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DK2758388T3 - Nye bicykliske dihydroquinolin-2-on-derivater - Google Patents

Nye bicykliske dihydroquinolin-2-on-derivater Download PDF

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DK2758388T3
DK2758388T3 DK12766628.7T DK12766628T DK2758388T3 DK 2758388 T3 DK2758388 T3 DK 2758388T3 DK 12766628 T DK12766628 T DK 12766628T DK 2758388 T3 DK2758388 T3 DK 2758388T3
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methyl
oxo
tetrahydro
propionamide
tetrahydroquinolin
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Johannes Aebi
Kurt Amrein
Serena Maria Fantasia
Benoit Hornsperger
Bernd Kuhn
Yongfu Liu
Alexander V Mayweg
Peter Mohr
Michelangelo Scalone
Xuefei Tan
Mingwei Zhou
Hans P Maerki
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Hoffmann La Roche
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P5/42—Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of mineralocorticosteroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

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  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Claims (20)

1. Forbindelser med formlen (I) hvor
R1 er (Ci-C7)-alkyl; R2 er H; R3 er H; R4 er H; R5 er H; R6 er H, halogen eller (Ci-C?)-alkyl; R7 er H; R8 er H; R9 er H; R10 er H; R11 erH; R12 er H eller halogen; A1 er CR13; A2erNR14 eller CR15R16; A3 er CR17; R13 er H eller halogen; R14 er -(CR20R21)q-(CR22R23)r-(CR24R25)p-NR26R27, hvor summen af q, r og p er mindst 2; R15 er -(CR20R21)q-(CR22R23)r-(CR24R25)p-NR26R27; R16 er H; eller R6 og R16 sammen med de carbonatomer, de er bundet til, danner en dobbeltbinding; R17 er H; R20 er H; R21 er Η; R22 er Η; R23 er H; R24 er H; R25 er H; R26 er H; R27 er H, -S(0)2R31, -C(0)R31 eller -C(0)0R31, hvor summen af q, r og p er mindst 1, såfremt R26 er H, og R27 er H; R31 er (Ci-C?)-alkyl, hydroxyl-(C 1-C7)-alkyl, (Ci-Cs)-cycloalkyl eller chlorpyridinyl; n er nul eller 1; p er nul eller 1; q er nul eller 1; r er nul eller 1; eller farmaceutisk acceptable salte eller estere.
2. Forbindelse ifølge krav 1, hvor R6 er H.
3. Forbindelse ifølge et hvilket somhelst af kravene 1 til 2, hvor R12 er H.
4. Forbindelse ifølge et hvilket som helst af kravene 1 til 3, hvor A2 er CRISR16.
5. Forbindelse ifølge et hvilket som helst af kravene 1 til 4, hvor R27 er -C(0)R31.
6. Forbindelse ifølge et hvilket som helst af kravene 1 til 5, hvor R31 er (Ci-C7)-alkyl.
7. Forbindelse ifølge et hvilket som helst af kravene 1 til 6, hvor n er 1.
8. Forbindelse ifølge et hvilket som helst af kravene 1 til 7, hvor q, r og p er nul.
9. Forbindelse ifølge et hvilket somhelst af kravene 1 til 8, der er valgt blandt (rac)-N-[4-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quino!in-6-yl)-5,6,7,8-tetrahydro- isoquinolin-8-yl]-propionamid; (-)-N-(4-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin- 8-yl)pr°pionamid; (+)-N-(4-( 1 -methyl-2 -oxo-1,2,3,4-tetrahydroquinolin-6 -yl)-5,6,7,8 -tetrahydroisoquinolin-8-yl)propionamid; (R) -N-(4-(l-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamid; (S) -N-(4-(l-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamid; (rac)-N-(4-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8- tetrahydroisoquinolin-8-yl)ethansulfonamid; (-)-N-(4-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin- 8-yl)ethansulfonamid; (+)-N-(4-(l-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)ethansulfonamid; (R) -N-(4-( 1 -methyl-2 -oxo-1,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)ethansulfonamid; (S) -N-(4-(l-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)ethansulfonamid; (rac)-N-(4-(l-methyl-2-o xo-1,2,3,4-tetrahydroquinolin-6-yl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)propionamid; (-)-N-(4-( 1 -methyl-2-oxo-l ,2,3,4-tetrahydroquinolin-6-yl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)propionamid; (+)-N-(4-(l-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)propionamid; (R) -N-(4-(l-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)propionamid; (S) -N-(4-( 1 -methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-6,7 -dihydro-5H-cyclopenta[c]pyridin-7-yl)propionamid; (rac)-N-(4-(l-methyl-2-o xo-1,2,3,4-tetrahydroquinolin-6-yl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)ethansulfonamid; {2-[5-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-3,4-dihydro-2H-[ 1,7]naphthyridin-1 -yl] -ethyl} -carbaminsyre-tert-butylester; 6-[ 1 -(2-amino-ethyl)-1,2,3,4-tetrahydro-[ 1,7]naphthyridin-5-yl]-1 -methyl-3,4-dihydro-1 H-quinolin-2-onhydrochlorid; N-{2-[5-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-3,4-dihydro-2H-[ 1,7]naphthyridin-1 -yl] -ethyl} -propionamid; N-(2-(5-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-3,4-dihydro-l,7-naphthyridin-1 (2H)-yl)ethyl)ethansulfonamid; og farmaceutisk acceptable salte deraf.
10. Forbindelse ifølge et hvilket som helst af kravene 1 til 8, der er valgt blandt (2R,S)-2-hydroxy-N-((4R,S)-4-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propanamid; (2R)-2-hydroxy-N-((4R,S)-4-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8- tetrahydroisoquinolin-8-yl)propanamid; (2S)-2-hydroxy-N-((4R,S)-4-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propanamid; (+)-(2R)-2-hydroxy-N-((4R eller 4S)-4-(l -methyl-2-oxo-1,2,3,4-tctrahydroquinolin-6-yl)- 5.6.7.8- tetrahydroisoquinolin-8-yl)propanamid; (-)-(2R)-2-hydroxy-N-((4S eller 4R)-4-(l -methyl-2-oxo-l ,2,3,4-tctrahydroquinolin-6-yl)- 5.6.7.8- tetrahydroisoquinolin-8-yl)propanamid; (-)-(2S)-2-hydroxy-N-((4S eller 4R)-4-(l-methyl-2-oxo-l ,2,3,4-tetrahydroquinolin-6-yl)- 5.6.7.8- tetrahydroisoquinolin-8-yl)propanamid; (+)-(2S)-2-hydroxy-N-((4R eller 4S)-4-(l -methyl-2-oxo-l ,2,3,4-tetrahydroquinolin-6-yl)- 5.6.7.8- tetrahydroisoquinolin-8-yl)propanamid; (rac)-N-(4-(7-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydroqumolin-6-yl)-6,7-dihydro-5H- cyclopenta[c]pyridin-7-yl)propionamid; (-)-(S eller R)-N-(4-(7-fluor-l -methyl-2-oxo-l ,2,3,4-tetrahydroquinolin-6-yl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)propionamid; (+)-(R eller S)-N-(4-(7-fluor-1 -methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)propionamid; (rac)-N-(4-(7-fluor-l-methyl-2-o xo-1,2,3,4-tetrahydroquinolin-6-yl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)ethansulfonamid; (-)-(S eller R)-N-(4-(7-fluor-l-methyl-2-oxo-l ,2,3,4-tetrahydroquinoIin-6-yl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)ethansulfonamid; (+)-(R eller S)-N-(4-(7-fluor-l -methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-6,7- dihydro-5H-cyclopenta[c]pyridin-7-yl)ethansulfonamid; (rac)-N-[4-(7-fluor-l-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; (-)-(S eller R)-N-[4-(7-fluor-l-methyl-2-oxo-l ,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; (+)-(R eller S)-N-[4-(7-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro -iso quino lin- 8 -yl] -propionamid; (-)-(S eller R)-ethansulfonsyre-[4-(7-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-amid; (+)-(R eller S)-ethansulfonsyre-[4-(7-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-amid; (rac)-N-[4-(8-chlor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro- isoquinoIin-8-yl]-propionamid; (rac)-ethansulfonsyre-[4-(7-chlor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)- 5.6.7.8- tetrahydro-isoquinolin-8-yl]-amid; N-[(R eller S)-4-(7-chlor-l-methyl-2-oxo-l ,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8- tetrahydro-isoquinolin-8-yl]-propionamid; (rac)-ethansulfonsyre-[4-(8-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)- 5.6.7.8- tetrahydro-isoquinolin-8-yl]-amid; (rac)-ethansulfonsyre-[4-(8-chlor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)- 5.6.7.8- tetrahydro-isoquinolin-8-yl]-amid; (+)-ethansulfonsyre-[(R eller S)-4-(8-chlor-1 -methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-amid; (-)-ethansulfonsyre-[(S eller R)-4-(8-chlor-1 -methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-amid; (-)-N-[(S eller R)-4-(8-chlor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8- tetrahydro -iso quino lin- 8 -yl] -propionamid; (+)-N-[(R eller S)-4-(8-chlor-l-methyl-2-oxo-l ,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro -iso quino lin- 8 -yl] -propionamid; (+)-N-[(7S,8R eller 7R,8S)-7-methyl-4-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; (-)-N-[(7S,8S eller 7R,8R)-4-(7-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-7-methyl-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; (-)-N-[(7R,8S eller 7S,8R)-4-(7-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinoIin-6-yl)- 7-methyl-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; (+)-N-[(7S,8R eller 7R,8S)-4-(7-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)- 7-methyl-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; (-)-N-[(7S,8S eller 7R,8R)-7-methyl-4-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)- 5.6.7.8- tetrahydro-isoquinolin-8-yl]-propionamid; (-)-N-[(7R,8S eller 7S,8R)-7-methyl-4-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)- 5.6.7.8- tetrahydro-isoquinolin-8-yl]-propionamid; (+)-N-[(7R,8R eller 7S,8S)-4-(7-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)- 7-methyl-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; (+)-N-[(7R,8R eller 7S,8S)-7-mcthyl-4-( 1 -methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; (-)-N-[(7R,8R eller 7S,8S)-7-fluor-4-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)- 5.6.7.8- tetrahydro-isoquinolin-8-yl]-propionamid; (-)-N-[(7S,8R eller 7R,8S)-7-fluor-4-( 1 -mcthyl-2-oxo-1,2,3,4-tetrahydro-quinoIin-6-yl)- 5.6.7.8- tetrahydro-isoquinolin-8-yl]-propionamid; (+)-N-[(7S,8S eller 7R,8R)-7-fluor-4-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)- 5.6.7.8- tetrahydro-isoquinolin-8-yl]-propionamid; (+)-N-[(7R,8S eller 7S,8R)-7-fluor-4-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)- 5.6.7.8- tetrahydro-isoquinolin-8-yl]-propionamid; (+)-N-[(7S,8S eller 7R,8R)-7-fluor-4-(7-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydro- quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; (+)-N-[(7R,8S eller 7S,8R)-7-fluor-4-(7-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydro- quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; (-)-N-[(7R,8R eller 7S,8S)-7-fluor-4-(7-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; (-)-N-[(7S,8R eller 7R,8S)-7-fluor-4-(7-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; (rac)-N-(4-(8-chlor-l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-6,7-dihydro-5H- cyclopenta[c]pyridin-7-yl)propionamid; (-)-(S eller R)-N-(4-(8-chlor-l -methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-6,7- dihydro-5H-cyclopenta[c]pyridin-7-yl)propionamid; (+)-(R eller S)-N-(4-(8-chlor-l -methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-6,7- dihydro-5H-cyclopenta[c]pyridin-7-yl)propionamid; (R)-6-(8-amino-5,6,7,8-tetrahydroisoquinolin-4-yl)-l -methyl-3,4-dihydroquinolin-2(lH)-on; 3-chlor-pyridin-2-carboxylsyre-[(R)-4-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)- 5,6,7,8-tetrahydro-isoquinolin-8-yl]-amid; N-[(R)-4-(l-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-acetamid; cyclopropancarboxylsyre-[(R)-4-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quinoIin-6-yl)-5,6,7,8 -tetrahydro-isoquinolin-8 -yl] -amid; N - [(R)-4-( 1 -methyl-2 -oxo-1,2,3,4-tetrahydro-quino lin-6-yl)-5,6,7,8 -tetrahydro-isoquinolin-8-yl]-methansulfonamid; cyclopropansulfonsyre-[(R)-4-(l -methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-amid; (rac)-6-(8-hydroxy-5,6,7,8-tetrahydro-isoquinolin-4-yl)-l-methyl-3,4-dihydroquinolin-2(lH)-on; (S eller R)-6-(8-hydroxy-5,6,7,8-tetrahydro-isoquinolin-4-yl)-l -methyl-3,4- dihydroquinolin-2( 1 H)-on; (R eller S)-6-(8-hydroxy-5,6,7,8-tetrahydro-isoquinolin-4-yl)-l -methyl-3,4- dihydroquinolin-2(lH)-on; l-methyl-6-(8-oxo-5,6,7,8-tetrahydro-isoquinolin-4-yl)-3,4-dihydro-lH-quinolin-2-on; N-[4-(l-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-5,6-dihydro-isoquinolin-8-yl]-propionamid; (+)-(R)-N-(4-(l -methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamid; og farmaceutisk acceptable salte deraf.
11. Forbindelse ifølge et hvilket som helst af kravene 1 til 9, der er valgt blandt (+)-N-(4-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin- 8-yl)propionamid; (+)-N-(4-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin- 8-yl)ethansulfonamid; (+)-N-(4-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-6,7-dihydro-5FI- cycIopenta[c]pyridin-7-yl)propionamid; (rac)-N-(4-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-6,7-dihydro-5H- cyclopenta[c]pyridin-7-yl)ethansulfonamid; N-{2-[5-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-3,4-dihydro-2H-[ 1,7]naphthyridin-1 -yl] -ethyl} -propionamid; og farmaceutisk acceptable salte deraf.
12. Forbindelse ifølge et hvilket som helst af kravene 1 til 8 og 10, der er valgt blandt (+)-(R eller S)-N-(4-(7-fluor-l -methyl-2-oxo-l ,2,3,4-tetrahydroquinolin-6-yl)-6,7- dihydro-5H-cyclopenta[c]pyridin-7-yl)propionamid; (+)-(R eller S)-N-(4-(7-fluor-l -methyl-2-oxo-l ,2,3,4-tetrahydroquinolin-6-yl)-6,7- dihydro-5H-cyclopenta[c]pyridin-7-yl)ethansulfonamid; (+)-(R eller S)-N-[4-(7-fluor-l-methyl-2-oxo-l ,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro -iso quino lin- 8 -yl] -propionamid; (+)-N-[(R eller S)-4-(8-chlor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro -iso quino lin- 8 -yl] -propionamid; (+)-N-[(7S,8R eller 7R,8S)-7-methyl-4-(l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; (+)-N-[(7R,8R eller 7S,8S)-4-(7-fluor-l-methyl-2-oxo-l,2,3,4-tetrahydro-quinolin-6-yl)- 7-methyl-5,6,7,8-tetrahydro-isoquinolin-8-yl]-propionamid; og farmaceutisk acceptable salte deraf.
13. Forbindelse ifølge et hvilket som helst af kravene 1 til 12, hvor forbindelsen er (+)-(S eller R)-N-(4-(l-mcthyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tctrahydroisoquinolin- 8-yl)propionamid eller farmaceutisk acceptable salte deraf.
14. Forbindelse ifølge et hvilket som helst af kravene 1 til 8, lOog 12, hvor forbindelsen er (+)-(R)-N-(4-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin- 8-yl)propionamid eller farmaceutisk acceptable salte deraf.
15. Forbindelse ifølge et hvilket som helst af kravene 1 til 14 til anvendelse som terapeutisk aktivt stof.
16. Forbindelse til anvendelse ifølge krav 15, hvor forbindelsen er (+)-(R)-N-(4-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamid eller farmaceutisk acceptable salte deraf.
17. Farmaceutisk sammensætning, der omfatter en forbindelse ifølge et hvilket som helst afkravene 1 til 14 og en terapeutisk inert bærer.
18. Farmaceutisk sammensætning ifølge krav 17, hvor forbindelsen er (+)-(R)-N-(4-(l -methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamid eller farmaceutisk acceptable salte deraf.
19. Forbindelse ifølge et hvilket som helst af kravene 1 til 14 til anvendelse ved behandling eller forebyggelse af kronisk nyresygdom, kongestiv hjerteinsufficiens, hypertension, primær aldosteronisme og Cushings syndrom.
20. Forbindelse til anvendelse ifølge krav 19, hvor forbindelsen er (+)-(R)-N-(4-(l-methyl-2-oxo-l,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamid eller farmaceutisk acceptable salte deraf.
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