A new synthesis of difluoromethanesulfonamides--a novel pharmacophore for carbonic anhydrase inhibition.
Preparation of the key intermediate carboxydifluoromethanesulfonamide provides direct synthetic access to a wide range of novel difluoromethanesulfonamides, including the acetazolamide analogue (2-ethanoylamino-1,3,4-thiadiazol-5-yl)-difluoromethanesulfonamide. Their water solubility and stability, ether partition coefficient, pK(a) and submicromolar dissociation constants for human carbonic anhydrase isozyme II (HCA II) make them promising candidates for topical glaucoma therapy.
Boyle
Nicholas A
NA
Krebs Institute, Chemistry Department, Sheffield University, Sheffield, UK S3 7HF.
Chegwidden
W Richard
WR
Blackburn
G Michael
GM
D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000737:chemistry*; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D012995:Solubility; D013237:Stereoisomerism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
D002257:Carbonic Anhydrase Inhibitors; D006845:Hydrocarbons, Fluorinated; D007527:Isoenzymes; D013449:Sulfonamides; D024402:Carbonic Anhydrase II