Details for Patent: 8,614,327

Title:	Modulators of ATP-binding cassette transporters
Abstract:	The present invention relates to modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.
Inventor(s):	Sheth; Urvi (San Diego, CA), Fanning; Lev T. D. (San Marcos, CA), Numa; Mehdi Michel Djamel (San Diego, CA), Binch; Hayley (Encinitas, CA), Hurley; Dennis (San Marcos, CA), Zhou; Jinglan (San Diego, CA), Hadida Ruah; Sara S. (La Jolla, CA), Hazlewood; Anna (San Diego, CA), Silina; Alina (San Diego, CA), Vairagoundar; Rajendran (Kalamazoo, MI), Van Goor; Fredrick (San Diego, CA), Grootenhuis; Peter D. J. (San Diego, CA), Botfield; Martyn (Concord, MA)
Assignee:	Vertex Pharmaceuticals Incorporated (Cambridge, MA)
Filing Date:	Nov 30, 2012
Application Number:	13/690,924
Claims:	1. A compound selected from: 6,7-difluoro-N-(2-fluoro-5-hydroxy-4-tert-butyl-phenyl)-4-oxo-1H-quinolin- e-3-carboxamide 5-hydroxy-N-[5-hydroxy-4-tert-butyl-2-(trifluoromethyl)phenyl]-4-oxo-1H-q- uinoline-3-carboxamide 4-oxo-N-[3-(1-piperidyl)-5-(trifluoromethyl)phenyl]-1H-quinoline-3-carbox- amide N-[4-(3,3-dimethylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl]-6-meth- yl-4-oxo-1H-quinoline-3-carboxamide 6-fluoro-N-(3-hydroxy-4-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxami- de N-(3-fluoro-4-tert-butyl-phenyl)-5-hydroxy-4-oxo-1H-quinoline-3-carboxa- mide methyl 1-[4-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-3-(trifluoromethyl)phenyl]pi- peridine-2-carboxylate 5-hydroxy-N-[4-[2-hydroxy-1-(hydroxymethyl)-1-methyl-ethyl]phenyl]-4-oxo-- 1H-quinoline-3-carboxamide 5-hydroxy-4-oxo-N-[5-(trifluoromethyl)-1H-indol-6-yl]-1H-quinoline-3-carb- oxamide 6-fluoro-4-oxo-N-[2-(trifluoromethyl)-1H-indol-6-yl]-1H-quinoline-- 3-carboxamide N-(5-hydroxy-2,4-ditert-butyl-phenyl)-6-methoxy-4-oxo-1H-quinoline-3-carb- oxamide N-[5-hydroxy-4-isopropyl-2-(trifluoromethyl)phenyl]-4-oxo-1H-quino- line-3-carboxamide N-[2-fluoro-5-hydroxy-4-(1-methylcyclohexyl)-phenyl]-5-methyl-4-oxo-1H-qu- inoline-3-carboxamide N-[2-fluoro-5-hydroxy-4-(1-methylcyclohexyl)-phenyl]-7-methyl-4-oxo-1H-qu- inoline-3-carboxamide 5-hydroxy-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide N-[2-fluoro-5-hydroxy-4-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-car- boxamide 5-hydroxy-N-[3-methoxy-5-(trifluoromethyl)phenyl]-4-oxo-1H-quinol- ine-3-carboxamide 6-methyl-N-[4-(2-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl]-4-oxo-- 1H-quinoline-3-carboxamide N-[4-(3,3-dimethylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl]-6-methoxy-4- -oxo-1H-quinoline-3-carboxamide 8-cyano-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carbox- amide N-[3-hydroxy-4-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-carboxa- mide N-(2-ethyl-5-hydroxy-4-tert-butyl-phenyl)-5-hydroxy-4-oxo-1H-quinolin- e-3-carboxamide 4-oxo-N-[3-tert-butyl-5-(trifluoromethyl)-1H-indol-6-yl]-1H-quinoline-3-c- arboxamide 6-fluoro-N-[5-hydroxy-4-tert-butyl-2-(trifluoromethyl)phenyl]-4- -oxo-1H-quinoline-3-carboxamide 4-oxo-N-[3-(1-piperidyl)-4-tert-butyl-phenyl]-1H-quinoline-3-carboxamide (S)-5-methyl-N-(4-(2-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4-- oxo-1,4-dihydroquinoline-3-carboxamide N-[4-cyclopentyl-5-hydroxy-2-(3-hydroxyprop-1-ynyl)phenyl]-4-oxo-1H-quino- line-3-carboxamide (S)--N-(4-(3-(dimethylamino)pyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4- -oxo-1,4-dihydroquinoline-3-carboxamide 4-oxo-N-[2-(1-piperidyl)-4-(trifluoromethyl)phenyl]-1H-quinoline-3-carbox- amide N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-6-(trifluoromethyl)-1H-q- uinoline-3-carboxamide N-(4-((2S,5S)-2,5-dimethylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-5-m- ethyl-4-oxo-1,4-dihydroquinoline-3-carboxamide 8-ethoxy-N-[4-isopropyl-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-c- arboxamide N-(5-hydroxy-2-methyl-4-tert-butyl-phenyl)-4-oxo-1H-quinoline-3- -carboxamide 8-cyano-N-(2-fluoro-5-hydroxy-4-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-c- arboxamide N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-5-(trifluoromethyl)- -1H-quinoline-3-carboxamide 6-fluoro-N-[4-(3-methyloxetan-3-yl)phenyl]-4-oxo-1H-quinoline-3-carboxami- de N-(4-cyclohexyl-3-hydroxy-phenyl)-5-hydroxy-4-oxo-1H-quinoline-3-carbox- amide N-[4-(3-methyloxetan-3-yl)phenyl]-4-oxo-1H-quinoline-3-carboxamide 6-ethoxy-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carbo- xamide 6-cyano-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-- carboxamide 8-ethoxy-N-(2-fluoro-5-hydroxy-4-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-- carboxamide 6-fluoro-N-(3-fluoro-4-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamid- e N-[4-(3,3-difluoropyrrolidin-1-yl)-2-(trifluoromethyl)phenyl]-5-methyl-4- -oxo-1H-quinoline-3-carboxamide 5-hydroxy-N-[4-(3-methyloxetan-3-yl)phenyl]-4-oxo-1H-quinoline-3-carboxam- ide (2S,3S)-methyl 3-methyl-1-(4-(4-oxo-1,4-dihydroquinoline-3-carboxamido)-3-(trifluorometh- yl)phenyl)pyrrolidine-2-carboxylate (1S,2S,5R)-methyl 3-(4-(4-oxo-1,4-dihydroquinoline-3-carboxamido)-3-(trifluoromethyl)phenyl- )-3-azabicyclo[3.1.0]hexane-2-carboxylate N-[2-chloro-4-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-carboxamide 6-methoxy-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide (R)--N-(4-(3-(dimethylamino)pyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4- -oxo-1,4-dihydroquinoline-3-carboxamide 5-hydroxy-4-oxo-N-(3-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide N-[4-(3,3-dimethylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl]-4-oxo-1H-qu- inoline-3-carboxamide 4-oxo-N-[2-(trifluoromethyl)-1H-indol-6-yl]-1H-quinoline-3-carboxamide N-[2-methyl-4-(trifluoromethoxy)phenyl]-4-oxo-1H-quinoline-3-carboxamide N-(4-((2R,5R)-2,5-dimethylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-5-m- ethyl-4-oxo-1,4-dihydroquinoline-3-carboxamide (R)-tert-butyl 1-(4-(4-oxo-1,4-dihydroquinoline-3-carboxamido)-3-(trifluoromethyl)phenyl- )pyrrolidine-2-carboxylate (R)--N-(4-(3-fluoropyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-5-methyl-4- -oxo-1,4-dihydroquinoline-3-carboxamide N-(5-hydroxy-2,4-ditert-butyl-phenyl)-5-methylamino-4-oxo-1H-quinoline-3-- carboxamide 4-oxo-N-[4-(1-piperidyl)phenyl]-1H-quinoline-3-carboxamide 6-dimethylamino-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-- 3-carboxamide 4-oxo-N-[3-(trifluoromethyl)-1H-indol-6-yl]-1H-quinoline-3-carboxamide 5-methyl-N-[4-(3-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl]-4-oxo-- 1H-quinoline-3-carboxamide N-[4-isopropoxy-2-(trifluoromethyl)phenyl]-5-methyl-4-oxo-1H-quinoline-3-- carboxamide 7-cyano-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carbox- amide 4-oxo-N-[3-(2-thienyl)phenyl]-1H-quinoline-3-carboxamide (2S,4R)-methyl 4-tert-butoxy-1-(4-(4-oxo-1,4-dihydroquinoline-3-carboxamido)-3-(trifluor- omethyl)phenyl)pyrrolidine-2-carboxylate N-(4-hydroxy-2-naphthyl)-4-oxo-1H-quinoline-3-carboxamide 5-fluoro-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carbo- xamide 6-bromo-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-- carboxamide 6-fluoro-4-oxo-N-(3-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide N-[4-(3-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinol- ine-3-carboxamide N-[4-(2,2-dimethylpropanoylamino)-2-(trifluoromethyl)phenyl]-4-oxo-1H-qui- noline-3-carboxamide 6-fluoro-N-[4-isopropyl-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-c- arboxamide 7-cyano-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-car- boxamide 4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-8-(trifluoromethyl)-1H-quino- line-3-carboxamide N-[4-(2,5-dimethylpyrrol-1-yl)-3-methoxy-phenyl]-4-oxo-1H-quinoline-3-car- boxamide 6-chloro-N-(2-fluoro-5-hydroxy-4-tert-butyl-phenyl)-4-oxo-1H-quin- oline-3-carboxamide 6-fluoro-4-oxo-N-[4-pyrrolidin-1-yl-2-(trifluoromethyl)phenyl]-1H-quinoli- ne-3-carboxamide N-[3-hydroxy-5-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-carboxamide N-(4-cyclohexyl-3-hydroxy-phenyl)-4-oxo-1H-quinoline-3-carboxamide 5-methyl-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide 6-fluoro-N-[1-(2-methoxyethyl)-5-(trifluoromethyl)indol-6-yl]-4-oxo-1H-qu- inoline-3-carboxamide (S)-1-[4-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-3-(trifluoromethyl)pheny- l]pyrrolidine-2-carboxylic acid N-(5-hydroxy-2,4-ditert-butyl-phenyl)-5-methyl-4-oxo-1H-quinoline-3-carbo- xamide N-(4-((2R,5R)-2,5-dimethylpyrrolidin-1-yl)-2-(trifluoromethyl)pheny- l)-6-methyl-4-oxo-1,4-dihydroquinoline-3-carboxamide N-[5-benzyloxy-4-isopropyl-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-- 3-carboxamide N-[6-methoxy-5-(trifluoromethyl)-2-pyridyl]-4-oxo-1H-quinoline-3-carboxam- ide (R)--N-(4-(2-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4-oxo-1- ,4-dihydroquinoline-3-carboxamide 8-fluoro-N-[4-isopropyl-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-c- arboxamide 6-fluoro-N-[3-hydroxy-5-(trifluoromethyl)phenyl]-4-oxo-1H-quino- line-3-carboxamide N-(3-hydroxy-4-isopropyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide 7-methyl-4-oxo-N-[5-(trifluoromethyl)-1H-indol-6-yl]-1H-quinoline-3-carbo- xamide N-[2-methyl-5-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-carboxa- mide N-[4-(3,3-dimethylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl]-5-methy- l-4-oxo-1H-quinoline-3-carboxamide 4-oxo-N-[3-pyrrolidin-1-yl-4-(trifluoromethoxy)phenyl]-1H-quinoline-3-car- boxamide N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-8-(trifluoromethyl)-1- H-quinoline-3-carboxamide (S)-5-methyl-N-(6-(2-methylpyrrolidin-1-yl)-2-(trifluoromethyl)pyridin-3-- yl)-4-oxo-1,4-dihydroquinoline-3-carboxamide N-(4-((1S,4R)-2-azabicyclo[2.2.1]heptan-2-yl)-2-(trifluoromethyl)phenyl)-- 5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxamide N-(5-hydroxy-2,4-ditert-butyl-phenyl)-7-methoxy-4-oxo-1H-quinoline-3-carb- oxamide N-[2-fluoro-5-hydroxy-4-(1-methylcyclohexyl)-phenyl]-6-methoxy-4-o- xo-1H-quinoline-3-carboxamide 5-amino-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carbox- amide (R)--N-(4-(2-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4-oxo- -5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide 5-hydroxy-N-(3-hydroxy-4-isopropyl-phenyl)-4-oxo-1H-quinoline-3-carboxami- de 5-hydroxy-N-(5-hydroxy-2-methyl-4-tert-butyl-phenyl)-4-oxo-1H-quinoline- -3-carboxamide 6,7-difluoro-N-[4-isopropyl-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline- -3-carboxamide N-[4-[2-hydroxy-1-(hydroxymethyl)-1-methyl-ethyl]phenyl]-4-oxo-1H-quinoli- ne-3-carboxamide N-(5-ethyl-1H-indol-6-yl)-5-hydroxy-4-oxo-1H-quinoline-3-carboxamide N-(4-((2R,5S)-2,5-dimethylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-5-m- ethyl-4-oxo-1,4-dihydroquinoline-3-carboxamide 4-oxo-N-[3-pyrrolidin-1-yl-5-(trifluoromethyl)phenyl]-1H-quinoline-3-carb- oxamide N-(3-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxa- mide N-[4-cyclopentoxy-2-(trifluoromethyl)phenyl]-5-methyl-4-oxo-1H-quinol- ine-3-carboxamide N-(5-fluoro-1H-indol-6-yl)-5-hydroxy-4-oxo-1H-quinoline-3-carboxamide 6-fluoro-N-(3-hydroxy-4-isopropyl-phenyl)-4-oxo-1H-quinoline-3-carboxamid- e N-[4-morpholino-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-carboxam- ide 5-hydroxy-N-[3-hydroxy-5-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3- -carboxamide tert-butyl [[4-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-3-(trifluoromethyl)phenyl]ami- no]formate (S)-6-methoxy-N-(4-(2-methylpyrrolidin-1-yl)-2-(trifluoromethyl- )phenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide 4-oxo-N-(3-tert-butylphenyl)-1H-quinoline-3-carboxamide 6-chloro-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide 7-acetyl-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carbo- xamide 8-ethyl-N-(2-fluoro-5-hydroxy-4-tert-butyl-phenyl)-4-oxo-1H-quinoli- ne-3-carboxamide 5-hydroxy-N-[3-hydroxy-4-(1-methylcyclohexyl)-phenyl]-4-oxo-1H-quinoline-- 3-carboxamide (S)-7-methyl-N-(4-(2-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4-- oxo-1,4-dihydroquinoline-3-carboxamide N-(2,4-dichloro-5-hydroxy-phenyl)-4-oxo-1H-quinoline-3-carboxamide 5-hydroxy-N-(5-hydroxy-2-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxam- ide 5-fluoro-N-(2-fluoro-5-hydroxy-4-tert-butyl-phenyl)-4-oxo-1H-quinoline- -3-carboxamide 7-fluoro-6-methoxy-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-ca- rboxamide N-[4-(3,3-dimethyl-1-piperidyl)-2-(trifluoromethyl)phenyl]-4-oxo- -1H-quinoline-3-carboxamide (R)-5-methyl-N-(4-(3-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4-- oxo-1,4-dihydroquinoline-3-carboxamide 4-oxo-N-[4-(3-pyridyloxy)phenyl]-1H-quinoline-3-carboxamide N-(2-methyl-4-pyrrolidin-1-yl-phenyl)-4-oxo-1H-quinoline-3-carboxamide 8-ethoxy-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carbo- xamide 6-fluoro-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-7-methoxy-4-oxo-1H-q- uinoline-3-carboxamide (S)--N-(4-(2-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4-oxo-1,4-- dihydroquinoline-3-carboxamide N-[4-cyclohexyl-5-hydroxy-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3- -carboxamide 5-hydroxy-4-oxo-N-(3-tert-butylphenyl)-1H-quinoline-3-carboxamide N-(5-hydroxy-2,4-ditert-butyl-phenyl)-8-methyl-4-oxo-1H-quinoline-3-carbo- xamide N-(2-cyano-4-pyrrolidin-1-yl-phenyl)-4-oxo-1H-quinoline-3-carboxami- de 6-chloro-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-car- boxamide N-[2-fluoro-5-hydroxy-4-(1-methylcyclohexyl)-phenyl]-6-methyl-4-o- xo-1H-quinoline-3-carboxamide N-(2-fluoro-5-hydroxy-4-tert-butyl-phenyl)-8-methyl-4-oxo-1H-quinoline-3-- carboxamide (S)--N-(4-(3-fluoropyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-5-methyl-4- -oxo-1,4-dihydroquinoline-3-carboxamide 6-fluoro-N-[4-[2-hydroxy-1-(hydroxymethyl)-1-methyl-ethyl]phenyl]-4-oxo-1- H-quinoline-3-carboxamide N-[2-chloro-4-(trifluoromethoxy)phenyl]-4-oxo-1H-quinoline-3-carboxamide (S)-tert-butyl 1-(4-(4-oxo-1,4-dihydroquinoline-3-carboxamido)-3-(trifluoromethyl)phenyl- )pyrrolidine-2-carboxylate N-[2,5-bis(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-carboxamide (S)-methyl 2-methyl-1-(4-(4-oxo-1,4-dihydroquinoline-3-carboxamido)-3-(trifluorometh- yl)phenyl)pyrrolidine-2-carboxylate 4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-7-(trifluoromethoxy)-1H-quinoline-3-- carboxamide 5-hydroxy-N-(3-hydroxy-4-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxam- ide (S)--N-(4-(2-(hydroxymethyl)pyrrolidin-1-yl)-2-(trifluoromethyl)phenyl- )-4-oxo-1,4-dihydroquinoline-3-carboxamide N-[2-chloro-4-(trifluoromethyl)phenyl]-5-hydroxy-4-oxo-1H-quinoline-3-car- boxamide N-[2-chloro-4-(trifluoromethyl)phenyl]-6-fluoro-4-oxo-1H-quinolin- e-3-carboxamide N-[4-isopropyl-2-(trifluoromethyl)phenyl]-8-methyl-4-oxo-1H-quinoline-3-c- arboxamide N-(2-fluoro-5-hydroxy-4-tert-butyl-phenyl)-4-oxo-8-(trifluorome- thyl)-1H-quinoline-3-carboxamide N-[4-(4-isopropylpiperazin-1-yl)-2-(trifluoromethyl)phenyl]-4-oxo-1H-quin- oline-3-carboxamide N-(5-hydroxy-2,4-ditert-butyl-phenyl)-7-methyl-4-oxo-1H-quinoline-3-carbo- xamide 8-ethoxy-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carbox- amide (S)-7-methoxy-N-(4-(2-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phen- yl)-4-oxo-1,4-dihydroquinoline-3-carboxamide 5-methyl-N-[4-(3-methyl-1-piperidyl)-2-(trifluoromethyl)phenyl]-4-oxo-1H-- quinoline-3-carboxamide 8-methyl-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide N-(3-fluoro-4-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide 6,7-difluoro-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxam- ide N-(4-cyclohexyl-2-methyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide 5-hydroxy-N-[4-isopropyl-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-- carboxamide N-(2-ethyl-5-hydroxy-4-tert-butyl-phenyl)-6-fluoro-4-oxo-1H-quinoline-3-c- arboxamide 6-fluoro-N-[3-hydroxy-4-(trifluoromethyl)phenyl]-4-oxo-1H-quino- line-3-carboxamide N-(4-cyclohexyl-3-hydroxy-phenyl)-6-fluoro-4-oxo-1H-quinoline-3-carboxami- de 7-hydroxy-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-ca- rboxamide 8-ethyl-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carb- oxamide N-[5-benzyloxy-4-cyclohexyl-2-(trifluoromethyl)phenyl]-4-oxo-1H-qu- inoline-3-carboxamide (S)--N-(4-(3-hydroxypyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4-oxo-1,4- -dihydroquinoline-3-carboxamide 5-fluoro-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide 6-chloro-N-[4-isopropyl-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-c- arboxamide 4-oxo-N-[4-pyrrolidin-1-yl-2-(trifluoromethyl)phenyl]-1H-quinol- ine-3-carboxamide N-(2-ethyl-5-hydroxy-4-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamid- e (S)-ethyl 1-(4-(4-oxo-1,4-dihydroquinoline-3-carboxamido)-3-(trifluoromethyl)phenyl- )piperidine-3-carboxylate 5-methyl-4-oxo-N-[5-(trifluoromethyl)-1H-indol-6-yl]-1H-quinoline-3-carbo- xamide N-(5-hydroxy-2-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide 8-chloro-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carbo- xamide 6-fluoro-4-oxo-N-(3-tert-butylphenyl)-1H-quinoline-3-carboxamide 6-fluoro-N-(5-hydroxy-2-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxami- de 6-fluoro-N-[3-methoxy-5-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-c- arboxamide (R)--N-(4-(4,4-difluoro-2-methylpyrrolidin-1-yl)-2-(trifluorome- thyl)phenyl)-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxamide N-[4-[4-(hydroxymethyl)-1-piperidyl]-2-(trifluoromethyl)phenyl]-4-oxo-1H-- quinoline-3-carboxamide (S)--N-(4-(2-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(t- rifluoromethyl)-1,4-dihydroquinoline-3-carboxamide (R)--N-(4-(2-(hydroxymethyl)pyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4- -oxo-1,4-dihydroquinoline-3-carboxamide N-(2-aminobenzothiazol-6-yl)-4-oxo-1H-quinoline-3-carboxamide 6,7-difluoro-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-c- arboxamide N-[4-[4-(2-hydroxyethyl)piperazin-1-yl]-2-(trifluoromethyl)phen- yl]-4-oxo-1H-quinoline-3-carboxamide 4-oxo-N-(4-pyrrolidin-1-ylphenyl)-1H-quinoline-3-carboxamide N-(2-methoxy-4-pyrrolidin-1-yl-phenyl)-4-oxo-1H-quinoline-3-carboxamide 5-hydroxy-N-[2-methyl-5-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-car- boxamide 7-cyano-N-(2-fluoro-5-hydroxy-4-tert-butyl-phenyl)-4-oxo-1H-quino- line-3-carboxamide 6-fluoro-N-[2-methyl-5-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-carb- oxamide 6-hydroxy-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carb- oxamide 8-fluoro-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carbo- xamide 6-ethoxy-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carbox- amide 8-ethyl-N-[4-isopropyl-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline- -3-carboxamide 6-fluoro-N-(5-hydroxy-2-methyl-4-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-- carboxamide (R)-6-fluoro-N-(4-(2-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4-- oxo-1,4-dihydroquinoline-3-carboxamide N-(4-((2R,5R)-2,5-dimethylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-6-m- ethoxy-4-oxo-1,4-dihydroquinoline-3-carboxamide 4-oxo-N-[4-(1-piperidyl)-2-(trifluoromethyl)phenyl]-1H-quinoline-3-carbox- amide 8-fluoro-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-- carboxamide N-(5-hydroxy-2,4-ditert-butyl-phenyl)-6-methyl-4-oxo-1H-quinoline-3-carbo- xamide N-[4-azetidin-1-yl-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-- carboxamide methyl 4-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-2-tert-butyl-thiophene-3-carbox- ylate N-[3-methoxy-5-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-carboxa- mide 4-oxo-N-[2-(2-pyridyl)phenyl]-1H-quinoline-3-carboxamide 5-hydroxy-4-oxo-N-[2-(trifluoromethyl)-1H-indol-6-yl]-1H-quinoline-3-carb- oxamide N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-7-(trifluoromethoxy)-1- H-quinoline-3-carboxamide N-(4-chloro-2-fluoro-5-hydroxy-phenyl)-4-oxo-1H-quinoline-3-carboxamide 4-oxo-N-[3-(1-piperidyl)-4-(trifluoromethoxy)phenyl]-1H-quinoline-3-carbo- xamide (R)-5-methyl-N-(4-(2-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phen- yl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (R)-1-[4-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-3-(trifluoromethyl)pheny- l]pyrrolidine-2-carboxylic acid 5-fluoro-N-[4-isopropyl-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-c- arboxamide 5-hydroxy-N-[3-hydroxy-4-(trifluoromethyl)phenyl]-4-oxo-1H-quin- oline-3-carboxamide N-(3-hydroxy-4-isopropoxy-phenyl)-5-methyl-4-oxo-1H-quinoline-3-carboxami- de 6-hydroxy-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-ca- rboxamide 6-fluoro-4-oxo-N-[5-(trifluoromethyl)-1H-indol-6-yl]-1H-quinolin- e-3-carboxamide 7-methyl-4-oxo-N-(5-tert-butyl-1H-indol-6-yl)-1H-quinoline-3-carboxamide (R)--N-(4-(3-hydroxypyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4-oxo-1,4- -dihydroquinoline-3-carboxamide N-[2-fluoro-5-hydroxy-4-(1-methylcyclohexyl)-phenyl]-4-oxo-5-(trifluorome- thyl)-1H-quinoline-3-carboxamide 4-oxo-N-(3-pyrrolidin-1-yl-4-tert-butyl-phenyl)-1H-quinoline-3-carboxamid- e 4-oxo-N-[4-phenyl-5-(trifluoromethyl)-3-thienyl]-1H-quinoline-3-carboxam- ide 7-fluoro-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-6-methoxy-4-oxo-1H-quin- oline-3-carboxamide 4-oxo-N-(1,4,4-trimethyl-2,3-dihydroquinolin-7-yl)-1H-quinoline-3-carboxa- mide 6-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-1H-indole-4-carboxylic acid N-[3-fluoro-4-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-carboxamide (S)--N-(4-(2-methylpiperidin-1-yl)-2-(trifluoromethyl)phenyl)-4-oxo-1,4-d- ihydroquinoline-3-carboxamide (S)-6-fluoro-N-(4-(2-methylpyrrolidin-1-yl)-2-(trifluoromethyl)phenyl)-4-- oxo-1,4-dihydroquinoline-3-carboxamide (S)-methyl 1-(4-(4-oxo-1,4-dihydroquinoline-3-carboxamido)-3-(trifluoromethyl)phenyl- )piperidine-2-carboxylate 8-chloro-N-[3-hydroxy-4-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-car- boxamide N-(4-methoxy-2-naphthyl)-4-oxo-1H-quinoline-3-carboxamide 5,8-difluoro-N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-c- arboxamide or a pharmaceutically acceptable salt thereof. 2. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or adjuvant. 3. The pharmaceutical composition according to claim 2, further comprising an additional agent selected from a mucolytic agent, a bronchodialator, an antibiotic, an anti-infective agent, an anti-inflammatory agent, a CFTR modulator, or a nutritional agent. 4. The pharmaceutical composition according to claim 3, wherein said additional agent is a CFTR modulator other than a compound according to claim 1. 5. A method of treating or lessening the severity of a disease in a patient, wherein said disease is selected from cystic fibrosis, pancreatitis, pancreatic insufficiency, hereditary emphysema, COPD, and dry-eye disease, said method comprising the step of administering to said patient an effective amount of a compound according to claim 1. 6. The method according to claim 5, wherein said disease is cystic fibrosis. 7. A kit for use in measuring the activity of CFTR or a fragment thereof in a biological sample in vitro or in vivo, comprising: (i) a composition comprising a compound according to claim 1; (ii) instructions for: a) contacting the composition with the biological sample; b) measuring activity of said CFTR or a fragment thereof. 8. The kit of claim 7 further comprising instructions for: a) contacting an additional composition with the biological sample; b) measuring the activity of said CFTR or a fragment thereof in the presence of said additional compound, and c) comparing the activity of the CFTR in the presence of the additional compound with the density of CFTR in the presence of a composition comprising a compound according to claim 1. 9. A method of modulating CFTR activity in a biological sample comprising the step of contacting said CFTR with a compound according claim 1.