DK2547679T3 - 2,3 dihydro-1h-inden-1-yl-2,7-diazaspiro[3.6]nonan-derivater og deres anvendelse som antagonister eller inverse agonister af ghrelin-receptoren - Google Patents

2,3 dihydro-1h-inden-1-yl-2,7-diazaspiro[3.6]nonan-derivater og deres anvendelse som antagonister eller inverse agonister af ghrelin-receptoren Download PDF

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DK2547679T3
DK2547679T3 DK11713083.1T DK11713083T DK2547679T3 DK 2547679 T3 DK2547679 T3 DK 2547679T3 DK 11713083 T DK11713083 T DK 11713083T DK 2547679 T3 DK2547679 T3 DK 2547679T3
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dihydro
diazaspiro
inden
acetyl
nonane
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Samit Kumar Bhattacharya
Kimberly O'keefe Cameron
Dilinie Prasadhini Fernando
Daniel Wei-Shung Kung
Allyn Timothy Londregan
Kim Francis Mcclure
Suvi Tuula Marjukka Simila
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Claims (17)

1. Forbindelse med formel (I)
(l) j hvor: R1 er -L1-R1, phenyl eller et 5- til 6-leddet heteroaryl indeholdende 1 til 4 heteroatomer, som hver især uafhængigt er udvalgt fra N, O eller S, hvor phenylet eller det 5- til 6-leddede heteroaryl eventuelt er kondenseret til et (C4-C7)cycloalkyl, (C5-C6)cycloalkenyl, phenyl, mættet eller delvist umættet 5-til 6-leddet heterocyclyl indeholdende 1 til 4 heteroatomer, som hver især uafhængigt er udvalgt fra N, O eller S, eller et 5- til 6-leddet heteroaryl indeholdende 1 til 4 heteroatomer, som hver især uafhængigt er udvalgt fra N, O eller S, hvor det eventuelt kondenserede phenyl og det eventuelt kondenserede 5- til 6-leddede heteroaryl eventuelt er substitueret med 1 til 3 substitu-enter udvalgt fra halogen, hydroxy, oxo, cyano, (C-i-C3)alkyl, halogensubstitueret (CrC3)alkyl, (CrC3)alkoxy, halogen-substitueret (CrC3)alkoxy, (CrC3)alkyl-S(0),-, (C3-C6)cycloalkyl, (C3-C6)cycloalkoxy, -(C0- C3)alkylNRxRy, -(C0-C3)alkylNRxC(O)Ry og -(C0-C3)alkylC(O)NRxRy; R1 er phenyl eller et 5- til 6-leddet heteroaryl indeholdende 1 til 4 heteroatomer, som hver især uafhængigt er udvalgt fra N, O eller S, hvor phenylet eller det 5- til 6-leddede heteroaryl eventuelt er kondenseret til et (C4-C7)cycloalkyl, (C5-C6)cycloalkenyl, phenyl, mættet eller delvist umættet 5- til 6-leddet heterocyclyl indeholdende 1 til 4 heteroatomer, som hver især uafhængigt er udvalgt fra N, O eller S, eller et 5- til 6-leddet heteroaryl indeholdende 1 til 4 heteroatomer, som hver især uafhængigt er udvalgt fra N, O eller S, hvor det eventuelt kondenserede phenyl og det eventuelt kondenserede 5- til 6-leddede heteroaryl eventuelt er substitueret med 1 til 3 substitu-enter udvalgt fra halogen, hydroxy, oxo, cyano, (CrC3)alkyl, halogen-substitueret (CrC3)alkyl, (CrC3)alkoxy, halogen-substitueret (CrC3)alkoxy, (CrC3)alkyl- S(0)n-, (C3-C6)cycloalkyl, (C3-C6)cycloalkoxy, -(C0-C3)alkylNRxRy, -(C0-C3)alkylNRxC(0)Ry og -(C0-C3)alkylC(O)NRxRy; L1 er O, S, NH, N(Ci-C3)alkyl eller (Ci-C3)alkylen; Ra ved hver forekomst uafhængigt er udvalgt fra hydrogen, (CrC3)alkyl og halogen; Z, Z1 og Z2 hver især uafhængigt er N eller CH eventuelt substitueret med halogen, (CrC3)alkoxy eller (CrC3)alkyl; L er en direkte binding O, S, NH, N(CrC3)alkyl eller (CrC3)alkylen; R2 er hydrogen, halogen, cyano, (CrC6)alkyl, (C3-C6)cycloalkyl, phenyl, mættet eller delvist umættet 5- til 6-leddet heterocyclyl indeholdende 1 til 4 heteroatomer, som hver især uafhængigt er udvalgt fra N, O eller S, eller 5-til 6-leddet heteroaryl indeholdende 1 til 4 heteroatomer, som hver især uafhængigt er udvalgt fra N, O eller S, hvor (CrC6)alkylet, (C3-C6)cycloalkylet, phenylet, det mættede eller delvist umættede 5- til 6-leddede heterocyclyl, eller det 5- til 6-leddede heteroaryl eventuelt er substitueret med 1 til 3 substi-tuenter uafhængigt udvalgt fra gruppen bestående af halogen, hydroxy, cyano, (CrC3)alkyl, halogen-substitueret (C-|-C3)alkyl, (CrC3)alkoxy, halogensubstitueret (CrC3)alkoxy, (C-|-C3)alkyl-S(0)n-, (C3-C6)cycloalkyl, (C3-C6)cycloalkoxy, -(C0-C3)alkylNRxRy, -(C0-C3)alkylNRxC(O)Ry og -(C0-C3)alkylC(0)NRxRy; forudsat at hvis L er O, S, NH eller N(CrC3)alkyl, så er R2 ikke halogen; n ved hver forekomst uafhængigt er 0, 1 eller 2; og Rx og Ry ved hver forekomst uafhængigt er udvalgt fra hydrogen og (Cr C6)alkyl, hvor (CrC6)alkylet eventuelt er afbrudt af en eller to grupper uafhængigt udvalgt fra NH, N(CrC3)alkyl, O og S, og eventuelt er substitueret med 1 til 4 halogener; eller Rx og Ry sammen er et (C2-C6)alkylen, som eventuelt er afbrudt af en eller to grupper uafhængigt udvalgt fra NH, N(Cr C3)alkyl, O og S; eller et farmaceutisk acceptabelt salt deraf.
2. Forbindelse ifølge kravl, hvor: R1 er phenyl eller et 5- til 6-leddet heteroaryl indeholdende 1 til 4 heteroatomer, som hver især uafhængigt er udvalgt fra N, O eller S, hvor phenylet eller det 5- til 6-leddede heteroaryl eventuelt er kondenseret til et (C4-C7)cycloalkyl, (C5-C6)cycloalkenyl, phenyl, mættet eller delvist umættet 5-til 6-leddet heterocyclyl indeholdende 1 til 4 heteroatomer, som hver især uafhængigt er udvalgt fra N, O eller S, eller et 5- til 6-leddet heteroaryl indeholdende 1 til 4 heteroatomer, som hver især uafhængigt er udvalgt fra N, O eller S, hvor det eventuelt kondenserede phenyl og det eventuelt kondenserede 5- til 6-leddede heteroaryl eventuelt er substitueret med 1 til 3 substitu-enter udvalgt fra halogen, hydroxy, oxo, cyano, (CrC3)alkyl, halogensubstitueret (CrC3)alkyl, (CrC3)alkoxy, halogen-substitueret (CrC3)alkoxy, (CrC3)alkyl-S(0)n-, (C3-C6)cycloalkyl, (C3-C6)cycloalkoxy, -(C0-C3)alkyl-NRxRy, -(C0-C3)alkyl-NRxC(O)Ry og -(C0-C3)alkyl-C(O)NRxRy; Ra ved hver forekomst uafhængigt er udvalgt fra hydrogen, (CrC3)alkyl og halogen; Z, Z1 og Z2 hver især uafhængigt er N eller CH eventuelt substitueret med halogen, (CrC3)alkoxy eller (CrC3)alkyl; L er en direkte binding, O, S, NH, N(CrC3)alkyl eller (CrC3)alkylen; R2 er hydrogen, halogen, cyano, (C-rC6)alkyl, (C3-C6)cycloalkyl, phenyl, mættet eller delvist umættet 5- til 6-leddet heterocyclyl indeholdende 1 til 4 heteroatomer, som hver især uafhængigt er udvalgt fra N, O eller S, eller 5- til 6-leddet heteroaryl indeholdende 1 til 4 heteroatomer, som hver især uafhængigt er udvalgt fra N, O eller S, hvor (C-|-C6)alkylet, (C3-C6)cycloalkylet, phenylet, det mættede eller delvist umættede 5- til 6-leddede heterocyclyl eller 5- til 6-leddede heteroaryl eventuelt er substitueret med 1 til 3 substituenter uafhængigt udvalgt fra gruppen bestående af halogen, hydroxy, cyano, (CrC3)alkyl, halogen-substitueret (CrC3)alkyl, (CrC3)alkoxy, halogen-substitueret (CrC3)alkoxy, (C-|-C3)alkyl-S(0)n-, (C3-C6)cycloalkyl, (C3-C6)cycloalkoxy, -(C0-C3)alkylNRxRy, -(C0-C3)alkylNRxC(O)Ry og -(C0-C3)alkylC(0)NRxRy; forudsat at hvis L er O, S, NH eller N(CrC3)alkyl, så er R2 ikke halogen; n ved hver forekomst uafhængigt er 0, 1 eller 2; og Rx og Ry ved hver forekomst uafhængigt er udvalgt fra hydrogen og (Cr C6)alkyl, hvor (CrC6)alkylet eventuelt er afbrudt af en eller to grupper, uafhængigt udvalgt fra NH, N(CrC3)alkyl, O og S, og eventuelt er substitueret med 1 til 4 halogener; eller Rx og Ry sammen er et (C2-C6)alkylen, som eventuelt er afbrudt af en eller to grupper uafhængigt udvalgt fra NH, N(Cr C3)alkyl, O og S; eller et farmaceutisk acceptabelt salt deraf.
3. Forbindelse ifølge krav 2, hvor: R1 er phenyl, naphthyl, imidazolyl, pyrazolyl, pyrazinyl, pyrimidinyl, thiazolyl, oxazolyl, thiazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, 2,3-dihydrobenzofuranyl, chromanyl, 3,4-dihydro-2H-pyrano[3,2-b]pyridinyl, 2,3-dihydrofurano[3,2-b]pyridinyl, indolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl, [1,2,4]triazolo[4,3-a]pyridin, imidazo[2,1-b][1,3]thiazolyl, pyridinyl, pyra-zolo[1,5-a]pyridinyl, imidazo[1,2-b][1,2,4]triazinyl, 1 H-pyrazolo[3,4-b]pyridinyl, 4.5.6.7- tetrahydropyrazolo[1,5-a]pyridinyl, imidazo[2,1 -b][ 1,3,4]thiadiazolyl, 1 H-indazolyl, pyridazinyl, oxadiazolyl eller imidazo[1,2-a]pyridinyl; imidazo[1,2-b]pyridazinyl, 2,3-dihydro[1,4]dioxino[2,3-b]pyridinyl (hver især eventuelt substitueret med 1 til 3 substituenter uafhængigt udvalgt fra fluor, chlor, (Cr C3)alkyl, (CrC3)alkoxy, trifluormethyl, trifluormethoxy, cyano, cyclopropyl, -C(0)NRxRy og -(C0-Ci)alkylNHC(O)CH3; eller et farmaceutisk acceptabelt salt deraf.
4. Forbindelse ifølge krav 3, hvor: R1 er phenyl, imidazo[2,1-b][1,3]thiazolyl, pyridinyl, pyrazolo[1,5-a]pyridinyl, 4.5.6.7- tetrahydropyrazolo[1,5-a]pyridinyl, imidazo[2,1 -b][ 1,3,4]thiadiazolyl, 1 H-indazolyl, pyridazinyl, oxadiazolyl eller imidazo[1,2-a]pyridinyl, imidazo[1,2-b]pyridazinyl, 1 H-pyrazolo[3,4-b]pyridinyl, imidazo[1,2-b]pyridazinyl, 2,3-dihydro[1,4]dioxino[2,3-b]pyridinyl: hver især eventuelt substitueret med 1 til 3 substituenter uafhængigt udvalgt fra methyl, methoxy, cyano, cyclopropyl, -C(0)NH2 og -NHC(0)CH3; Ra ved hver forekomst er hydrogen; og Z, Z1 og Z2 hver især er CH; eller et farmaceutisk acceptabelt salt deraf.
5. Forbindelse ifølge krav 2, hvor L er en direkte binding; og R2 er hydrogen, phenyl, pyrimidinyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, pyridinyl, oxazolyl, oxadiazolyl, pyrazolyl, pyridazinyl, triazinyl eller pyrazinyl; hver især eventuelt substitueret med 1 til 3 substituenter uafhængigt udvalgt fra methyl, trifluormethyl, ethyl, methoxy, cyano eller -C(0)NH2; eller et farmaceutisk acceptabelt salt deraf.
6. Forbindelse ifølge krav 2 med formel (IA)
(IA) eller et farmaceutisk acceptabelt salt deraf.
7. Forbindelse ifølge krav 6, hvor R1 er phenyl, naphthyl, imidazolyl, pyrazolyl, pyrazinyl, pyrimidinyl, thiazolyl, oxazolyl, thiazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, 2,3- dihydrobenzofuranyl, chromanyl, 3,4-dihydro-2FI-pyrano[3,2-b]pyridinyl, 2,3-dihydrofurano[3,2-b]pyridinyl, indolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl, [1,2,4]triazolo[4,3-a]pyridin, imidazo[2,1-b][1,3]thiazolyl, pyridinyl, pyra- zolo[1,5-a]pyridinyl, imidazo[1,2-b][1,2,4]triazinyl, 1 FI-pyrazolo[3,4-b]pyridinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridinyl, imidazo[2,1 -b][ 1,3,4]thiadiazolyl, 1 H-indazolyl, imidazo[1,2-b]pyridazinyl, 2,3-dihydro-[1,4]dioxino[2,3-b]pyridinyl eller imidazo[1,2-a]pyridinyl; hver især eventuelt substitueret med 1 til 3 sub-stituenter uafhængigt udvalgt fra fluor, chlor, (CrC3)alkyl, (CrC3)alkoxy, trifluormethyl, trifluormethoxy, cyano, cyclopropyl, -C(0)NFl2 og -NFIC(0)CFI3; eller et farmaceutisk acceptabelt salt deraf.
8. Forbindelse ifølge krav 7, hvor: R2 er phenyl, pyrimidinyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, pyridinyl, oxazolyl, oxadiazolyl, pyrazolyl, pyridazinyl, triazinyl eller pyrazinyl hver især eventuelt substitueret med 1 til 3 substituenter uafhængigt udvalgt fra methyl, ethyl, methoxy, cyano eller -C(0)NFl2; og L er en direkte binding eller O; eller et farmaceutisk acceptabelt salt deraf.
9. Forbindelse ifølge krav 8, hvor R2 er phenyl, pyrimidinyl, triazolyl, thiazolyl, pyridinyl, oxazolyl, pyrazolyl eller pyrazinyl; hver især eventuelt substitueret med 1 til 3 substituenter uafhængigt udvalgt fra methyl, ethyl, methoxy, cyano eller -C(0)NFl2; og L er en direkte binding; eller et farmaceutisk acceptabelt salt deraf.
10. Forbindelse ifølge krav 1 udvalgt fra gruppen bestående af: 5-[1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyrazin-2-carboxamid; 5-[1-{7-[(7-methylimidazo[1,2-a]pyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyrazin-2-carboxamid; 5- {1-[7-(imidazo[1,2-a]pyridin-2-ylacetyl)-2,7-diazaspiro[3.5]non-2-yl]-2,3-dihydro-1 H-inden-5-yl}pyrazin-2-carboxamid; 6- [1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyrimidin-4-carboxamid; 5-[1-{7-[(5-cycl°propylpyndin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyridin-2-carboxamid; 5- [1 -{7-[(2-methylimidazo[2,1 -b][1,3,4]thiadiazol-6-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyridin-2-carboxamid; 6- [1-{7-[(7-methylimidazo[1,2-a]pyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyrimidin-4-carboxamid; 5- [1-{7-[(5-ethylpyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyrazin-2-carboxamid; 6- [1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]nicotinamid; 7- [(4-methoxyphenyl)acetyl]-2-(5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl)- 2.7- diazaspiro[3.5]nonan; 7-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 3-(2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)-1 H-indazol; 7-[(4-methoxyphenyl)acetyl]-2-[5-(2-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(4-methoxyphenyl)acetyl]-2-[5-(5-methylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(1,3-thiazol-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(5-methyl-1,3-thiazol-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(2-methylimidazo[2,1 -b][1,3,4]thiadiazol-6-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-(5-phenoxy-2,3-dihydro-1 H-inden-1-yl)- 2.7- diazaspiro[3.5]nonan; 7-[(4-methoxyphenyl)acetyl]-2-[5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)acetyl]-2-[5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(5-methoxypyridin-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(2-methylpyridin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 2-(1-{7-[(5-methoxypyndin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl)isonicotinonitril; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(5-methylpyridin-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(5-methoxypyrimidin-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(6-methoxypyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(4-methylpyridin-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-(5-pyrazin-2-yl-2,3-dihydro-1 H-inden-1-yl)- 2.7- diazaspiro[3.5]nonan; 2-[5-(4,6-dimethylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1-yl]-7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(6-methylpyridin-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 2-[5-(5-ethylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1-yl]-7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonan; 2-[5-(6-ethylpyri midin-4-yl)-2,3-di hydro-1 H-inden-1-yl]-7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonan; 2-(2-{2-[5-(6-ethylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-5-methoxybenzonitril; 6- [1-{7-[(5-methoxypyndin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyrimidin-4-carbonitril; 7- [(4-methoxyphenyl)acetyl]-2-[5-(1,3-oxazol-2-yl)-2,3-dihydro-1 H-inden-1 -yl]- 2.7- diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-pyrimidin-4-yl-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-cyclopropylpyridin-2-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(1,3-oxazol-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 2-(5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl)-7-{[4-(trifluormethyl)phenyl] acetyl}-2,7-diazaspiro[3.5]nonan; 5-methoxy-2-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethoxy)benzonitril; 2-[2,3-dihydro-1 H-inden-1-yl]-7-[(4-methoxyphenyl)acetyl]-2,7-diazaspiro[3.5]nonan; 7-[(5-cyclopropylpyridin-2-yl)acetyl]-2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 2-[5-(4,6-dimethylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1-yl]-7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2,7-diazaspiro[3.5]nonan; 5- methoxy-2-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)benzonitril; 7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2-[5-(5-methylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 2-[5-(2,6-dimethylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2,7-diazaspiro[3.5]nonan; 6- [1-{7-[(7-methylimidazo[1,2-a]pyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyrimidin-4-carbonitril; N-[5-methoxy-2-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]- 2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)phenyl]acetamid; 7- [(2,3-dimethylimidazo[2,1-b][1,3]thiazol-6-yl)acetyl]-2-[5-(6-methylpyrimidin- 4-yl)-2,3-dihyd ro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(1 -ethyl-1 H-pyrazol-3-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 1 -methyl-3-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-1 H-pyrazolo[3,4-b]pyridin; 1 -ethyl-3-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-1 H-pyrazolo[3,4-b]pyridin; 7-[(1 -phenyl-1 H-imidazol-4-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-{[5-(difluormethyl)pyridin-2-yl]acetyl}-2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(3-methyl-1 H-pyrazol-5-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 6-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)imidazo[1,2-b][1,2,4]triazin; 6- [1-{7-[(5-cyclopropylpyndin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyrimidin-4-carbonitril; 7- [(5-methoxypyridin-2-yl)acetyl]-2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 6-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-2,3-dihydro[1,4]dioxino[2,3-b]pyridin; 6- (2-{2-[5-(2-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-2,3-dihydro[1,4]dioxino[2,3-b]pyridin; 7- [(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)acetyl]-2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(5-methylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methylpyridin-2-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl]- 2,7-diazaspiro[3.5]nonan; 2-[5-(1 -methyl-1 H-pyrazol-3-yl)-2,3-dihydro-1 H-inden-1 -yl]-7-[(5-methylpyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(2-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 2-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)imidazo[1,2-a]pyridin; 7-[(5-methylpyridin-2-yl)acetyl]-2-[5-(1,3-thiazol-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methylpyridin-2-yl)acetyl]-2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(1-methyl-1 H-pyrazol-3-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; N-[5-methoxy-2-(2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)phenyl]acetamid; 2-(2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)imidazo[1,2-a]pyridin; 6- (2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)-2,3-dihydro[1,4]dioxino[2,3-b]pyridin; 7- [(5-methoxypyridin-2-yl)acetyl]-2-[5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methylpyridin-2-yl)acetyl]-2-[5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 6- (2-{2-[5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-2,3-dihydro[1,4]dioxino[2,3-b]pyridin; 7- [(5-methoxypyridin-2-yl)acetyl]-2-[5-(6-methoxypyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 2-[5-(5-ethylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1-yl]-7-[(4-methoxyphenyl)acetyl]-2,7-diazaspiro[3.5]nonan; 7-methyl-2-(2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)imidazo[1,2-a]pyridin; 7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2-[5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 4- [1-{7-[(7-methylimidazo[1,2-a]pyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]benzamid; 5- [1-{7-[(5-rnethoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyridin-2-carbonitril; 4-[1-{7-[(5-ethylpyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]benzamid; 4-[1-{7-[(5-rnethoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]benzamid; 4-{1-[7-(imidazo[1,2-a]pyridin-2-ylacetyl)-2,7-diazaspiro[3.5]non-2-yl]-2,3-dihydro-1 H-inden-5-yl}benzamid; 7-[(4-cycl°propylphenyl)acetyl]-2-(5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl)-2,7-diazaspiro[3.5]nonan; 7-[(4-cyclopropylphenyl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl]- 2.7- diazaspiro[3.5]nonan; 7-[(5-ethylpyridin-2-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl]- 2.7- diazaspiro[3.5]nonan; 7-[(5-methylpyridin-2-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-ethylpyridin-2-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(4-methylphenyl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(4-ethylphenyl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 2-[5-(2,6-dimethylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonan; 2-{2-oxo-2-[2-(5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl)-2,7-diazaspiro[3.5]non-7-yl]ethyl}pyrazolo[1,5-a]pyridin; 2-{2-oxo-2-[2-(5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl)-2,7-diazaspiro[3.5]non-7-yl]ethyl}-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin; 7-methyl-2-(2-oxo-2-{2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1 H-inden-1 -yl]- 2,7-diazaspiro[3.5]non-7-yl}ethyl)imidazo[1,2-a]pyridin; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(4-methoxyphenyl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(2-methylimidazo[2,1 -b][1,3]thiazol-6-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)- 2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-ethoxypyridin-2-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; N-[5-methoxy-2-(2-oxo-2-{2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)phenyl]acetamid; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(1 H-1,2,4-triazol-1 -yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(5-methyl-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 5-methyl-2-(2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)benzamid; 5-methoxy-2-(2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)benzamid; 5-methoxy-2-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)benzamid; 5-methoxy-2-(3-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]non-7-yl}-3-oxopropyl)benzamid; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(4-methyl-1 H-pyrazol-1-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(4-methoxyphenyl)acetyl]-2-[5-(4-methyl-1 H-pyrazol-1 -yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(1 H-pyrazol-1 -yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 5-{1-[7-(2,3-dihydro[1,4]dioxino[2,3-b]pyridin-6-ylacetyl)-2,7-diazaspiro[3.5]non-2-yl]-2,3-dihydro-1 H-inden-5-yl}pyridin-2-carboxamid; 5-[1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyridin-2-carboxamid; 5-[1-{7-[(5-methylpyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyridin-2-carboxamid; 5-[1 -{7-[(2-methylimidazo[2,1 -b][1,3]thiazol-6-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyridin-2-carboxamid; 5-{1-[7-(imidazo[1,2-a]pyridin-2-ylacetyl)-2,7-diazaspiro[3.5]non-2-yl]-2,3-dihydro-1 H-inden-5-yl}pyridin-2-carboxamid; og 5-[1-{7-[(7-methylimidazo[1,2-a]pyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1 H-inden-5-yl]pyridin-2-carboxamid; eller et farmaceutisk acceptabelt salt deraf.
11. Forbindelse ifølge krav 6 udvalgt fra gruppen bestående af 7-[(2-methylimidazo[2,1 -b][1,3]thiazol-6-yl)acetyl]-2-[(1 R)-5-pyrimidi n-2-yl- 2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(4-methoxyphenyl)acetyl]-2-[(1 R)-5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[(1 R)-5-(1,3-thiazol-2-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 2-[(1 R)-5-(5-ethylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[(1 R)-5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[(1 R)-5-(5-methylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-ethylpyridin-2-yl)acetyl]-2-[(1 R)-5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1 - yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methoxypyridin-2-yl)acetyl]-2-[(1 R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 7-[(5-methylpyridin-2-yl)acetyl]-2-[(1 R)-5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 2-[(1 R)-5-(2,6-dimethylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonan; 7-[(2-methylimidazo[2,1 -b][1,3]thiazol-6-yl)acetyl]-2-[(1 R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 6- (2-{2-[(1 R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-2,3-dihydro[1,4]dioxino[2,3-b]pyridin; 5-{(1 R)-1 -[7-(2,3-dihydro[1,4]dioxino[2,3-b]pyridin-6-ylacetyl)-2,7-diazaspiro[3.5]non-2-yl]-2,3-dihydro-1 H-inden-5-yl}pyridin-2-carboxamid; 7- [(5-methoxypyridin-2-yl)acetyl]-2-[(1 R)-5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan; 2-(2-{2-[(1 R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)imidazo[1,2-a]pyridin; 7-[(2-methylimidazo[2,1 -b][1,3,4]thiadiazol-6-yl)acetyl]-2-[(1 R)-5-(6- methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1-yl]-2,7-diazaspiro[3.5]nonan; 5-methoxy-2-(2-oxo-2-{2-[(1 R)-5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1 -yl]- 2.7- diazaspiro[3.5]non-7-yl}ethyl)benzamid; 5- methoxy-2-(2-{2-[(1 R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)benzamid; N-[5-methoxy-2-(2-oxo-2-{2-[(1 R)-5-pyrimidin-2-yl-2,3-dihydro-1 H-inden-1 -yl]- 2.7- diazaspiro[3.5]non-7-yl}ethyl)phenyl]acetamid; og 6- (2-{2-[(1 R)-5-(2-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-2,3-dihydro[1,4]dioxino[2,3-b]pyridin; eller et farmaceutisk acceptabelt salt deraf.
12. Farmaceutisk sammensætning omfattende en forbindelse ifølge et af kravene 1 til 11 eller et farmaceutisk acceptabelt salt deraf og et farmaceutisk acceptabelt hjælpestof, fortyndingsmiddel eller bæremiddel.
13. Sammensætning ifølge krav 12, hvor forbindelsen eller det farmaceutisk acceptable salt deraf er til stede i en terapeutisk virksom mængde.
14. Forbindelse ifølge krav 1, som er 7-[(2-methylimidazo[2,1 -b][1,3]thiazol-6-yl)acetyl]-2-[(1 R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1 H-inden-1 -yl]-2,7-diazaspiro[3.5]nonan, eller et farmaceutisk acceptabelt salt deraf.
15. Forbindelse ifølge krav 1, som har strukturen
16. Forbindelse ifølge krav 1, som er 6-(2-{2-[(1 R)-5-(2-methylpyrimidin-4-yl)- 2,3-dihydro-1 FI-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-2,3-dihydro[1,4]dioxino[2,3-b]pyridin, eller et farmaceutisk acceptabelt salt deraf.
17. Forbindelse ifølge krav 1, som er 7-[(2-methylimidazo[2,1 -b][1,3,4]thiadiazol-6-yl)acetyl]-2-[(1 R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro- 1 FI-inden-1-yl]-2,7-diazaspiro[3.5]nonan, eller et farmaceutisk acceptabelt salt deraf.
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HK1182094A1 (zh) 2013-11-22
PH12012501800A1 (en) 2012-12-10
RU2524341C2 (ru) 2014-07-27
CA2792234A1 (en) 2011-09-22

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