1-(benzo [D] [1,3] dioxol-5-yl) -N- (phenyl) cyclopropane- carboxamide derivatives and related compounds as modulators of ATP-Binding Cassette transporters for the treatment of Cystic Fibrosis

    公开(公告)号:AU2006336504B2

    公开(公告)日:2012-07-26

    申请号:AU2006336504

    申请日:2006-12-28

    Applicant: VERTEX PHARMA

    Abstract: A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein: Each R1 is independently an optionally substituted C aliphatic, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted C membered cycloaliphatic or an optionally substituted 4 to 10 membered heterocycloaliphatic, carboxy, amido, amino, halo, or hydroxy, provided that at least one R is an optionally substituted aryl or an optionally substituted heteroaryl and said R is attached to the 3- or 4- position of the phenyl ring; R is hydrogen, an optionally substituted C aliphatic, an optionally substituted C cycloaliphatic, an optionally substituted phenyl, or an optionally substituted heteroaryl; Ring A is an optionally substituted cycloaliphatic or an optionally substituted heterocycloaliphatic where the atoms of ring A adjacent to C* are carbon atoms; Each R is an optionally substituted aryl or an optionally substituted heteroaryl; and n is 1, 2, 3, 4, or 5. Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator ("CFTR"). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

    Amide indole derivatives as modulators of ATP-binding cassette transporters

    公开(公告)号:NZ571803A

    公开(公告)日:2011-12-22

    申请号:NZ57180307

    申请日:2007-04-09

    Applicant: VERTEX PHARMA

    Abstract: Disclosed is a compound of formula Id e.g. 1-(Benzo[d][1,3]dioxol-5-yl)-N-(2-(2-methyl-4-(1H-tetrazol-5-yl)butan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide or a pharmaceutically acceptable salt thereof, wherein R1, R2, A, B and n are defined in the specification for treating or lessening the severity of a disease in a patient, wherein said disease is selected from cystic fibrosis, hereditary emphysema, hereditary hemochromatosis, coagulation-fibrinolysis deficiencies, Type 1 hereditary angioedema, Type 1 chylomicronemia, abetalipoproteinemia, lysosomal storage diseases, mucopolysaccharidoses, Sandhof/Tay-Sachs, Crigler-Najjar type II, polyendocrinopathy/hyperinsulemia, Diabetes mellitus, Laron dwarfism, myeloperoxidase deficiency, primary hypoparathyroidism, melanoma, glycanosis CDG type 1, congenital hyperthyroidism, osteogenesis imperfecta, hereditary hypofibrinogenemia, ACT deficiency, Diabetes insipidus, neurophyseal DI, neprogenic DI, Charcot-Marie Tooth syndrome, Perlizaeus-Merzbacher disease, neurodegenerative diseases, Parkinson's disease, amyotrophic lateral sclerosis, progressive supranuclear plasy, Pick's disease, polyglutamine neurological disorders, spongiform encephalopathies, Fabry disease, Straussler-Scheinker syndrome, COPD, dry-eye disease, or Sjogren's disease.

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