| abstract |
The present disclosure relates to 4-oxo-1H-quinoline-3-carboxamides as modulators of ATP-Binding Cassette (”ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present disclosure also relates to methods of treating ABC transporter mediated diseases using such modulators. 6,7-difluoro-N-(2-fluoro-5-hydroxy-4-tert-butyl-phenyl)-4-oxo-1H-quinoHne-3-carboxarnide; N-[4-(3,3-dimethylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl]-6-methyl-4-oxo-1H-quinoline-3-carboxamide; 8-cyano-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinaline-3-carboxamide; and (2S,3S)-methyl 3-methyl-1-(4-(4-oxo-1,4-dihydroquinoline-3-carboxamide)-3-(trifluoromethyl)phenyl)pyrrolidine-2-carboxylate. conditions which may be treated by the compounds of the disclosure include: cystic fibrosis, chronic bronchitis, recurrent bronchitis, acute bronchitis, male infertility caused by congenital bilateral absence of the vas deferens (CBAVD), female infertility caused by congenital absence of the uterus and vagina (CAUV), idiopathic chronic pancreatitis (ICP), idiopathic recurrent pancreatitis, idiopathic acute pancreatitis, chronic rhinosinusitis, primary sclerosing cholangitis, diabetes, dry eye, constipation, allergic bronchopulmonary aspergillosis (ABPA), bone diseases, and asthma |