Synthesis of alpha-fluoro- and alpha,alpha-difluoro-benzenemethanesulfonamides: new inhibitors of carbonic anhydrase.
Direct fluorination of arenemethanesulfonamide anions under mild conditions and in high yield has been accomplished using N-fluorobisbenzenesulfonimide, NFSi, on carbanions of N-tert-butyl- and N-bis-(4-methoxyphenyl-methyl)-benzenemethanesulfonamides giving novel alpha-fluoro- and alpha,alpha-difluoro-benzenemethanesulfonamides respectively: IC(50) and pK(a) data show that alpha-halogenation enhances sulfonamide acidity incrementally and correlates well with increased carbonic anhydrase inhibition, while lipophilicity is also enhanced.
Blackburn
G Michael
GM
University of Sheffield, Department of Chemistry, Sheffield, S3 7HF, England. g.m.blackburn@shef.ac.uk
Türkmen
Hasan
H
D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000187:drug effects; D005464:Fluorobenzenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D015394:Molecular Structure; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D002257:Carbonic Anhydrase Inhibitors; D005464:Fluorobenzenes; D006845:Hydrocarbons, Fluorinated; D007527:Isoenzymes; D013449:Sulfonamides; C511756:benzenefluoromethanesulfonamide; D002256:Carbonic Anhydrases