Sulfamoyl-4-oxoquinoline-3-carboxamides: novel potentiators of defective DeltaF508-cystic fibrosis transmembrane conductance regulator chloride channel gating.
The synthesis of a small collection of sulfamoyl-4-oxoquinoline-3-carboxamides is described for use as correctors of defective gating of the DeltaF508-cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Several compounds with submicromolar potency were obtained. N-Ethyl 6-(ethylphenylsulfamoyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (7b) was found to be the most effective sulfonamide corrector of defective DeltaF508-CFTR gating.
Suen
Yat Fan
YF
Department of Chemistry, University of California, Davis, CA 95616, USA.
Robins
Lori
L
Yang
Baoxue
B
Verkman
A S
AS
Nantz
Michael H
MH
Kurth
Mark J
MJ
D018118:Chloride Channels / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D008956:Models, Chemical; D015363:Quinolones / Q000138:chemical synthesis / Q000494:pharmacology; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology
D018118:Chloride Channels; D015363:Quinolones; D013449:Sulfonamides; C093349:cystic fibrosis transmembrane conductance regulator delta F508; D019005:Cystic Fibrosis Transmembrane Conductance Regulator