Fused ring 4-oxopyrimidine derivative

• US 20050182045A1
• Filed: 02/14/2005
• Published: 08/18/2005
• Est. Priority Date: 02/13/2004
• Status: Active Grant

• Current Assignee: MSD Kabushiki Kaisha (Merck & Co., Inc.)
• Original Assignee: Banyu Pharmaceutical Company Limited (Merck & Co., Inc.)
• Inventors: Nagase, Tsuyoshi, Sato, Nagaaki, Kanatani, Akio, Tokita, Shigeru
• Granted Patent: US 7,521,455 B2
• Time in Patent Office: Days
• US Class Current: 514/217.60
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/10 for petit-mal
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 3/12 : for electrolyte homeostasis
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07D 239/91 : with aryl or aralkyl radicals attached in position 2 or 3
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 487/08 : Bridged systems

Abstract

The present invention provides a compound represented by formula (I) below, or a pharmaceutically acceptable salt thereof, which, having histamine H3 receptor antagonist or inverse agonist activity, is useful in the prophylaxis or therapy of metabolic diseases, circulatory diseases, or nervous system diseases.
[where, for example, Ar is a divalent group formed by eliminating two hydrogen atoms from benzene, X¹ is a nitrogen atom, sulfur atom or oxygen atom, R¹ is a 5- to 6-membered heteroaryl group, Ring A is a 5- to 6-membered heteroaryl ring, R² and R³ are amino groups or alkylamino groups, and X² is represented by formula (II):
(where R⁴ and R⁵ are lower alkyl groups, and n is an integer from 2 to 4).]

Claims

1. A compound represented by formula (I):

2. The compound according to claim 1, wherein Ring A is a benzene ring, pyridine ring or pyrimidine ring, or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1, wherein Ring A is a benzene ring or a pyridine ring, or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1, wherein at least one of R² and R³ is a hydrogen atom, or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1, wherein one of R² and R³ is a hydrogen atom, and the other is a hydrogen atom, a halogen atom, hydroxy, lower alkyl (this lower alkyl group may be further substituted by halogen), lower alkoxy (this lower alkoxy group may be further substituted by halogen or hydroxy), aryl (this aryl group may be further substituted by lower alkyl), heteroaryl, lower alkylcarboxamide, arylcarboxamide, arylalkylcarboxamide or lower alkylsulfonylamino, or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1, 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 claim 1, wherein Ar is a divalent group formed by eliminating two hydrogen atoms from benzene or pyrimidine (this divalent group may be further substituted by a halogen atom, lower alkoxy (this lower alkoxy group may 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, wherein —

X² is represented by formula (II);

9. The compound according to claim 8, wherein 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 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 claim 8, wherein n is 3 or 4, and R⁴, R⁵ and a nitrogen atom together form a 6- to 10-membered bicyclo ring, or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 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 as a substituent group a halogen atom, or a lower alkyl group which may be substituted by halogen), or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 8, wherein n is 3, and R⁴, R⁵ and a nitrogen atom together form a 6- to 10-membered bicyclo ring, or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1, wherein —

X² is represented by formula (III);

14. The compound according to claim 1, wherein —

X² is represented by formula (IV);

15. The compound according to claim 1, wherein R¹ is a lower alkyl group having 1 to 3 carbon atoms (this lower alkyl group may be further substituted by halogen), or a phenyl group, or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 1, wherein R¹ is methyl, ethyl, n-propyl, isopropyl or trifluoromethyl, or a pharmaceutically acceptable salt thereof.

17. The compound according to claim 1, wherein the compound represented by formula (I) is:

2-ethyl-3-{4-[3-(1-pyrrolidinyl)propoxy]phenyl}-4(3H)-quinazolinone,

2-methyl-3-{4-[3-(1-piperidinyl)propoxy]phenyl}-4(3H)-quinazolinone,

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)-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-azocanyl)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-piperidinyl)propoxy]phenyl}-2-propyl-4(3H)-quinazolinone,

3-{4-[3-(1-piperidinyl)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]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-{4-[3-(1-piperidinyl)propoxy]phenyl}-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-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)proproxy]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]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}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-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]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]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-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-(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]phenyl}-4(3H)-quinazolinone,

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]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]phenyl}-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-piperidinyl)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]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]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-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-piperidinyl)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-piperidinyl)oxy]phenyl}-2-methylpyrido[2,3-d]pyrimidin-4(3H)-one,

3-{4-[(1-cyclobutyl-4-piperidinyl)oxy]phenyl}-2-ethylpyrido[2,3-d]-pyrimidin-4(3H)-one,

6-chloro-3-{4-[(1-cyclobutyl-4-piperidinyl)oxy]phenyl}-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-methylpyrido[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)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-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)-isoquinolinone,

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)-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-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-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-methylpiperidin-1-yl]propoxy}phenyl)-4(3H)-quinazolinone,

2-methyl-3-(4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}phenyl)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]propoxy}phenyl)-4(3H)-quinazolinone, or a pharmaceutically acceptable salt thereof.

18. The compound according to claim 1, wherein the compound represented by 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, wherein the compound represented by 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 claim 1, wherein the compound represented by 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 claim 1, wherein the compound represented by formula (I) is 2-methyl-3-(4-{3-[(3S)-3-methylpiperidin-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, wherein the compound represented by 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 claim 1, wherein the compound represented by 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 claim 1, wherein the compound represented by 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, wherein the compound represented by 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, wherein the compound represented by 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, wherein the compound represented by 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, wherein the compound represented by 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 claim 1, wherein the compound represented by 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, wherein the compound represented by 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, wherein the compound represented by 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, wherein the compound represented by 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, wherein the compound represented by 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, wherein the compound represented by 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 claim 1, wherein the compound represented by 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 claim 1, wherein the compound represented by 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, wherein the compound represented by 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, wherein the compound represented by 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 claim 1, wherein the compound represented by 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.

40. The compound according to claim 1, wherein the compound represented by formula (I) 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 claim 1, wherein the compound represented by formula (I) is 2-methyl-3-(4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}phenyl)pyrido[2,3-d]pyrimidin-4(3H)-one, or a pharmaceutically acceptable salt thereof.

42. The compound according to claim 1, wherein the compound represented by 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, wherein the compound represented by 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.

44. The compound according to claim 1, wherein the compound represented by 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, wherein the compound represented by 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.

46. A histamine H3 receptor antagonist consisting of the compound according to claim 1.

47. A histamine H3 receptor inverse agonist consisting of the compound according to claim 1.

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, or a pharmaceutically acceptable salt thereof.

49. The prophylactic or therapeutic agent according to claim 48, wherein the metabolic disease is at least one disease selected from the group consisting of obesity, diabetes mellitus, hormone secretion disorders, hyperlipidemia, gout and fatty liver.

50. The prophylactic or therapeutic agent according to claim 48, wherein the circulatory disease is at least one disease selected from the group consisting of angina pectoris, acute or congestive heart failure, myocardial infarction, annular arteriosclerosis, hypertension, kidney disease and electrolyte imbalance.

51. The prophylactic or therapeutic agent according to claim 48, wherein the nervous system disease is at least one selected from the group consisting of sleep disorder, disease 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, narcotics dependence, alcohol dependence and tremor.

52. The prophylactic or therapeutic agent according to claim 48, wherein the nervous system disease is at least one selected from the group consisting of idiopathic hypersomnia, repeatability hypersomnia, intrinsic hypersomnia, narcolepsy, periodic limb movement during sleep, sleep apnea syndrome, circadian rhythm hindrance, chronic fatigue syndrome, REM sleep hindrance, sleep loss in the elderly, night shift worker sleep insanitation, idiopathic insomnia, repeatability insomnia, intrinsic insomnia, depression, insecurity, schizophrenia.

53. A prophylactic or therapeutic agent for a metabolic disease, a circulatory disease or a nervous system disease containing as active ingredients the compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a concomitant drug.

54. The prophylactic or therapeutic agent according to claim 53, wherein the concomitant drug is anti-diabetic agents.

55. The prophylactic or therapeutic agent according to claim 53, wherein the concomitant drug is lipid lowering agents.

56. The prophylactic or therapeutic agent according to claim 53, wherein the concomitant drug is anti-hypertensive agents.

57. The prophylactic or therapeutic agent according to claim 53, wherein the concomitant drug is anti-obesity agents.

58. A prophylactic or therapeutic agent for a metabolic disease, a circulatory disease or a nervous system disease comprising the following (i) to (iii).

(i) the compound according to claim 1, or a pharmaceutically acceptable salt thereof;

(ii) one or more compound(s) selected from the group consisting of the following (a) to (g);

(a) Histamine H3 antagonist or inverse agonist other than (i),

(b) a biguanide,

(c) a PPAR agonist,

(d) insulin,

(e) somatostatin,

(f) an α

-glucosidase inhibitor, and

(g) insulin secretagogues; and

(iii) a pharmaceutically acceptable carrier.