrogen atom; R ³ and R ⁴ may be the same or different and are each a hydrogen atom or a lower alkyl group, or a carbon which may have a lower alkyl group by linking both R ³ and R ⁴ to each other; Number 2 or 4 Archi The emissions group; R ⁵ is a hydrogen atom, hydroxyl group, and salts thereof represented by lower alkyl or lower alkoxy group or linked to R ¹ means a bond,

General formula [I-b]

[I-I b]

In the formula, ring A and ring B are ortho-fused with each other, ring A is an aromatic carbon or heterocyclic ring; ring B is a 4- to 7-membered aliphatic carbon or nitrogen-containing heterocyclic ring, and the nitrogen atom is A ring that can be present only at the site of condensation with ring A; Ar is a halogen atom, Even if it has a substituent selected from the group consisting of a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, and an aromatic carbocyclic group R is selected from the group consisting of a halogen atom, a nitro group, a lower alkyl group, a lower alkoxy group, an aromatic carbocyclic group and a carbonyl group having an aromatic carbocyclic group. Means a substituent or a hydrogen atom (however,

The group represented by the formula

In the case of a group represented by the formula, Ar does not mean a phenyl group or a 4-chlorophenyl group)), a compound represented by the formula:

General formula CI-1 c]

Wherein Ar ¹ is an aryl group which may have a substituent selected from the group consisting of a halogen atom, a lower alkyl group and a halo-lower alkyl group; Ar ² is a halogen atom, a lower alkyl group, It may have a substituent selected from the group consisting of lower alkenyl, halo-lower alkyl, lower alkoxy, lower alkylthio, lower alkylamino, di-lower alkylamino and aryl. R ¹ and R ² are the same or different and are a hydrogen atom or a lower alkyl group; R ³ and R ⁴ are the same or different and are a hydrogen atom or a lower alkyl group, or R ³ and and both R ⁴ are connected to each other, it has a lower alkyl group, an alkylene group having 2 -C 4; R ⁵ represents a hydrogen atom, a lower alkyl group or a lower alkoxy group] Compounds represented and its salts, -General formula [I-I d]

[Wherein, Ar ¹ is a group consisting of a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, an acyl group and an aryl group. An aryl group or a heteroaromatic ring group which may have a substituent selected from the group consisting of Ar ² , a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkoxy group; An alkylthio group, a lower alkylamino group, a di-lower alkylamino group and a substituent selected from the group consisting of an aryl group, which may have an aryl group or a heteroaromatic ring group; R ¹ and R ² are the same or different and each represent a hydrogen atom or a lower alkyl group] and a salt thereof;

General formula [I-e]

Wherein Ar is a halogen atom, a nitro group, an amino group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, a lower alkanol group, and an aryl group An aryl group or a heteroaromatic group which may have a substituent selected from the group; R ¹ and R ² are the same or different, and a lower alkyl group or both R ¹ and R ² are linked to each other; R ³ represents an amino group, a lower alkyl group or a lower alkylamino group; Y represents an ethylene group, a trimethylene group, a vinylene group, a propenylene group, which may be via an oxygen atom or a sulfur atom; Or a group represented by 0—CH ₂ —, —S—CH ₂ — or —CH ₂ —NH—] and a salt thereof, -General formula [I-f]

In K, R ¹ represents a hydrogen atom or a lower alkyl group or a lower alkylene group which may be intervened with R ² to intervene with an oxygen atom; does R ² represent a lower alkyl group? or has the meaning together such connexion the the R ^1; R ³ and R ⁴ is a hydrogen atom simultaneously, or both means together such connexion single bond; and R ⁶ are simultaneously hydrogen R ⁷ and R ⁸ independently represent a hydrogen atom, a halogen atom, a nitro group, a hydroxyl group, a lower alkyl group or a lower alkylidene group which may mean an atom or may be joined together and an oxygen atom may be interposed. An alkyl group, a lower alkoxy group, an aryl group, an aralkyloxy group, a di-lower alkylamino group, a lower alkoxycarbonylamino group or an arylcarbonylamino group, or a lower alkylene group Or a benzene ring ortho-condensed with an adjacent ring; X represents an oxygen atom or a sulfur atom; Y represents a methine group or a nitrogen atom] (where 9-(2 —Hydroxy-1,4-dimethyl-1-6-oxo-1-cyclohexene-1-yl) -5-methoxy-1,3,3-dimethyl-2,3,4,9-tetrahydro-1H—xanthenoneone and 9 1- (2-hydroxy-4-methyl-6-oxo-1-cyclohexene-1-yl) -13-methyl-2,3,4,9-tetrahydro-1H-xanthen-1-one and its salts,

General formula [I-g] 0

Ar S— NH— L— K ■ W [i-g]

O

B is 1 or 2; j is an integer of 0 to 3; K is —CH ₂ —NR ⁸ —CHR ⁵ — (CH ₂ ) j—, —CH ₂ —NR ⁸ —CO— A group represented by (CH ₂ ) j— or one CH ₂ —NH—CO—NH— (CH ₂ ) j—; L is a pentamethylene group, a heptamethylene group or a formula

— (CH ₂ )-^>. "'" H (CH ₂ )-; p is an integer of 0 to 2; Q is nitrogen atom, oxygen atom, sulfur atom or one NR ⁷ — or one C (R ⁴⁾ ₂ - a group represented by; R ', R ² and R ³ are independently hydrogen atom, a halogen atom, a nitro group, a hydroxyl group, a lower alkoxy group, a hydroxy-lower alkyl group, a halo-lower alkyl group Or a group represented by N (R ⁴ ) ₂ ; R ⁴ is independently a lower alkyl group; R ⁵ is independently a hydrogen atom, a hydroxymethyl group or a lower alkoxymethyl group; R ⁶ is a hydrogen atom Atom, halogen atom, nitro group, hydroxyl group, oxo group, lower alkyl group, lower alkoxy group, hydroxy lower alkyl group, methoxy lower alkyl group, halo lower alkyl group or one N (R ⁴ ) ₂ , one NHCOR ⁴ , -N (COR ⁴ ) ₂ , — NHC0 ₂ R ⁴ ,-NHCONHR \ ― NHS〇 ₂ R ⁴ ,-N (S0 ₂ R ⁴ ) ₂ , —C0 ₂ R ⁴ , a group represented by CON (R ⁴ ) ₂ or —S0 ₂ N (R ⁴ ) ₂ ; R ⁷ is independently a hydrogen atom or a lower alkyl group; R ⁸ is Independently, a hydrogen atom or a lower alkyl group; V is a nitrogen atom, an oxygen atom, a sulfur atom or a group represented by —NR ⁴ —;

A compound represented by the formula:

General formula [I-h]

[Wherein alk represents a single bond or a lower alkylene group; n represents 0 or 1; R ¹ represents (i) a hydrogen atom, a halogen atom, a nitro group, a cyano group, a lower alkyl group, a lower alkenyl group; A lower alkynyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group, a halogen atom, a hydroxyl group, a lower alkoxy group, an amino group, a substituted amino group, a hydroxyl group, A lower alkoxycarbonyl group, (aryl or heteroaryl) a lower alkyl group substituted by a lower alkoxycarbonyl group, a rubamoyl group or an N-substituted rubamoyl group; (ii) an amino group or a substituted amino group; (Iii) hydroxyl group, lower alkoxy group, lower alkenyloxy group, lower alkynyloxy group, hydroxy A lower alkoxy group, a lower alkoxy lower grade alkoxy group, (Ariru or Heteroariru) lower alkoxy groups, lower grade alkoxycarbonyl O alkoxy group, (§ Li one Norre or Heteroari one Honoré) lower An alkoxycarbonyloxy group, an aminocarbonyloxy group or an N-substituted aminocarbonyloxy group; (iv) a carboxy group, a lower alkoxycarbonyl group, a lower alkoxylower alkoxycarbonyl group or (aryl or heteroaryl) a lower alkoxycarbonyl group; a (V) force Rubamoiru group or N- substituted Kanorebamoinore group; (vi) - CH (OH ) one R, - CO- R, one ^{NR 01 - CO - 0 - R} , one NR ⁰¹ - CO - R, one ^{^{NR 01 - CO - NR 01 -}} R, one ^{_{NR 01 - S0 2 - R,}} - NR 01 - S0 2 - NR 01 - R, - S0 2 - R, - S0 2 - NR 01 - R Or — SOz— NR ⁰¹ — a group represented by CO—R, wherein R and 1 have the meanings described below, or a group represented by —N (R) (R ⁰¹ ) is a dialkyl group represented by a lower alkylene group. Means a substituted amino group {the lower alkylene group is an oxygen atom Or (vii)-X ¹ (X may be via a group represented by S (0) „or NR °, and may be condensed with a benzene ring at two adjacent carbon atoms). ² ) a group represented by (X ³ ); wherein (a) when X ¹ is a group represented by —CH—, X ² and X ³ are taken together to form —X ⁴ — (CO _{) p - (CH 2) -} ., - (CH 2) q - X 4 - (CO) p - (CH 2) r - or _{_{- (CH 2) S - X}} 4 - CO - (CH 2) t - Or (b) when X ¹ is a nitrogen atom, X ² and X ³ together represent a group represented by —CO— (CH ₂ ) _U— , wherein X ⁴ is A group represented by one CH ₂ — or one N (R ⁰¹ ) — or an oxygen atom; o is an integer of 3 to 5; p is 0 or 1; q is 1 or 2; the; s is 1 or 2; t is 1 or 2; u is 3 to an integer of 5 (provided that when p force 0, X ⁴ is - CH ₂ - in just Table That does not mean group)]; R ² and R ³ independently of one another, (i) a hydrogen atom, lower alkyl group, lower alkenyl group, lower alkynyl group, Ariru group, hetero Ariru group or (Ariru or Heteroariru) Or (ii) a halogen atom, a hydroxyl group, a lower alkoxy group, a hydroxy lower alkoxy group, a lower alkoxy lower alkoxy group, an amino group, a substituted amino group, a carboxy group, a lower alkoxycarbonyl group, a lower alkoxy lower group; A substituent selected from the group consisting of an alkoxycarbonyl group, an aryloxy or heteroaryl) lower alkoxycarbonyl group, a rubamoyl group, an N-substituting rubamoyl group, and a group represented by one S (0) _n -R or means a lower alkyl group substituted by a; R ² and R ³ are such together connexion Means lower alkylene group {said low Grade alkylene group represents an oxygen atom or S (0) may also be via a group represented by _n or NR ^G, also have good even if condensed with the benzene ring in two adjacent carbon atoms}; X is a nitrogen atom Or a methine group; in the above definitions, all the aromatic ring moieties and benzo ring A are each unsubstituted or selected from the group consisting of (i) to (vi) shown below. (I) a halogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, an aryl group, a heteroaryl group, a lower alkoxy group, a lower alkenyl group. Oxy group, lower alkynyloxy group, hydroxyl group, lower alkanoyloxy group, (aryl or heteroaryl) lower alkanoyloxy group, lower alkanoyl group, (aryl or Is a heteroaryl) lower alkanol group, (aryl or heteroaryl) carbonyl group, nitro group, cyano group; (H) halogen atom, hydroxyl group, lower alkoxy group, (aryl or heteroaryl) oxy group, Aryl group, heteroaryl group, amino group, substituted amino group, carboxy group, lower alkoxycarbonyl group, lower alkoxy lower alkoxycarbonyl group, lower alkoxycarbonyl group (aryl or heteroaryl), lower alkoxycarbonyl group, carbamoyl group or N-substituted (Iii) a halogen atom, a hydroxyl group, a lower alkoxy group, an (aryl or heteroaryl) oxy group, an aryl group, a heteroaryl group, an amino group, a substituted amino group, and a carboxy group. , Low An alkoxycarbonyl group, a lower alkoxy lower alkoxycarbonyl group, (aryl or heteroaryl) a lower alkoxycarbonyl group, a lower alkoxy group substituted by a carbamoyl group or an N-substituted canolebamoinole group; (iv (V) carboxy group, lower alkoxycarbonyl group, lower alkoxy lower alkoxycarbonyl group, (aryl or heteroaryl) lower alkoxycarbonyl group; (vi) carbamoyl group and N-substituted rubamoyl group; substituted amino group, substituted amino group of N-substituted rubamoyl group and N-substituted aminocarbonyloxy group include (i) lower alkyl group, aryl group and heteroaryl group. Group or (aryl or heteroaryl) (Ii) disubstituted by a lower alkylene group. May be via an oxygen atom or a group represented by S (0) _n or NR °, and may be condensed with a benzene ring at two adjacent carbon atoms}; or (iii) one CO— (0) v means monosubstituted or disubstituted independently of one another by a group represented by R; V means 0 or 1; n means 0, 1 or 2; Is a hydrogen atom, lower alkyl group, lower alkenyl group, lower alkynyl group, aryl group, heteroaryl group, (aryl or heteroaryl) lower alkyl group, lower alkanoyl group, or Heteroariru) carbonylation Le group or single S0 ₂ - or means a group represented by R, or a halogen atom, means a substituted lower alkyl group with water acid group or lower alkoxy group; 1 is a hydrogen atom or a lower R represents a hydrogen atom, a lower alkyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group, or substituted by a halogen atom, a hydroxyl group or a lower alkoxy group; A lower alkyl group] and a salt thereof,

[Wherein, alk ¹ and alk ² independently represent a single bond or a lower alkylene group; R ¹ represents a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group; R ² represents an alkyl group, a lower alkoxy lower alkyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group; R ² represents (i) a hydrogen atom, a halogen atom, a nitro group, A cyano group, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group, or a halogen atom, a hydroxyl group, a lower alkoxy group, an amino group, Amino group, carboxy group, lower alkoxycarbonyl group, aryl or heteroaryl One Norre) a lower alkoxycarbonyl group, Karubamo (Ii) an amino group or a substituted amino group; (iii) a hydroxyl group, a lower alkoxy group, a lower alkenyloxy group, a lower alkynyl. Alkoxy group, hydroxy lower alkoxy group, lower alkoxy lower alkoxy group, (aryl or heteroaryl) lower alkoxy group, lower alkoxycarbonyloxy group, (aryl or heteroaryl) lower alkoxycarbonyloxy group, (Iv) a carboxy group, a lower alkoxycarbonyl group, a lower alkoxy lower alkoxycarbonyl group or a (aryl or heteroaryl) lower alkoxycarbonyl group; (V) Lubamoyl group Or N-substituting rubamoyl group; (vi) -CH (OH) -R, -CO-R, one NR ¹ -CO-0-R, -NR ¹ -CO-R, -NR ¹ -CO-NR ¹ — R, — NR ¹ — S0 ₂ — R,-NR ¹ -S0 ₂ -NR ¹ -R, one S0 ₂ -R, — S0 ₂ — NR ¹ -R or one SO ₂ — NR ¹ -CO one R Wherein R has the meaning given below, and R ¹ has the meaning given above, or the group represented by N (R) (R ¹ ) is disubstituted by a lower alkylene group A lower alkylene group may be an oxygen atom or a group represented by S (0) _n or NR °, and may be fused to a benzene ring at two adjacent carbon atoms. Or a group represented by (vii) -X ¹ (X ² ) (X ³ ); wherein (a) when X ¹ is a group represented by —CH—, X ² and X ³ are joined together: —X ⁴ — (CO) _P— (CH ₂ ). - one _{_{^{(CH 2) q - X 4}}} - (CO) p - (CH 2) r - or single _{_{^{(CH 2) S - X 4}}} - CO - (CH 2) t - a group represented by; or ( b) When X ¹ is a nitrogen atom, X ² and X ³ are taken together to represent a group represented by —CO— (CH ₂ ) _U— , wherein X ⁴ is —CH ₂ — or —N (R ¹ ) a group or oxygen atom represented by 1; 0 is an integer of 3 to 5; p is 0 or 1; q is 1 or 2; r is 1; s is 1 or 2; Represents 1 or 2; u represents an integer of 3 to 5 (however, when p is 0, X ⁴ does not represent a group represented by one CH _2- )]; R ³ and R ⁴ represent Independently of one another, (i) a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group; or (ii) a halogen atom, a hydroxyl group , Lower alkoxy group, hydro Shi lower alkoxy group, a lower alkoxy Lower alkoxy group, amino group, substituted amino group, carboxy group, lower alkoxycarbonyl group, lower alkoxy lower alkoxycarbonyl group, (aryl or heteroaryl) lower alkoxycarbonyl group, alkamoyl group, N-substituting power A lower alkyl group substituted by a substituent selected from the group consisting of a rubamoyl group and a group represented by —S (0) _n —R; R ³ and R ⁴ together form a lower alkylene group; {The lower alkylene group may be via an oxygen atom or a group represented by S (0)} or NR, or may be condensed with a benzene ring at two adjacent carbon atoms} X is a single bond, 1,2-ethenylene group, 1,2-ethynylene group, oxygen atom, carbonyl group, group represented by -S (0) „or 1 C (OR ') ₂ —, aryl Len One of R ′ represents a hydrogen atom, or two R ′ each represent a lower alkyl group or, together, a lower alkylene group; In the above, all the aromatic ring moieties and the benzo ring A are each unsubstituted or have one or more positions selected from the group consisting of (i) to (vi) shown below. (I) halogen atom, lower alkyl group, lower alkenyl group, lower alkynyl group, aryl group, heteroaryl group, lower alkoxy group, lower alkenyloxy group, lower alkynyloxy group. Group, hydroxyl group, lower alkanoyloxy group, (arinole or heteroaryl) lower alkanoyloxy group, lower alkanol group, (aryl or heteroaryl) lower alkyl Noyl group, (aryl or heteroaryl) carboxy group, nitro group, cyano group; (ii) halogen atom, hydroxyl group, lower alkoxy group, (aryl or heteroaryl) oxy group, aryl group A heteroaryl group, an amino group, a substituted amino group, a carboxy group, a lower alkoxycarbonyl group, a lower alkoxy lower alkoxycarbonyl group, a (aryl or heteroaryl) lower alkoxycarbonyl group, a carbamoyl group or an N-substituent A lower alkyl group substituted by a rubamoyl group; (iii) a halogen atom, a hydroxyl group, a lower alkoxy group, an (aryl or heteroaryl) oxy group, an aryl group, a heteroaryl group, an amino group, a substituted amino group, a carboxyl group, a lower group; Alkoxycarbonyl group, low Lower alkoxy lower alkoxycarbonyl group, (aryl or heteroaryl) lower alkoxycarbonyl group, A lower alkoxy group substituted by a carbamoyl group or an N-substituted lumino moyl group; (iv) an amino group, a substituted amino group; (V) a carboxy group, a lower alkoxycarbonyl group, a lower alkoxy lower alkoxy group Carbonyl group, (aryl or heteroaryl) lower alkoxycarbonyl group; (vi) substituted rubamoyl group and N-substituted rubamoyl group; substituted amino group, N-substituted carbamoyl group and N-substituted aminocarbonyl group Amino groups substituted with a xy group may be (i) monosubstituted or disubstituted independently of each other by a lower alkyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group. (Ϋ) disubstituted by a lower alkylene group {the lower alkylene group is an oxygen atom or S (0) _n or May be via a group represented by NR °, or may be condensed with a benzene ring at two adjacent carbon atoms}; or (iii) -CO-(0) _V— V means 0 or 1; n means 0, 1 or 2; monosubstituted or disubstituted independently of one another; Represents a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, an aryl group, a heteroaryl group, a (aryl or heteroaryl) lower alkyl group, a lower alkanoyl group, a (aryl or heteroaryl) carbonyl group or ₂ — represents a group represented by R, or a lower alkyl group substituted by a halogen atom, a hydroxyl group or a lower alkoxy group; R represents a hydrogen atom, a lower alkyl group, an aryl group, a heteroaryl group or (Aryl or heteroaryl) which means a lower alkyl group, or a lower alkyl group substituted by a halogen atom, a hydroxyl group or a lower alkoxy group] and a salt thereof, and a compound represented by the general formula [I-I]

[I-J]

Wherein, X ¹ is C ₃ - C ₈ cycloalkylene group, C ₃ - C ₈ Shikuroaruke two alkylene groups, c ₃ scratch. ₈ Cycloalkylidene group, C ₃ — C ₈ Cycloalkenylidene group, oxo C ₃ — C ₈ cycloalkylene group, Okiso C ₃ - C ₈ Shikuroaruke two alkylene groups, Okiso C ₃ - C ₈ cycloalkylidene group or Okiso C ₃ - C _e cycloalkenylene an isopropylidene group; X ² represents an oxygen atom or one S (0 ) _n— or a group represented by one N (R ⁴ ) —; alk ¹ , alk ² , R, R ² , R ³ , R ⁴ and the benzo ring A are represented by the above general formula [I—i] And cholesterol, hyperlipidemia, and hypercholesterolemia according to claim 1, which are one or more drugs selected from the group consisting of a compound represented by the formula: Agent for treating arteriosclerosis.

(3) Neuropeptide Y Y5 receptor antagonist has the formula [I-f-1-1]

2. The therapeutic agent for hypercholesterolemia, hyperlipidemia and arteriosclerosis according to claim 1, which is a compound represented by the formula:

(4) Hypercholesterolemia, hyperlipidemia, and arteriosclerosis containing a neuropeptide YY5 receptor antagonist and a cholesterol-lowering agent other than a neuropeptide YY5 receptor antagonist as an active ingredient Treatment agent.

(5) Neuropeptide Y Y5 receptor antagonist has the general formula [I-a]

[I-a]

In pot, A is a nitrogen atom or a C - a group represented by R ^5; Ar or a halogen atom, a lower An aryl group which may have a substituent selected from the group consisting of an alkyl group and a halo-lower alkyl group; Ar ² is a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group; R ¹ represents an aryl group or a heteroaromatic group, which may have a substituent selected from the group consisting of a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group and an aryl group; the bond in conjunction with a hydrogen atom or a lower alkyl group, or R ^5; R ² is a hydrogen atom or a lower alkyl group; R ³ and R ⁴ are the same or different, a hydrogen atom or a lower alkyl group, or R ³ and R ⁴ is linked to each other to form an alkylene group having 2 to 4 carbon atoms which may have a lower alkyl group; R ⁵ is a hydrogen atom, a hydroxyl group, a lower alkyl group or a lower alkoxy group; A bond in connection with a group or R ¹ ] and a salt thereof,

General formula [I-b]

Wherein ring A and ring B are ortho-fused with each other, ring A is an aromatic carbon or heterocyclic ring; ring B is a 4- to 7-membered aliphatic carbon or nitrogen-containing heterocyclic ring, and the nitrogen atom Is a ring that can be present only at the condensed site with ring A; Ar is a halogen atom, lower alkyl group, lower alkenyl group, halo-lower alkyl group, lower alkoxy group, lower alkylthio group, lower alkylamino group, di-lower An aromatic carbon or a heterocyclic group which may have a substituent selected from the group consisting of an alkylamino group and an aromatic carbocyclic group; R is a halogen atom, a nitrogen atom, a lower alkyl group, A substituent or a hydrogen atom selected from the group consisting of a lower alkoxy group, an aromatic carbocyclic group, and a carbonyl group having an aromatic carbocyclic group.

The group represented by the formula

General formula [I-Ic]

[Wherein, Ar ¹ represents an aryl group which may have a substituent selected from the group consisting of a halogen atom, a lower alkyl group and a lower alkyl group; Ar ² represents a halogen atom, a lower alkyl group, It may have a substituent selected from the group consisting of a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group and an aryl group. R ¹ and R ² are the same or different and are a hydrogen atom or a lower alkyl group; R ³ and R ⁴ are the same or different and are a hydrogen atom or a lower alkyl group; or linked both R ³ and R ⁴ together, having 2 to carbon atoms which may have a lower alkyl group and alkylene group 4; R ⁵ is a hydrogen atom, it means a lower alkyl group or a lower alkoxy group And salts thereof represented by, general formula [I one d]

[I-d]

[Wherein, Ar ¹ is a group consisting of a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, an acyl group and an aryl group. Ar ² is a halogen atom, a lower alkyl group, a lower alkenyl group, a halo-lower alkyl group, An aryl group or a heteroaromatic ring group which may have a substituent selected from the group consisting of a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group and an aryl group; R ¹ and R ² are the same or different and each represents a hydrogen atom or a lower alkyl group] and a salt thereof;

-General formula [I-e]

[Wherein, Ar comprises a halogen atom, a nitro group, an amino group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylamino group, a di-lower alkylamino group, a lower alkanol group and an aryl group. An aryl group or a heteroaromatic ring group which may have a substituent selected from the group; R ¹ and R ² are the same or different, and a lower alkyl group or both R ¹ and R ² are linked to each other; R ³ is an amino group, a lower alkyl group or a lower alkyl amino group; Y is an ethylene group, a trimethylene group, a vinylene group, a propenylene group or 0—CH ₂ —, a group represented by one S—CH ₂ — or one CH ₂ —NH—] and a salt thereof,

General formula [I-I f]

[Wherein, R ¹ represents a hydrogen atom or a lower alkyl group, or a lower alkylene group which may be intervened with R ² to represent an oxygen atom; R ² represents a lower alkyl group; either, or have the meanings together such connexion the the R ^1; R ³ and R ⁴ is a hydrogen atom simultaneously, or both means together such connexion single bond; R ⁵ and R ⁶ represents a hydrogen atom at the same time or a lower alkylidene group which may be joined together and an oxygen atom is interposed; R ⁷ and R ⁸ independently represent a hydrogen atom, a halogen atom, a nitro group , A hydroxyl group, a lower alkyl group, a lower alkoxy group, a benzyl group, an aralkyloxy group, a di-lower alkylamino group, a lower alkoxycarbonylamino group or an arylcarbonylamino group, or a combination of both. , Lower alk X represents an oxygen atom or a sulfur atom; and Y represents a methine group or a nitrogen atom. (2-Hydroxy 4,4-dimethyl-6-oxo-1-cyclohexene-1-inole) -1-5-methoxy-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthene-one-one and 9- (Excluding 2-hydroxy-4-methyl-6-oxo-1-cyclohexene-11-yl) —3-methyl-2,3,4,9-tetrahydro-1H-xanthen-1-one) and its salts ,

General formula [I-g]

B represents 1 or 2; j represents an integer of 0 to 3; K represents one CH ₂ —NR ⁸ —CHR ⁵ — (CH ₂ ) j—, — CH ₂ —NR ⁸ —CO— L represents a group represented by (CH ₂ ) j— or —CH ₂ —NH—CO—NH— (CH ₂ ) j—;

— (CH ₂ )-^ "a group represented by (CH ₂ ); p is an integer of 0 to 2; Q is a nitrogen atom, an oxygen atom, a sulfur atom or one NR ⁷ — or — C (R ⁴ ) ₂ RR ² and R ³ are independently a hydrogen atom, a halogen atom, a nitro group, a hydroxyl group, a lower alkoxy group, a hydroxy lower alkyl group, a halo lower alkyl group or 1 N (R ⁴ ) ₂ R ⁴ is independently a lower alkyl group; R ⁵ is independently a hydrogen atom, a hydroxymethyl group or a lower alkoxymethyl group; R ⁶ is a hydrogen atom, a halogen atom, a nitro group, a hydroxyl group , An oxo group, a lower alkyl group, a lower alkoxy group, a hydroxy lower alkyl group, a methoxy lower alkyl group, a halo lower alkyl group or one N (R ⁴ ) ₂ , — NHCOR ⁴ , — N (COR ⁴ ) ₂ , — NHC0 ₂ R ⁴ , — NHCONHR ⁴ , — NHS0 ₂ R ⁴ ,-N (S0 ₂ R ⁴ ) ₂ , — C0 ₂ R ⁴ , a group represented by CON (R ⁴ ) ₂ or —S 0 ₂ N (R ⁴ ) ₂ ; R ⁷ is independently a hydrogen atom or a lower alkyl group; R ⁸ is independently , A hydrogen atom or a lower alkyl group; V is a nitrogen atom, an oxygen atom, a sulfur atom or a group represented by NR ⁴ —;

A compound represented by the formula:

General formula [I-I h]

[Wherein, alk represents a single bond or a lower alkylene group; n represents 0 or 1; R ¹ represents (i) a hydrogen atom, a halogen atom, a nitro group, a cyano group, a lower alkyl group, a lower alkenyl group; A lower alkynyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) group means a lower alkyl group, a halogen atom, a hydroxyl group, a lower alkoxy group, an amino group, a substituted amino group, A lower alkoxycarbonyl group, (aryl or heteroaryl) a lower alkoxycarbonyl group, a canolebamoyl group or a lower alkyl group substituted by an N-substituent rubamoyl group; (ii) an amino group or a substituted amino group (Iii) a hydroxyl group, a lower alkoxy group, a lower alkenyloxy group, a lower alkynyloxy group, Alkoxy lower alkoxy group, a lower alkoxy lower grade alkoxy group, a lower alkoxy group (Arino Teroari one Honoré to the properly), low grade alkoxycarbonyl O alkoxy group, (Ariru or Heteroariru) lower An alkoxycarbonyloxy group, an aminocarbonyloxy group or an N-substituted aminocarbonyloxy group; (iv) a carboxy group, a lower alkoxycarbonyl group, a lower alkoxylower alkoxycarbonyl group or (aryl or heteroaryl) A lower alkoxycarbonyl group; (V) a rubamoyl group or an N-substituting rubamoyl group; (vi) -CH (OH) -R, -CO-R, -NR ⁰¹ -CO-0-R, one NR. 'Single CO - R, one ^{^{NR 01 - CO - NR 01 -}} R, one ^{_{NR 01 - S0 2 - R,}} - NR 01 - S0 2 - NR 01 - R, - S0 2 - R, - S0 2 - NR 01 - R or single S0 ₂ - NR ^W - CO- group [wherein represented by R, or R and R ^Q1 has the below meaning, or - N (R) group represented by (R ⁰¹⁾ is lower § Means an amino group di-substituted by a alkylene group (the lower alkylene group may be via an oxygen atom or a group represented by S (0) _n or NR °, and may be a benzene ring at two adjacent carbon atoms. Or a group represented by (vii) —X ¹ (X ² ) (X ³ ); wherein (a) a group wherein X ¹ is —CH— In the case of X ² and X ³ are joined together and —X ⁴ — (CO) p-(CH ₂ ). _{_{-, - (CH 2) q}} - X 4 - (CO) p - (CH 2) r - or _{_{- (CH 2) S - X}} 4 - CO- (CH 2) t - a group represented by; or ( b) When X ¹ is a nitrogen atom, X ² and X ³ together represent a group represented by —CO— (CH ₂ ) _U — [X ⁴ is — CH ₂ — or One N (R ⁰¹ ) a group represented by one or an oxygen atom; o is an integer of 3 to 5; p is 0 or 1; q is 1 or 2; r is 1; T represents 1 or 2; u represents an integer of 3 to 5 (however, when p is 0, X ⁴ does not represent a group represented by —CH ₂ —)]; R ² and R ³ independently of each other: (i) a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, an aryl group, a heteroaryl group or a (arino or heteroaryl) lower alkyl group; or ii) halogen atom, hydroxyl group, lower alkoxy group, hydroxy Lower alkoxy group, lower alkoxy lower alkoxy group, amino group, substituted amino group, carboxy group, lower alkoxycarbonyl group, lower alkoxy lower alkoxycarbonyl group, (aryl or heteroaryl) lower alkoxycarbonyl group, carbamoyl group , N- substituted force Rubamoiru group and - S (0) _n - R in either means a lower alkyl group substituted with a substituent selected from the group consisting of groups I Table; R ² and R ³ together Means a lower alkylene group (the lower alkylene group) The lower alkylene group may be via an oxygen atom or a group represented by S (0) _n or NR °, and may be fused to a benzene ring at two adjacent carbon atoms. Or a methine group; in the above definitions, all the aromatic ring moieties and benzo ring A are each unsubstituted or selected from the group consisting of (i) to (vi) shown below. (I) a halogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, an aryl group, a heteroaryl group, a lower alkoxy group, a lower alkenyl group. Alkoxy group, lower alkynyloxy group, hydroxyl group, lower alkanol group, (aryl or heteroaryl) lower alkanoyloxy group, lower alkanol group, (aryl or (Heteroaryl) lower alkanol group, (aryl or heteroaryl) carbonyl group, nitro group, cyano group; (ii) halogen atom, hydroxyl group, lower alkoxy group, (aryl or heteroaryl) oxy group, aryl group, heteroaryl group, Substituted by an amino group, a substituted amino group, a carboxy group, a lower alkoxycarbonyl group, a lower alkoxy lower alkoxycarbonyl group, a lower alkoxycarbonyl group (aryl or heteroaryl), a rubamoyl group or an N-substituted rubamoyl group A lower alkyl group; (iii) a halogen atom, a hydroxyl group, a lower alkoxy group, an (aryl or heteroaryl) oxy group, an arylene group, a heteroaryl group, an amino group, a substituted amino group, a carboxy group, A lower alkoxycarbonyl group, a lower alkoxy lower alkoxycarbonyl group, (an aryl or heteroaryl) a lower alkoxycarbonyl group, a lower alkoxy group substituted with a carbamoyl group or an N-substituted canolebamoinole group; ( iv) amino group, substituted amino group; (V) carboxy group, lower alkoxycarbonyl group, lower alkoxy lower alkoxycarbonyl group, (aryl or heteroaryl) lower alkoxycarbonyl group; (vi) carbamoyl group And substituted amino groups of N-substituted rubamoyl groups and N-substituted aminocarbonyloxy groups are (i) lower alkyl groups, , A heteroaryl group or a (aryl or heteroaryl) lower alkyl group (Ii) disubstitution with a lower alkylene group. May be via an oxygen atom or a group represented by S (0) _n or NR °, and may be condensed with a benzene ring at two adjacent carbon atoms}; or (iii) one CO— (O) means mono-substituted or di-substituted independently of each other by a group represented by v-R; V means 0 or 1; n means 0, 1 or 2; Is hydrogen atom, lower alkyl group, lower alkenyl group, lower alkynyl group, aryl group, heteroaryl group, (aryl or heteroaryl) lower alkyl group, lower alkanoyl group, (aryl or heteroaryl) carboxy the R ^ei is a hydrogen atom or a lower alkyl group; two Le group or - - S0 ₂ or means a group represented by R, or a halogen atom, with water acid group or lower alkoxy group means a substituted lower alkyl group R represents a hydrogen atom, a lower alkyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group, or represents a halogen atom, a hydroxyl group or a lower alkoxy group; A substituted lower alkyl group] and salts thereof,

[I-i i]

Wherein alk ¹ and alk ² independently represent a single bond or a lower alkylene group; R ¹ is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a halo-lower alkyl group, a hydroxy-lower alkyl group R ² represents (i) a hydrogen atom, a halogen atom, a nitro group, a cyano group, a lower alkyl group, a lower alkoxy lower alkyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group; A lower alkenyl group, a lower alkynyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group, a halogen atom, a hydroxyl group, a lower alkoxy group, an amino group, a substituted amino group, a carboxy group, Lower alkoxycarbonyl group, (aryl or heteroaryl) A lower alkoxycarbonyl group, Karubamo (Ii) an amino group or a substituted amino group; (iii) a hydroxyl group, a lower alkoxy group, a lower alkenyloxy group, a lower alkynyl. Alkoxy group, hydroxy lower alkoxy group, lower alkoxy lower alkoxy group, (aryl or heteroaryl) lower alkoxy group, lower alkoxycarbonyloxy group, (aryl or heteroaryl) lower alkoxycarbonyloxy group, aminocarbonyl (Iv) a carboxy group, a lower alkoxycarbonyl group, a lower alkoxy-lower alkoxycarbonyl group or a (alkynole or heteroaryl) lower alkoxycarbonyl group; Power Or N- substituted Carnot <Moinore group; (vi) - CH (OH ) - R, - CO - R, one ^{NR 1 - CO - 0- R,} - NR 1 - CO one R, - NR ¹ - CO- ^{^{NR 1 - R, - NR 1}} - S0 2 - R, - NR 1 - SO 2 - NR 1 - R, one S0 ₂ one R, one S0 ₂ - NR ¹ - R or single SO ₂ - NR ¹ - CO - A group represented by R wherein R has the meaning given below and R ¹ has the meaning given above, or the group represented by N (R) (R ¹ ) is disubstituted by a lower alkylene group (The lower alkylene group may be via an oxygen atom or a group represented by S (0) _n or NR, and may be fused to a benzene ring at two adjacent carbon atoms. Or a group represented by (vii)-X ¹ (X ² ) (X ^s ); wherein (a) when X ¹ is a group represented by -CH-, X ² and X ³ together, one ^{X 4 - (CO) p -} (CH 2). _{_{-, - (CH 2) q}} - X 4 - (CO) p - (CH 2) r - or _{_{- (CH 2) S - X}} 4 - CO - a group represented by the (CH _2); or (b ) When X ¹ is a nitrogen atom, X ² and X ³ together represent a group represented by —CO— (CH ₂ ) _U— [X ⁴ is —CH ₂ — or —N (R ¹ 0 is an integer from 3 to 5; p is 0 or 1; q is 1 or 2; r is 1; s is 1 or 2; 1 or 2; u means an integer of 3 to 5 (however, when p is 0, X ⁴ does not mean a group represented by -C]-)]; R ³ and R ⁴ are independent of each other And (ii) a halogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, an aryl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group; Atom, hydroxyl group, lower alkoxy group, hydroxy lower alkyl Coxy group, lower alkoxy A lower alkoxy group, an amino group, a substituted amino group, a carboxy group, a lower alkoxycarbonyl group, a lower alkoxy lower alkoxycarbonyl group, an aryloxy or heteroaryl, a lower alkoxycarbonyl group, a carbamoyl group, R ³ and R ⁴ together represent a lower alkyl group substituted by a substituent selected from the group consisting of a rubamoyl group and a group represented by S (O) n—R; means lower alkylene group {said lower alkylene group is an acid atom or S (0) may also be via a group represented by _n or NR ^Q, also have condensed with the benzene ring with two carbon atoms adjacent neighbors X is a single bond, a 1,2-ethenylene group, a 1,2-ethynylene group, an oxygen atom, a carbonyl group, a group represented by -S (0) „one or one C (OR ') ₂ —, Early One of R ′ represents a hydrogen atom, or two of R ′ each represent a lower alkyl group or, together, a lower alkylene group; In the definition, all aromatic ring moieties and benzo ring A are each unsubstituted or one or more selected from the group consisting of (i) to (vi) shown below. Ω halogen atom, lower alkyl group, lower alkenyl group, lower alkynyl group, aryl group, heteroaryl group, lower alkoxy group, lower alkenyloxy group, lower alkynyloxy group. , Hydroxy, lower alkanoyloxy, (aryl or heteroaryl) lower alkanoyloxy, lower alkanoyl, (aryl or heteroaryl) lower Lucanoinole group, (aryl or heteroaryl) carbonyl group, nitro group, cyano group; (ii) halogen atom, hydroxyl group, lower alkoxy group, (aryl or heteroaryl) oxy group, aryl group, heteroaryl group, amino group, substituted A lower alkyl group substituted by an amino group, a carboxy group, a lower alkoxycarbonyl group, a lower alkoxy lower alkoxycarbonyl group, an (aryl or heteroaryl) lower alkoxycarbonyl group, a carbamoyl group or an N-substituent rubamoyl group; iii) halogen atom, hydroxyl group, lower alkoxy group, (aryl or heteroaryl) oxy group, aryl group, heteroaryl group, amino group, substituted amino group, carboxyl group, lower alkoxycarbonyl group, Grade alkoxy-lower alkoxycarbonyl group, (§ re Ichiru or to Teroariru) a lower alkoxycarbonyl group, Lower alkoxy group substituted by a carboxylic acid group or N-substituted rubamoyl group; (iv) amino group, substituted amino group; (V) carboxy group, lower alkoxycarbonyl group, lower alkoxy lower Alkoxycarbonyl group, (arylene or heteroaryl) lower alkoxycarbinole group; (vi) substituted carbamoyl group and N-substituted rubamoyl group; substituted amino group, N-substituted carbamoyl group and N-substituted aminocarbonyl The amino group substituted with a methoxy group may be (i) mono-substituted or independently of each other by a lower alkyl group, a phenyl group, a heteroaryl group or a (aryl or heteroaryl) lower alkyl group. to be disubstituted Te; (ii) {said lower alkylene group to be disubstituted by lower alkylene group is an oxygen atom or S (0) _n young Or may be via a group represented by NR, or may be condensed with a benzene ring at two adjacent carbon atoms}; or (iii) a group represented by one CO— (O) v -R Means mono-substituted or di-substituted independently of each other; V means 0 or 1; n means 0, 1 or 2; Represents a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, an aryl group, a heteroaryl group, an aryl or heteroaryl group, a lower alkyl group, a lower alkanol group, a (aryl or heteroaryl) carbonyl group or ₂ represents a group represented by R, or a lower alkyl group substituted by a hydrogen atom, a halogen atom, a hydroxyl group or a lower alkoxy group; R represents a hydrogen atom, a lower alkyl group, an aryl group, a heteroaryl group; Or a (alkyl or heteroaryl) lower alkyl group, or a lower alkyl group substituted by a halogen atom, a hydroxyl group or a lower alkoxy group, and a salt thereof, and-a general formula [ I one j]

Wherein, X ¹ is C ₃ - C ₈ cycloalkylene group, c ₃ - c ₈ Shikuroaruke two alkylene groups, c ₃ - c ₈ cycloalkylidene group, c ₃ - C _B cycloalkenylene isopropylidene group, Okiso c ₃ - Flip ₈ cycloalkylene group, Okiso C ₃ - Ji ₈ cycloalkenylene, Okiso C ₃ - C ₈ cycloalkylidene group or Okiso C ₃ - C ₈ Shikuroaruke two isopropylidene group; X ² represents an oxygen atom or one S (0) _n — Or one N (R ⁴ ) means a group represented by alk alk ² , R \ R ² , R ³ , R ⁴ and benzo ring A are defined by the above general formula [I—i] And cholesterol monocholesterolemia, hyperlipidemia and arteriosclerosis according to claim 4, which are one or more drugs selected from the group consisting of a compound represented by the following formula: For treating sickness.

(6) Neuropeptide Y Y5 receptor antagonist has the formula [I-f-1-1]

5. The therapeutic agent for hypercholesterolemia, hyperlipidemia and arteriosclerosis according to claim 4, which is a compound represented by the formula:

(7) The treatment of hypercholesterolemia, hyperlipidemia and arteriosclerosis according to claim 4, wherein the cholesterol-lowering agent other than the neuropeptide Y Y5 receptor antagonist is a hydroxymethylglutaryl-CoA reductase inhibitor. Agent.

(8) the hydroxymethyldartharyl CoA reductase inhibitor is selected from the group consisting of oral pastatin, simpastatin, pravastatin and flupastatin

8. The therapeutic agent for hypercholesterolemia, hyperlipidemia and arteriosclerosis according to claim 7, which is one or more drugs.