MXPA06009244A

MXPA06009244A - Fused-ring 4-oxopyrimidine derivative

Info

Publication number: MXPA06009244A
Application number: MXPA/A/2006/009244A
Authority: MX
Inventors: Tsuyoshi Nagase; Nagaaki Sato; Akio Kanatani; Shigeru Tokita
Original assignee: Banyu Pharmaceutical Co Ltd
Priority date: 2004-02-13
Filing date: 2006-08-11
Publication date: 2007-04-10

Abstract

(I) [wherein Ar represents a divalent group formed by removing two hydrogen atoms from benzene, etc.;X1 represents nitrogen, sulfur, or oxygen;R1 represents 5- or 6-membered heteroaryl, etc.;ring A represents 5- or 6-membered heteroaryl ring, etc.;R2 and R3 each represents amino, alkylamino, etc.;and -X2 represents, e.g., a group represented by the formula (II):(II) (wherein R4 and R5 each represents lower alkyl, etc.;and n is an integer of 2 to 4)]or a pharmaceutically acceptable salt of the compound. The compound or salt has antagonistic activity against a histamine H3 receptor or inverse agonistic activity against a histamine H3 receptor and is useful in the prevention or treatment of metabolic diseases, circulatory diseases, or neurotic diseases.

Description

DERIVED OF 4-OXOPIRI .DINA WITH CONDENSED RING FIELD OF THE TECHNIQUE The present invention relates to 4-oxopyrimidine derivatives with fused ring.

BACKGROUND OF THE INVENTION In living creatures including mammals, histamine, an endogenous factor with physiological activity, functions as a neurotransmitter and has far-reaching pharmacological effects (eg, Life science, Vol. 17, page 503 (1975)). From the immunohistochemical investigation, it has become evident that the histaminergic bodies (production) are present in the nuclei of the mammillary tubercle of the posterior hypothalamic region, and the histaminergic nerve fibers extend over a very large area of the brain, suggesting that histamine has many different pharmacological actions (eg, Journal of Comprehensive Neurology, Vol. 273, page 283). The presence of a histaminergic nerve in the nuclei of the mammillary tubercle of the posterior hypothalamic region suggest that histamine plays a particularly important role in brain function in controlling the physiology of the hypothalamus, that is, in the rhythms of wakefulness, secretions internal, food / water intake and sexual behavior (eg, Progress in Neurobiology, Vol. 63, page 637 (2001)). The fact that there are projections of histaminergic nerve fibers to regions of the brain related to maintaining the waking state (for example, the cerebral cortex) suggests that histamine plays a role in maintaining the waking state or in the waking cycle and I dream. Also, the fact that there are projections of histaminergic nerve fibers to many peripheral structures such as the hippocampus or the amigdaliano complex suggests that it plays a role in the regulation of the autonomic nervous system and emotions, the control of motivation, learning and memory. After histamine is released by the cells that produce histamine, it interacts with specific polymers called receptors on the surface of the cell membrane or on the target cells, which explain their pharmacological effects and the regulation of bodily functions. To date, four types of histamine receptors have been discovered. Various pharmacological and physiological studies have shown that histamine H3 receptors participate in the function of central and peripheral nerves (eg, Trends in Pharmacological Science, Vol. 8, page 24 (1986)), and in recent years, have identified histamine H3 receptor genes in humans and rodents (eg, Molecular Pharmacology, Vol. 55, page 1101 (1999)).

It has been shown that histamine H3 receptors are present in the center or in the presynaptic membrane of peripheral nerve cells, functioning as autoreceptors, controlling the release of histamine and also controlling the release of other neurotransmitters. Specifically, it has been reported that the agonists, antagonists or inverse agonists of histamine H3 receptors regulate the release of histamine, noradrenaline, serotonin, acetylcholine or dopamine from the synaptic ends. For example, the release of neurotransmitters such as (R) - (a) -methylhistamine is suppressed by agonists, and is promoted by antagonists or inverse agonists such as thioperamide (e.g., Trends in Pharmacological Science, Vol. 19, page 177 (1998)).

DETAILED DESCRIPTION OF THE INVENTION It is therefore an object of the present invention to provide novel substances exhibiting antagonism of the histamine H3 receptor (action of inhibiting histamine binding to histamine H3 receptors) or inverse agonism (action of suppressing the constant activity of histamine receptors). histamine H3), ie novel substances that act as antagonists or inverse agonists of histamine H3 receptors in a living body. The inventors discovered that specific derivatives of 4-oxopyrimidine with fused rings act as antagonists or inverse agonists of histamine H3 receptors, and based on the findings, they came to the present invention. To achieve the object described above, the present invention provides the compounds described in (1) to (45) or its salt: (1) a compound represented by the formula (I): (I) where Ar is a divalent group formed by removing two hydrogen atoms from benzene, pyrimidine, pyridine, thiazole, oxazole, pyrazole, thiadiazole or thiophene (this divalent group may also be substituted by a halogen atom, lower alkoxy (this group lower alkoxy may further be substituted by halogen), hydroxy or lower alkyl); X1 is a nitrogen atom, sulfur atom or oxygen atom; R1 is a 5- or 6-membered heteroaryl group having 1 to 4 heteroatoms which are selected from nitrogen, sulfur and oxygen, heteroarylalkyl group (heteroaryl in this group has the same meaning as above), straight or branched chain lower alkyl (this lower alkyl group may be further substituted by hydroxy, halogen, alkoxy, allyloxy or aralkyloxy), phenyl, aralkyl, alkoxy, alkylthio or (lower alkyl) amino; ring A is a 5- or 6-membered heteroaryl ring having 1 or 2 nitrogen atoms or sulfur atoms in the ring, or a benzene ring; R2 and R3 may be the same or different, and each represents hydrogen, amino, alkylamino, dialkylamino, nitro, cyano, hydroxy, (lower alkyl) sulfonyl, halogen, lower alkyl (this lower alkyl group may also be substituted by halogen), lower cycloalkyl (this lower cycloalkyl group can be further substituted by halogen), lower alkoxy (this lower alkoxy group can be further substituted by halogen or hydroxy), lower cycloalkoxy (this lower cycloalkoxy group can be further substituted by halogen), aryloxy, aralkyloxy , heteroaryloxy, heteroarylalkyloxy, aryl, heteroaryl, arylcarbamoyl, heteroarylcarbamoyl, arylalkylcarbamoyl, heteroarylalkylcarbamoyl, mono (lower alkyl) carbamoyl, di (lower alkyl) carbamoyl, (lower alkyl) carboxamide, arylcarboxamide, heteroarylcarboxamide, arylalkylcarboxamide, heteroarylalkylcarboxamide, alkanoyl, arylcarbonyl , arylalkylcarbonyl, formyl, hydroxy, alkylthio, a lcoxycarbonylamino, (lower alkyl) sulfonamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, aralkyl, alkanoylamino or alkanoylalkylamino; And it is CH or a nitrogen atom; -X2 is a group represented by the formula (II): (II) (wherein R4 and R5 may be the same or different, and each is a lower alkyl group (this lower alkyl group may be further substituted by halogen) or a cycloalkyl group, or R4, R5 and a nitrogen atom together form a monocyclic ring of 5 to 8 members (this monocyclic ring may be substituted by a halogen atom, an oxo group, or a lower alkyl group which in turn may be substituted by halogen), or a bicyclic ring of from 6 to 10 members, n is an integer number of 2 to 4, and (CH2) n may be substituted by a lower alkyl group having 1 to 3 carbon atoms), by the formula (III): (I I I) (where m is an integer from 0 to 4, and R6 is an alkyl group or lower cycloalkyl), or by the formula (IV): (where the symbols have the same meaning as the previous ones), with the proviso that formula (I) excludes 3- [4- (2-diethylaminoethoxy) pheny] -2-methy1-3H-quinazolin-4 -one, 3- [4- (2-dimethylaminoethoxy) phenyl] -2-methyl-3H-quinazolin-4-one, 2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) phenyl] -3H-quinazolin-4-one, 3- [4- (3-dimethylaminopropoxy) phenyl] -2-methyl-3H-quinazolin-4-one, 3- [4- (3-diethylammonopropoxy) phenyl ] -2-methyl-3H-quinazolin-4-one and 3- [2- (2-diethylaminoethoxy) phenyl] -2-methyl-3H-quinazoln-4-one], or a pharmaceutically acceptable salt of the same; (2) The compound according to (1), wherein Ring A is a benzene ring, a pyridine ring or a pyrimidine ring, or a pharmaceutically acceptable salt thereof; (3) The compound according to (1), wherein Ring A is a benzene ring or a pyridine ring, or a pharmaceutically acceptable salt thereof; (4) The compound according to (1), (2) or (3), wherein at least one of R2 and R3 is a hydrogen atom, or a pharmaceutically acceptable salt thereof; (5) The compound according to (1), (2) or (3), wherein one of R2 and R3 is a hydrogen atom, and the other is a hydrogen atom, a halogen atom, lower alkyl (this lower alkyl group may be further substituted by halogen), lower alkoxy (this lower alkoxy group may be further substituted by a halogen atom or hydroxy), hydroxy, aryl (this aryl group may be further substituted by lower alkyl), heteroaryl, (lower alkyl) carboxamide, arylcarboxamide, arylalkylcarboxamide or (lower alkyl) sulfonylamino, or a pharmaceutically acceptable salt of the same; (6) The compound according to (1), (2) or (3), wherein one of R2 and R3 is a hydrogen atom, and the other is a hydrogen atom, a halogen atom, lower alkyl (this lower alkyl group may be further substituted by halogen), or lower alkoxy (this lower alkoxy group may be further substituted by halogen), or a pharmaceutically acceptable salt thereof; (7) The compound according to any one of (1) to (6), in that Ar is phenyl or pyrimidinyl, ie a divalent group that is formed eliminating two hydrogen atoms of benzene or pyrimidine (this group divalent may be further substituted by a halogen atom, alkoxy lower (this lower alkoxy group may also be substituted by halogen), hydroxy or lower alkyl), and n is 3 or 4, or a pharmaceutically acceptable salt thereof; (8) The compound according to any one of (1) to (7), in the one which -X2 is represented by the formula (II): (I I) [where the symbols have the same meaning as the previous ones], or a pharmaceutically acceptable salt thereof; (9) The compound according to (8), wherein n is 3 or 4, and R4, R5 and a nitrogen atom together form a monocyclic ring of 5 to 8 members (this monocyclic ring may have as a substituent group a halogen atom, or a lower alkyl group which may be substituted by halogen), or a pharmaceutically acceptable salt thereof; (10) The compound according to (8), wherein n is 3 or 4, and R4, R5 and a nitrogen atom together form a 6 to 10 membered bicyclic ring, or a pharmaceutically acceptable salt thereof; (11) The compound according to (8), wherein n is 3, and R4, R5 and a nitrogen atom together form a 5- to 8-membered monocyclic ring (this monocyclic ring may have one carbon atom as the substituent group). halogen, or a lower alkyl group which may be substituted by halogen), or a pharmaceutically acceptable salt thereof; (12) The compound according to (8), wherein n is 3, and R 4, R 5 and a nitrogen atom together form a 6 to 10 membered bicyclic ring, or a pharmaceutically acceptable salt thereof; (13) The compound according to any one of (1) to (7), wherein -X2 is represented by the formula (III): (I I I) [where the symbols have the same meaning as the previous ones], or a pharmaceutically acceptable salt thereof; (14) The compound according to any one of (1) to (7), wherein -X2 is represented by the formula (IV): [where the symbols have the same meaning as the above], or a pharmaceutically acceptable salt thereof; (15) The compound according to any one of (1) to (14), wherein R1 is a lower alkyl group having 1 to 3 carbon atoms (this lower alkyl group may also be substituted by halogen), or a phenyl group, or a pharmaceutically acceptable salt thereof; (16) The compound according to any one of (1) to (14), wherein R is methyl, ethyl, n-propyl, isopropyl or trifluoromethyl, or a pharmaceutically acceptable salt thereof; (17) The compound according to (1), wherein the compound represented by the formula (I) is: 2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolnone, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinonazolnone, 3-. { 4- [3- (diethylamino) propoxy) phenyl} -2-methyl-4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (2-methyl-1-pyrrolidinyl) -propoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 4- [3- (2,5-dimethyl-1-pyrrolidinyl) propoxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 2-methyl-3-. { 4- [4- (1-piperidinyl) butoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 4- [3- (1-azepanyl) propoxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- [3- (1-Azocanil) propoxy] -phenyl} -2-methyl-4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (2-methyl-1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (4-methyl-1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 3- (4- { 3 - [(2R) 6S) -2,6-dimethyl-1-piperidinyl] propoxy} phenyl) -2-methyl-4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (3-methyl-1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 4- [3- (3,5-dimethyl-1-piperidinyl) propoxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 2-methyl-3-. { 3- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 3-bromo-4- [3- (1-piperidinyl) propoxy] phenyl} -2-ethyl-4- (3H) -quinazolinone, 2-methyl-3-. { 4- [2- (1-piperidinyl) ethoxy] phenyl} -4- (3H) -quinazolinone, 2,5-dimethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 4- [3- (1-pperidinyl) propoxy] phenol} -2-propyl-4- (3H) -quinazolnone, 3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -2-trifluoromethyl-4- (3H) -quinazolinone, 2-isopropyI-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2,6-dimethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7-chloro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2,8-dimethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-ethyl-5-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-fluoro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-chloro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-hydroxy-2-methyl-3-trifluoroacetate. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-piperidin) propoxy] phenyl} -5-trifluoromethyl-4- (3H) -quinazolinone, 7-fluoro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6-fluoro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6,7-difluoro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6-bromo-2-methyl-3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6-chloro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6,7-dimethoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 8-chloro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 8-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2,6-dimethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-ethyl-5-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-fluoro-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenol} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -5-trifluoromethyl-4- (3H) -quinazolinone, 5-chloro-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenol} -4- (3H) -quazolinone, 2,5-dimethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (-piperidinyl) propoxy] phenyl} pyrido [2,3-d] pyrimide-4- (3H) -one, 2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [2,3-d] pyrimidin-4- (3H) -one, 6-chloro-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [4,3-d] pyrimidin-4- (3H) -one, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [4,3-d] pyrimidin-4- (3H) -one, 2-methyl-3-. { 2- [3- (1-piperidinyl) propoxy] -5-pyrimidinyl} -4- (3H) -quinazolinone, 2,5-dimethyl-3-. { 2- [3- (1-piperidinyl) propoxy] -5-pyrimidinyl} -4- (3H) -quinazolinone, 2-ethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [2,3-d] pyrimidn-4- (3H) -one, 6-chloro-2-ethyl-3-. { 4- [3- (1-pperidinyl) propoxy] phenyl} pyrid [3,4-d] pyrimidin-4- (3H) -one, 6-chloro-2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrid [3,4-d] pyrimidin-4- (3 H) -one, 2-ethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrid [3,4-d] pyrimidin-4- (3H) -one, 2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 2-ethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [4,3-d] pyrimidin-4- (3H) -one, 2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [4,3-d] pyrimidin-4- (3H) -one, 6-chloro-2-methyl-3. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido- [3,4-d] pyrimidin-4- (3H) -one, 3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- (acetylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- (butyrylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- (hexanelamlan) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- (benzolamlan) -2-methyl-3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} -4- (3H) -cholinezolinone, 6 - [(2-phenylacetyl) amino] 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- (2-naphthoylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-6 - [(methylsulfonyl) amino] -3-. { 4- [3- (1-piperidinium) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-6 - [(methylsulfonyl) amino] -3-. { 4- [3- (1-pyrrolidin) propoxy] phenyl} - 4- (3H) -quinazolinone, 7- (acetylamino) -2-methyl-3-. { 4- [3- (1-piperidin) propoxy] phenol} -4- (3H) -quinazolinone, 7- (butylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7- (hexanoylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7- (benzoylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7 - [(2-phenylacetyl) amino] 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} 4- (3H) -quinazolinone, 7- (2-naphthoylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone 6- [acetyl (methyl) amino] 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-6-phenyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-6- (4-methylphenyl) -3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-6- (3-methylphenyl) -3-. { 4- [3- (1-piperidinyl) propoxy] phenol} -4- (3H) -quinazolinone, 2-methyl-6- (2-methylphenyl) -3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -6- (3-pyridyl) -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-piperidiny) propoxy] phenyl} -6- (4-pyridyl) -4- (3H) -quinazolinone, 2-methyl-5-phenyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -6- (2-pyridyl) -4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- (1-cyclohexyl-4-piperidinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- (1-isopropyl-4-piperidinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- (1-ethyl-4-piperidinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- (1-Butyl-4-piperidinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methyl-5-trifluoromethyl-4- (3H) -quinazolinone, 3-. { 4- (1-cyclopentyl-4-piperidinyloxy) phenyl} -2,5-dimethyl-4- (3H) -quinazolinone, 7-chloro-3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenol} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenol} -2,6-dimethyl-4- (3H) -quinazolinone, 6-chloro-3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -6-methoxy-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methylpyrido [2,3-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methylpyrido [4,3-d] pyrimidin-4- (3H) -one, 6-chloro-3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] phenyl} -2,5-dimethyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-4-pyridinyl) oxy] phenyl} -5-methoxy-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-methyl-5-trifluoromethyl-4- (3H) -quinazolinone, 5-chloro-3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] phenyl} -2-methylpyrid [4,3-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] phenol} -2-ethylpyrid [4,3-d] pyrimidn-4- (3H) -one, 3-. { 4 - [(1-cyclobutyl-4-p-peridinyl) oxy] phenyl} -2-methylpyrido [2,3-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-ethylpyrid [2,3-d] -pyrimidin-4- (3H) -one, 6-chloro-3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] phenyl} -2-methy1pyrido [3,4-d] pyrimidin-4- (3H) -one, 6-chloro-3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] phenyl} -2-ethylpyrido [3,4-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] phenyl} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one, 2-phenyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenol} -4- (3H) -quinazolinone, cis-2-methyl-3- (4- { [4- (1-pyrrolidine) cyclohexyl] oxy] phenyl) -4- ( 3H) -quinazolinone, trans-2-methyl-3- (4 { [4- (1-pyrrolidinyl) cyclohexyl] oxy} phenyl) -4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-3-pyrrolidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-3-pyrrolidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone 3-. { 4 - [(1-cyclopentyl-4-azepanyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclo! Obutil-4-azepanyl) oxy] phenol} -2-methyl-4- (3H) -quinazolinone, 3-methyl-2-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -1- (2H) -isoquinolinone, 2-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -3-methyl-1- (2H) -isoquinolinone, 2-methyl-3- [4-. { [3- (1-pyrroidinyl) cyclopentyl] oxy} phenyl] -4- (3H) -quinazolinone, 2-etl-3- (4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy] phenyl) pyrido [2, 3-d] pyrimidin-4- (3H) -one, 2-methyl-3- (4-. {3 - [(3S) -3-methy1piperid-1-yl] propoxy]} phenyl) pyrido [4,3-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -5-fluoro-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -7-fluoro-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclobutylpiperidin-4-yl) oxy] phenyl} -6-methoxy-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -6-fluoro-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -8-fluoro-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutylpperidin-4-yl) oxy] phenyl} -6-fluoro-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one, 6-methoxy-2-methyl-3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 6-methoxy-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 5-methoxy-2-methyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy] phenyl) -4- (3H) -quinazolinone, 7-methoxy-2-methyl-3- (4-. {3 - [(3S) -3-methy1pyridin-1-yl] propoxy.} phenyl) -4- (3H) -quinazolinone, 2-methyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy.] phenol) pyrid [2,3-d] pyrimidin-4- (3H) -one, 5-fluoro-2-methyl-3- (4-. {3 - [(2R) -2-methylpyrrolidin-1) -yl] propoxy.} phenyl) -4- (3H) -quinazolinone, 2-methyl-3- (4- { 3 - [(2R) -2-methy1-pyrrolidin-1-yl] propoxy phenyl) pyrido [4,3-d] pyrimidin-4- (3H) -one, 6-methoxy-2-methyl-3- (4-. {3 - [(2R) -2-methylpyrrolidin- 1-yl] propoxy.} Phenyl) -4- (3H) -quinazolinone, or 6-methoxy-2-methyl-3- (4-. {3 - [(2S) -2-methylpyrrolidin-1-yl) ] propoxy, phenyl) -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (18) The compound according to (1), wherein the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-ethylpyrido [2,3-d] -pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof; (19) The compound according to (1), wherein the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-methylpyrido [4,3-d] -pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof; (20) The compound according to (1), wherein the compound represented by the formula (I) is 2-ethyl-3- (4-. {3 - [(3S) -3-methylpiperidin-) 1-yl] propoxy.} Phenyl) pyrido [2,3-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof; (21) The compound according to (1), wherein the compound represented by the formula (I) is 2-methyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1- L] propoxy, phenyl) pyrido [4,3-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof; (22) The compound according to (1), wherein the compound represented by the formula (I) is 3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] phenyl} -2,5- dimethyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (23) The compound according to (1), wherein the compound represented by the formula (I) is 3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] phenyl} -2-methyl-5-trifluoromethyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (24) The compound according to (1), wherein the compound represented by the formula (I) is 3-. { 4 - [(1-cyclobutyl-4-p-peridinyl) oxy] phenyl} -5-methoxy ^ -methyl-ISH ^ -quinazolinone, or a pharmaceutically acceptable salt thereof; (25) The compound according to (1), wherein the compound represented by the formula (I) is 3-. { 4 - [(1-cyclobutylpiperidin-4-yl) oxy] phenyl} -5-fluoro-2-methyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (26) The compound according to (1), wherein the compound represented by the formula (I) is 3-. { 4 - [(1-cyclobutylpiperidin-4-yl) oxy] phenyl} -7-fluoro-2-methyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (27) The compound according to (1), wherein the compound represented by the formula (I) is 3-. { 4 - [(1-cyclobutylpiperidin-4-yl) oxy] phenyl} -6-methoxy-2-methyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (28) The compound according to (1), wherein the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -6-fluoro-2-methyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (29) The compound according to (1), wherein the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -8-fluoro-2-methyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (30) The compound according to (1), wherein the compound represented by the formula (I) is 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methylpyrid [4,3-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof; (31) The compound according to (1), wherein the compound represented by the formula (I) is 3-. { 4 - [(1-cyclobutylpiperidin-4-yl) oxy] phenol} -6-fluoro ^ -methylpyridotS ^ -dlpyrimidin ^ SHJ-one, or a pharmaceutically acceptable salt thereof; (32) The compound according to (1), wherein the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-ethylpyrido [4,3-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof; (33) The compound according to (1), wherein the compound represented by the formula (I) is 6-methoxy-2-methyl-3-. { 4- [3- (1- piper-dynil) propoxy] phenyl} [3,4-d] pyrimidin-4- (3H) -one hydride, or a pharmaceutically acceptable salt thereof; (34) The compound according to (1), wherein the compound represented by the formula (I) is 6-methoxy-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof; (35) The compound according to (1), wherein the compound represented by the formula (I) is 2,5-dimethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (36) The compound according to (1), wherein the compound represented by the formula (I) is 2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenol} -5-trifluoromethyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (37) The compound according to (1), wherein the compound represented by the formula (I) is 5-fluoro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (38) The compound according to (1), wherein the compound represented by the formula (I) is 6-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (39) The compound according to (1), wherein the compound represented by the formula (I) is 5-methoxy-2-methyl-3- (4-. {3 - [(3S) -3- methylpiperidin-1-yl] propoxy.] phenyl) -4- (3 H) -cynazolinone, or a pharmaceutically acceptable salt thereof; (40) The compound according to (1), is 7-methoxy-2-methyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy] phenyl) -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (41) The compound according to (1), wherein the compound represented by the formula (I) is 2-methyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1- il] propoxy.} phenyl) pyrido [2,3-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof; (42) The compound according to (1), wherein the compound represented by the formula (I) is 5-fluoro-2-methyl-3- (4-. {3 - [(2R) -2- methylpyrrolidin-1-yl] propoxy, phenyl) -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; (43) The compound according to (1), wherein the compound represented by the formula (I) is 2-methyl-3- (4-. {3 - [(2R) -2-methylpyrrolidin-1- il] propoxy.} phenyl) pyrido [4,3-d] pyrimide-4- (3H) -one, or a pharmaceutically acceptable salt thereof; (44) The compound according to (1), wherein the compound represented by the formula (I) is 6-methoxy-2-methyl-3- (4-. {3 - [(2R) -2- methylpyridin-1-yl] propoxy, phenyl) -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof; and (45) The compound according to (1), wherein the compound represented by the formula (I) is 6-methoxy-2-methyl-3- (4-. {3 - [(2S) -2 -methylpyrrolidin-1-yl] propoxy.} phenyl) -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. The compound or salt according to any one of (1) to (45) acts as an antagonist or inverse agonist of the histamine H3 receptors. In other words, the present invention also provides an antagonist or inverse agonist of the histamine H3 receptors consisting of the compound according to any one of (1) to (45), or a pharmaceutically acceptable salt thereof. According to the most recent research, histamine H3 receptors are very active in the recipient cells and tissues, or in the membrane fractions that are derived from the recipient cells and tissues, and in the living body, they are constantly active ( endogenous, for example, the activity that is observed when histamine is absent) (eg, Nature, Vol. 408, page 860). It has been reported that this constant activity is suppressed by inverse agonists. For example, the constant autoreceptor activity is suppressed by thioperamide or ciproxifan and, as a result, the release of neurotransmitters from the synaptic ends is promoted, for example, the release and separation of histamine is promoted. In rats, from the fact that a selective high-level inhibitor of the synthetic histamine enzyme (histidine decarboxylase) interferes with wakefulness, histamine has been shown to function as a regulator of motivated wakefulness. In cats, administration of (R) - (a) -methylhistamine which is an agonist of histamine H3 receptors increases deep sleep with slow waves (eg, Brain Research, Vol. 523, page 325 (1990)). On the other hand, thioperamide which is an antagonist or inverse agonist of histamine H3 receptors increases insomnia in a dose-dependent manner. Also, thioperamide decreases slow wave and REM sleep (eg, Life Science, Vol. 48, page 2397 (1991)). In addition, thioperamide or GT-2331, which is an antagonist or inverse agonist of histamine H3, decreases emotional cataplexy and sleep in dogs with narcolepsy (eg, Brain Research, Vol. 793, page 279 (1998)). These findings suggest that H3 receptors participate in the adjustment of wakefulness and sleep and sleep disorders, and suggest that selective histamine H3 agonists, antagonists, or inverse agonists may be useful for the prevention or treatment of sleep disorders. and conditions accompanied by sleep disorders (eg, idiopathic hypersomnia, recurrent hypersomnia, genuine hypersomnia, narcolepsy, periodic limb movement during sleep, sleep apnea syndrome, circadian rhythm barrier, chronic fatigue syndrome, sleep disorder REM, insomnia in the elderly, lack of sleep in night shift workers, idiopathic insomnia, recurrent insomnia, inborn insomnia, depression and dysfunction syndrome in integration).

Therefore, the compound or salt according to any one of (1) to (45) which acts as an antagonist or inverse agonist of histamine H3 receptors is presumably useful in the prophylaxis or treatment of sleep disorders, and conditions accompanied by of sleep disorders. In rats, administration of thioperamide or GT-2331, which is an antagonist or inverse agonist of histamine H3, improves learning disability (LD) hyperkinetic disorder with attention deficit disorder (ADHD) (for example, Life Science , Vol. 69, page 469 (2001)). In rats, the administration of (R) - (a) -methylhistamine, which is an agonist of histamine H3 receptors, decreases the ability to recognize and learn in an object recognition test and a passive obstacle test. On the other hand, thioperamide, which is an antagonist or inverse agonist of histamine H3, improves the deficient memory induced by the drug scopolamine in an amnesia induction test in a dose-dependent manner (eg, Pharmacology, Biochemistry and Behavior, Vol. 68, page 735 (2001)). These findings suggest that antagonists or inverse agonists of histamine H3 receptors may be useful in the prevention and treatment of memory and learning disabilities and diseases accompanied by memory and learning disabilities, such as Alzheimer's disease, Parkinson's disease or attention deficit / hyperkinesia disorder.

Therefore, the compound or salt according to any one of (1) to (45) is presumably useful in the prophylaxis or treatment of memory and learning disability and diseases accompanied by memory and learning disability In rats, the Intraventricular administration of histamine suppresses the behavior of food intake, suggesting that histamine participates in the adjustment of food intake (eg, Journal of Physiology and Pharmacology Vol. 49, page 191 (1998)). In fact, thioperamide, which is an antagonist or inverse agonist of the histamine H3 receptor, suppresses the behavior of food intake in a dose-dependent manner, and also promotes the release of intracerebral histamine (eg, Behavioral Brain Research, Vol. 104, page 147 (1999)). These findings suggest that histamine H3 receptors are involved in the adjustment of food intake behavior and that antagonists or inverse histamine H3 agonists may be useful for the prevention or treatment of metabolic diseases such as eating disorder, obesity, diabetes mellitus , emaciation and hyperlipidemia. Therefore, the compound or salt according to any one of (1) to (45) is presumably useful in the prophylaxis or treatment of such metabolic diseases. In rats, the administration of (R) - (a) -methylhistamine, which is an agonist of the histamine H3 receptors, decreases the basic diastolic pressure in a dose-dependent manner. Thioperamide, which is an antagonist or inverse agonist of histamine H3, acts as an antagonist of these effects (for example, European Journal of Pharmacology, Vol. 234, page 129 (1993)). These findings suggest that histamine H3 receptors are involved in the adjustment of blood pressure, heartbeat and cardiovascular expenditure, and that agonists, antagonists or inverse agonists of histamine H3 receptors may be useful in the prevention or treatment of circulatory diseases such as hypertension and various cardiac problems. Therefore, the compound or salt according to any one of (1) to (45) is presumably useful in the prophylaxis or treatment of such circulatory diseases. In mice, thioperamide, which is an antagonist or inverse agonist of histamine H3, suppressed the seizures induced by stimuli with electroshock or epileptoid attacks induced by pentylenetetrazole (PTZ) in a dose-dependent manner, (eg, European Journal of Pharmacology, Vol. 234, page 129 (1993), and Pharmacology, Biochemistry and Behavior, Vol. 68, page 735 (2001)). These findings suggest that antagonists or inverse histamine H3 agonists may be useful for the prevention or treatment of epilepsy or convulsions of the central nervous system.

Therefore, the compound or salt according to any one of (1) to (45) is presumably useful in the prophylaxis or treatment of such epilepsy or convulsions of the central nervous system. In other words, the present invention further provides a prophylactic or therapeutic agent for a metabolic disease, a circulatory disease or a nervous system disease which contains as an active ingredient the compound according to any one of (1) a (45), or a pharmaceutically acceptable salt thereof. As a metabolic disease, at least one that is selected from the group consisting of obesity, diabetes mellitus, hormonal secretion disorders, hyperlipidemia, gout and fatty liver may be mentioned. As a circulatory disease, at least one that is selected from the group consisting of angina pectoris, acute or congestive heart failure, myocardial infarction, annular atherosclerosis, hypertension, renal disease and electrolyte imbalance can be mentioned. As a disease of the nervous system, at least one that is selected from the group consisting of sleep disorder, disease accompanied by sleep disorder, bulimia, emotional disorder, epilepsy, delirium, dementia, attention deficit / hyperactivity disorder, impairment may be mentioned. of memory, Alzheimer's disease, Parkinson's disease, cognitive disorder, movement disorder, dysesthesia, dysosmia, morphine resistance, narcotic dependence, alcohol dependence and tremor.

As a disease of the nervous system, at least one that is selected from the group consisting of idiopathic hypersomnia, recurrent hypersomnia, intrinsic hypersomnia, narcolepsy, periodic limb movement during sleep, sleep apnea syndrome, impediment to the circadian rhythm may also be mentioned. , chronic fatigue syndrome, impairment of REM sleep, loss of sleep in the elderly, insalubrity of sleep in workers at night shift, idiopathic insomnia, recurrent insomnia, intrinsic insomnia, depression, insecurity, schizophrenia. The compound or salt according to any one of (1) to (45) can be used in combination with concomitant drugs. In other words, the present invention further provides a prophylactic or therapeutic agent for a metabolic disease, a circulatory disease or a nervous system disease which contains as active ingredients the compound according to any one of (1) to (45), or a pharmaceutically acceptable salt thereof, and a concomitant drug. In the present specification, examples of the concomitant drug are anti-diabetes agents, lipid-lowering agents, antihypertensive agents and anti-obesity agents. Two or more of these concomitant drugs can be combined. In addition, as such prophylactic or therapeutic agent, a prophylactic or therapeutic agent is provided for a metabolic disease, a circulatory disease or a nervous system disease comprising the following (i) to (iii). (i) the compound according to any one of (1) to (45), or a pharmaceutically acceptable salt thereof; (ii) one or more compound (s) selected from the group consisting of (a) to (g) below: (a) antagonist or inverse agonist of histamine H3 other than (i), (b) a biguanide, (c) a PPAR agonist, (d) insulin, (e) somatostatin, (f) an a-glucosidase inhibitor, and (g) insulin secretagogues; and (ii) a pharmaceutically acceptable vehicle. Next, the terminology used in this specification will be described, and then the compound which relates to the present invention will be described in more detail. "Aryl group" means an aryl group of a hydrocarbon ring having from 6 to 14 carbon atoms, such as phenyl, naphthyl, biphenyl or anthryl. "Lower alkyl group" means a straight or branched chain alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isoamyl , neopentyl, isopentyl, 1,1-dimethylpropyl, 1-methylbutyl, 2-methylbutyl,1,2-dimethylpropyl, hexyl, isohexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3- dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1, 2,2-trimethylpropyl or 1-ethyl-2-methylpropyl. "Cycloalkyl group having from 3 to 9 carbon atoms" means, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or cyclononyl. "Alkoxy group" means a group in which the hydrogen atom of a hydroxy group is substituted by the lower alkyl group described above, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentyloxy, hexyloxy or isohexyloxy. "Alkylsulfonyl group" means a group in which the alkyl group described above is combined with sulfonyl, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl or butylsulfonyl. "Alkylsulfonylamino group" means a group in which one of the hydrogen atoms of an amino group is substituted by the alkylsulfonyl group described above, for example, methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, isopropylsulfonylamino, butylsulfonylamino, sec-butylsulfonylamino, tert-butylsulfonylamino , N-methyl-methylsulfonylamino, N-methyl-ethylsulfonylamino, N-methyl-propylsulfonylamino, N-methyl-isopropylsulfonylamino, N-methyl-butylsulfonylamino, N-methyl-sec-butylsulfonylamino, N-methyl-tert-butylsulfonylamino, N-ethyl -methylsulfonylamino, N-ethyl-ethylsulfonylamino, N-ethyl-propylsulfonylamino, N-ethyl-isopropylsulfonylamino, N-ethyl-butylsulfonylamino, N-ethyl-sec-butylsulfonylamino or N-ethyl-tert-butylsulfonylamino. "Group (lower cycloalkyl) sulfonyl" means a group in which the "cycloalkyl group having from 3 to 9 carbon atoms" described above is combined with sulfonyl, for example, cyclopropylsulfonyl, cyclobutylsulfonyl, cyclopentylsulfonyl, cyclohexylsulfonyl, cycloheptylsulfonyl, cyclooctylsulfonyl or cyclononylsulfonyl. "Aralkyl group" means a group in which the lower alkyl group described above has one of the aryl groups described above, ie, benzyl, 1-phenylethyl, 2-phenylethyl, 1-naphthylmethyl or 2-naphthyl methyl. "Heteroaryl group" means a 5- to 7-membered monocyclic group having 1 to 3 heteroatoms which are selected from the group consisting of oxygen, sulfur and nitrogen, or a bicyclic ring in which the monocyclic ring is fused to a ring of benzene or a pyridine ring, for example, furyl, thienyl, pyrrolyl, imidazolyl, triazolyl, thiazolyl, thiadiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazolyl, pydinidyl, quinolyl, isoquinolyl, quinazolinyl, quinolidinyl, quinoxanil, cinnoiinyl, benzoimidazolyl, imidazopyridyl, benzofuranyl, naphthylidenyl, 1, 2-benzoisoxazolyl, benzoxazolyl, benzothiazolyl, oxazolopyridyl, pyridothiazolyl, isothiazolopyridyl or benzothienyl. "Halogen atom" means fluorine, chlorine, bromine or iodine.

"Alkoxycarbonylamino group" is a group in which one of the hydrogen atoms in an amino group is substituted by the alkoxycarbonyl group described above, for example, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, isopropoxycarbonylamino, butoxycarbonylamino, sec-butoxycarbonylamino, tert-butoxycarbonylamino, pentyloxycarbonylamino, N-methylmethoxycarbonylamino, N-methylethoxycarbonylamino, N-methylpropoxycarbonylamino, N-methylisopropoxycarbonylamino, N-methylbutoxycarbonylamino, N-methyl-sec-butoxycarbonylamino, N-methyl-tert-butoxycarbonylamino, N-ethylmethoxycarbonylamino, N-ethylethoxycarbonylamino, N-ethylpropoxycarbonylamino, N-Ethyl isopropoxycarbonylamino, N-ethylbutoxycarbonylamino, N-ethyl-sec-butoxycarbonyl amino or N-ethyl-tert-butoxycarbonylamino. "Hydroxyalkyl group" means a group in which one of the hydrogen atoms of the lower alkyl group described above is substituted by hydroxy, for example, hydroxymethyl, hydroxyethyl, 1-hydroxypropyl, 1-hydroxyethyl, 2-hydroxypropyl or 2-hydroxy-1-methylethyl. "Mono (lower alkyl) carbamoyl group" means a group in which a carbamoyl group is monosubstituted by the lower alkyl group described above, for example, methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, sec-butylcarbamoyl or tert-butylcarbamoyl. "Group di (lower alkyl) carbamoyl" means a carbamoyl which is disubstituted by the same or different lower alkyl groups.

Examples of "di (lower alkyl) carbamoyl" groups are dimethylcarbamoyl, diethylcarbamoyl, ethylmethylcarbamoyl, dipropylcarbamoyl, methylpropylcarbamoyl and diisopropylcarbamoyl. "Di (lower alkyl) carbamoyl group" also includes a 5- to 8-membered monocyclic ring in which the nitrogen atom forming the carbamoyl group, and the same or different lower alkyl groups combined with the nitrogen atom, together form, or a bicyclic ring in which the monocyclic ring is fused with a benzene ring or a pyridine ring. Specific examples are groups represented by the following formulas.

"Alkylamino group" means a group in which an amino group is monosubstituted by the lower alkyl group described above, for example, methylamino, ethylamino, propylamino, isopropylamino, butylamino, sec-butylamino or tert-butylamino.

"Dialkylamino group" means a group in which an amino group is disubstituted by the same or different lower alkyl groups, for example, dimethylamino, diethylamino, dipropylamino, methylpropylamino or diisopropylamino. "Aminoalkyl group" means a group in which one of the hydrogen atoms forming the alkyl group described above is substituted by amino, for example, aminomethyl, aminoethyl or aminopropyl. "Alkanoyl group" means a group in which the alkyl group described above is combined with a carbonyl group, for example, methylcarbonyl, ethylcarbonyl, propylcarbonyl or isopropylcarbonyl. "Alkanoylamino group" means a group in which the alkanoyl group described above is combined with an amino group, for example, acetylamino, propanoylamino, butanoylamino, pentanoylamino, N-methylacetylamino, N-methylpropanoylamino, N-methylbutanoylamino, N-methylpentanoylamino, N-ethylacetylamino, N-ethylpropanoylamino, N-ethylbutanoylamino or N-ethylpentanoylamino. "Mono (lower alkyl) aminocarbonyloxy group" means a carbonyloxy group monosubstituted by the lower alkyl group described above, for example, methylaminocarbonyloxy, ethylaminocarbonyloxy, propylaminocarbonyloxy or isopropylaminocarbonyloxy. "Di (lower alkyl) aminocarbonyloxy group" means a carbonyloxy group disubstituted by the lower alkyl groups described above, for example, dimethylaminocarbonyloxy, diethylaminocarbonyloxy, diisopropylaminocarbonyloxy or ethylmethylaminocarbonyloxy. "Alkylthio group" means a group in which the alkyl group described above is combined with a sulfur atom, for example, methylthio, ethylthio, propylthio or isopropylthio. "Cycloalkoxy group" means a group in which the hydrogen atom of the hydroxy group is substituted by a cycloalkyl group having from 3 to 9 carbon atoms, for example, cyclopropoxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy or cycloheptyloxy. "Aryloxy group" means a group in which an oxygen atom is combined with the aryl group described above, for example, phenoxy, naphthalen-1-yl-oxy or naphthalen-2-yl-oxy. "Heteroaryloxy group" means a group in which the heteroaryl group described above is combined with an oxy group, for example, furan-2-yloxy group, furan-3-yloxy, thiophen-2-yloxy, thiophene-3. -iloxy, 1 H-pyrrol-2-yloxy, 1 H-pyrrol-3-yloxy, 1 H-imldazol-2-yloxy, 1 H-imidazol-4-yloxy, 3 H-imidazol-4-yloxy, 4 H - [1, 3,4] triazol-3-yloxy, 2H- [1, 2,4] triazol-3-yloxy, 1 H- [1, 2,4] triazol-3-yloxy, thiazole-2 iloxy, thiazol-4-yloxy, thiazol-5-yloxy, pyridin-2-yloxy, pyridin-3-yloxy, pyridin-4-yloxy, pyrimidin-2-yloxy, pyrimidin-4-yloxy, pyrimidin-5-yloxy, pyridazin-3-yloxy, pyridazin-4-yloxy, 2H-pyrazol-3-yloxy, 1 H-pyrazol-4-yloxy, 1 H-pyrazolyl-3oxy, pyrazin-3-yloxy, pyrazin-4-yloxy, quinolin- 2-Iloxy, quinolin-3-yloxy, quinolin-4-yloxy, isoquinolin-1-yloxy, isoquinolin-3-yloxy, isoquinolin-4-yloxy, quinazolin-2-yloxy, quinazolinyl-3-yloxy, quinoxalin-2- iloxy, quinoxalin-3-yloxy, cinnolin-3-yloxy, cinnolin-4-yloxy, 1H-benzimidazol-2-yloxy, 1H-imidazo [4,5-b] pyridin-5-yloxy, 1H-imidazo [4,5-b] pyridin-6-yloxy, 1 H- imidazo [4,5-b] pyridin-7-yloxy, benzo [d] isoxazol-4-yloxy, benzo [d] isoxazol-5-yloxy, benzo [d] isoxazol-6-yloxy, benzoxazol-4-yloxy, benzoxazol-5-yloxy or benzoxazol-6-yloxy. "Heteroarylalkyl group" means a group in which the heteroaryl group described above is combined with the alkyl group described above, for example, furan-3-ylmethyl, furan-2-ylmethyl, furan-3-ylethyl, furan-2 iletyl, furan-3-ylpropyl, furan-2-ylpropyl, thiophen-3-ylmethyl, thiophen-2-ylmethyl, thiophen-3-ylethyl, thiophen-2-ylethyl, thiophen-3-ylpropyl, thiophen-2-ylpropyl, 1 H-pyrrol-3-ylmethyl, 1 H-pyrrol-2-ylmethyl, 1 H-pyrrol-3-ylethyl, 1 H-pyrrol-2-ylethyl, 1 H-pyrrol-3-ylpropyl, 1 H-pyrrol- 2-ylpropyl, 1 H-imidazol-4-ylmethyl, 1 H-imidazol-2-ylmethyl, 1 H-imidazol-5-ylmethyl, 1 H-imidazol-4-ylethyl, 1 H-imidazol-2-ylethyl, 1 H-imidazol-5-ylethyl, 1 H-imidazol-4-ylpropyl, 1 H-imidazol-2-ylpropyl, 1 H-imidazol-5-ylpropyl, 1 H- [1,2,3] triazol-4-ylmethyl , 1 H- [1,2,3] triazol-5-ylmethyl, 1 H- [1,2,3] triazole-4-ylethyl, 1 H- [1,2,3] triazole-5-ylethyl, 1 H- [1,2,3] triazol-4-ylpropyl, 1 H- [1,2,3] triazol-5-ylpropyl, 1 H- [1,4] triazol-3-methylmethyl, 1 H - [1, 2,4] tr iazol-5-ylmethyl, 1 H- [1, 2,4] triazol-3-ylethyl, 1 H- [1,4] triazole-5-ylethyl, 1 H- [1,4] triazole- 3-ylpropyl, 1 H- [1, 2,4] triazol-5-ylpropyl, thiazol-4-ylmethyl, thiazol-3-ylmethyl, thiazol-2-ylmethyl, thiazol-4-ylethyl, thiazol-3-ylethyl, thiazol-2-ylethyl, thiazol-4-ylpropyl, thiazol-3-ylpropyl, thiazol-2-ylpropyl, [1,4] thiadiazol-3-methyl, [1,4] thiadiazol-3-ylethyl , [1, 2,4] thiadiazol-3-ylpropyl, [1, 2,4] thiadiazol-5-ylmethyl, [1] -thiadiazol-d-ylethyl, [1, 2,4] thiadiazol-5-ylpropyl, [1 , 3,4] thiadiazol-2-ylmethyl, [1, 3,4] thiadiazol-2-ylethyl or [1, 3,4] thiadiazol-2-ylpropyl, "Monoarylcarbamoyl group" means a carbamoyl group monosubstituted by the group aryl described above, for example, phenylcarbamoyl. Next, the compound represented by the formula (I) described above in relation to the present invention in more detail. First the symbols used in the Formula will be described (I) - (I) [where the symbols have the same meaning as above.] Ar is phenyl, pyrimidinyl, pyridyl, thiazolyl, oxazolyl, pyrazolyl, thiadiazolyl or thienyl, ie a divalent group that is formed by removing two hydrogen atoms from benzene, pyrimidine, pyridine, thiazole, oxazole, pyrazole, thiadiazole or thiophene, but among these, phenyl or pyrimidinyl is preferred, ie a divalent group that is formed by removing two hydrogen atoms from benzene or pyrimidine. Ar can be substituted by halogen, lower alkoxy, hydroxy and lower alkyl. Examples of this halogen are fluorine, bromine and chlorine. As lower alkoxy, methoxy and ethoxy may be mentioned. This lower alkoxy group may also be substituted by halogen. As lower alkyl, methyl and ethyl can be mentioned. X1 is a nitrogen atom, a sulfur atom or an oxygen atom, but among these, an oxygen atom is preferred. X2 is represented by the formula (II): (I I) [where the symbols have the same meaning as the previous ones], by the formula (III): (l l l) [where the symbols have the same meaning as the previous ones], or by the formula (IV): [where the symbols have the same meaning as the previous ones]. First, the case in which -X2 is represented by the formula (II) will be described.

(I I) [where the symbols have the same meaning as the previous ones.] n is an integer from 2 to 4, preferably 3 or 4, but more preferably 3. The "lower alkyl groups" represented by R4 and R5 are identical to the foregoing. More specifically, this lower alkyl group can be for example methyl, ethyl, propyl or isopropyl. The "lower alkyl groups" represented by R4 and R5 may be the same or different. The "cycloalkyl groups" represented by R4 and R5 are identical to the foregoing. This cycloalkyl group can be, for example, cyclopropyl, cyclobutyl or the like. R4, R5 and a nitrogen atom of the formula (II) described above can form a 5- to 8-membered monocyclic ring (in addition to the nitrogen atom linking R4 and R5, this ring can further have a heteroatom which is selected from a nitrogen atom, a sulfur atom and an oxygen atom). Examples of monocyclic ring are a pyrrolidine ring, a piperidine ring, a homopiperidine ring, a heptamethyleneimine ring, a piperazine ring, a morpholine ring and a homomorpholine ring. R4, R5 and the nitrogen atom of the formula (II) described above can also form a bicyclic ring. This bicyclic ring is an aza-bicyclic ring, and is a non-aromatic ring containing the nitrogen atom linking R4 and R5 in the formula (II) described above as the only hetero atom that forms the ring. This ring preferably has 6 to 10 atoms forming the ring, but more preferably 7 to 9 atoms forming the ring. Examples of this ring are groups represented by the formulas (V).

(V) (CH2) n in the formula (II) described above can be substituted by an Lower alkyl group having 1 to 3 carbon atoms. Examples of this lower alkyl group are methyl, ethyl, n-propyl and isopropyl. When X2 is a group represented by the formula (II) described above, it is preferred that n is 3 or 4, and R4, R5 and a nitrogen atom together form a monocyclic ring of 5 to 8 members (this monocyclic ring may have as substituent group a halogen atom, or a lower alkyl group which may be substituted by halogen), or form a bicyclic ring of 6 to 10 members, and is more preferred than n is 3, and R 4, R 5 and a nitrogen atom together form a monocyclic ring of 5. to 8 members (this monocyclic ring may have as a substituent group a halogen atom, or a lower alkyl group which may be substituted by halogen), or form a 6 to 10 membered bicyclic ring. Next, the case in which -X2 is represented by the formula (III) will be described.

(I I I) [where the symbols have the same meaning as the previous ones.] M is an integer from 0 to 4, among which is preferred, 2 or 3. R6 is a lower alkyl group or a cycloalkyl group. The "lower alkyl group" represented by R6 is identical to the previous ones. More specifically, this lower alkyl group can be, for example, methyl, ethyl, propyl, butyl or pentyl.

The "cycloalkyl group" represented by R6 is identical to the lower alkyl group described above, for example, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tert-butyl, pentyl, isoamyl, neopentyl, 1,1-dimethylpropyl, 1- methylbutyl, 2-methylbutyl, hexyl, isohexyl, 1-methylpentyl or 1,1-dimethylbutyl. When -X2 is represented by the formula (III), two carbon atoms different from the carbon atoms forming X2 can be joined by - (CH2) m11- (m11 is an integer from 1 to 3) forming a bicyclic ring. Examples of this bicyclic ring are groups represented by the formulas (III-2). ar. < M | -2 > Next, the case in which -X2 is represented by the formula (IV) will be described. [where the symbols have the same meaning as the previous ones.] m is an integer from 0 to 4, among which 2 or 3 are preferred.

R4 and R5 have the same meanings as the previous ones, and the preferred and most preferred aspects are identical to the aspects of R4 and R5 described above.

When -X2 is represented by the formula (IV), two atoms of carbon different from the carbon atoms that form X2 (with the exception of the carbon atoms of R4 and R5) can be joined by a single bond or - (CH2) m11- (m11 is an integer from 1 to 3) forming a ring bicyclic Examples of this bicyclic ring are the groups represented by the formulas (IV-2).

OV-2) [where the symbols have the same meaning as the above.] When -X2 is one of the bicyclic rings represented by the formulas (IV-2), the preferred aspects of R4 and R5 are identical to the previous Of the above, more specifically, X2 can be for example 2-dimethylaminoethyl, 2-diethylaminoethyl, 2-di-n-propylaminoethyl, 2-diisopropylaminoethyl, 3-dimethylaminopropyl, 3-diethylaminopropyl, 3-di-n-propylaminopropyl, 3- ducsopropylaminopropyl, 4-dimethylaminobutyl, 4-diethylaminobutyl, 4-di-n-propylaminobutyl, 4-diisopropylaminobutyl, 2- (ethylmethylamino) ethyl, 2- (ethylpropylamino) ethyl, 2- (ethylisopropylamino) ethylene, 2- (methylisopropylamino) ethyl, 2- (ethyl-n-propylamino) ethyl, 3- (ethylmethylamino) propyl, 3- (ethylpropylamino) propyl, 3- (ethylisopropylamino) propyl, 3- (methylisopropylamino) propyl, 2- (ethyl-n-propylamino) propyl, 4- (ethylmethylamino) butyl, 4- (ethylpropylamino) butyl, 4- (ethylisopropylamino) butyl, 2- (ethyl-n-propylamino) butyl, 2-dicyclopropylaminoethyl, 2-dicyclobutylaminoethyl, 2-dicyclopentylaminoethyl, 2- dicyclohexylaminoethyl, 3-dicyclopropylaminopropyl, 3-dicyclobutylaminopropyl, 3-dicyclopentylaminopropyl, 3-dicyclohexylaminopropyl, 4-dicyclopropylaminobu lime, 4-dicyclobutylaminobutyl, 4-dicyclopentylaminobutyl, 4-dicyclohexylaminobutyl, 2- (cyclobutyl-cyclopropylamino) ethyl, 2- (cyclobutyl-cyclopentylamino) ethyl, 2- (cyclohexyl-cyclopentyl) ethyl, 3- (cyclobuty-cyclopropylamino) propy 3- (cyclobutyl-cyclopentylamino) propyl, 3- (cyclohexyl-cyclopentylamino) propyl, 4- (cyclobutyl) cyclopropylaminobutyl, 4- (cyclobutyl) cyclopentylamino) butyl, 4- (cyclohexyl-cyclopentylamino) butyl, - (cyclopropylmethylamino) ethylene, 2- (cyclopropylethylamino) ethyl, 2- (cyclopropyl-n-propylamino) ethyl, 2- (cyclopropyl-isopropylamino) ethyl, 2- (cyclobutylmethylamino) ethyl, 2- (cyclobutylethylamino) ethyl, 2- ( cyclobutyl-n-propylamino) ethyl, 2- (cyclobutyl-isopropylamino) ethyl, 2- (cyclopentylmethylamino) ethyl, 2- (cyclopentylethylamino) ethyl, 2- (cyclopentyl-n-propylamino) ethyl, 2- (cyclopentyl-isopropylamino) -ethyl, 2- ( cyclohexylmethylamino) ethyl, 2- (cyclohexylethylamino) ethyl, 2- (cyclohexyl-n-propylamino) ethyl2- (cyclohexylisopropylamino) ethyl, 3- (cyclopropylmethylamino) propyl, 3- (cyclopropylethylamino) propyl, 3- (cyclopropyl-n-propylamino) propyl, 3- (cyclopropyl-isopropylamino) propyl, 3- (cyclobutylmethylamino) propyl, 3- ( cyclobutylethylamino) propyl, 3- (cyclobutyl-n-propylamino) propyl, 3- (cyclobutyl-isopropylamino) propyl, 3- (cyclopentylmethylamino) propyl, 3- (cyclopentylethylamino) propyl, 3- (cyclopentyl-n-propylamino) propyl, 3- ( ciclopentilisopropilamino) propyl, 3- (ciclohexilmetilamlno) propyl, 3- (cyclohexylethylamino) propyl, 3- (cyclohexyl-n-propylamino) propyl, 3- (ciclohexilisopropilamino) propyl, 4- (ciclopropilmetilam¡no) butyl, 4- (cyclopropylethylamino) butyl, 4- (cyclopropyl-n-propylamino) butyl, 4- (cyclopropyl-isopropylamino) butyl, 4- (cyclobutylmethylamino) butyl, 4- (cyclobutylethylamino) butyl, 4- (cyclobutyl-n-propylamino) butyl, 4- (cyclobutyl-isopropylamino) butyl, 4- (cyclopentylmethylamino) butyl, 4- (cyclopentylethylamino) butyl, 4- (cyclopentyl-n-propylamino) butyl, 4- (cyclop entilisopropilamino) butyl, 4- (ciclohexiImetilamino) butyl, 4- (cyclohexylethylamino) butyl, 4- (cyclohexyl-n-propylamino) butyl, 4- (ciclohexilisopropilamino) butyl, 2-pyrrolidin-1-yl-ethyl, 2-piperidin- 1-yl-ethyl, 2-homopiperidin-1-yl-ethyl, 2-heptamethylene-imin-1-yl-ethyl, 2-morpholin-4-yl-ethyl, 2-homomorpholin-4-yl-ethyl, 3-pyrrolidin- 1-yl-propyl, 3-pyridin-1-yl-propyl, 3-homopiperidin-1-yl-propyl, 3-heptamethylene-imin-1-yl-propyl, 3-morpholin-4-yl-propyl, 3- Homomorpholin-4-yl-propyl, 4-pyrrolidin-1-yl-butyl, 4-piperidin-1-yl-butyl, 4-homopiperidin-1-yl-butyl, 4-heptamethylene-imin-1-yl-butyl, 4- morpholin-4-yl-butyl, 4-homomorpholin-4-yl-butyl, 2- (5-aza-bicyclo [2,1, 1] hexan-5-yl-ethyl, 2- (6-aza) -bicyclo [3.1,1] heptan-6-yl-ethyl, 2- (7-aza-bicyclo [2,1,1] heptan-7-yl-ethyl), 2- (8-aza-bicyclo [3, 2,1] octan-8-yl-ethyl), 2- (9-aza-bicyclo [3.3.1] nonan-9-yl-ethyl), 3- (5-aza-bicyclo [2.1, 1] hexan-5-yl-propyl), 3- (6-aza-bicyclo [3.1.1] heptan-6-yl-propyl), 3- (7-aza-bicyclo [2.1, 1] heptan-7-i l-propyl), 3- (8-aza-bicyclo [3.2.1] octan-8-yl-propyl), 3- (9-aza-bicyclo [3.3.1] nonan-9-yl- propyl), 4- (5-aza-bicyclo [2,1, 1] hexan-5-yl-butyl), 4- (6-aza-bicyclo [3.1.1] heptan-6-yl-butyl) 4- (7-aza-bicyclo [2,1,1] heptan-7-yl-butyl) 4- (8-aza-bicyclo [3.2.1] octan-8-yl-butyl) 4- (9-aza-bicyclo [3.3.1] nonan-9-yl-butyl, 1-methylazetidin-3-yl, 1-methyl-azetidin-2-yl), 1-ethylazetidin-3-yl, yl 1-ethyl-azetidin-2-1-isopropylazetidin-3-yl, 1-isopropylazetidin-2-yl, 1-ciclopropilazetidin-3-yl, 1-ciclobutilazetidin-2-yl, 1-ciclobutilazetidin-3-yl, 1-ciclobutilazetidin-2-yl, 1-ciclopentilazetidin-2-1-ciclopentilazetidin-3-yl, 1-ciclohexiIazetidin-3-yl, 1-ciclohexilazetidin-2-yl, 1-methylpyrrolidin-3-yl, 1- methy1-pyrrolidin-2-yl, 1-ethylpyrrolidin-3-yl, 1-ethylpyrrolidin-3-yl, 1-ylpropyl-pyrrolidin-3-yl, 1-isopropylpyrroline-2-yl, 1- Cyclopropylpyrrolidin-3-yl, 1-cyclopropyl-pyrrolidin-2-yl, 1-cyclobutyl-pyrrolidin-3-yl, 1-cyclobutyl-pyrrolidin-2-yl, 1-cyclopentyl-pyr rolidin-3-yl, 1-cyclopentylpyrrolidin-2-yl, 1-cyclohexylpyrrolidin-3-yl, 1-cyclohexylpyrrolidin-2-yl, 1-methylpiperidin-4-yl, 1-methylpiperidin-3-yl , 1-methylpiperidin-2-yl, 1-etllperidin-4-yl, 1-ethylpiperidin-3-yl, 1-ylpperperidyl-2-yl, 1- Sodopropylperidin-4-yl, 1-isopropylpiperidin-3-yl, 1-isopropylpiperidin-2-yl, 1-cyclopropylpiperidin-4-yl, 1-cyclopropylpperiod-3- yl, 1-ciclopropiIpiper¡din-2-¡lo, 1-cyclobutylpiperidin-4-yl, 1-ciclobutilpiperidil-3-yl, 1-cyclobutylpiperidin-2-yl, 1-cyclopentylpiperidin-4-yl, 1-cyclopentylpiperidin-3 -yl-2-yl -ciclohexilpiperidin, 1-cyclopentylpiperidin yl-2-1 -ciclohexilpiperidin-4-yl, 1 -ciclohexilpiperidin-3-yl, 1, 3-dimetilaminociclobutilo, 3-dietilaminociclobutilo, 3-diisopropilaminociclobutilo, 3-diciclopropilaminobutilo , 3-dicyclobutylaminobutyl, 3-dicyclopentylaminobutyl, 3-dicyclohexylaminobutyl, 2-dimethylaminocyclobutyl, 2-diethylaminocyclobutyl, 2-diisopropylaminocyclobutyl, 2-dicyclop Ropylaminobutyl, 2-dicyclobutylaminobutyl, 2-dicyclopentylaminobutyl, 2-dicyclohexylaminobutyl, 3- (cyclopropylmethylamino) cyclobutyl, 3- (cyclopropylethylamino) cyclobutyl, 3- (cyclobutylmethylamino) cyclobutyl, 3- (cyclobutylethylamino) cyclobutyl, 3- (cyclopentylmethylamino) cyclobutyl, 3- (cyclopentylethylamino ) cyclobutyl, 3- (cyclohexylmethylamino) cyclobutyl, 2- (cyclopropylmethylamino) cyclobutyl, 2- (cyclopropylethylamino) cyclobutyl, 2- (cyclobutylmethylamino) cyclobutyl, 2- (cyclobutylethylamino) cyclobutyl, 2- (cyclopentylmethylamino) cyclobutyl, 2- ( cyclopentylethylamino) cyclobutyl, 2- (cyclohexylmethylamino) cyclobutyl, 3-pyrrolidin-1-yl-cyclobutyl, 2-pyrrolidin-1-yl-cyclobutyl, 3-pyrrolidin-1-yl-cyclopentyl, 2-pyrrolidin-1-yl-cyclopentyl , 4-pyrrolidin-1-yl-cyclohexyl, 3-pyrrolidin-1-yl-cyclohexyl, 2-pyrrolidin-1-ylclohexyl, 3-piperidin-1-yl-cyclobutyl, 2-piperidin-1- il-cyclobutyl, 3-piperidin-1-yl-cyclopentyl, 2-p-piperidin-1-yl-cyclopentyl, 4-piperidin-1-yl-cyclohexyl, 3-piperidin-1-yl-cyclohexyl, 2-pip eridin-1-yl-cyclohexyl, 3-homopiperidin-1-yl-cyclobutyl, 2-homopiperidin-1-yl-cyclobutyl, 3-homopiperidin-1-yl-cyclopentyl, 2-homopiperidin-1-yl- cyclopentyl, 4-homopiperidin-1-yl-cyclohexyl, 3-homopiperidin-1-yl-cyclohexyl, 2-homopiperidin-1-yl-cyclohexyl, 3-heptamethyleneimin-1-yl-cyclobutyl, 2-heptamethyleneimin 1-cyclobutyl, 3-heptamethyleneimin-1-yl-cyclopentyl, 2-heptamethyleneimin-1-yl-cyclopentyl, 4-heptamethyleneimin-1-yl-cyclohexyl, 3-heptamethyleneimin-1-yl-cyclohexyl, 2-heptamethyleneimin- 1-cyclohexyl, 2-morpholin-4-yl-cyclobutyl, 3-morpholin-4-yl-cyclobutyl, 2-morpholin-4-yl-cyclopentyl, 3-morpholin-4-yl-cyclopentyl, 2-morpholino- 4-yl-cyclohexyl, 3-morpholin-4-yl-cyclohexyl, 4-morpholin-4-yl-cyclohexyl, 2-homomorpholin-4-yl-cyclobutyl, 3-homomorpholin-4-yl-cyclobutyl, 4-homomorpholino- 4-yl-cyclobutyl, 2-homomorpholin-4-yl-cyclopentyl, 3-homomorpholin-4-yl-cyclopentyl, 4-homomorpholin-4-yl-cyclopentyl, 2-homomorpholin-4-yl-cyclohexyl, 3-homomorpholino- 4-il-ci clohexyl, 4-homomorpholin-4-yl-cyclohexyl, 2- (5-aza-bicyclo [2,1, 1] hexan-5-yl) cyclobutyl, 2- (6-aza-bicyclo [3.1, 1] heptan-6-yl) cyclobutyl, 2- (7-aza-bicyclo [2,1, 1] heptan-7-yl) cyclobutyl, 2- (8-aza-bicyclo [3.2.1] octane- 8-yl) cyclobutyl, 2- (9-aza-bicyclo [3.3.1] nonan-9-yl) cyclobutyl, 3- (5-aza-bicyclo [2,1, 1] hexan-5-yl) cyclobutyl, 3- (6-aza-bicyclo [3.1.1] heptan-6-yl) cyclobutyl, 3- (7-aza-bicyclo [2,1,1] heptane) -7-yl-cyclobutyl, 3 - (8-aza-bicyclo [3.2.1] octan-8-yl) cyclobutyl, 3- (9-aza-bicyclo [3.3.1] nonan-9-yl) cyclobutyl, 2- (5- aza-bicyclo [2,1, 1] hexan-5-yl) cyclopentyl, 2- (6-aza-bicyclo [3.1.1] heptan-6-yl) cyclopentyl, 2- (7-aza-bicyclo [ 2.1, 1] heptan-7-yl) cyclopentyl, 2- (8-aza-bicyclo [3.2.1] octan-8-yl) cyclopentyl, 2- (9-aza-bicyclo [3.3, 1] nonan-9-yl) cyclopentyl, 3- (5-aza-bicyclo [2,1, 1] hexan-5-yl) cyclopentyl, 3- (6-aza) -bicyclo [3.1.1] heptan -6-yl-cyclopentyl, 3- (7-aza-bicyclo [2,1, 1] heptan-7-yl) cyclopentyl, 3- (8-aza-bicyclo [3.2.1] octan-8-yl) ) cyclopentyl, 3- (9-aza-bicyclo [3.3, 1] nonan -9-yl) cyclopentyl, 2- (5-aza-bicyclo [2, 1, 1] hexan-5-yl) cyclohexyl, 2- (6-aza-bicyclo [3.1.1] heptan-6-yl) ) cyclohexyl, 2- (7-aza-bicyclo [2,1,1] heptan-7-yl) cyclohexyl, 2- (8-aza-bicyclo [3,2,1] octan-8-yl) cyclohexyl, 2 - (9-aza-bicyclo [3.3.1] nonan-9) -yl-cyclohexyl, 3- (5-aza-bicyclo [2,1, 1] hexan-5-yl) cyclohexyl, 3- (6 -aza-bicyclo [3.1, 1] heptan-6-yl) cyclohexyl, 3- (7-aza-bicyclo [2,1, 1] heptan-7-yl) cyclohexyl, 3- (8-aza-bicyclo) [3,2,1] octan-8-yl) cyclohexyl, 3- (9-aza-bicyclo [3,3,1] nonan-9-yl) cyclohexyl, 3- (7-aza-bicyclo [2.2 , 1] hept-7-yl) propyl, 3- (8-aza-bicyclo [3.2.1] oct-8-yl) propyl, 3- (3,3-difluoropyrrolidin-1-yl) propyl, - (3-fluoropiperidin-1-yl) propyl, 3 - [(3R) -3-fluoropyrrolidin-1-yl] propyl, 3- (4,4-difluoropiperidin-1-yl) propyl, 3- (4-fluoropiperidine) -1 -yl) propyl, 3- (3,3-difluoropiperidin-1-yl) propyl, 3 - [(3R) -3-methylpiperidin-1-yl] propyl, 3 - [(2R, 5R) -2, 5-dimethylpyrrolidin-1-yl] propyl, 3- [3-methylpyrrolidin-1-yl-propyl, 3 - [(2S) -2-methylpyrrolidin-1-yl] propyl, 3 - [(2R) -2 -methylpyrrolidin-1-yl] propion, 3 - [(3S) -3-methylpiperidin-1-yl] propyl, 3- (azepan-1-yl) propyl, 3 - [(2-oxopyrrolidin-1-yl)] propyl. Among these, 3-piperidin-1-yl-propyl, 1-cyclobutylpiperidin-4-yl, 1-cyclopentyl-piperidin-4-yl, 3 - [(3S) -3-methylpiperidin-1-ylpropyl, 3 - [( 2R) -2-metylpyrrolidin-1 -yl] propyl, 3 - [(2S) -2-methylpyrrolidin-1-yl] propyl, 1-cidopentylpiperidin-4-yl, 3- (pyrrolidin-1-yl) propyl, 3 - (piperidin-1-yl) propyl. R1 is a 5-6 membered heteroaryl group having 1 to 4 heteroatoms which are selected from nitrogen, sulfur and oxygen in the ring, a heteroarylalkyl group (in which heteroaryl in heteroarylalkyl has the same meaning as above), a straight or branched chain lower alkyl group (this lower alkyl group may be further substituted by hydroxy, halogen, alkoxy, allyloxy or aralkyloxy), a phenyl group, an aralkyl group, an alkoxy group, an alkylthio group or a lower alkyl group )Not me.

In the "5- to 6-membered heteroaryl group having 1 to 4 heteroatoms which are selected from nitrogen, sulfur and oxygen in the ring" represented by R 1, when the ring contains 2 to 4 heteroatoms, these heteroatoms may be equal or different Examples of 5-6 membered heteroaryl groups are furyl, thienyl, pyrrolyl, imidazolyl, triazolyl, thiazolyl, thiadiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazolyl and pyrazdinyl. The "heteroarylalkyl group" represented by R 1 has the same meaning as the previous one. R1 is preferably a lower alkyl group having 1 to 3 carbon atoms (this lower alkyl group may be further substituted by halogen), or phenyl, but more preferably, methyl, ethyl, n-propyl, isopropyl or trifluoromethyl. R2 and R3 may be the same or different, and each represents a hydrogen atom, amino, nitro, cyano, hydroxy, (lower alkyl) sulfonyl, a halogen atom, lower alkyl (this lower alkyl group may be further substituted by hydroxy or a halogen atom), lower cycloalkyl (this lower cycloalkyl group may be further substituted by a halogen atom), lower alkoxy (this lower alkoxy group may be further substituted by a halogen atom), lower cycloalkoxy (this lower cycloalkoxy group may be further substituted by a halogen atom), aryloxy, aralkyloxy, aryl, heteroaryl, mono (lower alkyl) carbamoyl, di (lower alkyl) carbamoyl, (lower alkyl) carboxamide, arylcarboxamide, heteroarylcarboxamide, alkanoyl, alkylthio, alkoxycarbonylamino, alkyl, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, aralkyl, alkanoylamino or alkanoylalkylamino. The "lower alkyl sulfonyl group" represented by R2 or R3 has the same meaning as the previous one. The "lower alkyl group" represented by R2 or R3 has the same meaning as the previous one. This lower alkyl group may be further substituted by a hydroxy group, or a halogen atom such as chlorine or fluorine. The "lower alkoxy group" represented by R2 or R3 has the same meaning as the previous one. The "lower cycloalkoxy group" represented by R2 or R3 means a group in which the lower cycloalkyl group described above is combined with an oxygen atom. This lower cycloalkoxy group may also be substituted by a halogen atom such as chlorine or fluorine. The "aryloxy group" represented by R2 or R3 has the same meaning as the previous one. The "aralkyloxy group" represented by R2 or R3 means a group in which the aralkyl group described above is combined with an oxygen atom. The "aryl group" represented by R2 or R3 has the same meaning as the previous one.

The "heteroaryl group" represented by R2 or R3 has the same meaning as the previous one. The "mono (lower alkyl) carbamoyl group" represented by R2 or R3 has the same meaning as the previous one. The "di (lower alkyl) carbamoyl group" represented by R2 or R3 has the same meaning as the previous one. The "lower alkylcarboxamide group" represented by R2 or R3 means a group in which the straight or branched chain alkyl group described above having 1 to 6 carbon atoms is combined with carboxamide, for example, methylcarboxamide, ethylcarboxamide or isopropylcarboxamide. The "alkanoyl group" represented by R2 or R3 means a group in which the alkyl group described above is combined with carbonyl, for example, methylcarbonyl, ethylcarbonyl, propylcarbonyl or isopropylcarbonyl. The "alkylthio group" represented by R2 or R3 means a group in which the alkyl group described above is combined with sulfur, for example, methylthio, ethylthio, propylthio or isopropylthio. The "alkoxycarboxamide group" represented by R2 or R3 means a group in which the alkoxy group described above is combined with carboxamide, for example, methoxycarboxamide, ethoxycarboxamide or isopropoxycarboxamide.

The "arylcarboxamide group" represented by R2 or R3 means a group in which the aryl group described above is combined with carboxamide, for example, phenylcarboxamide or naphthylcarboxamide. The "heteroarylcarboxamide group" represented by R2 or R3 means a group in which the heteroaryl group described above is combined with carboxamide, for example, furylcarboxamide, thienylcarboxamide or pyrrolylcarboxamide. The "arylsulfonylamino group" represented by R2 or R3 means a group in which the aryl group described above is combined with sulfonylamino, for example, phenylsulfonylamino or naphthylsulfonylamino. The "alkylaminosulfonyl group" represented by R2 or R3 means a group in which the alkyl group described above is combined with aminosulfonyl, for example, methylaminosulfonyl, ethylaminosulfonyl or isopropylaminosulfonyl. The "arylaminosulfonyl group" represented by R2 or R3 means a group in which the aryl group described above is combined with aminosulfonyl, for example, phenylaminosulfonylamino or naphthylaminosulfonylamino. The "aralkyl group" represented by R2 or R3 has the same meaning as the previous one. The "alkanoylalkylamino group" represented by R2 or R3 means a group in which the alkanoyl group described above is combined with the alkylamino described above, for example, acetylmethylamino or acetylethylamino. Ring A is a 4- to 5-membered heteroaryl ring having 1 or 2 heteroatoms which are selected from nitrogen or sulfur in the ring, or a benzene ring. This ring A can be for example a benzene ring, pyridine ring, pyrimidine ring, thiophene ring, or pyrazine ring, among which are preferred a benzene ring, pyridine ring and pyrimidine ring, and They prefer more a benzene ring and pyridine ring. When the 4- to 5-membered heteroaryl ring represented by Ring A has two heteroatoms, the heteroatoms may be the same or different. Ring A can have the substituent R2 or R3. The substituent groups R2 or R3 described above in this ring A may be the same or different. Of the above, the groups represented by the formula (VI): [where the symbols have the same meaning as the previous ones, and the formula (VI-0): n (VI-0) shows the link site] may be for example groups represented by the formulas (VI-1): (VI-1) [where the symbols have the same meaning as the previous ones], among which the groups represented by the formulas (VI-2) are preferred: (VI -2) [where the symbols have the same meaning as the previous ones] and among these, the groups represented by the formulas (VI-3) are more preferred: (VI-3) [where the symbols have the same meaning as the previous ones]. Any of the preferred aspects of Ar, X 1, X 2, Y, R 2, R 3, R 4, R 5, R 6, n, m and Ring A, which are described above, can be combined. More specifically, the compound represented by the formula (I): (I) [where the symbols have the same meaning as the above] is preferably 2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyI-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolnone, 2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 4- [3- (diethylamino) propoxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (2-methyl-1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolnone, 3-. { 4- [3- (2,5-dimethyl-1-pyrrolidinyl) propoxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 2-methyl-3-. { 4- [4- (1-piperidinyl) butoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 4- [3- (1-azepanyl) propoxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- [3- (1-Azocanil) propoxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (2-methyl-1-p.peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (4-methyl-1-p-peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone3- (4- { 3 - [(2R, 6S) -2,6-dimethyl-1-piperidinyl] propoxy.] Phenyl) -2-methyl-4- (3H) -quinazolinone, 2-met L-3-. { 4- [3- (3-methyl-1-p, pperidyl) propoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 4- [3- (3,5-dimethyl-1-piperidinyl) propoxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 2-methyl-3-. { 3- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 3-bromo-4- [3- (1-piperidinyl) propoxy] phenyl} -2-ethyl-4- (3H) -quinazolnone, 2-methyl-3-. { 4- [2- (1-piperidinyl) ethoxy] phenyl} -4- (3H) -quinazolinone, 2,5-dimethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolnone, 3-. { 4- [3- (1-piperidinyl) propoxy] phenol} -2-propyl-4- (3H) -quinazolinone, 3-. { 4- [3- (1-piperidiny) propoxy] phenyl} -2-trifluoromethyl-4- (3H) -quinazolinone, 2-isopropyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2,6-dimethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7-chloro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenol} -4- (3H) -quinnanolinone, 2,8-dimethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-ethyl-5-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-fluoro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-chloro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-hydroxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] pheniI} -4- (3H) -quinazolinone trifluoroacetate, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -5-trifluoromethyl-4- (3H) -quinazolinone, 7-fluoro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6-fluoro-2-methyl-3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6,7-difiuoro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6-bromo-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolnone, 6-chloro-2-methyl-3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6,7-dimethoxy-2-methyl-3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 8-chloro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 8-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-piperidin) propoxy] phenyl} benzo [g] -quinazoline-4- (3H) -one, 2,6-dimethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-ethyl-5-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-fluoro-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -5-trifluoromethyl-4- (3H) -quinazolinone, 5-chloro-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2,5-dimethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrid [2,3-d] pyrimidin-4- (3H) -one, 2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [2,3-d] pyrimidin-4- (3H) -one, 6-chloro-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 2-methyl-3-. { 4- [3- (1-piperidinium) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 2-methyl-3-. { 3- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [4,3-d] pyrimidin-4- (3H) -one, 2-methyl-3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} pyrido [4,3-d] pyrimidin-4- (3H) -one, 2-methyl-3-. { 2- [3- (1-piperidinyl) propoxy] -5-pyrimidinyl} -4- (3H) -quinazolinone, 2,5-dimethyl-3-. { 2- [3- (1-pperidinyl) propoxy] -5-pyrimidinyl} -4- (3H) -quinazolinone, 2-ethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrid [2,3-d] pyrimidin-4- (3H) -one, 6-chloro-2-ethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 6-chloro-2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenol} pyrid [3,4-d] pyrimidin-4- (3H) -one, 2-ethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrid [3,4-d] pyrimidin-4- (3H) -one, 2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 2-ethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [4,3-d] pyrimidin-4- (3H) -one, 2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [4,3-d] pyrimidin-4- (3H) -one, 6-chloro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [3, 4-d] pyrimidin-4- (3H) -one, 3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- (acetylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazoinone, 6- (butyrylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenol} -4- (3H) -quinazolinone, 6- (hexanoylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- (benzoylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6 - [(2-phenylacetyl) amino] -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- (2-naphthoylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-6 - [(methylsulfonyl) amino] -3-. { 4- [3- (1-piperidinyl) propoxy] pheniI} -4- (3H) -quinazoinone, 2-methyl-6 - [(methylsulfonyl) amino] -3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7- (acetylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7- (butyrylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] pheniI} -4- (3H) -quinazolinone, 7- (hexane -lamino) -2-methyl-3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7- (benzoylamino) -2-methyl-3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7 - [(2-phenylacetyl) amino] -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinonazolinone, 7- (2-naphthoylamino) -2-methyl-3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- [acetyl- (methyl) amino] -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-6-phenyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-6- (4-methylphenyl) -3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolnone, 2-methyl-6- (3-methylphenyl) -3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-6- (2-methylphenyl) -3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -6- (3-pyridyl) -4- (3H) -cynazolinone, 2-methyl-3-. { 4- [3- (1-pperidinyl) propoxy] phenyl} -6- (4-pyridyl) -4- (3H) -quinazoinone, 2-methyl-5-phenyl-3-. { 4- [3- (1-p -peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -6- (2-pyridyl) -4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] pheniI} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-pyridinyl) oxy] phenol} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- (1-cyclohexyl-4-piperidinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone) 3-. { 4- (1-isopropyl-4-p.peridinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- (1-ethyl-4-piperidinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- (1-butyI-4-piperidinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methyl-5-trifluoromethyl-4- (3H) -quinazoinone, 3-. { 4- (1-cyclopentyl-4-piperidinyloxy) phenyl} -2,5-dimethyl-4- (3H) -quinazolinone, 7-chloro-3-. { 4 - [(1-cyclopentyl-4-piperidinir) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2,6-dimethyl-4- (3H) -quinazoinone, 6-chloro-3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -6-methoxy-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methylpyrido [2,3-d] pyrimidn-4- (3H) -one, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenol} -2-methylpyrido [4,5-d] pyrimidin-4- (3H) -one, 6-chloro-3-. { 4 - [(1-cyclopentyl-4-p, pperidyl) oxy] phenyl} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methylpyrid [3,4-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2,5-dimethyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -5-methoxy-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-methyl-5-trifluoromethyl-4- (3H) -quinazolinone, 5-chloro-3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-4-pyridinyl) oxy] phenyl} -2-methy1pyrido [4,3-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] phenyl} -2-ethylpyrid [4,3-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] phenol} -2-methylpyrid [2,3-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-Cyclobutyl-4-pperidinyl) oxy] phenol} -2-ethylpyrido [2, 3-d] pyrimidin-4- (3H) -one, 6-chloro-3-. { 4 - [(1-cyclobutii-4-piperidinyl) oxy] phenyl} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one, 6-chloro-3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenol} -2-ethylpyrido [3,4-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] phenol} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-ethylpyrido [4,5-d] pyrimidin-4- (3H) -one, 2-phenyl-3-. { 4- [3- (1-piperidinium) propoxy] phenyl} -4- (3H) -quinazolinone, cis-2-methyl-3- (4- { [4- (1-pyrrolidinyl) cyclohexyl] oxy}. PhenyI) -4- (3H) -quinazolinone, and trans -2-methyl-3- (4- { [4- (1-pyrrolidinyl) cyclohexyl] oxy} phenol) -4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-3-pyrrolidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-3-pyrrolidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-azepanyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-4-azepanyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-methyl-2-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} -1- (2H) -isoquinoline, 2-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -3-methyl-1 - (2H) -isoquinoline, 2-methyl-3- [4-. { [3- (1-pyrrolidinyl) cyclopentyl] oxy} phenol] -4- (3H) -quinazolonone, 2-ethyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy] phenyl) pyrido [ 2,3-d] pyrimidin-4- (3H) -one, 2-methyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy.} Phenyl) pyrido [4,3-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclobutylpiperidin-4-yl) oxy] phenol} -5-fluoro-2-methyl-4- (3H) -cynazolinone, 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -7-fluoro-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -6-methoxy-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclobutylpiperidin-4-yl) oxy] phenyl} -6-fluoro-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclobutiIpiperidin-4-yl) oxy] phenyl} -8-fluoro-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -6-fluoro-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one, 6-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 6-methoxy-2-methyl-3-. { 4- [3- (1-pyrrolidinol) propoxy] phenyl} [3,4-d] pyrimidin-4- (3H) -one, 5-methoxy-2-methyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1-pyridyl) l] propoxy, phenyl) -4- (3H) -quinazolinone, 7-methoxy-2-methyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1) -yl] propoxy.} phenyl) -4- (3H) -quinazolinone, 2-methyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy. L) pyrido [2,3-d] pyrimidin-4- (3H) -one, 5-fluoro-2-methyl-3- (4-. {3 - [(2R) -2-methylpyrrolidin- 1-yl] propoxy, phenyl) -4- (3H) -quinazolinone, 2-methyl-3- (4-. {3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy. phenyl) pyrido [4,3-d] pyrimidin-4- (3H) -one, 6-methoxy-2-methyl-3- (4-. {3 - [(2R) -2-methylpyrrolidin-1-yl) ] propoxy, phenyl) -4- (3H) -quinazolinone, or 6-methoxy-2-methyl-3- (4-. {3 - [(2S) -2-methylpyrrolidin-1-yl] piOpoxy} phenyl) -4- (3H) -quinazolinone. Among the compounds having the formula (I) in reference to the present invention, the compound represented by the formula (1-1): [where the symbols have the same meaning as the previous ones] can be prepared for example by the following procedure. [where the symbols have the same meaning as the previous ones.] (Step 1) This step is a process for preparing the compound (3) by reacting an aminocarboxylic acid derivative (1) with an acid anhydride (2). The amount of acid anhydride (2) that is used is usually from 1 to 10 equivalents, but preferably from 2 to 5 equivalents, relative to 1 equivalent of the compound (1). The reaction temperature is from room temperature to 150 ° C, but preferably from 100 to 130 ° C. The reaction time is usually 1 to 24 hours, but preferably 1 to 6 hours. The reaction solvent has no particular limitations with the proviso that it does not interfere with the reaction, for example dimethylformamide, dimethyl sulfoxide, 1,4-dioxane or toluene, but between these, dimethylformamide and 1,4-dioxane are preferred. Alternatively, in this step, the compound (3) can be prepared by reacting the aminocarboxylic acid derivative (1) and acid anhydride (2) described above under the reaction conditions described above, without using a reaction solvent.

The compound (3) thus obtained can then be taken to the next step by isolating / purifying using means known in the art, for example, concentration, concentration under reduced pressure, crystallization, solvent extraction, reprecipitation or chromatography, or without isolating or purifying. The compound (3) obtained in this step can also be prepared by the following procedure. [wherein the symbols have the same meaning as the previous ones.] Step 1) is a process for preparing an amide compound represented by the formula (1-2) by reacting compound (1) and an acid chloride (2- 1) in the presence of a base. [where the symbols have the same meaning as the above.] The acid chloride (1-2) used in this step can be for example phenylacetyl chloride, 1-naphthoyl chloride, 2-naphthoyl chloride, cyclopropanecarbonyl, cyclobutanecarbonyl chloride, cyclopentanecarbonyl chloride or cyclohexanecarbonyl chloride. The amount of compound (2-1) that is used is usually 1 to equivalents, but preferably 1 to 1.5 equivalents, relative to 1 equivalent of the compound (1). The base used can be, for example, triethylamine, diisopropylamine, pyridine or the like, but preferably diisopropylamine, ethylamine or pyridine. The reaction temperature is usually 0 to 100 ° C, but preferably 0 to 80 ° C. The reaction time is usually 1 to 48 hours, but preferably 3 to 12 hours. The reaction solvent has no particular limitations with the proviso that it does not interfere with the reaction, but an inert solvent is preferred. Examples of this inert solvent are pyridine, methylene chloride, chloroform, tetrahydrofuran, 1,4-dioxane, diethyl ether and toluene, but among these, tetrahydrofuran or pyridine is preferred. The amide compound (1-2) that is produced after the reaction is used for the reaction of Step 2) without isolating / purifying, after removing the reaction solvent by filtration to obtain a residue.

Step 2) is a process for preparing the compound (3) by reacting the residue containing the amide compound (1-2) obtained in Step 1) described above with oxalyl chloride. The amount of oxalyl chloride that is used is generally from 1 to 10 equivalents, but preferably from 1 to 3 equivalents, relative to 1 equivalent of the compound (1). The reaction time is usually 1 to 48 hours, but preferably 1 to 12 hours. The reaction temperature is usually 0 to 100 ° C, but preferably 0 to 50 ° C. The reaction solvent has no particular limitations with the condition that it does not interfere with the reaction, but an inert solvent is preferred. Examples of this inert solvent are methylene chloride, chloroform, tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethyl sulfoxide and toluene, but among these, methylene chloride, chloroform, tetrahydrofuran and toluene are preferred. In this step, the reaction can be carried out by adding a catalytic amount of dimethylformamide to the reaction system. The catalytic amount of dimethylformamide is usually from 0.01 to 0.5 equivalents, but preferably from 0.01 to 0.2 equivalents, relative to 1 equivalent of the compound (1). The compound (3) thus obtained can then be taken to the next step by isolating / purifying using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, reprecipitation, crystallization or chromatography, or without isolating / purifying.

(Step 2) This step is a process for preparing the compound (5) by reacting the compound (3) and the compound (4) which were obtained by the Step 1 described above. The amount of compound (4) that is used is usually 0.5 to 10 equivalents, but preferably 1 to 3 equivalents, relative to 1 equivalent of compound (3). The reaction temperature is usually from 60 ° C to 160 ° C, but preferably from 80 ° C to 130 ° C. The reaction time is usually 2 to 48 hours, but preferably 5 to 10 hours. The reaction solvent that is used has no particular limitations with the proviso that it does not interfere with the reaction, but an inert solvent such as toluene, 1,4-dioxane, dimethylformamide and dimethyl sulfoxide is preferred. Specific examples of the compound (4) which is used in this step are 4-aminophenol, 5-amino-2-naphthol, 6-amino-2-naphthol, 2-amino-5-hydroxypyrimidine, 2-amino-5-hydroxypyridine, 3-amino-6-hydroxypyridine, 5-amino-3-hydroxy-1H-1, 2,4-triazole, 2-amino-4-hydroxythiazole, 3-amino-6-hydroxypyridazine, 2-amino-4-hydroxyoxazole, 2-amino-5-hydroxypyrazine, 5-amino-3-hydroxyisothiazole, 2-amino-5-hydroxy-1, 3,4-thiadiazole, 3-amino-5-hydroxy-1, 2,4-thiadiazole, 5-amino-3-hydroxy-1, 3,4-thiadiazole, 5-amino-3-hydroxyisoxazole, 2-amino-6-hydroxyquinoline, 2-amino-5-hydroxy-1H-benzimidazole , 5-amino-2-hydroxy-1 H-benzimidazole, 2-amino-5-hydroxythiazole [5,4-b] pyridine, 2-amino-5-hydroxybenzothiazole, 2-amino-5-hydroxybenzoxazole, 3-amino- 6-hydroxybenzoxazole. The compound (5) thus obtained can then be taken to the next step by isolating / purifying using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, crystallization, reprecipitation or chromatography, or without isolating / purifying.

(Step 3) This step is a process for preparing the compound (7) by reacting the compound (5) obtained in the Step 2 described above with the halogenated compound (6). The base used may be, for example, sodium hydrogencarbonate, potassium carbonate or sodium hydride, but preferably, potassium carbonate and sodium carbonate. The amount of base that is used is usually from 1 to 10 equivalents, but preferably from 1.5 to 5 equivalents, relative to 1 equivalent of the compound (5). The reaction time is usually 1 to 48 hours, but preferably 5 to 12 hours.

The reaction temperature is usually from 0 to 150 ° C, but preferably from 50 ° C to 100 ° C. The halogenated compound can be, for example, 1,3-bromochloropropane or 1,4-bromochlorobutane. The compound (7) thus obtained can then be taken to the next step by isolating / purifying using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, crystallization, reprecipitation or chromatography, or without isolating / purifying.

(Step 4) This step is a process for preparing the compound (1-1) according to the present invention by reacting the compound (7) obtained in the Step 3 described above with the amino compound (8) in the presence of a base. The base used in this step may be, for example, sodium hydrogencarbonate, sodium carbonate, potassium carbonate or sodium hydride, but among these, sodium carbonate and potassium carbonate are preferred. The amount of base that is used is usually from 1 to 10 equivalents, but preferably from 1 to 5 equivalents. The amount of the amino compound (8) that is used is usually from 1 to 10 equivalents, but preferably from 2 to 5 equivalents, in relation to 1 equivalent of the compound (7).

In this step, to increase the reactivity of the compound (7), preferably at the same time potassium iodide, tetra-n-butylammonium iodide and the like are present in the reaction system. The amount of potassium iodide used is usually 0.1 to 10 equivalents, but preferably 0.1 to 3 equivalents. The reaction temperature is usually 0 to 150 ° C., but preferably from 50 ° C to 100 ° C. The reaction time is usually 1 to 48 hours, but preferably 1 to 12 hours. The reaction solvent has no particular limitations with the proviso that it does not interfere with the reaction, but an inert solvent such as dimethylformamide, tetrahydrofuran, 1,4-dioxane, acetone or methyl ethyl ketone is preferred. The compound (1-1) according to the present invention thus obtained can then be isolated / purified using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, crystallization, reprecipitation or chromatography. The compound (1-1) related to the present invention can also be prepared by the following procedure: [where L1 is a leaving group, and the remaining symbols have the same meaning as the previous ones].

(Step 5) This step is a process for preparing the compound (1-1) by reacting the compound (5) obtained by the Step 2 described above with the amino compound (9). The amino compound (9) that is used has a leaving group in the molecule. The leaving group has no particular limitations with the condition that it separates producing the compound (1-1) in the reaction with the compound (5). Examples are halogen atoms such as chlorine and bromine, tosyl and mesyl, but among these, bromine and tosyl are preferred. The amount of the amino compound (9) that is used is usually from 1 to 10 equivalents, but preferably from 1 to 3 equivalents, relative to 1 equivalent of the compound (5). The base used in this step may be, for example, sodium hydrogencarbonate, sodium carbonate, potassium carbonate or sodium hydride, but among these, potassium carbonate and sodium carbonate are preferred. The reaction temperature is usually 0 to 150 ° C, but preferably 25 ° C to 100 ° C. The reaction time is usually from 1 to 72 hours, but preferably from 3 to 12 hours.

The reaction solvent has no particular limitations with the proviso that it does not interfere with the reaction, but an inert solvent such as dimethylformamide, tetrahydrofuran, 1,4-dioxane, acetone or methyl ethyl ketone is preferred. The compound (1-1) according to the present invention thus obtained can then be isolated / purified using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, crystallization, reprecipitation or chromatography. The compound related to the present invention can also be prepared by the following procedure using the compound (3) obtained in Step 1. [where the symbols have the same meaning as the previous ones.] (Step 6) This step is a process for preparing the compound (1-1) related to the present invention by reacting the compound (3) obtained by the Step 1 described above with the amino compound (10).

In this step, the amount of compound (10) that is used is from 1 to 10 equivalents, but preferably from 1 to 5 equivalents, relative to 1 equivalent of the compound (3). The reaction temperature is usually from -20 ° C to 180 ° C, but preferably from 0 ° C to 130 ° C. The reaction time is usually from 1 to 72 hours, but preferably from 3 to 12 hours. The reaction solvent has no particular limitations with the proviso that it does not interfere with the reaction, for example, an inert solvent such as dimethylformamide, dimethyl sulfoxide, acetic acid, 1,4-dioxane or toluene, but among these, it is preferred dimethylformamide or acetic acid. The compound (1-1) of the present invention thus obtained can then be taken to the next step by isolating / purifying using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, crystallization, reprecipitation or chromatography The compound (10) is not limited to the free amine, but an acid addition salt can also be used. This acid addition salt can be, for example, the hydrochloride, tosylate or trifluoroacetate. Among the compounds (10), the compound represented by the formula (10-1): (10-1) [where the symbols have the same meaning as the previous ones] can be prepared by the following procedure. (10A) (10C) (10-1) [where T is a hydroxy group or a fluorine atom, and the other symbols have the same meaning as the previous ones.] (Step 6-1) This step is a process of reacting the compound (10A) with the compound (10B) by preparing the compound (10C). In Formula (10A), when T is a hydroxy group (this compound will be referred to as (10A-1)), compound (10C) can be prepared using the compound (10A-1) and the compound (10B) in a reaction of Mitsunobu The Mitsunobu reaction can be carried out by the procedure described in the literature (for example, "The Use of Diethylazodicarboxylate and Triphenylphosphine in Synthesis and Transformation of Natural Products", Synthesis, Vol. 1, 1981, page 1-28, by O. Mitsunobu et al.) In the presence of phosphine and an azo compound, a process based thereon, or a combination of these procedures with conventional procedures. The amount of the compound (10B) that is used is usually 0.5 to 10 equivalents, but preferably 1 to 3 equivalents, per 1 equivalent of compound (10A-1). The phosphine compound which is used in this step is usually, for example, triphenylphosphine, triethylphosphine or the like. The amount of the phosphine compound that is used is usually 0.5 to 10 equivalents, but preferably 1 to 3 equivalents, per 1 equivalent of compound (10B). The azo compound which is used can be, for example, diethyl azodicarboxylate or diisopropyl azodicarboxylate. The amount of the azo compound that is used is usually from 0.5 to 10 equivalents, but preferably from 1 to 3 equivalents, per 1 equivalent of compound (10B). The reaction time in this step is usually from 1 to 48 hours, but preferably from 4 to 12 hours. The reaction temperature in this step is usually from room temperature to the boiling point of the reaction solvent, but preferably from 15 ° C to 30 ° C.

The reaction solvent that is used in this step has no particular limitations with the proviso that it does not interfere with the reaction, but specific examples are tetrahydrofuran and toluene. In Formula (10A), when T is a fluorine atom (this compound will be referred to as (10A-2)), compound (10C) can be prepared by reacting compound (10A-2) with compound (10B) in the presence from a base. The base used in this step can be, for example, sodium hydroxide. The amount of base used is usually from 1 to 10 equivalents, but preferably from 1 to 5 equivalents, per 1 equivalent of compound (10B). The amount of compound (10B) that is used is usually from 1 to 10 equivalents, but preferably from 2 to 5 equivalents, per 1 equivalent of compound (10A-2). In this step, to increase the reactivity of the compound (10A-2), preferably at the same time potassium iodide and tetra-n-butylammonium iodide are present in the reaction system. The amount of potassium iodide used is usually 0.1-10 equivalents, but preferably 0.1 to 3 equivalents. The reaction temperature is usually from 0 ° C to 150 ° C, but preferably from 50 ° C to 100 ° C. The reaction time is usually 1 to 48 hours, but preferably 1 to 12 hours.

The reaction solvent used in this stage does not have particular limitations on the condition that it does not interfere with the reaction, but specific examples are inert solvents such as dimethylformamide, tetrahydrofuran, 1,4-dioxane, acetone and methyl ethyl ketone.

The compound (10C) thus obtained in this step can then be be isolated / purified using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, crystallization, reprecipitation or chromatography.

The compound (10B) that is used in this step for example may have the formula given below. Me H0 -? - ^ N ^ HO / / ^ N '"HO / / ^ N (Stage 6-2) This step is a process for preparing the compound (10-1) by catalytic reduction of the compound (10C) obtained in step 6-1 described above, using palladium on activated carbon as the catalyst.

The amount of palladium on activated carbon that is used is usually 0.01 to 1 equivalent, but preferably 0.05 to 0.5 equivalents, per 1 equivalent of compound (10C).

The reaction temperature is usually from 0 ° C to 80 ° C. The reaction time is usually 1 to 48 hours, but preferably 1 to 12 hours. The compound (10-1) thus obtained in this step can then be isolated / purified using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, crystallization, reprecipitation or chromatography, or carried to the next step without isolating / purifying. Among the compounds (10), the compound represented by the formula (10-2): 1 1 (CH2) m "-AR (10-2) [where the symbols have the same meaning as the previous ones] can be prepared by the following procedure.

(CHA »C TMBCG HOA / Í10D} (10F) f10G) 0 = Re (101) (10-2) (Step 6-3) In this step, the compound (10F) can be prepared by reacting 4-aminophenol (10D) with the compound (10E). The reaction that is used in this stage is the Mitsunobu reaction described above. The amount of the compound (10E) alcohol that is used is usually 0.5 to 10 equivalents, but preferably 1 to 3 equivalents, per 1 equivalent of compound (10D). The protecting group for the amino group in the compound (10E) is not limited to Boc, and can be any amino group protecting group described in the "Protective Groups in Organic Synthesis", by TWGreen, Vol. 2, John Wiley &; Sons, 1991, described above which acts as a protective group for the amino group in Step 6-3 and can be removed in Step 6-4. The phosphine compound that is used in this step is usually, for example, triphenylphosphine or triethylphosphine. The amount of the phosphine compound that is used is usually from 0.5 to 10 equivalents, but preferably from 1 to 3 equivalents, per 1 equivalent of compound (10E). The azo compound which is used can be, for example, diethyl azodicarboxylate or diisopropyl azodicarboxylate. The amount of the azo compound that is used is usually from 0.5 to 10 equivalents, but preferably from 1 to 3 equivalents, per 1 equivalent of compound (10E).

The compound (10E) which is used in this step can be for example 1-Boc-4-piperidinol. The reaction time is usually 1 to 48 hours, but preferably 4 to 24 hours. The reaction temperature in this step is usually from room temperature to the boiling point of the reaction solvent, but is preferably from 15 ° C to 30 ° C. The reaction solvent that is used in this step has no particular limitations with the proviso that it does not interfere with the reaction, but specific examples are tetrahydrofuran and toluene. The compound (10F) thus obtained can then be isolated / purified using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, crystallization, reprecipitation or chromatography, or carried to the next step without isolating / purifying.

(Step 6-4) This step is a process for preparing the compound (10 G) by removing the protecting group of the amino group of the compound (10F) obtained in the Step described above 6-3. The protecting group can be removed by the procedure described in the literature (for example, "Protective Groups in Organic Synthesis", by TW Green, Vol. 2, John Wiley &Sons, 1991), a procedure based on the same. , or a combination of these procedures with conventional procedures. When the protecting group of the amino group is a Boc group, the Boc group can be eliminated for example using TFA. The compound (10G) thus obtained can then be isolated / purified using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, crystallization, reprecipitation or chromatography, or carried to the next step without isolating / purifying.

(Step 6-5) This step is a process for preparing the compound (101) by reacting the compound (10G) obtained in Step 6-4 with the compound (10H). The reaction of this stage is one that is called reductive amination. The amount of the compound (10H) that is used in this step is usually 1 to 10 moles, but preferably 2 to 4 moles, per 1 mole of compound (10 G). The compound (10H) which is used in this step can be for example cyclobutanone or cyclopentanone.

The reducing agent that is used can be an organometallic reagent such as sodium borohydride, sodium cyanoborohydride or sodium triacetoxyborohydride. The amount of the reducing agent is usually from 1 mole to 5 moles, preferably from 1 mol to 3 mol, of the compound (10G). A catalytic amount of ZnCl 2 may also be included in the reaction system. The reaction is usually carried out in an inert solvent, such as for example methanol, ethanol, benzene, toluene, xylene, methylene chloride, chloroform, dimethoxyethane, tetrahydrofuran, dioxane, dimethylformamide, or a mixture thereof. The reaction temperature is usually from room temperature to the boiling point of the solvent that is used for the reaction, but preferably from 20 ° C to 100 ° C. The reaction time is usually from 30 minutes to 7 days, but preferably from 3 hours to 2 days. The compound (101) thus obtained in this step can then be isolated / purified using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, crystallization, reprecipitation or chromatography, or carried to the next non-isolated step /purify.

In the reaction of this step, when R6 is a cyclopropyl group, the compound (101) can be prepared using (1-methoxycyclopropoxy) trimethylsilane instead of the compound (10H).

(Step 6-6) This step is a process for preparing the compound (10-2) by catalytic reduction of the compound (101), using palladium on activated carbon as the catalyst. The amount of palladium on activated carbon that is used is usually 0.01 to 1 equivalent, but preferably 0.05 to 0.5 equivalents, per 1 equivalent of compound (101). The reaction temperature is usually from 0 to 80 ° C. The reaction time is usually 1 to 48 hours, but preferably 1 to 12 hours. The compound (10-2) thus obtained can then be isolated / purified using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, crystallization, reprecipitation or chromatography, or carried to the next step without isolating. purify. Other examples of compound (10) are compounds or their acid addition salts represented by the following formulas.

When the compound related to the present invention that is included in Formula (I) has a substituent group in Ring A it can be prepared using an initial material that already has the corresponding substituent. When the introduction or deprotection of a protecting group into the substituent group is necessary, a method described in the literature, for example, "Protective Groups in Organic Synthesis", T.W. Green, 2nd Edition, John Wiley & Sons, Ltd., 1991, a method based on the same or a combination of these procedures with a conventional procedure. The compound related to the present invention can also be prepared by changing the functional group of Ring A, and introducing / removing a protecting group if necessary. A protecting group in the substituent group can be introduced or eliminated by the method described in "Protective Groups in Organic Synthesis", T.W. Green, 2nd Edition, John Wiley & Sons, Ltd., 1991, a procedure based on the same or a combination of these procedures with a conventional procedure. The functional group can be changed by a procedure described in the literature, for example, "Comprehensive Organic Synthesis", Vol. 6, Pergamon Press, 1991, or "Comprehensive Organic Transformations", Richard I et al., VCH Publishers, 1988, a procedure based on the same or a combination of these procedures with a conventional procedure.

When Ring A is a benzene ring, Ar is phenyl, meaning a divalent group that is formed by removing two hydrogen atoms from benzene, and Ring A having a nitro group, the substituent of Ring A can be modified again by the following procedures, for example. 0-ßJ [where R7 has the same meaning as R1, and the other symbols they have the same meaning as the previous ones.] (Step 7) In this step, the compound (1-4) related to the present invention having a nitro group as a substituent is catalytically reduced using palladium on activated carbon as a catalyst so that the nitro group becomes amino. The amount of palladium on activated carbon that is used in this step is usually 0.01 to 1 equivalent, but preferably 0.05 to 0.5 equivalents, relative to 1 equivalent of the compound (I-4). The reaction temperature is usually from 0 to 80 ° C. The reaction time is usually from 1 hour to 48 hours, or preferably from 1 to 12 hours. The "compound (I-5) thus obtained can then be taken to the next step by isolating / purifying using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, crystallization, reprecipitation or chromatography, or without isolating /purify.

(Step 8) This step is a process for preparing the compound (1-6) by reacting the compound (1-5) obtained in Step 7 with a carboxylic acid compound (11). This reaction is an amide bond reaction, and may be the usual amide formation reaction described in the literature, for example, "Theory and Experiment in Peptide Synthesis," Nobuo Izumiya, Maruzen, 1983, or "Comprehensive Organic Synthesis," Vol. 6, Pergamon Press , 1991, a method based thereon, or a combination thereof with a conventional method. Specifically, this can be done by those skilled in the art using a known condensation agent, or alternatively, it can be achieved by an ester activation process, a mixed acid anhydride process, an acid chloride process or a family carbodiimide process for those skilled in the art. Examples of this amide forming agent are thionyl chloride, oxazalyl chloride, N, N-dicyclohexylcarbodimidium, 1-methyl-2-bromopyridinium iodide, N, N'-carbonyldiimidazole, chloride of diphenylphosphoryl, diphenylphosphoryl azide, N, N'-disuccinimidyl carbonate, N, N'-disuccinimidyl oxalate, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride, ethyl chloroformate, isobutyl chloroformate and benzotriazole hexafluorophosphate 1-yl-oxy-tris (dimethylamino) phosphono, but among these, thionyl chloride, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride, N, N-dicyclohexylcarbodiimide and benzotriazo hexafluorophosphate are preferred. -1-yl-oxy-tris (dimethylamino) phosphonium. In the amide formation reaction, a base and a condensing agent may be used together with the amide forming agent described above. The base used may be a tertiary aliphatic amine such as trimethylamine, triethylamine, N, N-diisopropylethylamine, N-methylmorpholine, N-methylpyrrolidine, N-methylpiperidine, N, N-dimethylaniline, 1,8-diazabicyclo [5.4 , 0] undeca-7-ene (DBU) and 1,5-azabicyclo [4.3.0] nona-5-ene (DBN), or an aromatic amine, for example, pyridine, 4-dimethylaminopyridine, picoline, lutidine , quinoline or isoquinoline, but among these, tertiary amines are preferred, and triethylamine or N, N-diisopropylethylamine is particularly preferred. The condensation agent used can be, for example, N-hydroxybenzotriazole hydrate, N-hydroxysuccinimide, N-hydroxy-5-norbomeno-2,3-dicarboxyimide or 3-hydroxy-3,4-dihydro-4-oxo-1, 2,3-benzotriazole, but among these, N-hydroxybenzotriazole is particularly preferred. The amount of compound (1-5) that is used varies depending on the type of compound and solvent that is used, and other reaction conditions, but is usually from 0.1 to 10 equivalents and preferably from 0. 5 to 3 equivalents in relation to 1 equivalent of the carboxylic acid derivative (11) or its reactive derivative. The amount of the amide forming agent that is used varies with the type of compound and solvent that is used, and other reaction conditions, but is usually from 1 to 10 equivalents and preferably from 1 to 3 equivalents relative to 1 equivalent of the carboxylic acid derivative (11) or its reactive derivative. The amount of the condensing agent that is used varies with the type of compound and solvent that is used, and other reaction conditions, but is usually from 1 to 10 equivalents and preferably from 1 to 3 equivalents relative to 1 equivalent of the derivative of carboxylic acid (11) or its reactive derivative. The amount of base used varies with the type of compound and solvent that is used, and other reaction conditions, but is usually from 1 to 10 equivalents and preferably from 1 to 5 equivalents. The reaction solvent in this step may be example an inert solvent, and has no particular limitations provided it does not interfere with the reaction, with specific examples being methylene chloride, chloroform, 1,2-dichloroethane, N, N-dimethylformamide, ethyl acetate ester, methyl ester of acetic acid, acetonitrile, benzene, xylene, toluene, 1,4-dioxane, tetrahydrofuran, dimethoxyethane or solvents of mixtures thereof, but from the viewpoint of maintaining the appropriate reaction temperature, for example, chloride is preferred of methylene, chloroform, 1,2-dichloroethane, acetonitrile or N, N-dimethylformamide. The reaction temperature in this step is usually from -78 ° C to the boiling point of the solvent, but is preferably from 0 to 30 ° C. The reaction time in this step is usually from 0.5 to 96 hours, but preferably from 3 to 24 hours. The base, the amide forming agent and the condensing agent used in this step can be combined. The compound (1-6) according to the present invention thus obtained can then be isolated / purified using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, reprecipitation, crystallization or chromatography. When the substituent group of Ring A is an aryl group or a heteroaryl group, the compound (1-8) can be prepared by the following procedure using the compound (1-7) of the present invention having a halogen atom in the Ring A. ít-7 > [where X is a halogen atom, X4 is an aryl or a heteroaryl group, and the other symbols have the same meaning as the previous ones.] (Step 9) This step is a process for preparing the compound (1-8) of the present invention having an aryl or heteroaryl substituent group on Ring A by preparing another derivative of the compound (1-7) having a halogen atom such as chlorine, bromine or iodine in Ring A. To convert the compound (1-7) into the compound (1-8), a Suzuki coupling can be carried out.

More specifically, the compound (1-8) according to the present invention having an aryl or heteroaryl substituent group in the Ring A can be prepared by reacting the compound (1-7) having a halogen atom in Ring A with X4-B (OH) 2 in the presence of a base, a palladium catalyst and, if necessary, a ligand of phosphine. This step can be carried out by the method described in "Angew. Chem., Int. Ed. Eng.", 1999, 38 (16), pages 2413-2416, of J.P. Wolfe, S.l. Buchwaid et al., By a procedure based on it, or by a combination of these with a conventional procedure. The base used can be, for example, sodium carbonate, potassium carbonate, cesium carbonate, cesium fluoride, potassium fluoride or sodium fluoride. The amount of base used is usually from 1 to 10 equivalents, but preferably from 1 to 3 equivalents, relative to 1 equivalent of the compound (1-7). The palladium catalyst used can be, for example, Pd (PPh3) 4, Pd (OAc) 3; Pd3 (dba) 3 or PdCI3 (PPh3) 3. The amount of palladium catalyst that is used is usually 0.01 to 0.5 equivalents, but preferably 0.05 to 0.2 equivalents, relative to 1 equivalent of the compound (I-7). The phosphine ligand used can be, for example, PPh3, P (o-tol) 3 > P (tBu) 3, 2- [di (t-butyl) phosphino] -1, 1, -biphenyl, 2- [di (t-butyl) phosphino] -2'- dimethylamino-1,1 '-biphenyl , 2- [dicyclohexylphosphino] -1, 1'-biphenyl, or 2- [dicyclohexylphosphino] -2'-dimethylamino-1,1 '-biphenyl. The borane compound that is used can be a commercial arylboron derivative or a heteroarylboro derivative such as phenylboronic acid, an ester of phenylboric acid or dialkylphenylborane, or the boron target derivative can be prepared by a known process, a process based on the same or a combination of these with a conventional procedure. The amount of boron compound that is used is usually from 1 to 10 equivalents, but preferably from 2 to 5 equivalents. The amount of the boric acid compound X4-B (OH) 2 (X4 is the same as above) is usually 1 to 10 equivalents, but preferably 2 to 5 equivalents The compound (I-9) related to the present invention can be prepared by the following procedure. [where the symbols have the same meaning as the previous ones.] The reaction at this stage is known as the Mitsunobu reaction, and it is a procedure that is described in the literature, for example, Mitsunobu, O., "Use of diethylazodicarboxylate and triphenylphosphine. in synthesis and transformation of natural products ", Synthesis, Vol. 1, 1981, page 1-28, a process based thereon, or a combination thereof with a conventional procedure, in the presence of a phosphine compound and a compound of azo The amount of the alcohol compound (12) that is used in this step is usually from 0.5 to 10 equivalents, but preferably from 1 to 3 equivalents, relative to 1 equivalent of the compound (5). The phosphine compound that is used in this step is usually, for example, triphenylphosphine or triethylphosphine. The amount of phosphine compound that is used is usually 0.5 to 10 equivalents, but preferably 1 to 3 equivalents, relative to 1 equivalent of (5). The azo compound which is used can be, for example, diethyl azodicarboxylate or diisopropyl azodicarboxylate. The amount of azo compound that is used is usually 0.5 to 10 equivalents, but preferably 1 to 3 equivalents, relative to 1 equivalent of the compound (5). The reaction time of this step is usually from 1 to 48 hours, but preferably from 4 to 12 hours. The reaction temperature in this step is usually from room temperature to the boiling point of the reaction solvent, but preferably from 15 ° C to 30 ° C.

The reaction solvent in this step has no particular limitations if it does not interfere with the reaction, but specific examples are tetrahydrofuran or toluene. The compound (1-9) thus obtained can then be isolated / purified using means known in the art, for example, concentration, concentration under reduced pressure, solvent extraction, crystallization, reprecipitation or chromatography. The compound related to the present invention represented by the formula (I) can be easily isolated / purified by the usual means to isolate / purify. These means can be, for example, solvent extraction, recrystallization, reprecipitation, column chromatography or fractionation thin layer chromatography. These compounds can be transformed into salts or esters that are pharmaceutically acceptable by conventional methods, or conversely, the free compounds can be prepared from salts or esters by conventional methods. The fused ring 4-oxopyrimidine derivative of the present invention can exist in the form of a pharmaceutically acceptable salt, and this salt can be prepared according to conventional procedures using the compound represented by the formula (I) described above. Examples of this acid addition salt are salts of halide acids such as the hydrochloride, hydrofluoride, hydrobromide and hydroiodide; salts of inorganic acids such as nitrate, perchlorate, sulfate, phosphate and carbonate; salts of acids (lower alkyl) sulfonic acids such as the salt of methanesulfonic acid, trifluoromethanesulfonic acid salt and ethanesulfonic acid salt; arylsulfonates, such as the benzenesulfonic acid salt and p-toluenesulfonic acid salt; salts of organic acids, such as fumarate, succinate, citrate, tartrate, oxalate and maleate; and salts of amino acids such as glutamate and aspartate. Examples of a base addition base salt are alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium salt, and magnesium, ammonium salt, and salts of organic bases such as guanidine, triethylamine and dicyclohexylamine. The compound of the present invention may additionally exist in the form of a free compound, a hydrate of a salt, or a solvate. The compound represented by the formula (I) can be used to be administered orally or non-orally. When the compound of the present invention is used clinically, it can also be combined with other pharmaceutically acceptable additives in various pharmaceutical preparations depending on the mode of administration. These additives may be those which are commonly used as additives in pharmaceutical preparations, such as gelatin, lactose, white sugar, titanium oxide, starch, crystalline cellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, corn starch, microcrystalline wax, petrolatum, magnesium aluminometasilicate, phosphate. anhydrous calcium, citric acid, sodium tricitrate, hydroxypropylcellulose, sorbitol, sorbitan fatty acid ester, polysorbate, sucrose fatty acid ester, polyoxyethylene, hydrogenated castor oil, polyvinylpyrrolidone, magnesium stearate, light anhydrous silicic acid, talc, oil vegetable, benzyl alcohol, gum arabic, propylene glycol, polyalkylene glycol, cyclodextrin or hydroxypropylcyclodextrin. The form of administration of this pharmaceutical preparation in the form of a mixture with these additives can be a solid preparation, such as tablets, capsules, granules, powders or suppositories, or a liquid preparation such as syrups, elixirs or injections, and these can be prepared from according to the procedures that are commonly used for pharmaceutical preparations. In the case of a liquid preparation, it can be dissolved or suspended in water or other suitable means. Particularly, in the case of an injection, it may be dissolved or suspended in physiological saline or grape sugar, and buffers and preservatives may be added if necessary. These pharmaceutical preparations may contain from 1.0 to 100% by weight, but preferably 1.0 to 60% by weight, of the compound of the present invention relative to the total preparation. Pharmaceutical preparations containing the compound of the present invention can be prepared, for example, according to the following pharmaceutical examples.

PHARMACEUTICAL EXAMPLE 1 parts of the compound of Example 1, 15 parts of heavy magnesium oxide and 75 parts of lactose are uniformly mixed by preparing a powder or particulate substance of 350 μm or less. This powder is inserted into a capsule container to make a capsule.

PHARMACEUTICAL EXAMPLE 2 45 parts of the compound of the Example are uniformly mixed 1, 15 parts of starch, 16 parts of lactose, 21 parts of crystalline celluloses, 3 parts of polyvinyl alcohol and 30 parts of distilled water, are ground, dried and classified by size obtaining granules with a diameter of 1410 to 177μm .

PHARMACEUTICAL EXAMPLE 3 After producing granules by the same procedure as that of Pharmaceutical Example 2, 3 parts of calcium stearate are added to 96 parts of these granules and compressed into tablets of 10 mm diameter.

PHARMACEUTICAL EXAMPLE 4 parts of crystalline cellulose and 3 parts of calcium stearate are added to 90 parts of the granules obtained in Pharmaceutical Example 2, compressed into tablets of 8 mm diameter and a suspension of gelatin mixture of syrup and carbonate is added. precipitated calcium producing tablets coated with sugar. These pharmaceutical preparations may also contain other therapeutically useful compounds. The compound of the present invention may be used in conjunction with other agents useful for the treatment of metabolic disorders and / or eating disorders. These ingredients of these combinations may be administered at different times or simultaneously during the treatment, or they may be administered in the form of different medications or as a single pharmaceutical preparation. The present invention should therefore be understood to include simultaneous administration or administration at different times, and "administration" in the context of the present invention should be interpreted in that way. The range of combinations between the compound of the present invention and other agents useful in metabolic disorders and / or eating disorders, in principle covers combinations with all pharmaceutical preparations useful in the treatment of metabolic disorders and / or eating disorders.

The compound of the present invention can be used in combination with other drugs effective in the treatment, prevention, or control of disorders, such as hypertension, hypertension associated with obesity, disorders related to hypertension, cardiac hypertrophy, left ventricular hypertrophy, and syndrome. Metabolic, obesity and disorders related to obesity. In the prophylaxis or treatment of these disorders, such other drugs (concomitant drugs) can be administered simultaneously, separately or successively. When used simultaneously with another, two or more other drugs, it can be administered as a single dose. However, in polytherapy, the composition containing the compound of the present invention and the concomitant drugs can be administered simultaneously, separately or successively in the form of different packages. These can also be administered with a lapse of time. The dose amount of the concomitant drugs can be based on the dose that is used in clinical practice, and can be selected as appropriate, depending on the patient, the route of administration, the disease or the combination. The mode of administration of the concomitant drug has no particular limitations, it being sufficient that the compound of the present invention and the concomitant drug are combined in some way. Examples of the mode of administration are: 1) administration of a single pharmaceutical preparation which is obtained by simultaneously mixing the compound of the present invention with another drug; 2) simultaneous administration of two types of pharmaceutical preparation, which is obtained by separately preparing the compound of the present invention and another drug, by the same route of administration; 3) administration of two types of pharmaceutical preparation, which is obtained by separately preparing the compound of the present invention and another drug by the same route of administration, with a lapse of time; 4) simultaneous administration of two types of pharmaceutical preparation, which is obtained by preparing separately the compound of the present invention and another drug, by a different administration route, and 5) administration of two types of pharmaceutical preparation, which is obtained by preparing by separating the compound of the present invention and another drug, by a different administration route with a lapse of time (for example, administration of the compound of the present invention followed by the other drug, or in reverse order). The ratio in the mixture between the compound of the present invention and the other drug can be appropriately selected depending on the drugs that are administered, the route of administration and the disease. Examples of concomitant drugs that are used in the present invention are anti-diabetes agents, lipid-lowering agents, antihypertensive agents and anti-obesity agents. Two or more of these concomitant drugs can be combined in an appropriate ratio. Examples of agents against diabetes are: 1) PPARγ agonists such as glitazones (eg, ciglitazone, darglitazone, englitazone, isaglitazone (MCC-555), pioglitazone, rosiglitazone, troglitazone, BRL49653, CLX-0921, 5-BTZD, and the like. ), and GW-0207, LG-100641, and LY-300512, and the like; 2) biguanides such as buformin; metformin; and phenformin, and the like; 3) protein tyrosine phosphatase-1B inhibitors; 4) sulfonylureas such as acetohexamide; chlorpropamide; diabinese; glibenclamide; glipizide; glyburide; glimepiride; gliclazide; glipentide; gliquidone; glisolamide; tolazamide; and tolbutamide, and the like; 5) meglitinides such as repaglinide, and nateglinide, and the like; 6) alpha glucoside hydrolase inhibitors such as acarbose; adiposine; camiglibosa; emiglitato; miglitol; voglibose; pradimicin-Q; salbostatin; CKD-711; MDL-25,637; MDL-73,945; and MOR 14, and the like; 7) alpha-amylase inhibitors such as tendamistat, trestatin, and AI-3688, and the like; 8) insulin secretagogues such as linogliride; and A-4166, and the like; 9) fatty acid oxidation inhibitors, such as clomoxir, and etomoxir, and the like; 10) A2 antagonists, such as midaglizole; isaglidol; deriglidol; idazoxan; earoxan; and fluparoxan, and the like; 11) insulin or insulinomimetics, such as biota, LP-100, novarapid, insulin detemir, insulin lispro, insulin glargine, zinc insulin suspension; Lys-Pro insulin, GLP-1 (73-7); and GLP-1 (7-36) -NH2), and the like; 12) non-thiazolidinediones such as JT-501, and farglitazar, and the like; 13) Dual PPARa agonists /? such as CLX-0940, GW-1536, GW1929, GW-2433, KRP-297, I-796449, LR-90, and SB 219994, and the like; 14) other insulin sensitization drugs; and 15) VPAC2 receptor agonists. Examples of lipid-lowering agents are: 1) bile acid sequestrants such as cholestyramine, colesevelam, colestipol, dialkylaminoalkyl derivatives of a cross-linked dextran; Colestld®; LoCholest®; and Questran®, and the like; 2) HMG-CoA reductase inhibitors such as atorvastatin, itavastatin, fluvastatin, lovastatin, pravastatin, rivastatin, rosuvastatin, simvastatin, and ZD-4522, and the like; 3) HMG-CoA synthase inhibitors; 4) cholesterol absorption inhibitors such as esters of stanol, beta-sitosterol, sterolglycosides, ezetimibe, and the like; 5) acylcoenzyme A-cholesterolacyltransferase (ACAT) inhibitors such as avasimibe, eflucimibe, KY505, SMP 709, and the like; 6) CETP inhibitors such as JTT 705, torcetrapib, CP 532,632, BAY63-2149, SC 591, SC 795, and the like; 7) schylena synthetase inhibitors; 8) antioxidants such as probucol, and the like; 9) PPARα agonists such as beclofibrate, benzafibrate, ciprofibrate, clofibrate, etofibrate, fenofibrate, gemcabene, and gemfibrozil, GW 7647, BM 170744, LY518674; and fibric acid derivatives, such as Atromid®, Lopid® and Tricor®, and the like; 10) FXR receiver modulators such as GW 4064, SR 103912, and the like; 11) LXR receiver modulators such as GW 3965, T9013137, and XTCOI 79628, and the like; 12) inhibitors of lipoprotein synthesis such as niacin; 13) inhibitors of the renin angiotensin system; 14) PPARd partial agonists; 15) bile acid reabsorption inhibitors, such as BARI 1453, SC435, PHA384640, S-435, AZD7706, and the like; 16) PPARd agonists such as GW 501516, and GW 590735, and the like; 7) inhibitors of triglyceride synthesis; 18) Microsomial triglyceride transport inhibitors, such as inplitapide, LAB687, and CP346086, and the like; 19) transcription modulators; ) Escarcase epoxidase inhibitors; 21) inducers of low density lipoprotein (LDL) receptors; 22) inhibitors of platelet aggregation; 23) 5-LO or FLAP inhibitors; and 24) niacin receptor agonists. Examples of antihypertensive agents are: 1) diuretics, such as thiazides, which include chlorthalidone, chlortiazide, dichlorophenamide, hydroflumethiazide, indapamide, and hydrochlorothiazide; loop diuretics, such as bumetanide, ethacrynic acid, furosemide, and torsemide; sodium-limiting agents, such as amiloride, and triamterene; and aldosterone antagonists, such as spironolactone, epirenone, and the like; 2) beta-adrenergic blockers such as acebutolol, atenolol, betaxolol, bevantolol, bisoprolol, bopindolol, carteolol, carvedilol, celiprolol, esmolol, indenolol, metaprolol, nadolol, nebivolol, penbutolol, pindolol, propanolol, sotalol, tertatolol, tilisolol, and timolol , and the like; 3) calcium channel blockers such as amlodipine, aranidipine, azelidipine, bamidipine, benidipine, bepridil, cinaldipine, clevidipine, diltiazem, efonidipine, felodipine, gallopamil, isradipine, lacidipine, lemydipine, lercanidipine, nicardipine, nifedipine, nilvadipine, nimodepine, nisoldipine, nitrendipine, manidipine, pranidipine, and verapamil, and the like; 4) angiotensin converting enzyme (ECZA) inhibitors such as benazepril; captopril; cilazapril; delapril; enalapril; fosinopril; imidapril; losinopril; moexipril; quinapril; quinaprilat; ramipril; perindopril; perindropril; quanipril; espirapril; Tenocapril; trandolapril, and zofenopril, and the like; 5) neutral endopeptidase inhibitors such as omapatrilat, cadoxatrile and ecadotril, phosidotril, sampatrilat, AVE7688, ER4030, and the like; 6) endothelin antagonists such as tezosentan, A308165, and YM62899, and the like; 7) vasodilators such as hydralazine, clonidine, minoxidil, and nicotinyl alcohol, and the like; 8) angiotensin II receptor antagonists such as candesartan, eprosartan, rbesartan, losartan, pratosartan, tasosartan, telmisartan, valsaran, and EXP-3137, FI6828K, and RNH6270, and the like; 9) α / β adrenergic blockers such as nipradilol, arotinolol • and amosulalol, and the like; 10) Alpha 1 blockers, such as terazosin, urapidil, prazosin, bunazosin, trimazosin, doxazosin, naftopidil, indoramino, WHIP 164, and XEN010, and the like; 11) alpha 2 adrenergic agonists such as lofexidine, thiamenidine, moxonidine, rilmenidin and guanobenz, and the like; and 12) aldosterone inhibitors, and the like. Examples of anti-obesity agents are: 1) 5HT (serotonin) transporter inhibitors, such as paroxetine, fluoxetine, fenfluramine, fluvoxamine, sertraline, and imipramine; 2) NE (norepinephrine) transporter inhibitors, such as GW 320659, depiramine, talsupramo, and nomifensin; 3) antagonists / inverse agonists of CB-1 (cannabinoid-1 receptor), such as rimonabant (Sanofi Synthelabo), SR-147778 (Sanofi Synthelabo), BAY 65-2520 (Bayer), and SLV 319 (Solvay), and which are described in USP 5,532,237, USP 4,973,587, USP 5,013,837, USP 5,081,122, USP 5,112,820, USP 5,292,736, USP 5,624,941, USP 6,028,084; WO 96/33159, WO 98/33765, WO 98/43636, WO 98/43635, WO 01/09120, WO 01, 96330, WO 98/31227, WO 98/41519, WO 98/37061, WO 00/10967, WO 00/10968, WO 97/29079, WO 99/02499, WO 01/58869, WO 02/076949, WO 01/64632, WO 01/64633, WO 01/64634, WO 03/006007 and WO 03/007887; and EP-658546; 4) ghrelin antagonists, such as those described in WO 01/87335, and WO 02/08250; 5) inverse antagonists / agonists of H3 (histamine H3), such as thioperamide, 3- (1 H-imidazol-4-yl) propyl N- (4-pentenyl) carbamate, clobenpropit, iodophenpropit, imoproxifan, GT2395, and A331440 , and those described in WO02 / 15905; and 0- [3- (1H-imidazol-4-yl) propanol] carbamates, antagonists of histamine H3 receptors containing piperidine (Lazewska, D. et al., Pharmazie, 56: 927-32 (2001), derivatives of benzophenone (Sasse, A. et al., Arch. Pharm. (Weinheim) 334: 45-52 (2001)), N-substituted phenylcarbamates (Reidemeister, S. et al., Pharmazie, 55: 83-6 (2000 )), and proxyphan derivatives (Sasse, A. et al., J. Med. Chem., 43: 3335-43 (2000)); 6) antagonists of the melanin 1-conentrating hormone receptor (MCH1 R), such as T-226296 (Takeda), SNP-7941 (Synaptic), and those described in WO 01/82925, WO 01/87834, WO 02/051809, WO 02/06245, WO 02/076929, WO 02/076947, WO 02/04433, WO 02/51809, WO 02/083134, WO 02/094799 and WO 03/004027, and in Japanese Patent Application No. JP 2001-226269; 7) agonists / antagonists of MCH2R (melanin concentrating hormone 2R); 8) NPY1 (neuropeptide Y Y1) antagonists, such as BIBP3226, J-115814, BIBO 3304, LY-357897, CP-671906, and GI-264879; and those described in USP 6,001,836; WO 96/14307, WO 01/23387, WO 99/51600, WO 01/85690, WO 01/85098, WO 01/85173 and WO 01/89528; 9) NPY5 antagonists (neuropeptide Y Y5), such as 152,804, GW-569180A, GW-594884A, GW-587081X, GW-548118X; FR235.208; FR226928, FR240662, FR252384; 1229U91, GI-264879A, CGP71683A, LY-377897, LY-366377, PD-160170, SR-120562A, SR-120819A, JCF-104, and H409 / 22; and the compounds described in USP 6,140,354. USP 6,191,160. USP 6,258,837. USP 6,313,298. USP 6,337,332. USP 6,329,395 and USP 6,340,683; USP 6,326,375; USP 6,329,395; USP 6,337,332; USP 6,335,345; EP-01010691, and EP-01044970; and WO 97/19682, WO 97/20820, WO 97/20821, WO 97/20822, WO 97/20823, WO 98/27063, WO 00/107409, WO 00/185714, WO 00/185730, WO 00/64880. , WO 00/68197, WO 00/69849, WO 01/09120, WO 01/14376, WO 01/85714, WO 01/85730, WO 01/07409, WO 01/02379, WO 01/02379, WO 01/23388. , WO 01/23389, WO 01/44201, WO 01/62737, WO 01/62738, WO 01/09120, WO 02/20488, WO 02/22592, WO 02/48152, WO 02/49648 and WO 02/094789.; and Norman et al., J. Med. Chem. 43: 4288-4312 (2000); 10) leptin, such as (PEG-OB, Hoffman La Roche) and recombinant human methionyl leptin (Amgen); 11) leptin derivatives, such as those described in USP 5,552,524, USP 5,552,523, USP 5,552,522 and USP 5,521,283; and WO 96/23513, WO 96/23514, WO 96/23515, WO 96/23516, WO 96/23517, WO 96/23518, WO 96/23519 and WO 96/23520; 12) opioid antagonists, such as nalmefen (Revex ®), 3-methoxynaltrexone, naloxone, and naltrexone; and those described in WO 00/21509; 13) orexin antagonists, such as SB-334867-A; and those described in WO 01/96302, WO 01/68609, WO 02/51232, WO 02/51838 and WO 03/023561; 14) BRS3 agonists (bombesin receptor subtype 3); ) CCK-A agonists (cholecystokinin-A), such as AR-R 15849, Gl 181771, JMV-180, A-71378, A-71623 and SR146131, and those described in USP 5,739,106; 16) CNTF (ciliary neurotropic factors), such as GI-181771 (Glaxo-SmithKIine); SR146131 (Sanofi Synthelabo); butabindida; Y PD170.292, PD149164 (Pfizer); 17) derivatives of CNTF, such as axoquine (Regenerate); and those described in WO 94/09134, WO 98/22128, and WO 99/43813; 18) GHS agonists (growth hormone secretagogue receptor), such as NN703, hexarelin, MK-0677, SM-130686, CP-424,391, 1-692,429 and 1-163,255, and those described in USP documents 6358951, U.S. Patent Applications No. 2002/049196 and 2002/022637; and WO 01/56592 and WO 02/32888; 19) 5HT2c agonists (serotonin 2c receptor), such as BVT933, DPCA37215, IK264; PNU22394; WAY161503, R-1065, and YM348; and those described in USP 3,914,250; and WO 02/36596, WO 02/48124, WO 02/10169, WO 01/66548, WO 02/44152; WO 02/51844, WO 02/40456 and WO 02/40457; 20) Mc3r agonists (melanocortin 3 receptor); 21) Mc4r agonists (melanocortin 4 receptor), such as CHIR86036 (Chiron); ME-10142, and ME-10145 (Melacure), and those described in WO 99/64002, WO 00/74679, WO 01/991752, WO 01/74844, WO 01/70708, WO 01/70337, WO 01/91752, WO 02/059095, WO 02/059107, WO 02/059108, WO 02/059117, WO 02/12166, WO 02/11715, WO 02/12178, WO 02/15909, WO 02/068387, WO 02/068388, WO 02/067869, WO 03/007949 and WO 03/009847; 22) monoamine reuptake inhibitors, such as sibutrathmin (Meridia® / Reductil®) and a salt thereof, and the compounds described in USP 4,746,680, USP 4,806,570, and USP 5,436,272, and in U.S. Patent Publication No. 2002/0006964, and WO 01/27068 and WO 01/62341; 23) serotonin reuptake inhibitors, such as dexfenfluramine, fluoxetine, and those described in USP 6,365,633, and WO 01/27060, and WO 01/162341; 24) GLP-1 agonists (glucagonoid peptide 1); 25) Topiramate (Topimax®); 26) compound 57 of Phytopharm (CP 644,673); 27) ACC2 inhibitors (acetyl-CoA carboxylase-2); 28) β3 agonists (beta adrenergic receptor 3), such as AD9677 / TAK677 (Dainippon / Takeda), CL-316.243, SB 418790, BRL-37344, l-796568, BMS-196085, BRL-35135A, CGP12177A, BTA- 243, W 427353, Trecadrina, Zeneca D7114, and SR 59119A, and those described in USP 5,705,515, USP 5,451,677; and WO 01/74782 and WO 02/32897; 29) DGAT1 inhibitors (diacylglycerol acyltransferase 1); ) DGAT2 inhibitors (diacylglycerol acyltransferase 2); 31) FAS (fatty acid synthase) inhibitors, such as Cerulenin and C75; 32) PDE (phosphodiesterase) inhibitors, such as theophylline, pentoxifylin, zaprinast, sildenafil, amrinone, milrinone, cilostamide, rolipram, and cilomilast; 33) β-thyroid hormone agonists, such as KB-2611 (KaroBioBMS), and those described in WO 02/15845, and JP2000-256190; 34) activators of UCP-1 (decoupler protein 1), 2, or 3, such as titanic acid, 4 - [(E) -2- (5,6,7,8-tetrahydro-5,5,8, 8-tetramethyl-2-napthalenyl) -1-propenyl] benzoic acid (TTNPB), and retinoic acid; and those described in WO 99/00123; 35) acyl-oestrogens, such as oleoyl-estrone, which is described in Mar-Fat, M. et al., Obesity Research, 9: 202-9 (2001); 36) glucocorticoid antagonists; 37) inhibitors of 11 ß HSD-1 (11-beta-hydroxy-steroid dehydrogenase type 1), such as BVT 3498, BVT 2733, and the compounds described in WO 01/90091, WO 01/90090 and WO 01/90092; 38) SCD-1 inhibitors (stearoyl-CoA desaturase-1); 39) inhibitors of dipeptidyl peptidase IV (DP-IV), such as isoleucine thiazolidide, valine pyrrolidide, NVP-DPP728, AF237, P93 / 01, TSL 225, TMC-2A 2B / 2C, FE 999011, P9310 / K364, VIP 0177 , SDZ 274-444; and the compounds described in WO 03/004498, WO 03/004496, EP 1 258 476, WO 02/083128, WO 02/062764, WO 03/000250, WO 03/002530, WO 03/002531, WO 03/002553, WO 03/002593, WO 03/000180, and WO 03/000181; 40) lipase inhibitors, such as tetrahydrolipestatin (oriistat / Xenical®), Triton WR1339, RHC80267, lipestatin, teasaponin, and diethylumbeliferyl phosphate, FL-386, WAY-121898, Bay-N-3176, valilactone, sterazine, ebelactone A, ebelactone B, and RHC 80267, and those described in WO 01/77094, and USP 4,598,089, USP 4,452,813, USP 5,512,565, USP 5,391,571, USP 5,602,151, USP 4,405,644. , USP 4,189,438 and USP 4,242,453; 41) inhibitors of fatty acid transporters; 42) inhibitors of dicarboxylate transporters; 43) inhibitors of glucose transporters; 44) inhibitors of phosphate transporters; 45) melanocortin agonists, such as Melanotan II or those described in WO 99/64002 and WO 00/746799; 46) antagonists of melanin concentrating hormones; 47) galanin antagonists; 48) CCK agonists; 49) corticotropin-releasing hormone; and 50) phosphodiesterase-3B agonists (PDE3B); and similar.

The above combinations include combinations of a composition of the present invention not only with another active compound, but also with two or more other active compounds. Non-limiting examples include combinations of the compositions of the present invention with one, two or more active compounds (concomitant drugs) that are selected from lipid-lowering agents, and antihypertensive agents. Combinations of the compositions of the present invention with one, two or more active compounds (concomitant drugs) that are selected from lipid-lowering agents, and anti-diabetic agents are useful for treating, controlling or preventing the metabolic syndrome. In particular, compositions comprising an anti-obesity agent, an antihypertensive agent, in addition to an anti-diabetes agent and / or a lipid-lowering agent will be useful for treating, controlling or synergistically preventing the metabolic syndrome. When the compound of the present invention is used in a clinical setting, the dose and frequency of administration will depend on the sex, age, weight, condition of the patient and the type and magnitude of the effect desired. However, in oral administration to an adult, 0.01-100 mg / kg but preferably 0.3-1 mg / kg per day are administered in one or several doses, and in non-oral administration to an adult, 0.001-10 is administered. mg / kg but preferably 0.001-0.1 mg / kg per day in one or more doses. The doctor, veterinarian or health worker can easily determine a pharmacologically effective amount of the drug to prevent, suppress or stop a disease process.

EXAMPLES The present invention will be described below by means of examples, but it will be understood that the present invention is not limited in any way by them. For thin layer chromatography of the examples, Silicagel 60F245 (Merck) was used for the plates and a UV detector was used as detection method. Wakogel ™ C-300 (Wako Puré Chem.) Was used as silica gel for the columns and CL-SORB ™ SP-B-ODS (Chemco) or YMC-GEL ™ ODS-AQ120-S50 (Yamamura Chemical Research Institute) was used. as silica gel for the reverse phase columns. The mass spectrum was measured by the electrospray ionization process (IES) using Quattroll (product of Micromass Co.). To measure the NMR spectrum in a heavy dimethyl sulfoxide solution, the measurements were carried out using a Gemini-200 spectrometer (200 MHz, Varian), Gemini-300 (300 MHz, Varian), Mercury 400 (400 MHz, Varian) or Inova 400 (400 MHz, Varian) with dimethyl sulfoxide as internal reference, and all d values were expressed in terms of ppm. The meanings of the abbreviations in the examples below are as follows: i-Bu: isobutyl group n-Bu: n-butyl t-Bu: t-butyl Me: methyl group Et: ethyl group Ph: phenyl group i-Pr: isopropyl group n-Pr: n-propyl group CDCI3: heavy chloroform CD3OD: heavy methanol DMSO-d6: heavy dimethyl sulfoxide. The meanings of the abbreviations of the magnetic resonance spectra are the following: s: singiete d: doublet dd: double doublet t: triplet m: multiplet br: width q: quatrain J: coupling constant Hz: a hertz EXAMPLE 1 2- Ethyl-3-. { 4-f3- (1-piperidinyl) propoxyphenyl} -4- (3H) -quinazolinone (1) Preparation of 2-ethyl-4H-3,1-benzoxazin-4-one Anthranilic acid (10 g, 72.9 molimoles) and propionic anhydride (20.9 g, 160 molimoles) were mixed and stirred at 130 ° C for 2 hours. The reaction solution was concentrated under reduced pressure, the residue was dissolved in methylene chloride, the organic phase was washed with saturated aqueous sodium hydrogen carbonate solution and then distilled water and dried with anhydrous sodium sulfate. The target compound (12.5 g, 98%) was obtained as a colorless solid by filtering off the sodium sulfate and concentrating to dryness. (2) Preparation of 2-ethyl-3- (4-hydroxyphenyl) -4- (3H) -quinazolinone 2-ethyl-4H-3,1-benzoxazin-4-one (6.5 g, 37.1 molimoles) and 4-aminophenol (4.05 g, 37.1 molimoles) were dissolved in dimethylformamide (18 ml) and stirred at 140 ° C for 10 hours. After allowing to cool to room temperature, distilled water (94 ml) was added, and the solid precipitate was removed by filtration. The product was recrystallized (ethanol) and the target compound (6.52 g, 66%) was obtained as light brown crystals. (3) Preparation of 2-ethyl-3- [4- (3-chloropropoxy) phen-4- (3H) -quinazolinone 2-ethyl-3- (4-hydroxyphenyl) -4- (3H) -quinazolinone ( 17.9 g, 67.5 molimoles), 1,3-bromochloropropane (12.1 g, 70.3 molimoies) and potassium carbonate (19.7 g, 143 molimoles) were mixed in dimethylformamide (180 ml) and stirred at 80 ° C for 2 hours. After evaporating the solvent under reduced pressure, ethyl acetate and distilled water were added. After extracting with ethyl acetate, the organic phase was washed with distilled water and dried with anhydrous sodium sulfate. Sodium sulfate was removed by filtration, the filtrate was evaporated under reduced pressure and the solid obtained was washed with ethanol to obtain the target compound (19.1 g, 82%) as a light brown solid. (4) Preparation of 2-ethyl-3-. { 4- [3- (1-p-pentydinil) propoxy] phenyl > -4- (3H) -quinazolinone 2-Ethyl-3- [4- (3-chloropropoxy) phenyl] -4- (3H) -quinazolinone (19 g, 55.6 molimoles), piperidine (23.7 g, 278 molimoles), carbonate potassium (11.5 g, 83.4 molimoles) and potassium iodide (13.8 g, 83.4 molimoles) were mixed in dimethylformamide (400 ml) and stirred at 80 ° C for 24 hours. The solvent was evaporated under reduced pressure, the residue was dissolved in ethyl acetate and the organic phase was washed with distilled water and dried with anhydrous sodium sulfate.

After purification by silica gel column chromatography (chloroform / methanol = 30/1), the title compound (10.1 g, 47%) was obtained as colorless crystals by recrystallization from diethyl ether / heptane. NMR of? (400 MHz, CDCI3, d ppm): 1.22 (3H, t, J = 7.2 Hz), 1. 41-1.47 (2H, m), 1.57-1.64 (4H, m), 1.97-2.05 (2H, m), 2.36-2.58 (8H, m), 4.06 (2H, t, J = 6.4 Hz), 7.02 ( 2H, d, J = 8.4 Hz), 7.12 (2H, d, J = 8.4 Hz), 7.43 (1H, t, J = 7.6 Hz), 7.67-7.78 (2H, m), 8.25 (1 H, d, J = 8.4 Hz). The compound of Example 2-16 can be prepared by the same procedure as that of Example 1, a process based thereon or a combination thereof and a conventional procedure, using the corresponding anthranilic acid, acid anhydride, aminophenol, 1, 3 -bromochloroalkane and amine as starting materials.

EXAMPLE 2 2-Methyl-3-. { 4-r 3 - (1-piper.} Dinyl) propoxypropyl} -4- (3H) -quinazolinone The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and piperidine as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.55 (2H, m), 1.50-1.64 (4H, m), 1.97-2.04 (2H, m), 2.25 (3H, s), 2.37-2.46 (4H, brs), 2.49 (2H, t, J = 6.8 Hz), 4.06 (2H, t, J = 6.8 Hz), 7.03 (2H, d, J = 8.4 Hz), 7.12 (2H, d, J = 8.4 Hz), 7.44 (1 H, t, J = 8.0 Hz), 7.65 (1 H, d, J = 8.8 Hz), 7.74 (1 H, t, J = 8.0 Hz), 8.25 (1 H, d, J = 8.0 Hz).

EXAMPLE 3 2-Methyl-3- (4-r3- (1-pyrrolidinyl) propoxyphenyl) -4- (3H) -quinazolinone The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and pyrrolidine as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.49 (2H, m), 1.58-1.66 (4H, m), 2.25 (3H, s), 2.48-2.58 (4H, brs), 2.81 (2H , t, J = 6.0 Hz), 4.15 (2H, t, J = 5.6 Hz), 7.03 (2H, d, J = 9.2 Hz), 7.13 (2H, d, J = 9.2 Hz), 7.44 (1 H, t, J = 8.0 Hz), 7.65 (1 H, d, J = 8.0 Hz), 7.72 (1 H, t, J = 7.2 Hz), 8.25 (1 H, d, J = 8.0 Hz).

Example 4) 3-. { 4-r3- (Diethylamino) propoxyphenyl} -2-methyl-4- (3H) -quinazolinone The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and diethylamine as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.04 (6H, t, J = 7.2 Hz), 1.91-2.00 (2H, m), 2.25 (3H, s), 2.55 (4H, q, J = 6.8 Hz), 2.63 (2H, t, J = 6.8 Hz), 4.06 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz) , 7.44 (1 H, t, J = 8.4 Hz), 7.65 (1 H, d, J = 8.0 Hz), 7.74 (1 H, t, J = 8.0 Hz), 8.25 (1 H, d, J = 8.0 Hz ).

EXAMPLE 5 2-Methyl-3-. { 4-f3- (2-methyl-1-pyrrolidinyl) propoxphenyl-4- (3H) -quinonazolnone (racemic mixture) The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 2-methylpyrrolidine as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.10 (3H, d, J = 6.4 Hz), 1. 37-1.46 (1H, m), 1.65-1.72 (2H, m), 1.86-1.97 (1H, m), 1.99-2.17 (3H, m), 2.17-2.24 (1H, m), 2.25 (3H, s), 2.26-2.33 (1 H, m), 2.96-3.03 (1 H, m), 3.16- 3.23 (1 H, m), 4.05-4.10 (2H, m), 7.03 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.44 (1H, t, J = 8.0 Hz), 7.65 (1H, d, J = 8.8 Hz), 7.74 (1 H, t, J = 8.0 Hz), 8. 25 (1 H, d, J = 8.0 Hz).

EXAMPLE 6 3-. { 4-f3- (2,5-Dimethyl-1-pyrrolidinyl) propoxyphenyl > -2-methyl-4- (3H) -quinazolinone (mixture of cis and trans isomers) The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 2,5-dimethylpyrrolidine as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.12 (6H, d, J = 6.0 Hz), 1.35-1.40 (2H, m), 1.80-1.86 (2H, m), 1.94-2.00 (2H, m ), 2.57-2.66 (2H, m), 2. 76 (2H, t, J = 7.2 Hz), 4.06 (2H, t, J = 6.0 Hz), 7.02 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.44 (1 H, t, J = 7.2 Hz), 7.65 (1 H, d, J = 8.0 Hz), 7.74 (1 H, t, J = 8.4 Hz), 8.25 (1 H, d, J = 8.0 Hz).

EXAMPLE 7 2-Methyl-3-. { 4-R4- (1-piperidinyl) butoxy1phenyl} -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 1, using anthranilic acid, acetic anhydride, 1,4-bromochlorobutane and piperidine as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.53 (2H, m), 1.57-1.65 (4H, m), 1.66-1.75 (2H, m), 1.97-2.06 (2H, m), 2.25 (3H, s), 2.36-2.50 (6H, m), 4.03 (2H, t, J = 6.4 Hz), 7.01 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz) , 7.44 (1 H, t, J = 8.0 Hz), 7.65 (1 H, d, J = 7.6 Hz), 7.74 (1 H, t, J = 8.0 Hz), 8.25 (1 H, d, J = 8.0 Hz).

EXAMPLE 8 3-. { 4-r3- (1-azepanyl) propoxphenyl > -2-methyl-4- (3H) -quinazolinone The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and azepam as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.62-1.70 (8H, m), 2.25 (3H, s), 2.73 (4H, brs), 4.08 (2H, t, J = 6.2 Hz), 7.03 (2H, d, J = 8.4 Hz), 7.12 (2H, d, J = 8.4 Hz), 7.44 (1 H, t, J = 8.0 Hz), 7.65 (1 H, d, J = 8.8 Hz), 7.74 (1 H, t, J = 8.0 Hz), 8.25 (1 H, d, J = 8.0 Hz) .

EXAMPLE 9 3-. { 4-f3- (1-azocanil) propoxphenyl} -2-methyl-4- (3H) -quinazolinone The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and azocan as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.57-1.63 (8H, m), 2.26 (3H, s), 2.56 (4H, brs), 4.08 (2H, t, J = 6.2 Hz), 7.03 ( 2H, d, J = 8.4 Hz), 7.12 (2H, d, J = 8.4 Hz), 7.44 (1 H, t, J = 8.0 Hz), 7.65 (1 H, d, J = 8.8 Hz), 7.74 ( 1H, t, J = 8.0 Hz), 8.25 (1 H, d, J = 8.0 Hz).

EXAMPLE 10 2-Met.l-3-. { 4-f3- (2-methyl-1-piperidinyl) propoxphenol > -4- (3H) -quinazolinone (racemic mixture) The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 2-methylpiperidine as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.14 (3 H, d, J = 5.5 Hz), 1. 36 (1 H, brs), 1.36 (1 H, brs), 2.03 (1 H, brs), 2.26 (3 H, s), 2.42 (1 H, brs), 2.60 (1 H, brs), 2.93 (1 H, brs), 4.08 (2 H, t, J = 6.2 Hz), 7.03 (2 H, d, J = 8.4 Hz), 7.12 (2 H, d, J = 8.4 Hz) , 7.44 (1 H, t, J = 8.0 Hz), 7.65 (1 H, d, J = 8.8 Hz), 7.74 (1 H, t, J = 8.0 Hz), 8.25 (1 H, d, J = 8.0 Hz).

EXAMPLE 11 2-Methyl-3-f4-r3- (4-methyl-1-piperidinyl) propoxy1phenyl > -4- (3H) -quinazolinone The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 4-methylpiperidine as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.93 (3H, d, J = 6.6 Hz), 1. 25-1.30 (1 H, m), 1.36 (1H, brs), 1.62-1.65 (1H, m), 1.92-2.03 (1H, m), 2.25 (3H, s), 2.49-2.51 (1 H, m ), 2.90-2.93 (1 H, m), 4.06 (2H, t, J = 6.2 Hz), 7.02 (2H, d, J = 6.6 Hz), 7.12 (2H, d, J = 6.6 Hz), 7.46 (1 H, t, J = 6.5 Hz), 7.65 (1 H, d, J = 7.7 Hz), 7.76 (1H, t, J = 8.4 Hz), 8.26 (1 H, d, J = 8.4 Hz).

EXAMPLE 12 3- (4- { 3-r (r 2 R, 6 S) -2,6-Dimethyl-1-piperidininpropoxy phenyl) -2-methyl-4- (3 H) -quinazolinone The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and (2R, 6S) -2,6-dimethylpiperidine as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.18 (6H, d, J = 6.6 Hz), 1. 36 (2H, brs), 1.58-1.68 (2H, m), 1943 (1 H, brs), 2.25 (3H, s), 2.54 (2H, brs), 3. 00 (2H, m), 3.99 (2H, t, J = 5.8 Hz), 7.00 (2H, d, J = 5.9 Hz), 7.12 (2H, d, J = 5.9 Hz), 7.43 (1 H, t, J = 6.6 Hz), 7.64 (1 H, d, J = 8.0 Hz), 7.76 (1 H, t, J = 8.4 Hz), 8.23 (1 H, d, J = 8.0 Hz).

EXAMPLE 13 2-Methyl-3-. { 4-r3- (3-methyl-1-piperidinyl) propoxphenyl} -4- (3H) -quinazolinone (racemic mixture) The title compound was obtained by the procedure according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 3-methylpiperidine as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.87 (3 H, d, J = 6.6 Hz), 1.57-1.72 (2 H, m), 1.88 (1 H, td, J = 11.0, 2.9 Hz), 1.98 -2.06 (2H, m), 2.24 (3H, s), 2.52 (2H, t, J = 7.3 Hz), 2.85-2.92 (2H, m), 7.02 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.43 (1 H, t, J = 7.3 Hz), 7.64 (1 H, d, J = 8.0 Hz), 7.73 (1 H, t, J = 8.0 Hz), 8.23 (1 H, d, J = 8.6 Hz).

EXAMPLE 14 3-. { 4-r3- (3,5-Dimethyl-1-piperidininpropoxyphenyl) -2-methyl-4- (3H) -quinazolinone The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 3,5-dimethylpiperidine as starting materials.

NMR of H (400 MHz, CDCl 3, d ppm): 0.86 (6H, d, J = 6.8 Hz), 1. 49 (2H, t, J = 10.8), 1.70-1.72 (2H, m), 2.24 (3H, s), 2.53 (2H, t, J = 7.2 Hz), 2. 88-2.90 (2H, m), 4.04 (2H, t, J = 6.8 Hz), 7.00 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.42 (1 H, t, J = 7.2 Hz), 7.63 (1 H, d, J = 7.2 Hz), 7.72 (1 H, t, J = 8.0 Hz), 8.23 (1 H, d, J = 8.0 Hz).

EXAMPLE 15 2-Methyl-3-. { 3-r3- (1-piperidinyl) propoxylfenyl} -4- (3H) -quinazolinone The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 3-aminophenol, 1,3-bromochloropropane and piperidine as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.39-1.47 (2H, m), 1.54-1.62 (4H, m), 1.94-2.02 (2H, m), 2.28 (3H, s), 2.36-2.43 (4H, brs), 2.46 (2H, t, J = 7.2 Hz), 3.98-4.06 (2H, m), 6.77 (1 H, s), 6.81 (1 H, d, J = 8.0 Hz), 7.01 ( 1 H, d, J = 8.4 Hz), 7.39-7.47 (2H, m), 7.65 (1 H, d, J = 8.0 Hz), 7.75 (1 H, t, J = 8.0 Hz), 8.25 (1 H , d, J = 8.4 Hz).

EXAMPLE 16 3-. { 3-Bromo-4-r3- (1-piperidinyl) propoxy1phenyl} -2-ethyl-4- (3H) -quinazolinone (1) Preparation of 2-bromo-1- (3-chloropropoxy) -4-nitrobenzene 4-Amino-2-bromophenol (2.0 g, 9.17 molimoles), 1,3-bromochloropropane (907 μl, 9.17 molimoles) and potassium carbonate (1.90 g, 13.8 molimoles) were mixed in dimethylformamide (8 ml), and stirred at 80 ° C for 17 hours. Ethyl acetate was added, the mixture was washed with 1 N aqueous sodium hydroxide solution and distilled water in that order, and the organic phase was dried with anhydrous sodium sulfate. The product was purified by silica gel column chromatography (hexane / ethyl acetate = 9 / 1-7 / 3), and thus the target substance was obtained (1.3 g, 48%). 4-Amino-2-bromophenol was prepared by the procedure described in the literature (J. Org. Chem., Vol. 62, 1997, page 4504). (2) Preparation of 3-bromo-4- (3-chloropropoxy) aniline 2-Bromo-1- (3-chloropropoxy) -4-nitrobenzene (1.3 g), ammonium chloride (1.3 g) and iron (1.3 g) were added to a mixture of methanol solvents (8 ml) and distilled water (4 ml), and the mixture was heated to reflux for 2 hours. The reaction mixture was filtered with celite, and the filtrate was concentrated. The residue was dissolved in ethyl acetate, and washed with distilled water and saturated brine. The organic phase was dried with anhydrous sodium sulfate, concentrated and dried to obtain the target substance (0.92 g). (3) Preparation of 3- [3-bromo-4- (3-chloropropoxy) phenan-2-ethyl-4- (3H) -quinazolinone 3-Bromo-4- (3-chloropropoxy) aniline (0.92 g, 4.92 molimoles) and 2-ethyl-4H-3,1-benzoxadin-4-one (0.87 g, 4.92 molimoles) were dissolved in dimethylformamide (3 ml), and stirred at 140 ° C for 5 hours. Ethyl acetate and distilled water were added, and the mixture was extracted with ethyl acetate and dried with anhydrous sodium sulfate. Methanol was added to the residue, and the insoluble matter was removed by filtration. The filtrate was concentrated, the product was purified by silica gel column chromatography (hexane / ethyl acetate = 80 / 20-75 / 25), and thus the target substance was obtained (416 mg, 20%). (4) Preparation of 3-. { 3-bromo-4- [3- (1-piperidinyl) propoxy] phenyl) -2-ethyl-4- (3H) -quinazolinone 3- [3-Bromo-4- (3-chloropropoxy) phenyl] -2-ethyl-4- (3H) -quinazolinone (70 mg) was dissolved in piperidine (1 ml), and stirred at 80 ° C for 5 hours. The reaction solution was diluted with diethyl ether, and the insoluble matter was removed by filtration. The filtrate was concentrated, dried under vacuum, and thus the title compound (80 mg, 99%) was obtained as a light yellow solid. 1 H NMR (400 MHz, CDCl 3) d ppm): 1.23 (3H, t, J = 7.6 Hz), 1.43-1.53 (2H,), 1.54-1.66 (4H, m), 2.03-2.12 (2H, m) , 2.39-2.52 (6H, m), 2. 54-2.60 (2H, m), 4.13-4.18 (2H, m), 7.04 (1 H, d, J = 8.4 Hz), 7.15 (1 H, dd, J = 2.8, 8.4 Hz), 7.44-7.48 (2H, m), 7.71 (1 H, d, J = 8.0 Hz), 7.77 (1H, t, J = 7.2 Hz), 8.26 (1 H, d, J = 8.0 Hz).

EXAMPLE 17 2-Methyl-3-. { 4-F2- (1-piperidinyl) ethoxy1phenyl) -4- (3H) -quinazolinone 2-Methyl-3- (4-hydroxyphenyl) -4- (3H) quinazolinone (100 mg, 0.40 molimoles), 2- (1-piperidinyl) ethanol (89 mg, 0.50 molimoles) and triphenylphosphine (125 mg, 0.50 molimoles) they were dissolved in dry tetrahydrofuran (2 ml) and cooled in an ice bath. Diethyl azodicarboxylate (75 μl, 0.50 molimoles) was introduced dropwise at 0 ° C and stirred at room temperature for 48 hours. The solvent was removed by distillation under reduced pressure, ether was added, the solid precipitate was removed by filtration and the filtrate was concentrated. The residue was purified by silica gel column chromatography (chloroform / methanol = 30/1) and the title compound (124 mg, 86%) was obtained as a light brown oily substance. 2-Methyl-3- (4-hydroxyphenyl) -4- (3H) quinazolinone was synthesized according to Example 1- (1) and - (2). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.77-1.83 (4H, m), 2.01- 2.08 (2H, m), 2.25 (3H, s), 2.51-2.59 (4H, m), 2.64 (2H , t, J = 7.2 Hz), 4.08 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 9.2 Hz), 7.13 (2H, d, J = 9.2 Hz), 7.44 (1 H, t, J = 8.0 Hz), 7.65 (1 H, d, J = 8.0 Hz), 7.74 (1 H, t, J = 6.8 Hz), 8.25 (1 H, d, J = 8.0 Hz).

EXAMPLE 18 2,5-Dimethyl-3-. { 4-r3- (1-piperidinyl) propoxphenyl} -4- (3H) -quinazolinone (1) Preparation of 1-f3- (4-nitrophenoxy) propinpiperidine 3-Piperidin-1-yl-propan-1-ol (3.66 g, 25.6 molimoles), 4-nitrophenol (2.96 g, 21.3 molimoles) and triphenylphosphine (6.71 g, 25.6 molimoles) were dissolved in dry tetrahydrofuran under a stream of nitrogen, and cooled in the ice bath. Diisopropyl azodicarboxylate (5.0 ml, 25.6 molimoles) was introduced dropwise, and stirred at room temperature for 40 hours. The reaction liquid was concentrated, diethyl ether was added, and the solid precipitate was removed by filtration. The filtrate was concentrated, the product was purified by silica gel column chromatography (chloroform / methanol = 100 / 0-95 / 5), and thus the target substance (3.49 g, 62%) was obtained as an oily residue light yellow. 1- [3- (4-Nitrophenoxy) propyl] piperidine was also prepared by the following procedure. Sodium hydride (2.8 g) in dimethylformamide (20 ml) was precipitated in a stream of nitrogen, and 3-piperidin-1-yl-propan-1 -ol (5.0 g, 34.9 molimoles) was added slowly in the ice bath. After 1 hour stirring at room temperature, 1-fluoro-4-nitrobenzene (4.92 g, 34.9 molimoles) was added, and the mixture was stirred at room temperature for 15 hours. Distilled water and ethyl acetate were added, the mixture was extracted with ethyl acetate, and dried with anhydrous sodium sulfate. After concentration, the residue was purified by silica gel column chromatography (chloroform / methanol = 10 / 0-9 / 1), and thus the target substance was obtained (7.56 g, 82%) as a yellow oily residue Clear. (2) Preparation of 4- [3- (1-piperidinyl) propoxylanilin 1- [3- (4-Nitrophenoxy) propyl] piperidine was dissolved in methanol, and the target compound was obtained by catalytic reduction using a palladium catalyst on activated carbon in a stream of hydrogen. (3) Preparation of 2,5-dimethyl-3-. { 4- [3- (1-piperidine Dpropoxylphenyl) -4- (3H) -quinazolinone 2,5-Dimethyl-4H-3,1-benzoxadin-4-one (100 mg, 0.57 molimoles) and 4- [3- (1 -piperidinyl) propoxy] aniline (134 mg, 0.57 molimoles) were dissolved in acetic acid (3 ml), and stirred at 130 ° C for 10 hours. The solvent was removed by distillation under reduced pressure, and ethyl acetate and 1 N aqueous sodium hydroxide solution were added. The mixture was extracted with ethyl acetate, and the organic phase was dried with anhydrous sodium sulfate. After purification by silica gel column chromatography (chloroform / methanol = 20/1), the title compound (76 mg, 34%) was obtained as colorless crystals by recrystallization (ether / heptane). 2,5-Dimethyl-4H-3,1-benzoxadin-4-one was prepared according to the procedure of Example 1- (1), using 2-amino-6-methylbenzoic acid and acetic anhydride as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.50 (2H, m), 1.57-1.64 (4H, m), 1.97-2.04 (2H, m), 2.22 (3H, s), 2.37-2.45. (4H, brs), 2.50 (2H, t, J = 7.2 Hz), 2.81 (3H, s), 4.05 (2H, t, J = 6.4 Hz), 7.02 (2H, d, J = 9.2 Hz), 7.12 (2H, d, J = 9.2 Hz), 7.19 (1 H, d, J = 7.6 Hz), 7.48 (1 H, d, J = 7.6 Hz), 7.57 (1 H, t, J = 8.0 Hz). The NMR data for 4- [3- (1-piperidinyl) propoxy] aniline hydrochloride which is used for the preparation of the compound of this example are shown below. 1 H NMR (400 MHz, CDCl 3 / CD 3 OD = 5/1, d ppm): 1.40-1.49 (1H, m), 1.86-1.95 (3H, m), 2.14-2.24 (2H, m), 2.32-2.38 ( 2H, m), 2.68-2.75 (2H, m), 3.17-3.21 (2H, m), 3.62-3.57 (2H, m), 4.01 (2H, t, J = 5.6 Hz), 6.76 (2H, d, J = 8.8 Hz), 6.85 (2H, d, J = 8.8 Hz). The compound of Example 19-62 can be prepared by the same procedure as that of Example 18, a process based thereon or a combination thereof with a conventional procedure, using the corresponding anthranilic acid, 4- and 3- [3-] acid anhydride. (1-piperidinyl) propoxy] aniline, 4- [3- (1-pyrrolidinyl) propoxy] aniline or 5-amino-2- [3- (1-piperidinyl) propoxy] pyrimidine as starting materials.

EXAMPLE 19 3-. { 4-r3- (1-Piperidinyl) propoxphenyl} -2-propyl-4- (3H) -quinazolinone The title compound was obtained by the process according to Example 18, using anthranilic acid, butyric anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.88 (3H, t, J = 7.2 Hz), 1. 41-1.52 (2H, m), 1.55-1.62 (4H, m), 1.65-1.78 (2H, m), 1.97-2.06 (2H, m), 2. 37-2.46 (6H, m), 2.50 (2H, t, J = 6.8 Hz), 4.06 (2H, t, J = 6.8 Hz), 7.02 (2H, d, J = 8.4 Hz), 7.12 (2H, d , J = 8.4 Hz), 7.43 (1H, t, J = 8.0 Hz), 7.67 (1H, d, J = 8. 4 Hz), 7.73 (1 H, t, J = 8.0 Hz), 8.24 (1 H, d, J = 8.0 Hz).

EXAMPLE 20 3-. { 4- [3- (1-Piperidinyl) propoxphenyl > -2-trifluoromethyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using anthranilic acid, anhydrous trifluoroacetic acid and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.53 (2H, m), 1.59-1.64 (4H, m), 2.00-2.08 (2H, m), 2.38-2.49 (4H, brs), 2.52 (2H, t, J = 7.2 Hz), 4.06 (2H, t, J = 6.8 Hz), 7.00 (2H, d, J = 8.8 Hz), 7.17 (2H, d, J = 8.4 Hz), 7.60-7.65 (1 H, m), 7.84-7.89 (2H, m), 8.31 (1 H, d, J = 7.2 Hz).

EXAMPLE 21 2-lsopropyl-3-. { 4-f3- (1-piperidinyl) propoxy1phenyl} -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using anthranilic acid, anhydrous isobutyl acid and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.21 (6H, d, J = 6.4 Hz), 1. 41-1.53 (2H, m), 1.57-1.64 (4H, m), 1.97-2.06 (2H, m), 2.38-2.49 (4H, brs), 2. 51 (2H, t, J = 7.2 Hz), 2.72-2.79 (1 H, m), 4.06 (2H, t, J = 6.4 Hz), 7.01 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.41 (1 H, t, J = 7.6 Hz), 7.67-7.75 (2H, m), 8.23 (1 H, d, J = 8.0 Hz).

EXAMPLE 22 2,6-Dimethyl-3-. { 4-f3- (1-piperidinippropoxpfenil > -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-5-methylbenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.53 (2H, m), 1.57-1.64 (4H, m), 1.97-2.06 (2H, m), 2.23 (3H, s), 2.38-2.49 (4H, brs), 2.48 (3H, s), 2.49 (2H, t, J = 7.2 Hz), 4.05 (2H, t, J = 6.0 Hz), 7.01 (2H, d, J = 9.2 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.55 (2H, s), 8.03 (1 H, s) EXAMPLE 23 7-Chloro-2-metgl-3-. { 4-r3- (1-p.peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-4-chlorobenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3> d ppm): 1.41-1.53 (2H, m), 1.57- 1.65 (4H, m), 1.97-2.06 (2H, m), 2.24 (3H, s), 2.37- 2.48 (4H, brs), 2.50 (2H, t, J = 7.2 Hz), 4.06 (2H, t, J = 6.0 Hz), 7.01 (2H, d, J = 9.2 Hz), 7.12 (2H, d, J = 9.2 Hz), 7.38 (1 H, dd, J = 2.4, 8.4 Hz), 7.64 (1 H, d, J = 2.4 Hz), 8.16 (1 H, d, J = 8.8 Hz).

EXAMPLE 24 2,8-Dimethyl-3-. { 4-f3- (1-piperidinyl) propoxphenyl} -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-3-methylbenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.51 (2H, m), 1.56-1.65 (4H, m), 1.97-2.04 (2H, m), 2.26 (3H, s), 2.37-2.48 (4H, brs), 2.49 (2H, t, J = 6.8 Hz), 2.63 (3H, s), 4.05 (2H, t, J = 6.4 Hz), 7.01 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.31 (1 H, t, J = 8.0 Hz), 7.58 (1 H, d, J = 7.2 Hz), 8.09 (1 H, d, J = 8.4 Hz).

EXAMPLE 25 2-Ethyl-5-methyl-3-. { 4-y3- (1-piperidinyl) propoxphenyl} -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-6-methylbenzoic acid, propionic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.20 (3H, t, J = 7.6 Hz), 1.41-1.51 (2H, m), 1.57-1.65 (4H, m), 1.97-2.04 (2H, m ), 2.38-2.53 (8H, m), 2.81 (3H, s), 4.05 (2H, t, J = 6.4 Hz), 7.02 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.18 (1 H, d, J = 6.4 Hz), 7.50-7.60 (2H, m) EXAMPLE 26 5-Fluoro-2-methyl-3-. { 4-f3- (1-piperidinyl) propoxy1phenyl} -4- (3H) -quinazolinone The title compound was synthesized as a white solid (mp: 141-145 ° C) by the procedure according to Example 18, using 2-amino-6-fluorobenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting material, followed of recrystallization (ethyl acetate / n-pentane). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.51 (2H, m), 1.57-1.65 (4H, m), 1.97-2.04 (2H, m), 2.24 (3H, s), 2.37-2.48. (4H, brs), 2.50 (2H, t, J = 7.2 Hz), 4.06 (2H, t, J = 6.0 Hz), 7.01 (2H, d, J = 8.8 Hz), 7.05-7.13 (1 H, m ), 7.11 (2H, d, J = 8.8 Hz), 7.44 (1 H, d, J = 8.4 Hz), 7.63-7.69 (1 H, m) EXAMPLE 27 5-Chloro-2-methyl-3-. { 4-f3- (1-piperidinyl) propoxy-1-phenyl) -4- (3H) -quinazolinone The title compound was obtained by the process according to Example 18, using 2-amino-6-chlorobenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.50 (2H, m), 1.57-1.64 (4H, m), 1.97-2.04 (2H, m), 2.23 (3H, s), 2.37-2.45. (4H, brs), 2.48 (2H, t, J = 7.2 Hz), 4.05 (2H, t, J = 6.4 Hz), 7.01 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.43 (1 H, dd, J = 1.6, 8.0 Hz), 7.53-7.60 (2H, m) EXAMPLE 28 5-Methoxy-2-methyl-3-. { 4-f3- (1-piperidinyl) propoxphenyl} -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 3, using 2-amino-6-methoxybenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. NMR from H (400 MHz, CDCl 3, d ppm): 1.41-1.50 (2H, m), 1.57-1.64 (4H, m), 1.97-2.04 (2H, m), 2.21 (3H, s), 2.37-2.45 (4H, brs), 2.49 (2H, t, J = 7.2 Hz), 3.94 (3H, s), 4.04 (2H, t, J = 6.4 Hz), 6.85 (1 H, d, J = 8.4 Hz), 6.99 (2H, d, J = 8.8 Hz), 7.09 (2H, d, J = 8.8 Hz), 7.21 (1 H, d, J = 8.4 Hz), 7.62 (1 H, t, J = 8.0 Hz).

EXAMPLE 29 5-Hydroxy-2-methyl-3- trifluoroacetate. { 4-r3- (1-piperidinyl) propoxyphenyl) -4- (3H) -quinazolinone The title compound was obtained by demethylation of 5-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone synthesized in Example 28 using boron tribromide. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.90-2.04 (6H, m), 2.33 (3H, s), 2.85-3.00 (4H, m), 3.22-3.30 (2H, m), 3.71. -3.79 (2H, m), 4.13 (2H, t, J = 6.0 Hz), 6.94 (1 H, d, J = 8.4 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.17 (2H, d , J = 8.8 Hz), 7.22 (1 H, d, J = 8.0 Hz), 7.68 (1 H, t, J = 8.0 Hz).

EXAMPLE 30 2-Methyl-3-. { 4-r3- (1-piperidinyl) propoxyphenyl) -5-trifluoromethyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-6-trifluoromethylbenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.50 (2H, m), 1.57-1.64 (4H, m), 1.97-2.04 (2H, m), 2.26 (3H, s), 2.37-2.45. (4H, brs), 2.48 (2H, t, J = 7.2 Hz), 4.04 (2H, t, J = 6.0 Hz), 7.01 (2H, d, J = 8.4 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.77 (1 H, t, J = 8.0 Hz), 7.83-7.87 (2H, m).

EXAMPLE 31 7-Fluoro-2-methyl-3-f4-r3- (1-piperidinyl) propoxy1phenyl > -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-4-fluorobenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.42-1.49 (2H, m), 1.57-1.64 (4H, m), 1.96-2.06 (2H, m), 2.24 (3H, s), 2.37-2.46. (4H, brs), 2.49 (2H, t, J = 7.2 Hz), 4.06 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.16 (1H, dd, J = 2.4, 8.4 Hz), 7.29 (1 H, dd, J = 2.4, 9.6 Hz), 8.25 (1 H, dd, J = 6.0, 8.8 Hz).

EXAMPLE 32 6-Fluoro-2-methyl-3-. { 4-r3- (1-piperidintl) propoxphenyl V4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-5-fluorobenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.49 (2H, m), 1.56-1.65 (4H, m), 1.96-2.06 (2H, m), 2.24 (3H, s), 2.37-2.46. (4H, brs), 2.49 (2H, t, J = 6.8 Hz), 4.06 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8. 8 Hz), 7.42-7.48 (1 H, m), 7.65 (1 H, dd, J = 4.8, 9.2 Hz), 7.87 (1 H, dd, J = 2. 8, 8.4 Hz).

EXAMPLE 33 6 -Difluoro-2-methyl-3- (4-f3- (1-piperidinyl) propoxy-phenyl> -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-4,5-difluorobenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.42-1.49 (2H, m), 1.57-1.63 (4H, m), 1.96-2.05 (2H, m), 2.23 (3H, s), 2.37-2.46. (4H, brs), 2.49 (2H, t, J = 6.8 Hz), 4.06 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.42 (1 H, dd, J = 7.2, 11.2 Hz), 7.99 (1 H, dd, J = 8.4, 10 Hz).

EXAMPLE 34 6-Bromo-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxphenyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-5-bromobenzoic acid, acetic anhydride and 4- [3- (1-pyridinyl) propoxy] aniline as starting materials . 1 H NMR (400 MHz, CDCl 3, d ppm): 1.45 (2H, brs), 1.57-1.65 (4H, m), 1.98-2.03 (2H, m), 2.23 (3H, s), 2.41-2.51 (6H , m), 4.06 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.52 (1 H, d, J = 8.8 Hz), 7.81 (1 H, dd, J = 2.4, 8.8 Hz), 8.36 (1 H, s).

EXAMPLE 35 6-Chloro-2-methyl-3-. { 4-f3- (1-piperidinyl) propoxy1phenyl} -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-5-chlorobenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.49 (2H, m), 1.56-1.63 (4H, m), 1.97-2.05 (2H, m), 2.24 (3H, s), 2.37-2.45. (4H, brs), 2.49 (2H, t, J = 6.8 Hz), 4.06 (2H, t, J = 6.4 Hz), 7.02 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.59 (1H, d, J = 9.2 Hz), 7.66 (1H, dd, J = 2.8, 8.8 Hz), 8.20 (1 H, d, J = 2.4 Hz).

EXAMPLE 36 6-Methoxy-2-methyl-3-. { 4-f3- (1-piperidinyl) propoxphenyl-4- (3H) -quinazolinone The title compound was synthesized as a white solid (mp: 136-138 ° C) by the procedure according to Example 18, using 2-amino-5-methoxybenzoic acid, acetic anhydride and 4- (3-piperidinyl) propoxyaniline as starting materials, followed by recrystallization (ethyl acetate). ethyl / diethyl ether / n-pentane). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.49 (2H, m), 1.56-1.63 (4H, m), 1.98-2.05 (2H, m), 2.22 (3H, s), 2.37-2.46. (4H, brs), 2.49 (2H, t, J = 7.6 Hz), 3.89 (3H, s), 4.06 (2H, t, J = 6.0 Hz), 7.02 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.33 (1H, dd, J = 2.8, 8.8 Hz), 7.58 (1 H, d, J = 8.8 Hz), 7.61 (1 H, d, J = 3.2 Hz) .

EXAMPLE 37 6-Dimethoxy-2-methyl-3-. { 4-r3- (1-piperidinyl) propoxphenyl > -4- (3H) - quinazolinone The title compound was obtained by the procedure according to Example 18. using 2-amino-4,5-dimethoxybenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.49 (2H, m), 1.57-1.65 (4H, m), 1.98-2.05 (2H, m), 2.22 (3H, s), 2.37-2.46. (4H, brs), 2.49 (2H, t, J = 7.6 Hz), 3.97 (3H, s), 4.00 (3H, s), 4.06 (2H, t, J = 6.0 Hz), 7.02 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.24 (1 H, s), 7.56 (1 H, s).

EXAMPLE 38 8-Chloro-2-metiN3-f4-r3- (1-piperidinyl) propoxy-phenyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-3-chlorobenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. NMR from H (400 MHz, CDCl 3, d ppm): 1.41-1.48 (2H, m), 1.57-1.63 (4H, m), 1.97-2.04 (2H, m), 2.32 (3H, s), 2.37-2.45 (4H, brs), 2.49 (2H, t, J = 7.6 Hz), 4.06 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.35 (1 H, t, J = 7.6 Hz), 7.81 (1 H, dd, J = 1.2, 8.0 Hz), 8.17 (1 H, dd, J = 1.2, 8.0 Hz).

EXAMPLE 39 8-Methoxy-2-methyl-3-. { 4-r3- (1-piperidinyl) propoxphenyl} -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-3-methoxybenzoic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H-NMR (400 MHz, CDCl 3, d ppm): 1.41-1.48 (2H, m), 1.57-1.63 (4H, m), 1.97-2.04 (2H, m), 2.31 (3H, s), 2.37- 2.45 (4H, brs), 2.49 (2H, t, J = 7.2 Hz), 4.03 (3H, s), 4.05 (2H, t, J = 6.4 Hz), 7.02 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.19 (1 H, dd, J = 1.2, 8.0 Hz), 7.38 (1 H, t, J = 8.0 Hz), 7.83 (1H, dd, J = 1.2, 8.0 Hz).

EXAMPLE 40 2-Methyl-3-. { 4-r3- (1-piperidinyl) propoxphenyl} benzofg1-quinazolin-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 3-amino-2-naphthoic acid, acetic anhydride and 4- [3- (1-pyrrolidinyl) propoxy] aniin as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.52 (2H, m), 1.57-1.64 (4H, m), 1.98-2.06 (2H, m), 2.28 (3H, s), 2.38-2.46 (4H, brs), 2.50 (2H, t, J = 7.2 Hz), 4.07 (2H, t, J = 6.8 Hz), 7.04 (2H, d, J = 8.8 Hz), 7.17 (2H, d, J = 8. 8 Hz), 7.51 (1H, t, J = 7.6 Hz), 7.59 (1H, t, J = 7.6 Hz), 7.97 (1H, d, J = 8.4 Hz), 8.03 (1 H, d, J = 8.0 Hz), 8.12 (1H, s), 8.86 (1 H, s).

EXAMPLE 41 2,6-Dimethyl-3-. { 4-R3- (1-pyrrolidinyl) propoxy1phenyl} -4- (3H) -quinazolinone (1) Preparation of 4- [3r (1-pyrrolidinyl) propoxy] aniline The target compound was obtained by the procedure according to Example 18, using 3-pyrrolidin-1-yl-propan-1-ol, and 4-nitrophenol or 1-fluoro-4-nitrobenzene as starting materials. (2) Preparation of 2,6-dimethyl-3-. { 4- [3- (1-pyrrolidiniDpropoxpfenir, -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-5-methylbenzoic acidacetic anhydride and 4- [3- (1-pyrrolidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.76-1.84 (4H, m), 2.00- 2.09 (2H, m), 2.23 (3H, s), 2.47 (3H, s), 2.50-2.58 (4H) , m), 2.64 (2H, t, J = 7.2 Hz), 4.08 (2H, t, J = 6.4 Hz), 7.02 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz ), 7.55 (2H, s), 8.03 (1 H, s) The NMR data for 4- [3- (1-pyrrolidinyl) propoxy] aninyl which is used for the preparation of the compound of this example below. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.77-1.80 (4H, m), 1.93-2.00 (2H, m), 2.49-2.54 (4H, m), 2.60 (2H, t, J = 7.6 Hz ), 3.41 (2H, brs), 3.95 (2H, t, J = 6.6 Hz), 6.63 (2H, d, J = 8.8 Hz), 6.74 (2H, d, J = 9.3 Hz). 4- [3- (1-Pyrrolidinyl) propoxy] aniline can also be obtained in the form of 4- [3- (1-pyrrolidinyl) propoxy] aniline ditosylate by treating with 2 equivalents of p-toluenesulfonic acid. The NMR data for this tosyl salt are shown below. 1 H NMR (DMSO-d 6) d: 1.81-1.90 (2H, m), 1.96-2.05 (2H, m), 2. 06-2.13 (2H, m), 2.29 (6H, s), 3.02-3.04 (2H, m), 3.28-3.30 (2H, m), 3.57- 3.59 (2H, m), 4.05 (2H, t, J = 6.1 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.12 (4H, d, J = 7. 8 Hz), 7.28 (2H, d, J = 8.8 Hz), 7.49 (4H, d, J = 7.8 Hz), 9.49 (1 H, brs), 9.73 (2H, brs) EXAMPLE 42 2-Ethyl-5-methyl-3-. { 4-f3- (1-pyrrolidinyl) propoxy1phenyl > -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-6-methylbenzoic acid, propionic anhydride and 4- [3- (1-pyrrolidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.20 (3H, t, J = 7.2 Hz), 1.76-1.85 (4H, m), 2.00-2.09 (2H, m), 2.43 (2H, q, J = 7.6 Hz), 2.50-2.59 (4H, m), 2.65 (2H, t, J = 7.2 Hz), 2.81 (3H, s), 4.07 (2H, t, J = 6.0 Hz), 7.03 (2H, d , J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.18 (1H, d, J = 6.8 Hz), 7.51-7.59 (2H, m) EXAMPLE 43 5-Fluoro-2-methyl-3-. { 4- (1-pyrrolidinyl) propoxyphenyl} -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-6-fluorobenzoic acid, acetic anhydride and 4- [3- (1-pyrroiidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.77-1.83 (4H, m), 2.00-2.08 (2H, m), 2.23 (3H, s), 2.51-2.56 (4H, m), 2.64 (2H , t, J = 7.2 Hz), 4.08 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.02-7.11 (1 H, m), 7.12 (2H, d, J = 8.8 Hz), 7.43 (1 H, d, J = 8.0 Hz), 7.63-7.68 (1 H, m).

EXAMPLE 44 2-Met.l-3-. { 4-r3- (1-pyrroH diny) propoxy-phenyl > -5-trifluoromethyl-4- (3H) -quinazolinone The title compound was synthesized as a white solid (mp: 137-140 ° C) by the procedure according to Example 18, using 2-amino-6-trifluoromethylbenzoic acid, acetic anhydride and 4 - [(3- ( 1- pyrrolidinyl) propoxy] aniline as starting materials, followed by recrystallization (ethyl acetate / n-pentane). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.77-1.83 (4H, m), 2.00-2.08 ( 2H, m), 2.26 (3H, s), 2.51-2.57 (4H, m), 2.63 (2H, t, J = 7.2 Hz), 4.07 (2H, t, J = 6.8 Hz), 7.03 (2H, d , J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.79 (1H, t, J = 7.6 Hz), 7.82-7.88 (2H, m).

EXAMPLE 45 5-Chloro-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxphenyl} -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-6-chlorobenzoic acid, acetic anhydride and 4- [3- (1-pyrrolidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.77-1.84 (4H, m), 2.00-2.08 (2H, m), 2.22 (3H, s), 2.51-2.56 (4H, m), 2.64 (2H , t, J = 6.8 Hz), 4.07 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.43 (1 H, dd, J = 2.0, 7.6 Hz), 7.44-7.60 (2H, m).

EXAMPLE 46 2-Ethyl-3- (4-f3- (1-pyrrolidinyl) propoxy-1-phenyl} -4- (3H) -q-nazolinone The title compound was obtained by the procedure according to Example 18, using anthranilic acid, propionic anhydride and 4- [3- (1-pyrrolidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.21 (3H, t, J = 7.2 Hz), 1. 77-1.84 (4H, m), 2.01-2.09 (2H, m), 2.46 (2H, q, J = 7.2 Hz), 2.51-2.58 (4H, m), 2.65 (2H, t, J = 6.8 Hz) , 4.08 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.43 (1 H, t, J = 8.0 Hz), 7.67-7.76 (2H, m), 8.24 (1 H, d, J = 8.4 Hz).

EXAMPLE 47 2,5-Dimethyl-3- (4-r 3 - (1-pyrrolidinyl) propoxy] phenyl] -4- 3 H) -quinazolinone The title compound was synthesized as a white solid (mp: 112-113 ° C) by the procedure according to Example 18, using 2-amino-6-methylbenzoic acid, acetic anhydride and 4 - [(3- (1-pyrrolidinyl) propoxy] aniline as starting materials, followed by recrystallization (ethyl acetate / diethyl ether) 1 H NMR (400 MHz, CDCl 3, d ppm): 1.77-1.84 (4H, m), 2.01-2.09 (2H, m), 2.22 (3H, s), 2.51-2.58 (4H, m), 2.63 (2H, t, J = 7.2 Hz), 2.81 (3H, s), 4.07 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 8.8 Hz ), 7.12 (2H, d, J = 8.8 Hz), 7.19 (1 H, d, J = 7.6 Hz), 7.48 (1 H, d, J = 8.0 Hz), 7.57 (1 H, t, J = 8.0) Hz).

EXAMPLE 48 2-Methyl-3-. { 4-r3- (1-piperidininpropoxy1phenyl pyridor2.3-d1pyrimidin-4- (3H) -one The title compound was obtained by the process according to Example 18, using 2-aminonicotinic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3: CD 3 OD = 6: 1, d ppm): 1.42-1.53 (2H, m), 1.59-1.67 (4H, m), 2.00-2.07 (2H, m), 2.33 (3H, s), 2.41-2.48 (4H, brs), 2.53 (2H, t, J = 7.2 Hz ), 4.06 (2H, t, J = 6.4 Hz), 7.05 (2H, d, J = 8.8 Hz), 7. 13 (2H, d, J = 8.8 Hz), 7.43 (1 H, dd, J = 4.4, 7.6 Hz), 8.58 (1 H, dd, J = 2.4, 7.6 Hz), 8.95 (1 H, dd, J = 2.0,4.8 Hz).

EXAMPLE 49 2-Methyl-3- (4-r3- (1-pyrrolidinyl) propoxy-1-phenyl> pyrido2.3-d1-pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 2-aminonicotinic acid, acetic anhydride and 4- [3- (1-pyrrolidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.76-1.84 (4H, m), 2.00- 2.10 (2H, m), 2.34 (3H, s), 2.50-2.59 (4H, m), 2.65 (2H , t, J = 6.8 Hz), 4.08 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.39 (1 H, dd, J = 4.8, 8.8 Hz), 8.56 (1H, dd, J = 2.4, 8.4 Hz), 8.96 (1H, dd, J = 2.4, 4.4 Hz).

EXAMPLE 50 6-Chloro-2-methyl-3-. { 4-f3- (1-pyrroHdinyl) propoxy1phenyl} pyrido [3,4-d1-pyridin-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 5-amino-2-chloroisonicotinic acid, acetic anhydride and 4- [3- (1-pyrrolidinyl) propoxy] aniline as starting materials.

The 5-amino-2-chloroisonicotinic acid was prepared according to the procedure described in the literature (J. Chem. Soc. Perkin Trans. 1, 1996, page 2221). 1 H NMR (400 MHz, CD3OD, d ppm): 2.08-2.16 (4H, brs), 2.24- 2.32 (5H, m), 3.37-3.48 (6H, m), 4.21 (2H, t, J = 5.6 Hz ), 7.16 (2H, d, J = 9.2 Hz), 7.31 (2H, d, J = 9.2 Hz), 8.03 (1 H, s), 8.83 (1 H, s).

EXAMPLE 51 2-Methyl-3-. { 4-f3- (1-piperidinyl) propoxyphenyl} pyridof3,4-d1pyrimidin-4- (3H) -one The title compound was obtained by catalytic reduction of 6-chloro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one synthesized in Example 63 in ethyl acetate using a palladium on activated carbon catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.50 (2H, m), 1.57-1.64 (4H, m), 1.98-2.05 (2H, m), 2.29 (3H, s), 2.39-2.45 (4H, brs), 2.50 (2H, t, J = 7.2 Hz), 4.06 (2H, t, J = 6.4 Hz), 7.05 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 8.01 (1 H, d, J = 5.2 Hz), 8.65 (1 H, d, J = 5.2 Hz), 9.10 (1 H, s).

EXAMPLE 52 2-Methyl-3-f4-r3- (1-pyrrolidinyl) propoxyphenyl pyrido4,3-d1-pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 4-aminonicotinic acid, acetic anhydride and 4- [3- (1-pyrrolidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CD3OD, d ppm): 2.23-2.33 (4H, m), 2.23-2.33 (5H, m), 3.36-3.49 (6H, brt, J = 8.0 Hz), 4.20 (2H, t , J = 6.0 Hz), 7.14 (2H, d, J = 8.8 Hz), 7.30 (2H, d, J = 8.8 Hz), 7.57 (1 H, dd, J = 0.8, 6.0 Hz), 8.78 (1 H , d, J = 5.6 Hz), 9.28 (1 H, d, J = 0.8 Hz).

EXAMPLE 53 2-Methyl-3- (4-r3- (1-piperidinyl) propoxylphenyl) pyrido4,3-d] pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 4-aminonicotinic acid, acetic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.40-1.49 (2H, m), 1.53- 1.66 (4H, m), 1.97-2.05 (2H, m), 2.29 (3H, s), 2.35-2.45 (4H, brs), 2.50 (2H, t, J = 6.8 Hz), 4.07 (2H, t, J = 6.4 Hz), 7.04 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8. 8 Hz), 7.47 (1 H, dd, J = 0.8, 5.2 Hz), 8.82 (1 H, d, J = 5.6 Hz), 9.45 (1 H, d, J = 0.8 Hz).

EXAMPLE 54 2-Methyl-3-. { 2-y3- (1-piperidinyl) propoxy] -5-pyrimidinyl > -4- (3H) -quinazolinone (1) Preparation of 5-nitro-2- (3-piperidin-1-lpropoxy) pyrimidine 2-Chloro-5-nitropyrimidine (300 mg, 1.88 molimoles), 3-piperidin-1-yl-propan-1-ol (323 mg, 2.26 molimoles) and cesium carbonate (725 mg, 3.76 molimoles) were mixed in dry dimethylformamide (5 ml), and stirred for 2 days at room temperature. The solvent was distilled off under reduced pressure, ethyl acetate and 1 N aqueous sodium hydroxide solution were added, and the mixture was extracted with ethyl acetate. After drying with anhydrous sodium sulfate, the product was purified by silica gel column chromatography (chloroform / methanol = 30/1), and the target compound (110 mg, 22%) was obtained as a light brown solid. 2-Chloro-5-nitropyrimidine was prepared by the procedure described in the literature (Heterocycles, 1984, Vol. 22, page 79). (2) Preparation of 5-amino-2- (3-piperidin-1-yl-propoxy) pyrimidine 5-Nitro-2- (3-piperidin-1-yl-propoxy) pyrimidine (100 mg, 0.38 molimoles) was dissolved in a mixture of methanol solvents (2 ml) and distilled water (2 ml), sodium dithionite (Na2S204) (655 mg) was added, and the mixture was stirred for 30 minutes at room temperature. The solvent was removed by distillation under reduced pressure, methanol was added to the residue, and the precipitate was removed by filtration. The filtrate was concentrated, and the target compound (60 mg, 68%) was obtained as a yellow oily residue. (3) Preparation of 2-methy1-3- (2-f3- (1-piperidinyl) propoxp-5-pyrimidinyl) -4- (3H) -quinazolinone The title compound was obtained by the process according to Example 18, using anthranilic acid, acetic anhydride and 5-amino-2- [3- (1-piperidinyl) propoxy] pyrimidine as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.47 (2H, m), 1.57-1.64 (4H, m), 2.02-2.10 (2H, m), 2.30 (3H, s), 2.37-2.46. (4H, brs), 2.53 (2H, t, J = 7.2 Hz), 4.49 (2H, t, J = 6.4 Hz), 7.49 (1 H, dt, J = 0.8, 7.6 Hz), 7.67 (1 H, d, J = 7.6 Hz), 7.79 (1 H, dt, J = 1.6, 7.6 Hz), 8.24 (1 H, dd, J = 1.6, 8.0 Hz), 8.43 (2H, s).

EXAMPLE 55 2.5-Dimethyl-3- (2-r3- (1-piperidinyl) propoxp-5-pyrimidinyl -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-6-methylbenzoic acid, acetic anhydride and 5-amino-2- [3- (1-piperidinyl) propoxy] pyrimidine as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.40-1.48 (2H, m), 1.57-1.64 (4H, m), 2.02-2.10 (2H, m), 2.27 (3H, s), 2.37-2.47 (4H, brs), 2.49 (3H, s), 2.53 (2H, t, J = 7.2 Hz), 4.48 (2H, t, J = 6.4 Hz), 7.55-7.62 (2H, m), 8.02 (1 H , s), 8.42 (2H, s).

EXAMPLE 56 2-Ethyl-3-. { 4- | 3- (1-piperidinyl) propoxy1phenyl > pyridoF2,3-d1pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 2-aminonicotinic acid, propionic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, CD 3 OD, d ppm): 1.30 (3H, t, J = 7. 2 Hz), 1.42-1.52 (2H, brs), 1.59-1.67 (4H, m), 1.97-2.07 (2H, m), 2.47-2.58 (8H, m), 4.07 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.39 (1 H, dd, J = 4.8, 8.0 Hz), 8.57 (1 H, dd, J = 2.0, 7.6 Hz), 8.96 (1 H, dd, J = 2.4, 4.8 Hz).

EXAMPLE 57 6-Chloro-2-ethyl-3-. { 4-r3- (1-piperidinyl) propoxyphenyl} p3ridor3,4-d1pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 5-amino-2-chloroisonicotinic acid, propionic anhydride and 4- [3- (1-pperidinyl) propoxy] aniline. as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.23 (3H, t, J = 7.2 Hz), 1.41-1.50 (2H, m), 1.57-1.64 (4H, m), 1.98-2.05 (2H, m ), 2.39-2.53 (8H, m), 4.07 (2H, t, J = 6.4 Hz), 7.05 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 8.06 (1 H, s), 8.94 (1 H, s).

EXAMPLE 58 6-Chloro-2-ethyl-3-. { 4-r3- (1-pyrrolidinyl) propox?] Phenyl} 3-3-d1-pyrimidine-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 5-amino-2-chloroisonicotinic acid, propionic anhydride and 4- [3- (1-pyrrolidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.23 (3H, t, J = 7.6 Hz), 1.79-1.86 (4H, m), 2.01-2.11 (2H, m), 2.46 (2H, q, J = 7.6 Hz), 2.50-2.62 (4H, brs), 2.67 (2H, t, J = 6.8 Hz), 4.09 (2H, t, J = 6.4 Hz), 7.05 (2H, d, J = 8.8 Hz), 7.10 (2H, d, J = 8.8 Hz), 8.03 (1 H, s), 8.91 (1 H, s).

EXAMPLE 59 2-Eti-3. { 4-r3- (1-piperidinyl) propoxy1phenyl} pyrido [3,4-d1-pyrimidin-4- (3H) -one The title compound was obtained by catalytic reduction of 6-chloro-2-ethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one synthesized in Example 57 using palladium on activated carbon as a catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.24 (3H, t, J = 7.2 Hz), 1.41-1.49 (2H, m), 1.57-1.65 (4H, m), 1.98-2.06 (2H, m ), 2.39-2.56 (8H, m), 4.07 (2H, t, J = 6.4 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz), 8.00 (1 H, dd, J = 0.8, 4.8 Hz), 8.64 (1 H, dd, J = 4.8 Hz), 9.13 (1 H, d, J = 0.8 Hz).

EXAMPLE 60 2-Ethyl ° 3-. { 4-r3- (1-pyrrolidinyl) propoxpfenH > piridor3,4-dlpirimidin-4- (3H) -one The title compound was obtained by catalytic reduction of 6-chloro-2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one synthesized in Example 58 using palladium on activated carbon as a catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.24 (3H, t, J = 7.2 Hz), 1. 81-1.86 (4H, m), 2.05-2.13 (2H, m), 2.48 (2H, q, J = 7.2 Hz), 2.59-2.67 (4H, brs), 2.72 (2H, t, J = 7.2 Hz) , 4.09 (2H, t, J = 6.0 Hz), 7.03 (2H, d, J = 8.8 Hz), 7. 11 (2H, d, J = 8.8 Hz), 8.00 (1 H, dd, J = 0.8, 5.2 Hz), 8.64 (1 H, dd, J = 4.8 Hz), 9.13 (1 H, d, J = 0.8 Hz).

EXAMPLE 61 2-Ethyl-3-. { 4-r3- (1-piperidinyl) propoxyphenyl} pyridof4,3-dlpyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 4-aminonicotinic acid, propionic anhydride and 4- [3- (1-piperidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.23 (3H, t, J = 7.6 Hz), 1.42-1.51 (2H, m), 1.59-1.67 (4H, m), 2.00-2.09 (2H, m ), 2.42-2.58 (8H, m), 4.08 (2H, t, J = 6.4 Hz), 7.05 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.53 (1 H, d, J = 6.0 Hz), 8.84 (1 H, d, J = 5.6 Hz), 9.47 (1 H, s).

EXAMPLE 62 2-Ethyl-3-. { 4-f3- (1-pyrrolidinyl) propoxphenyl} pyridof4,3-d1pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 4-aminonicotinic acid, propionic anhydride and 4- [3- (1-pyrrolidinyl) propoxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.23 (3H, t, J = 7.2 Hz), 1.99-2.07 (4H, m), 2.25-2.35 (2H, m), 2.48 (2H, q, J = 7.6 Hz), 2.96-3.07 (4H, brs), 4.14 (2H, t, J = 6.0 Hz), 7.05 (2H, d, J = 8.8 Hz), 7.15 (2H, d, J = 8.8 Hz), 7.53 (1 H, d, J = 5.6 Hz), 8.84 (1 H, d, J = 5.6 Hz), 9.47 (1 H, s).

EXAMPLE 63 6-Chloro-2-methyl-3-. { 4-r3- (1-piperidinyl) propoxy1phenyl pyrido3,4-dlpyrimidin-4- (3H) -one 6-Chloro-2-methyl-3- (4-hydroxyphenyl) pyrido [3,4-d] pyrimidine-4- (3H) -one (52 mg, 0.18 molimoles), 1- (3-bromopropyl) piperidine hydrobromide (78 mg, 0.27 molimoles) and potassium carbonate (100 mg, 0.72 molimoles) were mixed in dimethylformamide (1 ml) and stirred at 80 ° C. for 1 hour. The solvent was removed by distillation under reduced pressure, distilled water was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with distilled water, and dried with anhydrous sodium sulfate. The title compound (45 mg, 60%) was obtained as colorless crystals by purification by silica gel column chromatography (chloroform / methanol = 30/1) and recrystallizing (ethanol). 6-Chloro-2-methyl-3- (4-hydroxyphenyl) pyrido [3,4-d] pyrimidin-4- (3H) -one was synthesized according to Example 1- (1) and - (2), using 5-amino-4-carboxy-2-chloropyridine and acetic anhydride as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.50 (2H, m), 1.57-1.64 (4H, m), 1.98-2.05 (2H, m), 2.28 (3H, s), 2.39-2.46. (4H, brs), 2.50 (2H, t, J = 7.2 Hz), 4.06 (2H, t, J = 6.4 Hz), 7.04 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 8.04 (1 H, s), 8.88 (1 H, s).

EXAMPLE 64 3-. { 4-f3- (1-piperidinyl) propoxphenyl} -4- (3H) -quinazolinone The title compound was obtained by alkylating 3- (4-hydroxyphenyl) -4- (3H) quinazolinone and 1- (3-bromopropyl) piperidine hydrobromide according to Example 63. 3- (4-Hydroxyphenyl) -4- ( 3H) quinazolinone was prepared by the procedure described in the literature (Heterocycles, 1993, Vol. 35, page 775). NMR of? (400 MHz, CDCl 3, d ppm): 1.41-1.50 (2H, m), 1.56-1.63 (4H, m), 1.97-2.04 (2H, m), 2.38-2.45 (4H, brs), 2.49 (2H, t, J = 7.2 Hz), 4.06 (2H, t, J = 6.8 Hz), 7.02 (2H, d, J = 8.8 Hz), 7.29 (2H, d, J = 8.8 Hz), 7.52 (1H, t, J = 8.0 Hz), 7.72-7.80 (2H, m), 8.09 (1 H, s), 8.34 (1 H, d, J = 8.0 Hz).

EXAMPLE 65 6- (Acetylamino) -2-methyl-3-. { 4-r3- (1-piperidinyl) propoxphenyl > -4- (3H) - quinazolinone (1) Preparation of 6-amino-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone 2-Methyl-6-nitro-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone (110 mg, 0.26 molimoles) synthesized according to Example 1 was dissolved in methanol (3 ml), and the atmosphere of the system was replaced by nitrogen. After adding 10% palladium on activated carbon (100 mg), the atmosphere was replaced with hydrogen, and the mixture was stirred at room temperature for 1 hour. The catalyst was removed by filtration, and the filtrate was concentrated to dryness to obtain the target compound (91 mg, 89%) as a light yellow solid. (2) Preparation of 6- (acetylamino) -2-methyl-3- (4-3- (1-piperidiniDpropoxpfeniiy4- (3H) -quinazolinone 6-Amino-2-methyl-3- { 4- [3- (1-piperidinyl) propoxy] phenol.} -4- (3H) -quinazolinone (228 mg, 0.58 molimoles) was dissolved in a mixture of dry tetrahydrofuran (5 ml) and dry pyridine (1 ml) solvents. ), and cooled in an ice bath, acetyl chloride (68 mg, 0.87 molimoles) was added dropwise, and the mixture was stirred at room temperature overnight, ethyl acetate and 1 N aqueous solution were added. Sodium hydroxide, the mixture was extracted with ethyl acetate, and the organic phase was dried with anhydrous sodium sulfate The product was purified by silica gel column chromatography (chloroform / methanol = 20/1), and the title compound (156 mg, 62%) was obtained in the form of colorless crystals by recrystallization from diethyl ether / heptane, 1 H NMR (400 MHz, CDCl 3, d ppm): 1.40-1.49 (2H, m), 1.52-1.65 (4H, m), 1.97-2.07 (2H, m), 2.02 (3H, s), 2.23 (3H, s), 2.38-2.46 (4H, brs), 2. 50 (2H, t, J = 7.2 Hz), 4.05 (2H, t, J = 6.0 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.64 (1 H, d, J = 8.8 Hz), 7.86-7.92 (1 H, brs), 7.99 (1 H, d, J = 2.8 Hz), 8.40 (1 H, dd, J = 2.0, 8.8 Hz).

The compound of Example 66-79 was obtained by condensation of amino-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with the corresponding acid chloride or carboxylic acid according to the procedure of Example 65.

EXAMPLE 66 6- (Butyrylamino) -2-methyl-3-f4-r3- (1-piperidininpropoxy-1-phenyl) -4- (3H) -quinazolinone The title compound was obtained by condensing 6-amino-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with butanoyl chloride according to the procedure of Example 65. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.99 (3H, t, J = 7.6 Hz), 1.42-1.50 ( 2H, m), 1.56-1.66 (4H, m), 1.68-1.78 (2H, m), 1.98-2.07 (2H, m), 2.23 (3H, s), 2.25 (2H, t, J = 7.6 Hz) , 2.38-2.46 (2H, brs), 2.49 (2H, t, J = 7.2 Hz), 4.05 (2H, t, J = 6.0 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.63 (1 H, d, J = 8.8 Hz), 7.65 (1 H, s), 7.97 (1 H, d, J = 2.4 Hz), 8.38 (1 H, d, J = 9.2 Hz).

EXAMPLE 67 6- (Hexanoylamino) -2-methyl-3-. { 4-f3- (1-piperidinyl) propoxy] phenyl > -4- (3H) - quinazolinone The title compound was obtained by condensing 6-amino-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -chinazolinone with hexanoyl chloride according to the procedure of Example 65. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.91 (3H, t, J = 6.8 Hz), 1.29- 1.40 (4H, m), 1.41-1.49 (2H, m), 1.58-1.65 (4H, m), 1.66-1.78 (2H, m), 1.97-2.06 (2H, m), 2.23 (3H, s), 2.28 (2H, t, J = 7.6 Hz), 2.38-2.46 (4H, brs), 2.49 (2H, t, J = 7.2 Hz), 4.05 (2H, t, J = 6.0 Hz), 7.03 (2H, d , J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.63 (1 H, d, J = 8.8 Hz), 7.64 (1 H, s), 7.97 (1 H, d, J = 2.8 Hz), 8.38 (1 H, dd, J = 2.4, 8.4 Hz).

EXAMPLE 68 6- (Benzoylamino) -2-methyl-3-. { 4-f3- (1-piperidinyl) propoxphenyl} -4- (3H) - quinazolinone The title compound was obtained by condensing 6-amino-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with benzoyl chloride according to the procedure of Example 65. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.40-1.49 (2H, m), 1.55-1.65 (4H, m ), 1.95-2.05 (2H, m), 2.24 (3H, s), 2.37-2.46 (4H, brs), 2.48 (2H, t, J = 7.2 Hz), 4.02 (2H, t, J = 6.0 Hz) , 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.48 (2H, t, J = 7.6 Hz), 7.52-7.57 (1 H, m), 7.70 (1 H, d, J = 8.8 Hz), 7.86 (2H, d, J = 7.6 Hz), 8.09 (1 H, d, J = 2.4 Hz), 8.15 (1H, brs), 8.48 (1 H, dd, J = 2.8, 8.8 Hz).

EXAMPLE 69 6-r (2-Phenylacetyl-amino-2-methyl-3- {4-r3- (1-piperidinipropoxyphenylV4- (3H) -quinazolinone The title compound was obtained by condensation of 6-amino-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenol} -4- (3H) -quinazolinone with benzyloyl chloride according to the procedure of Example 65. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.40-1.49 (2H, brs), 1.50-1.65 (4H, m ), 1.93-2.05 (2H, m), 2.21 (3H, s), 2.37-2.45 (4H, brs), 2.48 (2H, t, J = 7.2 Hz), 3.60 (2H, s), 3.97 (2H, brt), 6.97 (2H, d, J = 8.0 Hz), 7.10 (2H, d, J = 8.0 Hz), 7.20-7.41 (5H, m), 7.61 (1 H, d, J = 9.2 Hz), 7.69 (1 H, s), 7.89 (1 H, s), 8.33 (1 H, d, J = 8.8 Hz).

EXAMPLE 70 6- (2-Naphthoylamino) -2-methyl-3-. { 4-r3- (1-piperidinyl) propoxyphenyl) 4- (3H) -quinazolinone The title compound was obtained by condensing 6-amino-2-methyl-3-. { 4- [3- (1-piperidin) propoxy] phenyl} -4- (3H) -quinazolinone with 2-naphthoyl chloride according to the procedure of Example 65. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.40-1.49 (2H, m), 1.55-1.65 (4H , m), 1.92-2.00 (2H, m), 2.23 (3H, s), 2.37-2.50 (6H, m), 3.93 (2H, t, J = 6.0 Hz), 6.93 (2H, d, J = 8.8 Hz), 7.09 (2H, d, J = 8.8 Hz), 7.53-7.62 (2H, m), 7. 72 (1 H, d, J = 8.8 Hz), 7.86-7.95 (4H, m), 8.17 (1 H, d, J = 2.4 Hz), 8.39 (1 H, s), 8.44 (1 H, s) , 8.55 (1 H, dd, J = 2.4, 9.2 Hz).

EXAMPLE 71 2-Methyl-6-r-methylsulfonyl) amino-3- (3-r3- (1-piperidinyl) propoxyphenyl-4- (3H) -quinazolinone The title compound was obtained by condensation of 6-amino-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with mesyl chloride according to the procedure of Example 65. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.49-1.60 (2H, m), 1.71-1.80 (4H, m ), 2.12-2.20 (2H, m), 2.24 (3H, s), 2.62-2.70 (4H, brs), 2.73 (2H, t, J = 7.6 Hz), 2.97 (3H, s), 4.07 (2H, t, J = 6.0 Hz), 7.01 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.63 (1 H, d, J = 8.4 Hz), 7.74 (1 H, dd, J = 2.4, 8.4 Hz), 8.02 (1 H, d, J = 2.4 Hz).

EXAMPLE 72 2-MetH-6-r (methylsulfonipamino-3- (4-r3- (1-pyrrolidinyl) propoxyphenol> -4- (3H) -quinazolinone The title compound was obtained by condensation of 6-amino-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with mesyl chloride according to the procedure of Example 65. 1 H NMR (400 MHz, CDCl 3, d ppm): 2.01-2.09 (4H, m), 2.24 (3H, s), 2.25-2.34 (2H, m), 3.01 (3H, s), 3.05-3.18 (6H, m), 4.13 (2H, t, J = 6.0 Hz), 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.65 (1 H, d, J = 8.8 Hz), 7.77 (1 H, dd, J = 2.4, 8.4 Hz), 7.91 (1 H, d, J = 2.4 Hz ).

EXAMPLE 73 7- (Acetylamino) -2-methyl-3- (4-r3- (1-piperidinyl) propoxphenyl) -4- (3H) -quinazolinone The title compound was obtained by condensing 7-amino-2-methyl-3-. { 4- [3- (1-pperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with acetyl chloride according to the procedure of Example 65. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.53-1.40 (2H, m), 1.69-1.59 (4H, m), 2.10-2.00 (2H, m), 2.21 (3H, s), 2.22 (3H , s), 2.55-2.46 (4H, m), 2.58 (2H, t, J = 7.3 Hz), 4.04 (2H, t, J = 6.2 Hz), 6.99 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.58 (2H, m), 7.82 (1 H, brs), 8.16 (1 H, d, J = 8.8 Hz).

EXAMPLE 74 7- (Butyrylamino) -2-methyl-3- (4-r3- (1-piperidinyl) propoxphenyl-> -4- (3H) -quinazolinone The title compound was obtained by condensation of 7-amino-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with butanoyl chloride according to the procedure of Example 65. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.52-1.40 (2H, m), 1.66-1.58 (4H, m ), 1.77 (2H, m), 2.00 (2H, t, J = 10.0 Hz), 2.21 (3H, s), 2.38 (2H, t, J = 6.6 Hz), 2.52 (2H, brs), 2.55 (2H) , t, J = 12.2 Hz), 4.03 (2H, t, J = 6.2 Hz). 6.99 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.54 (1H, s), 7.61 (1H, dd, J = 8.4, 1.8 Hz), 7.79 (1 H, d, J = 2.2 Hz), 1.01 (3 H, t, J = 7.3 Hz), 8.15 (1 H, d, J = 8.8 Hz).

EXAMPLE 75 7- (Hexanoylamino) -2-methyl-3-. { 4-r3- (1-piperidinyl) propoxylphenyl > -4- (3H) - quinazolinone The title compound was obtained by condensation of 7-amino-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with hexanoyl chloride according to the procedure of Example 65. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.91 (3H, t, J = 7.0 Hz), 1.41-1.29 ( 4H, m), 1.53-1.41 (2H, m), 1.68-1.57 (4H, m), 1.81-1.68 (2H, m), 2.08-1.97 (2H, m), 2.22 (3H, s), 2.39 ( 2H, t, J = 10.0 Hz), 2.47 (4H, m), 2.56 (2H, t, J = 10.0 Hz), 4.04 (2H, t, J = 6.2 Hz), 7.00 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.63 (1 H, d, J = 8.8 Hz), 7.72 (1 H, brs), 7.80 (1 H, brs), 8.15 (1 H, d , J = 8.8 Hz).

EXAMPLE 76 7- (Benzoylamino) -2-methyl-3-. { 4-r3- (1-piperidinyl) propoxyphenyl} -4- (3H) - quinazolinone The title compound was obtained by condensation of 7-amino-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with benzoyl chloride according to the procedure of Example 65. 1 H NMR (400 MHz, CD3OD, d ppm): 1.57-1.47 (2H, m), 1.72-1.63 (4H, m ), 2.12-2.02 (2H, m), 2.24 (3H, s), 2.63-2.54 (2H, m), 2.66 (2H, t, J = 10.8 Hz), 3.32-3.28 (8H, m), 4.11 ( 2H, t, J = 5.9 Hz), 7.10 (2H, d, J = 8.8 Hz), 7.25 (2H, d, J = 8.8 Hz), 7.52 (2H, t, J = 7.3 Hz), 7.60 (1 H , t, J = 7.3 Hz), 7.79 (1 H, dd, J = 8.8, 2.2 Hz), 7.96 (2H, d, J = 7.3 Hz), 8.14 (1 H, d, J = 8.8 Hz), 8.27 (1 H, d, J = 2.2 Hz).

EXAMPLE 77 7-f (2-Phenylacetyl) amino-2-methyl-3-. { 4-f3- (1-piperidinyl) propoxy1phenyl} -4- (3H) - quinazolinone The title compound was obtained by condensation of 7-amino-2-methyl-3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone with benzyloyl chloride according to the procedure of Example 65. 1 H NMR (400 MHz, CD3OD, d ppm): 1.62-1.47 (2H, m), 1.78-1.63 (4H, m ), 2.16-2.02 (2H, m), 2.21 (3H, s), 2.67-2.56 (4H, m), 2.70 (2H, t, J = 10.0 Hz), 3.74 (2H, s), 4.11 (2H, t, J = 5.9 Hz), 7.09 (2H, d, J = 8.8 Hz), 7.42-7.20 (8H, m), 7.63 (1 H, d, J = 8.8 Hz), 8.09 (2H, d, J = 8.1 Hz).

EXAMPLE 78 7- (2-Naphthoylamino) -2-methyl-3- (4-r3- (1-piperidinyl) propoxyphenyl > -4- (3H) -quinazolinone The title compound was obtained by condensation of 7-amino-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with 2-naphthoyl chloride according to the procedure of Example 65. 1 H NMR (400 MHz, CD3OD, d ppm): 1.74-1.61 (2H, m), 1.90-1.77 (4H , m), 2.26 (3H, s), 3.24-3.05 (4H, m), 3.34-3.27 (2H, m), 4.19 (2H, t, J = 5.5 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.30 (2H, d, J = 8.8 Hz), 7.68-7.57 (2H, m), 7. 88-7.84 (2H, m), 7.96 (1 H, d, J = 8.8 Hz), 8.08-8.00 (3H, m), 8.17 (1 H, d, J = 8. 8 Hz), 8.34 (1 H, d, J = 2.2 Hz), 8.56 (1 H, s) EXAMPLE 79 6-f-Acetyl (methyl) aminol-2-methyl-3-. { 4-r3- (1-piperidinyl) propoxy-phenyl> -4- (3H) - quinazolinone The title compound was obtained by treating 6- (acetylamino) -2-methyl-3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone synthesized in Example 65 with sodium hydride in dimethylformamide, and methylating with methyl iodide. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.42-1.50 (2H, m), 1.58-1.66 (4H, m), 1.98-2.08 (2H, m), 2.27 (3H, s), 2.40-2.50 (4H, brs), 2.53 (2H, t, J = 7.6 Hz), 3.31 (3H, s), 4.07 (2H, t, J = 6.4 Hz), 7.02 (2H, d, J = 8.4 Hz), 7.12 (2H, d, J = 8.4 Hz), 7.55 (1 H, d, J = 8.4 Hz), 7.70 (1 H, d, J = 8.4 Hz), 8.05 (1 H, s).

EXAMPLE 80 2-Methyl-6-phenyl-3-. { 4-r3- (1-piperidinyl) propoxy phenyl > -4- (3H) -quinazolinone 2-Methyl-6-bromo-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone (100 mg, 0.25 molimoles) and boronic acid (40 mg, 0.32 molimoles) were dissolved in dimethoxyethane (1 ml), and the atmosphere of the system was replaced by nitrogen. 2 M aqueous sodium carbonate solution (0.3 ml) and tetrakis (triphenylphosphine) and palladium complex (10 mg, 0.012 molimoles) were added and stirred at 80 ° C for 3 hours. Ethyl acetate and distilled water were added to the reaction mixture to perform an extraction with ethyl acetate. The organic phase was washed with saturated brine and dried with anhydrous sodium sulfate. The product was purified by silica gel column chromatography (chloroform / methanol = 20/1), and the target substance (61 mg, 61%) was obtained as a colorless solid. 2-Methyl-6-bromo-3- was used. { 4- [3- (1-piperidinyl) propoxl] phenol} -4- (3H) -quinnanolinone which was synthesized in Example 34. 1 H-NMR (400 MHz, CDCl 3, d ppm): 1.45 (2H, brs), 1.58-1.63 (4H, m), 2.00-2.04 (2H, m), 2.27 (3H, s), 2.42 (4H, brs), 2.50 (2H, t, J = 7.2 Hz), 4.07 (2H, t, J = 6.4 Hz), 7.04 (2H, d, J = 8.8 Hz), 7.15 (2H, d, J = 8.8 Hz), 7.36 (1 H, t, J = 7.6 Hz), 7.46 (2H, t, J = 7.6 Hz), 7.67 (2H, d, J = 7.2 Hz), 7.72 (1 H, d, J = 8.4 Hz), 7.98 (1 H, d, J = 2.0 Hz), 8.46 (1 H, s).

EXAMPLE 81 2-Methyl-6- (4-methylphenyl) -3- (4-r3- (1-p-peridinyl) propoxyphenyl) -4- (3H) -quinazolinone The title compound was obtained by Suzuki coupling of 2-methyl-6-bromo-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with 4-methylboronic acid according to the procedure of Example 80. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.46 (2H, brs), 1.59-1.63 (4H, m), 2.01-2.04 (2H, m), 2.28 (3H, s), 2.41 (7H, brs), 2.49-2.53 (2H, m), 4. 08 (2H, t, J = 6.0 Hz), 7.05 (2H, d, J = 8.8 Hz), 7.16 (2H, d, J = 8.8 Hz), 7.27 (2H, d, J = 8.0 Hz), 7.58 ( 2H, d, J = 8.0 Hz), 7.71 (1 H, d, J = 8.8 Hz), 7.97-8.00 (1H, m), 8.46 (1 H, s).

EXAMPLE 82 2-Methyl-6- (3-methylphenyl) -3- (4-r3- (1-piperidinyl) propoxyphenyl) -4- (3H) -quinazolinone The title compound was obtained by Suzuki coupling of 2-methyl-6-bromo-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with 3-methylboronic acid according to the procedure of Example 80. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.47 (2H, brs), 1.59-1.64 (4H, m), 2.02-2.06 (2H, m), 2.28 (3H, s), 2.44 (7H, m), 2.52 (2H, t, J = 7.2 Hz), 4.08 (2H, t, J = 6.4 Hz), 7.05 (2H, d, J = 7.2 Hz), 7.15-7.20 (3H, m), 7.35 (1 H, t, J = 7.2 Hz), 7.47-7.50 (2H, m), 7.72 (1 H, dd, J = 2.0, 8.8 Hz), 7.98-8.01 (1 H, m), 8.46 (1 H, s).

EXAMPLE 83 2-Methyl-6- (2-methylphenyl) -3-f4-r3- (1-piperidinyl) propoxy-1-phenyl) -4- (3H) -quinazolinone The title compound was obtained by means of Suzuki coupling of 2-methyl-6-bromo-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with 2-methylboronic acid according to the procedure of Example 80. NMR of H (400 MHz, CDCl 3, d ppm): 1.46 (2H, brs), 1.59-1.64 (4H, m) , 2.01-2.05 (2H, m), 2.29 (3H, s), 2.30 (3H, s), 2.43 (4H, brs), 2.51 (2H, t, J = 7.2 Hz), 4.07 (2H, t, J = 6.8 Hz), 7.04 (2H, d, J = 8.8 Hz), 7.16 (2H, d, J = 8.8 Hz), 7.24-7.30 (4H, m), 7.71 (2H, brs), 8.21 (1 H, brs).

EXAMPLE 84 2-Methyl-3-. { 4-r3- (1-piperidnol) propoxy-phenyl > -6- (3-pyridyl) -4- (3H) -quinazolinone The title compound was obtained by coupling Suzuki 2-methyl-6-bromo-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with 3-pyridylboronic acid according to the procedure of Example 80. 1 H NMR (400 MHz, CD3OD, d ppm): 1.51-1.53 (2H, m), 1.63-1.67 (4H, m), 2.04-2.08 (2H, m), 2.28 (3H, s), 2.59 (4H, brs), 2.61-2.63 (2H, m), 4.11 (2H, t, J = 6.4 Hz), 7.11 (2H) , d, J = 9.2 Hz), 7.28 (2H, d, J = 8.8 Hz), 7. 53-7.757 (1 H, m), 7.79 (1H, d, J = 8.4 Hz), 8.14-8.21 (4H, m), 8.45 (1 H, d, J = 2.4 Hz), 8.55 (1 H, dd, J = 1.8, 5.0 Hz), 8.89 (1 H, dd, J = 0.6, 2.2 Hz).

EXAMPLE 85 2-Methyl-3-. { 4-r3- (1-piperidinyl) propoxyphenyl) -6- (4-pyridyl) -4- (3H) -quinazolinone The title compound was obtained by Suzuki coupling of 2-methyl-6-bromo-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone with 4-pyridylboronic acid according to the procedure of Example 80. 1 H NMR (400 MHz, CD3OD, d ppm): 1.51-1.52 (2H, m), 1.63-1.68 (4H, m), 2.04-2.08 (2H, m), 2.28 (3H, s), 2.54 (4H , brs), 2.58-2.62 (2H, m), 4.11 (2H, t, J = 6.0 Hz), 7.11 (2H, d, J = 8.4 Hz), 7.28 (2H, d, J = 8.8 Hz), 7. 78-7.81 (3H, m), 8.23 (1 H, dd, J = 2.4, 8.4 Hz), 8.54 (1 H, s), 8.61 (2H, d, J = 6.4 Hz).

EXAMPLE 86 2-Methyl-5-phenyl-3- (4-r3- (1-piperidinyl) propoxyphenyl) -4- (3H) -q-nazolinone -Chloro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone (100 mg, 0.24 molimoles), phenylboronic acid (90 mg, 0.73 molimoles) and cesium carbonate (480 mg, 1.45 molimoles) were mixed in 1,4-dioxane (1 ml), and the atmosphere of the system was replaced by nitrogen. Pd2 (dba) 3 (15 mg, 0.012 molimole) and tri-t-butylphosphine (10 mg, 0.036 molimole) were added, and stirred at 100 ° C for 12 hours. Chloroform and distilled water were added to the reaction mixture, and the mixture was extracted with chloroform. The organic phase was washed with saturated brine, and dried with anhydrous sodium sulfate. The product was purified by thin layer chromatography on silica gel, and the title compound (20 mg, 18%) was obtained as a colorless solid. The 5-chloro-2-methyl-3- was used. { 4- [3- (1-piperidinyl) propoxy] phenol} -4- (3H) -quinazolinone which was synthesized in Example 27. 1 H-NMR (400 MHz, CDCl 3, d ppm): 1.44 (2H, brs), 1.56-1.62 (4H, m), 1.95-1.99 (2H , m), 2.23 (3H, s), 2.40 (4H, brs), 2.46 (2H, t, J = 6.8 Hz), 3.99 (2H, t, J = 6.8 Hz), 6.94 (2H, d, J = 8.8 Hz), 7.06 (2H, d, J = 8.8 Hz), 7.23-7.33 (6H, m), 7.66-7.73 (2H, m).

EXAMPLE 87 2-Methyl-3-. { 4-r3- (1-piperidinyl) propoxy1phenyl > -6- (2-pyridyl) -4- (3H) -quinazolinone 6-Bromo-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone (100 mg, 0.25 molimoles) and 2- (tributylstannyl) pyridine (90 mg, 0.25 molimoles) were dissolved in toluene (1 ml), and the atmosphere of the system was replaced by nitrogen. Tetrakis (triphenylphosphine) and palladium complex (30 mg, 0.025 molimoles) was added, and it was stirred at 120 ° C for 12 hours. The insoluble matter was removed by filtration with celite, chloroform was added to the filtrate, the organic phase was washed with distilled water, and dried with anhydrous sodium sulfate. The product was purified by silica gel column chromatography (chloroform / methanol = 9/1), and the target substance (20 mg, 20%) was obtained as a colorless solid. The 6-bromo-2-methyl-3- was used. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone which was synthesized in Example 34. 1 H NMR (400 MHz, CD3OD, d ppm): 1.50-1.51 (2H, m), 1.62-1.67 (4H, m), 2.03-2.08 (2H, m), 2.28 (3H, s), 2.51 (4H, brs), 2.56-2.60 (2H, m), 4.11 (2H, t, J = 5.6 Hz), 7.11 (2H, d, J = 9.2 Hz), 7.28 (2H, d, J = 9.2 Hz), 7.37-7.40 (1 H, m), 7.76 (1 H, d, J = 8.8 Hz), 7.89-7.98 (4H, m), 8.45 (1 H, dd, J = 2.0, 8.4 Hz), 8.63-8.65 (2H, m) EXAMPLE 88 3- (4-r (1-Cyclobutyl-4-piperidinyl) oxphenyl) -2-methyl-4- (3H) -quinazolinone (1) Preparation of 3-. { 4 - [(1-t-Butoxycarbonyl-4-piperidinyl oxy] phenyl) -2-methyl-4- (3H) -quinazolinone 2-Methyl-3- (4-hydroxyphenyl) -4- (3H) quinazolinone synthesized in accordance with Example 1- (1) and - (2) (1.0 g, 3.96 molimoles), N- (t-butoxycarbonyl) -4-piperidinol (956 mg, 4.75 molimoles) and triphenylphosphine (1.56 g, 5.94 molimoles) were dissolved in dry tetrahydrofuran (2 ml) in a stream of nitrogen, and cooled in an ice bath. Diethyl azodicarboxylate (1.17 ml, 5.94 molimoles) was added dropwise at 0 ° C, and it was stirred at room temperature for 48 hours. The solvent was removed by distillation under reduced pressure, ether was added, the solid precipitate was removed by filtration, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 7/3), and the target substance (1.1 g, 64%) was obtained as a light brown solid. 2-Methyl-3- (4-hydroxyphenyl) -4- (3H) quinazolinone was synthesized according to Example 1- (1) and - (2). (2) Preparation of 2-methyl-3-r4- (4-piperidinyloxy) phenan-4- (3H) -quinazolinone 3-. { 4 - [(1-t-Butoxyarylbonyl-4-pyridinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone (1.1 g, 2.53 molimoles) was dissolved in chloroform (10 ml), trifluoroacetic acid (10 ml) was added and the mixture was stirred at room temperature for 30 minutes. The solvent was distilled off under reduced pressure, ethyl acetate and 2N aqueous sodium hydroxide solution were added, the mixture was extracted with ethyl acetate, and the organic phase was dried with anhydrous sodium sulfate. Sodium sulfate was removed by filtration, and the filtrate was concentrated and dried to obtain the target substance (0.83 g, 98%) as a lavender solid. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.67-1.81 (2H, m), 2.01-2.10 (2H, m), 2.26 (3H, s), 2.72-2.80 (2H, m), 3.13-3.20 (2H, m), 4.40-4.47 (1 H, m), 7.03 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.44 (1 H, t, J = 8.0 Hz), 7.65 (1 H, d, J = 7.6 Hz), 7.74 (1 H, t, J = 7.6 Hz), 8.25 (1 H, d, J = 8.0 Hz). (3) Preparation of 3-. { 4-f (1-cyclobutyl-4-piperidinyl) oxy] phenol) -2-methyl-4- (3H) -quinazolinone 2-Methyl-3- [4- (4-piperidinyloxy) phenyl } -4- (3H) -quinazolinone (370 mg, 1.10 molimoles) and cyclobutanone (155 mg, 2.20 molimoles) were dissolved in a 0.5 M solution in methanol (6 ml) of zinc chloride (II) and sodium cyanoborohydride, and they were stirred at room temperature for 1 hour. The solvent was removed by distillation under reduced pressure. Ethyl acetate and distilled water were added, the mixture was extracted with ethyl acetate, and the organic phase was washed with distilled water. After drying with anhydrous sodium sulfate, the product was purified by silica gel column chromatography (chloroform / methanol = 30/1), and the title compound (165 mg, 39%) was obtained as a colorless solid. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.63-1.76 (2H, m), 1.84-1.95 (4H, m), 1.99-2.10 (4H, m), 2.14-2.23 (2H, m), 2.26 (3H, s), 2.59-2.67 (2H, m), 2.70-2.79 (1 H, m), 4.33-4.41 (1 H, m), 7.01 (2H, d, J = 8.8 Hz), 7.44 (1 H, t, J = 8.0 Hz), 7.65 (1 H, d, J = 8.4 Hz), 7.74 (1 H, t, J = 7.6 Hz), 8.24 (1 H, d, J = 7.6 Hz) .

EXAMPLE 89 3-. { 4-f (1-Cyclopentyl-4-piperidinyl) oxphenyl) -2-methyl-4- (3H) -quinazolinone The title compound was obtained by performing a reductive amination according to the procedure of Example 88- (3), using 2-methyl-3- [4- (4-piperidinyloxy) phenyl} -4- (3H) -quinazolinone, N-Boc-4-piperidinol and cyclopentanone as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.25-1.48 (2H, m), 1.52-1.61 (2H, m), 1.66-1.73 (2H, m), 1.83-1.93 (4H, m), 2.01 -2.12 (2H, m), 2.25 (3H, s), 2.32-2.40 (2H, m), 2.49-2.58 (1H, m), 2.79-2.95 (2H, m), 4.33-4.41 (1H, m), 7.03 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.44 (1 H, t, J = 7.2 Hz), 7.65 (1 H, d, J = 7.6 Hz), 7.74 (1 H, t, J = 7.2 Hz), 8.25 (1 H, d, J = 7.6 Hz).

EXAMPLE 90 3-. { 4- (1-Cyclohexyl-4-p-peridinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone The title compound was obtained by conducting a reductive amination according to the procedure of Example 88- (3), using 2-methyl-3- [4- (4-p-pperidinyloxy) phenyl} -4- (3H) -quinazolinone, N-Boc-4-piperidinol and cyclohexanone as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.18-1.30 (6H, m), 1.78-1.90 (6H, m), 2.01-2.08 (2H, m), 2.26 (3H, s), 2.27-2.36 (1 H, m), 2.42-2.51 (2H, m), 2.81-2.89 (2H, m), 4.30-4.38 (1 H, m), 7.03 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.44 (1 H, t, J = 8.0 Hz), 7.65 (1H, d, J = 8.0 Hz), 7.74 (1 H, t, J = 8.0 Hz), 8.25 (1 H, d, J = 8.0 Hz).

EXAMPLE 91 3-. { 4- (1-lsopropyl-4-piperidinyloxy) phenyl) -2-methyl-4- (3H) -quinazolinone The title compound was obtained by performing a reductive amination according to the procedure of Example 88- (3), using 2-methyl-3- [4- (4-piperidinyloxy) phenyl} -4- (3H) -quinazolinone, N-Boc-4-piperidinol and acetone as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.07 (6H, d, J = 6.4 Hz), 1.82-1.92 (2H, m), 2.02-2.11 (2H, m), 2.26 (3H, s), 2.37-2.46 (2H, m), 2.72-2.84 (3H, m), 4.31-4.40 (1 H, m), 7.03 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz ), 7.44 (1 H, t, J = 8.0 Hz), 7.65 (1 H, d, J = 8.0 Hz), 7.74 (1 H, t, J = 8.0 Hz), 8.25 (1 H, d, J = 8.0 Hz).

EXAMPLE 92 3-. { 4- (1-Ethyl-4-piperidinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone 2-Met.l-3- [4- (4-p.peridinyloxy) phenyl} -4- (3H) -quinazolinone (50 mg, 0.15 molimoles), ethyl iodide (23 mg, 0.15 molimoles) and potassium carbonate (0.30 molimoles) were mixed in dimethylformamide (1 ml), and stirred at room temperature for 1 hour . The solvent was distilled off under reduced pressure, ethyl acetate and 1 N aqueous sodium hydroxide solution were added, and the mixture was extracted with ethyl acetate. The organic phase was washed with distilled water, dried with anhydrous sodium sulfate, and the product was purified by silica gel column chromatography (chloroform / methanol = 30/1) to obtain the title compound (25 mg, 46%). in the form of a colorless solid. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.12 (3H, t, J = 6.8 Hz), 1.83-1.95 (2H, m), 2.02-2.10 (2H, m), 2.26 (3H, s), 2.26-2.39 (2H, m), 2.45 (2H, q, J = 7.2 Hz), 2.72-2.81 (2H, m), 4.35-4.43 (1 H, m), 7.03 (2H, d, J = 8.8 Hz ), 7.13 (2H, d, J = 8.8 Hz), 7.44 (1 H, t, J = 8.0 Hz), 7.65 (1 H, d, J = 8.0 Hz), 7.74 (1 H, t, J = 8.0) Hz), 8.25 (1 H, d, J = 8.0 Hz).

EXAMPLE 93 3-. { 4- (1-Butyl-4-piperidinyloxy) phenyl > -2-methyl-4- (3H) -quinazolinone The title compound was obtained by N-alkylation, using 2-methyl-3- [4- (4-piperidinyloxy) phenyl} -4- (3H) -quinazolinone and butyl iodide according to Example 92. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.93 (3H, t, J = 7.2 Hz), 1. 28-1.39 (2H, m), 1.46-1.54 (2H, m), 1.83-1.93 (2H, m), 2.01-2.10 (2H, m), 2. 26 (3H, s), 2.26-2.39 (4H, m), 2.72-2.81 (2H, m), 4.33-4.41 (1H, m), 7.03 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.44 (1 H, t, J = 8.0 Hz), 7.65 (1 H, d, J = 8.0 Hz), 7.74 (1 H, t, J = 8.0 Hz), 8.25 (1 H, d, J = 8.0 Hz).

EXAMPLE 94 3-. { 4 - [(1-Cyclopentyl-4-piperidinyl) oxphenyl} -2-methyl-5-trifluoromethyl-4- (3H) -quinazolinone (1) Preparation of 4- (4-nitrophenoxy) piperidine N-Boc-4-piperidinol (10 g, 50 molimoles), 4-nitrophenol (7.0 g, 50 molimoles) and triphenylphosphine (15.7 g, 60 molimoles) are dissolved in dry tetrahydrofuran (150 ml), and cooled in the ice bath. Diisopropyl azodicarboxylate (11.8 ml, 60 mollmoles) was added slowly, and stirred for 2 days at room temperature. The solvent was removed by distillation under reduced pressure, diethyl ether was added, and the solid precipitate was removed by filtration. The filtrate was concentrated and the product was purified by column chromatography on silica gel (hexane / ethyl acetate = 6/1). Trifluoroacetic acid was added to the obtained residue and stirred at room temperature for 1 hour. After distillation under reduced pressure, 1 N aqueous sodium hydroxide solution was added, and the mixture was extracted with ethyl acetate. After drying with anhydrous sodium sulfate, the product was concentrated and dried to obtain the target substance (6.75 g, 61%). (2) Preparation of 1-cyclopentyl-4- (4-nitrophenoxy) piperidine 4- (4-nitrophenoxy) piperidine (1.03 g, 4.65 molimoles) and cyclopentanone (783 mg, 9.31 molimoles) were dissolved in a methanol solution 0.5 M (20 ml) of zinc chloride (II) and sodium cyanoborohydride, and stirred at room temperature for 10 hours. The solvent was distilled off under reduced pressure, ethyl acetate and 1 N aqueous sodium hydroxide solution were added, the mixture was extracted with ethyl acetate, and the organic phase was washed with distilled water. After drying with anhydrous sodium sulfate, the product was concentrated, and thereby the target compound (1.31 g, 96%) was obtained as a light brown solid. (3) Preparation of 4-f (1-cyclopentylpiperidin-4-yl) oxy] aniline 1-Cyclopentyl-4- (4-nitrophenoxy) piperidine (1.30 g) was dissolved in methanol, and the compound target (1.0 g, 86%) was obtained as a light brown solid by catalytic reduction using an activated carbon palladium catalyst. (4) Preparation of 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl) -2-methyl-5-trifluoromethyl-4- (3H) -quinazolinone 2-Methyl-5-trifluoromethyl-4H-3,1-benzoxadine -4-one (71 mg, 0.31 molimoles) and 4 - [(1-cyclopentyl-4-piperidinyl) oxy] aniline (80 mg, 0.31 molimoles) were dissolved in acetic acid (0.5 ml), and stirred at 130 °. C for 6 hours. The solvent was removed by distillation under reduced pressure, and ethyl acetate and 1 N aqueous sodium hydroxide solution were added. The mixture was extracted with ethyl acetate, and the organic phase was dried with anhydrous sodium sulfate. The product was purified by silica gel column chromatography (chloroform / methanol = 20/1), and thus the title compound (88 mg, 61%) was obtained as a light brown solid. 2-Methyl-5-trifluoromethyl-4H-3,1-benzoxadin-4-one was prepared by the procedure according to Example 1- (1), using 2-amino-6-trifluoromethylbenzoic acid and acetic anhydride as starting materials . 1 H NMR (400 MHz, CDCl 3, d ppm): 1.38-1.49 (2H, m), 1.51-1.62 (2H, m), 1.65-1.76 (2H, m), 1.82-1.94 (4H, m), 2.00 -2.09 (2H, m), 2.26 (3H, s), 2.32-2.42 (2H, m), 2.48-2.58 (1H, m), 2.76-2.86 (2H, m), 4.32-4.40 (1H, m), 7.02 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.78 (1 H, t, J = 8.0 Hz), 7.83-7.88 (2H, m).

The NMR data for 4 - [(1-cyclopentylpiperidin-4-yl) oxy] aniline which is used for the preparation of the compound of this example are shown below. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.36-1.45 (2H, m), 1.49-1.58 (2H, m), 1.64-1.99 (10H, m), 2.24-2.31 (2H, m), 2.45 -2.54 (1H, m), 2.80 (2H, brs), 3.43 (2H, brs), 4.12 (1 H, s), 6.63 (2H, d, J = 8.8 Hz), 6.76 (2H, d, J = 8.8 Hz). The product of Examples 95-115 can be prepared by a procedure identical to! of Example 94, a method based thereon or a combination thereof with a conventional procedure, using the corresponding anthranilic acid, acid anhydride and 4 - [(1-cyclopentyl-4-piperidinyl) oxy] aniline or 4 - [( 1-cyclobutyl-4-piperidinyl) oxy] aniline as starting materials.

EXAMPLE 95 3-. { 4- (1-Cyclopentyl-4-piperidinyloxy) phenyl) -2,5-dimethyl-4- (3H) -quinazolinone The title compound was obtained by cyclization, using 2,5-dimethyl-4H-3,1-benzoxazin-4-one and 4 - [(1-cyclopentyl-4-piperidinyl) oxy] aniline, according to the procedure of Example 94. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.37-1.50 (2H, m), 1.54-1.61 (2H, m), 1.64-1.78 (4H, m), 1.82-1.96 (4H, m ), 2.00-2.10 (2H, m), 2.22 (3H, s), 2.32-2.42 (2H, m), 2.49-2.59 (1 H, m), 2.81 (3H, s), 4.32-4.41 (1 H) , m), 7.03 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.19 (1 H, d, J = 7.2 Hz), 7.48 (1 H, d, J = 7.6 Hz), 7.57 (1 H, t, J = 8.0 Hz).

EXAMPLE 96 7-Chloro-3-. { 4-r (1-cyclopentyl-4-piperidinyl) oxy-phenyl-V2-methyl-4- (3H) -quinazolinone The title compound was obtained by cyclization, using 7-chloro-2-methyl-4H-3,1-benzoxazin-4-one and 4 - [(1-cyclopentyl-4-piperidinyl) oxy] ani ln according to the procedure of Example 94. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.37-1.49 (2H, m), 1.50-1.63 (2H, m), 1.65-1.76 (2H, m ), 1.82-1.94 (4H, m), 2.00-2.10 (2H, m), 2.25 (3H, s), 2.30-2.41 (2H, m), 2.48-2.58 (1 H, m), 2.77-2.87 (2H, m), 4.33-4.41 (1H, m), 7.02 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.38 (1 H, dd, J = 2.4, 8.4 Hz), 7.64 (1 H, d, J = 2.4 Hz), 8.16 (1 H, d, J = 8.4 Hz).

EXAMPLE 97 3-. { 4-r (1-Cyclopentyl-4-piperidinyl) oxphenyl} -2,6-dimethyl-4- (3H) -quinazolinone The title compound was obtained by cyclization, using 2,6-dimethyl-4H-3,1-benzoxazin-4-one and 4 - [(1-cyclopentyl-4-piperidinyl) oxy] aniline according to the procedure of Example 94 1 H NMR (400 MHz, CDCl 3, d ppm): 1.38-1.49 (2H, m), 1.50-1.63 (2H, m), 1.65-1.76 (2H, m), 1.84-1.95 (4H, m), 2.00 -2.11 (2H, m), 2.23 (3H, s), 2.31-2.42 (2H, m), 2.48 (3H, s), 2.48-2.58 (1H, m), 2.78-2.86 (2H, m), 4. 33-4.41 (1 H, m), 7.02 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.55 (2H, s), 8.02 (1 H, s).

EXAMPLE 98 6-Chloro-3-f4-r (1-cyclopentyl-4-piperidinyl) oxypihenyl > -2-methyl-4- (3H) -quinazolinone The title compound was obtained by cyclization, using 6-chloro-2-methyl-4H-3,1-benzoxazin-4-one and 4 - [(1-cyclopentyl-4-piperidinyl) oxy] aniline according to the procedure of Example 94. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.37-1.48 (2H, m), 1.50-1.62 (2H, m), 1.65-1.77 (2H, m), 1.84-1.94 ( 4H, m), 2.00-2.10 (2H, m), 2.24 (3H, s), 2.30-2.41 (2H, m), 2.48-2.59 (1 H, m), 2.78-2.87 (2H, m), 4.33-4.41 (1 H, m), 7.02 (2 H, d, J = 8.8 Hz), 7.11 (2 H, d, J = 8.8 Hz), 7.58 (1 H, d, J = 8.8 Hz), 7.68 (1 H, dd, J = 2.4.8.8 Hz), 8.19 (1 H, d, J = 2.8 Hz).

EXAMPLE 99 3-. { 4"f (1-Cyclopentyl-4-piperidinyl) oxy1phenyl} - 6-methoxy-2-methyl-4- (3H) -quinazolinone The title compound was obtained by cyclization, using 6-methoxy-2-methyl-4H-3,1-benzoxazin-4-one and 4 - [(1-cyclopentyl-4-piperidinyl) oxy] aniline according to the procedure of Example 94. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.37-1.48 (2H, m), 1.50-1.62 (2H, m), 1.65-1.77 (2H, m), 1.84-1.94 ( 4H, m), 2.00-2.10 (2H, m), 2.23 (3H, s), 2.30-2.41 (2H, m), 2.49-2.58 (1H, m), 2.78-2.87 (2H, m), 3.89 (3H, s), 4. 33-4.41 (1 H, m), 7.02 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.33 (1 H, dd, J = 2.8, 8.8 Hz), 7.58 (1 H, d, J = 8.8 Hz), 7.61 (1 H, d, J = 3.2 Hz).

EXAMPLE 100 3-f4-r (1-Cyclopentyl-4-piperidinyl) oxphenyl) -2-methylpyridor-2,3-d-pyrimidin-4- (3H) -one The title compound was obtained by cyclization, using 2-methyl-4H-pyrido [2,3-d] [1, 3] oxadin-4-one and 4 - [(1-cyclopentyl-4-piperidinyl) oxy] aniline according to the procedure of Example 94. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.37-1.48 (2H, m), 1.49-1.63 (2H, m), 1.64-1.74 (2H, m), 1.83-1.93 (4H, m), 2.00-2.10 (2H, m), 2.34 (3H, s), 2.29-2.40 (2H, m), 2.49-2.58 (1H, m), 2.78-2.88 (2H, m ), 4.33-4.41 (1 H, m), 7.04 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.39 (1 H, dd, J = 4.0, 7.6 Hz) , 8.56 (1 H, dd, J = 2.4, 7.6 Hz), 8.96 (1 H, dd, J = 2.4, 4.8 Hz).

EXAMPLE 101 3- (4-r (1-Cyclopentyl-4-piperidinyl) oxypihenyl> 2-methylpyridrrr4,3-dlpyrimidin-4- (3H) -one The title compound was obtained as a white solid (mp: 140-143 ° C) by cyclization, using 2-methyl-4H-pyrido [4,3-d] [1, 3] oxazin-4-one and - [(1-cyclopentyl-4-piperidinyl) oxy] aniline according to the procedure of Example 94, followed by recrystallization (ethyl acetate / diethyl ether). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.39-1.49 (2H, m), 1.49-1.63 (2H, m), 1.64-1.78 (2H, m), 1.83-1.95 (4H, m), 2.00 -2.12 (2H, m), 2.29 (3H, s), 2.32-2.45 (2H, m), 2.50-2.61 (1H, m), 2.78-2.88 (2H, m), 4.34-4.41 (1H, m), 7.05 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.47 (1 H, d, J = 5.6 Hz), 8.82 (1 H, d, J = 5.6 Hz), 9.45 (1 H, s).

EXAMPLE 102 6-Chloro-3-. { 4-f (1-cyclopentyl-4-piperidinyl) oxphenyl} -2-methylpyridof3,4-d1pyrimidin-4- (3H) -one The title compound was obtained by cyclization, using 6-chloro-2-methyl-4H-pyrido [3,4-d] [1, 3] oxadin-4-one and 4 - [(1-cyclopentyl-4-p Peridinyl) oxy] aniline according to the procedure of Example 94. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.37-1.48 (2H, m), 1.50-1.62 (2H, m), 1.65-1.76 ( 2H, m), 1.83-1.94 (4H, m), 2.00-2.10 (2H, m), 2.28 (3H, s), 2.32-2.42 (2H, m), 2.48-2.58 (1 H, m), 2.78 -2.87 (2H, m), 4.33-4.41 (1 H, m), 7.04 (2 H, d, J = 8.8 Hz), 7.10 (2 H, d, J = 8.8 Hz), 8.03 (1 H, s), 8.88 (1 H, s).

EXAMPLE 103 3-. { 4 - [(1-Cyclopentyl-4-piperidinyl) oxy-phenyl} -2-methylpyridor3,4-d1pyrimidin-4- (3H) -one The title compound was obtained by catalytic reduction of 6-chloro-3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one synthesized in Example 102 using palladium on activated carbon as the catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.40-1.64 (4H, m), 1.65-1.79 (2H, m), 1.84-1.99 (4H, m), 2.01-2.10 (2H, m), 2.29 (3H, s), 2.37-2.45 (2H, m), 2.49-2.64 (1 H, m), 2.78-2.87 (2H, m), 4.33-4.47 (1 H, m), 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 8.00 (1 H, d, J = 5.2 Hz), 8.65 (1 H, d, J = 5.2 Hz), 9.10 (1 H, s ).

EXAMPLE 104 3-. { 4-r (1-Cyclobutyl-4-p-peridinyl) oxyphenyl > -2,5-dimethyl-4- (3H) -quinazolinone (1) Preparation of 4 - [(1-cyclobutyl-4-piperidinyl) oxylaniline The target compound was obtained as a light brown solid by the procedure according to Example 94, using 4- (4-nitrophenoxy) piperidine and cyclobutanone as starting materials. 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] aniline monotosylate can also be prepared by treating the 4 - [(1-cyclobutyl-4-piperidinyl) oxy] aniline obtained with one equivalent of p-toluenesulfonic acid. The 4- (4-nitrophenoxy) piperidine that was synthesized in Example 94 was used. (2) Preparation of 3-. { 4-f (1-cyclobutyl-4-piperidinyl) oxy] phenyl > -2,5-dimethyl-4- (3H) -quinazolinone The title compound was synthesized as a white solid (mp: 142-143 ° C) by the procedure according to Example 94, using 2-amino acid 6-methylbenzoic acid, acetic anhydride and 4 - [(1-cyclobutyl-4-pyridinyl) oxy] aniline as starting materials, followed by recrystallization (ethyl acetate). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.63-1.75 (2H, m), 1.82-1.96 (4H, m), 1.99-2.10 (4H, m), 2.13-2.22 (2H, m), 2.22 (3H, s), 2.58-2.67 (2H, m), 2.69-2.79 (1 H, m), 2.81 (3H, s), 4.33-4.40 (1 H, m), 7.02 (2H, d, J = 8. 8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.19 (1H, d, J = 8.0 Hz), 7.48 (1H, d, J = 8.0 Hz), 7.57 (1 H, t, J = 8.0 Hz). The NMR data for 4 - [(1-cyclobutyl-4-piperidinyl) oxy] aniline which is used for the preparation of the compound of this example are shown below. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.62-2.10 (12H, m), 2.58-2.65 (2H, m), 2.67-2.76 (1 H, m), 3.43 (1 H, brs), 4.15 -4.10 (H, m), 6.62 (2H, d, J = 8.8 Hz), 6.76 (2H, d, J = 8.8 Hz). The NMR data for 4 - [(1-cyclobutyl-4-piperidinyl) oxy] aniline monotosylate are shown below. 1 H NMR (400 MHz, CDCl 3 / CD 3 OD = 4/1, d ppm): 1.68-1.79 (1 H, m), 1.81-1.90 (1 H, m), 2.09-2.15 (2H, m), 2.19- 2.27 (2H, m), 2.34-2.43 (5H, m), 2.52-2.61 (2H, m), 2.86-2.93 (2H, m), 3.34-3.44 (3H, m), 4.52 (1H, brs) , 6.70-6.75 (4H, m), 7.21 (2H, d, J = 7.8 Hz), 7.79 (2H, d, J = 7.8 Hz).

EXAMPLE 105 3- (4-R (1-Cyclobutyl-4-piperidinyl) oxphenyl-5-methoxy-2-methyl-4- (3H) -quinazolinone The title compound was synthesized as a light yellow solid (mp: 153-156 ° C) by the procedure according to Example 94, using 2-amino-6-methoxybenzoic acid, acetic anhydride and 4- (1-cyclobutyl) -4-piperidinyl) oxyaniline as starting materials, followed by recrystallization (ethyl acetate / diethyl ether / n-heptane). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.63-1.77 (2H, m), 1.82-1.96 (4H, m), 1.98-2.09 (4H, m), 2.12-2.23 (2H, m), 2.21 (3H, s), 2.58-2.67 (2H, m), 2.69-2.79 (1 H, m), 3.94 (3H, s), 4.33-4.40 (1H, m), 6.85 (1 H, d, J = 8.8 Hz), 6.99 (2H, d, J = 8.8 Hz), 7.08 (2H, d, J = 8.8 Hz), 7.21 (1 H, d, J = 8.0 Hz), 7.62 (1H, t, J = 8.0 Hz).

EXAMPLE 106 3-. { 4-r (1-Cyclobutyl-4-piperidininoxphenyl) V2-methyl-5-trifluoromethyl-4- (3H) -quinazolinone The title compound was synthesized as a white solid (mp: 132-134 ° C) by the procedure according to Example 94, using 2-amino-6-trifluoromethylbenzoic acid, acetic anhydride and 4 - [(1-cyclobutyl-4-piperidinyl) oxy] aniline as starting materials , followed by recrystallization (ethyl acetate). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.63-1.77 (2H, m), 1.82-1.96 (4H, m), 1.98-2.09 (4H, m), 2.13-2.23 (2H, m), 2.26 (3H, s), 2.58-2.66 (2H, m), 2.70-2.79 (1H, m), 4.33-4.40 (1H, m), 7.01 (2H, d, J = 8.8 Hz), 7.12 (2H , d, J = 8.8 Hz), 7.77 (1 H, d, J = 8.0 Hz), 7.82-7.88 (2H, m).

EXAMPLE 107 5-Chloro-3- (4-r (1-cyclobutyl-4-piperidinyl) oxylphenol) -2-methyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 94, using 2-amino-6-chlorobenzoic acid, acetic anhydride and 4 - [(1-cyclobutyl-4-piperidinyl) oxy] aniline as materials initials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.63-1.77 (2H, m), 1.82-1.96 (4H, m), 1.99-2.09 (4H, m), 2.13-2.23 (2H, m), 2.23 (3H, s), 2.58-2.66 (2H, m), 2.69-2.79 (1H, m), 4.33-4.40 (1H, m), 7.00 (2H, d, J = 8.8 Hz), 7.12 (2H , d, J = 8.8 Hz), 7.43 (1 H, dd, J = 1.6, 7.2 Hz), 7.52-7.61 (2H, m).

EXAMPLE 108 3-f4-r (1-Cyclobutyl-4-piperidinyl) oxy-phenyl} -2-methylpyridor4,3-d1pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 94, using 4-aminonicotinic acid, acetic anhydride and 4 - [(1-cyclobutyl-4-piperidinyl) oxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.63-1.77 (2H, m), 1.82-1.96 (4H, m), 1.99-2.11 (4H, m), 2.14-2.24 (2H, m), 2.29 (3H, s), 2.60-2.68 (2H, m), 2.70-2.80 (1H, m), 4.33-4.41 (1H, m), 7.03 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.47 (1H, d, J = 5.2 Hz), 8.82 (1H, d, J = 5.2 Hz), 9.45 (1 H, s).

EXAMPLE 109 3-. { 4-f (1-Cyclobutyl-4-piperidinit) ox? "| Phenol.} -2-ethylpyrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrr The title compound was synthesized as a white solid (mp: 186-189 ° C) by the procedure according to Example 94, using 4-aminonicotinic acid, propionic anhydride and 4 - [(1-cyclobutii-4-piperidinyl) oxy] aniline as starting materials, followed of recrystallization (ethyl acetate / diethyl ether). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.23 (3H, t, J = 7.2 Hz), 1. 64-1.78 (2H, m), 1.83-1.97 (4H, m), 2.00-2.11 (4H, m), 2.14-2.23 (2H, m), 2. 49 (2H, q, J = 7.2 Hz), 2.60-2.68 (2H, m), 2.70-2.80 (1 H, m), 4.36-4.42 (1 H, m), 7.06 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.53 (1 H, d, J = 6.0 Hz), 8.84 (1 H, d, J = 6.0 Hz), 9.47 (1 H, s).

EXAMPLE 110 3-. { 4-r (1-Cyclobutyl-4-piperidin) oxyphenyl} -2-methylpyridor2,3-d1pyrimidin-4- (3H -one The title compound was obtained by the procedure according to Example 94, using 2-aminonicotinic acid, acetic anhydride and 4 - [(1-cyclobutyl-4-piperidinyl) oxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.63-1.77 (2H, m), 1.82-1.95 (4H, m), 1.99-2.11 (4H, m), 2.15-2.23 (2H, m), 2.34 (3H, s), 2.60-2.68 (2H, m), 2.70-2.80 (1 H, m), 4.33-4.41 (1 H, m), 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.39 (1 H, dd, J = 4.4, 8.0 Hz), 8.56 (1 H, dd, J = 2.0, 7.6 Hz), 8.96 (1 H, dd, J = 2.4, 4.8 Hz).

EXAMPLE 111 3-. { 4-r (l-Cyclobutyl-4-piperidinyl) oxy-phenyl-2-ethylpyridor-2,3-d-pyrimidin-4- (3H) -one The title compound was synthesized as a white solid (mp: 146-148 ° C) by the procedure according to Example 94, using 2-aminonicotinic acid, propionic anhydride and 4 - [(1-cyclobutyl-4-piperidinyl) oxy] aniline, followed by recrystallization (ethyl acetate). ethyl / diethyl ether). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.30 (3H, t, J = 7.2 Hz), 1. 65-1.75 (2H, m), 1.82-1.95 (4H, m), 1.99-2.11 (4H, m), 2.14-2.23 (2H, m), 2.51 (2H, q, J = 7.2 Hz), 2.60- 2.68 (2H, m), 2.70-2.79 (1 H, m), 4.34-4.41 (1 H, m), 7.02 (2H, d, J = 8.8 Hz), 7.10 (2H, d, J = 8.8 Hz) , 7.39 (1 H, dd, J = 4.4, 8.8 Hz), 8.57 (1 H, dd, J = 2.0, 8.0 Hz), 8.96 (1 H, dd, J = 2.4, 4.8 Hz).

EXAMPLE 112 6-Chloro-3- (4-r (1-cyclobutyl-4-piperidinipoxy-phenyl-2-methylpyridon-3,4-d-pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 94, using 5-amino-2-chloroisonicotinic acid, acetic anhydride and 4 - [(1-cyclobutyl-4-piperidinyl) oxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.63-1.77 (2H, m), 1.82-1.96 (4H, m), 1.99-2.11 (4H, m), 2.14-2.22 (2H, m), 2.28 (3H, s), 2.60-2.68 (2H, m), 2.70-2.79 (1 H, m), 4.33-4.41 (1 H, m), 7.02 (2H, d, J = 8.8 Hz), 7.10 (2H , d, J = 8.8 Hz), 8.03 (1 H, s), 8.87 (1 H, s).

EXAMPLE 113 6-Chloro-3-. { 4-f (1-cyclobutyl-4-piperidinyl) oxypihenyl > -2-ethylpyridor3,4-d1pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 94, using 5-amino-2-c! Oroisonicotinic acid, propionic anhydride and 4 - [(1-cyclobutyl-4-piperidinyl) oxy] aniline as materials initials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.23 (3H, t, J = 7.6 Hz), 1.62-1.75 (2H, m), 1.82-1.95 (4H, m), 1.99-2.10 (4H, m ), 2.10-2.24 (2H, m), 2.46 (2H, q, J = 7.2 Hz), 2.60-2.68 (2H, m), 2.70-2.79 (1 H, m), 4.34-4.41 (1 H, m ), 7.02 (2H, d, J = 8.8 Hz), 7.08 (2H, d, J = 8.8 Hz), 8.03 (1 H, s), 8.91 (1 H, s).

EXAMPLE 114 3-. { 4-r (1-Cyclobutyl-4-piperidinyl) oxy phenyl} -2-methylpyridor3,4-d] pyrimidin-4- (3H) -one The title compound was obtained as a light yellow solid (mp: 169-171 ° C) by catalytic reduction of 6-chloro-3-. { 4 - [(Cyclobutyl-4-piperidin) oxy] phenyl} -2-methy1pyrido [3,4-d] pyrimidine-4- (3H) -one synthesized in Example 112 in ethyl acetate using palladium on activated carbon as catalyst in the presence of triethylamine, followed by recrystallization (ethyl acetate /diethyl ether). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.63-1.77 (2H, m), 1.82-1.95 (4H, m), 1.99-2.11 (4H, m), 2.15-2.23 (2H, m), 2.29 (3H, s), 2.60-2.69 (2H, m), 2.73-2.83 (1H, m), 4.36-4.43 (1H, m), 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d) , J = 8.8 Hz), 8.01 (1 H, dd, J = 0.8, 5.6 Hz), 8.65 (1 H, d, J = 5.2 Hz), 9.09 (1 H, d, J = 0.8 Hz).

EXAMPLE 115 3-. { 4-f (1-Cyclobutyl-4-piperidinyl) oxy-phenyl} -2-ethylpyrid3.4-d] pyrimidin-4- (3H) -one The title compound was obtained by catalytic reduction of 6-chloro-3-. { 4 - [(1-cyclobutyl-4-p-peridinyl) oxy] phenol} -2-ethylpyrido [3,4-d] pyrimidin-4- (3H) -one synthesized in Example 113 using palladium on activated carbon as the catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.23 (3H, t, J = 7.2 Hz), 1. 65-1.75 (2H, m), 1.82-1.96 (4H, m), 2.00-2.11 (4H, m), 2.14-2.23 (2H, m), 2.48 (2H, q, J = 7.6 Hz), 2.60- 2.68 (2H, m), 2.70-2.79 (1 H, m), 4.33-4.42 (1 H, m), 7.02 (2H, d, J = 8.8 Hz), 7.10 (2H, d, J = 8.8 Hz) , 8.00 (1 H, dd, J = 0.8, 5.2 Hz), 8.64 (1 H, d, J = 5.2 Hz), 9.13 (1 H, d, J = 0.8 Hz).

EXAMPLE 116 2-Phenol-3- [4- (3-pperidin-1-ylpropoxy) phen.p-4- (3H) -quinazolinone (1) Preparation of 2-phenyl-4H-3,1-benzoxazin-4-one Anthranilic acid (1.0 g, 7.29 molimoles) was dissolved in pyridine (10 ml), benzoyl chloride (1.13 g, 8.02 molimoles) was added slowly in an ice bath, and stirred at 50 ° C overnight. The solvent was distilled off under reduced pressure, the residue was dissolved in dry methylene chloride (20 ml), oxalyl chloride (925 mg, 7.29 molimoles) and a catalytic amount of dimethylformamide were added in an ice bath, and stirred at room temperature for 4 hours. Saturated aqueous sodium hydrogencarbonate solution was added, the mixture was extracted with methylene chloride, and the organic phase was dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, the residue was washed with diethyl ether / heptane, and the target substance (1.13 g, 69%) was obtained as a light yellow solid. (2) Preparation of 2-phenyl-3- [4- (3-p1peridin-1-ylpropoxy) phen-4- (3H) -quinazolinone The title compound was obtained by 2-phenyl-4H cyclization -3,1-benzoxazin-4-one and 4- (3-piperidin-1-ylpropoxy) aniline according to Example 18- (2). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.50 (2H, m), 1.54- 1.62 (4H, m), 1.90-1.99 (2H, m), 2.34-2.42 (4H, brs), 2.44 (2H, t, J = 7.2 Hz), 3. 94 (2H, t, J = 6.4 Hz), 6.79 (2H, d, J = 8.8 Hz), 7.01 (2H, d, J = 8.8 Hz), 7.19- 7.25 (3H, m), 7.30-7.34 (2H , m), 7.48-7.53 (1 H, m), 7.77-7.80 (2H, m), 8.33 (1 H, d, J = 8.4 Hz).

EXAMPLE 117 cis-2-Methyl-3- (4- {4- (1-pyrrolidinyl) cyclohexinoxy phenyl) -4- (3H) -quinazolinone and trans-2-methyl-3- (4- { [ 4- (1-pyrrolidinyl) cyclohexyl] oxy} phenol) -4- (3H) -quinazolinone (1) Preparation of 1,4-dioxaspiro [4,51decan-8-ol 1,4-Dioxaspiro [4,5] decan-8-one (1.0 g, 6.40 molimoles) was dissolved in methanol (10 ml), added sodium borohydride (242 mg, 6.40 molimoles) slowly, and stirred at room temperature for 5 minutes. The mixture was cooled in an ice bath, 10% ai hydrochloric acid aqueous solution and sodium chloride were added, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, and dried with anhydrous sodium sulfate. Sodium sulfate was removed by filtration, and the product was concentrated under reduced pressure to obtain the target compound (614 mg, 61%) as a light yellow oily substance. (2) Preparation of 2-methyl-3-. { 4 - [(4-oxocyclohexyl) oxy] phenyl} -4- (3H) -quinazolinone 2-Methyl-3- (4-hydroxyphenyl) -4- (3H) quinazolinone (665 mg, 2.63 molimoles), 1,4-dioxaspiro [4,5] decan-8-ol ( 500 mg, 3.16 molimoles) and triphenylphosphine (1.03 g, 3.96 molimoles) were dissolved in dry tetrahydrofuran (5 ml), and cooled in an ice bath. Diisopropyl azodicarboxylate (777 μl, 3.96 molimoles) was added dropwise at 0 ° C, and it was stirred at room temperature for 48 hours. Distilled water was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, the residue was purified by silica gel column chromatography (hexane / ethyl acetate = 2 / 8-0 / 10), the protected ketal compound was obtained, and then brought to Check out the deprotection. Aqueous 10% hydrochloric acid solution was added to the residue, and it was stirred at room temperature for 3 hours. 2 N aqueous sodium hydroxide solution was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine solution and dried with anhydrous sodium sulfate. The product was purified by silica gel column chromatography (chloroform / methanol = 20/1) to obtain the target substance (511 mg, 49%) as a light orange solid. 2-Methyl-3- (4-hydroxyphenyl) -4- (3H) quinazolinone was synthesized according to Example 1- (1) and - (2). (3) Preparation of cis-2-methyl-3- (4- { [4- (1-pyrrolidinyl) cyclohexyl-oxo-phenyl) -4- (3H) -quinazolinone and trans-2-methyl-3- (4 - { [4- (1-pyrrolidinyl) cyclohexylpoxy] phenyl] -4- (3H) -quinazolinone 2-Methyl-3-. { 4 - [(4-oxocyclohexyl) oxy] phenyl} -4- (3H) -quinazolinone (484 mg, 1.39 molimoles) and pyrrolidine (99 mg, 1.39 molimoles) were dissolved in 0.5 M aqueous methanolic solution of zinc chloride (ll) / sodium cyanoborohydride (1.7 ml), and stirred at room temperature for 3 hours. 2 N aqueous sodium hydroxide solution was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and dried with anhydrous sodium sulfate. The product was purified by silica gel column chromatography (hexane / ethyl acetate = 8 / 2-5 / 5), and the cis isomer (260 mg) and the trans isomer (180 mg) of the title in the form of colorless solids. cis-2-Methyl-3- (4 { [4- (1-pyrrolidinyl) cyclohexyl] oxy} phenyl) -4- (3H) -quinazolinone 1 H NMR (400 MHz, CDCl 3, d ppm): 1.58-1.66 (2H, m), 1.73-1.81 (8H, m), 2.10-2.13 (2H, m), 2.26 (3H, s), 2.61 (4H, brs), 4.53 (1H, m ), 7.01 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.44 (1 H, t, J = 8.1 Hz), 7.65 (1 H, d, J = 8.1 Hz ), 7.74 (1 H, t, J = 8.1 Hz), 8.24 (1 H, d, J = 8.1 Hz). trans-2-Methyl-3- (4- { [4- (1-pyrrolidinyl) cyclohexyl] oxy} phenyl) -4- (3H) -quinazolinone 1 H NMR (400 MHz, CDCl 3, d ppm) : 1.07-1.66 (4H, m), 1.77- 1.81 (4H, m), 2.16-2.06 (4H, m), 2.25 (3H, s), 2.61 (4H, brs), 4.19-4.26 (1 H, m ), 7.00 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.44 (1 H, t, J = 8.1 Hz), 7.65 (1 H, d, J = 8.1 Hz ), 7.74 (1 H, t, J = 8.1 Hz), 8.25 (1 H, d, J = 8.1 Hz).

EXAMPLE 118 3-. { 4-r (1-Cyclopentyl-3-pyrrolidinyl) oxypihenyl > -2-methyl-4- (3H) -quinazolinone (racemic mixture) 1-Benzyl-3-pyrrolidinone was reduced with sodium borohydride according to Example 117- (1), and the target compound was obtained. (2) Preparation of 3-. { 4 - [(1-benzyl-3-pyrrolidinyl) oxphyphenyl) -2-methyl-4- (3H) -quinazolinone 1-Benzyl-3-pyrro-idinol and 2-methyl-3- (4-hydroxyphenyl) -4- (3 H) quinazolinone were etherified by the Mitsunobu reaction, and thus the target compound was obtained. 2-Methyl-3- (4-hydroxyphenyl) -4- (3H) quinazolinone was synthesized according to Example 1 - (1) and - (2). (3) Preparation of 3- (4-r (3-pyrrolidinyl) oxy-phenyl-V2-methyl-4- (3H) -quinazolinone The target compound was obtained by catalytic reduction of 3-. {4 - [(1-benzyl) -3-pyrrolidinyl) oxy] phenyl.} -2-methyl-4- (3H) -quinazolinone using palladium hydroxide as catalyst in methanol. (4) Preparation of 3-. {4 - [(1-cyclopentyl- 3-pyrrolidinyl) oxpholine D-2-methyl-4- (3H) -quinazolinone (racemic mixture) The title compound was obtained by reductive amination according to Example 88- (3), using 3-. {4 - [(3-pyrrolidinyl) oxy] phenyl] -2-methyl-4- (3H) -quinazolinone and cyclopentanone 1 H-NMR (400 MHz, CDCl 3, d ppm): 1.45-1.57 (2H, m), 1.70-1.73 (4H, m), 1.72-1.85 (2H, m), 1.83-2.04 (1H, m), 2.25 (3H, s), 2.31-2.36 (1H, m), 2.46-2.52 (1H, m), 2.52-2.61 (1 H, m), 2.79-2.84 (2H, m), 3.00-2.97 (1 H, m), 4.82-4.87 (1 H, m), 6.96 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.44 (1 H, t, J = 8.1 Hz), 7.64 (1 H, d, J = 8.1 Hz), 7.74 (1 H, t, J = 8.1 Hz), 8.24 (1H, d, J = 8.1 Hz) .

EXAMPLE 119 3-. { 4-f (1-Cyclobutyl-3-pyrrolidinyl) oxy] phenyl > -2-methyl-4- (3H) -quinazolinone (racemic mixture) The title compound was obtained by reductive amination according to the procedure of Example 118, using 3-. { 4 - [(3-pyrrolidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone and cyclobutanone. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.68-1.78 (2H, m), 1.94-2.07 (5H, m), 2.25 (3H, s), 2.30-2.35 (1 H, m), 2.46- 2.52 (1 H, m), 2.71-2.76 (2H, m), 2.86-2.91 (1 H, m), 2.93-3.00 (1 H, m), 4.83-4.87 (1 H, m), 6.96 (2 H) , d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.44 (1 H, t, J = 8.1 Hz), 7.64 (1 H, d, J = 8. 1 Hz), 7.74 (1 H, t, J = 8.1 Hz), 8.24 (1 H, d, J = 8.1 Hz).

EXAMPLE 120 3-. { 4-r (1-Cyclopentyl-4-azepanyl) oxy] phenyl} -2-methyl-4- (3H) -quinazoIinone (racemic mixture) (1) Preparation of 3-. { 4-f (4-azepanyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone 2-Methyl-3- (4-hydroxyphenyl) -4- (3H) quinazolinone and 1- (t-butoxycarbonyl) -4-hydroxyazepan were etherified by the Mitsunobu reaction of according to the procedure of Example 117- (2), and the target compound was obtained by deprotection with trifluoroacetic acid. 2-Methyl-3- (4-hydroxyphenyl) -4- (3H) quinazolinone was synthesized as in Example 1- (2). (2) Preparation of 3-. { 4 - [(1-cyclopentyl-4-azepanyl) oxy] phenyl > -2-methyl-4- (3H) -quinazolinone (racemic mixture) The title compound was obtained by reductive amination according to Example 117- (3), using 3-. { 4 - [(4-azepanyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone and cyclopentanone. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.47-1.59 (4H, m), 1.63-1.75 (2H, m), 1.83-1.97 (4H, m), 2.02-2.16 (2H, m), 2.17 -2.28 (5H, m), 2.73- 2.87 (2H, m), 2.88-2.97 (2H, m), 2.98-3.07 (1H, m), 4.57-4.64 (1H, m), 6.97 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.43 (1 H, t, J = 8.0 Hz), 7.64 (1 H, d, J = 7.2 Hz), 7.73 (1H, t, J = 7.2 Hz), 8.23 (1H, d, J = 8.0 Hz).

EXAMPLE 121 3-. { 4-f (1-Cyclobutyl-4-azepanyl) oxy-phenyl} -2-methyl-4- (3H) -quinazolinone (racemic mixture) The title compound was obtained by reductive amination according to Example 120, using 3-. { 4 - [(4-azepanyl) oxy] phenyl} -2-methyI-4- (3H) -quinazolinone and cyclobutanone. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.56-1.69 (4H, m), 1.80-1.89 (4H, m), 1.98-2.06 (2H, m), 2.08-2.19 (2H, m), 2.24 (3H, s), 2.39-2.50 (2H, m), 2.53-2.62 (2H, m), 2.85-2.95 (1 H, m), 4.54-4.61 (1 H, m), 6.96 (2H, d, J = 8.8 Hz), 7.10 (2H, d, J = 8.8 Hz), 7.43 (1 H, t, J = 8.0 Hz), 7.63 (1 H, d, J = 7.2 Hz), 7.72 (1 H, t , J = 7.2 Hz), 8.23 (1 H, d, J = 8.0 Hz).

EXAMPLE 122 3-Methyl-2-. { 4- [3-piperidin-1-ylpropoxyphenyl]} -1- (2H) -isoquinolinone (1) Preparation of 3- (1-hydroxyethyl) -2-benzofuran-1 (3H) -one A solution in dry tetrahydrofuran (100 ml) of lithium diisopropylamide (26.9 molimoles) was cooled to -78 ° C in a stream of nitrogen, and a solution in tetrahydrofuran (100 ml) of phthalide (3.0 g, 22.4 molimoles) was added dropwise. After stirring at -78 ° C for 30 minutes, acetaldehyde (1.19 g, 26.9 molimoles) was added slowly and stirred at -50 ° C for 4 hours. After the temperature was raised to room temperature, distilled water was added and the mixture was extracted with ethyl acetate. The organic phase was washed with distilled water and saturated brine, and dried with anhydrous sodium sulfate. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 4/6), and the target compound (1.96 g, 49%) was obtained as a yellow oily residue. (2) Preparation of 3-methyl-1 H-isocroman-1-one 3- (1-hydroxyethyl) -2-benzofuran-1- (3 H) -one (1.3 g, 7.30 molimoles) and p-toluenesulfonic acid monohydrate ( 3.46 g, 18.2 molimoles) were dissolved in toluene (50 ml), and refluxed for 4 hours. Saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried with anhydrous sodium sulfate. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 10 / 0-5 / 5), and the target compound (0.64 g, 55%) was obtained as an orange solid. (3) Preparation of 2- (2-oxopropyl) benzoic acid 3-Methyl-1 H -isocroman-1-one (320 mg, 2.0 molimoles) was dissolved in ethanol (5 ml), a 2 N aqueous solution of Sodium hydroxide (3 ml), and stirred at 80 ° C for 5 hours. The ethanol was distilled off under reduced pressure, 8 N aqueous hydrochloric acid solution was added, and the mixture was extracted with ethyl acetate. The organic phase was dried with anhydrous sodium sulfate, concentrated and dried to obtain the target compound (280 mg, 79%) as a yellow solid. (4) Preparation of 2- (4-methoxyphenyl) -3-methyl-1- (2H) -isoquinolinone 2- (2-oxopropyl) benzoic acid (100 mg, 0.56 molimole), 4-methoxyaniline (76 mg, 0.56 molimole) ), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.84 molimoles) and pyridine (0.5 ml) were dissolved in chloroform (5 ml) and stirred at room temperature overnight. Chloroform was added, the organic phase was washed with aqueous citric acid solution, aqueous sodium hydrogencarbonate solution and saturated brine in that order, and dried with anhydrous sodium sulfate. The product was purified by silica gel column chromatography (hexane / ethyl acetate = 10 / 0-3 / 7) to obtain the target compound (66 mg, 44%) as a light brown solid. (5) Preparation of 2- (4-hydroxyphenyl) -3-methyl-1- (2H) -isoquinolinone 2- (4-Methoxyphenyl) -3-methyl-1- (2H) -isoquinolinone (56 mg, 0.21 molimoles) was dissolved in dry methylene chloride, a 1 M solution in methylene chloride (0.63 ml) of boron tribromide was added slowly at -10 ° C, and it was stirred at room temperature for 2 hours. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction mixture, and the methylene chloride was distilled off under reduced pressure. 8N aqueous solution of hydrochloric acid was added, and the solid precipitate was removed by filtration and dried to obtain the target compound (48 mg, 91%) as a colorless solid. (6) Preparation of 3-methyl-2- (4- [3-piperidin-1-ylpropoxy] phenyl) -1 - (2 H) -isoquinolinone 2- (4-H, -droxyphenyl) -3-methyl-1- ( 2H) -isoquinolonone (30 mg, 0.12 molimoles), 1- (3-bromopropyl) piperidine hydrobromide (51 mg, 0.18 molimoles) and potassium carbonate (49 mg, 0.36 molimoles) were mixed in dimethylformamide (3 ml) and they were stirred at 80 ° C for 3 hours. The solvent was removed by distillation under reduced pressure, distilled water was added, and the mixture was extracted with ethyl acetate. The organic phase was dried with anhydrous sodium sulfate, and the product was purified by column chromatography on silica gel (chloroform / methanol = 20/1) to obtain the title compound (18 mg, 40%) as a colorless solid. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.49 (2H, m), 1.56-1.63 (4H, m), 1.97-2.04 (5H, m), 2.38-2.48 (4H, brs), 2.51 (2H, t, J = 7.0 Hz), 4.06 (2H, t, J = 6.4 Hz), 6.42 (1 H, s), 7.01 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.39-7.47 (2H, m), 7.63 (1 H, t, J = 8.0 Hz), 8.37 (1 H, d, J = 8.0 Hz).

Example 123 2-. { 4-f (1-Cyclobutyl-4-piperidinyl) oxphenyl} -3-methyl-1- (2H) -isoquinolinone A Mitsunobu reaction and a reductive amination reaction were performed in that order according to the procedure of Example 88, using 2- (4-hydroxyphenyl) -3-methyl-1- (2H) -isoquinolinone, N- (t -butoxycarbonyl) -4-piperidinol and cyclobutanone as starting materials, and thus the title compound was obtained as a colorless solid. 2- (4-Hydroxyphenyl) -3-methyl-1- (2H) -lsoquinoloneone was used which was synthesized in Example 122- (5). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.62-1.77 (2H, m), 1.82-1.98 (4H, m), 2.02 (3H, s), 2.02-2.10 (4H, m), 2.16-2.26 (2H, m), 2.60-2.69 (2H, m), 2.72-2.80 (1H, m), 4.35-4.42 (1H, m), 6.42 (1H, s), 7.01 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.40-7.44 (2H, m), 7.63 (1 H, t, J = 8.0 Hz), 8.37 (1 H, d, J = 8.0 Hz ).

EXAMPLE 124 2-Methyl-3-f4- (r3- (1-pyrrolidinyl) cyclopentinoxy > fenin-4- (3H) -quinazolinone (trans isomer) (1) Preparation of 3-. { 4 - [(3-hydroxy-cyclopentyl) oxy] phenyl) -2-methyl-4- (3H) -quinazolinone 3- (4-Hydroxyphenyl) -2-methyl-4- (3H) -quinazolinone (300 mg, 1.19 molimoles), 1,3-cyclopentanediol (242 mg, 2.37 molimoles) and triphenylphosphine (468 mg, 1.78 molimoles) were dissolved in tetrahydrofuran (3 ml), and diisopropyl azodicarboxylate (0.35 ml, 1.78 molimoles) was added dropwise at 0 ° C and was stirred at room temperature for 2 hours. Distilled water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine and dried with anhydrous magnesium sulfate. The product was purified by silica gel column chromatography (hexane / ethyl acetate = 40 / 60-0 / 100), and the target compound (520 mg) was obtained as a light brown oily residue. (2) Preparation of 3- [4- ( { 3 - [(methylsulfonyl) oxy] cyclopentyl.} Oxy) phenl] -2-methyl-4- (3H) -quinazolinone 3-. { 4 - [(3-Hydroxycyclopentyl) oxy] phenol} -2-methyl-4- (3H) -quinazolinone (520 mg, 1.19 molimole) and triethylamine (0.33 ml, 2.32 molimole) were mixed in methylene chloride and cooled in an ice bath. Mesyl chloride (0.12 ml, 1.55 molimoles) was added dropwise and stirred for 10 minutes at room temperature. Distilled water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic phase was washed with distilled water, and dried with anhydrous magnesium sulfate. The residue was concentrated to dryness, and thus the target compound (553 mg) was obtained. (3) Preparation of 2-methyl-3- [4-f [3- (1-pyrrolidinyl) cyclopentyl] oxy} phen.n-4- (3H) -quinazolnone (trans isomer). 3- [4- ( { 3 - [(Methylsulfonyl) oxy] cyclopentyl.} Oxy) phenyl] -2-methyl-4- (3H) -quinazolinone (550 mg, 1.33 molimoles), pyrrolidine (474 mg, 6.7 molimoles) and potassium carbonate (277 mg, 2.0 molimoles) were mixed in dimethylformamide (10 ml) and stirred at 80 ° C overnight. Distilled water was added, and the mixture was extracted with ethyl acetate. The organic phase was dried with anhydrous magnesium sulfate, and the obtained residue was purified by silica gel column chromatography (chloroform / methanol = 20/1) to obtain the title compound (143 mg) as a colorless solid. 2-Methyl-3- [4-. { [3- (1-pyrrolidinyl) cyclopentyl] oxy} phenyl] -4- (3H) -quinazolinone (trans isomer) 1 H NMR (400 MHz, CDCl 3, d ppm): 1.57-1.67 (1 H, m), 1.78-1.81 (4H, m), 1.85-1.92 ( 2H, m), 2.03-2.08 (1 H, m), 2.14-2.19 (1 H, m), 2.22-2.23 (1 H, m), 2.24 (3H, s), 2.76-2.83 (1 H, m ), 4.81-4.86 (1 H, m), 6.96 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.44 (1 H, t, J = 8.1 Hz), 7.66 (1 H, d, J = 8.1 Hz), 7.73 (1 H, t, J = 8.1 Hz), 8.23 (1 H, d, J = 8.1 Hz).

EXAMPLE 125 3-4-r3- (7-Azabicyclo2.2.nhept-7-yl) propoxphenil > -2-methyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 7-azabicyclo [2.2.1] heptane hydrochloride as starting materials. 7-azabicyclo [2.2.1] heptane hydrochloride was prepared by the procedure described in the literature (J. Am. Chem. Soc, 2003, Vol. 125, page 15191). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.34-1.35 (4H m), 1.76-1.84 (4H, m), 2.02-2.09 (2H, m), 2.28 (3H, s), 2.59-2.63 ( 2H, m), 3.37 (2H, brs), 4.12 (2H, t, J = 6.2 Hz), 7.04 (2H, d, J = 9.0 Hz), 7.16 (2H, d, J = 8.4 Hz), 7.46- 7.50 (1 H, m), 7.67 (1 H, d, J = 7.8 Hz), 7.76-7.80 (1 H, m), 8.28 (1 H, dd, J = 8.6, 1.6 Hz).

EXAMPLE 126 3-. { 4-r3- (8-azabicyclo3.2.noct-8-yl) propoxy1feniiy-2-methyl-4- (3H) -quinazolinone (1) Preparation of 8-azabicyclo [3.2.1] octane hydrochloride Tropane (1.0 ml, 7.44 molimoles) was dissolved in toluene (10 ml), chloroethyl carbonate (2.2 ml, 23 molimoles) was added slowly, and the mixture was stirred at 80 ° C for 24 hours. Distilled water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic phase was dried and concentrated with anhydrous magnesium sulfate. The oily residue obtained was dissolved in concentrated hydrochloric acid (10 ml), and heated with stirring at 100 ° C for 2 hours. The solvent was distilled off under reduced pressure, toluene was added to the residue, and the mixture was distilled off under reduced pressure to obtain the target substance (820 mg, 72%) as a colorless solid. (2) Preparation of 3- (4- [3- (8-azabicyclo [3.2.noct-8-yl) propoxy] phenyl) -2-methyl-4- (3H) -quinazolinone The title compound was obtained by Process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 8-azabicyclo [3.2.1] octane hydrochloride as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.37-2.06 (12H, m), 2.60 (2H, t, J = 7.2 Hz), 3.29 (2H, brs), 4.13 (2H, t, J = 6.2 Hz), 7.07 (2H, d, J = 6.1 Hz), 7.17 (2H, d, J = 6.1 Hz), 7.46-7.50 (1 H, m), 7.69 (1 H, d, J = 7.8 Hz), 7.76-7.80 (1 H, m), 8.29 (1 H, dd, J = 7.8, 1.2 Hz).

EXAMPLE 127 3- (4-R3- (3,3-difluoropyrrolidin-1-yl) propoxy-phenyl) -2- methyl-5- (trifluoromethyl) -4- (3H) -quinazolinone trifluoroacetate The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 3,3-difluoropyrrolidine hydrochloride as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 2.27 (3H, s), 2.29 (2H, m), 2.70 (2H, m), 3.58 (2H, dd, J = 8.8, 8.8 Hz), 3.81 ( 2H, brs), 4.02 (2H, m), 4.23 (2H, t, J = 5.6 Hz), 7.17 (2H, d, J = 8.8 Hz), 7.33 (2H, d, J = 8.8 Hz), 7.95 ( 3H, m).

EXAMPLE 128 3- (4. {3-R (3R) -3-fluoropyrrolidin-1-yl] propoxy} phenyl) -2-methyl-5- (trifluoromethyl) -4- (3H) trifluoroacetate ) -quinazol? nona The title compound was obtained by the procedure according to Example 1, using 2-amino-6- (trifluoromethyl) benzoic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and (3R) -3- hydrochloride. fluoropyrrolidine as starting materials. 1 H NMR (400 MHz, CDCl 3 (d ppm): 2.20-2.80 (2H, m), 2.28 (3H, s), 2.31 (2H, m), 3.20-3.60 (2H, m), 3.53 (2H, m) ), 3.80-4.20 (2H, m), 4.22 (2H, t, J = 5.6 Hz), 5.49 (1 H, d, J = 60 Hz), 7.17 (2H, d, J = 9.2 Hz), 7.32 ( 2H, d, J = 9.2 Hz), 7.95 (3H, m).

EXAMPLE 129 3- Trifluoroacetate. { 4-r3- (4,4-difluoropiperidin-1-yl) propoxy] phenyl) -2-methyl-5- (trifluoromethyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 1, using 2-amino-6- (trifluoromethyl) benzoic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 4,4-difluoropiperidine hydrochloride as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 2.20-2.60 (6H, m), 2.27 (3H, s), 3.20-3.50 (2H, m), 3.49 (2H, t, J = 8.0 Hz), 3.78 (2H, m), 4.23 (2H, t, J = 5.6 Hz), 7.17 (2H, d, J = 6.6 Hz), 7.32 (2H, d, J = 6.6 Hz), 7.95 (3H, m).

EXAMPLE 130 Trifluoroacetate of 3-. { 4-f3- (4-fluoropiperidin-1-yl) propoxy-1-phenyl} -2-methyl-5- (trifluoromethyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 1, using 2-amino-6- (trifluoromethyl) benzoic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 4-fluoropiperidine hydrochloride as starting materials . 1 H NMR (400 MHz, CDCl 3, d ppm): 2.18-2.43 (9H, m), 3.11 (2H, m), 3.29 (2H, t, J = 7.8 Hz), 3.60 (2H, m), 4.13 ( 2H, t, J = 5.6 Hz), 5.02 (1 H, m), 7.03 (2H, d, J = 9.0 Hz), 7.19 (2H, d, J = 9.0 Hz), 7.82-7.83 (1 H, m ), 7.89-7.90 (2H, m).

EXAMPLE 131 Trifluoroacetate of 3-f4-r3- (3,3-difluoropiperidin-1-yl) propoxy1phenyl '} -2- methyl-5- (trifluoromethyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 1, using 2-amino-6- (trifluoromethyl) benzoic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 3,3-difluoropiperidine hydrochloride as initial materials. 1 H NMR (400 MHz, DMSO-d 6, d ppm): 2.15-2.18 (5H, m), 3.32-3.34 (2H, m), 3.74-3.76 (8H, m), 4.14 (2H, t, J = 5.9 Hz), 7.11 (2H, d, J = 9.0 Hz), 7.39 (2H, d, J = 9.0 Hz), 7.92-7.99 (3H, m).

EXAMPLE 132 3- Trifluoroacetate. { 4-r3- (3-fluoropiperidin-1-yl) propoxyphenyl} -2-methyl-5- (trifluoromethyl) -4- (3H) -quinazolinone (racemic mixture) The title compound was obtained by the procedure according to Example 1, using 2-amino-6- (trifluoromethyl) benzoic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 3-fluoropiperidine hydrochloride as starting materials . 1 H NMR (400 MHz, DMSO-d 6, d ppm): 1.66-2.01 (4H, m), 2. 15-2.17 (5H, m), 3.15-3.38 (4H, m), 3.83-4.09 (4H, m), 5.17 (1H, m), 7.11 (2H, d, J = 9.0 Hz), 7.39 (2H , d, J = 9.0 Hz), 7.94-7.98 (3H, m).

EXAMPLE 133 2-Methyl-3- (4-. {3-r (3R) -3-methylpiperidin-1-inpropoxy> phenyl) -4- (3H) -quinazolinone The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and (R) - (-) - mandelate of (3R) -3-methylpiperidine as initial materials. (R) - (-) - (3R) -3-methylpiperidine mandelate was prepared by the process described in the literature (J. Org. Chem., 1987, Vol. 52, page 5466). 1 H NMR (400 MHz, CDCl 3, d ppm): 0.87 (4H, m), 1.50-1.95 (6H, m), 2.00 (2H, m), 2.26 (3H, s), 2.50 (2H, t, J = 6.8 Hz), 2.87 (2H, m), 4.07 (2H, t, J = 6.4 Hz), 7.05 (2H, d, J = 8.6 Hz), 7.15 (2H, d, J = 8.6 Hz), 7.46 ( 1 H, t, J = 8.0 Hz), 7.67 (1 H, d, J = 8.0 Hz), 7.76 (1 H, t, J = 8.4 Hz), 8.27 (1 H, d, J = 8.0 Hz).

EXAMPLE 134 3- (4- { 3-r (2R, 5R) -2,5-D-methylpyrrolidin-1-inpropoxy > phenyl) -2-methyl-4- (3H) -quinazolinone The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and (2R, 5R) -2,5-dimethylpyrrolidine as starting materials. NMR of H (400 MHz, CDCl 3, d ppm): 1.00 (6H, d, J = 6.0 Hz), 1. 40 (2H, m), 2.05 (4H, m), 2.26 (3H, s), 2.60 (1H, m), 2.80 (1H, m), 3.10 (2H, m), 4.10 (2H, m) , 7.05 (2H, d, J = 8.8 Hz), 7.15 (2H, d, J = 8.8 Hz), 7.46 (1 H, t, J = 8.0 Hz), 7.67 (1 H, d, J = 8.0 Hz), 7.76 (1 H, t, J = 7.6 Hz), 8.27 (1 H, d, J = 8. 0 Hz).

EXAMPLE 135 2-Methyl-3- (4-. {3-r3-methylpyrrolidin-1-illpropoxy.} Phenyl) -4- (3H) -quinazolinone (racemic mixture) The title compound was obtained by the process according to Example 1, using anthranilic acid, acetic anhydride, 4-aminophenol, 1,3-bromochloropropane and 3-methylpyrrolidine as starting materials. 3-Methylpyrrolidine was prepared by the procedure described in the literature (J. Med. Chem., 2000, Vol. 43, page 4388). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.05 (3H, d, J = 6.8 Hz), 1.38-1.42 (1 H, m), 2.02-2.09 (4H, m), 2.26 (3H, s) , 2.28-2.30 (1 H, m), 2.54-2.56 (1 H, m), 2.63-2.72 (2H, m), 2.78-2.80 (1 H, m), 2.92 (1 H, t, J = 8.3 Hz), 4.09 (2H, t, J = 6.3 Hz), 7.04 (2H, td, J = 6.0, 3.6 Hz), 7.15 (2H, td, J = 6.0, 3.6 Hz), 7.46 (1 H, t, J = 8.0 Hz), 7.67 (1 H, d, J = 7.8 Hz), 7.74-7.78 (1 H, m), 8.27 (1 H, dd, J = 7.8, 1.5 Hz).

EXAMPLE 136 5-Methoxy-3-r4- (3-piperidin-1-ylpropoxy) phenin-2-propyl-4- (3H) -quinazolinone The title compound was obtained by the process according to Example 18, using 2-amino-6-methoxybenzoic acid, butyric anhydride and 4- (3-piperidin-1-yl propoxy) aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.87 (3H, t, J = 7.6 Hz), 1. 41-1.50 (2H, m), 1.52-1.63 (4H, m), 1.66-1.73 (2H, m), 1.97-2.04 (2H, m), 2.36-2.46 (6H, m), 2.51 (2.H) , t, J = 7.6 Hz), 3.94 (3H, s), 4.06 (2H, t, J = 6.4 Hz), 6.86 (1 H, d, J = 7.6 Hz), 7.01 (2H, d, J = 9.2 Hz), 7.09 (2H, d, J = 9.2 Hz), 7. 25 (1 H, d, J = 8.4 Hz), 7.64 (1 H, t, J = 8.4 Hz).

EXAMPLE 137 5-Methoxy-2-propyl-3-f4- (3-pyrrolidin-1-ylpropoxy) phenin-4- (3H) -quinazoinone The title compound was obtained by the procedure according to Example 18, using 2-amino-6-methoxybenzoic acid, butyric anhydride and 4- (3-pyrrolidin-1-yl-propoxy) aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.87 (3H, t, J = 7.6 Hz), 1. 64-1.84 (2H, m), 1.78-1.82 (4H, m), 2.02-2.08 (2H, m), 2.37 (2H, t, J = 8.0 Hz), 2.52-2.56 (4H, m), 2.65 ( 2H, t, J = 7.6 Hz), 3.94 (3H, s), 4.08 (2H, t, J = 6.4 Hz), 6.86 (1 H, dd, J = 0.8, 8.4 Hz), 7.02 (2H, d, J = 9.2 Hz), 7.10 (2H, d, J = 9.2 Hz), 7.25 (1 H, dd, J = 0.8, 8.4 Hz), 7.64 (1 H, t, J = 8.4 Hz).

EXAMPLE 138 2-Methyl-3- (4-. {3-r (2S) -2-methylpyrrolidin-1-inpropoxy phenyl) -4- (3H) -quinazolinone (1) Preparation of 3-f (2S) -2-methylpyrrolidin-1-yl] propan-1-ol (2S) -2-methylpyrrolidine hydrobromide (2.70 g, 16.3 molimoles), 3-bromopropanol (2.49 g, 17.9 molimoles) and potassium carbonate (6.75 g, 48.9 molimoles) were mixed in tetrahydrofuran (20 ml), and stirred at 60 ° C for 18 hours. The precipitate was removed by filtration, and the filtrate was concentrated. The residue was distilled under reduced pressure, and thus the target compound (1.88 g, 80%) was obtained as a colorless oily substance. (2S) -2-methyl-pyrrolidine hydrobromide was prepared by the method described in the literature (J. Org. Chem., 1989, Vol. 54, page 209) using D-prolinol as initial material. 22) Preparation of (2S) -2-methyl-1-f3- (4-nitrophenoxpropylpyrrolidine) The target compound was obtained by the procedure according to Example 18, using 3 - [(2S) -2-methylpyrrolidin-1 -yl] propanol and 4-nitrophenol as starting materials. (3) Preparation of 4-. { 3 - [(2S) -2-methylpyrrolidin-1-npropoxy) aniline The target compound was obtained by catalytic reduction of (2S) -2-methyl-1- [3- (4-nitrophenoxy) propyl] pyrrolidine in methanol, using a palladium on activated carbon catalyst. (4) Preparation of 2-methyl-3- (4- (3 - [(2S) -2-methylpyrrolidin-1-nitropoxy) phenyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using anthranilic acid, acetic anhydride and 4-. { 3 - [(2S) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.12 (3H, d, J = 6.0 Hz), 1. 40-1.50 (1 H, m), 1.60-2.37 (11 H, m), 2.97-3.03 (1H, m), 3.18-3.23 (1H, m), 4. 07-4.11 (2H, m), 7.05 (2H, d, J = 9.2 Hz), 7.15 (2H, d, J = 9.2 Hz), 7.46 (1H, t, J = 7.6 Hz), 7.67 (1 H, d, J = 7.6 Hz), 7.76 (1H, t, J = 7.6 Hz), 8.27 (1 H, d, J = 7.6 Hz). The NMR data for 4-. { 3 - [(2S) -2-methylpyrrolidin-1-yl] propoxy} Aniline which is used for the preparation of the compound of this example are shown below. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.60 (3 H, d, J = 6.4 Hz), 1.93-2.12 (2 H, m), 2.18-2.30 (3 H, m), 2.41-2.49 (1 H, m), 2.95-3.34 (5H, m), 3.46-3.53 (1H, m), 3.86-3.92 (1H, m), 4.07 (2H, t, J = 6.4 Hz), 6.89 (2H, d, J = 9.2 Hz), 7.31 (2H, d, J = 9.2 Hz).

EXAMPLE 139 2,5-Dimethyl-3- (4-. {3-r (2S) -2-methylpyrrolidin-1-inpropoxy> phenyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-6-methylbenzoic acid, acetic anhydride and 4-. { 3 - [(2S) -2-methyl-pyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.11 (3H, d, J = 6.0 Hz), 1.38-1.48 (1 H, m), 1.59-2.33 (11H, m), 2.82 (3H, s) , 2.97-3.03 (1 H, m), 3.17-3.22 (1 H, m), 4.06-4.10 (2H, m), 7.04 (2H, d, J = 9.2 Hz), 7.15 (2H, d, J = 9.2 Hz), 7.21 (1 H, d, J = 7.2 Hz), 7.50 (1 H, d, J = 7.2 Hz), 7.59 (1 H, t, J = 7.2 Hz).

EXAMPLE 140 2,6-Dimethyl-3- (4-f3-r (2S) -2-methylpyrrolidin-1-inpropoxy > phenyl) -4-y3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-5-methylbenzoic acid, acetic anhydride and 4-. { 3 - [(2S) -2-methyl-pyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.12 (3 H, d, J = 6.0 Hz), 1.38-1.48 (1 H, m), 1.59-2.37 (11 H, m), 2.48 (3 H, s ), 2.97-3.03 (1 H, m), 3.17- 3.23 (1 H, m), 4.07-4.11 (2H, m), 7.04 (2H, d, J = 9.2 Hz), 7.14 (2H, d, J) = 9.2 Hz), 7.57-7.58 (2H, m), 8.05 (1H, s).

EXAMPLE 141 2-Ethyl-3- (4- { 3-r, 2 S) -2-methylpyrroHdin-1-ippropoxy) phenyl) -4-f 3 H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using anthranilic acid, propionic anhydride and 4-. { 3 - [(2S) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.12 (3H, d, J = 6.0 Hz), 1. 22 (3H, t, J = 7.2 Hz), 1.40-1.50 (1 H, m), 1.60-2.37 (8H, m), 2.47 (2H, q, J = 7. 2 Hz), 2.97-3.04 (1 H, m), 3.18-3.23 (1 H, m), 4.07-4.11 (2H, m), 7.05 (2H, d, J = 9.2 Hz), 7.15 (2H, d, J = 9.2 Hz), 7.45 (1H, t, J = 7.6 Hz), 7.71 (1 H, d, J = 7.6 Hz), 7.76 (1 H, t, J = 7.6 Hz), 8.27 (1 H, d, J = 7.6 Hz).

EXAMPLE 142 6-Chloro-2-ethyl-3- (4- | 3-r (2S) -2-methylpyrrolidin-1-inpropoxy) phenyl) pyrid3,4-d1-pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 5-amino-2-chloroisonicotinic acid, propionic anhydride and 4-. { 3 - [(2S) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.11 (3H, d, J = 6.0 Hz), 1. 23 (3H, t, J = 7.2 Hz), 1.40-1.50 (1 H, m), 1.60-2.37 (8H, m), 2.46 (2H, q, J = 7.2 Hz), 2.97-3.04 (1 H, m), 3.18-3.23 (1 H, m), 4.08-4.11 (2H, m), 7.06 (2H, d, J = 9.2 Hz), 7.12 (2H, d, J = 9.2 Hz), 8.06 (1 H, d, J = 0.8 Hz), 8.94 (1H, d, J = 0. 8 Hz).

EXAMPLE 143 6-Methoxy-2-methyl-3- [4- (3-pyrrolidin-1-ylpropoxy) phenn-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-5-methoxybenzoic acid, acetic anhydride and 4- (3-pyrrolidin-1-yl-propoxy) aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.79-1.83 (4H, m), 2.03-2.09 (2H, m), 2.23 (3H, s), 2.52-2.58 (4H, m), 2.66 (2H , t, J = 7.2 Hz), 3.91 (3H, s), 4.10 (2H, t, J = 6.4 Hz), 7.05 (2H, d, J = 9.2 Hz), 7.14 (2H, d, J = 9.2 Hz ), 7.36 (1 H, dd, J = 2.8, 8.8 Hz), 7.61 (1 H, d, J = 8.8 Hz), 7.63 (1 H, d, J = 3.2 Hz).

EXAMPLE 144 6-Methoxy-2-methyl-3-γ-3-r (2S) -2-methylpyrrolidin-1-inpropoxy > phenyl) -4- (3H) -quinazolinone The title compound was synthesized as a white solid (p.f .: 102-106 ° C) by the procedure according to Example 18, using 2-amino-5-methoxybenzoic acid, acetic anhydride and 4-. { 3 - [(2S) -2-methylpyrrolidin-1-yl] propoxy} aniIin as starting materials, followed by recrystallization (ethyl acetate / diethyl ether). 1 H NMR (400 MHz, CDCl 3 d ppm): 1.12 (3 H, d, J = 6.0 Hz), 1. 38-1.48 (1 H, m), 1.59-2.37 (1 1 H, m), 2.97-3.03 (1 H, m), 3.17-3.23 (1 H, m), 3.91 (3 H, s), 4.08- 4.11 (2H, m), 7.05 (2H, d, J = 9.2 Hz), 7.15 (2H, d, J = 9.2 Hz), 7.35 (1 H, dd, J = 2.8, 8.8 Hz), 7.61 (1 H , d, J = 9.2 Hz), 7.63 (1 H, d, J = 3.2 Hz). EXAMPLE 145 2-Methyl-3- (4-f3-r (3S) -3-methylpiperidin-1-inpropoxy > phenyl) -4- (3H) -quinazolinone (1) Preparation of 3 - [(3S) -3-methyl-piperidin-1-propan-1-ol (S) - (+) - (3S) -3-methylpiperidine mandelate (19.9 g, 79.1 molimoles) , 3-bromo-1-propanol (10 g, 71.9 molimoles) and potassium carbonate (14.9 g, 108 molimoles) were mixed in tetrahydrofuran (200 ml), and heated at reflux for 30 hours. The insoluble matter was removed by filtration, the filtrate was concentrated, and ethyl acetate and hexane were added to the residue. The insoluble matter that was produced was removed by filtration, the filtrate was concentrated and the target substance (9.6 g, 85%) was obtained as a colorless oily material by distillation under reduced pressure. (S) - (+) - (3S) -3-methyl-piperidine mandelate was prepared by the procedure described in the literature (J. Org. Chem., 1987, Vol. 52, page 5466). (2) Monotosylate preparation of 4-. { 3-f (3S) -3-methylpiperidin-1-yl] propoxy) aniline 4-. { 3 - [(3S) -3-Methylpiperidin-1-yl] propoxy} Aniline was obtained as a light brown oily substance by the procedure according to Example 18, using 4-nitrophenol and 3 - [(3S) -3-methylpiperidin-1-yl] propan-1-ol as starting materials. The oily substance obtained was dissolved in ethyl acetate, 1 equivalent of a methanol solution of p-toluenesulfonic acid monohydrate was added, and the target compound was obtained as a light peach solid by filtering off the solid that is produced. (3) Preparation of 2-methyl-3- (4- (3 - [(3S) -3-methylpiperidin-1-yl-1-propoxy) phenyl) -4- (3H) -quinazolinone The title compound was obtained by the process of according to Example 18, using anthranilic acid, acetic anhydride and monotosylate of 4-. { 3 - [(3S) -3-methy1piperidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.87-0.89 (4H, m), 1.56-1.76 (5H, m), 1.84-1.91 (1H, m), 2.02-2.06 (2H, m), 2.26 (3H, s), 2.53 (2H, t, J = 7.2 Hz), 2.85-2.93 (2H, m), 4.07 (2H, t, J = 6.3 Hz), 7.04 (2H, d, J = 9.0 Hz), 7. 15 (2H, d, J = 9.0 Hz), 7.46 (1 H, t, J = 7.6 Hz), 7.67 (1 H, d, J = 7.6 Hz), 7.76 (1H, t, J = 7.6 Hz), 8.27 (1 H, d, J = 7.6 Hz). The NMR data for monotosylate of 4-. { 3 - [(3S) -3-methylpiperidin-1-yl] propoxy} Aniline which is used for the preparation of the compound of this example are shown below. 1 H NMR (400 MHz, CDCb / CD ^ D = 10/1, d ppm): 0.95-1.10 (4H, m), 1.87-1.92 (2H, m), 2.02-2.32 (7H, m), 2.36 ( 3H, s), 2.51-2.58 (1 H, m), 3.22-3.26 (2H, m), 3.52-3.56 (1H, m), 3.66-3.69 (1H, m), 3.95 (2H, t, J = 5.6 Hz), 6.64-6.70 (4H, m), 7.19 (2H, d, J = 8.3 Hz), 7.76 (2H, d, J = 8.3 Hz).

EXAMPLE 146 5-Bromo-2-methyl-3-r4- (3-pyrrotidin-1-ylpropoxy) phenyl] -4- (3H) -quinazolinone (1) Preparation of 2-amino-6-bromobenzoic acid The target compound was obtained by reducing 2-bromo-6-nitrobenzoic acid with iron in a mixture of methanol solvents and aqueous solution of ammonium chloride. 2-Bromo-6-nitrobenzoic acid was prepared by the procedure described in the literature (J. Chem. Soc. Perkin Trans. 1, 1991, page 1565) using 2-bromo-6-n -trotoluene as starting material. (2) Preparation of 5-bromo-2-methyl-3- [4- (3-pyrrolidin-1-yl-propoxy) phenylH-4- (3H) -quinazolinone The title compound was obtained by measuring the process according to Example 18, using 2-amino-6-bromobenzoic acid, acetic anhydride and 4- (3-pyrrolidin-1-ylpropoxy) aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.80-1.84 (4H, m), 2.03-2.09 (2H, m), 2.23 (3H, s), 2.60-2.56 (4H, m), 2.68 (2H , t, J = 7.6 Hz), 4.08 (2H, t, J = 6.3 Hz), 7.04 (2H, d, J = 9.3 Hz), 7.14 (2H, d, J = 8.8 Hz), 7.51 (1H, t , J = 8.0 Hz), 7.62 (1 H, dd, J = 8.3, 1.5 Hz), 7.70 (1 H, dd, J = 7.8, 1.5 Hz).

EXAMPLE 147 5-Fluoro-2-methyl-3- (4-. {3-r (3S) -3-methylpiperidin-1-inpropoxy-phenyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-6-fluorobenzoic acid, acetic anhydride and monotosylate of 4. { 3 - [(3S) -3-methylpiperidin-1-yl] propoxy} Anlina as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.83-0.91 (4H, m), 1.54-1.73 (5H, m), 1.83-1.89 (1H, m), 1.98-2.05 (2H, m), 2.24 (3H, s), 2.50 (2H, t, J = 7.3 Hz), 2.83-2.90 (2H, m), 4.07 (2H, t, J = 6.3 Hz), 7.04 (2H, d, J = 9.3 Hz) , 7.07-7.12 (1 H, m), 7.13 (2H, d, J = 9.3 Hz), 7.46 (1 H, d, J = 8.3 Hz), 7.70-7.65 (1H, m).

EXAMPLE 148 2-Ethyl-5-fluoro-3- (4-. {3-r (3S) -3-methyl-piperidin-1-nitropoxy> phenyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-6-fluorobenzoic acid, propionic anhydride and 4- monotosylate. { 3 - [(3S) -3-methylpiperidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.85-0.90 (4H, m), 1.21 (3H, t, J = 7.3 Hz). 1.54-1.73 (5H, m), 1.83-1.90 (1 H, m), 1.99-2.05 (2H, m), 2.44 (2H, q, J = 7.5 Hz), 2.50 (2H, t, J = 7.3 Hz ), 2.83-2.91 (2H, m), 4.07 (2H, t, J = 6.3 Hz), 7.02-7.14 (5H, m), 7.50 (1H, d, J = 8.3 Hz), 7.70-7.64 (1H, m).

EXAMPLE 149 6-Fluoro-2-methyl-3- (4-l3-rf3S) -3-methylpiperidin-1-inpropoxy) phenyl) pyrid3,4-d1-pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 5-amino-2-fluoroisonicotinic acid, acetic anhydride and monotosylate of 4-. { 3 - [(3S) -3-methylp.peridin-1-yl] propoxy} aniline as initial materials. 5-Amino-2-fluoroisonicotinic acid was prepared by the procedure described in the literature (J. Chem. Soc. Perkin Trans. 1, 1996, page 2221). 1 H NMR (400 MHz, CDCl 3, d ppm): 0.83-0.93 (4H, m), 1.61-1.75 (5H, m), 1.86-1.92 (1 H, m), 2.01-2.08 (2H, m), 2.28 (3H, s), 2.53 (2H, t, J = 7.3 Hz), 2.94-2.85 (2H, m), 4.08 (2H, t, J = 6.3 Hz), 7.06 (2H, d, J = 9.3 Hz ), 7.14 (2H, d, J = 9.3 Hz), 7.65 (1H, d, J = 3.9 Hz), 8.77 (1 H, s).

EXAMPLE 150 2-Ethyl-6-fluoro-3- (4-. {3-rf3S) -3-methyl-piperidin-1-npropoxy > phenyl) pyrido3,4-d1pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 5-amino-2-fluoroisonicotinic acid, propionic anhydride and monotosylate of 4-. { 3 - [(3S) -3-methylpiperidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.83-0.92 (4H, m), 1.23 (3H, t, J = 7.3 Hz), 1.56-1.74 (5H, m), 1.84-1.90 (1H, m ), 2.00-2.07 (2H, m), 2.44-2.53 (4H, m), 2.83-2.91 (2H, m), 4.08 (2H, t, J = 6.3 Hz), 7.06 (2H, d, J = 9.3 Hz), 7.13 (2H, d, J = 8.8 Hz), 7.65 (1 H, d, J = 3.9 Hz), 8.80 (1 H, s).

EXAMPLE 151 6-Chloro-2-methyl-3- (4-. {3-r (3S) -3-methyl-piperidin-1-1-1-propoxy) phenyl) pyrido-3,4-d-1-pyrimidin-4- (3H) - ona The title compound was obtained by the procedure according to Example 18, using 5-amino-2-chloroisonicotinic acid, acetic anhydride and monotosylate of 4-. { 3 - [(3S) -3-methylpiperidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.83-0.92 (4H, m), 1.23 (3H, t, J = 7.3 Hz), 1.58-1.74 (5H, m), 1.84-1.90 (1H, m ), 2.00-2.07 (2H, m), 2.44-2.53 (4H, m), 2.91-2.84 (2H, m), 4.08 (2H, t, J = 6.3 Hz), 7.06 (2H, d, J = 9.3) Hz), 7.13 (2H, d, J = 9.3 Hz), 7.65 (1 H, d, J = 3.9 Hz), 8.80 (1H, s).

EXAMPLE 152 6-Chloro-2-etl-3- (4-3-r (3S) -3-methyl-piperidin-1-inpropoxy) phenyl) pyrido3,4-d1-pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 18, using 5-amino-2-chloroisonicotinic acid, propionic anhydride and monotosylate of 4-. { 3 - [(3S) -3-methylpiperidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.83-0.93 (4H, m), 1.23 (3H, t, J = 7.3 Hz). 1.58-1.74 (5H, m), 1.86-1.92 (1 H, m), 2.01-2.07 (2H, m), 2.47 (2H, q, J = 7.3 Hz), 2.52 (2H, t, J = 7.6 Hz ), 2.92-2.85 (2H, m), 4.08 (2H, t, J = 6.3 Hz), 7.06 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 8.06 (1 H, d, J = 1.0 Hz), 8.94 (1H, d, J = 1.0 Hz).

EXAMPLE 153 2-Methyl-3- (4. {3-r (3S) -3-metHpiperidin-1-illpropoxy) phenyl) pyrido [2,3-d] pyrimidin-4- (3H) -one monochlorhydrate The title compound was synthesized as a white solid (mp: 255-262 ° C) by the procedure according to Example 18, using 2-aminonicotinic acid, acetic anhydride and monotosylate of 4-. { 3 - [(3S) -3-methy1-pyridin-1-yl] propoxy} aniline as starting materials and treating with 1 equivalent of a base (4 N solution of ethyl acetate), followed by recrystallization (ethanol / ethyl acetate). 1 H NMR (400 MHz, CDCl 3 / CD 3 OD = 10/1, d ppm) 1.01 (3H, d, J = 6.3 Hz), 1.05-1.15 (1 H, m), 1.90-1.99 (2H, m), 2.25-2.51 (8H, m), 2.57-2.64 (1H, m), 3.21-3.25 (2H, m ), 3.51-3.54 (1 H, m), 3.63-3.67 (1H, m), 4.18 (2H, t, J = 5.6 Hz), 7.06 (2H, d, J = 8.8 Hz), 7.19 (2H, d , J = 8.8 Hz), 7.51 (1 H, dd, J = 7.8.4.9 Hz), 8.66 (1H, dd, J = 7.8, 2.0 Hz), 9.03 (1H, dd, J = 4.9, 2.0 Hz).

EXAMPLE 154 2-Ethyl-3- (4- (3-r (3S) -3-methyl-piperidin-1-yl] propoxy) phenyl) pyrido [2,3-d] pyrimidine-4 (3H) monohydrochloride -one The title compound was synthesized as a white solid (p.p.: 245-252 ° C) by the procedure according to Example 18, using 2-aminonicotinic acid, propionic anhydride and monotosylate of 4-. { 3 - [(3S) -3-methylpyridin-1-yl] propoxy} aniline as starting materials and treating with 1 equivalent of a base (4 N solution of ethyl acetate), followed by recrystallization (ethanol / ethyl acetate). 1 H NMR (400 MHz, CDCl 3 / CD 3 OD = 10/1, d ppm): 0.99 (3 H, d, J = 6.3 Hz), 1.07-1.14 (1 H, m), 1.31 (3 H, t, J = 7.3 Hz ), 1.88-1.99 (2H, m), 2.22-2.30 (1 H, m), 2.38-2.58 (7H, m), 3.16-3.22 (2H, m), 3.47-3.52 (1 H, m), 3.60 -3.64 (1 H, m), 4.17 (2H, t, J = 5.4 Hz), 7.04 (2H, d, J = 8.8 Hz), 7.17 (2H, d, J = 8.8 Hz), 7.43 (1H, dd , J = 7.8, 4.1 Hz), 8.60 (1 H, dd, J = 7.8, 2.0 Hz), 9.00 (1H, dd, J = 4.1, 2.0 Hz).

EXAMPLE 155 2-Methyl-3- (4- (3-r (3S) -3-methylpiperidin-1-inpropoxy) phenyl) pyridof4,3-d] pyrimidin-4- (3H) -one monosylate The title compound was synthesized as a light yellow solid (mp .: 185-188 ° C) by the procedure according to Example 18, using 4-aminonicotinic acid, acetic anhydride and monotosylate of 4-. { 3 - [(3S) -3-methylpyridin-1-yl] propoxy} aniline as starting materials and treating with 1 equivalent of p-toluenesulfonic acid, followed by recrystallization (ethanol / ethyl acetate). 1 H NMR (400 MHz, CDCl 3 / CD 3 OD = 10/1, d ppm): 0.99 (3 H, d, J = 6.8 Hz), 1.04-1.12 (1 H, m), 1.90-1.94 (2H, m), 2.06-2.21 (2H, m), 2.28-2.44 (10H, m), 3.27-3.32 (2H, m), 3.56-3.60 (1 H, m), 3.70-3.74 (1H, m), 4.15 (2H, t, J = 5.6 Hz), 7.04-7.07 (2H, m), 7.15-7.18 (2H, m), 7.21 (2H, d, J = 7.8 Hz), 7.59 (1 H, d, J = 5.9 Hz) , 7.77 (2H, d, J = 8.3 Hz), 8.85 (1H, d, J = 5.9 Hz), 9.45 (1 H, s).

EXAMPLE 156 2-Ethyl-5-methoxy-3- (4-. {3-r (3S) -3-methylpyridin-1-yl] propoxy) phenyl) -4- (3H) -quinazolinone hydrochloride The title compound was obtained by the procedure according to Example 18, using 2-amino-6-methoxybenzoic acid, propionic anhydride and 4- monotosylate. { 3 - [(3S) -3-methylpiperidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.99 (3H, d, J = 6.8 Hz), 1. 04-1.15 (1 H, m), 1.33 (3H, t, J = 7.3 Hz), 1.88-1.98 (2H, m), 2.22-2.31 (1 H, m), 2.34-2.43 (1 H, m) , 2.47-2.61 (4H, m), 2.98-3.05 (2H, m), 3.16-3.22 (2H, m), 3.50 (1 H, d, J = 10.2 Hz), 3.63 (1 H, d, J = 11.2 Hz), 3.99 (3H, s), 4.19 (2H, t, J = 5.1 Hz), 7.04-7.07 (3H, m), 7.18 (2H, d, J = 8.3 Hz), 7.82 (1 H, t , J = 8.3 Hz), 7.98 (1 H, d, J = 8.3 Hz).

EXAMPLE 157 2-Methyl-3- (4-3-r (3S) -3-methylpperidin-1-propoxy) pheny1) pyrido3,4-d1-pyrimidin-4- (3H) -one The title compound was obtained by catalytic reduction of 6-chloro-2-methyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy.} Phenyl) pyrido [3 , 4-d] pyrimidin-4- (3H) -one synthesized in Example 151 using a palladium on activated carbon catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.85-0.93 (4H, m), 1.58-1.75 (5H, m), 1.86-1.93 (1H, m), 2.01-2.08 (2H, m), 2.30 (3H, s), 2.53 (2H, t, J = 7.6 Hz), 2.93-2.86 (2H, m), 4.08 (2H, t, J = 6.3 Hz), 7.06 (2H, d, J = 8.8 Hz), 7.14 (2H, d, J = 8.8 Hz), 8.03 (1 H, d, J = 5.9 Hz), 8.68 (1H, d, J = 5.4 Hz), 9.12 (1H, s).

EXAMPLE 158 2-Ethyl-3- (4- { 3-r (3S) -3-methylpiperidin-1-ippropoxy> phenyl) pyrido3,4-dlpyrimidin-4- (3H) -one The title compound was obtained by catalytic reduction of 6-chloro-2-ethyl-3- (4-. {3 - [(3S) -3-methylpyridin-1-yl] propoxy] phenol. pyrido [3,4-d] pyrimidin-4- (3H) -one synthesized in Example 152 using a palladium on activated carbon catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.83-0.92 (4H, m), 1.24 (3H, t, J = 7.3 Hz). 1.56-1.76 (5H,), 1.85-1.92 (1H, m), 2.01-2.07 (2H, m), 2.46-2.54 (4H, m), 2.85-2.92 (2H, m), 4.08 (2H, t, J = 6.3 Hz), 7.06 (2H, d, J = 9. 3 Hz), 7.13 (2H, d, J = 8.8 Hz), 8.03 (1 H, d, J = 4.9 Hz), 8.67 (1 H, d, J = 4.9 Hz), 9.16 (1H, s).

EXAMPLE 159 8-Fluoro-2-methyl-3- (4- (3-r (3S) -3-methylpiperidol-1-1-propoxy) phenyl) -4- (3H) -quinazolinone hydrochloride The title compound was obtained by the procedure according to Example 18, using 2-amino-3-fluorobenzoic acid, acetic anhydride and monotosylate of 4. { 3 - [(3S) -3-methylpiperidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3 / CD 3 OD = 10/1, d ppm): 0.99 (3 H, d, J = 6.8 Hz), 1.05-1.14 (1 H, m), 1.88-1.98 (2 H, m), 2.17-2.31 (3H, m), 2.39 (3H, s), 2.45-2.61 (3H, m), 3.17-3.22 (2H, m), 3.50 (1 H, d, J = 11.7 Hz), 3.63 (1 H, d, J = 10.7 Hz), 4.17 (2H, t, J = 5.4 Hz), 7.04 (2H, d, J = 8.3 Hz), 7.19 (2H, d, J = 8.3 Hz), 7.41-7.46 (1H, m), 7.50-7.55 (1H , m), 8.05 (1 H, d, J = 7.8 Hz).

EXAMPLE 160 8-Fluoro-2-methyl-3- hydrochloride. { 4- [3-pyrrolidin-1-ylpropoxflfenl] -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-3-fluorobenzoic acid, acetic anhydride and 4- (3-pyrrolidin-1-yl propoxy) aniline as starting materials. 1 H NMR (400 MHz, CDCl 3 / CD 3 OD = 10/1, d ppm): 2.09-2.18 (2H, m), 2.21-2.29 (2H, m), 2.39-2.47 (5H, m), 2.86-2.95 (2H, m), 3.37-3.32 (2H, m), 3.83-3.89 (2H, m) , 4.18 (2H, t, J = 5.4 Hz), 7.07 (2H, d, J = 8.3 Hz), 7. 22 (2H, d, J = 8.8 Hz), 7.46-7.52 (1 H, m), 7.57 (1 H, t, J = 9.0 Hz), 8.06 (1H, d, J = 8.3 Hz).

Example 161 6- (2-Fluoroethoxy-2-methyl-3-r4- (3-piperidin-1-ylpropoxy) phenin-4- (3H) -quinazolinone The title compound was obtained by demethylation and alkylation of 6-methoxy-2-methyl-3- [4- (3-piperidin-1-ylpropoxy) phenyl] -4- (3H) -quinazolinone and 2-fluoroethyl tosylate as materials initials for the procedure according to Example 192. 6-Methoxy-2-methyl-3- [4- (3-piperidin-1-ylpropoxy) phenyl] -4- (3H) -quinazolinone was used which was synthesized in the Example 36 1 H NMR (400 MHz, CDCl 3, d ppm): 1.42-1.48 (2H, m), 1.58-1.63 (4H, m), 2.00-2.05 (2H, m), 2.23 (3H, s), 2.39-2.45. (4H, m), 2.51 (2H, t, J = 7.2 Hz), 4.07 (2H, t, J = 6.4 Hz). 4.27-4.29 (1 H, m), 4.34-4.36 (1 H, m), 4.73- 4.75 (1H, m), 4.844.87 (1 H, m), 7.04 (2H, d, J = 9.2 Hz) , 7.15 (2H, d, J = 9.2 Hz), 7.41 (1 H, dd, J = 2.8, 8.8 Hz), 7.61-7.64 (2H, m).

EXAMPLE 162 6- (2-Fluoroethoxy) -2-methyl-3-r4- (3-pyrrolidin-1-ylpropoxy) phenin-4- (3H) -quinazolinone The title compound was obtained by demethylation and alkylation of 6-methoxy-2-methyl-3- [4- (3-pyrrolidin-1-ylpropoxy) phenyl] -4- (3H) -quinazolinone synthesized in Example 143 by the procedure according to Example 192. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.81-1.84 (4H, m), 2.03-2.12 (2H, m), 2.23 (3H, s), 2.57-2.63 ( 4H, m), 2.70 (2H, t, J = 7.2 Hz), 4.10 (2H, t, J = 6.4 Hz), 4.27-4.29 (1H, m), 4.34-4.36 (1H, m), 4.73- 4.75 (1H, m), 4.85-4.87 (1 H, m), 7.04 (2H, d, J = 9.2 Hz), 7.14 (2H, d, J = 9.2 Hz), 7.41 (1 H, dd, J = 2.8, 8.8 Hz), 7.61- EXAMPLE 163 5-Methoxy-2-methyl-3-r4- (3-pyrrolidin-1-ylpropoxy) phenin-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 18, using 2-amino-6-methoxybenzoic acid, acetic anhydride and 4- (3-pyrrolidin-1-ylpropoxy) aniline as starting materials. NMR from H (400 MHz, CDCl 3, d ppm): 1.80-1.85 (4H, m), 2.03-2.10 (2H, m), 2.21 (3H, s), 2.55-2.61 (4H, m), 2.66-2.70. (2H, m), 3.95 (3H, s), 4. 08 (2H, t, J = 6.1 Hz), 6.87 (1 H, d, J = 8.3 Hz), 7.01 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 9.3 Hz), 7.23 (1 H, d, J = 8.3 Hz), 7.65 (1 H, t, J = 8.3 Hz).

EXAMPLE 164 5-Methoxy-2-methyl-3- (4- | 3-r (3S) -3-methylpiperdin-1-inpropoxy> phenol) -4- (3H) -quinazolinone The title compound was synthesized as a white solid (p.p.: 144-146 ° C) by the procedure according to Example 18, using 2-amino-6-methoxybenzoic acid, acetic anhydride and monotosylate of 4-. { 3- [(3S) -3-methylpyridin-1-yl] propoxy} aniline as starting materials, followed by recrystallization (ethyl acetate / diethyl ether / n-heptane). 1 H NMR (400 MHz, CDCl 3, d ppm): 0.85-0.90 (4H, m), 1.58-1.74 (5H, m), 1.83-1.91 (1H, m), 1.98-2.06 (2H, m), 2.21 (3H, s), 2.49-2.54 (2H, m), 2.84-2.92 (3H, m), 3.95 (3H, s), 4.06 (2H, t, J = 7.0 Hz), 6.87 (1 H, d, J = 8.3 Hz), 7.01 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.23 (1 H, d, J = 8.3 Hz), 7.65 (1H, t, J = 8.3 Hz).

EXAMPLE 165 6-Methoxy-2-methyl-3- (4- | 3-r (3S) -3-methylpiperidin-1-npropoxy > phenyl) -4- (3H) -quinazolinone (1) Preparation of 6-methoxy-2-methyl-4H-3,1-benzoxazin-4-one The target compound was obtained by the procedure according to Example 1- (1), using 2-amino-5-acid. -methoxybenzoic acid and acetic anhydride as starting materials. (2) Preparation of 6-methoxy-2-methyl-3- [4- (3-pyrrolidin-1-ylpropoxy) phenin-4- (3H) -quinazolinone 6-methoxy-2-methyl-4H-3, 1-benzoxazon-4-one (80 mg, 0.42 molimoles) and monotosylate of 4-. { 3 - [(3S) -3-methylpiperidin-1-yl] propoxy} Aniline (176 mg, 0.42 molimoles) were dissolved in acetic acid (2 ml), and stirred at room temperature for 20 hours. The acetic acid was distilled off under reduced pressure, ethyl acetate and 1 N aqueous sodium hydroxide solution were added, the mixture was extracted with ethyl acetate and dried with anhydrous sodium sulfate. After purification by silica gel column chromatography (chloroform / methanol = 20/1), the title compound (110 mg, 62%) was obtained as colorless crystals by recrystallization (ethyl acetate / diethyl ether). 1 H NMR (400 MHz, CDCl 3, d ppm): 0.84-0.91 (4H, m), 1.57-1.75 (5H, m), 1.85-1.93 (1H, m), 2.01-2.08 (2H, m), 2.23 (3H, s), 2.51-2.56 (2H, m), 2.85-2.94 (2H, m), 3.91 (3H, s), 4.08 (2H, t, J = 6.3 Hz), 7.04 (2H, d, J = 8.8 Hz), 7.15 (2H, d, J = 9.3 Hz), 7.36 (1 H, dd, J = 9.0, 3.2 Hz), 7.61 (1 H, d, J = 8.8 Hz), 7.63 (1 H, d, J = 2.9 Hz).

EXAMPLE 166 6-fDifluoromethoxy) -2-methyl-3- (4-f3-r (3S) -3-methyl-p -peridin-1-mpropoxy) phenyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 253, using 3- (4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy, phenyl) -4- ( 3H) -quinazolinone synthesized in Example 165 and sodium chlorodifluoroacetate as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.84-0.92 (4H, m), 1.54-1.74 (5H, m), 1.84-1.90 (1 H, m), 1.99-2.06 (2H, m), 2.25 (3H, s), 2.51 (2H, t, J = 7.3 Hz), 2.92-2.84 (2H, m), 4.07 (2H, t, J = 6.3 Hz), 6.61 (1 H, t, J = 73.4 Hz), 7.05 (2H, d, J = 8.8 Hz) , 7.14 (2H, d, J = 8.8 Hz), 7.53 (1H, dd, J = 8.8, 2.9 Hz), 7.69 (1 H, d, J = 8.8 Hz), 7.94 (1 H, d, J = 4 Hz).

EXAMPLE 167 5- (Difluoromethoxy) -2-methy1-3-f4-f3-r (3S) -3-methylpperidin-1-inpropoxy > phenyl) - 4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 253, using 5-methoxy-2-methyl-3- (4-. {3 - [(3S) -3-methyl-piperidin-1-yl] propoxy, phenyl) -4- (3H) -quinazolinone and sodium chlorodifluoroacetate as starting materials. 5-Methoxy-2-methyl-3- (4-. {3 - [(3S) -3-methyl-piperidin-1-yl] propoxy] phenyl) -4- (3H) -quinazoinone was used. was synthesized in Example 164. 1 H-NMR (400 MHz, CDCl 3, d ppm): 0.83-0.92 (4H, m), 1.54-1.73 (5H, m), 1.83-1.90 (1H, m), 1.99-2.06 (2H, m), 2.25 (3H, s), 2.50 (2H, t, J = 7.6 Hz), 2.84-2.91 (2H, m), 4.06 (2H, t, J = 6.3 Hz), 6.67 (1 H , t, J = 75.9 Hz), 7.04 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 9.3 Hz), 7.24 (1H, d, J = 7.3 Hz), 7.58 (1H, dd , J = 8.3, 1.0 Hz), 7.71 (1H, t, J = 8.3 Hz).

EXAMPLE 168 7-Methoxy-2-methyl-3-f4-f3-pyrrolidin-1-ylpropoxy) phenin-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-4-methoxybenzoic acid, acetic anhydride and 4- (3-pyrrolidin-1-ylpropoxy) aniline as starting materials. 2-Amino-4-methoxybenzoic acid was prepared by the procedure described in the literature (J. Chem. Soc. Perkin Trans. 1, 1997, page 3261). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.79-1.82 (4H, m), 2.01-2.08 (2H, m), 2.24 (3H, s), 2.53-2.56 (4H, m), 2.65 (2H , t, J = 7.6 Hz), 3.93 (3H, s), 4.09 (2H, t, J = 6.3 Hz), 7.06-7.01 (4H, m), 7.14 (2H, d, J = 8.8 Hz), 8.16 (1H, d, J = 8.8 Hz).

EXAMPLE 169 7-Methoxy-2-methyl-3- [4- (3-piperidin-1-ylpropoxy) phenin-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-4-methoxybenzoic acid, acetic anhydride and 4- (3-piperidin-1-ylpropoxy) aniline monohydrochloride. as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.43-1.48 (2H, m), 1.58-1.64 (4H, m), 1.98-2.05 (2H, m), 2.24 (3H, s), 2.39-2.46. (4H, m), 2.51 (2H, t, J = 7.6 Hz), 3.93 (3H, s), 4.07 (2H, t, J = 6.3 Hz), 7.07-7.01 (4H, m), 7.14 (2H, d, J = 8.8 Hz), 8.16 (1 H, d, J = 8.8 Hz).

EXAMPLE 170 7-Methoxy-2-methyl-3- (4- (3-r (3S) -3-methylpiperidin-1-inpropoxy> phenyl) -4- (3H) -quinazolinone The title compound was synthesized as a light yellow solid (mp .: 94-96 ° C) by the procedure according to Example 165, using 2-amino-4-methoxybenzoic acid, acetic anhydride and monotosylate of 4. { 3 - [(3S) -3-methylpyridin-1-yl] propoxy} aniline as starting materials, followed by recrystallization (ethyl acetate / diethyl ether). 1 H NMR (400 MHz, CDCl 3, d ppm): 0.83-0.92 (4H, m), 1.54-1.73 (5H, m), 1.83-1.89 (1H, m), 1.98-2.06 (2H, m), 2.24 (3H, s), 2.50 (2H, t, J = 7.6 Hz), 2.83-2.91 (2H, m), 3.93 (3H, s), 4.07 (2H, t, J = 6.3 Hz), 7.06-7.01 ( 4H, m), 7.14 (2H, d, J = 8.8 Hz), 8.16 (1 H, d, J = 8.8 Hz).

EXAMPLE 171 5-Methoxy-2-methyl-3- (4-. {3-r (2R) -2-methylpyrrolidin-1-inpropoxy > phenyl) -4-f3H) -quinazinone (1) Monotosylate preparation of 4-. { 3-f (2R) -2-methylpyrrolidin-1-ippropoxylaniline 4-. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} Aniline was obtained as a light brown oily substance by the procedure according to Example 138, using (2R) -2-methylpyrrolidine hydrobromide, 3-bromopropanol and 4-nitrophenol as starting materials. The obtained oily substance was dissolved in ethyl acetate, 1 equivalent of a methanol solution of p-toluenesulfonic acid monohydrate was added, and the target compound was obtained as a colorless solid by filtering off the solid that was produced. The (2R) -2-methylpyrrolidine hydrobromide was prepared by the procedure described in the literature (J. Org. Chem., 1989, Vol. 54, page 209) using l-Prolinol as starting material. (2) Preparation of 5-methoxy-2-methyl-3- (4-. {3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy) phenyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-6-methoxybenzoic acid, acetic anhydride and monotosylate of 4-. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.11 (3 H, d, J = 5.9 Hz), 1. 38-1.48 (1H, m), 1.59-1.82 (2H, m), 1.89-2.33 (9H, m), 2.97-3.03 (1H, m), 3.17-3.22 (1H, m), 3.95 (3H, s), 4.05-4.10 (2H, m), 6.87 (1H, d, J = 8.3 Hz), 7.02 (2H, d, J = 9.3 Hz), 7.11 (2H, d, J = 9.3 Hz), 7.24 ( 1H, d, J = 8.3 Hz), 7.65 (1H, t, J = 8.0 Hz). The NMR data for monotosylate of 4-. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} Aniline which is used for the preparation of the compound of this example are shown below. 1 H NMR (400 MHz, CDCl 3 / CD 3 OD = 5/1, d ppm): 1.54 (3 H, d, J = 5.4 Hz), 1.89-2.06 (2 H, m), 2.18-2.43 (6 H, m), 2.61 (4H, brs), 2.90-3.08 (1H, m), 3.21-3.26 (1H, m), 3.44-3.52 (1H, m), 3.91-4.02 (3H, m), 6.67-6.72 (4H, m ), 7.19 (2H, d, J = 8.3 Hz), 7.75 (2H, d, J = 8.3 Hz).

EXAMPLE 172 6-Methoxy-2-methyl-3- (4- (3-r (2R) -2-methylpyrrolidin-1-inpropoxy) phenyl) -4- (3H) -quinazolinone The title compound was synthesized as a white solid (p.p .: 106-108 ° C) by the procedure according to Example 165, using 2-amino-5-methoxybenzoic acid, acetic anhydride and monotosylate of 4-. { 3 - [(2R) -3-methylpyridin-1-yl] propoxy} aniline as starting materials, followed by recrystallization (ethyl acetate / diethyl ether). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.11 (3 H, d, J = 5.9 Hz), 1. 39-1.48 (1H, m), 1.59-1.83 (2H, m), 1.89-2.07 (3H, m), 2.10-2.34 (6H, m), 2.97-3.04 (1H, m), 3.17-3.22 (1H , m), 3.91 (3H, s), 4.07-4.12 (2H, m), 7.05 (2H, d, J = 8.8 Hz), 7.15 (2H, d, J = 8.8 Hz), 7.36 (1 H, dd , J = 8.8, 2.9 Hz), 7.61 (1H, d, J = 8.8 Hz), 7.63 (1 H, d, J = 2.9 Hz).

EXAMPLE 173 7-Methoxy-2-methyl-3- (4-. {3-r (2R) -2-met? Lpyrrolidin-1-inpropoxy.} Phenyl) -4-f3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-4-methoxybenzoic acid, acetic anhydride and monotosylate of 4. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.11 (3H, d, J = 6.3 Hz), 1.39-1.48 (1 H, m), 1.58-1.83 (2H, m), 1.89-2.07 (3H, m), 2.10-2.51 (6H, m), 2.97-3.04 (1H, m), 3.17-3.22 (1H, m), 3.93 (3H, s), 4.10-4.06 (2H, m), 7.01- 7.06 (4H, m), 7.15 (2H, d, J = 8.8 Hz), 8.16 (1H, d, J = 8.8 Hz).

EXAMPLE 174 3- [4- (3-Azepan-1-ylpropoxy) phenin-2,6-dimethyl-4- (3H) -quinazolinone (1) Preparation of 4- (3-azepan-1-ylpropoxy) aniline The target compound was obtained by the procedure according to Example 138, using azepam, 3-bromopropanol and 4-nitrophenol as starting materials. (2) Preparation of 3-f4- (3-azepan-1-ylpropoxy) phenyp-2,6-dimethyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-5-methylbenzoic acid, acetic anhydride and 4- (3-azepan-1-yl-propoxy) aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.62-1.64 (8H, m), 1.96-2.02 (2H, m), 2.24 (3H, t, J = 11.7 Hz), 2.48 (3H, t, J) = 11.7 Hz), 2.68 (6H, t, J = 7.3 Hz), 4.07-4.09 (2H, m), 7.04 (2H, dt, J = 6.0, 3.6 Hz), 7.14 (2H, dt, J = 12.2, 6.1 Hz), 7.57 (2H, d, J = 1.0 Hz), 8.05 (1 H, s).

EXAMPLE 175 3-r4- (3-Azepan-1-ylpropoxy) phenin-5-fluoro-2-methyl-4-f3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-6-f-luorobenzoic acid, acetic anhydride and 4- (3-azepan-1-yl-propoxy) aniolin as starting materials. NMR of H (400 MHz, CDCl 3, d ppm): 1.61-1.63 (8H, m), 1.95-2.02 (2H, m), 2.22 (3H, t, J = 10.0 Hz), 2.67-2.68 (6H, m) ), 4.08 (2H, t, J = 6.3 Hz), 7.03-7.15 (5H, m), 7.46 (1 H, d, J = 8.3 Hz), 7.68 (1 H, td, J = 8.3, 5.4 Hz) .

EXAMPLE 176 3-r4- (3-Azepan-1-ylpropoxy) phenan-7-fluoro-2-methyl-4- (3H) -q-inazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-4-fluorobenzoic acid, acetic anhydride and 4- (3-azepan-1-yl-propoxy) aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.62-1.65 (8H, m), 1.95-2.02 (2H, m), 2.23 (3H, t, J = 14.6 Hz), 2.67-2.68 (6H, m) ), 4.08 (2H, t, J = 6.3 Hz), 7.04-7.06 (2H, m), 7.12-7.20 (3H, m), 7.31 (1H, dd, J = 9.8, 2.4 Hz), 8.28 (1H, dd, J = 8.8, 5.9 Hz).

EXAMPLE 177 3-r4- (3-Azepan-1-ylpropoxy) phenan-5-methoxy-2-methyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-6-methoxybenzoic acid, acetic anhydride and 4- (3-azepan-1-ylpropoxy) aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.63-1.66 (8H, m), 1.96-2.03 (2H, m), 2.20 (3H, s), 2.68 (6H, d, J = 6.8 Hz), 3.96 (3H, s), 4.08 (2H, t, J = 6.3 Hz), 6.88 (1 H, d, J = 7.8 Hz), 7.01-7.04 (2H, m), 7.10-7.13 (2H, m), 7.24 (1H, d, J = 4.1 Hz), 7.65 (1H, t, J = 8.0 Hz).

EXAMPLE 178 3-r4- (3-Azepan-1-ylpropoxy) phenyl] -6-methoxy-2-methyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-5-methoxybenzoic acid, acetic anhydride and 4- (3-azepan-1-yl-propoxy) aniline as starting materials. NMR from H (400 MHz, CDCl 3, d ppm): 1.62-1.66 (8H, m), 1.96-2.03 (2H, m), 2.20 (3H, s), 2.68-2.70 (6H, m), 3.91 (3H , s), 4.09 (2H, t, J = 6.3 Hz), 7.05 (2H, td, J = 6.0, 3.6 Hz), 7.13-7.16 (2H, m), 7.36 (1 H, dd, J = 9.0, 3.2 Hz), 7.60 (1 H, s), 7.63 (1H, t, J = 3.4 Hz).

EXAMPLE 179 2,7-Dimethyl-3- (4- 3-r (3S) -3-methylpiperidin-1-inpropoxyphenyl> -4- (3H) -quinazolinone.

The title compound was obtained as white crystals, by the procedure according to Example 165, using 2-amino-6-methoxybenzoic acid, acetic anhydride and monotosylate of 4-. { 3 - [(3S) -2-methylpyrrolidin-1-yl] propoxy} aniline as starting materials, and treating with 1 equivalent of a solution in ethyl acetate 4 N hydrochloric acid, followed by recrystallization (from ethanol / ethyl acetate). 1 H NMR (400 MHz, CDCl 3 / CD 3 OD = 10/1, d ppm): 1.01 (3H, d, J = 6.3 Hz), 1.07-1.12 (1H, m), 1.90-1.99 (2H, m), 2.25 -2.52 (11H, m), 2.56- 2.63 (1H, m), 3.20-3.24 (2H, m), 3.51-3.54 (1H, m), 3.63-3.67 (1H, m), 4.15-4.18 (2H, m), 7.04 (2H, d, J = 8.3 Hz), 7.18 (2H, d, J = 8.3 Hz), 7.60-7.64 (2H, m), 8.04 (1 H, s).

EXAMPLE 180 3-r4- (3-Azepan-1-ylpropoxy) phenin-2-methylpyrid4,3-dlpyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 165, using 4-aminonicotinic acid, acetic anhydride and 4- (3-azepan-1-yl-propoxy) aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.63 (4H, brs), 1.72 (4H, brs), 2.06-2.08 (2H, m), 2.30 (3H, s), 2.76 (6H, brs), 4.10 (2H, t, J = 6.3 Hz), 7.05-7.08 (2H, m), 7.13-7.16 (2H, m), 7.49 (1H, d, J = 2.9 Hz), 8.85 (1H, d, J = 5.9 Hz), 9.47 (1 H, s).

EXAMPLE 181 2-Methyl-3- (4-f3-r (2R) -2-methylpyrrolidin-1-inpropoxy > phenyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using anthranilic acid, acetic anhydride and monotosylate of 4-. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.14 (3 H, d, J = 5.9 Hz), 1. 43-1.55 (1H, m), 1.69-1.85 (2H, m), 1.93-2.54 (9H, m), 2.99-3.07 (1H, m), 3. 21-3.26 (1 H, m), 4.06-4.11 (2H, m), 7.05 (2H, d, J = 8.8 Hz), 7.15 (2H, d, J = 8. 8 Hz), 7.46 (1H, t, J = 7.6 Hz), 7.67 (1H, d, J = 7.8 Hz), 7.78-7.74 (1 H, m), 8.27 (1 H, dd, J = 8.0, 1.2 Hz).

EXAMPLE 182 2,5-D-methyl-3-r2-methoxy-4-r3- (1-piperidinyl) propoxpfenin-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 63, using 2-amino-6-methylbenzoic acid, acetic anhydride, 4-amino-3-methoxyphenol and 1- (3-bromopropyl) piperidine hydrobromide as starting materials . 4-Amino-3-methoxyphenot was prepared by the procedure described in the literature (J. Med. Chem., 1995, Vol. 38, page 2748). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.42-1.48 (2H, m), 1.58-1.64 (4H, m), 1.97-2.04 (2H, m), 2.19 (3H, s), 2.39-2.44. (4H, m), 2.50 (2H, t, J = 7.2 Hz), 2.82 (3H, s), 3.77 (3H, s), 4.06 (2H, t, J = 6.4 Hz), 6.59-6.62 (2H, m), 7.08 (1H, d, J = 8.8 Hz), 7.19 (1H, d, J = 8.0 Hz), 7.49 (1 H, d, J = 8.0 Hz), 7.58 (1 H, t, J = 8.0) Hz).

EXAMPLE 183 2,5-Dimethyl-3- (2-methoxy-4- [3-pyrrolidin-1-ylpropoxyphenyl] -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 63, using 2-amino-6-methylbenzoic acid, acetic anhydride, 4-amino-3-methoxyphenol and 1- (3-bromopropyl) pyrrolidine hydrobromide as starting materials . 1 H NMR (400 MHz, CDCl 3, d ppm): 1.80-1.83 (4H, m), 2.01-2.07 (2H, m), 2.19 (3H, s), 2.54-2.58 (4H, m), 2.66 (2H , t, J = 7.2 Hz), 2.82 (3H, s), 3.77 (3H, s), 4.08 (2H, t, J = 6.4 Hz), 6.59-6.62 (2H, m), 7.08 (1 H, d, J = 8.8 Hz), 7.19 (1 H, d, J = 8.0 Hz), 7.49 (1 H, d, J = 8.0 Hz), 7.58 (1 H, t, J = 8.0 Hz).

EXAMPLE 184 6-Chloro-3-r2-methoxy-4- (3-piperidin-1-ylpropoxy) phenin-2-methylpyridof3,4-d1-pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 63, using 5-amino-2-chloroisonthinic acid, acetic anhydride, 4-amino-3-methoxyphenol and 1- (3-bromopropyl) piperidine hydrobromide as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.42-1.48 (2H, m), 1.58-1.64 (4H, m), 2.00-2.05 (2H, m), 2.25 (3H, s), 2.40-2.45 (4H, m), 2.51 (2H, t, J = 7.2 Hz), 3.77 (3H, s), 4.07 (2H, t, J = 6.4 Hz), 6.61-6.64 (2H, m), 7.07 (1H , d, J = 9.2 Hz), 8.06 (1H, d, J = 0.8 Hz), 8.90 (1H, d, J = 0.8 Hz).

EXAMPLE 185 6-Chloro-3-. { 2-methoxy-4-f3-pyrrolidin-1-ylpropoxphenyl) -2-methylpyrid3,4-d] pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 63, using 5-amino-2-chloroisonicotinic acid, acetic anhydride, 4-amino-3-methoxyphenol and 1- (3-bromopropyl) pyrrolidine hydrobromide as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.80-1.84 (4H, m), 2.02-2.09 (2H, m), 2.25 (3H, s), 2.55-2.60 (4H, m), 2.68 (2H , t, J = 7.2 Hz), 3.77 (3H, s), 4.10 (2H, t, J = 6.4 Hz), 6.61-6.64 (2H, m), 7.06 (1 H, d, J = 9.2 Hz), 8.06 (1 H, d, J = 0.8 Hz), 8.89 (1 H, d, J = 0.8 Hz).

EXAMPLE 186 6-Fluoro-3-r2-methoxy-4- (3-piperidin-1-ylpropoxy) phenyl] -2-methylpyrido [3,4-d1-pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 63, using 5-amino-2-fluoroisonicotinic acid, acetic anhydride, 4-amino-3-methoxyphenol and 1- (3-bromopropyl) piperidine hydrobromide as starting materials . 1 H NMR (400 MHz, CDCl 3, d ppm): 1.42-1.51 (2H, m), 1.58-1.64 (4H, m), 1.98-2.06 (2H, m), 2.25 (3H, s), 2.40-2.45 (4H, m), 2.51 (2H, t, J = 7.2 Hz), 3.78 (3H, s), 4.07 (2H, t, J = 6.4 Hz), 6.61-6.64 (2H, m), 7.07 (1H , d, J = 9.2 Hz), 7.64-7.65 (1 H, m), 8.76 (1 H, s).

EXAMPLE 187 6-Fluoro-3-. { 2-methoxy-4-f3-pyrrolidin-1-ylpropoxphenyl) -2-methylpyridof3,4-dlpyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 63, using 5-amino-2-fluoroisonicotinic acid, acetic anhydride, 4-amino-3-methoxyphenol and 1- (3-bromopropyl) pyrrolidine hydrobromide as starting materials . 1 H NMR (400 MHz, CDCl 3, d ppm): 1.80-1.84 (4H, m), 2.02-2.09 (2H, m), 2.24 (3H, s), 2.55-2.60 (4H, m), 2.67 (2H , t, J = 7.2 Hz), 3.77 (3H, s), 4.10 (2H, t, J = 6.4 Hz), 6.61-6.64 (2H, m), 7.07 (1H, d, J = 9.2 Hz), 7.64 -7.66 (1 H, m), 8.76 (1 H, s).

EXAMPLE 188 3-f2-Methoxy-4- (3-piperidin-1-ylpropoxy) phenin-2-methylpyridr3,4-d] -pyrimidin-4- (3H) -one The title compound was obtained by catalytic reduction of 6-chloro-3- [2-methoxy-4- (3-piperidin-1-ylpropoxy) phenyl] -2-methylpyrido [3,4-d] pyrimidin-4 - (3 H) -one synthesized in Example 184 using a palladium on activated carbon catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.42-1.48 (2H, m), 1.58-1.63 (4H, m), 1.98-2.06 (2H, m), 2.27 (3H, s), 2.40-2.45 (4H, m), 2.51 (2H, t, J = 7.2 Hz), 3.77 (3H, s), 4.07 (2H, t, J = 6.4 Hz), 6.61-6.64 (2H, m), 7.07 (1 H, d, J = 9.2 Hz), 8.03 (1 H , dd, J = 0.8, 5.2 Hz), 8.66 (1 H, d, J = 5.2 Hz), 9.12 (1 H, d, J = 0.8 Hz).

EXAMPLE 189 3- 2-Methoxy-4- [3-pyrrolidin-1-ylpropoxphenyl) -2-methylpyridr3,4-d] -pyrimidin-4- (3H) -one The title compound was obtained by catalytic reduction of 6-chloro-3-. { 2-methoxy-4- [3-pyrrolidin-1-ylpropoxy] phenyl} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one synthesized in Example 185 using a palladium on activated carbon catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.82-1.86 (4H, m), 2.04-2.11 (2H, m), 2.27 (3H, s), 2.59-2.63 (4H, m), 2.70 (2H , t, J = 7.2 Hz), 3.77 (3H, s), 4.10 (2H, t, J = 6.4 Hz), 6.61-6.64 (2H, m), 7.07 (1 H, d, J = 9.2 Hz), 8. 03 (1H, dd, J = 0.8, 5.2 Hz), 8.66 (1H, d, J = 5.2 Hz), 9.12 (1H, d, J = 0.8 Hz).

EXAMPLE 190 3-r 2 -Metoxy-4- (3-piperidin-1-ylpropoxy) -phenin-2-methylpyridr-4,3-dlpyrimidin-4- (3 H) -one The title compound was obtained by the procedure according to Example 63, using 4-aminonicotinic acid, acetic anhydride, 4-amino-3-methoxyphenol and 1- (3-bromopropyl) piperidine hydrobromide as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.42-1.48 (2H, m), 1.58-1.63 (4H, m), 1.98-2.06 (2H, m), 2.26 (3H, s), 2.40-2.45. (4H, m), 2.50 (2H, t, J = 7.2 Hz), 3.78 (3H, s), 4.07 (2H, t, J = 6.4 Hz), 6.61-6.64 (2H, m), 7.08 (1 H, d, J = 8.8 Hz), 7.48 (1 H , dd, J = 0.8, 5.6 Hz), 8.83 (1 H, d, J = 5.6 Hz), 9.47 (1 H, d, J = 0.8 Hz).

EXAMPLE 191 3-. { 3-Bromo-4- [3-pyrrolidin-1-ylpropoxy-phenyl > -2-methyl-5- (trifluoromethyl) -4- (3H) -quinazolinone (1) Preparation of 4-amino-2-bromophenol The target compound was obtained by reducing 2-bromo-4-nitrophenol with iron in a mixed solution of methanol and aqueous solution of ammonium chloride. 2-Bromo-4-nitrophenol was prepared by the method described in the literature (J. Org. Chem., Vol. 62, 1997, page 4504). (2) Preparation of 3-. { 3-bromo-4- [3-pyrrolidin-1-ylpropoxy] phenyl} -2-methyl-5- (trifluoromethyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 63, using 2-amino-6- (trifluoromethyl) benzoic acid, acetic anhydride, 4-Amino-2-bromophenol and 1- (3-bromopropyl) pyrrolidine hydrobromide as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.81 (4H, m), 2.10 (2H, m), 2.28 (3H, s), 2.57 (4H, m), 2.70 (2H, m), 4.13 ( 2H, m), 7.05 (1H, d, J = 8.8 Hz), 7.17 (1 H, d, J = 8.8 Hz), 7.46 (1H, s), 7.83 (1 H, d, J = 8.0 Hz), 7.88 (2H, d, J = 8.0 Hz).

EXAMPLE 192 6-Chloro-3-r2-fluoroethoxy-4- (3-piperidin-1-ylpropoxy) phenyl] -2-methylpyridr3,4-dlpyrimidin-4- (3H) -one (1) Preparation of 6-chloro-3- [2-hydroxy-4- (3-piperidin-1-ylpropoxy) -phenin-2-methylpyrid [3,4-d] pyrimidine -4- (3H) -one 6-Chloro-3- [2-methoxy-4- (3-p1peridin-1-ylpropoxy) phenyl] -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one synthesized in the Example 3-3 (143 mg, 0.32 molimoles) was dissolved in methylene chloride (3 ml), boron tribromide (1 M solution of methylene chloride, 3.2 molimoles) was added in an ice bath, stirred at room temperature for 15 hours, and stirred at 40 ° C for 3 hours. Saturated carbonated water was added to stop the reaction, the mixture was extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The product was purified by silica gel column chromatography (chloroform / methanol = 20/1), and the target compound (49 mg, 35%) was obtained as a light yellow solid. NMR of H (400 MHz, CDCl 3, d ppm): 1.38-1.43 (2H, m), 1.52-1.59 (4H, m), 2.01-2.07 (2H, m), 2.32 (3H, s), 2.51-2.57 (4H, m), 2.64-2.80 (2H, m), 3.99 (2H, t, J = 6.4 Hz), 6.41-6.45 (2H, m), 6.99 (1 H, d, J = 8.4 Hz), 8.05 (1H, d, J = 0.8 Hz), 8.90 (1H, d, J = 0.8 Hz). (2) Preparation of 6-chloro-3- [2-fluoroethoxy-4- (3-piperidin-1-ylpropoxy) -phenip-2-methylpyrid [3,4-d1-pyrimidin-4- (3H) -one] 6-Chloro-3- [2-hydroxy-4- (3-piperidin-1-ylpropoxy) phenyl] -2-methylpyrido [3,4-d] -pyrimidin-4- (3 H) -one (10 mg), 2-fluoethyl tosylate (7.6 mg) and potassium carbonate (16 mg) were mixed in dimethylformamide (2 ml) and stirred at 80 ° C for 10 hours. Distilled water was added, the mixture was extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The product was purified by thin layer chromatography on silica gel (chloroform / methanol = 10/1), and the title compound (8.5 mg, 77%) was obtained as a colorless solid. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.42-1.48 (2H, m), 1.58-1.64 (4H, m), 1.98-2.05 (2H, m), 2.28 (3H, s), 2.40-2.45. (4H, m), 2.50 (2H, t, J = 7.2 Hz), 4.07 (2H, t, J = 6.4 Hz). 4.10-4.36 (2H, m), 4.49-4.52 (1 H, m), 4.61-4.64 (1 H, m), 6.64 (1 H, d, J = 2.4 Hz), 6.67 (1 H, dd, J = 2.4, 8.4 Hz), 7.09 (1 H, d, J = 8.4 Hz), 8.05 (1 H, s), 8.90 (1 H, s).

EXAMPLE 193 2,5-Dimethyl-3-r 2 -hydroxy-4- (3-piperidin-1-ylpropoxy) phenin-4- (3 H) -quinazolinone 2,5-Dimethyl-3-. { 2-methoxy-4- [3-pyrrolidin-1-ylpropoxy] phenyl} -4- (3H) -quinazolinone synthesized in Example 182 was demethylated using the procedure according to Example 192- (1), and thus the title compound was obtained. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.38-1.45 (2H, m), 1.55-1.61 (4H, m), 1.97-2.04 (2H, m), 2.27 (3H, s), 2.43-2.52 (4H, m), 2.55-2.64 (2H, m), 2.80 (3H, s), 3.92-3.98 (2H, m), 6.44-6.48 (2H, m), 6.99 (1 H, d, J = 8. 0 Hz), 7.16 (1 H, d, J = 8.0 Hz), 7.49 (1 H, d, J = 8.0 Hz), 7.56 (1 H, t, J = 8.0 Hz).

EXAMPLE 194 2,5-Dimethyl-3-. { 2-fluoroethoxy-4-r3-piperidin-1-ylpropoxpfenil > -4-f3H) - quinazolinone The title compound was obtained by the procedure according to Example 192- (2) using 2,5-dimethyl-3-. { 2-hydroxy-4- [3-pyrrolidin-1-ylpropoxy] phenyl} -4- (3H) -quinazolinone, and 2-fluoroethyl tosylate as starting materials. 2,5-dimethyl-3- was used. { 2-hydroxy-4- [3-pyrrolidin-1-ylpropoxy] phenyl} -4- (3H) -quinazolinone which was synthesized in Example 193. 1 H NMR (400 MHz, CDCl 3 d ppm): 1.42-1.49 (2H, m), 1.59-1.65 (4H, m), 1.98-2.06 ( 2H, m), 2.22 (3H, s), 2.40-2.49 (4H, m), 2.52 (2H, t, J = 7.2 Hz), 2.82 (3H, s), 4.05 (2H, t, J = 6.4 Hz ), 4.10-4.33 (2H, m), 4.50-4.54 (1H, m), 4.62-4.66 (1 H, m), 6.62 (1 H, d, J = 2.4 Hz), 6.65 (1 H, dd, J = 2.4, 8.4 Hz), 7.10 (1 H, d, J = 8.4 Hz), 7.20 (1 H, d, J = 8.0 Hz), 7.51 (1 H, d, J = 8.0 Hz), 7.58 (1 H , t, J = 8.0 Hz).

EXAMPLE 195 3- 2-Fluoroethoxy-4-f3-piperidin-1-ylpropoxphenyl-2-methylpyridof3,4-d1-pyrimidin-4- (3H) -one The title compound was obtained by catalytic reduction of 6-chloro-3-. { 2-fluoroethoxy- [3-piperidin-1-ylpropoxy] phenyl} -2-methylpyrido [3,4-] pyrimidine- (3H) -one synthesized in Example 192 using a palladium on activated carbon catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.42-1.49 (2H, m), 1.58-1.64 (4H, m), 1.98-2.06 (2H, m), 2.29 (3H, s), 2.40-2.47 (4H, m), 2.51 (2H, t, J = 7.2 Hz), 4.07 (2H, t, J = 6.4 Hz), 4.10-4.36 (2H, m), 4.49-4.52 (1 H, m), 4.61 -4.64 (1 H, m), 6.64 (1 H, d, J = 2.4 Hz), 6.67 (1 H, dd, J = 2.4, 8.4 Hz), 7.10 (1 H, d, J = 8.4 Hz), 8.02 (1 H, dd, J = 0.8, 5.2 Hz), 8.66 (1H, d, J = 5.2 Hz), 9.12 (1H, d, J = 0.8 Hz).

EXAMPLE 196 3-. { 2-Fluoroethoxy-4- [3-piperidin-1-ylpropoxyphenyl) -2-methylpyridr4,3-dj ~ pyrimidine- (3H) -one The title compound was obtained by the procedure according to Example 192, using 3-. { 2-methoxy-4- [3-piperidin-1-ylpropoxy] phenyl} -2-methylpyrido [4,3-d] pyrimidin-4- (3H) -one and 2-fluoroethyl tosylate as starting materials. It was used 3-. { 2-methoxy-4- [3-piperidin-1-ylpropoxy] phenyl} -2-methylpyrido [4,3-d] pyrimidin-4- (3H) -one which was synthesized in Example 190. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.42-1.49 (2H, m), 1.58-1.64 (4H, m), 2.01-2.05 (2H, m), 2.29 (3H, s), 2.41-2.47 (4H, m), 2.52 (2H, t, J = 7.2 Hz), 4.07 (2H, t, J = 6.4 Hz), 4.10-4.38 (2H, m), 4.50-4.53 (1H, m), 4.62-4.64 (1 H, m), 6.64 (1 H, d, J = 2.4 Hz), 6.67 (1H, dd, J = 2.4, 8.4 Hz), 7.11 (1H, d, J = 8.4 Hz), 7.49 (1 H, dd, J = 0.8, 5.6 Hz), 8.84 (1H, d, J = 5.6 Hz ), 9.46 (1H, d, J = 0.8 Hz).

EXAMPLE 197 3- (4-Hydroxy-phenol) -6-methoxy-2-methylpyridof3,4-d1-pyrimidin-4- (3H) -one (1) Preparation of 6-chloro-3- (4-hydroxyphenyl) -2-methylpyrido [3,4-d1-pyrimidin-4- (3H) -one The target compound was obtained by the process according to Example 1- (1) and - (2), using 5-amino-2-chloroisonicotinic acid, acetic anhydride and 4-aminophenol as starting materials. (2) Preparation of 3- (4-hydroxyphenyl) -6-methoxy-2-methylpyrido [3,4-d1-pyrimidin-4- (3H) -one 6-chloro-3- (4-hydroxyphenyl) -2- methylpyrido [3,4-d] pyrimidin-4- (3H) -one (300 mg, 1.04 molimoles) was dissolved in dry methanol (15 ml) in a stream of nitrogen, sodium methoxide (7 molimoles) was added and the mixture was heated to reflux for 20 hours. After allowing to cool, acetic acid was added and the solvent was removed by distillation under reduced pressure. Distilled water was added to the residue, the solid precipitate was removed by filtration, and thus the title compound (259 mg, 88%) was obtained as a lavender solid. 1 H NMR (400 MHz, CDCl 3 / CD 3 OD = 5/1, d ppm): 2.21 (3H, s), 3.99 (3H, s), 6.94 (2H, d, J = 8.8 Hz), 7.01 (2H, d) , J = 8.8 Hz), 7.40 (1 H, s), 8.71 (1 H, s).

EXAMPLE 198 2-Ethyl-3- (4-hydroxyphenip-6-methoxypyridof3,4-dlpyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 197, using 5-amino-2-chloroisonicotinic acid, propionic anhydride, 4-aminophenol and sodium methoxide as starting materials. 1 H NMR (400 MHz, CDCl 3 / CD 3 OD = 5/1, d ppm): 1.21 (3 H, t, J = 7.6 Hz), 2.47 (2 H, q, J = 7.6 Hz), 4.03 (3 H, s), 6.98 (2H, d, J = 8.8 Hz), 7.04 (2H, d, J = 8.8 Hz), 7.44 (1H, s), 8.79 (1 H, s).

EXAMPLE 199 6-Methoxy-2-methyl-3-r4- (3-pyridin-1-ylpropoxy) phenanpyridof3,4-d] pyrimidin-4- (3H) -one The title compound was synthesized as a white solid (mp: 145-147 ° C) by the procedure according to Example 63, using 3- (4-hydroxyphenyl) -6-methoxy-2-methy1pyrido [3,4-d] pyrimidin-4- ( 3H) -one and 1- (3-bromopropyl) pyridine hydrobromide as starting materials, followed by recrystallization (ethyl acetate / diethyl ether). 3- (4-Hydroxyphenyl) -6-methoxy-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one was synthesized in Example 197. 1 H NMR (400 MHz, CDCI3, d ppm): 1.43-1.49 (2H, m), 1.58-1.64 (4H, m), 2.00-2.06 (2H, m), 2.24 (3H, s), 2.40-2.47 (4H, m), 2.52 (2H, t, J = 7.2 Hz), 4.03 (3H, s), 4.07 (2H, t, J = 6.4 Hz), 7.05 (2H, d, J = 9.2 Hz), 7.13 (2H, d, J = 9.2 Hz), 7.45 (1 H, d, J = 0.8 Hz), 8.75 (1 H, d, J = 0.8 Hz).

EXAMPLE 200 6-Methoxy-2-methyl-3-r 4 -3-pyrrolidin-1-ylpropoxy) phenylpyridof3,4-d1-pyrimidin-4- (3H) -one The title compound was synthesized as a white solid (mp: 123-126 ° C) by the procedure according to Example 63, using 3- (4-hydroxyphenyl) -6-methoxy-2-methylpyrido [3.4 -d] pyrimidin-4- (3H) -one and 1- (3-bromopropyl) pyrrolidine hydrobromide as starting materials, followed by recrystallization (ethyl acetate / diethyl ether). 3- (4-Hydroxyphenyl) -6-methoxy-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one was used which was synthesized in Example 197. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.80-1.84 (4H, m), 2.02- 2.08 (2H, m), 2.23 (3H, s), 2.55-2.61 (4H, m), 2.68 (2H, t, J = 7.2 Hz), 4.03 (3H, s), 4.10 (2H, t, J = 6.4 Hz), 7.05 (2H, d, J = 9.2 Hz), 7.13 (2H, d, J = 9.2 Hz), 7.45 (1 H, d, J = 0.8 Hz), 8.75 (1 H, d, J = 0.8 Hz).

EXAMPLE 201 2-Ethyl-6-methoxy-3-f4-r3-piperidin-1-ylpropoxpfenil > piridor3,4-dlpirimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 63, using 2-ethyl-3- (4-hydroxyphenyl) -6-methoxypyrido [3,4-d] pyrimidin-4- (3H) -one and hydrobromide of 1- (3-bromopropyl) piperidine as starting materials. 2-Ethyl-3- (4-hydroxyphenyl) -6-methoxypyrido [3,4-d] pyrimidin-4- (3H) -one was used which was synthesized in Example 198. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.21 (3H, t, J = 7.6 Hz), 1.43-1.49 (2H, m), 1.58-1.64 (4H, m), 2.00-2.06 (2H, m), 2.40-2.58 (8H, m ), 4.01 ^ 4.08 (5H, m), 7.05 (2H, d, J = 9.2 Hz), 7.13 (2H, d, J = 9.2 Hz), 7.45 (1H, s), 8.77 (1 H, s).

EXAMPLE 202 2-Ethyl-6-methoxy-3-. { 4-r3-pyrrolidin-1-ylpropoxphenyl) pyrido3,4-d1-pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 63, using 2-ethyl-3- (4-hydroxyphenyl) -6-methoxypyrido [3,4-d] pyrimidin-4- (3H) -one and hydrobromide of 1- (3-bromopropyl) pyrrolidine as starting materials. 2-Ethyl-3- (4-hydroxyphenyl) -6-methoxypyrido [3,4-d] pyrimidin-4- (3H) -one was used which was synthesized in Example 198. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.22 (3H, t, J = 7.6 Hz), 1. 82-1.86 (4H, m), 2.04-2.11 (2H, m), 2.44 (2H, q, J = 7.2 Hz), 2.58-2.63 (4H, m), 2.70 (2H, t, J = 7.2 Hz) , 4.04 (3H, s), 4.10 (2H, t, J = 6.4 Hz), 7.05 (2H, d, J = 9.2 Hz), 7.13 (2H, d, J = 9.2 Hz), 7.45 (1 H, s ), 8.79 (1 H, s).

EXAMPLE 203 6-Methoxy-3- (2-methoxy-4-f3-pyrrolidin-1-ylpropoxphenyl) -2-methylpyrido [3,4-d1-pyrim-din-4- (3H) -one (1) Preparation of 3- (4-hydroxy-2-methoxyphenyl) -6-methoxy-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one The target compound was obtained by the procedure according to with Example 197, using 5-amino-2-chloroisonicotinic acid, acetic anhydride, 4-amino-3-methoxyphenol and sodium methoxide as starting materials. (2) Preparation of 6-methoxy-3-. { 2-methoxy-4-f3-pyrrolidin-1-ylpropoxphenyl) -2-methy1pyridof3,4-dlpyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 63, using - (4-hydroxy-2-methoxyphenyl) -6-methoxy-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one and 1- (3-bromopropyl) pyrrolidine hydrobromide as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.80-1.84 (4H, m), 2.02-2.07 (2H, m), 2.20 (3H, s), 2.55-2.60 (4H, m), 2.68 (2H , t, J = 7.2 Hz), 3.77 (3H, s), 4.02 (3H, s), 4.09 (2H, t, J = 6.4 Hz), 6.60-6.63 (2H, m), 7.07 (1H, d, J = 8.8 Hz), 7.45 (1H, s), 8.75 (1 H, s).

EXAMPLE 204 6-Bromo-3-. { 2-fluoroethoxy-4-r3-pyrrolidin-1-ylpropoxphenyl} -2-methyl-4- (3H) -quinazolinone (1) Preparation of 6-bromo-3-. { 2-methoxy-4- [3-pyrrolidin-1-ylpropoxphenyl) -2-methyl-4- (3H) -quinazolinone The target compound was obtained by the procedure according to Example 63, using 2-amino-5-acid. -bromobenzoic acid, acetic anhydride, 4-amino-3-methoxyphenol and 1- (3-bromopropyl) pyrrolidine hydrobromide as starting materials. (2) Preparation of 6-bromo-3-. { 2-fluoroethoxy-4- [3-pyrrolidin-1-ylpropoxy] phenyl) -2-methyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 192 using 6-bromo-3 -. { 2-methoxy-4- [3-pyrrolidin-1-ylpropoxy] phenyl} -2-methyl-4- (3H) -quinazolinone and 2-fluoethyl tosylate as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.82-1.86 (4H, m), 2.05-2.12 (2H, m), 2.23 (3H, s), 2.62-2.66 (4H, m), 2.72 (2H , t, J = 7.2 Hz), 4.10 (2H, t, J = 6.4 Hz), 4.12-4.34 (2H, m), 4.50 (1 H, t, J = 4.0 Hz), 4.62 (1 H, t, J = 4.0 Hz), 6.64-6.68 (2H, m), 7.09 (1 H, d, J = 8.8 Hz), 7.55 (1 H, d, J = 8.4 Hz), 7.82 (1 H, dd, J = 8.8 , 2.4 Hz), 8.37 (1H, d, J = 2.4 Hz).

EXAMPLE 205 6-Ethoxycarbonyl-3-fluoroethoxy-4-r3-pyrrolidin-1-ylpropoxy] phenyl > -2-methyl-4- (3H) -quinnanolinone 6-Bromo-3-. { 2-fluoroethoxy-4- [3-pyrrolidin-1-ylpropoxy] phenyl} -2-methyl-4- (3H) -quinazolinone (37 mg), palladium (II) acetate (2 mg), dppf (1,1'-bis (diphenylphosphino) ferrocene) (8.2 mg) and triethylamine (22 mg) ) were mixed in ethanol (5 ml), and the atmosphere of the system was replaced by carbon monoxide. The mixture was then heated to reflux in the carbon monoxide atmosphere for 2 days. Ethyl acetate was added to the reaction liquid, and the solid precipitate was removed by filtration. The filtrate was concentrated, purified by thin layer chromatography on silica gel (chloroform / methanol = 10/1), and thus the title compound (23 mg, 63%) was obtained as a light gray solid. 6-Bromo-3- was used. { 2-fluoroethoxy-4- [3-pyrrolidin-1-ylpropoxy] phenyl} -2-methyl-4- (3H) -quinazolinone which was synthesized in Example 204. NMR of H (400 MHz, CDCl 3, d ppm): 1.41 (3H, t, J = 7.2 Hz), 1.60-1.81 (4H , m), 2.17-2.21 (4H, m), 2.27 (3H, s), 2.43-2.50 (2H, m), 3.23-3.32 (2H, m), 4.13-4.38 (4H, m), 4.41 (2H , q, J = 7.2 Hz), 4.50-4.53 (1 H, m), 4.62-4.64 (1 H, m), 6.65 (1H, dd, J = 2.4, 8.8 Hz), 6.70 (1H, d, J = 2.4 Hz), 7.13 (1H, d, J = 8.8 Hz), 7.71 (1 H, d, J = 8.8 Hz), 8.38 (1 H, dd, J = 2.4, 8.8 Hz), 8.93 (1 H, d, J = 2.4 Hz).

EXAMPLE 206 3-. { 2-Fluoroethoxy-4-r3-pyrrolidin-1-ylpropoxy] -phenyl > -6-methoxycarbonyl-2- methyl 4- (3H) -quinazolinone 6-Ethoxycarbonyl-3-. { 2-fluoroethoxy-4- [3-pyrrolidin-1-ylpropoxy] -phenyl} -2-methyl-4- (3H) -quinazolinone synthesized in Example 205 was treated with sodium methoxide in dry methanol, and thus the title compound was obtained. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.82-1.88 (4H, m), 2.05-2.12 (2H, m), 2.27 (3H, s), 2.62-2.66 (4H, m), 2.72 (2H , t, J = 7.3 Hz), 3.95 (3H, s), 4.10 (2H, t, J = 6.3 Hz), 4.17-4.34 (2H, m), 4.50 (1H, t, J = 4.1 Hz), 4. 62 (1 H, t, J = 4.1 Hz), 6.65-6.68 (2H, m), 7.11 (1 H, d, J = 8.3 Hz), 7.70 (1 H, d, J = 8.3 Hz), 8.37 ( 1H, dd, J = 8.5, 2.2 Hz), 8.93 (1 H, d, J = 2.0 Hz).

EXAMPLE 207 3-. { 3-Fluoro-4- [3-piperidin-1-ylpropoxphenyl) -2-methyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 63, using anthranilic acid, acetic anhydride, 4-amino-2-fluorophenol and 1- (3-bromopropyl) piperidine hydrobromide as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.43-1.48 (2H, m), 1.57-1.63 (4H, m), 2.02-2.09 (2H, m), 2.28 (3H, s), 2.39-2.45. (4H, m), 2.52 (2H, t, J = 7.1 Hz), 4.16 (2H, t, J = 6.3 Hz), 6.96-7.06 (2H, m), 7.13 (1 H, t, J = 8.8 Hz ), 7.49-7.45 (1H, m), 7.67 (1H, d, J = 8.3 Hz), 7.75-7.79 (1H, m), 8.27 (1H, dd, J = 7.8, 1.5 Hz).

EXAMPLE 208 3-. { 2-Fluoro-4-r3-piperidn-1-ylpropoxyphenyl) -2-methyl 4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 63, using anthranilic acid, acetic anhydride, 4-amino-3-fluorophenol and 1- (3-bromopropyl) piperidine hydrobromide as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.42-1.49 (2H, m), 1.58-1.63 (4H, m), 1.98-2.04 (2H, m), 2.29 (3H, s), 2.38-2.44. (4H, m), 2.49 (2H, t, J = 7.3 Hz), 4.06 (2H, t, J = 6.3 Hz), 6.82-6.86 (2H, m), 7.17 (1H, t, J = 8.5 Hz) , 7. 45-7.49 (1H, m), 7.68 (1H, d, J = 7.3 Hz), 7.75-7.79 (1H, m), 8.27 (1 H, dd, J = 8.0, 1.2 Hz).

EXAMPLE 209 2-Methyl-3- (3-methyl-4-r3-piperidin-1-ylpropoxy-1-phenyl) -4- (3H) -q-nazolinone The title compound was obtained by the procedure according to Example 63, using anthranilic acid, acetic anhydride, 4-amino-2-methylphenol and 1- (3-bromopropyl) piperidine hydrobromide as starting materials. NMR from H (400 MHz, CDCl 3, d ppm): 1.43-1.49 (2H, m), 1.59-1.64 (4H, m), 2.01-2.08 (2H, m), 2.26 (3H, s), 2.27 (3H , s), 2.40-2.46 (4H, m), 2.51-2.55 (2H, m), 4.03-4.11 (2H, m), 6.94 (1 H, d, J = 8.8 Hz), 7.00-7.03 (2H, m), 7.45 (1 H, td, J = 7.6, 1.3 Hz), 7.67 (1 H, d, J = 7.3 Hz), 7.73-7.78 (1 H, m), 8.27 (1H, dd, J = 7.8 , 1.0 Hz).

EXAMPLE 210 2-Methyl-3- 2-methyl-4-f3-piperidin-1-ylpropoxy] pheny1) -4- (3H) -q-nazolinone The title compound was obtained by the procedure according to Example 63, using anthranilic acid, acetic anhydride, 4-amino-3-methyl phenol and 1- (3-bromopropyl) piperidine hydrobromide as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.43-1.48 (2H, m), 1.58-1.64 (4H, m), 1.98-2.05 (2H, m), 2.08 (3H, s), 2.20 (3H , s), 2.39-2.46 (4H, m), 2. 50 (2H, t, J = 7.4 Hz), 4.05 (2H, t, J = 6.3 Hz), 6.92-6.86 (2H, m), 7.04 (1 H, d, J = 8.3 Hz), 7.45-7.49 (1H, m), 7.68 (1H, d, J = 7.8 Hz), 7.75-7.79 (1H, m), 8.28 (1 H, dd, J = 8.0, 1.7 Hz) .

EXAMPLE 211 3-4-R1-Cyclobutylpiperidin-4-yl) oxy1-2-methoxyphenyl > -2,5-dimethyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 88, using 2-amino-6-methylbenzoic acid, acetic anhydride, 4-amino-3-methoxyphenol, 4-hydroxypiperidin-1-t-butyl carboxylate and cyclobutanone as initial materials. 1 H NMR (400 MHz, CDCl 3 d ppm): 1.65-1.77 (2H, m), 1.84-1.95 (4H, m), 2.01-2.10 (4H, m), 2.17-2.25 (5H, m), 2.59- 2.68 (2H, m), 2.73-2.81 (1H, m), 2.83 (3H, s), 3.77 (3H, s), 4.33-4.41 (1H, m), 6.58-6.63 (2H, m), 7. 07 (1 H, d, J = 8.4 Hz), 7.20 (1 H, d, J = 8.4 Hz), 7.50 (1 H, d, J = 8.4 Hz), 7.58 (1 H, t, J = 8.4 Hz).

EXAMPLE 212 3- (4-r (1-Cyclobutylpiperidin-4-yl) oxphenyl) -6-methoxy-2-methy1pyrido3,4-d1-pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 88, using 3- (4-hydroxyphenyl) -6-methoxy-2-methylpyrid [3,4-d] pyrimidine-4- (3H) - ona, t-butyl 4-hydroxypiperidin-1-carboxylate and cyclobutanone as starting materials. 6-Methoxy-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one was used which was synthesized in Example 197. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.65-1.77 ( 2H, m), 1.84-1.95 (4H, m), 2.01-2.10 (4H, m), 2.17-2.24 (2H, m), 2.25 (3H, s), 2.61-2.69 (2H, m), 2.73- 2.81 (1H, m), 4.04 (3H, s), 4.37-4.43 (1H, m), 7.05 (2H, d, J = 8. 8 Hz), 7.14 (2H, d, J = 8.8 Hz), 7.46 (1 H, s), 8.77 (1 H, s).

EXAMPLE 213 3-f4-r (1-Cyclopentyl-piperidin-4-yl) oxy-phenyl} -6-methoxy-2-methylpyridor3,4-dlpyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 88, using 3- (4-hydroxyphenyl) -6-methoxy-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one, 4-hydroxy-piperidin-1-t-butylcarboxylate and cyclopentanone as starting materials. 3- (4-Hydroxyphenyl) -6-methoxy-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one was used which was synthesized in Example 197. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.40-1.49 (2H, m), 1.52- 1.62 (2H, m), 1.67-1.75 (2H, m), 1.85-1.95 (4H, m), 2.03-2.13 (2H, m), 2.24 (3H, s), 2.34-2.42 (2H, m), 2.53-2.58 (1H, m), 2.80-2.86 (2H, m), 4.03 (3H, s), 4.36-4.41 (1H, m), 7.05 (2H, d, J = 8.8 Hz), 7.14 (2H, d, J = 8.8 Hz), 7.45 (1H, s), 8.75 (1 H, s).

EXAMPLE 214 6-Chloro-3-. { 4 - [(1-cyclobutylpiperidin-4-yl) oxy] -2-rnetoxy-phenyl-2-methylpyridyl [3,4-d] pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 88, using 5-amino-2-chloroisonicotinic acid, acetic anhydride, 4-amino-3-methoxyphenol and 4-hydroxypiperidin-1-t-butyl carboxylate and cyclobutanone as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.64-1.77 (2H, m), 1.84-1.95 (4H, m), 2.01-2.10 (4H, m), 2.17-2.25 (5H, m), 2.59 -2.68 (2H, m), 2.73-2.82 (1H, m), 3.77 (3H, s), 4.36-4.42 (1H, m), 6.58-6.63 (2H, m), 7.07 (1H, d, J = 8.4 Hz), 8.06 (1H, s), 8.90 (1H, s).

EXAMPLE 215 3-4-r (1-Cyclobutylpiperidin-4-yl) oxp-2-methoxyphenyl > -2-methylpyridor4,3- d1pyrimidin-4- (3H) -one The title compound was obtained by the process according to Example 88, using 4-aminonicotinic acid, acetic anhydride, 4-amino-3-methoxyfenol, 4-hydroxypiperidin-1-t-butyl carboxylate and cyclobutanone as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.65-1.74 (2H, m), 1.82-1.95 (4H, m), 2.01-2.10 (4H, m), 2.17-2.24 (2H, m), 2.26 (3H, s), 2.62-2.69 (2H, m), 2.73-2.80, (1H, m), 3.77 (3H, s), 4.36-4.41 (1H, m), 6.59-6.63 (2H, m ), 7.07 (1H, d, J = 8.4 Hz), 7.48 (1H, d, J = 5.6 Hz), 8.83 (1H, d, J = 5.6 Hz), 9.46 (1H, s).

EXAMPLE 216 3-4-r (1-Cyclobutylpiperidin-4-yl) oxp-3-fluorophenyl) -2-methyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 88, using anthranilic acid, acetic anhydride, 4-amino-2-fluorophenol, 4-hydroxypiperidin-1-t-butyl carboxylate and cyclobutanone as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.64-1.75 (2H, m), 1.85-1.96 (4H, m), 1.99-2.10 (4H, m), 2.16-2.26 (2H, m), 2.28 (3H, s), 2.59-2.70 (2H, m), 2.72-2.81 (1H, m), 4.37-4.45 (1H, m), 6.95-6.98 (1H, m), 7.03 (1H, dd, J = 10.7, 2.4 Hz), 7.12 (1H, t, J = 8.8 Hz), 7.46-7.50 (1H, m), 7.67 (1H, d, J = 7. 3 Hz), 7.78 (1H, td, J = 7.7, 1.6 Hz), 8.26 (1H, dd, J = 7.8, 1.5 Hz).

EXAMPLE 217 3-. { 4-r (1-Cyclopentylpperidin-4-yl) oxn-3-fluorophenyl) -2-methyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 88, using anthranilic acid, acetic anhydride, 4-amino-2-fluorophenol, 4-hydroxypiperidin-1-t-butyl carboxylate and cyclopentanone as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.39-1.49 (2H, m), 1.53-1.61 (2H, m), 1.68-1.74 (2H, m), 1.86-1.98 (4H, m), 2.03 -2.11 (2H, m), 2.28 (3H, s), 2.35-2.46 (2H, m), 2.52-2.59 (1H, m), 2.87-2.79 (2H, m), 4.39-4.44 (1H, m ), 6.95-6.98 (1 H, m), 7.03 (1 H, dd, J = 10.7, 2.4 Hz), 7.13 (1 H, t, J = 8.5 Hz), 7.48 (1 H, t, J = 8.0 Hz) ), 7.67 (1H, d, J = 7.8 Hz), 7.76-7.80 (1H, m), 8.27 (1H, dd, J = 7.8, 1.5 Hz).

EXAMPLE 218 3-. { 4-r (1-Cyclobutylpiperidin-4-yl) oxy-2-fluorophenyl > -2-methyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 88, using anthranilic acid, acetic anhydride, 4-amino-3-fluorophenol, 4-hydroxypiperidin-1-t-butyl carboxylate and cyclobutanone as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.65-1.75 (2H, m), 1.84-1.95 (4H, m), 2.01-2.10 (4H, m), 2.17-2.27 (2H, m), 2.29 (3H, s), 2.59-2.67 (2H, m), 2.73-2.81 (1H,), 4.39-4.34 (1H, m), 6.80-6.85 (2H, m), 7.17 (1H, t, J = 8.8 Hz), 7.46-7.49 (1 H, m), 7.68 (1 H, d, J = 8.3 Hz), 7.75-7.79 (1H, m), 8.27 (1H, dd, J = 8.0, 1.2 Hz) .

EXAMPLE 219 3- (4-R (1-Cyclopentyl-piperidin-4-yl) -oxp-2-fluorophenyl> -2-methyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 88, using anthranilic acid, acetic anhydride, 4-amino-3-fluorophenol, 4-hydroxypiperidin-1-t-butyl carboxylate and cyclopentanone as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.41-1.49 (2H, m), 1.53-1.60 (2H, m), 1.68-1.75 (2H, m), 1.86-1.94 (4H, m), 2.03 -2.11 (2H, m), 2.29 (3H, s), 2.37-2.45 (2H, m), 2.53-2.60 (1 H, m), 2.79-2.85 (2H, m), 4.40-4.34 (1H, m), 6.80-6.85 (2H, m), 7.17 (1H, t, J = 8.8 Hz), 7.45-7.49 (1H, m), 7.68 (1H, d, J = 7.8 Hz), 7.75-7.79 (1 H, m), 8.27 (1H, dd, J = 8.3, 1.5 Hz).

EXAMPLE 220 2-Methyl-3-f 4-f (1-cyclobutylpyridin-4-yl) oxy] -2-methylphenyl > -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 88, using anthranilic acid, acetic anhydride, 4-amino-3-methylphenol, 4-hydroxypiperidin-1-t-butyl carboxylate and cyclobutanone as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.73-1.85 (2H, m), 2.12 (3H, s), 2.17-2.30 (4H, m), 2.69-2.90 (7H, m), 3.34-3.45 (4H, m), 4.78-4.83 (1H, m), 6.93-7.00 (2H, m), 7.23-7.15 (1H, m), 7.70 (1H, t, J = 7.6 Hz), 7.95 (1H , t, J = 7.3 Hz), 8.32 (1 H, d, J = 7.8 Hz), 8.41 (1 H, d, J = 7.3 Hz).

EXAMPLE 221 2-Met.l-3-f4 - [(1-cyclopentylpiperidin-4-yl) oxyl-2-methylphenyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 88, using anthranilic acid, acetic anhydride, 4-amino-3-methylphenol, 4-hydroxypiperidin-1-t-butyl carboxylate and cyclopentanone as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.40-1.49 (2H, m), 1.53-1.59 (2H, m), 1.67-1.74 (2H,), 1.85-1.93 (4H, m), 2.02- 2.09 (5H, m), 2.20 (3H, s), 2.35-2.43 (2H, m), 2.51-2.58 (1H, m), 2.79-2.86 (2H, m), 4.34-4.40 (1H, m), 6.87 (1H, dd, J = 8.8.2.9 Hz), 6.92 (1H, d, J = 2.4 Hz), 7.04 (1H, d, J = 8.3 Hz), 7.45-7.49 (1 H, m), 7.68 ( 1H, d, J = 7.3 Hz), 7.75-7.80 (1H, m), 8.29 (1H, dd, J = 8.0, 1.2 Hz).

EXAMPLE 222 3-. { 4-r (1-Cyclopentylpiperidin-4-yl) oxp-2- (2-fluoroethoxy) phenyl > -2- methylpyridof4,3-d] pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 192, using 3-. { 4 - [(1-Cyclobutyl-piperidin-4-yl) oxy] -2-methoxyphenyl} -2-methylpyrido [4,3-d] pyrimidin-4- (3H) -one and 2-fluoethyl tosylate as starting materials. It was used 3-. { 4 - [(1-Cyclobutyl-piperidin-4-yl) oxy] -2-methoxyphenyl} -2-methylpyrido [4,3-d] pyrimidin-4- (3H) -one which was synthesized in Example 221. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.65-1.77 (2H, m), 1.84-1.95 (4H, m), 2.01-2.11 (4H, m), 2.15-2.23 (2H, m), 2.29 (3H, s), 2.61-2.69 (2H, m), 2.71-2.80 (1H, m ), 4.10-4.34 (2H, m), 4.35-4.41 (1H, m), 4.50-4.52 (1H, m), 4.62-4.64 (1H, m), 6.64-6.67 (2H, m), 7.10 (1 H, d, J = 8.4 Hz), 7.48 (1H, d, J = 5.6 Hz), 8.84 (1H, d, J = 5.6 Hz), 9.46 (1H, s).

EXAMPLE 223 3-4-r (1-Cyclobutylpiperidin-4-yl) oxphenyl) -5-fluoroethoxy-2-methyl- - (3H) -quinazolinone The title compound was obtained by the procedure according to Example 192, using 3-. { 4 - [(1-cyclobuti-piperidin-4-yl) oxy] phenyl} -5-methoxy-2-methyl-4- (3H) -quinazolinone and 2-fluoethyl tosylate as starting materials. It was used 3-. { 4 - [(1-cyclobutylpiperidin-4-yl) oxy] phenol} -5-methoxy-2-methyl-4- (3H) -quinazolinone which was synthesized in Example 105. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.65-1.76 (2H m), 1.84-1.96 ( 4H, m), 2.01-2.10 (4H, m), 2.18-2.25 (5H, m), 2.61-2.69 (2H, m), 2.73-2.81 (1H, m), 4.28-4.31 (1H, m ), 4.36-4.40 (2H, m), 4.75-4.77 (1 H, m), 4.87-4.89 (1 H, m), 6.89 (1H, d, J = 8.4 Hz), 7.01 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8. 8 Hz), 8.29 (1H, d, J = 8.0 Hz), 7.64 (1 H, t, J = 8.0 Hz).

EXAMPLE 224 6-Chloro-3-T4-r (1-cyclobutylpiperidin-4-yl) oxp-2- (2-fluoroethoxy) phenyl) -2-methylpyrido [3,4-d1-pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 192, using 6-chloro-3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] -2-methoxyphenyl} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one and 2-fluoethyl tosylate as starting materials. 6-chloro-3- was used. { 4 - [(1-cyclobutylpiperidin-4-yl) oxy] -2-methoxyphenyl} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one which was synthesized in Example 220. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.67-1.75 (2H, m), 1.84-1.95 (4H, m), 2.01-2.10 (4H, m), 2.15-2.24 (2H, m), 2.28 (3H, s), 2.61-2.69 (2H, m), 2.73-2.81 (1H, m ), 4.10-4.32 (2H, m), 4.34-4.40 (1H, m), 4.49-4.51 (1H, m), 4.61-4.63 (1H, m), 6.64-6.66 (2H, m), 7.08 (1 H, d, J = 8.4 Hz), 8.05 (1H, s), 8.90 (1 H, s).

EXAMPLE 225 3-4-f (1-Cyclobutylpiperidin-4-yl) oxp-2- (2-fluoroethoxyphenyl) -2-methylpyridof3,4-dlpyrimidin-4- (3H) -one The title compound was obtained by catalytic reduction of 6-chloro-3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] -2- (2-fluoroethoxy) phenyl} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one synthesized in Example 230, using palladium on activated carbon as a catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.66-1.77 (2H, m), 1.84-1.95 (4H, m), 2.01-2.10 (4H, m), 2.15-2.24 (2H, m), 2.29 (3H, s), 2.61-2.69 (2H, m), 2.72-2.81 (1 H, m), 4.10-4.33 (2H, m), 4.35-4.41 (1 H, m), 4.49-4.51 (1H, m), 4.61-4.63 (1 H, m), 6.64-6.67 (2H, m), 7.10 (1 H, d, J = 8.4 Hz), 8.02 (1H, dd, J = 1.2, 5.6 Hz), 8.66 (1 H, d, J = 5.6 Hz), 9.12 (1 H, d, J = 1.2 Hz).

EXAMPLE 226 3-. { 2-r (1-Cyclobutylpiperidin-4-yl) oxp-pyrimidin-5-yl} -2-methyl-5- (trifluoromethyl) -4- (3H) -quinazolinone (1) Preparation of 4 - [(5-nitropyrimidin-2-yl) oxy] piperidine-1-carboxylate t-butyl 2-chloro-5-nitropyrimidine (80 mg, 0.5 molimoles), 4-hydroxypiperidine 1-t-butyl carboxylate (100 mg, 0.5 molimoles) and cesium fluoride (114 mg, 0.75 molimoles) were mixed in dimethylformamide, and stirred at room temperature for 12 hours. The solvent was removed by distillation under reduced pressure, the product was purified by silica gel column chromatography (hexane / ethyl acetate = 10 / 0-3 / 7), and thus the target compound was obtained (61 mg, 38 %) in the form of a light yellow solid. (2) Preparation of 4 - [(5-Nitropyrimidin-2-yl) oxy] piperidin-1-carboxylate t - butyl 4 - [(5-aminopyrimidin-2-yl) oxopiperdin-1-carboxylate t-butyl) Butyl (500 mg, 1.54 molimoles) was dissolved in a mixture of methanol solvents (10 ml) and tetrahydrofuran (10 ml), and palladium on activated carbon (10%, 200 mg) was added in a stream of nitrogen. The atmosphere of the system was replaced by hydrogen, and the mixture was stirred at room temperature for 3 hours. The reaction liquid was filtered with celite, the filtrate was concentrated, dried, and thus the target compound was obtained (439 mg, 97%). (3) 2-Methyl-3- [2- (piperidin-4-yl-oxy) pyridin-5-yn-5- (trifluoromethyl) -4- (3 H) -quinazolinone 2- Met.I-5- (trifluoromethyl) -4H-3,1-benzoxadin-4-one (78 mg, 0.34 molimoles) and 4 - [(5-aminopyrimidin-2-yl) oxy] piperidine-1-carboxylate t- butyl (100 mg, 0.34 molimoles) were dissolved in acetic acid (2 ml), and stirred at 130 ° C for 6 hours. The acetic acid was distilled off under reduced pressure, 1N aqueous sodium hydroxide solution was added, and the mixture was extracted with ethyl acetate. The product was dried with anhydrous sodium sulfate, and concentrated to obtain the target compound (112 mg, 81%) as an amorphous brown solid. (4) Preparation of 3- (2-f (1-cyclobutylpiperidin-4-yl) oxy] pyrimidin-5-yl) -2-methyl-5-trifluoromethyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 88- (3), using 2-methyl-3- [2- (piperidin-4-yl-oxy) pyridin-5-yl] -5- (trifluoromethyl) -4- (3H) -quinazolinone and cyclobutanone as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.64-1.75 (2H, m), 1.86-2.01 (4H, m), 2.01-2.15 (4H, m), 2.17-2.28 (2H, m), 2.32 (3H, s), 2.64-2.74 (2H, m), 2.74-2.81 (1H, m), 5.10-5.18 (1 H, brs), 7.83-7.93 (3H, m), 8.46 (2H, s).

EXAMPLE 227 3- (4-f (1-Cyclobutylpiperidin-4-yl) oxphenyl) -5-methoxy-2-propyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 94, using 2-amino-6-methoxybenzoic acid, butyric anhydride and 4 - [(1-cyclobutylpiperidin-4-yl) oxy] aniline as materials initials. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.86 (3H, t, J = 7.2 Hz), 1. 64-1.75 (4H, m), 1.83-1.95 (4H, m), 2.01-2.11 (4H, m), 2.14-2.22 (2H, m), 2. 36-2.40 (2H, m), 2.60-2.70 (2H, m), 2.72-2.80 (1 H, m), 3.94 (3H, s), 4.35-4.42 (1 H, m), 6.86 (1 H, dd, J = 0.8, 8.4 Hz), 7.00 (2H, d, J = 8.8 Hz), 7.10 (2H, d, J = 8.8 Hz), 7.26 (1H, dd, J = 0.8, 8.0 Hz), 7.64 ( 1H, t, J = 8.0 Hz).

EXAMPLE 228 3- (4-rf1-Cyclobutylpiperidin-4-yl) oxypihenyl > -6-methoxy-2-methyl-4- (3H) -quinazolinone The title compound was synthesized as a white solid (mp: 171-173 ° C) by the procedure according to Example 94, using 2-amino-5-methoxybenzoic acid, acetic anhydride and 4 - [(1) monotosylate. -cyclobutylpiperidin-4-yl) oxy] aniline as starting materials, followed by recrystallization (ethyl acetate / diethyl ether). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.64-1.74 (2H, m), 1.85-1.96 (4H, m), 2.01-2.13 (4H, m), 2.15-2.24 (2H, m), 2.23 (3H, s), 2.60-2.72 (2H, m), 2.72-2.81 (1H, m), 3.91 (3H, s), 4.35-4.42 (1H, brs), 7.04 (2H, d, J = 6.8 Hz), 7.13 (2H, d, J = 6.8 Hz), 7.36 (1 H, dd, J = 3.2, 9.2 Hz), 7.61 (1 H, d, J = 9.2 Hz), 7.63 (1 H, d, J = 3.2 Hz).

EXAMPLE 229 3-4-r (1-Cyclobutylpiperidin-4-yl) oxphenyl) -2-etl-6-fluoropyrroter3,4-d] pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 94, using 5-amino-2-fluoroisonicotinic acid, propionic anhydride and 4 - [(1-cyclobutylpiperidin-4-yl) oxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.23 (3H, t, J = 7.2 Hz), 1.65-1.76 (2H, m), 1.85-1.96 (4H, m), 2.03-2.15 (4H, m ), 2.16-2.28 (2H, m), 2. 46 (2H, q, J = 7.2 Hz). 2.62-2.72 (2H, m), 2.73-2.82 (1 H, m), 4.38-4.44 (1 H, m), 7.06 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 6.8 Hz), 7.65 (1 H, d, J = 3.2 Hz), 8. 81 (1 H, s).

EXAMPLE 230 3-. { 4-r (1-Cyclobutylpiperidin-4-ipoxphenyl) -6-fluoro-2-methylpyrido3,4-d1-pyrimidin-4- (3H) -one The title compound was synthesized as a white solid (mp: 161-163 ° C) by the procedure according to Example 94, using 5-amino-2-fluoroisonicotinic acid, acetic anhydride and 4 - [(1-cyclobutylpiperid N-4-yl) oxy] aniline as starting materials, followed by recrystallization (ethyl acetate / diethyl ether / n-heptane).

NMR of H (400 MHz, CDCl 3, d ppm): 1.65-1.75 (2H, m), 1.80-1.93 (4H, m), 2.00-2.11 (4H, m), 2.12-2.24 (2H, m), 2.28 (3H, s), 2.60-2.70 (2H, m), 2.72-2.78 (1H, m), 4.36-4.42 (1H, m), 7.05 (2H, d, J = 6.8 Hz), 7.13 (2H, d) , J = 6.8 Hz), 7.65 (1 H, d, J = 4.0 Hz), 8.77 (1 H, s).

EXAMPLE 231 3 4-r (1-Cyclobutylpiperidin-4-yl) oxphenyl) -5-fluoro-2-methyl-4- (3H) -quinazolinone The title compound was synthesized as a white solid (mp: 190-192 ° C) by the procedure according to Example 94, using 2-amino-6-fluorobenzoic acid, acetic anhydride and 4 - [(1-cyclobutylpiperidin-4-yl) oxy] monotosylate] AniLine as starting materials, followed by recrystallization (ethyl acetate). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.65-1.75 (2H, m), 1.83-1.93 (4H, m), 2.00-2.11 (4H, m), 2.13-2.24 (2H, m), 2.24 (3H, s), 2.60-2.68 (2H, m), 2.72-2.79 (1 H, m), 4.36-4.41 (1 H, m), 7.04 (2H, d, J = 8.8 Hz), 7.08-7.14 (3H, m), 7.46 (1H, d, J = 8.0 Hz), 7.65-7.71 (1H, m).

EXAMPLE 232 3-4-r (1-Cyclobutylpiperidin ^ -yl) oxphenyl) -6-fluoro-2-methyl-4- (3H) -quinazolinone The title compound was synthesized as a light yellow solid (mp: 122-125 ° C) by the procedure according to Example 94, using 2-amino-5-fluorobenzoic acid, acetic anhydride and monotosylate 4 - [( 1-cyclobutylpiperidin-4-yl) oxy] aniline as starting materials, followed by recrystallization (ethyl acetate / diethyl ether). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.63-1.75 (2H, m), 1.84-1.92 (4H, m), 2.01-2.12 (4H, m), 2.16-2.24 (2H, m), 2.25 (3H, s), 2.61-2.70 (2H, m), 2.72-2.81 (1H, m), 4.36-4.42 (1H, m), 7.04 (2H, d, J = 8.8 Hz), 7.14 (2H, d) , J = 8.8 Hz), 7.45-7.51 (1 H, m), 7.68 (1 H, dd, J = 4.8, 8.8 Hz), 7.89 (1 H, dd, J = 3.2, 8.0 Hz).

EXAMPLE 233 3-. { 4-r (1-Cyclobutylpiperidin-4-yl) oxnphenyl > -7-fluoro-2-methyl-4- (3H) -quinazolinone The title compound was synthesized as a white solid (mp: 163-166 ° C) by the procedure according to Example 94, using 2-amino-4-fluorobenzoic acid, acetic anhydride and 4 - [(1-cyclobutylpiperidin-4-yl) oxy] anili monotosylate. na as starting materials, followed by recrystallization (ethyl acetate / diethyl ether). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.65-1.75 (2H, m), 1.82-1.96 (4H, m), 2.00-2.11 (4H, m), 2.14-2.24 (2H, m), 2.25 (3H, s), 2.60-2.68 (2H, m), 2.72-2.79 (1H, m), 4.36-4.41 (1H, m), 7.04 (2H, d, J = 8.4 Hz), 7.12-7.20 ( 3H, m), 7.31 (1 H, dd, J = 2.0, 9.6 Hz), 8.27 (1 H, dd, J = 6.0, 8.4 Hz).

EXAMPLE 234 3-. { 4-r (1-Cyclobutylpiperidin-4-yl) oxphenyl) -6-difluoro-2-methyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 94, using 2-amino-4,5-difluorobenzoic acid, acetic anhydride and 4 - [(1-cyclobutylpiperidin-4-yl) oxy] aniline monotosylate as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.66-1.75 (2H, m), 1.83-1.95 (4H, m), 2.00-2.11 (4H, m), 2.16-2.24 (2H, m), 2.24 (3H, s), 2.60-2.68 (2H, m), 2.72-2.79 (1H, m), 4.35-4.42 (1H, m), 7.04 (2H, d, J = 8.4 Hz), 7.13 (2H, d, J = 8.4 Hz), 7.44 (1 H, dd, J = 6.8, 10.4 Hz), 8.01 (1 H, dd, J = 8.4, 9.6 Hz).

EXAMPLE 235 3-4-r (1-Cyclobutylpyridin-4-yl) oxpfenl > -2-ethyl-5-methyl-4- (3H) -quinazolinone The title compound was obtained by the process according to Example 94, using 2 - amino - 6 - methylbenzoic acid, propionic anhydride and 4 - [(1-cyclobutylpyperidin-4-yl) oxy] aninyl monotosylate as materials initials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.20 (3H, t, J = 7.0 Hz), 1.69 (2H, m), 1.88 (4H, m), 2.05 (4H, m), 2.19 (2H, m), 2.44 (2H, q, J = 7.0 Hz), 2.63 (2H, m), 2.75 (1 H, m), 2.82 (3H, s), 4.37 (1 H, m), 7.04 (2H, d, J = 8.4 Hz), 7.13 (2H, d, J = 8.4 Hz), 7.21 (1 H, d, J = 7.2 Hz), 7.54 (1H, d, J = 8.0 Hz), 7. 59 (1 H, dd, J = 7.2, 8.0 Hz).

EXAMPLE 236 3-4-r (1-Cyclobutylpiperidin-4-yl) oxpfenl > -2-ethyl-5-fluoro-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 94, using 2-amino-6-fluorobenzoic acid, propionic anhydride and 4 - [(1-cyclobutylpiperidin-4-yl) oxy] aniline monotosylate as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.20 (3H, t, J = 7.2 Hz), 1. 64-1.76 (2H, m), 1.83-1.96 (4H, m), 2.00-2.10 (4H, m), 2.14-2.23 (2H, m), 2. 44 (2H, q, J = 7.2 Hz). 2.60-2.68 (2H, m), 2.71-2.79 (1 H, m), 4.35-4.40 (1H, m), 7.04 (2H, d, J = 8.8 Hz), 7.06-7.08 (1 H, m), 7.12 (2H, d, J = 8.8 Hz), 7.49 (1 H, d, J = 8.0 Hz), 7.64-7.70 (1 H, m).

EXAMPLE 237 3- (4-r (1-Cyclobutylpiperidin-4-yl) oxylphenyl) -2-etl-5-methoxy-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 94, using 2-amino-6-methoxybenzoic acid, propionic anhydride and 4 - [(1-cyclobutylpiperidine 4-yl) oxy] aniline monotosylate as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.20 (3H, t, J = 7.2 Hz), 1. 64-1.76 (2H, m), 1.83-1.96 (4H, m), 2.00-2.10 (4H, m), 2.14-2.22 (2H, m), 2.43 (2H, q, J = 7.2 Hz). 2.60-2.68 (2H, m), 2.71-2.79 (1 H, m), 3.95 (3H, s), 4.35-4.40 (1H, m), 6.86 (1 H, d, J = 8.0 Hz), 7.01 ( 2H, d, J = 8.8 Hz), 7.10 (2H, d, J = 8.8 Hz), 7.28 (1H, d, J = 8.0 Hz), 7.64 (1 H, t, J = 8.0 Hz).

EXAMPLE 238 5-Chloro-3- (4-r (1-cyclobutylpiperidin-4-yl) oxphenyl) -2-ethyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 94, using 2-amino-6-chlorobenzoic acid, propionic anhydride and 4 - [(1-cyclobutylpperidin-4-yl) oxy] oxynitol monotosylate. as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.20 (3H, t, J = 7.2 Hz), 1.62-1.78 (2H, m), 1.83-1.96 (4H, m), 2.00--2.10 (4H, m) ), 2.14-2.22 (2H, m), 2. 44 (2H, q, J = 7.2 Hz), 2.60-2.68 (2H, m), 2.71-2.79 (1 H, m), 4.35-4.40 (1 H, m), 7.03 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.45 (1H, dd, J = 2.8, 6.4 Hz), 7.57-7.62 (2H, m).

EXAMPLE 239 3- 3-Bromo-4-f (1-cyclobutylpiperidin-4-yl) oxy-phenyl) -5-fluoro-2-methyl-4- (3H) -quinazolinone (1) Preparation of monosylate of 3-bromo-4-f (1-cyclobutylpiperidin-4-yl) oxpaniline 3-Bromo-4 - [(1-cyclobutylpiperidin-4-yl) oxy] aniline is obtained according to the procedure of Example 94, using 2-bromo-4-nitrophenol, N-Boc-4-piperidinol and cyclobutanone as starting materials. Treating this with 1 equivalent of p-toluenesulfonic acid monohydrate, the target compound was obtained as a colorless solid. 2-Bromo-4-nitrophenol was prepared by the method described in the literature (J. Org. Chem., Vol. 62, 1997, page 4504). (2) Preparation of 3-. { 3-bromo-4-f (1-cyclobutylpiperidin-4-yl) oxy] phenyl > -5-fluoro-2-methyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 94, using 2-amino-6-fluorobenzoic acid, acetic anhydride and 3-bromo monotosylate. -4 - [(1-cyclobutylpiperidin-4-yl) oxy] aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.67-1.75 (2H, m), 1.86-2.10 (8H, m), 2.26 (3H, s), 2.28-2.38 (2H, m), 2.52-2.63 (2H, m), 2.74-2.83 (1H, m), 4.50-4.54 (1H, m), 7.03 (1H, d, J = 8.8 Hz), 7.08-7.15 (2H, m), 7.45-7.47 (2H , m), 7.72-7.66 (1H, m).

EXAMPLE 240 3- (3-Bromo-4-r (1-cyclobutylpiperidin-4-yl) oxy-phenyl) -2,5-dimethyl-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 94, using 2-amino-6-methylbenzoic acid, acetic anhydride and 3-bromo-4 - [(1-cyclobutylpiperidin-4-yl) oxy] aniline monotosylate. as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.72 (2H, m), 1.80-2.15 (8H, m), 2.24 (3H, s), 2.34 (2H, m), 2.44 (2H, m), 2.78 (1H, m), 2.81 (3H, s), 4.52 (1 H, brs), 7.04 (1H, d, J = 8.8 Hz), 7.14 (1H, dd, J = 2.4, 8.8 Hz), 7.23 (1H, d, J = 7.8 Hz), 7.46 (1H, d, J = 2.4 Hz), 7.50 (1H, d, J = 7.8 Hz), 7.60 (1H, t, J = 7.8 Hz).

EXAMPLE 241 3- (4-R (1-Cyclobutylpiperidin-4-yl) oxy-phenyl) -2-ethyl-5- (trifluoromethyl) -4- (3H) -quinazolinone hydrochloride The title compound was obtained by the procedure according to Example 94, using 2-amino-6- (trifluoromethyl) benzoic acid, propionic anhydride, 4 - [(1-cyclobutylpiperidin-4-yl) oxy] aniline monotosylate. as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.32 (3H, t, J = 6.8 Hz), 1.75-1.83 (1 H, m), 1.98-2.07 (1 H, m), 2.17-2.29 (4H , m), 2.72-2.91 (8H, m), 3.35-3.43 (3H, m), 4.78-4.81 (1H, m), 7.08 (2H, d, J = 8.0 Hz), 7.24 (2H, d, J = 8.4 Hz), 7.92-8.00 (2H, m), 8.40 (1H, d, J = 7.8 Hz).

EXAMPLE 242 3-4-r (1-Cyclobutylpiperidin-4-yl) oxpphenyl > -8-fluoro-2-methyl-4-y3H) -quinazolinone The title compound was synthesized as a light brown solid (mp: 177-179 ° C) by the procedure according to Example 94, using 2-amino-3-fluorobenzoic acid, acetic anhydride and monotosylate 4 - [( 1-cyclobutylpiperidin-4-yl) oxy] aniline as starting materials, followed by recrystallization (ethyl acetate / diethyl ether). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.66-1.75 (2H, m), 1.84-1.95 (4H, m), 2.02-2.11 (4H, m), 2.17-2.28 (2H, m), 2.31 (3H, s), 2.61-2.68 (2H, m), 2.75-2.80 (1H, m), 4.37-4.43 (1H, m), 7.05 (2H, d, J = 9.3 Hz), 7.14 (2H, d) , J = 9.3 Hz), 7.42-7.37 (1H, m), 7.47-7.52 (1 H, m), 8.05 (1 H, d, J = 7.8 Hz).

EXAMPLE 243 2-r 3 - (Benzyloxy) propyl] -3-. { 4-F (1-cyclopentylpiperidin-4-yl) oxy] pheni > pyridof2,3- d] pyrimidin-4- (3H) -one (1) Preparation of acid 2-. { [4- (benzyloxy) butanoyl] amino) nicotinic 4- (benzyloxy) butyric acid (154 mg, 0.79 molimoles) was dissolved in chloroform, thionyl chloride (158 mg) was added, and the mixture was stirred at room temperature for 1 hour. The solvent and excess thionyl chloride were removed by distillation under reduced pressure, the residue was dissolved in chloroform, triethylamine (0.46 ml) and 2-aminonicotinic acid ethyl ester (110 mg, 0.66 molimoles) were added, and the mixture was added. it was stirred at room temperature for 2 hours. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction liquid, the mixture was extracted with chloroform, and dried with anhydrous sodium sulfate. The residue obtained was dissolved in methanol, 2N aqueous solution of sodium hydroxide (0.66 ml) was added, and the mixture was stirred at room temperature for 2 hours. After adding aqueous solution of hydrochloric acid to the reaction liquid to make it slightly acidic, the solvent was removed by distillation under reduced pressure. Ethyl acetate and a small amount of ethanol were added to the residue, the solid precipitate was removed by filtration, and thus the target compound (166 mg, 80%) was obtained as a colorless solid. (2) Preparation of 2- [3- (benzyloxy) propin-4H-pyrido [2,3-d] [1,3] oxadin-4-one 2- Acid. { [4- (benzyloxy) butanoyl] amino} Nicotinic (100 mg, 0.32 molimoles) was dissolved in chloroform (4 ml) in a stream of nitrogen, oxalyl chloride (50 μl) was added, and the mixture was stirred at room temperature for 2 hours. Triethylamine (0.2 ml) was added to the reaction liquid, and stirred for 1 hour. Saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with chloroform. This was dried with anhydrous sodium sulfate, concentrated, and thus the target compound (42 mg, 45%) was obtained as a brown oily residue. (3) Preparation of 2- [3- (benzyloxy) propi-3-. { 4-f (1-cyclopentylpiperidin-4-yl) oxpfenyl) pyrid [2,3-d1-pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 94 , using 2- [3- (benzyloxy) propyl] -4H-pyrido [2,3-d] [1, 3] oxazin-4-one and 4 - [(1-cyclopentyl-piperidin-4-yl) oxy] aniline as initial materials. 1H NMR (400 MHz, CDCl3, d ppm): 1.43-1.53 (2H, m), 1.53- 1.62 (2H, m), 1.68-1.76 (2H, m), 1.86-1.94 (4H, m), 2.03 -2.12 (2H, m), 2.13-2.19 (2H, m), 2.35-2.46 (2H, m), 2.55-2.61 (1H, m), 2.62 (2H, t, J = 7.2 Hz), 2.82-2.88 (2H, m), 3.54 (2H, t, J = 5.6 Hz), 4.37-4.42 (1H, m), 4.40 (2H, s) 7.02 (2H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.17 (2H, d, J = 8.0 Hz), 7.22-7.28 (3H, m), 7.41 (1H, dd, J = 4.8, 8.0 Hz), 8.58 (1H, dd, J = 2.0, 8.0 Hz), 8.98 (1H, dd, J = 2.0, 4.4 Hz) ..

EXAMPLE 244 2-r 2 - (Allyloxy) et.n-6-chloro-3- < 4-r (1-cyclobutylpiperidin-4-yl) oxy] phenyl) pyridof3,4-d] pyrimidine-4- (3H) -one (1) Preparation of 2- [2- (allyloxy) ethyl-1-6-chloro-4H-pyridino-3,4-d1 [1.31-oxadin-4-one The target compound was obtained by the process according to Example 243, using 5-amino-2-chloroisonicotinic acid ethyl ester and 3- (allyloxy) propionic acid ethyl ester as starting materials. (2) Preparation of 2- [2- (allyloxy) etn-6-chloro-3- [4-r (1-cyclobutylpiperidin-1) oxphenyl) pyridof3.4-d] pyr Midin-4- (3H) -one The title compound was obtained by the procedure according to Example 94, using 2- [2- (allyloxy) ethyl] -6-chloro-4H-pyrid [3, 4-d] [1, 3] oxadin-4-one and 4 - [(1-cyclobutylpiperidin-4-yl) oxy] aniline as starting materials. 1H NMR (400 MHz, CDCl3, d ppm): 1.65-1.75 (2H, m), 1.83- 1.94 (4H, m), 2.00-2.11 (4H, m), 2.16-2.23 (2H, m), 2.60 -2.69 (2H, m), 2.76 (2H, t, J = 6.4 Hz), 3.86 (2H, t, J = 6.4 Hz), 3.97 (2H, dt, J = 1.2.6.0 Hz), 4.35-4.42 (1H, m), 5.17 (2H, dd, J = 1.2.10.4 Hz), 5.22-5.28 (2H, m), 5.81-5.90 (1 H, m), 7.03 (2H, d, J = 8.8 Hz), 7.10 (2H, d, J = 8.8 Hz), 8.06 (1 H, s), 8.91 (1 H, s).

EXAMPLE 245 6-Chloro-3- (4 - [(1-cyclopropylpiperidin-4-yl) oxphenyl) -2-methylpyridof3,4-dlpyrimidin-4- (3H) -one (1) Preparation of 1-cicloprop¡l-4- (4-nitrophenoxy) piperidine 4- (4-nitrophenoxy) piperidine (1.92 g, 8.63 millimoles) and [(1-ethoxycyclopropyl) oxy] (trimethyl) silane (27.02 g , 12.9 millimoles) were dissolved in a solvent mixture of acetic acid (20 ml) and methanol (20 ml), sodium cyanoborohydride (1.08 g, 17.3 millimoles) was added, and the mixture was stirred at 65 ° C for 18 hours. The solvent was distilled off under reduced pressure, ethyl acetate and 1 N aqueous sodium hydroxide solution were added, the mixture was extracted with ethyl acetate, and the organic phase was washed with distilled water. After drying with anhydrous sodium sulfate, the product was concentrated, and thus the target compound (1.94 g, 86%) was obtained as a light brown oily substance. 4- (4-Nitrophenoxy) piperidine was used which was prepared in Example 94. (2) Preparation of 4-f (1-cyclopropyl piperidin-4-yl) oxylaniline The target compound was obtained by catalytic reduction of 1-cyclopropyl-4- (4-nitrophenoxy) piperidine in a solvent mixture of methanol and ethyl acetate. ethyl, using a palladium on activated carbon catalyst. (3) Preparation of 6-chloro-3-. { 4 - [(1-Cyclopropylpiperidin-4-yl) oxphenyl) -2-methylpyridof3,4-d] pyrimidin-4- (3H) -one The title compound was obtained by the process according to the Example 94, using 5-amino-2-chloroisonicotinic acid, acetic anhydride and 4 - [(1-cyclopropylpiperidin-4-yl) oxy] aniline as starting materials. 1H NMR (400 MHz, CDCl3, d ppm): 0.41 to 0.50 (4H, m), 1.62- 1.65 (1H, m), 1.80-1.88 (2H, m), 1.97-2.04 (2H, m), 2.29 (3H, s), 2.48-2.57 (2H, m), 2.90-2.96 (2H, m), 4.37-4.42 (1H, m), 7.06 (2H, d, J = 8.8 Hz), 7.13 (2H, d) , J = 8.8 Hz), 8.06 (1 H, s), 8.90 (1 H, s).

EXAMPLE 246 3 4-r (1-Cyclopropylpiperidin-4-yl) oxphenyl) -2-methylpyridon-3,4-d-pyrimidin-4- (3H) -one The title compound was obtained by catalytic reduction of 6-chloro-3-. { 4 - [(1-cyclopropyl-p-peridin-4-yl) oxy] phenyl} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one synthesized in Example 251 using a palladium on activated carbon catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.41-0.50 (4H, m), 1.62- 1.66 (1 H, m), 1.79-1.88 (2H, m), 1.97-2.04 (2H, m), 2.30 (3H, s), 2.49-2.56 (2H, m), 2.90-2.96 (2H, m), 4.37-4.42 (1H, m), 7.06 (2H, d, J = 8.8 Hz), 7.13 (2H) , d, J = 8.8 Hz), 8.03 (1 H, d, J = 5.2 Hz), 8.68 (1 H, d, J = 5.2 Hz), 9.13 (1 H, s).

EXAMPLE 247 3-. { 4-r (1-Cyclobutylpperidin-4-yl) oxy] phenyl) -6- (difluoromethoxy) -2-methyl- (3H) -quinazolinone (1) Preparation of 3- (4 - [(1-cyclobutylpiperidin-yl) oxy] phenyl) -6-hydroxy-2-methyl- (3H) -quinazolinone The target compound was obtained by demethylation of 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -6-methoxy-2-methyl-4- (3H) -quinnanolinone synthesized in Example 234 by the procedure according to Example 192 (1). (2) Preparation of 3-. { 4- [1-cyclobutylpiperidin-4-yl) oxy] phenyl] -6- (difluoromethoxy) -2-methyl-4- (3H) -quinazolinone 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} 6-hydroxy-2-methyl-4- (3H) -quinazolinone (37 mg), sodium chlorodifluoroacetate (17 mg) and potassium carbonate (25 mg) were mixed in dimethylformamide, and stirred at 120 ° C for 2 hours. Distilled water was added to the reaction liquid, the mixture was extracted with chloroform, and dried with anhydrous sodium sulfate. The product was purified by silica gel column chromatography (chloroform / methanol = 15/1), and thus the title compound (19 mg, 46%) was obtained as an oily light yellow residue. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.65-1.77 (2H, m), 1.84-1.97 (4H, m), 2.01-2.10 (4H, m), 2.17-2.27 (5H, m), 2.61 -2.68 (2H, m), 2.74-2.81 (1H, m), 4.42-4.36 (1H, m), 6.61 (1H, t, J = 73.2 Hz), 7.04 (2H, d, J = 9.3 Hz), 7.14 (2H, d, J = 8.8 Hz), 7.53 (1H, dd, J = 9.0.2.7 Hz), 7.69 (1 H, d, J = 8.8 Hz), 7.94 (1H, d, J = 2.9 Hz).

EXAMPLE 248 3-. { 4-r (1-Cyclobutylpiperidin-4-yl) oxpphenyl > -7-methoxy-2-methyl-4-y3H) - quinazolinone The title compound was obtained by the procedure according to Example 94, using 2-amino-4-methoxybenzoic acid, acetic anhydride and 4 - [(1-cyclobutylpiperidin-4-yl) oxy] aniline as materials initials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.65-1.76 (2H, m), 1.83-1.95 (4H, m), 2.00-2.09 (4H,), 2.15-2.23 (2H, m), 2.24 ( 3H, s), 2.60-2.68 (2H, m), 2.71-2.79 (1H, m), 3.93 (3H, s), 4.35-4.41 (1H, m), 7.06-7.01 (4H, m), 7.14 (2H, d, J = 9.3 Hz), 8.16 (1 H, d, J = 8.8 Hz).

EXAMPLE 249 6-Chloro-3- (2-methoxy-4-l3-r (3S) -3-methylpperidin-1-inpropoxy) phenyl) -2-methylpyridr3,4-d1-pyrimidin-4- (3H -one (1) Preparation of 6-chloro-3- (4-hydroxy-2-methoxyphenyl) -2-methylpyrid [3,4-d] pyrimidin-4- (3H) -one The title compound was obtained by means of the procedure according to Example 1- (1) and - (2), using 5-amino-2-chloroisonicotinic acid, acetic anhydride and 4-amino-3-methoxyphenol as starting materials. (2) Preparation of 6-chloro-3- (2-methoxy-4-. {3 - [(3S) -3-methylpiperidin-1-1-1propoxy) phenyl) -2-methylpyridof3,4-d1-pyrimidine 4- (3H) -one 6-Chloro-3- (4-hydroxy-2-methoxyphenyl) -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one (250 mg, 0.79 molimoles), 3 - [(3S) -3-methylpiperidin-1-yl] propan-1-ol (186 mg, 1.2 molimoles) and triphenylphosphine (310 mg, 1.2 molimoles) were dissolved in dry tetrahydrofuran (6 ml) in a stream of nitrogen, and cooled in an ice bath. Dipopropyl azodicarboxylate (0.23 ml, 1.2 molimoles) was added dropwise, and stirred for 2 days at room temperature. The mixture was concentrated under reduced pressure, diethyl ether was added, and the solid precipitate was removed by filtration. The filtrate was concentrated, the product was purified by silica gel column chromatography (chloroform / methanol = 100 / 0-95 / 5), and thus the title compound (200 mg, 56%) was obtained as crystals colorless 1 H NMR (400 MHz, CDCl 3, d ppm): 0.83-0.93 (4H, m), 1.55-1.74 (5H, m), 1.84-1.89 (1 H, m), 1.99-2.06 (2H, m), 2.25 (3H, s), 2.50 (2H, t, J = 7.3 Hz), 2.83-2.91 (2H, m), 3.77 (3H, s), 4.07 (2H, t, J = 6.3 Hz), 6.61-6.64 (2H, m), 7.05-7.07 (1 H, m), 8.05 (1H, s), 8.89 (1 H, s).

EXAMPLE 250 6-Chloro-3- (2-hydroxy-4- (3-r (3S) -3-methylpiperidin-1-inpropoxy> phenyl) -2-methylpyridon-3,4-d-pyrimidin-4- (3H) -one 6-Chloro-3- (2-methoxy-4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy] phenyl) -2-methylpyrido [3,4-d] pyrimidine -4- (3H) -one synthesized in Example 249 was demethoxylated by the procedure according to Example 192 (1), and thus the title compound was obtained. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.77-0.89 (4H, m), 1.52-1.74 (5H, m), 1.97-2.07 (3H, m), 2.32 (3H, s), 2.64-2.81 (2H, m), 2.96-3.07 (2H, m), 3.97 (2H, t, J = 5.6 Hz), 6.41-6.39 (1 H, m), 6.44 (1H, dd, J = 8.8, 2.4 Hz) , 6.98 (1H, d, J = 8.3 Hz), 8.04 (1 H, s), 8.89 (1H, s).

EXAMPLE 251 6-Chloro-3- (2- (2-fluoroethoxy) -4- (3-r (3S) -3-methylpiperidin-1-inpropoxy > phenyl) -2-methylpyridof3,4-d] pyrimidin-4 - (3H) -one The title compound was obtained by the procedure according to Example 192 (1), using 6-chloro-3- (2-hydroxy-4-. {3 - [(3S) -3-methylpiperidine) -1-l] propoxy, phenyl) -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one and 2-fluoethyl tosylate as starting materials. 6-Chloro-3- (2-hydroxy-4-. {3 - [(3S) -3-methyl-piperidin-1-yl] -propoxy}. Phenyl] -2-methylpyrido [3,4-] d] pyrimidin-4- (3H) -one which was synthesized in Example 250. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.83-0.93 (4H, m), 1.53-1.74 (5H, m), 1.84-1.91 (1 H, m), 1.99-2.06 (2H, m), 2.27 (3H, s), 2.51 (2H, t, J = 7.3 Hz), 2.83-2.92 (2H, m), 4.07 (2H , t, J = 6.3 Hz), 4.10-4.34 (2H, m), 4.49-4.51 (1H, m), 4.63-4.61 (1H, m), 6.64 (1 H, d, J = 2.4 Hz), 6.67 (1H, dd, J = 8.8, 2.4 Hz), 7.09 (1 H, d, J = 8.8 Hz), 8.05 (1 H, s), 8.90 (1 H, s).

EXAMPLE 252 2-Ethyl-6-methoxy-3- (4 3-r (2S) -2-methylpyrrolidin-1-inpropoxy) phenyl) pyridine 3-4- "d1-pyrimidine ^ (3H) -one The title compound was obtained by the procedure according to Example 249, using 2-ethyl-6-methoxy-3- (4-hydroxyphenyl) pyrido [3,4-d] pyrimidine-4- (3H) -one and 3 - [(2S) -2-methylpyrrolidin-1-yl] propan-1-ol as starting materials. 2-Ethyl-6-methoxy-3- (4-hydroxyphenyl) pyrido [3,4-d] pyrimidin-4- (3H) -one was used which was synthesized in Example 198. 1 H NMR (400 MHz, CDCl 3 , d ppm): 1.11 (3H, d, J = 6.0 Hz), 1.23 (3H, t, J = 7.2 Hz), 1.40-1.50 (1 H, m), 1.60-2.37 (8H, m), 2.44 ( 2H, q, J = 7.2 Hz), 2.97-3.03 (1H, m), 3.18-3.23 (1H, m), 4.03 (3H, s), 4.07-4.11 (2H, m), 7.05 (2H, d, J = 9.2 Hz), 7.12 (2H, d, J = 9.2 Hz), 7.45 (1 H, s), 8.78 (1 H, s).

EXAMPLE 253 2-Ethyl-6-methoxy-3- (4- (3-r (3S) -3-methylpiperidin-1-ippropoxy) pheny1) pyrido3,4-d1-pyrimidine- (3H) -one hydrochloride The title compound was obtained by the procedure according to Example 249, using 2-ethyl-6-methoxy-3- (4-hydroxyphenyl) pyrido [3,4-d] pyrimidin-4- (3H) -one and 3 - [(3S) -3-methylpiperidin-1-yl] propan-1-ol as starting materials. 2-Ethyl-6-methoxy-3- (4-hydroxyphenyl) pyrido [3,4-d] pyrimidin-4- (3H) -one was used which was synthesized in Example 198. 1 H NMR (400 MHz ', CDCl 3, d ppm): 1.00 (3H, d, J = 6.8 Hz), 1.07-1.13 (1H, m), 1.22 (3H, t, J = 7.6 Hz), 1.82-1.98 (6H, m), 2.40- 2.54 (4H, m), 3.17-3.23 (2H, m), 3.47-3.65 (2H, m), 4.03 (3H, s), 4.16 (2H, t, J = 5.4 Hz), 7.02 (2H, d, J = 8.8 Hz), 7.15 (2H, d, J = 8.8 Hz), 7.44 (1 H, s), 8.79 (1H, s).

EXAMPLE 254 6-Methoxy-3- (2-methoxy-4-f3-r (3S) -3-methylpiperidin-1-inpropoxy) phenyl) -2-methylpyrido [3,4-d] pyrimidine- (3H) -one The title compound was obtained by the procedure according to Example 249, using 6-methoxy-3- (4-hydroxy-2-methoxyphenyl) -2-methylpyrido [3,4-d] pyrimidine-4- (3H) -one and 3 - [(3S) -3-methylpiperidin-1-yl] propan-1-ol as starting materials. 6-Methoxy-3- (4-hydroxy-2-methoxyphenyl) -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one was used which was synthesized in Example 203 (1). NMR from H (400 MHz, CDCl 3, d ppm): 0.82-0.93 (4H, m), 1.57-1.74 (5H, m), 1.84-1.91 (1H, m), 1.99-2.06 (2H, m), 2.20 (3H, s), 2.52 (2H, t, J = 7.3 Hz), 2.85-2.92 (2H, m), 3.76 (3H, s), 4.02 (3H, s), 4.07 (2H, t, J = 6.3 Hz), 6.59-6.62 (2H, m), 7.07 (1H, d, J = 8.8 Hz), 7.45 (1H, s), 8.75 (1 H, s).

EXAMPLE 255 6-Methoxy-2-methyl-3- (4- (3-f (3S) -3-methylpiperidin-1-yl] propoxy) phenyl) pyrido3,4-dlpyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 249, using 3- (4-hydroxy-phenyl) -6-methoxy-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one and - [(3S) -3-methylpiperidin-1-yl] propan-1-ol as starting materials. 3- (4-Hydroxyphenyl) -6-methoxy-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one was used which was synthesized in Example 197. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.86-0.91 (4H, m), 1.56-1.75 (5H, m), 1.85-1.93 (1H, m), 2.00-2.08 (2H, m), 2.24 (3H, s), 2.50-2.56 (2H, m), 2.85-2.95 (2H, m), 4.03 (3H, s), 4.07 (2H, t, J = 6.0 Hz), 7.05 (2H, d, J = 8.8 Hz), 7.14 (2H, d, J = 8.8 Hz), 7.45 (1 H, s), 8.75 (1 H, s).

EXAMPLE 256 6-Methoxy-2-methyl-3- (4- (3-r (2R) -2-methylpyrrolidin-1-inpropoxy) pheny1) pyrido3,4-d] pyrimidine-4- (3H) -one The title compound was obtained by the procedure according to Example 249, using 3- (4-hydroxyphenyl) -6-methoxy-2-methylpyrid [3,4-d] pyrimidine-4- (3H) -one and 3 - [(2R) -2-methylpyrrolidn-1-yl] propan-1-ol as starting materials. 3- (4-Hydroxyphenyl) -6-methoxy-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one was synthesized in Example 197. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.17 (3H, d, J = 4.9 Hz), 1. 47-2.50 (12H, m), 3.01-3.10 (1H, m), 3.23-3.31 (1H, m), 4.03 (3H, s), 4.12-4.08 (2H, m), 7.05 (2H, d) , J = 8.8 Hz), 7.14 (2H, d, J = 8.8 Hz), 7.45 (1 H, s), 8.75 (1 H, s).

EXAMPLE 257 2,5-Dimethyl-3-f4-. { 3-rf2R) -2-methylpyrrolidin-1-inpropoxy > phenol) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-6-methylbenzoic acid, acetic anhydride and monotosylate of 4-. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.13 (3H, d, J = 5.9 Hz), 1.42-1.51 (1H, m), 1.61-2.09 (5H, m), 2.17-2.54 (6H, m ), 2.82 (3H, s), 2.99- 3.04 (1H, m), 3.20-3.25 (1H, m), 4.05-4.11 (2H, m), 7.03-7.07 (2H, m), 7.13- 7.16 (2H) , m), 7.21 (1 H, d, J = 7.3 Hz), 7.50 (1 H, d, J = 7.8 Hz), 7.59 (1 H, t, J = 7. 8 Hz).

EXAMPLE 258 2-Methyl-3- (4-. {3-r (2R) -2-methylpyrrolidin-1-inpropoxy) phenyl) -5- (trifluoromethyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-6- (trifluoromethyl) benzoic acid, acetic anhydride and monotosylate of 4. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.14 (3H, d, J = 6.3 Hz), 1.42-1.51 (1H, m), 1.61-1.86 (2H, m), 1.91-2.10 (3H, m ), 2.15-2.43 (6H, m), 2.98-3.06 (1H, m), 3.20-3.25 (1H, m), 4.04-4.11 (2H, m), 7.03-7.06 (2H, m), 7.14- 7.18 (2H, m), 7.80 (1 H, t, J = 7.8 Hz), 7.86-7.89 (2H, m).

EXAMPLE 259 5-Chloro-2-methyl-3- (4- (3-r (2R) -2-methylpyrrolidin-1-inpropoxy) phenyl) -4-f3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-6-chlorobenzoic acid, acetic anhydride and monotosylate of 4. { 3 - [(2R) -2-methylpyrroline-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.13 (3H, d, J = 5.9 Hz), 1.41-1.51 (1 H, m), 1.59-2.08 (5H, m), 2.14-2.54 (6H, m), 2.99-3.04 (1 H, m), 3.20-3.25 (1H, m), 4.04-4.13 (2H, m), 7.03-7.06 (2H, m), 7.12-7.16 (2H, m), 7.45 (1 H, dd, J = 7.3, 1.5 Hz), 7.55-7.62 (2H, m).

EXAMPLE 260 5-Ftuoro-2-methyl-3- (4-. {3-p2R) -2-methylpyrrolidin-1-y? Propoxy phenyl) -4- (3H) -quinazolinone The title compound was synthesized as a white solid (p.p.: 125-127 ° C) by the procedure according to Example 165, using 2-amino-6-fluorobenzoic acid, acetic anhydride and monotosylate of 4-. { 3 - [(2R) -2-methylpyrrolidin-1-yl) propoxy] aniline as starting materials, followed by recrystallization (ethyl acetate / diethyl ether). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.13 (3 H, d, J = 6.3 Hz), 1. 41-1.51 (1 H, m), 1.60-1.85 (2H, m), 1.91-2.09 (3H, m), 2.14-2.54 (6H, m), 2.99-3.06 (1 H, m), 3.20-3.25 (1H, m), 4.05-4.13 (2H, m), 7.03-7.15 (6H, m), 7.46 (1H, d, J = 8.3 Hz), 7.65-7.70 (1H, m).

EXAMPLE 261 6-Fluoro-2-methyl-3-f4-f3-rf2R) -2-methylpyrrolidin-1-npropoxy pheny1) -4-f3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-5-fluorobenzoic acid, acetic anhydride and monotosylate of 4-. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.13 (3H, d, J = 5.9 Hz), 1.42-1.51 (1H, m), 1.59-1.86 (2H, m), 1.91-2.09 (3H, m ), 2.15-2.54 (6H, m), 2.99-3.06 (1H, m), 3.20-3.25 (1H, m), 4.06-4.12 (2H, m), 7.04-7.07 (2H, m), 7.13- 7.16 (2H, m), 7.45-7.50 (1H, m), 7.66-7.69 (1H, m), 7.88-7.91 (1H, m).

EXAMPLE 262 7-Fluoro-2-methyl-3- (4-. {3-r (2R) -2-methylpyrrolidin-1-inpropoxy > fenin-4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-4-fluorobenzoic acid, acetic anhydride and monotosylate of 4-. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.15 (3H, d, J = 5.9 Hz), 1.44-1.53 (1 H, m), 1.60-1.87 (2H, m), 1.92-2.11 (3H, m), 2.20-2.56 (6H, m), 3.01-3.08 (1H, m), 3.23-3.27 (1H, m), 4.06-4.14 (2H, m), 7.04-7.07 (2H, m), 7.13 -7.20 (3H, m), 7.31 (1H, dd, J = 9.3, 2.4 Hz), 8.27 (1H, dd, J = 8.8, 6.3 Hz).

EXAMPLE 263 8-Fluoro-2-methyl-3- (4- (3-r (2R) -2-methylpyrrolidin-1-npropoxy> phenol) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-3-fluorobenzoic acid, acetic anhydride and monotosylate of 4-. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.16 (3H, d, J = 6.3 Hz), 1.44-1.54 (1 H, m), 1.62-1.85 (2H, m), 1.93-2.12 (3H, m), 2.21-2.41 (6H, m), 3. 01-3.08 (1 H, m), 3.23-3.28 (1H, m), 4.06-4.14 (2H, m), 7.05-7.08 (2H, m), 7. 13-7.17 (2H, m), 7.37-7.42 (1H, m), 7.47-7.51 (1H, m), 8.05 (1H, d, J = 7.8 Hz).

EXAMPLE 264 2,6-D-methyl-3-f4- (3-r (2R) -2-methylpyrrolidin-1-ippropoxy phenyl) -4- (3H) -quinazolinone The title compound was obtained by the procedure according to Example 165, using 2-amino-5-methylbenzoic acid, acetic anhydride and monotosylate of 4. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.15 (3H, d, J = 6.3 Hz), 1.47-1.53 (1 H, m), 1.62-1.84 (2H, m), 1.92-2.11 (3H, m), 2.20-2.54 (9H, m), 3.01-3.08 (1H, m), 3.23-3.27 (1H, m), 4.06-4.12 (2H, m), 7.03-7.06 (2H, m), 7.13-7.16 (2H, m), 7.57-7.57 (2H, m), 8.05 (1H, s).

EXAMPLE 265 2-Methyl-3- (4 3-r (2R) -2-methylpyrrolidin-1-inpropoxy) phenyl) pyrimidor-2,3-d] pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 165, using 2-aminonicotinic acid, acetic anhydride and monotosylate of 4-. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.15 (3H, d, J = 6.3 Hz), 1.44-1.53 (1H, m), 1.63-1.87 (2H, m), 1.92-2.11 (3H, m ), 2.18-2.40 (6H, m), 3.01-3.08 (1H, m), 3.22-3.27 (1H, m), 4.06-4.14 (2H, m), 7.05-7.08 (2H, m), 7.14 -7.17 (2H, m), 7.40-7.43 (1H, m), 8.59 (1H, dd, J = 7.8, 2.0 Hz), 8.98-8.99 (1H, m).

EXAMPLE 266 2-Methyl-3- (4- { 3-r (2R) -2-methylpyrrolidin-1-inpropoxy> phenyl) pyrido 4,3-d1-pyrimidin-4- (3H) -one The title compound was synthesized as a light yellow solid (m.p .: 238-250 ° C) by the procedure according to Example 165, using 4-aminonicotinic acid, acetic anhydride and monotosylate of 4-. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy] aniline as starting materials, followed by recrystallization (ethyl acetate / diethyl ether / n-heptane). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.14 (3 H, d, J = 6.3 Hz), 1. 42-1.51 (1 H, m), 1.61-1.85 (2H, m), 1.91-2.10 (3H, m), 2.15-2.38 (6H, m), 3.00-3.07 (1 H, m), 3.21-3.25 (1 H, m), 4.08-4.12 (2H, m), 7.05-7.09 (2H, m), 7.13-7.16 (2H, m), 7.48-7.50 (1H, m), 8.85 (1H, d, J = 5.9 Hz), 9.47 (1 H, d, J = 1.0 Hz).

EXAMPLE 267 2-Methyl-3- (4- 3-r (2R) -2-methylpyrrolidin-1-inpropoxy) phenoliphenyl 3-4-dlpyrimidin-4- (3H) -one (1) Preparation of 6-chloro-2-methyl-3- (4- (3-f (2R) -2-methylpyrrolidin-1-npropoxy) phenyl] pyrido [3,4-dlpyrimidin-4] - (3H) -one The target compound was obtained by the procedure according to Example 165, using 5-amino-2-chloroisonicotinic acid, acetic anhydride and monotosylate of 4-. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. (2) Preparation of 2-methyl-3- (4-. {3-f (2R) -2-methylpyrrolidin-1-illpropoxylphenyl) pyrid [3,4-dlpyrimidin-4- (3H) -one The The title compound was obtained by dissolving 6-chloro-2-methyl-3- (4-. {3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy, phenyl) [3,4-d] pyrimidin-4- (3H) -one in ethyl acetate, and performing the catalytic reduction with a palladium on activated carbon catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.11 (3H, d, J = 5.9 Hz), 1. 39-1.48 (1 H, m), 1.59-1.85 (2H, m), 1.89-2.08 (3H, m), 2.10-2.41 (6H, m), 2.97-3.04 (1 H, m), 3.17-3.22 (1 H, m), 4.08-4.12 (2H, m), 7.06-7.09 (2H, m), 7.13-7.16 (2H, m), 8.03 (1 H, dd, J = 5.4.1.0 Hz), 8.67 (1 H, d, J = 5.4 Hz), 9.12 (1 H, d, J = 1.0 Hz).

EXAMPLE 268 2-Methyl-3- [4- (3-piperidin-1-ylpropoxy) feninpyridof3,2-dlpyrimidin-4- (3H) -one (1) Preparation of 3-nitropyridine-2-carboxylic acid This was prepared by the procedure described in the literature (Tetrahedron, 1998, Vol. 54, page 6311; and J. Am. Chem. Soc, 1954, Vol. 76, page 3167) using 2-chloro-3-nitropyridine as starting material. (2) Preparation of 3-aminopyridine-2-carboxylic acid 3-Nitropyridine-2-carboxylic acid (2.72 g, 16.2 molimoles) and sodium hydrogencarbonate (1.34 g, 16.2 molimoles) were dissolved in distilled water (20 ml), and the atmosphere of the system was replaced by nitrogen. After adding 10% palladium on activated carbon (1.72 g), the atmosphere of the system was replaced by hydrogen, and the mixture was stirred at room temperature for 50 hours. Aqueous 1 N hydrochloric acid solution was added, and the pH of the reaction solution was adjusted to slightly acidic. The solvent was removed by distillation under reduced pressure, a small amount of ethanol and ethyl acetate was added to the residue, and the precipitate that was produced was removed by filtration. The filtrate was concentrated, and thus the target substance (1.50 g, 67%) was obtained as a light yellow solid. (3) Preparation of 2-methy1-3- [4- (3-p1perdin-1-yl-propox-pheny1n-pyrido [3,2-d] pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 165, using 3-aminopyridine-2-carboxylic acid, acetic anhydride and 4- (3-piperidin-1-yl-propoxy) aniline monotosylate as starting materials. 1 H (400 MHz, CDCl 3, d ppm): 1.49-1.43 (2H, m), 1.58-1.63 (4H, m), 2.02 (2H, dt, J = 14.6.6.3 Hz), 2.27 (3H, s) , 2.37-2.45 (4H, m), 2.50 (2H, t, J = 7.6 Hz), 4.07 (2H, t, J = 6.3 Hz), 7.06 (2H, td, J = 2.4, 9.3 Hz), 7.17 ( 2H, td, J = 2.4, 9.3 Hz), 7.68 (1 H, dd, J = 8.3, 4.4 Hz), 8.01 (1 H, dd, J = 8.3, 1.5 Hz), 8.86 (1 H, dd, J = 4.4, 1.5 Hz).

EXAMPLE 269 2-Methyl-3- (4-f3-rf2R) -2-methylpyrrolidin-1-inpropoxy > phenyl) pyrido3,2- d1pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 165, using 3-aminopyridine-2-carboxylic acid, acetic anhydride and monotosylate of 4-. { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy} aniline as initial materials. 3-Aminopyridine-2-carboxylic acid was used which was synthesized in Example 268. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.13 (3 H, d, J = 5.9 Hz), 1. 51-1.42 (1 H, m), 1.68-1.87 (2H, m), 1.93-2.00 (1 H, m), 2.01-2.10 (2H, m), 2.16-2.30 (4H, m), 2.27 (3H , s), 2.32-2.42 (1 H, m), 3.03 (1 H, dt, J = 12.2, 7.8 Hz), 3.23 (1 H, td, J = 8.3, 2.9 Hz), 4.09 (2H, td, J = 5.9, 2.4 Hz), 7.06 (2H, d, J = 8.8 Hz), 7.17 (2H, d, J = 8.8 Hz), 7.68 (1 H, dd, J = 8.3, 4.4 Hz), 8.01 (1 H, dd, J = 8.3, 1.5 Hz), 8.86 (1 H, dd, J = 4.4, 1.5 Hz).

EXAMPLE 270 2-Methyl-3- [4- (3-pyrrolidin-1-ylpropoxy) phenyl] pyrido3,2-d] pyrimidine-4- (3H) -one The title compound was obtained by the procedure according to Example 165, using 3-aminopyridine-2-carboxylic acid, acetic anhydride and 4- (3-pyrrolidin-1-ylpropoxy) aniline as starting mater. 3-Aminopyridine-2-carboxylic acid was used which was synthesized in Example 268. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.79-1.86 (4H, m), 2.03-2.10 (2H, m), 2.27. (3H, s), 2.56-2.62 (4H, m), 2.69 (2H, t, J = 7.3 Hz), 4.09 (2H, t, J = 6.3 Hz), 7.06 (2H, td, J = 2.4, 8.8 Hz), 7.17 (2H, td, J = 2.4, 8.8 Hz), 7. 68 (1 H, dd, J = 8.3, 4.4 Hz), 8.01 (1 H, dd, J = 8.3,1.5 Hz), 8.85 (1 H, dd, J = 4. 4, 1.5 Hz).

EXAMPLE 271 2-Methyl-3- (4- (3-r (3S) -3-methyl-piperidin-1-ippropoxy-phenypyripyr3,2-dlpyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 165, using 3-aminopyridine-2-carboxylic acid, acetic anhydride and monotosylate of 4-. { 3 - [(3S) -3-methylpiperidin-1-yl] propoxy} aniline as initmater. 3-Aminopyridine-2-carboxylic acid was used which was synthesized in Example 268. 1 H NMR (400 MHz, CDCl 3, d ppm): 0.94-0.82 (1 H, m), 0.88 (3 H, d, J = 6.8 Hz), 1.57-1.74 (5H, m), 1.89 (1H, td, J = 11.2, 2.9 Hz), 2.04 (2H, q, J = 6.3 Hz), 2.27 (3H, s), 2.53 (2H, t, J = 7.6 Hz), 2.86-2.93 (2H, m), 4.07 ( 2H, t, J = 6.3 Hz), 7.05 (2H, d, J = 8.8 Hz), 7.17 (2H, d, J = 8.8 Hz), 7.67 (1 H, dd, J = 8.3, 4.4 Hz), 8.00 (1 H, dd, J = 8.3, 1.5 Hz), 8.84 (1 H, dd, J = 4.4, 1.5 Hz).

EXAMPLE 272 3-l4-r (1-Cyclobutylpiperidin-4-yl) oxphenyl) -2-methylpyridof3,2-dlpyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 165, using 3-aminopyridine-2-carboxylic acid, acetic anhydride and 4 - [(1-cyclobutylpiperidin-4-yl) oxy] aniline monotosylate as starting mater. 3-Aminopyridine-2-carboxylic acid was used which was synthesized in Example 268. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.67-1.74 (2H, m), 1.96-1.84 (4H, m), 2.03 -2.10 (4H, m), 2.17-2.25 (2H, m), 2.27 (3H, s), 2.59-2.71 (2H, m), 2.73-2.79 (1H, m), 4.36-4.42 (1H, m) , 7.05 (2H, td, J = 2.0, 8.8 Hz), 7.17 (2H, td, J = 2.0, 8.8 Hz), 7.67 (1H, dd, J = 8.3, 4.4 Hz), 8.00 (1H, dd, J = 8.3, 1.5 Hz), 8.84 (1H, dd, J = 4.4, 1.5 Hz).

EXAMPLE 273 3-4-r (1-Cyclobutyl-piperidin-4-yl) oxphenyl} -2-ethylpyrido [3,2-d] pyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 165, using 3-aminopyridine-2-carboxylic acid, propionic anhydride and 4 - [(1-cyclobutylpiperidin-4-yl) oxy] aniline monotosylate as mater init. 3-Aminopyridine-2-carboxylic acid was used which was synthesized in Example 268. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.22 (3H, t, J = 7.3 Hz), 1. 64-1.76 (2H, m), 1.84-1.95 (4H, m), 2.00-2.10 (4H, m), 2.15-2.23 (2H, m), 2.46 (2H, q, J = 7.3 Hz), 2.60- 2.69 (2H, m), 2.73-2.79 (1 H, m), 4.34-4.42 (1 H, m), 7.04 (2H, d, J = 8.8 Hz), 7.15 (2H, d, J = 8.8 Hz) , 7.67 (1 H, dd, J = 8.3, 4.4 Hz), 8.05 (1 H, dd, J = 8.3, 1.5 Hz), 8.85 (1 H, dd, J = 4.4, 1.5 Hz).

EXAMPLE 274 3-r4- (3-Azepan-1-ylpropoxy) phenan-2-methylpyridr3,4-d1-pyrimidin-4- (3H) -one (1) Preparation of 3-f4- (3-azepan-1-ylpropoxy) phenyl] -6-chloro-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one The target compound was obtained by the process according to Example 165, using 5-amino-2-chloroison-trinic acid, acetic anhydride and 4- (3-azepan-1-ylpropoxy) aniline as starting mater. (2) Preparation of 3- [4- (3-azepan-1-lpropoxy) phen.p-6-chloro-2-methylpyrido [3,4-d1-pyrimidin-4- (3H) -one The title compound was obtained by catalytic reduction of 3- [4- (3-azepan-1-yl-propoxy) phenyl] -6-chloro-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one in acetate of ethyl using a palladium on activated carbon catalyst in the presence of triethylamine. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.64-1.73 (8H, m), 2.08-2.10 (2H, m), 2.30 (3H, s), 2.77-2.79 (6H, m), 4.11 (2H , t, J = 6.1 Hz), 7.07 (2H, d, J = 9.5 Hz), 7.15 (2H, d, J = 11.7 Hz), 8.03 (1 H, dd, J = 5.4, 1.0 Hz), 8.68 ( 1 H, d, J = 4.9 Hz), 9.13 (1 H, s).

EXAMPLE 275 3- [4- (3-Azepan-1-ylpropoxy) fenip-6-methoxy-2-methylpyridr3,4-dlpyrimidin-4- (3H) -one The title compound was obtained by the procedure according to Example 249, using 3- (4-hydroxyphenyl) -6-methoxy-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one and - (azepan-1-yl) propan-1-ol as starting materials. 3- (4-Hydroxyphenyl) -6-methoxy-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one was synthesized in Example 268. 1 H NMR (400 MHz, CDCl 3 , d ppm): 1.63-1.69 (8H, m), 2.01-2.04 (2H, m), 2.24 (3H, s), 2.71-2.74 (6H, m), 4.03 (3H, s), 4.09 (2H, t, J = 6.1 Hz), 7.05 (2H, d, J = 8.8 Hz), 7.14 (2H, d, J = 6.6 Hz), 7.45 (1 H, d, J = 1.0 Hz), 8.76 (1H, s ).

EXAMPLE 276 3-f4- (3-Azepan-1-ylpropoxy) phenan-2-methylpyridr3,4-d1-pyrimidin-4- (3H) -one The target compound was obtained by the procedure according to Example 165, using 2-aminonicotinic acid, acetic anhydride and 4- (3-azepan-1-ylpropoxy) aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.62-1.65 (8H, m), 1.95-2.02 (2H, m), 2.35 (3H, s), 2.65-2.69 (6H, m), 4.09 (2H , t, J = 6.3 Hz), 7.07 (2H, d, J = 11.7 Hz), 7.15 (2H, d, J = 12.2 Hz), 7.42 (1 H, dd, J = 7.8, 4.9 Hz), 8.59 ( 1 H, dd, J = 7.8, 2.0 Hz), 8.99 (1 H, q, J = 2.3 Hz).

EXAMPLE 277 5-Fluoro-2-methyl-3-f4- (3-pyrrolidin-1-ylbutoxy) phenin-4- (3H) -quinazolinone (racemic mixture) (1) Preparation of 4- (3-pyrrolidin-1-ylbutoxy) aniline (racemic mixture) The target compound was obtained by the procedure according to Example 18, using 3-pyrrolidin-1-ylbutan-1-ol (mixture racemic) and 4-nitrofluorobenzene as starting materials. 3-Pyrrolidin-1-ylbutan-1-ol (racemic mixture) was prepared by the procedure described in the literature (J. Org. Chem., 1949, Vol. 14, page 862). 1 H NMR (400 MHz, CDCl 3, d ppm): 1.14 (3H, d, J = 6.3 Hz), 1.82-1.65 (5H, m), 2.10 (1 H, m), 2.61-2.53 (5H, m) , 3.41 (1H, brs), 3.97 (2H, m), 6.64 (2H, d, J = 9.0 Hz), 6.75 (2H, d, J = 9.0 Hz). (2) Preparation of 5-fluoro-2-methyl-3- [4- (3-pyrrolidin-1-ylbutoxy) phenyl] -4- (3H) -quinazolinone (racemic mixture) The title compound was obtained by the procedure according to Example 18, using 2-amino-6-fluorobenzoic acid, acetic anhydride and 4- (3-pyrrolidin-1-ylbutoxy) aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.17 (3 H, d, J = 6.8 Hz), 1.79 (4 H, m), 1.88 (1 H, m), 2.15 (1 H, m), 2.24 ( 3H, s), 2.61 (5H, m), 4.10 (2H, m), 7.05 (2H, d, J = 9.0 Hz), 7.08 (1H, m), 7.14 (2H, d, J = 9.0 Hz), 7.46 (1 H, d, J = 8.3 Hz), 7.68 (1 H, m).

EXAMPLE 278 2-Met l-3-r4- (3-pyrrolidin-1-ylbutoxy) phenn-5- (trifluoromethyl) -4- (3H) -quinazolinone (racemic mixture) The title compound was obtained by the procedure according to Example 18, using 2-amino-6- (trifluoromethyl) benzoic acid, acetic anhydride and 4- (3-pyrrolidin-1-ylbutoxy) aniline as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.17 (3 H, d, J = 6.8 Hz), 1.80 (4 H, m), 1.88 (1 H, m), 2.15 (1 H, m), 2.27 ( 3H, s), 4.09 (2H, m), 2.62 (5H, m), 7.05 (2H, d, J = 9.0 Hz), 7.16 (2H, d, J = 9.0 Hz), 7.80 (1 H, t, J = 7.8 Hz), 7.87 (1 H, d, J = 7.8 Hz), 7.88 (1 H, d, J = 7.8 Hz).

EXAMPLE 279 2,5-Dimethyl-3- [4- (3-pyrrolidin-1-ylbutoxy) phenyl] -4- (3H) -quinazolinone (racemic mixture) The title compound was obtained by the procedure according to Example 18, using 2-amino-6-methylbenzoic acid, acetic anhydride and 4- (3-pyrrolidin-1-ylbutoxy) aniolin as starting materials. 1 H NMR (400 MHz, CDCl 3, d ppm): 1.17 (3 H, d, J = 6.3 Hz), 1.80 (4 H, m), 1.88 (1 H, m), 2.15 (1 H, m), 2.22 ( 3H, s), 2.62 (5H, m), 2.82 (3H, s), 4.09 (2H, m), 7.05 (2H, d, J = 8.8 Hz), 7.15 (2H, d, J = 8.8 Hz), 7.21 (1 H, d, J = 7.6 Hz), 7.50 (1 H, d, J = 7.6 Hz), 7.59 (1 H, t, J = 7.6 Hz). Below are examples of pharmacological tests, in which 2-ethyl-3- was used. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone (the compound of Example 1) as the test compound.

EXAMPLE 1 OF PHARMACOLOGICAL TEST Histamine analogue coupling inhibition test A cDNA sequence [specification of international patent publication WO 00/39164] which encodes the human histamine H3 receptor was cloned using the expression vectors pCR2.1, pEF1x (product of Invitrogen), and pCI-neo (product from Promega Inc.). The expression vector obtained was used to transfect the host cells, HEK293 and CHO-K1 (American type culture collection), using the cationic lipid process [Proceedings of the National Academy of Sciences of the United States of America, Vol. 84, page 7413 (1987), and thus cells expressing the histamine H3 receptor were obtained. A preparation made from membranes of the cells exhibiting the histamine H3 receptor, the test compound (the compound of Example 1) and 20,000 cpm of [3 H] Na-methyl-ishstamine (NEN product) was incubated in a solution of Assay buffer (50 mM Tris buffer solution, at pH 7.4) at 25 ° C for 2 hours, and filtered with a GF / C glass filter. After washing with 50 mM Tris buffer at pH 7.4, the radioactivity of the crystal filter was found. The non-specific bonds were measured in the presence of 10 μM thioperamide (product of SIGMA), and the concentration of 50% inhibition (CI value or) of the test compound was found with respect to the specific Na-methylhistamine bonds (Molecular Pharmacology , Vol. 55, page 1101 (1999)). As resolved, the Cl50 value of the test compound was 15 nM. As described above, the compound of Example 1 potently prevented the binding of N-α-methylhistamine to the histamine H 3 receptor (histamine analog).

EXAMPLE 2 PHARMACOLOGICAL TEST Behavior antagonism test of beverage intake induced by R-α-methylhistamine, a selective histamine H3 receptor agonist With ketamine / xylazine-induced anesthesia (74 mg / kg and 11 mg / kg, intraperitoneal administration, single dose), a prolonged guide cannula (caliber 26, length 11 mm) was inserted into the ventriculus tertius of a male SD rat ( 7-10 weeks of age, 200-300 g) using an apparatus for cerebral stereotaxy and fixed by dental resin. The position of the tip of the guide cannula was 2.2 mm behind the temporal, and at a depth of 8 mm from the surface of the skull in the midline. After approximately 1 week of convalescence, R-α-methylhistamine (0.3 μg / 1 μl / head, 30% in propylene glycol solution) was administered to the ventriculus tertius. The test compound (the compound of Example 1) suspended in 0.5% aqueous solution of methylcellulose was orally administered 2 hours before the administration of Ra-methylhistamine, and the amount of water drunk 1 hour after administration was measured. of Ra-methylhistamine. As a result, the test compound (10 mg / kg) significantly suppressed the increase in drinking water due to the R-α-methylhistamine administered to the ventriculus tertius.

EXAMPLE 3 PHARMACOLOGICAL TEST In vivo kinetic test) The test compound (the compound of Example 1) was administered orally or intravenously to male SD-type rats (7-10 weeks of age, 200-400 g) that had abstained from eating overnight, and were harvested approximately 100 μl of blood from a caudal vein using a heparinized capillary tube at a predetermined time. The blood was centrifuged (4 ° C, 6000 rpm, 10 minutes), and plasma was obtained. The amount of ethanol (containing an internal reference) was added three times to the plasma, stirred, left for 20 minutes at -20 ° C, and centrifuged (4 ° C, 10,000 rpm, 10 minutes). The supernatant was analyzed by LC / MS / MS, and the concentration in plasma was measured by the relative calibration curve procedure. As a result, the test compound showed a bioavailability of 60%, and a half-life of 6.3 hours in blood.

EXAMPLE 4 PHARMACOLOGICAL TEST Activity test in brain and cerebrospinal fluid) The test compound (the compound of Example 1) was administered orally or intravenously to male SD-type rats (7-10 weeks of age, 200-400 g), and bleeding was performed through the abdominal aorta with ether anesthesia using a heparin treatment syringe at a predetermined time. The skin was cut from the back of the head, pierced with a 30G dental needle between the cervical vertebrae, and inserted into the subarachnoid space. 50-100 μl of cerebrospinal fluid was removed by a 1 ml syringe through a tube connected to the 30G needle, and the brain was removed. A blood sample was centrifuged (4 ° C, 6000 rpm, 10 minutes), and the amount of ethanol (containing an internal reference) was added three times to the plasma and stirred. 2 ml of water was added to a brain sample, homogenized, a part was removed, and the amount of ethanol (containing an internal reference) was added three times and stirred. The cerebrospinal fluid was taken, the amount of ethanol (which contained an internal reference) was added three times, and stirred. The previous sample was left at -20 ° C for 20 minutes, centrifuged (4 ° C, 12,000 g, 10 minutes), the supernatant liquid was analyzed by LC / MS / MS, and the concentration in plasma, brain and blood was measured. cerebrospinal fluid by the relative calibration curve procedure. As a result, the test compound had an intracerebral concentration of 3.16 nmol / g, a cerebrospinal fluid concentration of 0.142 μM, and a plasma concentration of 2.32 μM 2 hours after oral administration (10 mg / kg).

INDUSTRIAL APPLICABILITY The novel fused-ring 4-oxopyrimidine derivative represented by the formula (I), or a pharmaceutically acceptable salt thereof, has a potent activity as an antagonist or inverse agonist of histamine, and is therefore useful in the prophylaxis or treatment of metabolic diseases such as obesity, diabetes mellitus, hormonal secretion disorders, hyperlipidemia, gout and fatty liver; circulatory diseases such as angina pectoris, acute or congestive heart failure, myocardial infarction, annular atherosclerosis, hypertension, kidney disease and electrolyte imbalance; or central or peripheral nervous system diseases such as sleep disorders or diseases accompanied by sleep disorders (eg, idiopathic hypersomnia, recurrent hypersomnia, intrinsic hypersomnia, narcolepsy, periodic limb movement during sleep, sleep apnea syndrome, impairment for the circadian rhythm, chronic fatigue syndrome, impairment of REM sleep, loss of sleep in the elderly, insalubrity of sleep in night shift workers, idiopathic insomnia, recurrent insomnia, intrinsic insomnia, depression, insecurity and schizophrenia), bulimia, emotional disorders, epilepsy, delirium, dementia, attention deficit hyperactivity disorder, memory impairment, Alzheimer's disease, Parkinson's disease, cognitive disorder, movement disorder, dysesthesia, dysosmia, morphine resistance, dependence on narcotics, alcohol dependence and tremor.

Claims

NOVELTY OF THE INVENTION CLAIMS 1. - A compound represented by the formula (I): (i) where Ar is a divalent group that is formed by removing two hydrogen atoms from benzene, pyrimidine, pyridine, thiazole, oxazole, pyrazole, thiadiazole or thiophene (this divalent group may also be substituted by a halogen atom, lower alkoxy ( this lower alkoxy group can be further substituted by halogen), hydroxy or lower alkyl); X1 is a nitrogen atom, sulfur atom or oxygen atom; R1 is a 5- or 6-membered heteroaryl group having 1 to 4 heteroatoms which are selected from nitrogen, sulfur and oxygen, heteroarylalkyl group (heteroaryl in this group has the same meaning as above), straight or branched chain lower alkyl (this lower alkyl group may be further substituted by hydroxy, halogen, alkoxy, allyloxy or aralkyloxy), phenyl, aralkyl, alkoxy, alkylthio or (lower alkyl) amine; Ring A is a 5- or 6-membered heteroaryl ring having 1 or 2 nitrogen atoms or sulfur atoms in the ring, or a benzene ring; R2 and R3 may be the same or different, and each represents hydrogen, amino, alkylamino, dialkylamino, nitro, cyano, hydroxy, (lower alkyl) sulfonyl, halogen, lower alkyl (this lower alkyl group may also be substituted by halogen), lower cycloalkyl (this lower cycloalkyl group can be further substituted by halogen), lower alkoxy (this lower alkoxy group can be further substituted by halogen or hydroxy), lower cycloalkoxy (this lower cycloalkoxy group can be further substituted by halogen), aryloxy, aralkyloxy , heteroaryloxy, heteroarylalkyloxy, aryl, heteroaryl, arylcarbamoyl, heteroarylcarbamoyl, arylalkylcarbamoyl, heteroarylalkylcarbamoyl, mono (lower alkyl) carbamoyl, di (lower alkyl) carbamoyl, (lower alkyl) carboxamide, arylcarboxamide, heteroarylcarboxamide, arylalkylcarboxamide, heteroarylalkylcarboxamide, alkanoyl, arylcarbonyl, arylalkylcarbonyl , formyl, hydroxy, alkylthio, alkoxycarbonylamino, (lower alkyl) sulfonylamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, aralkyl, alkanoylamino or alkanoylalkylamino; And it is CH or a nitrogen atom; -X2 is a group represented by the formula (II): (II) (wherein R4 and R5 may be the same or different, and each is a lower alkyl group (this lower alkyl group may be further substituted by halogen) or a cycloalkyl group, or R4, R5 and a nitrogen atom together form a 5 to 8 membered monocyclic ring (this monocyclic ring may be substituted by a halogen atom, an oxo group, or a lower alkyl group which in turn may be substituted by halogen), or a bicyclic ring of from 6 to 10 members , n is an integer from 2 to 4, and (CH2) n can be substituted by a lower alkyl group having 1 to 3 carbon atoms), by the formula (III): (l l l) (where m is an integer from 0 to 4, and R6 is an alkyl or lower cycloalkyl group), or by formula (IV): (where the symbols have the same meaning as above), with the proviso that formula (I) excludes 3- [4- (2-diethylaminoethoxy) phenyl] -2-methyl-3H-quinazolin-4-one, 3 - [4- (2-dimethylamino-ethoxy) phenyl] -2-methyl-3H-quinazolin-4-one, 2-methyl-3- [4- (2-piperidin-1-yl-ethoxy) phenyl] -3H-quinozolin-4-one, 3- [4- (3-dimethylamidopropoxy) phenyl] -2-methyl-3H-quinazolin-4-one, 3- [4- (3-diethylaminopropoxy) phenyl] -2-methyl-3H-quinazolin-4-one and 3- [2- (2-diethylaminoethoxy) phenyl] -2-methyl-3H-quinazoln-4-one], or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1, further characterized in that ring A is a benzene ring, pyridine ring or pyrimidine ring, or a pharmaceutically acceptable salt thereof.
3. The compound according to claim 1, further characterized in that ring A is a benzene ring or a pyridine ring, or a pharmaceutically acceptable salt thereof.
4. The compound according to claim 1-3, further characterized in that at least one of R2 and R3 is a hydrogen atom, or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 1-3, further characterized in that one of R2 and R3 is a hydrogen atom, and the other is a hydrogen atom, a halogen atom, lower alkyl (this lower alkyl group can further substituted by halogen), lower alkoxy (this lower alkoxy group may be further substituted by halogen or hydroxy), hydroxy, aryl (this aryl group may be further substituted by lower alkyl), heteroaryl, (lower alkyl) carboxamide , arylcarboxamide, arylalkylcarboxamide or (lower alkyl) sulfonylamino, or a pharmaceutically acceptable salt thereof.
6. The compound according to claim 1-3, further characterized in that one of R2 and R3 is a hydrogen atom, and the other is a hydrogen atom, a halogen atom, lower alkyl (this lower alkyl group can further substituted by halogen), or lower alkoxy (this lower alkoxy group may further be substituted by halogen), or a pharmaceutically acceptable salt thereof.
7. The compound according to claim 1-6, further characterized in that Ar is a divalent group that is formed by removing two hydrogen atoms from benzene or pyrimidine (this divalent group can be further substituted by a halogen atom, lower alkoxy (this lower alkoxy group can be further substituted by halogen), hydroxy or lower alkyl), and n is 3 or 4, or a pharmaceutically acceptable salt thereof.
8. The compound according to claim 1-7, further characterized in that -X2 is represented by the formula (II): R5 - (CH2) - N R4 (ID [where the symbols have the same meaning as the above], or a pharmaceutically acceptable salt thereof 9. The compound according to claim 8, further characterized in that n is 3 or 4, and R4, R5 and a nitrogen atom together form a 5- to 8-membered monocyclic ring (this monocyclic ring may have a halogen atom as a substituent group, or a "lower alkyl group which may be substituted by halogen), or a pharmaceutically acceptable salt thereof. 10. The compound according to claim 8, further characterized in that n is 3 or 4, and R4, R5 and a nitrogen atom together form a bicyclic ring of 6 to 10 members, or a pharmaceutically acceptable salt thereof. 11. The compound according to claim 8, further characterized in that n is 3, and R4, R5 and a nitrogen atom together form a 5- to 8-membered monocyclic ring (this monocyclic ring may have a carbon atom as the substituent group). halogen, or a lower alkyl group which may be substituted by halogen), or a pharmaceutically acceptable salt thereof. 12. The compound according to claim 8, further characterized in that n is 3, and R4, R5 and a nitrogen atom together form a bicyclic ring of 6 to 10 members, or a pharmaceutically acceptable salt thereof. 13. The compound according to claim 1-7, further characterized in that -X2 is represented by the formula (III): (I I I) [where the symbols have the same meaning as the previous ones], or a pharmaceutically acceptable salt thereof. 14. The compound according to claim 1-7, further characterized in that -X2 is represented by the formula (IV): [where the symbols have the same meaning as the above], or a pharmaceutically acceptable salt thereof. 15. The compound according to claim 1-14, further characterized in that R1 is a lower alkyl group having 1 to 3 carbon atoms (this lower alkyl group may further be substituted by halogen), or a phenyl group, or a pharmaceutically acceptable salt thereof. 16. The compound according to claim 1-14, further characterized in that R1 is methyl, ethyl, n-propyl, isopropyl or trifluoromethyl, or a pharmaceutically acceptable salt thereof. 17. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is: 2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenol} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-pperidinyl) propoxy] phenyl} -4- (3H) -quinazolnone, 2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 4- [3- (diethylamino) propoxy] phenyl} -2-methyl-4- (3H) -quinazoinone, 2-methyl-3-. { 4- [3- (2-methyl-1-pyrrolidinyl) -propoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 4- [3- (2,5-dimethyl-1-pyrrolidinyl) propoxy] phenol} -2-methyl-4- (3H) -quinazolinone, 2-methyl-3-. { 4- [4- (1-piperidinyl) butoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 4- [3- (1- azepanyl) propoxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- [3- (1-Azocanil) propoxy] -phenyl} -2-methyl-4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (2-methyl-1-piperidinium) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (4-methyl-1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 3- (4- { 3 - [(2R, 6S) -2,6-dimethyl-1-piperidinyl] propoxy.} Phenyl) -2-methyl-4- ( 3H) -quinazolinone, 2-methyl-3-. { 4- [3- (3-methyl-1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 4- [3- (3,5-dimethyl-1-piperidinyl) propoxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 2-methyl-3-. { 3- [3- (1-p.peridinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 3-bromo-4- [3- (1-piperidinyl) propoxy] phenyl} -2-ethyl-4- (3H) -quinazolinone, 2-methyl-3-. { 4- [2- (1-piperidinyl) ethoxy] phenol} -4- (3H) -quinazolinone, 2,5-dimethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -2-propyl-4- (3H) -quinazolinone, 3-. { 4- [3- (1-piperidinyl) propoxy] phenol} -2-trifluoromethyl-4- (3H) -quinnanolinone, 2-isopropyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolnone, 2,6-dimethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7-cioro-2-metiI-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2,8-dimethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-ethyl-5-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenol} -4- (3H) -quinazolinone, 5-fluoro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-chloro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-hydroxy-2-methyl-3-trifluoroacetate. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -5-trifluoromethyl-4- (3H) -quinazolinone, 7- fluoro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6-fluoro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6,7-difluoro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6-bromo-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6-chloro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6,7-dimethoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 8-chloro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolnone, 8-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2,6-dimethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-ethyl-5-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 5-fluoro-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinonazolnone, 2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -5-trifluoromethyl-4- (3H) -quinazolinone, 5-chloro-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2,5-dimethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [2,3-d] pyrimidin-4- (3H) -one, 2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [2,3-d] pyrimidin-4- (3H) -one, 6-chloro-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 2-methyl-3-. { 4- [3- (1-p.peridinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [4,3-d] pyrimidin-4- (3H) -one, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [4,3-d] pyrimidin-4- (3H) -one, 2-methyl-3. { 2- [3- (1-piperidinyl) propoxy] -5-pyrimidinyl} -4- (3H) -nazamolinone, 2,5-dimethyl-3-. { 2- [3- (1-piperidinium) propoxy] -5-pyrimidinyl} -4- (3H) -quinazolinone, 2-ethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrid [2,3-d] pyrimidin-4- (3H) -one, 6-chloro-2-ethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrid [3,4-d] pyrimidin-4- (3 H) -one, 6-chloro-2-ethyl-3-. { 4- [3- (1-pyrroidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 2-ethyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 2-etl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, 2-ethyl-3-. { 4- [3- (1-piperidinyl) propoxy] pheniI} pyrido [4,3-d] pyrimidin-4- (3H) -one, 2-ethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [4,3-d] pyrimidin-4- (3H) -one, 6-chloro-2-methi-3. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido- [3,4-d] pyrimidin-4- (3H) -one, 3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- (acetylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- (butylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenol} -4- (3H) -quinazolinone, 6- (hexanoylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- (benzoylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6 - [(2-phenylacetyl) amino] -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- (2-naphthoylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) prppoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-6 - [(methylsulfonyl) amino] -3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-6 - [(methylsulfonyl) amino] -3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenol} -4- (3H) -quinazolinone7- (acetylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7- (butyrylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7- (hexanoylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7- (benzoylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7 - [(2-phenylacetyl) amino] -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 7- (2-naphthoylamino) -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 6- [acetyl (methyl) amino] -2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quazolinone, 2-methyl-6-phenyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolnone, 2-methyl-6- (4-methylphenyl) -3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-6- (3-methylphenyl) -3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-6- (2-methylphenyl) -3-. { 4- [3- (1-piperidinyl) propoxy] pheniI} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenol} -6- (3-pyridyl) -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -6- (4-pyridyl) -4- (3H) -quinazolinone, 2-methyl-5-phenyl-3. { 4- [3- (1-pperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, 2-methyl-3-. { 4- [3- (1-piperidiny) propoxy] phenyl} -6- (2-pyridyl) -4- (3H) -cynazolinone, 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenol} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- (1-cyclohexyl-4-piperidinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- (1-isopropyl-4-piperidinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- (1-ethyl-4-piperidinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- (1-Butyl-4-piperidinyloxy) phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methyI-5-trifluoromethyl-4- (3H) -quinazolinone, 3-. { 4- (1-cyclopentyl-4-piperidinyloxy) phenyl} -2,5-dimethyl-4- (3H) -quinazolinone, 7-chloro-3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4- [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2,6-dimethyl-4- (3H) -quinazolinone, 6-chloro-3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenol} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -6-methoxy-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methylpyrido [2,3-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-Cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methylpyrido [4,3-d] pyrimidin-4- (3H) -one, 6-chloro-3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenol} -2-methypyridyl [3,4-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenol} -2,5-dimethyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -5-methoxy-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-4-p-peridinyl) oxy] phenyl} -2-methyl-5-trifluoromethyl-4- (3H) -quinazolinone, 5-chloro-3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-4-pyridinyl) oxy] phenyl} -2-methylpyrido [4,3-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-ethylpyrido [4,3-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclobutyl-4-piperidnol) oxy] phenyl} -2-methylpyrido [2,3-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclobutyl-4-pyridinyl) oxy] phenyl} -2-ethylpyrido [2,3-d] -pyrimidin-4- (3H) -one, 6-chloro-3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] fenii} -2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one, 6-chloro-3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-ethylpyrido [3,4-d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-cyclobutyl-4-piperidinyl) oxy] phenyl} -2-methylpyridyl [3,4-d] pyrimidin-4- (3H) -one, 2-phenyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, cis-2-methyl-3- (4- { [4- (1-pyrrolidinyl) cyclohexyl] oxy} phenyl) -4- (3H) -quinazolinone, trans- 2-methyl-3- (4- { [4- (1-pyrrolidinyl) c-chlorhexyl] oxy} phenyl) -4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-3-pyrrolidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-3-pyrrolidinyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-cyclopentyl-4-azepanyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutyl-4-azepanyl) oxy] phenyl} -2-methyl-4- (3H) -quinazolinone, 3-methyl-2-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -1- (2H) -isoquinolinone, 2-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -3-methyl-1- (2H) -isoquinol-none, 2-methyl-3- [4-. { [3- (1-pyrrolidinyl) cyclopentyl] oxy} phenyl] -4- (3H) -quinazolinone, 2-ethyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy] phenyl) pyrido [2,3- d] pyrimidin-4- (3H) -one, 2-methyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy] phenyl) pyrido [4.3 -d] pyrimidin-4- (3H) -one, 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -5-fluoro-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -7-fluoro-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -6-methoxy-2-methyl-4- (3H) -quinazolnone, 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -6-fluoro-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -8-fluoro-2-methyl-4- (3H) -quinazolinone, 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -6-fluoro-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one, 6-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrid [3,4-d] pyrimidin-4- (3 H) -one, 6-methoxy-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenol} pyrido [3,4-d] pyrimidin-4- (3H) -one, 5-methoxy-2-methyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy] phenyl) -4- (3H) -quinazolinone, 7-methoxy-2-methyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1-yl] propoxy] phenyl ) -4- (3H) -quinazolonone, 2-methyl-3- (4-. {3 - [(3S) -3-methyl-1-pyridin-1-yl] propoxy] phenyl ) pyrido [2,3-d] pyrimidin-4- (3H) -one, 5-fluoro-2-methyl-3- (4-. {3 - [(2R) -2-methylpyrrolidin-1-) il] propoxy, phenyl) -4- (3H) -quinazolinone, 2-methyl-3- (4-. {3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy, phenyl) pyrido [4,3-d] pyrimidin-4- (3H) -one, 6-methoxy-2-methyl-3- (4- { 3 - [(2R) -2-methylpyrrolidin-1-yl] propoxy .}. phenyl) -4- (3H) -quinazolinone, or 6-methoxy-2-methyl-3- (4-. {3 - [(2S) -2-methylpyrrolidin-1-yl] propoxy. phenyl) -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 18. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-ethylpyrido [2,3-d] -pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof. 19. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutyl-4-pyridinyl) oxy] phenyl} -2-methylpyraz [4,3-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof. 20. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 2-ethyl-3- (4-. {3 - [(3S) -3-methylpiperidin-1- L] propoxy] phenyl) pyrid [2,3-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof. 21. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 2-methyl-3- (4-. {3 - [(3S) -3-methylpiper- dinate) 1-yl] propoxy.} Phenyl) pyrido [4,3-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof. 22. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 3-. { 4 - [(1-cyclobutyl-4-p-peridinyl) oxy] phenyl} -2,5-dimethyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 23. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenol} -2-methyl-5-trifluoromethyl-4- (3H) -zolinezolinone, or a pharmaceutically acceptable salt thereof. 24. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -5-methoxy-2-methyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 25. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -5-fluoro-2-methyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 26. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -7-fluoro-2-methyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 27. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -6-methoxy-2-methyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 28. The compound according to claim 1, further characterized in that the compound represented by the formula (!) Is 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -6-fluoro-2-methyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 29. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutylpiperidin-4-yl) oxy] phenyl} -8-fluoro-2-methyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 30. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 3-. { 4 - [(1-cyclopentyl-4-piperidinyl) oxy] phenyl} -2-methylpyrido [4,3-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof. 31. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 3-. { 4 - [(1-cyclobutylpiperidin-4-yl) oxy] phenyl} -6-fluoro-2-methylpyrido [3,4-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof. 32. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 3-. { 4 - [(1-Cyclobutyl-4-piperidinyl) oxy] phenyl} -2-ethylpyrido [4,3-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof. 33. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 6-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof. 34. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 6-methoxy-2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} pyrido [3,4-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 2,5-dimethyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -4- (3H) -quinnanolinone, or a pharmaceutically acceptable salt thereof. 36. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 2-methyl-3-. { 4- [3- (1-pyrrolidinyl) propoxy] phenyl} -5-trifluoromethyl-4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 37. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 5-fluoro-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 38.- The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 6-methoxy-2-methyl-3-. { 4- [3- (1-piperidinyl) propoxy] phenyl} -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 5-methoxy-2-methyl-3- (4-. {3 - [(3S) -3- methylpiperidin-1-yl] propoxy, phenyl) -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 7-methoxy-2-methyl-3- (4-. {3 - [(3S) - 3-methyl-piperidin-1-yl] -propoxy, phenyl) -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 41. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 2-methyl-3- (4-. {3 - [(3S) -3-methylpiper- dinate) 1-yl] propoxy, phenyl) pyrid [2,3-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 5-fluoro-2-methyl-3- (4-. {3 - [(2R) -2- methylpyrrolidin-1-yl] propoxy, phenyl) -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 43. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 2-methyl-3- (4-. {3 - [(2R) -2-methylpyrrolidin- 1-yl] propoxy, phenyl) pyrido [4,3-d] pyrimidin-4- (3H) -one, or a pharmaceutically acceptable salt thereof. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 6-methoxy-2-methyl-3- (4-. {3 - [(2R) -2- methylpyrrolidin-1-yl] propoxy, phenyl) -4- (3H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 45. The compound according to claim 1, further characterized in that the compound represented by the formula (I) is 6-methoxy-2-methyl-3- (4-. {3 - [(2S) -2-methylpyrrolidin- 1-yl] propoxy, phenyl) -4- (3 H) -quinazolinone, or a pharmaceutically acceptable salt thereof. 46. An histamine H3 receptor antagonist consisting of the compound according to claim 1-45, or a pharmaceutically acceptable salt thereof. 47. An inverse agonist of histamine H3 receptors consisting of the compound according to claim 1-45, or a pharmaceutically acceptable salt thereof. 48. A prophylactic or therapeutic agent for a metabolic disease, a circulatory disease or a nervous system disease containing as an active ingredient the compound according to claim 1 to 45, or a pharmaceutically acceptable salt thereof. 49.- The prophylactic or therapeutic agent according to claim 48, further characterized in that the metabolic disease is at least one disease that is selected from the group consisting of obesity, diabetes mellitus, hormonal secretion disorders, hyperlipidemia, gout and fatty liver . 50.- The prophylactic or therapeutic agent according to claim 48, further characterized in that the circulatory disease is at least one disease that is selected from the group consisting of angina pectoris, acute or congestive heart failure, myocardial infarction, annular atherosclerosis , hypertension, kidney disease and electrolyte imbalance. 51.- The prophylactic or therapeutic agent according to claim 48, further characterized in that the disease of the nervous system is at least one that is selected from the group consisting of sleep disorder, illness accompanied by sleep disorder, bulimia, emotional disorder , epilepsy, delirium, dementia, attention deficit hyperactivity disorder, memory impairment, Alzheimer's disease, Parkinson's disease, cognitive disorder, movement disorder, dysesthesia, dysosmia, morphine resistance, dependence on narcotics, dependence on alcohol and tremor. 52.- The prophylactic or therapeutic agent according to claim 48, further characterized in that the disease of the nervous system is at least one that is selected from the group consisting of idiopathic hypersomnia, recurrent hypersomnia, intrinsic hypersomnia, narcolepsy, periodic limb movement during sleep, sleep apnea syndrome, impediment to circadian rhythm, chronic fatigue syndrome, impairment of REM sleep, loss of sleep in the elderly, sleep insanity in workers at night shift, idiopathic insomnia, recurrent insomnia , intrinsic insomnia, depression, insecurity, schizophrenia. 53. A prophylactic or therapeutic agent for a metabolic disease, a circulatory disease or a nervous system disease that contains as active ingredients the compound according to claim 1-45, or a pharmaceutically acceptable salt thereof, and a concomitant drug . 54.- The prophylactic or therapeutic agent according to claim 53, further characterized in that the concomitant drug is anti-diabetes agents. 55.- The prophylactic or therapeutic agent according to claim 53, further characterized in that the concomitant drug is hypolipidemic agents. 56.- The prophylactic or therapeutic agent according to claim 53, further characterized in that the concomitant drug is antihypertensive agents. 57.- The prophylactic or therapeutic agent according to claim 53, further characterized in that the concomitant drug is anti-obesity agents. 58.- A prophylactic or therapeutic agent for a metabolic disease, a circulatory disease or a disease of the nervous system comprising the following (i) to (iii); (i) the compound according to claim 1-45, or a pharmaceutically acceptable salt thereof; (ii) one or more compound (s) selected from the group consisting of the following (a) to (g): (a) antagonist or inverse agonist of histamine H3 other than (i), (b) a biguanide, (c) a PPAR agonist, (d) insulin, (e) somatostatin, (f) an a-glucosidase inhibitor, and (g) insulin secretagogues; and (iii) a vehicle pharmaceutically acceptable.