Bicyclic nitrogenous fused-ring compound

• US 20040082781A1
• Filed: 06/25/2003
• Published: 04/29/2004
• Est. Priority Date: 02/08/2001
• Status: Active Grant

• Current Assignee: Eisai R & D Management Company Limited (Eisai Medical Research Incorporated)
• Original Assignee: Eisai R & D Management Company Limited (Eisai Medical Research Incorporated)
• Inventors: Shin, Kogyoku, Soejima, Motohiro, Ono, Mutsuko, Takahashi, Yoshinori, Hoshino, Yorihisa, Hibi, Shigeki, Yoshiuchi, Tatsuya, Kikuchi, Koichi, Shibata, Hisashi, Ino, Mitsuhiro
• Granted Patent: US 7,078,405 B2
• Time in Patent Office: Days
• US Class Current: 544/182
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• 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 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• 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 25/30 : for treating abuse or dependence
• CPC Class Codes: A61P 25/32 : Alcohol-abuse
• CPC Class Codes: A61P 27/00 : Drugs for disorders of the senses
• CPC Class Codes: A61P 27/06 : Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/02 : Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• 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 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems

Abstract

The present invention provides a novel compound having an excellent corticotrophin-releasing-factor receptor antagonistic activity. That is, it provides a compound represented by the following formula or a salt thereof.

Wherein R¹ denotes a hydrogen atom, a C_1-6 alkyl group, a C_1-6 alkoxy group and the like; R² denotes a halogen atom, a cyano group, a nitro group, a C_1-10 alkyl group, a C_2-10 alkenyl group, C_2-10 alkynyl group and the like; R³ denotes a C_6-14 aromatic hydrocarbon cyclic group or a 5- to 14-membered aromatic heterocyclic group, each of which may have a substituent; and X, Y and X are independent of each other and each denotes N or CR⁴ (wherein R⁴ denotes a hydrogen atom, a halogen atom, a cyano group, a nitro group, an optionally halogenated C_1-6 alkyl group and the like) and, in this case, at least two of X, Y and Z denote CR⁴.

Claims

1. A compound represented by the formula:

2. The compound according to claim 1 or a salt thereof, wherein R¹ is a C_1-6 alkyl group, a C_2-8 alkenyl group, a C_2-8 alkynyl group, a C_1-6 alkoxy group, a C_1-6 alkylthio group, a C_1-6 alkylsulfinyl group or a C_1-6 alkylsulfonyl group.

3. The compound according to claim 1 or a salt thereof, wherein R¹ is a methyl group, an ethyl group, a n-propyl group, an iso-propyl group, a methoxy group, an ethoxy group, a n-propyloxy group, an iso-propyloxy group, a methylthio group, an ethylthio group, a n-propylthio group, an iso-propylthio group, a methylsulfinyl group, an ethylsulfinyl group, a methylsulfonyl group or an ethylsulfonyl group.

4. The compound according to claim 1 or a salt thereof, wherein R¹ is -G⁴-CH₃ (wherein G⁴ denotes a single bond, CH₂, O or S).

5. The compound according to claim 1 or a salt thereof, wherein R² denotes a C_1-6alkyl group, C_1-6alkoxy C_1-6alkyl group, a C_1-6alkylsulfonyl group, a C_2-6alkenylsulfonyl group or —

NR^2aR^2b (R^2a and R^2b have the same meanings as defined above), each of which may be substituted.

6. The compound according to claim 1 or a salt thereof, wherein R² is —

NR^2aaR^2bb (wherein R^2aa and R^2bb are independent of each other and each denotes a hydrogen atom, a C_1-8 alkyl group, a C_2-8 alkenyl group, a C_2-6 alkynyl group, a C_1-6 alkyl group substituted with a 5- to 14-membered non-aromatic heterocyclic group, a C_1-8 alkoxy group, a C^1-8 alkoxy C_1-8 alkyl group, a C_1-6 alkylsulfinyl group, a C_1-6 alkylsulfonyl group, a C_3-8 cycloalkyl group, a C_3-8cycloalkyl C_1-6alkyl group or a 5- to 14-membered heterocyclic group, and further, the R^2aa and R^2bb are independent of each other and each may be substituted with a halogen atom).

7. The compound according to claim 1 or a salt thereof, wherein R² is a di(C_1-6alkyl)amino group.

8. The compound according to claim 1 or a salt thereof, wherein R³ is a phenyl group or a pyridyl group, each of which may be substituted.

9. The compound according to claim 1 or a salt thereof, wherein R³ is a phenyl group or a pyridyl group, each of which may be substituted with 1 to 4 group(s) selected from a halogen atom, a C_1-6 alkyl group, a halogeno-C_1-6 alkyl group, a C_1-6 alkoxy group, a halogeno-C_1-6 alkoxy group, a C_1-6 alkylthio group and a 5- to 8-membered aromatic heterocyclic group.

10. The compound according to claim 1 or a salt thereof, wherein R³ is a phenyl group or a pyridyl group, each of which may be substituted with 1 to 3 group(s) selected from a fluorine atom, a chlorine atom, a bromine atom, a methyl group, an ethyl group, a trifluoromethyl group, a methoxy group, a trifluoromethoxy group, a methylthio group and a pyrrolyl group.

11. The compound according to claim 1 or a salt thereof, wherein any one of X, Y and Z is N, and remaining two are CR^4′

(wherein R^4′

denotes a hydrogen atom, a halogen atom, a cyano group, a C_1-6alkyl group or a C_1-6alkoxy group).

12. The compound according to claim 1 or a salt thereof, wherein X and Y are CR^4′

(wherein R^4′

has the same meaning as defined above); and

Z is N.

13. The compound according to claim 1 or a salt thereof, wherein X, Y and Z are a group represented by CR⁴ (wherein R⁴ has the same meaning as defined above).

14. The compound according to any one of claims 11 to 13 or a salt thereof, wherein R^4′

is a hydrogen atom, a halogen atom, a methyl group, an ethyl group, a methoxy group or an ethoxy group.

15. The compound according to any one of claims 11 to 13 or a salt thereof, wherein R^4′

is a hydrogen atom.

16. The compound according to claim 1 which is represented by the following formula or a salt thereof.

17. The compound according to claim 16 or a salt thereof, wherein R² is —

NR^2aaR^2bb (wherein R^2aa and R^2bb are independent of each other and each denotes a hydrogen atom, a C_1-8 alkyl group, a C_2-8alkenyl group, a C_2-6 alkynyl group, a C_1-6 alkyl group which may be substituted with a 5- to 14-membered non-aromatic heterocyclic group, a C_1-8 alkoxy group, a C_1-8 alkoxy C_1-8 alkyl group, a C_1-6 alkylsulfinyl group, a C_1-6 alkylsulfonyl group, a C_3-8 cycloalkyl group, a C_3-8 cycloalkyl C_1-6 alkyl group or a 5- to 14-membered heterocyclic group, and further, the R^2aa and R^2bb are independent of each other and each may be substituted with a halogen atom).

18. The compound according to claim 16 or a salt thereof, wherein R² is a di(C_1-6alkyl)amino group.

19. The compound according to claim 16 or a salt thereof, wherein R³ is a phenyl group or a pyridyl group, each of which may be substituted.

20. The compound according to claim 16 or a salt thereof, wherein R³ is a phenyl group or a pyridyl group, each of which may be substituted with 1 to 4 group(s) selected from a halogen group, a C_1-6alkyl group, a halogeno-C_1-6alkyl group, a halogeno-C_1-6alkoxy group, a C_1-6alkoxy group, a C_1-6alkylthio group and a 5- to 8-membered aromatic heterocyclic group.

21. The compound according to claim 1 which is represented by the following formula or a salt thereof.

22. The compound according to claim 21 or a salt thereof, wherein R^2a and R^2b are independent of each other and each represents a hydrogen atom, a C_1-8 alkyl group, a C_2-8 alkenyl group, a C_2-6 alkynyl group, a C_1-6 alkyl group which may be substituted with a 5- to 14-membered non-aromatic heterocyclic group, a C_1-8 alkoxy C_1-8 alkyl group, a C_3-8 cycloalkyl group or a C_3-8 cycloalkyl C_1-6 alkyl group, and further, each of which may be substituted with a halogen atom.

23. The compound according to claim 21 or a salt thereof, wherein R^2a and R^2b are a C_1-6alkyl group.

24. The compound according to claim 21 or a salt thereof, wherein the ring M is a benzene ring which may be further substituted with 1 to 3 group(s) selected from a halogen atom, a C_1-6alkyl group, a C_1-6alkoxy group, a halogeno-C_1-6alkyl group and a halogeno-C_1-6alkoxy group.

25. The compound according to claim 1 or a salt thereof, wherein the compound is:

N-(2-ethyl-8-mesitylimidazo[1,2-a]pyrazin-3-yl)-N,N-dipropylamine hydrochloride,

N-(2-ethyl-8-mesitylimidazo[1,2-a]pyrazin-3-yl)-N-(1-ethylpropyl)amine,

N-[8-(2-chloro-4-methoxyphenyl)-2-ethylimdazo[1,2-a]pyrazin-3-yl]-N,N-dipropylamine hydrochloride,

N-cyclopropylmethyl-N-[8-(2,4-dichloropheyl)-2-ethylimidazo[1,2-a]pyrazin-3-yl]-N-isobutylamine,

N-[8-(2,4-dichlorophenyl)-2-ethylimidazo[1,2-a]pyrazin-3-yl]-N-propyl-N-tetrahydro-3-thiophenylamine,

N3,N3-dipropyl-2-isopropyl-8-(2-methoxy-4,6-dimethylphenyl)imidazo[1,2-a]pyrazin-3-amine,

N-[2-ethyl-8-(6-methyl-1,3-benzodioxol-5-yl)imidazo[1,2-a]pyrazin-3-yl]-N,N-dipropylamine,

N-[2-ethyl-8-(4-methoxy-2,5dimethylphenyl)imidazo[1,2-a]pyrazin-3-yl]-N,N-dipropylamine,

N-cyclopropylmethyl-N-[8-(2,4-dichlorophenyl)-2-ethylimidazo[1,2-a]pyrazin-3-yl]-N-(2-methoxyethyl)amine hydrochloride,

N-[8-(2-chloro-4-methoxyphenyl)-2-ethylimidazo[1,2-a]pyrazin-3-yl]-N,N-dicyclopropylmethylamine,

N-8-[5-chloro-4-(2,5-dimethyl-1H-1-pyrroyl)-2-methoxyphenyl]-2-ethylimidazo[1,2-a]pyrazin-3-yl-N,N-dicyclopropylmethylamine,

N-[8-(2,4-dichlorophenyl)-2-ethyl-6-methylimidazo[1,2-a]pyrazin-3-yl]-N,N-dipropylamine hydrochloride,

N3,N3-dipropyl-5-bromo-8-(2,4-dichlorophenyl)-2-ethylimidazo[1,2-a]pyrazin-3-amine,

8-(2,4-dichlorophenyl)-3-(dipropylamino)-2-ethylimidazo[1,2-a]pyrazin-6-yl cyanide,

N-[8-(2,4-dichlorophenyl)-2-ethyl-6-methoxyimidazo[1,2-a]pyrazin-3-yl]-N,N-dipropylamine,

N-[6-chloro-2-ethyl-8-(2-methoxy-4,6-dimethylphenyl)imidazo[1,2-a]pyrazin-3-yl]-N,N-dipropylamine,

N3,N3-dipropyl-8-(2,4-dichlorophenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-amine,

N,N-dicyclopropylmethyl-N-[8-(2-methoxy-4,6-dimethylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]amine,

N-[8-(2-chloro-4-methoxyphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]-N-cyclopropylmethyl-N-propylamine,

N-[8-(2-bromo-4-methoxyphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]-N-cyclopropylmethyl-N-(3-fluoropropyl)amine,

N-[8-(2-chloro-6-methoxy-4-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]-N,N-dicyclopropylmethylamine,

N-[8-(2-chloro-4-methoxyphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]-N-cyclopropylmethyl-N-isobutylamine,

N-cyclopropylmethyl-N-[8-[2-methyl-4-(methylsulfinyl)phenyl]-2-(methylsulfinyl)imidazo[1,2-a]pyrazin-3-yl]-N-propylamine,

N-[8-(2-chloro-4-methoxyphenyl)-2-(methylsulfonyl)imidazo[1,2-a]pyrazin-3-yl]-N-cyclopropylmethyl-N-propylamine,

N-[8-[2-chloro-4-(trifluoromethoxy)phenyl]-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]-N,N-dicyclopropylmethylamine,

1-[[8-[2-chloro-4-(trifluoromethoxy)phenyl]-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl](cyclopropylmethyl)amino]-2-propanol,

2-[[8-[2-chloro-4-(trifluoromethoxy)phenyl]-2(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl](cyclopropylmethyl)amino]acetamide,

4-[3-[di(cyclopropylmethyl)amino]-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-8-yl]-3-methoxybenzonitrile,

N,N-dicyclopropylmethyl-N-[8-(2-methoxy-4-tetrahydro-1H-1-pyrrolylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]amine,

N2-[8-[2-chloro-4-(trifluoromethoxy)phenyl]-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]-N2-cyclopropylmethyl-2-furamide,

N-[8-[2-chloro-4-(trifluoromethoxy)phenyl]-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]-N-cyclopropylmethyl-N-(2-furylmethyl)amine,

N-[8-[2-chloro-4-(trifluoromethoxy)phenyl]-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]-N-cyclopropylmethyl-N-(2-morpholinoethyl)amine,

N-[8-[2-chloro-4-(trifluoromethoxy)phenyl]-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]-N-cyclopropylmethyl-N-[2-(1H-1-pyrazoyl)ethyl]amine,

N-[8-[2-chloro-4-(trifluoromethoxy)phenyl]-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]-N-cyclopropylmethyl-N-[2-(1H-1-imidazoyl)ethyl]amine,

2-[2-ethyl-3-(1-ethylpropyl)imidazo[1,2-a]pyrazin-8-yl]-3,5-dimethylphenyl methyl ether,

3-(1-ethoxybutyl)-2-ethyl-8-(2-methoxy-4,6-dimethylphenyl)imidazo[1,2-a]pyrazine,

1-[8-(2-chloro-4-methoxyphenyl)-2-ethylimidazo[1,2-a]pyrazin-3-yl]-1-butanone O1-methyloxime,

3-(1-ethoxybutyl)-8-(2-methoxy-4,6-dimethylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyrazine,

N-[8-(2-chloro-4-methoxyphenyl)-2-methoxyimidazo[1,2-a]pyrazin-3-yl]-N-cyclopropylmethyl-N-propylamine,

N-[2-ethyl-8-(4-methoxy-2-methylphenyl)imidazo[1,2-b]pyridazin-3-yl]-N,N-dipropylamine,

N-[2-ethyl-8-(2-methoxy-4,6-dimethylphenyl)imidazo[1,2-b]pridazin-3-yl]-N,N-dipropylamine,

N,N-dicyclopropylmethyl-N-[2-ethyl-8-(2-methoxy-4,6-dimethylphenyl)imidazo[1,2-b]pyridazin-3-yl]amine,

N-[8-(4-methoxy-2-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-b]pyridazin-3-yl]-N,N-dipropylamine,

N-[8-(2,4-dichlorophenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N,N-dipropylamine,

N-[8-(2-methoxy-4,6-dimethylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N,N-dipropylamine,

N-[8-(2,6-dimethoxy-4-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N,N-dipropylamine,

N-[8-(2,4-dimethoxy-6-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N,N-dipropylamine,

N-[8-(2-chloro-6-methoxy-4-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N,N-dipropylamine,

N-[8-(2,4-dichlorophenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N-propyl-N-(2-propynyl)amine,

N-[8-(4-chloro-2-methoxyphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N,N-dipropylamine,

N-[8-(2,6-dimethoxy-4-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N-propyl-N-(3-thienyl)amine,

N-[8-(4-methoxy-2-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N,N-dipropylamine,

N-cyclobutylmethyl-N-[8-(2,6-dimethoxy-4-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N-propylamine,

N-[8-(4-chloro-2,6-dimethoxyphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N,N-dipropylamine,

N-[8-(4-chloro-2,6-dimethoxyphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N-cyclobutylmethyl-N-propylamine,

N-butyl-N-cyclobutylmethyl-N-[8-(2,6-dimethoxy-4-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]amine,

N-cyclobutylmethyl-N-cyclopropylmethyl-N-[8-(2,6-dimethoxy-4-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]amine,

N3,N3-dipropyl-8-[6-(dimethylamino)-4-methyl-3-pyridyl]-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-amine,

N-[8-(2,6-dimethoxy-4-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N-propyl-N-tetrahydro-2H-4-pyranylamine,

N3-cyclobutylmethyl-N-3-propyl-8-[6-(dimethylamino)-4-methyl-3-pyridyl]-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-amine,

N3-cyclobutylmethyl-N-3-(3-fluoropropyl)-8-[6-(dimethylamino)-4-methyl-3-pyridyl]-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-amine,

N3,N3-dicyclopropylmethyl-8-[6-(dimethylamino)-4-methyl-3-pyridyl]-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-amine,

N3-propyl-N-3-tetrahydro-2H-4-pyranyl-8-[6-(dimethylamino)-4-methyl-3-pyridyl]-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-amine,

N-[8-(2,6-dimethoxy-4-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N-cyclobutylmethyl-N-tetrahydro-2H-4-pyranylamine, or

N-cyclopropylmethyl-N-[8-(2,6-dimethoxy-4-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N-tetrahydro-2H-4-pyranylamine.

26. A pharmaceutical composition comprising the compound according to claim 1 or a salt thereof, and a pharmacologically acceptable carrier.

27. The composition according to claim 26, which is an agent for treating or preventing a disease to which corticotrophin-releasing factor (hereinafter, referred to as “

CRF”

) and/or a CRF receptor relate.

28. The composition according to claim 26, which is a CRF receptor antagonist.

29. The composition according to claim 26, which is an antagonist for a CRF1 receptor or CRF2 receptor.

30. The composition according to claim 26, which is an agent for treating or preventing depression, depressive symptom, mania, anxiety, generalized anxiety disorder, panic disorder, phobia, compulsive disorder, posttraumatic stress disorder, Tourette syndrome, autism, emotional disorder, sentimental disorder, bipolar disorder, cyclothymia or schizophrenia.

31. The composition according to claim 30, which is an agent for treating or preventing depressive symptoms which is great depression, monostotic depression, recurrent depression, infant tyrannism by depression or postpartum depression.

32. The composition according to claim 26, which is an agent for treating or preventing peptic ulcer, irritable bowel syndrome, ulcerative colitis, Crohn'"'"'s disease, diarrhea, coprostasis, postoperational ileus, gastrointestinal function abnormality associated with stress or neural vomiting.

33. The composition according to claim 26, which is an agent for treating or preventing Alzheimer'"'"'s disease, Alzheimer-type senile dementia, neurodegenerative disease, multi-infarct dementia, senile dementia, neurotic anorexia, diet disorder, obesity, diabetes, alcohol dependence, pharmacophilia, drug abstinence symptoms, alcohol abstinence symptoms, sleep disorder, insomnia, migraine, stress headache, myotonic headache, ischemic neuropathy, excitation toxic neuropathy, cerebral apoplexy, progressive supranuclear palsy, amyotrophic lateral sclerosis, multiple sclerosis, muscular convulsion, chronic fatigue syndrome, mental social growth failure, epilepsy, head trauma, spinal trauma, graphospasm, spasmodic torticollis, muscular convulsion, neck-shoulder-arm syndrome, primary glaucoma, Meniere syndrome, autonomic imbalance, alopecia, neurosis, hypertension, cardiovascular disorder, tachycardia, congestive cardioplegia, hyperpnea syndrome, bronchial asthma, apnea syndrome, infant sudden death syndrome, inflammatory disorder, pain, allergic disease, impotence, climacteric disorder, fertilization disorder, infertility, cancer, immune function abnormality upon infection with HIV, immune function abnormality by stress, hemorrhagic stress, Cushing syndrome, thyroid function disorder, encephalomyelitis, acromegaly, incontinence or osteoporosis.

34. Use of the compound according to claim 1 or a salt thereof for producing an antagonist for a CRF receptor.

35. Use of the compound according to claim 1 or a salt thereof for producing an antagonist for a CRF1 receptor or a CRF2 receptor.

36. Use of the compound according to claim 1 or a salt thereof for producing an agent for treating or preventing depression, depressive symptom, mania, anxiety, generalized anxiety disorder, panic disorder, phobia, compulsive disorder, posttraumatic stress disorder, Tourette syndrome, autism, emotional disorder, sentimental disorder, bipolar disorder, cyclothymia, schizophrenia, peptic ulcer, irritable bowel syndrome, ulcerative colitis, Crohn'"'"'s disease, diarrhea, coprostasis, postoperational ileus, gastrointestinal function abnormality associated with stress or neural vomiting.

37. A method for treating or preventing a disease to which a CRF receptor relate, which comprises administering a therapeutically effective amount of the compound according to claim 1 or a salt thereof once or multiple times to a patient who is suffering from a disease to which a CRF receptor relate.

38. A medicine comprising the compound according to claim 1 or a salt thereof as the active ingredient.

39. The medicine according to claim 38, which is an agent for treating or preventing a disease to which a CRF and/or CRF receptor relate.

40. The medicine according to claim 38, which is a CRF receptor antagonist.

41. The medicine according to claim 38, which is an antagonist for a CRF1 receptor or a CRF2 receptor.

42. The medicine according to claim 38, which is an agent for treating or preventing depressive symptom, mania, anxiety, generalized anxiety disorder, panic disorder, phobia, compulsive disorder, posttraumatic stress disorder, Tourette syndrome, autism, emotional disorder, sentimental disorder, bipolar disorder, cyclothymia or schizophrenia.

43. The medicine according to claim 42, which is an agent for treating or preventing depressive symptoms which is great depression, monostotic depression, recurrent depression, infant tyrannism by depression or postpartum depression.

44. The medicine according to claim 38, which is an agent for treating or preventing peptic ulcer, irritable bowel syndrome, ulcerative colitis, Crohn'"'"'s disease, diarrhea, coprostasis, postoperational ileus, gastrointestinal function abnormality associated with stress or neural vomiting.

45. The medicine according to claim 38, which is an agent for treating or preventing Alzheimer'"'"'s disease, Alzheimer-type senile dementia, neurodegenerative disease, multi-infarct dementia, senile dementia, neurotic anorexia, diet disorder, obesity, diabetes, alcohol dependence, pharmacophilia, drug abstinence symptoms, alcohol abstinence symptoms, sleep disorder, insomnia, migraine, stress headache, myotonic headache, ischemic neuropathy, excitation toxic neuropathy, cerebral apoplexy, progressive supranuclear palsy, amyotrophic lateral sclerosis, multiple sclerosis, muscular convulsion, chronic fatigue syndrome, mental social growth failure, epilepsy, head trauma, spinal trauma, graphospasm, spasmodic torticollis, muscular convulsion, neck-shoulder-arm syndrome, primary glaucoma, Meniere syndrome, autonomic imbalance, alopecia, neurosis, hypertension, cardiovascular disorder, tachycardia, congestive cardioplegia, hyperpnea syndrome, bronchial asthma, apnea syndrome, infant sudden death syndrome, inflammatory disorder, pain, allergic disease, impotence, climacteric disorder, fertilization disorder, infertility, cancer, immune function abnormality upon infection with HIV, immune function abnormality by stress, hemorrhagic stress, Cushing syndrome, thyroid function disorder, encephalomyelitis, acromegaly, incontinence or osteoporosis.

46. Use of the compound according to claim 1 or a salt thereof, for producing an agent for treating or preventing a disease to which a CRF and/or CRF receptor relate.

47. The use according to claim 36, wherein the depressive symptom is great depression, monostotic depression, recurrent depression, infant tyrannism by depression or postpartum depression.

48. Use of the compound according to claim 1 or a salt thereof, for producing an agent for treating or preventing Alzheimer'"'"'s disease, Alzheimer-type senile dementia, neurodegenerative disease, multi-infarct dementia, senile dementia, neurotic anorexia, diet disorder, obesity, diabetes, alcohol dependence, pharmacophilia, drug abstinence symptoms, alcohol abstinence symptoms, sleep disorder, insomnia, migraine, stress headache, myotonic headache, ischemic neuropathy, excitation toxic neuropathy, cerebral apoplexy, progressive supranuclear palsy, amyotrophic lateral sclerosis, multiple sclerosis, muscular convulsion, chronic fatigue syndrome, mental social growth failure, epilepsy, head trauma, spinal trauma, graphospasm, spasmodic torticollis, muscular convulsion, neck-shoulder-arm syndrome, primary glaucoma, Meniere syndrome, autonomic imbalance, alopecia, neurosis, hypertension, cardiovascular disorder, tachycardia, congestive cardioplegia, hyperpnea syndrome, bronchial asthma, apnea syndrome, infant sudden death syndrome, inflammatory disorder, pain, allergic disease, impotence, climacteric disorder, fertilization disorder, infertility, cancer, immune function abnormality upon infection with HIV, immune function abnormality by stress, hemorrhagic stress, Cushing syndrome, thyroid function disorder, encephalomyelitis, acromegaly, incontinence or osteoporosis.

49. A method for treating or preventing a disease to which a CRF and/or CRF receptor relate, by administering a pharmacologically effective amount of the compound according to claim 1 or a salt thereof to a patient.

50. A method for treating or preventing a disease against which the CRF receptor antagonistic activity is efficacious for treatment or prevention, by administering a pharmacologically effective amount of the compound as defined in claim 1 or a salt thereof to a patient.

51. A method for treating or preventing a disease against which a CRF1 receptor or CRF2 receptor antagonistic activity is efficacious for treatment or prevention, by administering a pharmacologically effective amount of the compound as defined in claim 1 or a salt thereof to a patient.

52. A method for treating or preventing depression, depressive symptom, mania, anxiety, generalized anxiety disorder, panic disorder, phobia, compulsive disorder, posttraumatic stress disorder, Tourette syndrome, autism, emotional disorder, sentimental disorder, bipolar disorder, cyclothymia, schizophrenia, peptic ulcer, irritable bowel syndrome, ulcerative colitis, Crohn'"'"'s disease, diarrhea, coprostasis, postoperational ileus, gastrointestinal function abnormality associated with stress or neural vomiting, by administering a pharmacologically effective amount of the compound according to claim 1 or a salt thereof to a patient.

53. The method according to claim 52, wherein the depressive symptom is great depression, monostotic depression, recurrent depression, infant tyrannism by depression or postpartum depression.

54. A method for treating or preventing Alzheimer'"'"'s disease, Alzheimer-type senile dementia, neurodegenerative disease, multi-infarct dementia, senile dementia, neurotic anorexia, diet disorder, obesity, diabetes, alcohol dependence, pharmacophilia, drug abstinence symptoms, alcohol abstinence symptoms, sleep disorder, insomnia, migraine, stress headache, myotonic headache, ischemic neuropathy, excitation toxic neuropathy, cerebral apoplexy, progressive supranuclear palsy, amyotrophic lateral sclerosis, multiple sclerosis, muscular convulsion, chronic fatigue syndrome, mental social growth failure, epilepsy, head trauma, spinal trauma, graphospasm, spasmodic torticollis, muscular convulsion, neck-shoulder-arm syndrome, primary glaucoma, Meniere syndrome, autonomic imbalance, alopecia, neurosis, hypertension, cardiovascular disorder, tachycardia, congestive cardioplegia, hyperpnea syndrome, bronchial asthma, apnea syndrome, infant sudden death syndrome, inflammatory disorder, pain, allergic disease, impotence, climacteric disorder, fertilization disorder, infertility, cancer, immune function abnormality upon infection with HIV, immune function abnormality by stress, hemorrhagic stress, Cushing syndrome, thyroid function disorder, encephalomyelitis, acromegaly, incontinence or osteoporosis, by administering a pharmacologically effective amount of the compound according to claim 1 or a salt thereof to a patient.