Modulators of ATP-binding cassette transporters
AssigneeVertex Pharmaceuticals Incorporated
InventorsSara S. Hadida Ruah, Matthew Hamilton, Mark T. Miller, Peter D. J. Grootenhuis, Brian Richard Bear, Jason McCartney, Jinglan Zhou
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Abstract
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.
Claims45
A method of modulating CFTR transporter activity comprising the step of contacting said ABC transporter with a compound of formula (I):
- wherein:
- each R1 is an optionally substituted C1-6 aliphatic, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted C3-10 cycloaliphatic, an optionally substituted 3 to 10 membered heterocycloaliphatic, carboxy, amido, amino, halo, or hydroxy, provided that at least one R1 is an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally substituted aryl, or an optionally substituted heteroaryl attached to the 5- or 6-position of the pyridyl ring;
- each R2 is hydrogen, an optionally substituted C1-6 aliphatic, an optionally substituted C3-6 cycloaliphatic, an optionally substituted phenyl, or an optionally substituted heteroaryl;
- each R3 and R′3 together with the carbon atom to which they are attached form an optionally substituted C3-7 cycloaliphatic or an optionally substituted heterocycloaliphatic;
- each R4 is an optionally substituted aryl or an optionally substituted heteroaryl;
- and
- each n is 1-4.
A method of treating or lessening the severity of a disease in a patient, wherein said disease is selected from cystic fibrosis, hereditary emphysema, or COPD, said method comprising the step of administering to said patient an effective amount of a compound of formula I:
- or a pharmaceutically acceptable salt thereof,
- wherein:
- Each R1 is an optionally substituted C1-6 aliphatic, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted C3-10 cycloaliphatic, an optionally substituted 3 to 10 membered heterocycloaliphatic, carboxy, amido, amino, halo, or hydroxy, provided that at least one R1 is an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally substituted aryl, or an optionally substituted heteroaryl attached to the 5- or 6- position of the pyridyl ring;
- Each R2 is hydrogen, an optionally substituted C1-6 aliphatic, an optionally substituted C3-6 cycloaliphatic, an optionally substituted phenyl, or an optionally substituted heteroaryl;
- Each R3 and R′3 together with the carbon atom to which they are attached form an optionally substituted C3-7 cycloaliphatic or an optionally substituted heterocycloaliphatic;
- Each R4 is an optionally substituted aryl or an optionally substituted heteroaryl;
- and
- Each n is 1, 2, 3 or 4.
Dependencies are inferred from the claim text.