Deprecated: The each() function is deprecated. This message will be suppressed on further calls in /home/zhenxiangba/zhenxiangba.com/public_html/phproxy-improved-master/index.php on line 456
NZ745188B2 - 3-((hetero-)aryl)-alkyl-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives - Google Patents
[go: Go Back, main page]

NZ745188B2 - 3-((hetero-)aryl)-alkyl-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives - Google Patents

3-((hetero-)aryl)-alkyl-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives Download PDF

Info

Publication number
NZ745188B2
NZ745188B2 NZ745188A NZ74518817A NZ745188B2 NZ 745188 B2 NZ745188 B2 NZ 745188B2 NZ 745188 A NZ745188 A NZ 745188A NZ 74518817 A NZ74518817 A NZ 74518817A NZ 745188 B2 NZ745188 B2 NZ 745188B2
Authority
NZ
New Zealand
Prior art keywords
methyl
diazaspiro
decanone
unsubstituted
methoxyphenyl
Prior art date
Application number
NZ745188A
Other versions
NZ745188A (en
Inventor
Ruth Jostock
Achim Kless
Thomas Koch
Rene Michael Koenigs
Ingo Konetzki
Sven Kuhnert
Klaus Linz
Paul Ratcliffe
Klaus Schiene
Wolfgang Schroder
Original Assignee
Grünenthal GmbH
Filing date
Publication date
Application filed by Grünenthal GmbH filed Critical Grünenthal GmbH
Priority claimed from PCT/EP2017/025006 external-priority patent/WO2017121648A1/en
Publication of NZ745188A publication Critical patent/NZ745188A/en
Publication of NZ745188B2 publication Critical patent/NZ745188B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Abstract

The invention relates to 3-((hetero-)aryl)-alkyl-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives, their preparation and their use in medicine, particularly in the treatment of pain.

Claims (1)

1.patent claims . [0014a] In a first embodiment there is provided a medicament sing a compound according to general formula (I) R7 R8 R13 R14R15 R16 R11 R12 R1 R5 N R2 R4 R18R19 R17 R20 wherein n means 1, 2 or 3; R1 and R2 independently of one another mean -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -OH, -OCH3, -CN and -CO2CH3; a 3membered cycloalkyl moiety, saturated or rated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -OH, -OCH3, -CN and 3; wherein said 3membered cycloalkyl moiety is optionally connected through -C1- C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted; or a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another ed from the group consisting of -F, -Cl, -Br, -I, -OH, -OCH3, -CN and -CO2CH3; wherein said embered heterocycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or rated, unsubstituted; R1 and R2 together with the nitrogen atom to which they are attached form a ring and mean -(CH2)3; -(CH2)2-O-(CH2)2-; or -(CH2)2-NRA-(CH2)2-, wherein RA means -H or -C1-C6-alkyl, linear or branched, saturated or unsaturated, tituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br and -I; R3 means -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, monoor polysubstituted; wherein said 3membered cycloalkyl moiety is optionally connected h -C1-C6-alkylene-, linear or ed, saturated or unsaturated, tituted, mono- or polysubstituted; a embered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or bstituted; wherein said 3membered heterocycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, ted or unsaturated, unsubstituted, mono- or polysubstituted; a 6membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said embered aryl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is optionally connected through -C1- C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; R4 means -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said -C1-C6-alkyl is optionally connected through -C(=O)-, O-, or -S(=O)2-; a 3membered lkyl moiety, saturated or unsaturated, unsubstituted, monoor polysubstituted; wherein said 3membered cycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or n said 3membered cycloalkyl moiety is optionally connected h -C(=O)-, -C(=O)O-, -C(=O)O-CH2-, or - a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or bstituted; wherein said 3membered heterocycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 3 membered heterocycloalkyl moiety is optionally connected through -C(=O)-, - C(=O)O-, -C(=O)O-CH2-, or -S(=O)2-; a 6membered aryl moiety, unsubstituted, mono- or polysubstituted; n said 6membered aryl moiety is ally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said embered aryl moiety is ally connected through -C(=O)-, - C(=O)O-, -C(=O)O-CH2-, or -S(=O)2-; or a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is optionally connected through -C1- C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 5membered heteroaryl moiety is optionally connected through -C(=O)-, -C(=O)O-, -C(=O)O-CH2-, or 2-; R5 means a 6membered aryl moiety, unsubstituted, mono- or polysubstituted; or a 5membered aryl moiety, unsubstituted, mono- or polysubstituted; R7, R8, R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20 independently of one another mean -H, -F, -Cl, -Br, -I, -OH, or -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein R7 and R8 together with the carbon atom to which they are attached form a ring and mean -(CH2)2- or -(CH2)3-; wherein "mono- or polysubstituted" means that one or more hydrogen atoms are ed by a substituent independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -R21, -C(=O)R21, -C(=O)OR21, -C(=O)NR21R22, - O-(CH2CH2-O)1H, -O-(CH2CH2-O)1CH3, =O, -OR21, -OC(=O)R21, - OC(=O)OR21, -OC(=O)NR21R22, -NO2, -NR21R22, -NR21-(CH2)1C(=O)R22, - NR21-(CH2)1C(=O)OR22, -NR23-(CH2)1C(=O)NR21R22, -NR21C(=O)R22, - NR21C(=O)-OR22, -NR23C(=O)NR21R22, -NR21S(=O)2R22, -SR21, -S(=O)R21, - S(=O)2R21, 2OR21, and -S(=O)2NR21R22; wherein R21, R22 and R23 independently of one another mean -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -OH, -NH2, and C6-alkyl; a 3membered cycloalkyl moiety, ted or unsaturated, unsubstituted; wherein said 3membered cycloalkyl moiety is optionally ted through - alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -OH, -NH2, -C1-C6-alkyl and -O-C1-C6- alkyl; a embered cycloalkyl moiety, saturated or unsaturated, unsubstituted; wherein said 3membered heterocycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents ndently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -OH, -NH2, -C1-C6-alkyl and -O-C1-C6-alkyl; a 6membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6membered aryl moiety is optionally ted through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents ndently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -OH, -NH2, -C1-C6-alkyl and -O-C1-C6-alkyl; a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said embered heteroaryl moiety is ally connected through -C1- C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -OH, -NH2, -C1-C6-alkyl and -O-C1-C6-alkyl; or R21 and R22 within -C(=O)NR21R22, -OC(=O)NR21R22, -NR21R22, -NR23-(CH2)1- 21R22, 6-C(=O)NR -NR23C(=O)NR21R22, or -S(=O)2NR21R22 together with the nitrogen atom to which they are attached form a ring and mean -(CH2)3; -(CH2)2- O-(CH2)2-; or -(CH2)2-NRB-(CH2)2-, wherein RB means -H or -C1-C6-alkyl, linear or ed, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br and -I; or a physiologically acceptable salt f [0014b] In a second ment there is provided a compound which is ed from the group consisting of cis(Cyclobutyl-methyl)dimethylamino[(4-methylsulfonyl-phenyl)-methyl]- 8-phenyl-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)dimethylamino[(3-methoxyphenyl)-methyl] phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylaminoisopropyl[(4-methoxyphenyl)-methyl]phenyl-1,3- diazaspiro[4.5]decanone; cis(Cyclopropyl-methyl)dimethylamino[(4-methoxyphenyl)-methyl] -1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)[(4-methoxyphenyl)-methyl][methyl-(2-methylpropyl )-amino]phenyl-1,3-diazaspiro[4.5]decanone; cis[[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-benzamide; cis(Cyclobutyl-methyl)dimethylaminophenyl(pyrazinyl-methyl)-1,3- diazaspiro[4.5]decanone; cis(Allyl-methyl-amino)(cyclobutyl-methyl)[(4-methoxyphenyl)-methyl]- 8-phenyl-1,3-diazaspiro[4.5]decanone; cis[[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-benzamide; cis(Cyclobutyl-methyl)dimethylamino(3-fluorophenyl)[(4- yphenyl)-methyl]-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)dimethylamino(4-fluorophenyl)[(4- methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)dimethylamino(3-methoxyphenyl)[(4- methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)dimethylamino(4-methoxyphenyl)[(4- methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decanone; Dimethylamino[(4-methoxyphenyl)-methyl](2-methyl-propyl) phenyl-1,3-diazaspiro[4.5]decanone; Butyldimethylamino[(4-methoxyphenyl)-methyl]phenyl-1,3- diazaspiro[4.5]decanone; cisDimethylamino(4-fluorophenyl)[(4-methoxyphenyl)-methyl]-1,3- diazaspiro[4.5]decanone; cisDimethylamino(3-fluorophenyl)[(4-methoxyphenyl)-methyl]-1,3- diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)dimethylamino(3-hydroxyphenyl)[(4- methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)dimethylaminophenyl(pyridinyl-methyl)-1,3- diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)dimethylamino[[3-[2-[2-[2-[2-[2-(2-methoxyethoxy )-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethoxy]-phenyl]-methyl]phenyl-1,3- diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)dimethylamino(4-hydroxyphenyl)[(4- methoxyphenyl)-methyl]-1,3-diazaspiro[4.5]decanone hydrochloride; cisDimethylamino[(1-hydroxy-cyclobutyl)-methyl][(3-methoxyphenyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cis(Cyclopentyl-methyl)dimethylamino[(4-methoxyphenyl)-methyl] phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino(2-hydroxymethyl-propyl)[(4-methoxyphenyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino(2-methoxymethyl-propyl)[(4-methoxyphenyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)[(3-methoxyphenyl)-methyl]methylamino phenyl-1,3-diazaspiro[4.5]decanone; cis[[1-(Cyclobutyl-methyl)(ethyl-methyl-amino)oxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-benzonitrile; cis(Cyclobutyl-methyl)[(3-methoxyphenyl)-methyl](methyl-propylamino )phenyl-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)(ethyl-methyl-amino)[(3-methoxyphenyl)-methyl]- 8-phenyl-1,3-diazaspiro[4.5]decanone; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-propionitrile; cis(Cyclobutyl-methyl)methylaminophenyl(pyridinyl-methyl)-1,3- diazaspiro[4.5]decanone; Dimethylamino[(4-methoxyphenyl)-methyl](oxetanyl-methyl) phenyl-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)(ethyl-methyl-amino)phenyl(pyridinylmethyl )-1,3-diazaspiro[4.5]decanone; cisDimethylamino(2-hydroxy-ethyl)[(4-methoxyphenyl)-methyl]phenyl- 1,3-diazaspiro[4.5]decanone; cisDimethylamino(2,2-dimethyl-propyl)[(4-methoxyphenyl)-methyl] phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino[(4-methoxyphenyl)-methyl](3-methyl-butyl)phenyl- 1,3-diazaspiro[4.5]decanone; cisDimethylamino[(4-methoxyphenyl)-methyl]phenyl[3- (trifluoromethyloxy)-propyl]-1,3-diazaspiro[4.5]decanone; cis(2-Cyclobutyl-ethyl)dimethylamino[(4-methoxyphenyl)-methyl] -1,3-diazaspiro[4.5]decanone; cis[(3,3-Difluoro-cyclobutyl)-methyl]dimethylamino[(4-methoxyphenyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cis[[1-(Cyclobutyl-methyl)[(4-methoxyphenyl)-methyl]oxophenyl-1,3- piro[4.5]decanyl]-methyl-amino]-acetonitrile; cis(Cyclobutyl-methyl)[(2-methoxy-ethyl)-methyl-amino][(4- methoxyphenyl)-methyl]phenyl-1,3-diazaspiro[4.5]decanone; [8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-acetic acid tert-butyl ester; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-acetic acid; 2,2,2-trifluoro-acetic acid salt; cis(Cyclobutyl-methyl)[(4-methoxyphenyl)-methyl]methylamino phenyl-1,3-diazaspiro[4.5]decanone; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-acetic acid methyl ester; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-acetamide; Benzyldimethylamino[(4-methoxyphenyl)-methyl]phenyl-1,3- diazaspiro[4.5]decanone; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-N-methyl-acetamide; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-N-propyl-acetamide; cisDimethylamino[(4-methoxyphenyl)-methyl](3-methoxy-propyl) phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino[(1-hydroxy-cyclobutyl)-methyl][(4-methoxyphenyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino(2-methoxy-ethyl)[(4-methoxyphenyl)-methyl] phenyl-1,3-diazaspiro[4.5]decanone; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-acetonitrile; cisDimethylaminohexyl[(4-methoxyphenyl)-methyl]phenyl-1,3- diazaspiro[4.5]decanone; cisDimethylamino[(4-methoxyphenyl)-methyl]phenyl(tetrahydro-pyran- 4-yl-methyl)-1,3-diazaspiro[4.5]decanone; cis(Cyclohexyl-methyl)dimethylamino[(4-methoxyphenyl)-methyl] phenyl-1,3-diazaspiro[4.5]decanone; (Cyano-methyl)[8-dimethylamino[(4-methoxyphenyl)-methyl]oxo phenyl-1,3-diazaspiro[4.5]decanyl]-acetamide; cisDimethylamino[(4-methoxyphenyl)-methyl]phenyl(pyridinylmethyl )-1,3-diazaspiro[4.5]decanone; cisDimethylamino[(4-methoxyphenyl)-methyl](3-methoxy-propyl)-1,3- diazaspiro[4.5]decanone; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-N-(2-methoxy-ethyl)-acetamide; cisDimethylamino[(4-methoxyphenyl)-methyl](2-oxopyrrolidinylethyl )phenyl-1,3-diazaspiro[4.5]decanone; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-N,N-dimethyl-acetamide; cis-N-(1-Cyano-cyclopropyl)[8-dimethylamino[(4-methoxyphenyl)-methyl]- 2-oxophenyl-1,3-diazaspiro[4.5]decanyl]-acetamide; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-N-methyl-N-propyl-acetamide; cis(Cyclobutyl-methyl)dimethylamino[(4-methoxyphenyl)-methyl](3- methoxy-propyl)-1,3-diazaspiro[4.5]decanone; cisDimethylamino(3-hydroxy-propyl)[(4-methoxyphenyl)-methyl] -1,3-diazaspiro[4.5]decanone; cisDimethylamino(4-methoxy-butyl)[(4-methoxyphenyl)-methyl] -1,3-diazaspiro[4.5]decanone; cisDimethylamino[(4-methoxyphenyl)-methyl][(1-methyl-cyclobutyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino[(1-hydroxy-cyclohexyl)-methyl][(4-methoxyphenyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- piro[4.5]decanyl]-pentanenitrile; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-propionamide; cis(Cyclobutyl-methyl)[(2-hydroxy-ethyl)-methyl-amino][(4- methoxyphenyl)-methyl]phenyl-1,3-diazaspiro[4.5]decanone; cis[[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-cyclobutanecarbonitrile; cisDimethylamino[(1-hydroxy-cyclopentyl)-methyl][(4-methoxyphenyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cis[(2-Bromophenyl)-methyl](cyclobutyl-methyl)dimethylaminophenyl- 1,3-diazaspiro[4.5]decanone; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-N-methyl-propionamide; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- piro[4.5]decanyl]-N-propyl-propionamide; cisDimethylamino[(1-fluoro-cyclobutyl)-methyl][(4-methoxyphenyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cis(2-Cyclohexyl-ethyl)dimethylamino[(4-methoxyphenyl)-methyl] phenyl-1,3-diazaspiro[4.5]decanone; cis[[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-benzonitrile; cisDimethylamino[(4-methoxyphenyl)-methyl]methylphenyl-1,3- diazaspiro[4.5]decanone; cisDimethylamino[2-[2-[2-[2-[2-[2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy]- ]-ethoxy]-ethoxy]-ethoxy]-ethyl][(4-methoxyphenyl)-methyl]phenyl- 1,3-diazaspiro[4.5]decanone; cisDimethylamino[(4-methoxyphenyl)-methyl]phenyl(2-tetrahydropyranyl-ethyl )-1,3-diazaspiro[4.5]decanone; cis[[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-benzonitrile; (Cyclobutyl-methyl)dimethylaminophenyl[[6-(trifluoromethyl)- pyridinyl]-methyl]-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)dimethylamino[[4-[2-[2-[2-[2-[2-[2-[2-(2-methoxyethoxy )-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethoxy]-phenyl]- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cis[[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-benzamide; cis(Cyclobutyl-methyl)dimethylamino[(4-hydroxyphenyl)-methyl] phenyl-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)(ethyl-methyl-amino)[(4-methoxyphenyl)-methyl]- 8-phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino[(1-methoxy-cyclobutyl)-methyl][(4-methoxyphenyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cis[[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-benzonitrile; cis(Cyclobutyl-methyl)dimethylamino[(3-methylsulfonyl-phenyl)-methyl]- 8-phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylaminoethyl[(4-methoxyphenyl)-methyl]phenyl-1,3- diazaspiro[4.5]decanone; Dimethylamino[(4-methoxyphenyl)-methyl]phenylpropyl-1,3- diazaspiro[4.5]decanone; cisBenzyl(cyclobutyl-methyl)dimethylaminophenyl-1,3- diazaspiro[4.5]decanone; cisDimethylamino[(4-methoxyphenyl)-methyl]phenyl-1,3- diazaspiro[4.5]decanone; cisDimethylamino[(4-methoxyphenyl)-methyl]phenyl(pyrimidinylmethyl )-1,3-diazaspiro[4.5]decanone; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-2,2-dimethyl-propionitrile; cis[[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-benzoic acid methyl ester; cis(Cyclobutyl-methyl)dimethylaminophenyl(pyridinyl-methyl)-1,3- diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)dimethylaminophenyl(pyridinyl-methyl)-1,3- diazaspiro[4.5]decanone; cisDimethylamino[(4-methoxyphenyl)-methyl]phenyl(tetrahydro-furan- 3-yl-methyl)-1,3-diazaspiro[4.5]decanone; (Cyclobutyl-methyl)dimethylaminophenyl(pyrimidinyl-methyl)- 1,3-diazaspiro[4.5]decanone; cis[[1-[(5-Cyanomethoxy-phenyl)-methyl]dimethylaminooxophenyl- 1,3-diazaspiro[4.5]decanyl]-methyl]methoxy-benzonitrile; cisDimethylamino(3-hydroxymethyl-butyl)[(4-methoxyphenyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino(3-methoxymethyl-butyl)[(4-methoxyphenyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cis[[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-benzamide; cis[[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-benzamide; cisDimethylamino[(4-methoxyphenyl)-methyl](2-methylsulfonyl-ethyl) phenyl-1,3-diazaspiro[4.5]decanone; cis[(1-Hydroxy-cyclobutyl)-methyl][(4-methoxyphenyl)-methyl] methylaminophenyl-1,3-diazaspiro[4.5]decanone; Dimethylamino[(4-methoxyphenyl)-methyl]phenyl(tetrahydro-furan- 2-yl-methyl)-1,3-diazaspiro[4.5]decanone; cisBenzyldimethylaminophenyl-1,3-diazaspiro[4.5]decanone; cisBenzyldimethylaminoethylphenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino[(4-methoxyphenyl)-methyl][2-(methylsulfinyl)-ethyl]- yl-1,3-diazaspiro[4.5]decanone; cisDimethylamino[(2R)hydroxy-propyl][(4-methoxyphenyl)-methyl] phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino[(2S)hydroxy-propyl][(4-methoxyphenyl)-methyl] phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino[(4-methoxyphenyl)-methyl]phenyl(tetrahydro-furan- 3-yl-methyl)-1,3-diazaspiro[4.5]decanone; cisDimethylaminoethyl[(4-methoxyphenyl)-methyl]phenyl-1,3- diazaspiro[4.5]decanone; cisAmino[(1-hydroxy-cyclobutyl)-methyl][(4-methoxyphenyl)-methyl] phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino[(1-hydroxy-cyclobutyl)-methyl]phenyl(2-phenylethyl )-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)dimethylaminophenyl[(4-methoxyphenyl)- methyl]-1,3-diazaspiro[4.5]decanone; cis[[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]methoxy-benzonitrile; cisDimethylaminoethylphenyl(pyridinyl-methyl)-1,3- diazaspiro[4.5]decanone; cisDimethylamino[2-(1-methoxy-cyclobutyl)-ethyl][(4-methoxyphenyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino[3-(methoxymethyloxy)-phenyl][(4-methoxyphenyl)- methyl]-1,3-diazaspiro[4.5]decanone; Dimethylamino[4-(methoxymethyloxy)-phenyl][(4-methoxyphenyl)- methyl]-1,3-diazaspiro[4.5]decanone; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-propionic acid; cis[8-Dimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-propionic acid tert-butyl ester; cis[[1-(Cyclobutyl-methyl)[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl-amino]-acetic acid methyl ester; cisDimethylamino[(4-methoxyphenyl)-methyl](3-methyl-butenyl) phenyl-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)dimethylamino[(3-methylsulfanyl-phenyl)-methyl]- 8-phenyl-1,3-diazaspiro[4.5]decanone; cis[(3-Bromophenyl)-methyl](cyclobutyl-methyl)dimethylaminophenyl- 1,3-diazaspiro[4.5]decanone; ((8-(dimethylamino)((1-hydroxycyclobutyl)methyl)oxophenyl-1,3- diazaspiro[4.5]decanyl)methyl)benzonitrile; cisDimethylamino(3-methoxyphenyl)[(4-methoxyphenyl)-methyl]-1,3- diazaspiro[4.5]decanone; cisDimethylamino(4-methoxyphenyl)[(4-methoxyphenyl)-methyl]-1,3- piro[4.5]decanone; cis((8-(dimethylamino)((1-hydroxycyclobutyl)methyl)oxophenyl-1,3- diazaspiro[4.5]decanyl)methyl)benzonitrile; cis((8-(dimethylamino)oxophenyl-1,3-diazaspiro[4.5]decanyl)methyl)- 4-methoxybenzonitrile; cisDimethylaminophenyl(1H-[1,2,3]triazolyl-methyl)-1,3- diazaspiro[4.5]decanone; cisDimethylamino[[1-(2-hydroxy-ethyl)-1H-[1,2,3]triazolyl]-methyl] phenyl-1,3-diazaspiro[4.5]decanone; cis[4-[(8-Dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)- ]-1H-[1,2,3]triazolyl]-acetamide; cisMethylaminophenyl(1H-[1,2,3]triazolyl-methyl)-1,3- diazaspiro[4.5]decanone; cisDimethylamino[(4-methoxyphenyl)-methyl]phenyl(p-tolylsulfonyl)- 1,3-diazaspiro[4.5]decanone; cis[4-[(8-Methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-methyl]- 1H-[1,2,3]triazolyl]-acetamide; cisDimethylamino[(4-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanecarboxylic acid benzyl ester; cis[[1-(2-Hydroxy-ethyl)-1H-[1,2,3]triazolyl]-methyl]methylamino phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylaminophenyl(2-pyridinyl-ethyl)-1,3-diazaspiro[4.5]decane- 2,4-dione; cisDimethylaminophenyl(2-pyridinyl-ethyl)-1,3-diazaspiro[4.5]decan cisDimethylamino[(1-hydroxy-cyclobutyl)-methyl][[1-(2-hydroxy-ethyl)- 1H-[1,2,3]triazolyl]-methyl]phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino[2-(1H-imidazolyl)-ethyl]phenyl-1,3- diazaspiro[4.5]decane-2,4-dione; cis[4-[[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl- 1,3-diazaspiro[4.5]decanyl]-methyl]-1H-[1,2,3]triazolyl]-acetamide; cis[(1-Hydroxy-cyclobutyl)-methyl][[1-(2-hydroxy-ethyl)-1H-[1,2,3]triazol yl]-methyl]methylaminophenyl-1,3-diazaspiro[4.5]decanone; cisDimethylaminophenyl(2-pyridinyl-ethyl)-1,3-diazaspiro[4.5]decane- 2,4-dione; cisDimethylaminophenyl(2-pyridinyl-ethyl)-1,3-diazaspiro[4.5]decane- 2,4-dione; cis[4-[[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-1H-[1,2,3]triazolyl]-acetamide; cis(Cyclobutyl-methyl)dimethylamino[[1-(2-hydroxy-ethyl)-1H- ]triazolyl]-methyl]phenyl-1,3-diazaspiro[4.5]decanone; cis[4-[[1-[(1-Hydroxy-cyclobutyl)-methyl]methylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-1H-[1,2,3]triazolyl]-acetamide; (Cyclobutyl-methyl)[[1-(2-hydroxy-ethyl)-1H-[1,2,3]triazolyl]-methyl]- ylaminophenyl-1,3-diazaspiro[4.5]decanone; cis[4-[[1-(Cyclobutyl-methyl)methylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-1H-[1,2,3]triazolyl]-acetamide; cisDimethylaminophenyl(2-pyridinyl-ethyl)-1,3-diazaspiro[4.5]decan cisDimethylamino[2-(1H-imidazolyl)-ethyl]phenyl-1,3- diazaspiro[4.5]decanone; cisDimethylaminophenyl(2-pyridinyl-ethyl)-1,3-diazaspiro[4.5]decan cisDimethylaminophenyl(2-pyrimidinyl-ethyl)-1,3- diazaspiro[4.5]decanone; cisDimethylaminophenyl(2-pyrimidinyl-ethyl)-1,3- diazaspiro[4.5]decanone; cisDimethylaminoethyl[(4-methylsulfonyl-phenyl)-methyl]phenyl-1,3- diazaspiro[4.5]decanone; cisDimethylamino(1-methylphenyl-ethyl)phenyl-1,3- diazaspiro[4.5]decanone; cisDimethylaminophenyl(1-phenyl-cyclopropyl)-1,3-diazaspiro[4.5]decan- 2-one; cisDimethylamino-1,3-bis[(2-methoxyphenyl)-methyl]phenyl-1,3- diazaspiro[4.5]decanone; cisDimethylamino[(3-methylsulfonyl-phenyl)-methyl]phenyl-1,3- diazaspiro[4.5]decanone; cisDimethylamino[(1-hydroxy-cyclobutyl)-methyl](1-methylphenylethyl )phenyl-1,3-diazaspiro[4.5]decanone; [(3-Cyclopropyl-phenyl)-methyl]dimethylaminophenyl-1,3- diazaspiro[4.5]decanone; cis(1,3-Benzodioxolyl-methyl)dimethylaminophenyl-1,3- diazaspiro[4.5]decanone; Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]phenyl(1-phenylcyclopropyl )-1,3-diazaspiro[4.5]decanone; cis[[8-Dimethylamino[(2-methoxyphenyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-methyl]-benzonitrile; cisDimethylamino[(2-methoxyphenyl)-methyl]phenyl-1,3- diazaspiro[4.5]decanone; cisDimethylaminophenyl(pyridinyl-methyl)-1,3-diazaspiro[4.5]decan cisDimethylaminophenyl(pyridinyl-methyl)-1,3-diazaspiro[4.5]decan cisDimethylaminophenyl(pyridinyl-methyl)-1,3-diazaspiro[4.5]decan Dimethylamino[[2-(4-methyl-piperazinyl)-pyridinyl]-methyl] phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylaminophenyl[(2-piperidinyl-pyridinyl)-methyl]-1,3- diazaspiro[4.5]decanone; cisDimethylamino[(2-morpholinyl-pyridinyl)-methyl]phenyl-1,3- diazaspiro[4.5]decanone; cisDimethylaminophenyl[(2-piperazinyl-pyridinyl)-methyl]-1,3- diazaspiro[4.5]decanone; and the physiologically acceptable salts thereof. [0014c] In a third ment there is provided use of the compound according to the second ment for the manufacture of a medicament for treating pain. [0014d] In a fourth embodiment there is provided a medicament comprising a compound according to the second embodiment. A first aspect of the invention relates to 3-((hetero-)aryl)-alkylaminooxo-1,3- diaza-spiro-[4.5]-decane derivatives according to general formula (I) R7 R8 R13 R14R15 R16 R11 R12 R1 R5 N R2 R4 R18R19 R17 R20 wherein n means 1, 2 or 3; R1 and R2 independently of one another mean -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -OH, -OCH3, -CN and -CO2CH3; a 3membered lkyl moiety, saturated or unsaturated, tituted or substituted with one, two, three or four substituents independently of one another ed from the group consisting of -F, -Cl, -Br, -I, -OH, -OCH3, -CN and -CO2CH3; wherein said 3 membered cycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted; or a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -OH, -OCH3, -CN and -CO2CH3; wherein said 3membered heterocycloalkyl moiety is optionally ted h -C1-C6-alkylene- , linear or branched, saturated or unsaturated, unsubstituted; R1 and R2 together with the nitrogen atom to which they are attached form a ring and mean 3; -(CH2)2-O-(CH2)2-; or -(CH2)2-NRA-(CH2)2-, n RA means -H or -C1-C6- alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br and -I; preferably with the proviso that R1 and R2 do not aneously mean -H; R3 means -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; NEXT PAGE IS PAGE 4 a embered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; n said 3membered cycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono— or polysubstituted; a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3membered heterocycloalkyl moiety is optionally connected h -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono— or polysubstituted; a 6membered aryl moiety, tituted, mono— or polysubstituted; wherein said embered aryl moiety is ally connected through —C1—C6—all unsubstituted, mono- or polysubstituted; or a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is optionally connected through -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; R4 means -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said -C1-C6-alkyl is optionally ted through -C(=O)-, O—, or —S(=O)2-; a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3membered cycloalkyl moiety is ally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 3membered cycloalkyl moiety is optionally connected h -C(=O)—, —C(=O)O-, -C(=O)O-CH2-, or -S(=O)2-; a 3membered heterocycloalkyl moiety, saturated or unsaturated, tituted, mono- or bstituted; wherein said 3membered cycloalkyl moiety is ally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono— or polysubstituted; or wherein said embered heterocycloalkyl moiety is optionally ted through —C(=O)—, —C(=O)O-, -C(=O)O-CH2-, or -S(=O)2-; a 6-l4-membered aryl moiety, unsubstituted, mono— or polysubstituted; wherein said 6membered aryl moiety is optionally connected through —C1—C6—alkylene—, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 6—14—membered aryl moiety is optionally ted through -C(=O)—, -C(=O)O-, -C(=O)O-CH2—, or —S(=O)2—; or a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 5membered heteroaryl moiety is optionally connected through -C(=O)-, —C(=O)O—, O—CH2—, or —S(=O)2—; R5 means a 6membered aryl moiety, tituted, mono— or polysubstituted; or a 5membered heteroaryl moiety, unsubstituted, mono— or polysubstituted; R7, R8, R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20 independently of one another mean -H, -F, -Cl, -Br, -I, - OH, or -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein R7 and R8 together with the carbon atom to which they are attached form a ring and mean -(CH2)2- or '(CH2)3'; wherein "mono- or polysubstituted" means that one or more hydrogen atoms are replaced by a tuent independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -R21, -C(=O)R21, - C(=O)OR21, -C(=0)NR“R22, -O-(CH2CH2-O)1_30-H, -O-(CH2CH2-O)1_3o-CH3, =0, -OR21, )R21, - OC(=O)OR21, -OC(=O)NR21R22, -Noz, -NR21R22, -NR2‘-(CH2)M-C(=O)R22, -NR21-(CH2)1_6-C(=O)OR22, -NR23- (CH2)1_6-C(=O)NR21R22, -NR21C(=O)R22, -NR2‘C(=O)-OR22, -NR23C(=O)NR21R22, -NRZIS(=O)2R22, -SR21, - S(=O)R21, -S(=O)2R21, -S(=O)20R21, and -S(=O)2NR2‘R22; wherein R21, R22 and R23 independently of one r mean -C1-C6-alkyl, linear or branched, ted or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -1, -CN, -OH, - NHZ, and C6-alkyl; a 3membered lkyl moiety, saturated or rated, unsubstituted; wherein said 3membered cycloalkyl moiety is optionally connected through -alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents ndently of one r selected from the group consisting of -F, -Cl, -Br, -1, -CN, -OH, —NH2, -C1-C6-alkyl and -O-C1-C6-alkyl; a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted; wherein said 3membered heterocycloalkyl moiety is optionally connected h —C1—C6-alkylene-, linear or branched, saturated or unsaturated, tituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -1, -CN, -OH, -NH2, -C1-C6-all a 6membered aryl moiety, unsubstituted, mono— or polysubstituted; wherein said 6membered aryl moiety is optionally connected through —C1—C6—a]kylene—, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -1, -CN, -OH, -NH2, -C1-C6-alkyl and -O-C1-C5-alkyl; a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is optionally ted through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted or tuted with one, two, three or four substituents ndently of one another selected from the group consisting of -F, -Cl, -Br, -1, -CN, —OH, —NH2, —C1—C6—alkyl and -O-C1-C5-alkyl; or R21 and R22 within -C(=O)NR21R22, -OC(=O)NR“RZZ, 22, -NR23-(CH2)1_6-C(=O)NR21R22, — NR23C(=O)NR21R22, or -S(=O)2NR21R22 together with the nitrogen atom to which they are attached form a ring and mean -(CH2)3_6-; -(CH2)2-O-(CH2)2-; or -(CH2)2—NRB-(CH2)2-, wherein RB means -H or -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four tuents independently of one another selected from the group consisting of -F, -Cl, -Br and -I; or a physiologically acceptable salt f. Preferably, aryl includes but is not d to phenyl and naphthyl. Preferably, heteroaryl includes but is not limited to -1,2-benzodioxole, inyl, —pyridazinyl, —pyridinyl, —pyrimidinyl, -thienyl, -imidazoly1, - benzimidazolyl, -thiazoly1, -1,3,4-thiadiazolyl, -benzothiazolyl, -oxazolyl, xazoly1, -pyrazoly1, -quinolinyl, -isoquinolinyl, -quinazoliny1, -indolyl, -indolinyl, -benzo[c][l,2,5]oxadiazolyl, -imidazo[1,2-a]pyrazinyl, or -lH- pyrrolo[2,3-b]pyridinyl. ably, cycloalkyl includes but is not limited to -cyclopropyl, -cyclobutyl, - entyl and -cyclohexyl. Preferably, heterocycloalkyl includes but is not limited to -aziridinyl, -azetidinyl, - pyrrolidinyl, -piperidinyl, -piperazinyl, -morpholinyl, -sulfamorpholinyl, -0xiridinyl, -oxetanyl, - tetrahydropyranyl, and -pyranyl. When a moiety is connected through an asymmetric group such as -C(=O)O- or -C(=O)O-CH2-, said asymmetric group may be arranged in either direction. For example, When R4 is connected to the core structure through -C(=O)O-, the arrangement may be either R4—C(=O)O—core or core-C(=O)O-R4. In preferred embodiments of the compound ing to the invention, R7, R8, R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20 independently of one another mean -H, —F, -OH, or -C1-C6-alkyl; preferably -H. In preferred embodiments of the compound according to the invention, R7 and R8 together with the carbon atom to which they are attached form a ring and mean -(CH2)2- (i.e. form a cyclopropyl ring) or -(CH2)3- (i.e. form a cyclobutyl ring). In a red ment of the compound according to the ion, Rl means -H; and R2 means - C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted. Preferably, R1 means -H and R2 means -CH3. In another preferred embodiment of the nd according to the invention, R1 means -CH3; and R2 means -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or bstituted. Preferably, R1 means -CH3 and R2 means -CH3. In still another preferred embodiment of the compound according to the invention, R1 and R2 together with the en atom to which they are attached form a ring and mean -(CH2)3_6-. Preferably, R1 and R2 together with the nitrogen atom to Which they are attached form a ring and mean -(CH2)3-. In yet another preferred embodiment, - Rl means -H or -CH3; and - R2 means a 3-l2-membered cycloalkyl moiety, saturated or unsaturated, tituted; wherein said 3 membered cycloalkyl moiety is ted through —CH2-, unsubstituted; preferably -CH2-cycloalkyl, -CH2- cyclobutyl or -CH2-cyclopentyl; or R2 means a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted; wherein said embered heterocycloalkyl moiety is ted through -CH2- or -CH2-tetrahydrofuranyl. , unsubstituted; preferably -CH2-oxetanyl In a preferred embodiment of the compound according to the invention, R3 means -alkyl, linear or branched, ted or rated, unsubstituted, mono— or polysubstituted. Preferably, R3 means -C1-C5- alkyl, linear or branched, saturated or unsaturated, unsubstituted or monosubstituted with -OCH3. In another preferred embodiment of the compound according to the invention, R3 means a 6 membered aryl moiety, unsubstituted, mono- or polysubstituted, optionally connected through -C1-C5-alkylene-, linear or branched, saturated or unsaturated, unsubstituted. In a preferred embodiment, R3 means -phenyl unsubstituted, mono- or polysubstituted. More preferably, R3 means l unsubstituted, mono- or disubstituted with -F, -Cl, -CH3, -CF3, —OH, —OCH;, —OCF3 or —OCHZOCH3, preferably -F. In another preferred embodiment, R3 means -benzyl unsubstituted, mono— or polysubstituted. More preferably, R3 means -benzyl unsubstituted, mono- or disubstituted with -F, -Cl, —CH3, —CF3, —OH, —OCH3, -OCF3 or -OCH20CH3, preferably - In still another preferred embodiment of the compound according to the invention, R3 means a 5 ed aryl moiety, unsubstituted, mono- or polysubstituted. Preferably, R3 means -thienyl or - pyridinyl, in each case unsubstituted, mono- or polysubstituted. More preferably, R3 means -thienyl, -pyridinyl, - imidazolyl or benzimidazolyl, in each case unsubstituted or monosubstituted with -F, -Cl or -CH3. In a preferred embodiment of the compound according to the invention, R4 means -H. In another preferred embodiment of the compound according to the invention, R4 means -alkyl, linear or branched, ted or unsaturated, unsubstituted, mono— or polysubstituted. ably, R4 means -C1- yl, linear or branched, saturated or unsaturated, unsubstituted or monosubstituted with a substituent ed from the group consisting of -F, -Cl, -Br, -1, -CN, -CF3, -OH, -O-C1-C4-all 30-H, -O-(CH2CH2-O)1_30-CH3, -OC(=O)C1-C4-alkyl, -C(=O)C1-C4-alkyl, —C(=O)OH, -C(=O)OC1-C4-alkyl, - C(=O)NH2, -C(=O)NHC1-C4-alkyl, -C(=O)NHC1-C4-alky1ene-CN, -C(=O)NHC1—C4—a1ky1ene-O-C1-C4-a1ky1, - C(=O)N(C1-C4-alky1)2; -S(=O)C1-C4-a1kyl, and 2C1-C4-alkyl; or with -C(=O)NR21R22 wherein R21 and R22 together with the nitrogen atom to which they are attached form a ring and mean -(CH2)3_5-, -(CH2)2-O-(CH2)2-, or -(CH2)2-NRB-(CH2)2-, wherein RB means -H or -C1-C6-alkyl; or with -C(=O)NH12-membered cycloalkyl, saturated or unsaturated, unsubstituted or monosubstituted with -F, -Cl, -Br, -1, -CN, or -OH; or with -C(=O)NH- 3membered heterocycloalkyl, ted or unsaturated, unsubstituted or monosubstituted with -F, -Cl, -Br, -1, -CN, or -OH. More ably, R4 means -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted or monosubstituted with -O-C1-C4-alkyl or N(C1-C4-alkyl)z. In still another preferred embodiment of the compound according to the invention, R4 means a 3-l2- membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein the 3- lZ-membered cycloalkyl moiety is connected through -alkylene-, linear or branched, saturated or unsaturated, tituted, mono- or polysubstituted. Preferably, R4 means a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono— or polysubstituted; n said 3membered cycloalkyl moiety is ted through -CH2- or -CH2CH2-. More preferably, R4 means a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted or tuted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -1, -CN, -OH, -C1-C4-alkyl, -OC1-C4-alkyl , -C(=O)OH, -C(=O)OC1-C4-alkyl, —C(=O)NH2, -C(=0)NHC1-C4-alkyl, -C(=O)N(C1-C4-alkyl)2, - S(=O)C1-C4-alkyl and -S(=O)2C1-C4-alkyl; wherein said 3—12—membered cycloalkyl moiety is connected through -CH2- or -CH2CH2-. In a preferred embodiment of the compound according to the invention, R4 means a 3membered cycloalkyl , saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3 membered heterocycloalkyl moiety is connected through -C1-C6-alkylene-, linear or branched, ted or unsaturated, unsubstituted, mono— or polysubstituted. Preferably, R4 means a 3membered heterocycloalkyl moiety, ted or unsaturated, unsubstituted, mono— or polysubstituted; n said embered heterocycloalkyl moiety is connected through —CH2— or —CH2CH2—. More preferably, R4 means -oxetanyl, - tetrahydrofuranyl or -tetrahydropyranyl, in each case unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -1, -CN, -OH, -C1- C4-alkyl, -O-C1-C4-alkyl, -C(=O)OH, -C(=O)OC1-C4-alkyl, —C(=O)NH2, -C(=O)NHC1-C4-alkyl, -C(=O)N(C1- C4-alkyl)2, -S(=O)C1-C4-alkyl and -S(=O)2C1-C4-alkyl; wherein said -oxetanyl, -tetrahydrofuranyl or - tetrahydropyranyl is ted through -CH2- or -CH2CH2-. In yet another preferred embodiment of the compound ing to the invention, R4 means a 6-l4- membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6membered aryl moiety is connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, tituted, mono- or polysubstituted. Preferably, R4 means -phenyl, unsubstituted, mono- or polysubstituted; wherein said -phenyl is connected through -CH2- or -CH2CH2-. More preferably, R4 means -phenyl, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, - Br, -1, -CN, -OH, -C1-C4-alkyl, -O-C1-C4-alkyl, -C(=O)OH, -C(=O)OC1—C4-alkyl, -C(=O)NH2, -C(=O)NHC1-C4- alkyl, -C(=O)N(C1-C4-alkyl)2, C1-C4-alkyl and -S(=O)2Cl-C4-all through -CH2- or -CH2CH2-. In a further preferred ment of the compound according to the invention, R4 means a 5 membered heteroaryl moiety, tituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or bstituted. Preferably, R4 means a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said l is connected through -CH2- or -CH2CH2-. More ably, R4 means - pyridinyl, -pyrimidinyl, -pyrazinyl, or -pyrazolinyl, in each case unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -1, -CN, - OH, -C1-C4-alkyl, -O-C1-C4-alkyl, -C(=O)OH, —C(=O)OC1—C4—alkyl, -C(=O)NH2, -C(=O)NHC1-C4-alkyl, — C(=O)N(C1-C4-alkyl)2, -S(=O)C1-C4-alkyl and —S(=O)2C1-C4-alkyl; wherein said -pyridinyl, -pyrimidinyl, - pyrazinyl, or olinyl is ted through —CH2— or —CH2CH2-. In a preferred embodiment of the compound according to the ion, n means 1 or 2. Preferably, n means
1. In a preferred embodiment of the compound according to the invention, R5 means -phenyl, unsubstituted, mono- or polysubstituted. Preferably, R5 means —phenyl unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F; -Cl; -Br; -1; -CN; -OH; -C1-C4-a1ky1; -CF3; 12-membered cycloalkyl, saturated or unsaturated, tituted, mono- or polysubstituted; preferably -cyclopropyl, saturated, unsubstituted; 12-membered heterocycloalkyl, ted or unsaturated, unsubstituted, mono- or polysubstituted; preferably -pyrrolidiny1, -piperidiny1, -morpholiny1, - piperazinyl, -thiomorpholiny1, or -thiomorpholinyl dioxide, in each case saturated, unsubstituted or bstituted With -C1-C4-alkyl; —O—CH2-O- (such that it is condensed with a dioxolanyl ring); -O-C1-C4- alkyl; -O-(CH2CH2-O)1.3o-H; -O-(CH2CH2-0)1-3o-CH3; -C(=O)OH; -C(=O)OC1-C4-alky1; -C(=O)NH2; - C(=O)NHC1-C4-alkyl; -C(=O)N(C1-C4-alkyl)2; —S(=O)C1—C4—alkyl and —S(=O)2C1-C4-alkyl. In another preferred embodiment of the compound according to the invention, R5 means -pyrazinyl, - pyridazinyl, -pyridinyl, -pyrimidinyl, -thienyl, -imidazolyl, triazolyl, or -l,3-benzodioxolyl, in each case unsubstituted, mono- or polysubstituted. Preferably, R5 means —pyrazinyl, -pyridazinyl, -pyridinyl, -pyrimidinyl, -thienyl, -imidazolyl, triazolyl, or -1,3-benzodioxolyl, in each case unsubstituted or substituted with one, two, three or four tuents independently of one another selected from the group ting of -F; -Cl; -Br; -I; - CN; -OH; -C1-C4-alkyl; -CF3; -C1-C4-alkyl-OH; —C1-C4-alkyl-C(=O)NH2; 12-membered cycloalkyl, saturated or rated, unsubstituted, mono- or polysubstituted; preferably -cyclopropyl, saturated, unsubstituted; 12- membered heterocycloalkyl, saturated or unsaturated, tituted, mono- or polysubstituted; preferably - pyrrolidinyl, -piperidinyl, -morpholinyl, -piperazinyl, -thiomorpholinyl, or orpholinyl dioxide, in each case saturated, unsubstituted or monosubstituted with —C1—C4—alky1; -O-CH2-O- (such that it is condensed with a dioxolanyl ring); -O-C1-C4-alkyl; -O-(CH2CH2—O)1_30—H; —O—(CH2CH2-O)1_30-CH3; OH; -C(=O)OC1-C4- alkyl; -C(=O)NH2; -C(=O)NHC1-C4-alkyl; —C(=O)N(C1—C4-alkyl)2; -SC1-C4-alkyl; -S(=O)C1-C4-alkyl and - S(=O)2C1-C4-alkyl. [003 6] In preferred embodiments, the compound ing to the invention has a structure according to any of general formulas (II-A) to (VIII-C): (II-A) (II-B) RS/ (CI—L2)”N MR2 )
NZ745188A 2017-01-13 3-((hetero-)aryl)-alkyl-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives NZ745188B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP16151013 2016-01-13
PCT/EP2017/025006 WO2017121648A1 (en) 2016-01-13 2017-01-13 3-((hetero-)aryl)-alkyl-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives

Publications (2)

Publication Number Publication Date
NZ745188A NZ745188A (en) 2024-05-31
NZ745188B2 true NZ745188B2 (en) 2024-09-03

Family

ID=

Similar Documents

Publication Publication Date Title
US20230338373A1 (en) Inhibitor of indoleamine-2,3-dioxygenase (ido)
JP2019501939A5 (en)
ES2644870T3 (en) Oxathiazine derivatives as antibacterial and anticancer agents
ES2799582T3 (en) Process for the synthesis of an indoleamine 2,3-dioxygenase inhibitor
EP2571501B1 (en) Sigma ligands for the prevention and/or treatment of emesis induced by chemotherapy or radiotherapy
CN117820226A (en) Compounds for the treatment of kinase dependent disorders
TWI636048B (en) 3-((hetero-)aryl)-alkyl-8-amino-2-oxo-1,3-1,3-diaza-spiro-[4.5]-nonane derivative
RU2012141536A (en) IMIDAZOPYRIDINES, COMPOSITIONS AND METHODS OF APPLICATION
EP3215160A1 (en) Use of compositions modulating chromatin structure for graft versus host disease (gvhd)
US9023848B2 (en) Small-molecules as therapeutics
BRPI0409787B1 (en) 2-ALKINYL AND 2-ALKENYL-PIRAZOL- [4,3-e] -1,2,4-TRIAZOL- [1,5-c] -PYRIMIDINE ADENOSINE A2a RECEPTOR ANTAGONISTS
EP3442943B1 (en) Aminobenzoic acid derivatives for use as anti-inflammatory agents, anti-metastatic agents and/or anticancer agents
WO2022105852A1 (en) Triazine dione derivative, preparation method therefor and application thereof in medicine
US20240294460A1 (en) Deuterated analogs and derivatives of 4-bromo-2,5-dimethoxyphenethylamine and uses thereof
NZ745188B2 (en) 3-((hetero-)aryl)-alkyl-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives
AU2016204389B2 (en) Kinase inhibitors for the treatment of cancer
WO2017106520A1 (en) Compounds, compositions and methods of treating cancer
EP3006432B1 (en) 2,3-butanediamide epoxide compound and preparation method and use thereof
EP4658641A1 (en) Novel compounds that can be used as therapeutic agents
WO2020077459A1 (en) Aminobenzoic acid derivatives for use as anti-inflammatory agents, anti-metastatic agents and/or anticancer agents
de L. Ferreira et al. Synthesis and cytotoxic evaluation of disubstituted N-acylhydrazones pyrazinecarbohydrazide derivatives
US20220324849A1 (en) Truncated itraconazole analogues and methods of use thereof
CN121873098A (en) Spirocyclic compounds, their preparation methods and their pharmaceutical applications
HK1183447B (en) Sigma ligands for the prevention and/or treatment of emesis induced by chemotherapy or radiotherapy
HK1124837A (en) Pyrazole derivatives and their medical use