Sulfonylmethanesulfonamide inhibitors of carbonic anhydrase

A series of sulfonylmethanesulfonamide derivatives is described, which are inhibitors of carbonic anhydrase (CA). The most potent of these is the racemic fluoro sulfone 9, which inhibits carbon dioxide hydration catalyzed by human CA II (CA-II) with an IC50 of 3 nM. Binding competition studies versu...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 1993-07, Vol.36 (15), p.2134-2141
Main Authors: Scholz, Thomas H, Sondey, John M, Randall, William C, Schwam, Harvey, Thompson, Wayne J, Mallorga, Pierre J, Sugrue, Michael F, Graham, Samuel L
Format: Article
Language:English
Subjects:
Aliphatic compounds
Animals
Binding, Competitive
Carbonic Anhydrase Inhibitors - chemical synthesis
Carbonic Anhydrase Inhibitors - chemistry
Carbonic Anhydrase Inhibitors - metabolism
Chemistry
Exact sciences and technology
Humans
Organic chemistry
Preparations and properties
Rabbits
Structure-Activity Relationship
Sulfonamides - chemical synthesis
Sulfonamides - chemistry
Sulfonamides - metabolism
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A series of sulfonylmethanesulfonamide derivatives is described, which are inhibitors of carbonic anhydrase (CA). The most potent of these is the racemic fluoro sulfone 9, which inhibits carbon dioxide hydration catalyzed by human CA II (CA-II) with an IC50 of 3 nM. Binding competition studies versus dansylamide indicate that the enantiomers of 9 have different affinities for CA-II, with equilibrium dissociation constants of 3.6 and 0.6 nM. QSAR analysis suggests that the key factors involved in achieving high affinity in this series are sulfonamide acidity, hydrophobicity, and minimization of steric demands at the carbon atom adjacent to the sulfonamide group.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00067a012