DK2774925T3 - Heterocycliske modulatorer af ATP-bindings-kassettetransportere - Google Patents

Heterocycliske modulatorer af ATP-bindings-kassettetransportere Download PDF

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DK2774925T3
DK2774925T3 DK14163968.2T DK14163968T DK2774925T3 DK 2774925 T3 DK2774925 T3 DK 2774925T3 DK 14163968 T DK14163968 T DK 14163968T DK 2774925 T3 DK2774925 T3 DK 2774925T3
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optionally substituted
compound
aliphatic
heteroaryl
alkyl
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DK14163968.2T
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Ruah Sarah Hadida
Matthew Hamilton
Mark Miller
Peter D J Grootenhuis
Brian Bear
Jason Mccarthy
Jinglan Zhou
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Vertex Pharma
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
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    • C07—ORGANIC CHEMISTRY
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    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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Claims (20)

1. Forbindelse med formel VI-A-i eller formel VI-A-ii:
VI-A-i VI-A-ii; eller et farmaceutisk acceptabelt salt deraf, hvor: T er -CHz-, -CF2-, eller -C(CH3)2-; Ri' er H, Ci-6 alifatisk, halo, CF3, CHF2, -0(Ci-e alifatisk), C3-C5 cycloalkyl, eller C4-C6 heterocycloalkyl indeholdende et oxygenatom; RD1 er ZDR9, hvor ZD er valgt fra CONH, NHCO, SO2NH, S02N(Ci-6 alkyl), NHSO2, CH2NHSO2, CH2N(CH3)S02, CH2NHCO, COO, SO2, eller CO; og Rg er H eller C1-6 alifatisk; og RD2 er H, hydroxyl, halo, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl, eller NH2.
2. Forbindelsen ifølge krav 1, hvor T er -CF2-.
3. Forbindelsen ifølge krav 1, hvor Ri' er H, methyl, ethyl, /'-propyl, t-butyl, F, Cl, CF3, CHF2, -OCH3, -OCH2CH3, -0-(/'-propyl), -O-(f--butyl), cyclopropyl, eller oxetanyl.
4. Forbindelsen ifølge krav 1, hvor Ri' er H, methyl, ethyl, CF3, eller oxetanyl.
5. Forbindelsen ifølge krav 1, hvor Ri' er methyl.
6. Forbindelsen ifølge krav 1, hvor ZD er CONH, SO2NH, S02N(Ci-6 alkyl), CH2NHSO2, CH2N(CH3)S02, CH2NHCO, COO, SO2, eller CO.
7. Forbindelsen ifølge krav 1, hvor ZD er COO.
8. Forbindelsen ifølge krav 1, hvor R.9 er H eller Ci-6 alkyl.
9. Forbindelsen ifølge krav 1, hvor Rg er H eller methyl.
10. Forbindelsen ifølge krav 1, hvor R9 er H.
11. Forbindelsen ifølge krav 1, hvor ZD er COO og R9 er H.
12. Forbindelsen ifølge krav 1, hvor RD2 er H eller C1-6 alkyl.
13. Forbindelsen ifølge krav 1, hvor RD2 er H eller methyl.
14. Forbindelsen ifølge krav 1, hvor RD2 er H.
15. Farmaceutisk sammensætning omfattende: (i) en forbindelse ifølge et hvilket som helst af kravene 1 til 14; og (ii) en farmaceutisk acceptabel bærer.
16. Sammensætningen ifølge krav 15, eventuelt yderligere omfattende et mucolytisk middel, en bronchodialator, et antibiotika, et anti-infektivt middel, et anti-inflammatorisk middel, en CFTR-modulator, elleret næringsmiddel.
17. Forbindelsen med formel VI-A-i eller formel VI-A-ii ifølge et hvilket som helst af kravene 1 til 14 eller en sammensætning af kravene 15 og 16 til anvendelse i en fremgangsmåde til behandling eller formindskelse af alvorligheden af cystisk fibrose, hvor patienten har et defekt gen der forårsager en deletion af phenylalanin ved position 508 af den cystiske fibrose transmembrane-konduktans-regulator-aminosyresekvens.
18. Kit til anvendelse i måling af aktiviteten af en ABC-transporter eller et fragment deraf i en biologisk prøve in vitro eller in vivo, omfattende: (i) en sammensætning omfattende forbindelse med formel VI-A-i eller formel VI-A-ii ifølge et hvilket som helst af kravene 1 til 14; og (ii) instruktioner til at: a) bringe den biologiske prøve i kontakt med sammensætningen; og b) måle aktiviteten af ABC-transporteren eller et fragment deraf.
19. Kittet ifølge krav 18, yderligere omfattende instruktioner til at a) bringe en yderligere sammensætning i kontakt med den biologiske prøve; b) måle aktiviteten af ABC-transporteren eller et fragment deraf i tilstedeværelsen af den yderligere forbindelse, og c) sammenligne aktiviteten af ABC-transporteren i tilstedeværelse af den yderligere forbindelse med densiteten af ABC-transporteren i tilstedeværelse af en sammensætning med formel VI-A-i eller formel VI-A-ii.
20. Kittet ifølge krav 19, hvor kittet anvendes til at måle densiteten af CFTR.
DK14163968.2T 2005-11-08 2006-11-08 Heterocycliske modulatorer af ATP-bindings-kassettetransportere DK2774925T3 (da)

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