Novel spiro compounds

• US 20020188124A1
• Filed: 03/08/2002
• Published: 12/12/2002
• Est. Priority Date: 08/20/1999
• Status: Active Grant

• Current Assignee: MSD Kabushiki Kaisha (Merck & Co., Inc.)
• Original Assignee: Banyu Pharmaceutical Company Limited (Merck & Co., Inc.)
• Inventors: Takahashi, Toshiyuki, Sakamoto, Toshihiro, Haga, Yuji, Ishii, Yasuyuki, Kanatani, Akio, Itoh, Takahiro, Ishihara, Akane, Fukami, Takehiro
• Granted Patent: US 6,803,372 B2
• Time in Patent Office: Days
• US Class Current: 544/230
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• 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 25/22 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 27/06 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 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• 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 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 213/61 : Halogen atoms or nitro radicals
• CPC Class Codes: C07D 307/94 : spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/10 : Spiro-condensed systems
• CPC Class Codes: C07D 491/10 : Spiro-condensed systems

Abstract

Compounds of the general formula (I):

wherein Ar¹ represents optionally substituted aryl or heteroaryl;

n represents 0 or 1;

T, U, V, and W each independently represent nitrogen atom or optionally substituted methine group, where at least two of them represent the said methine group;

X represents methine or hydroxy substituted methine;

Y represents an optionally substituted imino or oxygen atom are described and claimed. These novel spiro compounds are useful as neuropeptide Y receptor antagonists and as agents for the treatment of various kinds of cardiovascular disorders, central nervous system disorders, metabolic diseases and the like.

Claims

1. A compound represented by the general formula (I):

2. The compound of claim 1, wherein the aryl in Ar¹ is phenyl.

3. The compound of claim 1, wherein the heteroaryl in Ar¹ is pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, 1,2,3-triazolyl, 1,2,4-thiadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, 1,2,4-triazinyl, benzoxazolyl, benzothiazolyl, quinolyl or pyrido[3,2-b]pyridyl.

4. The compound of claim 1, wherein each of T, U, V and W is methine which may have a substituent selected from the group consisting of halogen, lower alkyl, hydroxy and lower alkoxy.

5. The compound of claim 4, wherein each of T, U, V and W is methine which may be substituted with halogen.

6. The compound of claim 1, wherein one of T, U, V and W is nitrogen.

7. The compound of claim 6 which is a N-oxide derivative.

8. The compound of claim 1, wherein X is hydroxy substituted methine.

9. The compound of claim 1, wherein Y is an unsubstituted imino or oxygen.

10. The compound of claim 1, wherein Y is oxygen.

11. The compound of claim 1 which is represented by the general formula (I-b):

12. The compound of claim 11, wherein the aryl in Ar¹ is phenyl.

13. The compound of claim 11, wherein the heteroaryl in Ar¹ is pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, 1,2,3-triazolyl, 1,2,4-thiadiazolyl, pyridyl, pyrazinyl, pyrimidinyl or 1,2,4-triazinyl.

14. The compound of claim 11, wherein one of T, U, V and W is nitrogen.

15. The compound of claim 14 which is a N-oxide derivative.

16. The compound of claim 11, wherein V is nitrogen and each of T, U and W is an unsubstituted methine group.

17. The compound of claim 1, which is

cis-N-(4-benzoylphenyl)-4-hydroxy-3′

-oxospiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

trans-N-[5-(4-hydroxyphenyl)-2-pyrazinyl]-3′

-oxospiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

cis-4-hydroxy-3′

-oxo-N-(5-phenyl-2-pyrazinyl)spiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

cis-4-hydroxy-N-[5-(4-hydroxyphenyl)-2-pyrazinyl]-3′

-oxospiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

trans-N-[1-(4-hydroxyphenyl)-4-imidazolyl]-3′

-oxospiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

cis-4-hydroxy-3′

-oxo-N-(1-phenyl-4-imidazolyl)spiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

cis-4-hydroxy-N-[1-(4-hydroxyphenyl)-4-imidazolyl]-3′

-oxospiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

trans-N-[5-(4-hydroxyphenyl)-2-pyrimidinyl]-3′

-oxospiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

cis-4-hydroxy-3′

-oxo-N-(5-phenyl-2-pyrimidinyl)-spiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

cis-4-hydroxy-3′

-oxo-N-[5-(4-hydroxyphenyl)-2-pyrimidinyl]-spiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

cis-N-[1-(3,5-difluorophenyl)-4-imidazolyl]-4-hydroxy-3′

-oxospiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

cis-4-hydroxy-3′

-oxo-N-(5-phenyl-3-pyrazolyl)spiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

cis-N-[1-(2-fluorophenyl)-4-imidazolyl]-4-hydroxy-3′

-oxospiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

cis-N-(4-acetyl-3-trifluoromethylphenyl)-4-hydroxy-3′

-oxospiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

cis-4-hydroxy-3′

-oxo-N-[1-(3-quinolyl)-4-imidazolyl]spiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

cis-N-[1-(3-cyanophenyl)-4-imidazolyl]-4-hydroxy-3′

-oxospiro[cyclohexane-1,1′

(3′

H)-isobenzofuran]-4-carboxamide,

cis-N-(4-benzoylphenyl)-4′

-hydroxy-3-oxospiro[4-azaisobenzofuran-1(3H),1′

- cyclohexane]-4′

-carboxamide,

cis-4′

-hydroxy-3-oxo-N-(5-phenyl-2-pyrazinyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(5-phenyl-2-pyrazinyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 4-oxide,

cis-4′

-hydroxy-3-oxo-N-(5-phenyl-2-pyrazinyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 4-oxide,

cis-4′

-hydroxy-3-oxo-N-(3-phenyl-5-isoxazolyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(3-phenyl-5-isoxazolyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 4-oxide,

cis-4′

-hydroxy-3-oxo-N-(5-phenyl-2-pyrimidinyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 4-oxide,

cis-N-(4-benzoylphenyl)-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

- cyclohexane]-4′

-carboxamide,

trans-N-(4-benzoylphenyl)-3-oxospiro[5-azaisobenzofuran-1(3H),1′

- cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-(4-benzoylphenyl)-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-(4-benzoylphenyl)-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

- cyclohexane]-4′

-carboxamide,

trans-N-(4-benzoylphenyl)-3-oxospiro[6-azaisobenzofuran-1(3H),1′

- cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-(4-benzoylphenyl)-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

- cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(5-phenyl-2-pyrimidinyl)spiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(5-phenyl-2-pyrimidinyl)spiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-4′

-hydroxy-3-oxo-N-(5-phenyl-2-pyrimidinyl)spiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(3-fluorophenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(3-fluorophenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(3-fluorophenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(2-fluorophenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(2-fluorophenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(2-fluorophenyl)-2-pyrimidinyl]-4,-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-4′

-hydroxy-3-oxo-N-(4-phenyl-2-oxazolyl)spiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(4-phenyl-2-oxazolyl)spiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-4′

-hydroxy-3-oxo-N-(4-phenyl-2-oxazolyl)spiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(2-methylphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(2-methylphenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(2-methylphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(3-methylphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(3-methylphenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(3-methylphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(3-fluoromethoxyphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(3-fluoromethoxyphenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(3-fluoromethoxyphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(3-fluoromethylphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(3-fluoromethylphenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(3-fluoromethylphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(3-fluoro-5-methoxyphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(3-fluoro-5-methoxyphenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(3-fluoro-5-methoxyphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(2-fluoro-5-methylphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(2-fluoro-5-methylphenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[5-(2-fluoro-5-methylphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[4-(3-fluoromethoxyphenyl)-2-oxazolyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[4-(3-fluoromethoxyphenyl)-2-oxazolyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-N-[4-(3-fluoromethoxyphenyl)-2-oxazolyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-4′

-hydroxy-N-[5-(3-hydroxymethylphenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(3-hydroxymethylphenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-4′

-hydroxy-N-[5-(3-hydroxymethylphenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-4′

-hydroxy-N-[5-(3-hydroxyphenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(3-hydroxyphenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-4′

-hydroxy-N-[5-(3-hydroxyphenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide,

cis-4′

-hydroxy-3-oxo-N-(5-phenyl-2-pyrimidinyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(5-phenyl-2-pyrimidinyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(5-phenyl-2-pyrimidinyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[5-(3-fluoromethylphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(3-fluoromethylphenyl)-2-pyrimidinyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[5-(3-fluoromethylphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[5-(3-fluoromethoxyphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(3-fluoromethoxyphenyl)-2-pyrimidinyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[5-(3-fluoromethoxyphenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(6-phenyl-1,2,4-triazin-3-yl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(6-phenyl-1,2,4-triazin-3-yl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(6-phenyl-1,2,4-triazin-3-yl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[5-(2-difluoromethoxyphenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(2-difluoromethoxyphenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1l-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[5-(2-difluoromethoxyphenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[5-(3-difluoromethoxyphenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(3-difluoromethoxyphenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[5-(3-difluoromethoxyphenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[5-(3-fluorophenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(3-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[5-(3-fluorophenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[5-(4-fluorophenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[5-(4-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[5-(4-fluorophenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-(4-benzoylphenyl)-4′

-hydroxy-3-oxospiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-(4-benzoylphenyl)-3-oxospiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide,

cis-N-(4-benzoylphenyl)-4′

-hydroxy-3-oxospiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide,

cis-N-[1-(3,5-difluorophenyl)-4-imidazolyl]-4′

-hydroxy-3-oxospiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[1-(3,5-difluorophenyl)-4-imidazolyl]-3-oxospiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide,

cis-N-[1-(3,5-difluorophenyl)-4-imidazolyl]-4′

-hydroxy-3-oxospiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide,

cis-4′

-hydroxy-3-oxo-N-[2-phenyl-4-pyridyl]spiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-[2-phenyl-4-pyridyl]spiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide,

cis-4′

-hydroxy-3-oxo-N-[2-phenyl-4-pyridyl]spiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide,

cis-4′

-hydroxy-3-oxo-N-(1-phenyl-4-pyrazolyl)spiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(1-phenyl-4-pyrazolyl)spiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide,

cis-4′

-hydroxy-3-oxo-N-(1-phenyl-4-pyrazolyl)spiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide,

cis-4′

-hydroxy-3-oxo-N-(1-phenyl-3-pyrrolyl)spiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(1-phenyl-3-pyrrolyl)spiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide,

cis-4′

-hydroxy-3-oxo-N-(1-phenyl-3-pyrrolyl)spiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide,

cis-N-[1-(4-fluorophenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[1-(4-fluorophenyl)-3-pyrazolyl]-3-oxospiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide,

cis-N-[1-(4-fluorophenyl)-3-pyrazolyl]-4,-hydroxy-3-oxospiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide,

cis-4′

-hydroxy-3-oxo-N-(1-phenyl-3-pyrazolyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(1-phenyl-3-pyrazolyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]4′

-carboxamide4-oxide,

cis-4′

-hydroxy-3-oxo-N-(1-phenyl-3-pyrazolyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 4-oxide,

cis-4′

-hydroxy-3-oxo-N-(1-phenyl-4-pyrazolyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(1-phenyl-4-pyrazolyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 4-oxide,

cis-4′

-hydroxy-3-oxo-N-(1-phenyl-4-pyrazolyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 4-oxide,

cis-N-[1-(3-fluorophenyl)-4-pyrazolyl]-4′

-hydroxy-3-oxospiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[1-(3-fluorophenyl)-4-pyrazolyl]-3-oxospiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 4-oxide,

cis-N-[1-(3-fluorophenyl)-4-pyrazolyl]-4′

-hydroxy-3-oxospiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 4-oxide,

cis-4′

-hydroxy-3-oxo-N-(1-phenyl-3-pyrazolyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(1-phenyl-3-pyrazolyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(1-phenyl-3-pyrazolyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[1-(4-fluorophenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[1-(4-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[1-(4-fluorophenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

trans-N-[1-(2-fluoro-4-hydroxyphenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

cis-N-[1-(2-fluorophenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[1-(2-fluoro-4-hydroxyphenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-N-[1-(2-fluoro-4-hydroxyphenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[1-(2-fluorophenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-N-[1-(2-fluoro-4-hydroxyphenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(5-phenyl-1,2,4-thiadiazol-3-yl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(5-phenyl-1,2,4-thiadiazol-3-yl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(5-phenyl-1,2,4-thiadiazol-3-yl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(5-phenyl-3-isoxazolyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(5-phenyl-3-isoxazolyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(5-phenyl-3-isoxazolyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(6-phenyl-3-pyridyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(6-phenyl-3-pyridyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(6-phenyl-3-pyridyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(2-phenyl-3-thiazolyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(2-phenyl-3-thiazolyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(2-phenyl-3-thiazolyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide,

cis-4′

-hydroxy-3-oxo-N-(2-phenyl-1,2,3-triazol-4-yl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide,

trans-3-oxo-N-(2-phenyl-1,2,3-triazol-4-yl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide or

cis-4′

-hydroxy-3-oxo-N-(2-phenyl-1,2,3-triazol-4-yl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide.

18. The compound of claim 1, which is

cis-N-[5-(3-fluorophenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

19. The compound of claim 1, which is

trans-N-[5-(3-fluorophenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide.

20. The compound of claim 1, which is

cis-N-[5-(2-fluorophenyl)-2-pyrimidinyl]-4′

-hydroxy-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

21. The compound of claim 1, which is

trans-N-[5-(2-fluorophenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 5-oxide.

22. The compound of claim 1, which is

trans-N-[5-(2-difluoromethoxyphenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

23. The compound of claim 1, which is

cis-N-[5-(2-difluoromethoxyphenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

24. The compound of claim 1, which is

trans-N-[5-(2-difluoromethoxyphenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide.

25. The compound of claim 1, which is

cis-N-[1-(3,5-difluorophenyl)-4-imidazolyl]-4′

-hydroxy-3-oxospiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

26. The compound of claim 1, which is

trans-N-[1-(3,5-difluorophenyl)-4-imidazolyl]-3-oxospiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide.

27. The compound of claim 1, which is

trans-3-oxo-N-[2-phenyl-4-pyridyl]spiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

28. The compound of claim 1, which is

cis-4′

-hydroxy-3-oxo-N-[2-phenyl-4-pyridyl]spiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

29. The compound of claim 1, which is

trans-3-oxo-N-[2-phenyl-4-pyridyl]spiro[7-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 7-oxide.

30. The compound of claim 1, which is

cis-4′

-hydroxy-3-oxo-N-(1-phenyl-3-pyrazolyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

31. The compound of claim 1, which is

trans-3-oxo-N-(1-phenyl-3-pyrazolyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 4-oxide.

32. The compound of claim 1, which is

trans-3-oxo-N-(1-phenyl-4-pyrazolyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

33. The compound of claim 1, which is

cis-4′

-hydroxy-3-oxo-N-(1-phenyl-4-pyrazolyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

34. The compound of claim 1, which is

trans-3-oxo-N-(1-phenyl-4-pyrazolyl)spiro[4-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 4-oxide.

35. The compound of claim 1, which is

trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

36. The compound of claim 1, which is

trans-N-[1-(2-fluoro-4-hydroxyphenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

37. The compound of claim 1, which is

cis-N-[1-(2-fluorophenyl)-3-pyrazolyl]-4′

-hydroxy-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

38. The compound of claim 1, which is

trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide.

39. The compound of claim 1, which is

trans-3-oxo-N-(2-phenyl-3-thiazolyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

40. The compound of claim 1, which is

cis-4′

-hydroxy-3-oxo-N-(2-phenyl-3-thiazolyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

41. The compound of claim 1, which is

trans-3-oxo-N-(2-phenyl-3-thiazolyl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide.

42. The compound of claim 1, which is

cis-4′

-hydroxy-3-oxo-N-(2-phenyl-1,2,3-triazol-4-yl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide.

43. The compound of claim 1, which is

trans-3-oxo-N-(2-phenyl-1,2,3-triazol-4-yl)spiro[6-azaisobenzofuran-1(3H),1′

-cyclohexane]-4′

-carboxamide 6-oxide.

47. A pharmaceutical composition for the treatment of bulimia, obesity or diabetes which comprises a pharmaceutically effective amount of a compound of claim 1 together with a pharmaceutically acceptable additive.

44. A process for producing a compound of the general formula (I-2):

45. Neuropeptide Y receptor antagonist which comprises a compound of the general formula (I):

46. A method for the treatment of bulimia, obesity or diabetes which comprises administering a therapeutically effective amount of a compound of the general formula (I):