1-(BENZO [D] [1,3] DI0X0L-5-YL) -N- (PHENYL) CYCLOPROPANE- CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS FOR THE TREATMENT OF CYSTIC FIBROSIS

摘要

A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein: Each R1 is independently an optionally substituted C_1-6 aliphatic, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted C_3-10 membered cycloaliphatic or an optionally substituted 4 to 10 membered heterocycloaliphatic, carboxy, amido, amino, halo, or hydroxy, provided that at least one R₁ is an optionally substituted aryl or an optionally substituted heteroaryl and said R₁ is attached to the 3- or 4- position of the phenyl ring; R₂ is hydrogen, an optionally substituted C_1-6 aliphatic, an optionally substituted C_3-6 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 R₄ 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.