DK3169666T3 - Substituerede azaspiro(4.5)decan-derivater - Google Patents

Substituerede azaspiro(4.5)decan-derivater Download PDF

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DK3169666T3
DK3169666T3 DK15738274.8T DK15738274T DK3169666T3 DK 3169666 T3 DK3169666 T3 DK 3169666T3 DK 15738274 T DK15738274 T DK 15738274T DK 3169666 T3 DK3169666 T3 DK 3169666T3
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group
aryl
mmol
solution
aliphatic
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DK15738274.8T
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English (en)
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Sven Kühnert
Bert Nolte
Klaus Linz
Babette-Yvonne Kögel
Olga Gröger
Birgit Braun
Anita Wegert
René Michael Koenigs
Stephanie Harlfinger
Paul Ratcliffe
Fritz Theil
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Gruenenthal Gmbh
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    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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Claims (15)

  1. 1. Forbindelse med den almene formel (1) χ3·ZI /\ \ X3Y3' Y3 Y4 (l) hvor Υι, Υι', Y2, Y2', Y3, Y3', Y4 og Y4' i hvert tilfælde uafhængigt af hinanden er valgt fra gruppen bestående af -H, -F, -Cl, -Br, -I, -CN, -NO2, -CHO, -Ro, -C(=O)R0, -C(=O)H, -C(=O)-OH, -C(=O)OR0, -C(=O)NH2, -C(=O)NHR0, -C(=O)N(R0)2, -OH, -ORo, -OC(=O)H, -OC(=O)R0, -OC(=O)OR0, -OC(=O)NHR0, -OC(=O)N(R0)2, -SH, -SRo, -SO3H, -S(=0)i.2-Ro, -S(=O)i.2NH2, -S(=O)i-2-NHR0, -S(=O)i-2-N(R0)2, -NH2, -NHRo, -N(Ro)2, -N+(Ro)3, -N+(Ro)20‘, -NHC(=O)R0, -NHC(=O)OR0, - NHC(=O)NH2, -NHC(=O)NHR0 og -NHC(=O)N (R0)2; eller ΥΊ og Y? eller Y2 og Y2' eller Y3 og Y3' eller Y4 og Y4' tilsammen angiver =0; Xi, Xi', X2, X2', X3 og X3' i hvert tilfælde uafhængigt af hinanden angiver -H, -F, -Cl, -Br, -I, -N02, -CF3, -0R5, -SR5, -SO2R5, -S(=O)2OR5, -CN, -COOR5, -CONR5, -NR6R7 eller -Ro; eller Xi og X/ eller X2 og X2' eller X3 og X3' tilsammen angiver =0; eller Xi og X2 eller X2 og X3 tilsammen angiver -(CH2)2.6-, hvor individuelle hydrogenatomer også kan udskiftes med -F, -Cl, -Br, -I, -N02, -CF3, -0R5, -CN eller -Ci-6-alifatisk gruppe; eller Xi og X/ eller X2 og X2' eller X3 og X3' i hvert tilfælde tilsammen angiver en C3-6-cycloalifatisk gruppe, hvor individuelle hydrogenatomer også kan udskiftes med -F, -Cl, -Br, -I, -N02, -CF3, -0R5, -CN eller -Ci_6-al ifatisk gruppe; Ro i hvert tilfælde uafhængigt af hinanden angiver -Ci_8-alifatisk gruppe, -C3-12-cycloalifatisk gruppe, -aryl, -heteroaryl, -Ci-8-alifatisk gruppe-C3-i2-cycloalifatisk gruppe, -Ci_8-alifatisk gruppe-aryl, -Ci_8-alifatisk gruppe-heteroaryl, -C3-8-cycloalifatisk gruppe-Ci-8-alifatisk gruppe, -C3-8-cycloalifatisk gruppe-aryl eller -C3-8-cycloalifatisk gruppe-heteroaryl; Ri og R2 uafhængigt af hinanden angiver -H eller -Ro; eller R^g R2 tilsammen angiver -CH2CH2OCH2CH2-, -CH2CH2NR8CH2CH2- eller -(CH2)3.6-; R3 angiver -Ro; R4 angiver -Ru, -C(=O)Rn, -C(=O)ORi2, -C(=O)N(Ri2)2; -S(=O)Rn eller -S(=O)2Rii; R5 i hvert tilfælde uafhængigt af hinanden angiver -H eller -Ro; R6 og R7 uafhængigt af hinanden angiver -H eller -Ro; eller R6 og R7 tilsammen angiver -CH2CH2OCH2CH2-, -CH2CH2NRi0CH2CH2- eller -(CH2)3.6-; R8 angiver -H, -Ro eller -C(=O)R0; R10 angiver -H eller -Ci_6-alifatisk gruppe; R11 angiver a) -Ci-6-alkyl, -C3-6-cycloalkyl eller -Ci-3-alkyl-C3-6-cycloalkyl, hvor et ringcarbonatom i C3-6-cycloalkylgruppen kan udskiftes med et oxygenatom, og -Ci-6-alkyl, -C3-6-cycloalkyl eller -Ci-3-alkyl-C3-6-cycloalkyl er mono- eller polysubstitueret med substituenter, der uafhængigt af hinanden er valgt fra gruppen bestående af -NO2, -CHO, =0, -C(=O)R0, -C(=O)H, -C(=O)-OH, -C(=O)OR0, -C(=O)NH2,-C(=O)NHR0, -C(=O)N(R0)2j -OH, -OR0, -OC(=O)H, -OC(=O)R0, -OC(=O)OR0, -OC(=O)NHR0, -OC(=O)N(R0)2, -SH, -SR0, -SO3H, -S(=0)i.2-Ro, -S(=O)i-2NH2,-S(=O)i.2-NHR0, -S(=O)i-2-N(R0)2, -NH2, -NHRo, -N(R0)2, -N+Ro)3, -N-(R0)2O", -NHC(=O)R0, -NHC(=O)OR0, -NHC(=O)NH2, -NHC(=O)NHR0, -NH-C(=O)N(R0)2, -SI(Ro)3 og -PO(OR0)2; eller b) usubstitueret eller mono- eller polysubstitueret -C7-8-alkyl, -C7-i2-cyloalkyl eller C3-i2-cycloheteroalkyl med op til 3 heteroatomer i ringen, som er valgt fra gruppen af O, N og S, med det forbehold at heterocykliske grupper med kun ét oxygenatom som et heteroatom er udelukket, eller c) -aryl, -heteroaryl, -C4-8-cycloalkyl-C3-i2-cycloalifatisk gruppe, -Ci-8-alifatisk gruppe-aryl, -Ci-8-alifatisk gruppe-heteroaryl, -C3-8-cycloalifatisk gruppe-Ci_8-alifatisk gruppe, -C3-8-cycloalifatisk gruppe-aryl eller -C3-8-cycloalifatisk gruppe-heteroaryl, og R12 angiver H, -Ci_8-alifatisk gruppe, -C3-i2-cycloalifatisk gruppe, -aryl, -heteroaryl, -Ci_8-alifatisk gruppe-C3-i2-cycloalifatisk gruppe, -Ci_8-alifatisk gruppe-aryl, -Ci-8-alifatisk gruppe-heteroaryl, -C3-8-cycloalifatisk gruppe-Ci-8-alifatisk gruppe, -C3-8-cycloalifatisk gruppe-aryl eller -C3-8-cycloalifatisk gruppe-heteroaryl; hvor "alifatisk gruppe" i hvert tilfælde er et forgrenet eller ikke-forgrenet, mættet eller en mono- eller polyumættet, usubstitueret eller mono- eller polysubstitueret, alifatisk hydrocarbonradikal; "cycloalifatisk gruppe" i hvert tilfælde er et mættet eller mono- eller polyumættet, usubstitueret eller mono- eller polysubstitueret, alicyklisk, mono- eller multicyklisk hydrocarbonradikal; hvor "mono- eller polysubstitueret" med hensyn til "alifatisk gruppe", herunder -C4-8-alkyl, -C7-i2-alkyl og "cycloalifatisk gruppe", herunder -C7-i2-cycloalkyl og -C3. 12-cycloheteroalkyl, skal betegne substitution af ét eller flere hydrogenatomer med -F, -Cl, -Br, -I, -CN, -NO2, -CHO, =0, -Ro, -C(=O)R0, -C(=O)H, -C(=O)-OH, -C(=O)OR0, -C(=O)NH2, -C(=O)NHR0, -C(=O)N(R0)2, -OH, -OR0, -OC(=O)H, -OC(=O)R0, -OC(=O)OR0, -OC(=O)NHR0, -OC(=O)N(R0)2, -SH, -SR0, -SO3H, -S(=0)i-2-Ro, -S(=O)i.2NH2, -NH2, -NHRq, -N(Ro)2, -N+(Ro)3, -N+(R0)2O-, -NHC(=O)R0, -NHC(=O)OR0, -NHC(=O)NH2, -NHC(=O)NHR0, -NH-C(=O)N(R0)2, -Si(R0)3, -PO(ORo)2; "aryl" i hvert tilfælde uafhængigt af hinanden angiver et carbocyklisk ringsystem med mindst én aromatisk ring, men uden heteroatomer i ringen, hvor arylradikalerne valgfrit kan kondenseres med yderligere mættede, (delvist) umættede eller aromatiske ringsystemer, og hvert arylradikal kan være usubstitueret eller mono- eller polysubstitueret, hvor substituenterne på aryl kan være identiske eller forskellige og kan være i en hvilken som helst ønsket og mulig position i arylet; "heteroaryl" angiver et 5-, 6- eller 7-leddet cyklisk aromatisk radikal, der indeholder 1, 2, 3, 4 eller 5 heteroatomer, hvor heteroatomerne er identiske eller forskellige og er nitrogen, oxygen eller svovl, og den heterocykliske gruppe kan være usubstitueret eller mono- eller polysubstitueret; hvor substituenterne i tilfælde af substitution på den heterocykliske gruppe kan være identiske eller forskellige og kan være i en hvilken som helst ønsket og mulig position i heteroarylet; og hvor den heterocykliske gruppe også kan være led i et bi- eller polycyklisk system; hvor "mono- eller polysubstitueret" med hensyn til "aryl" og "heteroaryl" skal betegne substitution én gang eller adskillige gange af ét eller flere hydrogenatomer i ringsystemet med substituenter, der er valgt fra gruppen bestående af -F, -Cl, -Br, -I, -CN, -NO2, -CHO, =0, -Ro, -C(=O)R0, -C(=O)H, -C(=O)OH, -C(=O)OR0, -C(=O)NH2, -C(=O)NHR0, -C(=O)-N(R0)2j -OH, -O(CH2)i-20-, -ORo, -OC(=O)H, -OC(=O)R0, -OC(=O)OR0, -OC(=O)NHR0, -OC(=O)N(R0)2, -SH, -SRo, -SO3H, -S(=O)i-2-R0, -S(=O)i-2NH2, -NH2, -NHRo, -N(Ro)2, -N+(Ro)3, -N+(R0)2O', -NHC(=0)Ro, -NHC(=O)OR0, -NH-C(=O)NH2, -NHC(=0)NHRo, -NHC(=O)N(R0)2, -Si(R0)3, -PO(OR0)2; hvor N-ringatomer, som valgfrit forekommer, i hvert tilfælde kan oxideres (N-oxid); i form af en individuel stereoisomer eller en blanding deraf, den frie forbindelse og/eller det fysiologisk acceptable salt og/eller solvat.
  2. 2. Forbindelse ifølge krav 1, hvor Y/, Y2', Y3' og Y4' hver især angiver -H.
  3. 3. Forbindelse ifølge krav 1 eller 2, hvor Ro i hvert tilfælde uafhængigt af hinanden angiver -Ci-s-alifatisk gruppe, -C3-12-cycloalifatisk gruppe, -aryl, -heteroaryl, -Ci-8-alifatisk gruppe-C3-i2-cycloalifatisk gruppe, -Ci-s-alifatisk gruppe-aryl, -Ci-8-alifatisk gruppe-heteroaryl, -C3-8-cycloalifatisk gruppe-Ci_ 8-alifatisk gruppe, -C3-8-cycloalifatisk gruppe-aryl eller -C3-8-cycloalifatisk gruppe-heteroaryl; hvor disse er usubstitueret eller mono- eller polysubstitueret med substituenter uafhængigt af hinanden, der er valgt fra gruppen bestående af -F, -Cl, -Br,
    -CN, -CH3, -C2H5, -NH2, -NO2, -SH, -CF3, OH, -OCH3, -OC2H5 og -N(CH3)2.
  4. 4. Forbindelse ifølge et af kravene 1 til 3, hvor R3 angiver -Ci_8-alifatisk gruppe, -aryl, -heteroaryl, -Ci_3-alifatisk gruppe-aryl, -Ci_3-alifatisk gruppe-heteroaryl eller -Ci_3-alifatisk gruppe-C5-6-cycloalifatisk gruppe; hvor disse er usubstitueret eller mono- eller polysubstitueret med substituenter uafhængigt af hinanden, der er valgt fra gruppen bestående af -F, -Cl, -Br, -CN, -CH3, -C2H5, -NH2, -NO2, -SH, -CF3, OH, -OCH3, -OC2H5 og -N(CH3)2; R4 angiver -Ru eller -C(=O)Rn; og Xi, Xi', X2, X2', X3, X3' i hvert tilfælde uafhængigt af hinanden angiver -H, -F, -Cl, -Br, -I, -NO2, -CF3, -OR5, -SRs, -SO2R5, -S(=O)2OR5, -CN, -COOR5, -CONR5, -NR6R7 eller -Ro; eller Xi og X/ eller X2 og X2' eller X3 og X3' tilsammen angiver =0.
  5. 5. Forbindelse ifølge et af kravene 1 til 4, hvor Y1, Y/, Y2, Y2', Y3, Y3', Y4 og Y4' hver især angiver -H.
  6. 6. Forbindelse ifølge et af kravene 1 til 5, der har den almene formel (3.1) Pyøé χ3 xy (3.1)
  7. 7. Forbindelse ifølge et af kravene 1 til 6, hvor Xi, Xi'. X2, X2', X3 og X3' angiver H; eller X2 og X2' eller X3 og X3' tilsammen angiver =0; Ro i hvert tilfælde uafhængigt af hinanden angiver -Ci-s-alifatisk gruppe, -C3-12-cycloalifatisk gruppe, -aryl, -heteroaryl, -Ci-8-alifatisk gruppe-C3-i2-cycloalifatisk gruppe, -Ci-s-alifatisk gruppe-aryl, -Ci-8-alifatisk gruppe-heteroaryl, -C3-8-cycloalifatisk gruppe-Ci_ 8-alifatisk gruppe, -C3-8-cycloalifatisk gruppe-aryl eller -C3-8-cycloalifatisk gruppe- heteroaryl; hvor disse er usubstitueret eller mono- eller polysubstitueret med substituenter uafhængigt af hinanden, der er valgt fra gruppen bestående af -F, -Cl, -Br, -CN, -CH3, -C2H5, -NH2, -NO2, -SH, -CF3, OH, -OCH3, -OC2H5 og -N(CH3)2; Ri angiver CH3; R2 angiver -H eller -CH3; eller Ri og R2 tilsammen danner en ring og angiver -(CH2)3-4-; og R3 angiver -Ci-8-alifatisk gruppe, -aryl, -heteroaryl, -Ci_3-alifatisk gruppe-aryl, -C1-3-alifatisk gruppe-heteroaryl eller -Ci_3-alifatisk gruppe-C5-6-cycloalifatisk gruppe; hvor disse er usubstitueret eller mono- eller polysubstitueret med substituenter uafhængigt af hinanden, der er valgt fra gruppen bestående af -F, -Cl, -Br, -CN, -CH3, -C2H5, -NH2, -NO2, -SH, -CF3, OH, -OCH3, -OC2H5 og -N(CH3)2; R4 angiver -Ru eller -C(=O)Rn; R5 i hvert tilfælde uafhængigt af hinanden angiver -H eller Ro; R6 og R7 uafhængigt af hinanden angiver -H eller Ro; eller R6 og R7 tilsammen angiver -CH2CH2OCH2CH2-, -CH2CH2NR10CH2CH2- eller -(CH2)3.6-; R10 angiver -H eller -Ci-6-alifatisk gruppe, og R11 angiver C3-i2-cycloheteroalkyl med op til 3 heteroatomer i ringen, der er valgt fra gruppen af O, N og S, med det forbehold at heterocykliske grupper med kun ét oxygenatom som et heteroatom er udelukket, -aryl, -heteroaryl, -C4-8-cycloalkyl-C3-i2-cycloalifatisk gruppe.
  8. 8. Forbindelse ifølge et af kravene 1 til 7, hvor Ri og R2 hver især angiver -CH3.
  9. 9. Forbindelse ifølge et af kravene 1 til 8, hvor R3 er valgt fra gruppen bestående af phenyl, benzyl, pyrazolyl, pyridinyl, pyrazinyl og 2-thienyl, hvor radikalet kan være usubstitueret eller mono- eller polysubstitueret med substituenter, der uafhængigt af hinanden er valgt fra gruppen bestående af -F, -Cl, -Br, -CN, -CH3, -C2H5, -NH2, -NO2, -SH, -CF3, OH, -OCH3, -OC2H5 og -N(CH3)2, eller R3 er valgt fra gruppen bestående af -ethyl, -n-propyl, -n-butyl, -vinyl eller -allyl, usubstitueret eller mono- eller polysubstitueret med -OCH3, -OH eller -OC2H5, især med -OCH3 eller -OC2H5.
  10. 10. Forbindelse ifølge et af kravene 1 til 9, der har den almene formel (5) 'Mol· (5) hvor: Xi er valgt blandt -H, benzyl eller Ci.3-alkoxy-substitueret-Ci.4-alkyl; X2 og X2' enten begge er -H eller tilsammen angiver =0, Ri er methyl, og R2 er -H eller -methyl; R3 angiver -Ci-8-alifatisk gruppe, -aryl, -heteroaryl, -Ci-3-alifatisk gruppe-aryl, -Ci_ 3-alifatisk gruppe-heteroaryl eller -Ci_3-alifatisk gruppe-C5-6-cycloalifatisk gruppe; hvor disse er usubstitueret eller mono- eller polysubstitueret med substituenter uafhængigt af hinanden, der er valgt fra gruppen bestående af -F, -Cl, -Br, -CN, -CH3, -C2H5, -NH2, -N02, -SH, -CF3, OH, -OCH3, -OC2H5 og -N(CH3)2; og R4 er en gruppe ifølge den almene formel (6) r4i R40 R40 (6) hvor n = 1,2, 3 eller 4 R4o, R4o' og R4i uafhængigt af hinanden er enten H eller substitueret eller usubstitueret Ci_3-alkyl.
  11. 11. Forbindelse med formlen (I) som vist i krav 1, hvor R4 er valgt fra gruppen bestående af
    -ο-x -O-* -0^ 1 1 1 I -θ-Λ * Υ<* <%Åa δ phenyl, benzyl, zs ZZxS\ VTX , lJr^< F L/~>r ζΧχ CH<. CCa P^, cP, rO>, dx <>* <k Xu, -<P oddrJMoicR^R S ,0 r^\ ζ,θ _xs\z>° /sx^·0 PPP c xsx /z° ~ύ)~^ ΓΊίΜ 1 ’ 1 I ) ptv,-.// p°>0 O s H Qg ..
    eller blandt yX Xv XX ° ° / H HOXX; hoX^X; γ-0Χ</·. __>_ O 9 O -0X_<X. ΗοΧχζΧ 'O'/X. o o o H0X^\x. '-οΧ^λ- */CX ? 00 X’/X^'X · H2N ; H2N . O O O η2ΝΧ^Λ η2νΧ<Λ η’νΛ*ΟΧ η·Χλ 'βΧ"': ^yc* Ο 0 0 '''ΝΧ-~-''\>ζ '''Οχχ/''ΝΧ-\' Η ; Η ; Η ; Ο Ο Ο /θ-^-Ν-Χ^Χ ^οΧ-'^'^-Χ/'Χ ^νΧχ Η Η ; Η Χ^νΧϊ χΧ ^νΧ/χ Η, ; Η ; Η
    0^^'N O νΆ 0 j| H ; nA; M-^A δ o δ ΛυΑα'Χ n'V'nV^' II η il T H A LI H A V N ; V f 1 f A σ.....’X Φ...... A^z; I 9 Η Ν*Ά H V A 0a A “Ο*· Ηο·^-"γΑ(· v\A* N / 0 O ; ° ° 1 "AV* ΆβΆ-''" 0 z ' ; 0 ' / VA og hvor ΥΊ, Y/, Y2, Y2', Y3, Y3', Y4, Y4', Xi, Xi', X2, X2', Xs, Xs', Ri, R2 og R3 har den betydning, der er angivet i kravene 1-9.
  12. 12. Forbindelse, der er valgt fra gruppen:
    (SC- kis-2-(8-dimethylamino-3-oxo-8-phenyl-2-azaspiro[4.5]decan- I 1191) ^2-yl)-N-(3-hydroxy-3-methyl-butyl)-acetamid; (SC- kis-N-[3-(8-dimethylamino-3-oxo-8-phenyl-2- 1192) ^azaspiro[4.5]decan-2-yl)-propyl]-2-isoxazol-3-yl-acetamid; (SC- kis-N-[3-(8-dimethylamino-3-oxo-8-phenyl-2- 1193) ^azaspiro[4.5]decan-2-yl)-propyl]-4-methyl-isoxazol-5-carboxylsyreamid; (SC- ^cis-4-[2-(8-dimethylamino-3-oxo-8-phenyl-2- 1194) bzaspiro[4.5]decan-2-yl)-ethyl]-tetrahydro-pyran-4-^carboxylsyre-2,2,2-trifluor-acetat (SC- kis-4-[2-(8-dimethylamino-3-oxo-8-phenyl-2- 1195) ^azaspiro[4.5]decan-2-yl)-ethyl]-1,1-dioxo-thian-4-carboxylsyre- i 2,2,2-trifluor-acetat (SC- ^cis-N-butyl-2-(8-dimethylamino-3-oxo-8-phenyl-2- 1198) bzaspiro[4.5]decan-2-yl)-acetamid; (SC- ^cis-N-(cyclopropyl-methyl)-2-(8-dimethylamino-3-oxo-8-phenyl- i 1199) ^2-azaspiro[4.5]decan-2-yl)-acetamid; (SC- ^cis-2-(8-dimethylamino-3-oxo-8-phenyl-2-azaspiro[4.5]decan- i 1200) ^2-yl)-N-propyl-acetamid; (SC- ^cis-2-(8-dimethylamino-3-oxo-8-phenyl-2-azaspiro[4.5]decan- i 1201) 2-yl)-eddikesyre (SC- ^methyl 2-((trans-8-(dimethylamino)-3-oxo-8-phenyl-2-i 1202) hzaspiro[4.5]decan-2-yl)methyl)-benzoat; i form af en individuel stereoisomer eller en blanding deraf, den frie forbindelse og/eller det fysiologisk acceptable salt og/eller solvat.
  13. 13. Medikament, der indeholder mindst én forbindelse ifølge et af kravene 1 til 12 i form af en individuel stereoisomer eller en blanding deraf, den frie forbindelse og/eller det fysiologisk acceptable salt og/eller solvat og valgfrit egnede tilsætningsstoffer og/eller hjælpestoffer og/eller valgfrit yderligere aktive forbindelser.
  14. 14. Forbindelse ifølge et af kravene 1 til 12 i form af en individuel stereoisomer eller en blanding deraf, den frie forbindelse og/eller det fysiologisk acceptable salt og/eller solvat til anvendelse til behandling af smerte.
  15. 15. Forbindelse ifølge et af kravene 1 til 12 i form af en individuel stereoisomer eller en blanding deraf, den frie forbindelse og/eller det fysiologisk acceptable salt og/eller solvat til anvendelse ved behandling af angsttilstande, stress og syndromer, der er forbundet med stress, depressioner, epilepsi, Alzheimers sygdom, senildemens, generelle kognitive dysfunktioner, indlærings- og hukommelseslidelser (som et nootropisk middel), abstinenssymptomer, alkohol- og/eller lægemiddel- og/eller medikamentmisbrug og/eller -afhængighed, seksuelle dysfunktioner, kardiovaskulære sygdomme, hypotension, hypertension, tinnitus, pruritus, migræne, svækket hørelse, mangel på intestinal motilitet, svækket fødevareindtag, anoreksi, adipositas, lokomotoriske lidelser, diarré, kakeksi, urininkontinens eller som et muskelafslappende middel, antikonvulsivt eller anæstetisk middel eller til coadministration ved behandling med et opioidanalgetikum eller med et anæstetisk middel, til diurese eller antinatriurese, anxiolyse, til modulering af motorisk aktivitet, til modulering af neurotransmittersekretion og behandling af neurodegenerative sygdomme, der er forbundet dermed, til behandling af abstinenssymptomer og/eller til reduktion af afhængighedspotentialet af opioider.
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