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NZ745184B2 - 3-(carboxymethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives - Google Patents
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NZ745184B2 - 3-(carboxymethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives - Google Patents

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

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NZ745184B2
NZ745184B2 NZ745184A NZ74518417A NZ745184B2 NZ 745184 B2 NZ745184 B2 NZ 745184B2 NZ 745184 A NZ745184 A NZ 745184A NZ 74518417 A NZ74518417 A NZ 74518417A NZ 745184 B2 NZ745184 B2 NZ 745184B2
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New Zealand
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methyl
diazaspiro
cis
cyclobutyl
decanyl
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NZ745184A
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NZ745184A (en
Inventor
Florian Jakob
Ruth Jostock
Achim Kless
Thomas Koch
Rene Michael Koenigs
Sven Kuhnert
Klaus Linz
Paul Ratcliffe
Klaus Schiene
Wolfgang Schroder
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Grünenthal GmbH
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Priority claimed from PCT/EP2017/025007 external-priority patent/WO2017121649A1/en
Publication of NZ745184A publication Critical patent/NZ745184A/en
Publication of NZ745184B2 publication Critical patent/NZ745184B2/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic 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
    • A61K31/41641,3-Diazoles
    • A61K31/41841,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
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    • C07D401/06Heterocyclic 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
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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 chain containing hetero atoms as chain links
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/06Heterocyclic 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
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/12Heterocyclic 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 chain containing hetero atoms as chain links
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/12Heterocyclic 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 chain containing hetero atoms as chain links
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
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    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06008Dipeptides with the first amino acid being neutral
    • C07K5/06017Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06026Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala

Abstract

The invention relates to 3-(carboxymethyl)-8-amino-2-oxo-l,3-diaza- spiro-[4.5]-decane derivatives of general formula (I), their preparation and their use in medicine, particularly in the treatment of pain.

Claims (15)

patent claims :
1. A compound according to general formula (I) R 13 16 R 10 R 9 R 14 R 15 R R 12 R 1 5 N R N R 2 O R 3 R 4 R 18 R 19 R 17 R 20 wherein R1 and R2 independently of one another mean -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, -I, - OH, -OCH3, -CN and 3; 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 lkyl 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 selected from the group consisting of -F, -Cl, -Br, -I, -OH, -OCH3, -CN and -CO2CH3; wherein said 3 membered heterocycloalkyl moiety is ally connected through -C1-C6-alkylene-, linear or ed, saturated or unsaturated, 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, unsubstituted or substituted with one, two, three or four substituents independently of one another ed from the group consisting of -F, -Cl, -Br and -I; R3 means -C1-C6-alkyl, linear or ed, saturated or unsaturated, tituted, mono- or polysubstituted; a embered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3membered cycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or ed, saturated or rated, unsubstituted, mono- or polysubstituted; a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted ; n said 3membered heterocycloalkyl moiety is ally connected through -C1-C6- alkylene-, linear or branched, saturated or rated, unsubstituted, mono- or polysubstituted; a 6membered 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 a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is ally 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, tituted, mono- or polysubstituted; wherein said -C1-C6-alkyl is optionally connected through -C(=O)-, -C(=O)O-, or -S(=O)2-; a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or bstituted; 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 3 membered cycloalkyl moiety is optionally ted through -C(=O)-, -C(=O)O-, -C(=O)O-CH2-, or - S(=O)2-; a 3membered heterocycloalkyl , saturated or unsaturated, unsubstituted, mono- or polysubstituted ; wherein said 3membered heterocycloalkyl moiety is ally connected through -C1-C6- alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 3membered 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; wherein said 6membered aryl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or n said embered aryl moiety is optionally connected through -C(=O)-, -C(=O)O-, -C(=O)O-CH2-, or -S(=O)2-; or a 5membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said embered heteroaryl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or bstituted; or wherein said 5membered heteroaryl moiety is optionally connected through -, -C(=O)O-, -C(=O)O-CH2-, or 2-; X means -O-, -S- or -NR6-; R5 means -C1-C6-alkyl, linear or branched, saturated or rated, unsubstituted, mono- or polysubstituted; a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3membered cycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, ted or unsaturated, unsubstituted, mono- or bstituted; a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted ; wherein said 3membered heterocycloalkyl moiety is optionally connected through -C1-C6- alkylene-, linear or ed, saturated or unsaturated, unsubstituted, mono- or polysubstituted; a embered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6membered aryl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or rated, unsubstituted, mono- or polysubstituted; or 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 rated, unsubstituted, mono- or polysubstituted; in case X means NR6, R6 means -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; a 3membered cycloalkyl , saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3membered cycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, ted or unsaturated, tituted, mono- or polysubstituted; a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted ; wherein said 3membered heterocycloalkyl moiety is optionally connected through -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 optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 5membered heteroaryl moiety, unsubstituted, mono- or bstituted; wherein said 5membered heteroaryl moiety is optionally connected through -C1-C6-alkylene-, linear or ed, saturated or unsaturated, tituted, mono- or polysubstituted; or in case X means NR6, R5 and R6 together with the nitrogen atom to which they are attached form a 3- 12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; R9, R10, 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; wherein "mono- or polysubstituted" means that one or more hydrogen atoms are replaced by a substituent independently of one another ed 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, -S(=O)2OR21, and -S(=O)2NR21R22; wherein R21, R22 and R23 independently of one another mean -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, -I, - CN, -OH, -NH2, and -O-C1-C6-alkyl; a 3membered cycloalkyl moiety, ted or unsaturated, unsubstituted; wherein said 3membered lkyl moiety is optionally connected through -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, -I, -CN, -OH, -NH2, -C1-C6-alkyl and -O-C1-C6- alkyl; a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted; wherein said 3 membered heterocycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or ed, saturated or rated, unsubstituted or tuted 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 -OC1-C6-alkyl a 6membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6membered aryl moiety is optionally connected through -C1-C6-alkylene-, 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, -I, -CN, -OH, -NH2, -alkyl and -O-C1-C6-alkyl; a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is optionally connected h -C1-C6-alkylene-, linear or ed, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group ting of -F, -Cl, -Br, -I, -CN, -OH, -NH2, -C1-C6-alkyl and -O-C1-C6- alkyl; or R21 and R22 within NR21R22, -OC(=O)NR21R22, -NR21R22, -NR23-(CH2)1C(=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; -(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 substituents independently of one another selected from the group consisting of -F, -Cl, -Br and -I; or a physiologically acceptable salt thereof.
2. The compound according to claim 1, wherein R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20 independently of one another mean -H, -F, -OH, or -C1-C6-alkyl.
3. The compound ing to claim 1 or 2, wherein (i) R1 means -H; and R2 means -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (ii) R1 means -CH3; and R2 means -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (iii) R1 means -H or -CH3; and wherein R2 means -CH2-cycloalkyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-oxetanyl or -CH2-tetrahydrofuranyl; or (iv) R1 and R2 together with the nitrogen atom to which they are attached form a ring and mean -(CH2)3.
4. The compound according to any one of the preceding claims, wherein (i) R3 means -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (ii) R3 means a 6membered aryl moiety, unsubstituted, mono- or polysubstituted; or (iii) R3 means a 5membered heteroaryl moiety, tituted, mono- or polysubstituted.
5. The compound according to any one of the preceding claims, wherein (i) R4 means -H; or (ii) R4 means -C1-C6-alkyl, linear or branched, saturated or rated, unsubstituted, mono- or polysubstituted; or (iii) R4 means a 3membered cycloalkyl moiety, saturated or rated, unsubstituted, mono- or polysubstituted; wherein the 3membered cycloalkyl moiety is connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or bstituted; or (iv) R4 means a 3membered heterocycloalkyl moiety, ted or unsaturated, unsubstituted, mono- or bstituted; wherein said 3membered heterocycloalkyl moiety is connected through -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (v) R4 means a embered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6membered aryl moiety is connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (vi) R4 means a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, monoor polysubstituted.
6. The nd according to any one of the ing , wherein R5 means -H.
7. The compound according to any one of claims 1 to 5, wherein (i) R5 means -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (ii) R5 means a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted, wherein said 3 membered cycloalkyl moiety is optionally connected h -C1-C6-alkylene-, linear or branched, saturated or unsaturated, tituted, mono- or polysubstituted; or (iii) R5 means a 3membered heterocycloalkyl , saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3- 12-membered cycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (iv) R5 means a 5 membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said embered heteroaryl moiety is ally connected h -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted.
8. The compound according to any one of the preceding claims, wherein (i) X means NR6 and R5 and R6 together with the nitrogen atom to which they are attached form a 3membered heterocycloalkyl , saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (ii) NR6 and R6 means -H or -C1-C6- alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted.
9. The compound according to any one of the preceding claims, which has a structure according to any of general formulas (II-A) to (VIII-C): X X 5 N 2 5 NH R N R R N O O N N O O R 4 R 4 R D D (II-A) (II-B) R R 5 N R 2 R5 O R 3 (II-C) RD R C X X 5 N N R N R 5 N O R 3 O R 3 N N O O R R C (III-C) (III-B) R1 R 1 X X R5 N R2 5 N R N O R3 O R 3 N N O O -3 (CH 2) 2 - 3 H3CO H 3CO (IV-A) (IV-B) N R 5 N N R 2 R5 N O R3 N N O (CH2)2-3 H3CO R C (IV-C) (V-A) X X R5 N R 5 N O O N N O O RD R (V-C) (V-B) N X R 5 N R 2 N R 5 N O O N N O O (CH 2) 2 - 3 (CH 2) 2 - 3 D R D H 3CO R H 3CO (VI-A) (VI-B) X X N R 5 N 2 R 5 N N R O N N O (CH 2) 2 - 3 R D R D H 3CO (VI-C) (VII-A) N X R5 N R 5 N O O N N O O (VII-C) (VII-B) R1 R 1 X X R5 N R2 R 5 N O O N N O H O H (VIII-A) (VIII-B) RD RD R 5 N O H (VIII-C) wherein in each case R1, R2, R3, R4, R5, R6 and X are d as in any one of the preceding claims, RC means -H, -OH, -F, -CN or -C1-C4-alkyl; RD means -H or -F; or a physiologically acceptable salt thereof.
10. The compound according to any one of the preceding claims, n the substructure R 10 R 9 has a meaning selected from the group consisting of: H H2N N N O O H 2N H O O N N H 2N N O O O O N N N H 2N O O N N H 2N H O O N N N N O O N N N O O O H2NOC O H H N N OH O O O H HO O O O O H H N N O O N H H H N N OH O O H H N N OH OH O O H N N S N O O N H H N N N S O N O H N N N N O O N S N N O N HO N N O O 2S O OH O N H O O N O H H N N HO HO O O N N HO HO O O H H NC N N O O H O 2 H N S N S N O 2 H O O H H N H N O O 1-30 1-30 O O N N H N O O HO O N O N N N N O N O O N N H O N N O N N O H H N N N O N O H O N NC N N N N O N O H H N N N N N O N O N OH N N O N O N H H N N N N O O HO N N H H NC N N N N O O NC N H N N O N N O H H O N N N O N O N O N H H N N N O N O N N N N H H 3CO 2C N N CO 2CH 3 N N N N H 3CO 2C CONH 2 H H N N N N O O CO2CH3 CONHCH 3 H H N N N N N N H H2NOC N N H2NOC N N N N H O N O N N N O H H N N N O O O N O N N H N O N N NC N N N N N N NC O N N H N O F F H N N F N H H N N N O O N F N N N O N O H H N N N O O N H N N N O N N H N N N N H H N N N O O N N H O 2S N N H N N OS N N N N H S N N H N N N OH N H H N N HO N N O O N H N N O O H H N N N N O O H H N N N O O N N H N N O O H H N N N O N O O O H H N N N N N O O H H N N N N O O N H N N N N N N H N N N N O H3CO2S N N N O O S H 2NOC H 3CO 2S N N O O
11. The compound according to any one of the preceding claims, wherein R1 means -H or -CH3; R2 means -CH3, -CH2CH3 or -CH2-C(H)(CH3)2; R3 means -phenyl, yl or -pyridinyl, in each case unsubstituted or bstituted with -F; R4 means -C1-C6-alkyl, linear or branched, saturated, 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, =O, -N(CH3)2 and -O-CH3; or propyl, butyl, -cyclopentyl or -cyclohexyl, unsubstituted or monosubstituted with -F, -OH, - CN or -CH3, wherein said -cyclopropyl, -cyclobutyl, -cyclopentyl or -cyclohexyl is connected through - CH2- or -CH2CH2-; -oxetanyl unsubstituted or monosubstituted with -F, -OH, -CN or -CH3, wherein said -oxetanyl is connected through -CH2- or -CH2CH2-; X means -O- or -NR6-; R5 means -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, -O-CH3, 2-CH2-O)1H, -O-(CH2CH2-O)1CH3, -C(=O)OH, OCH3, -C(=O)NH2, - C(=O)NHCH3, -C(=O)N(CH3)2, -OH, -S(=O)CH3, -S(=O)2CH3, unsubstituted -C(=O)-morpholinyl, -NHC (=O)-CH3, -N(CH3)2 and NH-S(=O)2-CH3; -cyclopropyl, -cyclobutyl, -cyclopentyl or -cyclohexyl, unsubstituted or bstituted with -F, -OH, - CN or -CH3, n said -cyclopropyl, -cyclobutyl, cyclopentyl or cyclohexyl is ally connected through -CH2- or -CH2CH2-; -heterocyclobutyl, -heterocyclopentyl, or -heterocyclohexyl, 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, -I, -CN, -O-CH3, -O-(CH2-CH2-O)1H, 2CH2-O)1CH3, -alkyl, -C(=O)OH, - C(=O)OCH3, NH2, -C(=O)NHCH3, -C(=O)N(CH3)2, =O, -OH, -SCH3, -S(=O)CH3, -S(=O)2CH3, unsubstituted -C(=O)-morpholinyl, -NH-C(=O)-CH3, )2 and NH-S(=O)2-CH3; wherein said -heterocyclobutyl , -heterocyclopentyl, or ocyclohexyl is optionally connected through -CH2- or -CH2CH2-; -oxazolyl, -isoxazolyl, olyl, -pyridinyl, -pyridazinyl, -pyrazinyl, -thiazolyl, -thiadiazolyl, - imidazolyl, -pyrimidinyl, or 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine, in each case unsubstituted or substituted with one, two, three or four substituents independently of one r selected from the group consisting of -F, -Cl, Br, -I, -CN, -OH, -CH3, -O-CH3, -C(=O)OH, -C(=O)OCH3, NH2, - C(=O)NHCH3, -C(=O)N(CH3)2, S(=O)CH3, -S(=O)2CH3 and -S-CH3, wherein said -oxazolyl, -isoxazolyl, -pyrazolyl, -pyridinyl, azinyl, -pyrazinyl, -thiazolyl, -thiadiazolyl, -imidazolyl, -pyrimidinyl, or 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine is optionally connected through -CH2-; or -phenyl, 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, -CH3, -O-CH3, -C(=O)OH, -C(=O)OCH3, - C(=O)NH2, NHCH3, N(CH3)2, S(=O)CH3, -S(=O)2 CH3 and -S-CH3, wherein said -phenyl is optionally connected through -CH2-; in case X means NR6, R6 means -H or -CH3; or in case X means NR6, R5 and R6 together with the nitrogen atom to which they are attached form a - pyrrolidinyl, -piperidinyl, -piperazinyl, -morpholinyl, -thiomorpholinyl, -thiomorpholinyl dioxide or - (methylsulfonyl)piperazinyl, in each case unsubstituted or substituted with one, two, three or four substituents independently of one r selected from the group consisting of =O, -OH, -CH2-OH, - C(=O)NH2, and -S(=O)2CH3, wherein said -pyrrolidinyl, -piperidinyl, -piperazinyl, -morpholinyl, - thiomorpholinyl,- thiomorpholinyl dioxide or -(methylsulfonyl)piperazinyl is optionally condensed with an imidazole moiety, unsubstituted; and R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20 mean -H.
12. The compound according to any one of the preceding claims, which has (i) a structure according to general formula (I') R 13 16 10 9 R 14 R R R 15 R 11 R R 12 R 1 5 N R N R 2 O R 3 R 4 R 18 R 19 R 17 R 20 wherein R1 to R5, R9 to R20, and X are d as in any one of the preceding claims, or a physiologically able salt f; or. which has (ii) a ure according to general formula (IX) R 10 R 9 R 5 N O R (IX) (CH 2) 1 - 2 wherein RC means -H or -OH; R3 means -phenyl or fluorophenyl; R5 means -H, -CH3, -CH2CH2OH, or -CH2C(=O)NH2; R6 means -H or -CH3; or R5 and R6 together with the nitrogen atom to which they are attached form a ring and mean -(CH2)5-, wherein said ring is unsubstituted or substituted with one or two substituents independently of one another selected from the group consisting of -CH3, -OH, -S(=O)2CH3 and -C(=O)NH2; R9 and R10 independently of one another mean -H or -CH3; or a physiologically acceptable salt thereof.
13. The compound according to any one of the preceding claims, which is selected from the group consisting [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[2-[2- [2-[2-[2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethyl]-acetamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-pyridinecarboxylic acid methyl ester; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(1R)- 2-hydroxymethyl-ethyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(1S)- 2-hydroxymethyl-ethyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-methyl- N-(methylcarbamoyl-methyl)-acetamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-nicotinic acid methyl ester; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]-methyl-amino]methyl-propionamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-N,2-dimethyl-propionamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]-methyl-amino]-N,2-dimethyl-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- [(dimethyl-carbamoyl)-methyl]-N-methyl-acetamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]methyl-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- methoxy-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methoxy-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(4- methoxy-pyridinyl)-acetamide; [[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-N-methyl-pyridinecarboxylic acid amide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(3- hydroxy-cyclobutyl)-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(3- hydroxy-cyclobutyl)-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(1- hydroxy-cyclopropyl)-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(3- morpholinyloxo-propyl)-acetamide; (1-Cyano-cyclopropyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(3- hydroxy-cyclopentyl)-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[[(2R)- 2-hydroxy-cyclohexyl]-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[2-[2- [2-(2-methoxy-ethoxy)-ethoxy]-ethoxy]-ethyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(1- hydroxy-cyclohexyl)-methyl]-acetamide; [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[2-[2- [2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy]-ethoxy]-ethyl]-acetamide; cis-N-(6-Cyano-pyridinyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-acetamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-nicotinic acid methyl ester; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(3- methoxy-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[2-[2- [2-[2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethyl]-acetamide; cis-N-(4-Cyano-pyridinyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- piro[4.5]decanyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- methoxy-pyrimidinyl)-acetamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-isonicotinic acid methyl ester; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- methoxy-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- fluoro-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- methyl-pyrimidinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- methyl-pyrimidinyl)-acetamide; [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(3- fluoro-pyridinyl)-acetamide; [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(3- fluoro-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methoxy-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- methyl-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(4- methyl-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(3- methyl-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methyl-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- fluoro-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- methyl-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(4- methyl-pyridinyl)-acetamide; [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(3- methyl-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(3- methoxy-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methoxy-pyridazinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- methylsulfonyl-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- methoxy-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methylsulfonyl-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methoxy-pyrazinyl)-acetamide; [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(4- methoxy-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(4- methoxy-pyrimidinyl)-acetamide; [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (oxazolyl-methyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (oxazolyl-methyl)-acetamide; (Cyclobutyl-methyl)[2-[(3S,4S)-3,4-dihydroxy-piperidinyl]oxo-ethyl]dimethylamino phenyl-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)[2-[(3S,4S)-3,4-dihydroxy-pyrrolidinyl]oxo-ethyl]dimethylamino- 8-phenyl-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)[2-[(3S,4R)-3,4-dihydroxy-pyrrolidinyl]oxo-ethyl]dimethylamino- 8-phenyl-1,3-diazaspiro[4.5]decanone; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- cyclopropyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- hydroxy-ethyl)-N-methyl-acetamide; cis(Cyclobutyl-methyl)dimethylamino[2-(3-hydroxy-piperidinyl)oxo-ethyl]phenyl-1,3- diazaspiro[4.5]decanone; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(1- hydroxy-cyclobutyl)-methyl]-acetamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-N,N-dimethyl-acetamide; cis(Cyclobutyl-methyl)dimethylamino[2-oxo(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazin- 7-yl)-ethyl]phenyl-1,3-diazaspiro[4.5]decanone; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-N,N-dimethyl-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[2-[2- [2-[2-[2-[2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(4- y-pyrimidinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- methoxy-pyrimidinyl)-acetamide; cis-N-(5-Cyano-pyridinyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-acetamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-N-methyl-pyridinecarboxylic acid amide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- methoxy-pyrimidinyl)-acetamide; cis-N-(2-Cyano-pyrimidinyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- piro[4.5]decanyl]-acetamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-pyridinecarboxylic acid amide; cis-N-(3-Cyano-pyridinyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-acetamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-acetamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-pyridinecarboxylic acid amide; cis-N-(4-Cyano-pyrimidinyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- piro[4.5]decanyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- ([1,3,4]thiadiazolyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-thiazol- 2-yl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- methyl-isoxazolyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- isoxazolyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(1- methyl-1H-pyrazolyl)-acetamide; cis- N-(4-Cyanomethylsulfanyl-1H-pyrazolyl)[1-(cyclobutyl-methyl)dimethylaminooxo phenyl-1,3-diazaspiro[4.5]decanyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- methoxy-pyrazinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (pyridazinyl-methyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(2- hydroxyphenyl)-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(1- methyl-1H-imidazolyl)-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(4- methyl-pyridinyl)-methyl]-acetamide; [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (pyrimidinyl-methyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (pyridazinyl-methyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (pyrimidinyl-methyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (pyrazinyl-methyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (oxazolyl-methyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(2- methyl-pyridinyl)-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(2- methoxy-pyridinyl)-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(4- methoxy-pyridinyl)-methyl]-acetamide; [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(6- methyl-pyridinyl)-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(6- y-pyridinyl)-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(2- methoxyphenyl)-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(otolyl-methyl amide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-N-methyl-pyridinecarboxylic acid amide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-pyridinecarboxylic acid amide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methoxy-pyrimidinyl)-acetamide; [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- methoxy-pyrimidinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(4- hydroxy-pyrimidinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- hydroxy-pyrimidinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- hydroxy-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(1,1- dioxo-thianyl)-acetamide; cis(Cyclobutyl-methyl)dimethylamino[2-(1,1-dioxo-[1,4]thiazinanyl)oxo-ethyl]phenyl- 1,3-diazaspiro[4.5]decanone; [8-Dimethylamino(2-methoxy-ethyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N- pyrimidinyl-acetamide; cis[8-Dimethylamino(2-methoxy-ethyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-methylacetamide cis-N-(5-Cyano-pyrimidinyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- methylsulfanyl-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(4- methoxy-pyrimidinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methylsulfanyl-pyridinyl)-acetamide; cis[8-Dimethylamino(2-methoxy-ethyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- hydroxy-ethyl)-acetamide; cis[[2-[8-Dimethylamino(2-methoxy-ethyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-methylacetamide cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- hydroxy-ethyl)-acetamide; [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- hydroxy-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(2- methoxy-pyrimidinyl)-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(4- methoxy-pyrimidinyl)-methyl]-acetamide; cis-N-(2-Cyano-pyrimidinyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-acetamide; [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[6- (methylsulfinyl)-pyridinyl]-acetamide; cis[[2-[1-(Cyclobutyl-methyl)methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]methyl-propionamide; cis[[2-[1-(Cyclobutyl-methyl)methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-N-methyl-acetamide; [[2-[1-(Cyclobutyl-methyl)methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[2-[2- (2-methoxy-ethoxy)-ethoxy]-ethyl]-acetamide; cis-N-(Carbamoyl-methyl)[1-(cyclobutyl-methyl)methylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-N-methyl-acetamide; cis[1-(Cyclobutyl-methyl)methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-methyl- N-(methylcarbamoyl-methyl)-acetamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(2-methylsulfonyl-ethyl)-acetamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-pyrimidinyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methylsulfonyl-pyridinyl)-acetamide; cis[8-Dimethylamino[(dimethyl-carbamoyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(2-hydroxy-ethyl)-acetamide; cis[[2-[1-(Cyclobutyl-methyl)methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-acetyl]- methyl-amino]methyl-propionamide; cis(Cyclobutyl-methyl)[2-(1,1-dioxo-[1,4]thiazinanyl)oxo-ethyl]methylaminophenyl- azaspiro[4.5]decanone; cis[1-(Cyclobutyl-methyl)methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[2-[2-[2- [2-[2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethyl]-acetamide; cis[[2-[1-(Cyclobutyl-methyl)methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-N,N-dimethyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- hydroxy-pyrimidinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(4- methylsulfonyl-pyridinyl)-acetamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-N-methyl-acetamide; cis-N-(Carbamoyl-methyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-N-methyl-acetamide; cis(8-Dimethylaminooxophenylpropyl-1,3-diazaspiro[4.5]decanyl)-N-methyl-acetamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-methylacetamide cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[4- (methylsulfinyl)-pyridinyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(3- hydroxy-pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- sulfonyl-ethyl)-acetamide; cis(Cyclobutyl-methyl)[2-[(3S,4R)-3,4-dihydroxy-pyrrolidinyl]oxo-ethyl]dimethylamino- 8-phenyl-1,3-diazaspiro[4.5]decanone; cis[1-(Cyclobutyl-methyl)methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- hydroxy-ethyl)-acetamide; cis[8-Dimethylamino[(dimethyl-carbamoyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan pyrimidinyl-acetamide; cis[8-Dimethylamino[(dimethyl-carbamoyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-methyl-acetamide; cis[[2-[8-Dimethylamino(2-methyl-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-acetamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-acetamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan methyl-acetamide; [[2-[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]- ]amino]-acetamide; cis[8-Dimethylamino(2-methyl-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-methylacetamide cis(Cyclobutyl-methyl)[2-[(3S,4R)-3,4-dihydroxy-pyrrolidinyl]oxo-ethyl]methylamino phenyl-1,3-diazaspiro[4.5]decanone; cis[8-Dimethylamino[(1-methyl-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-methyl-acetamide; cis[8-Dimethylamino[(1-methyl-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-pyrimidinyl-acetamide; cis[[2-[8-Dimethylamino[(1-methyl-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan- 3-yl]-acetyl]amino]-acetamide; cis[8-Dimethylamino[(1-methyl-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(2-hydroxy-ethyl)-acetamide; cis[[2-[1-(Cyclopropyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-acetamide; cis[1-(Cyclobutyl-methyl)(ethyl-methyl-amino)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N- methyl-acetamide; cis[[2-(8-Dimethylaminooxophenylpropyl-1,3-diazaspiro[4.5]decanyl)-acetyl]amino]- acetamide; cis[[2-[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-acetyl]amino]-acetamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(2-hydroxy-ethyl)-acetamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(1,1-dioxo-thianyl)-acetamide; cis[1-(Cyclopropyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- methyl-acetamide; cis[1-[(1-Cyano-cyclobutyl)-methyl]dimethylaminooxophenyl-1,3-diazaspiro[4.5]decan yl]-N-methyl-acetamide; cis[1-(Cyclobutyl-methyl)(ethyl-methyl-amino)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (2-hydroxy-ethyl)-acetamide; cis[[2-[1-(Cyclobutyl-methyl)(ethyl-methyl-amino)oxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-acetamide; cis[[2-[1-(Cyclobutyl-methyl)methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-N,2-dimethyl-propionamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- hydroxy-ethyl)-acetamide; [8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-methyl- N-(methylcarbamoyl-methyl)-acetamide; cisDimethylamino(3-methoxy-propyl)[2-oxo(3-oxo-piperazinyl)-ethyl]phenyl-1,3- diazaspiro[4.5]decanone; cis-N-(Carbamoyl-methyl)[8-dimethylamino(3-methoxy-propyl)oxophenyl-1,3- piro[4.5]decanyl]-N-methyl-acetamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(3- hydroxy-cyclobutyl)-methyl]-acetamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(3- y-cyclobutyl)-methyl]-acetamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(3- hydroxy-cyclopentyl)-methyl]-acetamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N- pyridazinyl-acetamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methoxy-pyridinyl)-acetamide; cis-N-(2-Cyanoethyl)[8-dimethylamino(3-methoxy-propyl)oxophenyl-1,3- diazaspiro[4.5]decanyl]-acetamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N- pyrimidinyl-acetamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N- pyrimidinyl-acetamide; cis[1-(Cyclobutyl-methyl)(ethyl-methyl-amino)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (6-methoxy-pyridinyl)-acetamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-pyridinyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetamide; [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- pyrimidinyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- methoxy-ethyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- hydroxy-ethyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[2-[2- [2-[2-[2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethoxy]-ethyl]-acetamide; cis[1-(Cyclobutyl-methyl)methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-methylacetamide cis-(2S)[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]-pyrrolidinecarboxylic acid amide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-N,N-dimethyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (oxetanyl)-acetamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-acetamide; cis(Cyclobutyl-methyl)dimethylamino[2-oxo(3-oxo-piperazinyl)-ethyl]phenyl-1,3- diazaspiro[4.5]decanone; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(1,1- dioxo-thianyl)-acetamide; cis(Cyclobutyl-methyl)dimethylamino[2-[2-(hydroxymethyl)-morpholinyl]oxo-ethyl] -1,3-diazaspiro[4.5]decanone; cis-N-(Carbamoyl-methyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- piro[4.5]decanyl]-N-methyl-acetamide; cis-N-(Cyano-methyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-acetamide; cis-N-(2-Acetylamino-ethyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- methylsulfonyl-ethyl)-acetamide; cis(Cyclobutyl-methyl)dimethylamino[2-(1,1-dioxo-[1,4]thiazinanyl)oxo-ethyl]phenyl- 1,3-diazaspiro[4.5]decanone; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(1,1- dioxo-thianyl)-methyl]-acetamide; cis(Cyclobutyl-methyl)dimethylamino[2-(4-methylsulfonyl-piperazinyl)oxo-ethyl] phenyl-1,3-diazaspiro[4.5]decanone; cis-N-(2-Cyanoethyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- hydroxymethyl-propyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- morpholinyloxo-ethyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[2-(2- hydroxy-ethoxy)-ethyl]-acetamide; cis[[2-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]amino]-N-methyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[2- (methanesulfonamido)-ethyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(1- hydroxy-cyclopentyl)-methyl]-acetamide; [1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(4- hydroxy-cyclohexyl)-methyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[2-(2- y-ethoxy)-ethyl]-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[2- (dimethylamino)ethyl]-acetamide; [1-(Cyclobutyl-methyl)[methyl-(2-methyl-propyl)-amino]oxophenyl-1,3- diazaspiro[4.5]decanyl]-N-methyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-methylacetamide cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- pyrimidinyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- -pyridinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- pyridazinyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- pyrimidinyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- pyridazinyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methoxy-pyrimidinyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- methyl-pyridinyl)-acetamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-pyridinyl-acetamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(oxetanyl)-acetamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(2-methoxy-ethyl)-acetamide; cis[1-[(1-Hydroxy-cyclobutyl)-methyl]methylaminooxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(oxetanyl)-acetamide; cis[1-[(1-Hydroxy-cyclobutyl)-methyl]methylaminooxophenyl-1,3-diazaspiro[4.5]decan (2-methoxy-ethyl)-acetamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(4- methoxy-pyridinyl)-acetamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (pyrimidinyl-methyl)-acetamide; cisDimethylamino[2-(1,1-dioxo-[1,4]thiazinanyl)oxo-ethyl]phenylpropyl-1,3- diazaspiro[4.5]decanone; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-pyridinyl-acetamide; cis[1-[(1-Cyano-cyclobutyl)-methyl]dimethylaminooxophenyl-1,3-diazaspiro[4.5]decan yl]-acetamide; cis[[2-[1-[(1-Cyano-cyclobutyl)-methyl]dimethylaminooxophenyl-1,3-diazaspiro[4.5]decan- 3-yl]-acetyl]amino]-acetamide; cis[1-[(1-Hydroxy-cyclobutyl)-methyl]methylaminooxophenyl-1,3-diazaspiro[4.5]decan yl]-N-methyl-acetamide; cis[2-(1,1-Dioxo-[1,4]thiazinanyl)oxo-ethyl]methylaminophenylpropyl-1,3- diazaspiro[4.5]decanone; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- pyridinyl-acetamide; cisDimethylamino[(1-hydroxy-cyclobutyl)-methyl](2-morpholinyloxo-ethyl)phenyl-1,3- diazaspiro[4.5]decanone; cis[1-[(1-Hydroxy-cyclobutyl)-methyl]methylaminooxophenyl-1,3-diazaspiro[4.5]decan yl]-acetamide; cis(Cyclobutyl-methyl)dimethylamino(2-morpholinyloxo-ethyl)phenyl-1,3- diazaspiro[4.5]decanone; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(4- methylsulfanyl-pyridinyl)-acetamide; cis[2-(1,1-Dioxo-[1,4]thiazinanyl)oxo-ethyl]methylaminophenyl-1,3-diazaspiro[4.5]decan- 2-one; (8-Methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-acetamide; cis(8-Dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-acetamide; [2-(1,1-Dioxo-[1,4]thiazinanyl)oxo-ethyl]ethylaminophenyl-1,3-diazaspiro[4.5]decan trans[2-(1,1-Dioxo-[1,4]thiazinanyl)oxo-ethyl]ethylaminophenyl-1,3-diazaspiro[4.5]decan- 2-one; cis[1-(Cyclobutyl-methyl)methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-methylacetamide cis(8-Ethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-acetamide; trans(8-Ethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-acetamide; cis(8-Dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-N-(2-hydroxy-ethyl)-N-methylacetamide cisDimethylamino[2-(1,1-dioxo-[1,4]thiazinanyl)oxo-ethyl][(1-hydroxy-cyclobutyl)- methyl]phenyl-1,3-diazaspiro[4.5]decane-2,4-dione; cis(8-Dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-N-phenyl-acetamide; cis-N-(Carbamoyl-methyl)[1-(cyclopropyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-N-methyl-acetamide; cis(8-Dimethylamino-2,4-dioxophenyl-1,3-diazaspiro[4.5]decanyl)-N-phenyl-acetamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-[2-[2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy]-ethyl]-acetamide; cis[2-(1,1-Dioxo-[1,4]thiazinanyl)oxo-ethyl][(1-hydroxy-cyclobutyl)-methyl]methylamino- 8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione; cis(8-Dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-N-[2-[2-[2-(2-methoxy-ethoxy)- ethoxy]-ethoxy]-ethyl]-acetamide; cis-N-(Carbamoyl-methyl)-N-methyl(8-methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)- acetamide; (Carbamoyl-methyl)(8-dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-N- methyl-acetamide; cis-N-(Carbamoyl-methyl)[8-dimethylamino(oxetanyl-methyl)oxophenyl-1,3- diazaspiro[4.5]decanyl]-N-methyl-acetamide; cis-N-(2-Hydroxy-ethyl)-N-methyl(8-methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)- acetamide; cis[1-(Cyclopropyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetamide; [1-(Cyclopropyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- hydroxy-ethyl)-acetamide; cis[1-(Cyclobutyl-methyl)dimethylamino(3-fluorophenyl)oxo-1,3-diazaspiro[4.5]decanyl]- N-(2-hydroxy-ethyl)-N-methyl-acetamide; [1-(Cyclobutyl-methyl)dimethylamino(3-fluorophenyl)oxo-1,3-diazaspiro[4.5]decanyl]- acetic acid tert-butyl ester; cis[1-(Cyclopropyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- hydroxy-ethyl)-N-methyl-acetamide; cis[1-(Cyclopropyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- methylsulfonyl-ethyl)-acetamide; cis-N-(Carbamoyl-methyl)[1-(cyclobutyl-methyl)dimethylamino(3-fluorophenyl)oxo-1,3- diazaspiro[4.5]decanyl]-N-methyl-acetamide; cis[2-[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan- 3-yl]-acetyl]-piperidinecarboxylic acid amide; cisDimethylamino[(1-hydroxy-cyclobutyl)-methyl][2-(4-methylsulfonyl-piperidinyl)oxoethyl ]phenyl-1,3-diazaspiro[4.5]decanone; cis[1-(Cyclobutyl-methyl)dimethylamino(3-fluorophenyl)oxo-1,3-diazaspiro[4.5]decanyl]- N-(2-hydroxy-ethyl)-acetamide; trans[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- hydroxy-ethyl)-acetamide; trans-N-(Carbamoyl-methyl)[1-(cyclobutyl-methyl)dimethylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-N-methyl-acetamide; cisDimethylamino[(1-hydroxy-cyclobutyl)-methyl][2-(4-hydroxymethyl-piperidinyl) oxo-ethyl]phenyl-1,3-diazaspiro[4.5]decanone; cis[1-(Cyclobutyl-methyl)dimethylamino(4-fluorophenyl)oxo-1,3-diazaspiro[4.5]decanyl]- N-(2-hydroxy-ethyl)-acetamide; trans(Cyclopropyl-methyl)dimethylamino(2-morpholinyloxo-ethyl)phenyl-1,3- diazaspiro[4.5]decanone; transDimethylamino(2-morpholinyloxo-ethyl)phenyl-1,3-diazaspiro[4.5]decanone; cis[1-(Cyclobutyl-methyl)dimethylamino(4-fluorophenyl)oxo-1,3-diazaspiro[4.5]decanyl]- N-(2-hydroxy-ethyl)-N-methyl-acetamide; cis-N-(Carbamoyl-methyl)[1-(cyclobutyl-methyl)dimethylamino(4-fluorophenyl)oxo-1,3- diazaspiro[4.5]decanyl]-N-methyl-acetamide; cis(Cyclopropyl-methyl)dimethylamino[2-(4-hydroxymethyl-piperidinyl)oxo-ethyl] phenyl-1,3-diazaspiro[4.5]decanone; cis[2-[1-(Cyclopropyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetyl]-piperidinecarboxylic acid amide; trans[1-(Cyclopropyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- acetamide; trans[1-(Cyclopropyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- -acetamide; 1-(Cyclopropyl-methyl)dimethylamino[2-(1,1-dioxo-[1,4]thiazinanyl)oxo-ethyl] phenyl-1,3-diazaspiro[4.5]decanone; (Cyclopropyl-methyl)dimethylamino[2-(4-methylsulfonyl-piperidinyl)oxo-ethyl] phenyl-1,3-diazaspiro[4.5]decanone; cisDimethylamino[2-(1,1-dioxo-[1,4]thiazinanyl)oxo-ethyl][(1-hydroxy-cyclobutyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; trans(8-Dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-acetamide; transDimethylamino[2-(1,1-dioxo-[1,4]thiazinanyl)oxo-ethyl]phenyl-1,3- diazaspiro[4.5]decanone; cis(dimethylamino)phenyl(2,2,2-trifluoroethyl)(2-(trifluoromethyl)pyrimidinyl)-1,3- diazaspiro[4.5]decanone; cis(dimethylamino)phenyl(2-(trifluoromethyl)pyrimidinyl)(3,3,3-trifluoropropyl)-1,3- diazaspiro[4.5]decanone and the physiologically acceptable salts thereof.
14. Use of the compound according to any one of the preceding claims for the cture of a medicament for treating pain.
15. A medicament comprising a compound according to any one of claims 1 to 13.
NZ745184A 2017-01-13 3-(carboxymethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives NZ745184B2 (en)

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EP16151014 2016-01-13
PCT/EP2017/025007 WO2017121649A1 (en) 2016-01-13 2017-01-13 3-(carboxymethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives

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NZ745184A NZ745184A (en) 2024-03-22
NZ745184B2 true NZ745184B2 (en) 2024-06-25

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