Sulfamoyl-4-oxoquinoline-3-carboxamides: novel potentiators of defective DeltaF508-cystic fibrosis transmembrane conductance regulator chloride channel gating

Yat Fan Suen; Lori Robins; Baoxue Yang; A S Verkman; Michael H Nantz; Mark J Kurth

doi:10.1016/j.bmcl.2005.10.050

Sulfamoyl-4-oxoquinoline-3-carboxamides: novel potentiators of defective DeltaF508-cystic fibrosis transmembrane conductance regulator chloride channel gating

Bioorg Med Chem Lett. 2006 Feb;16(3):537-40. doi: 10.1016/j.bmcl.2005.10.050. Epub 2005 Nov 8.

Authors

Yat Fan Suen¹, Lori Robins, Baoxue Yang, A S Verkman, Michael H Nantz, Mark J Kurth

Affiliation

¹ Department of Chemistry, University of California, Davis, CA 95616, USA.

PMID: 16288863
DOI: 10.1016/j.bmcl.2005.10.050

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Chloride Channels / metabolism*
Cystic Fibrosis Transmembrane Conductance Regulator / drug effects
Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
Dose-Response Relationship, Drug
Humans
Ion Channel Gating / drug effects*
Ion Channel Gating / physiology
Models, Chemical
Quinolones / chemical synthesis
Quinolones / pharmacology
Sulfonamides / chemical synthesis
Sulfonamides / pharmacology

Substances

Chloride Channels
Quinolones
Sulfonamides
cystic fibrosis transmembrane conductance regulator delta F508
Cystic Fibrosis Transmembrane Conductance Regulator

Grants and funding

DK 072517/DK/NIDDK NIH HHS/United States