Carbonic anhydrase inhibitors - Part 29: Interaction of isozymes I, II and IV with benzolamide-like derivatives

Reaction of 5-amino-1,3,4-thiadiazole-2-sulfonamide and 5-imino-4-methyl-2-sulfonamido-delta(2)-1,3,4-thiadiazoline with sulfonyl halides/sulfonic acid anhydrides afforded benzolamide-like derivatives possessing very strong inhibitory effects towards three isozymes of carbonic anhydrase (CA), CA I, II and IV. Some of the compounds were designed in such a way to possess good leaving groups (such as nitro-; 2,4,6-triphenyl-pyridinium, etc.) for aromatic nucleophilic substitution reactions with fluoride, in order to introduce positron-emitting isotopes in their molecule, such as F-18. Reactions done initially with the stable isotope of fluorine were not very effective, as the yields in the desired fluoro-derivatives were low, and a complex reaction mixture was obtained. By using this type of approach, and optimizing the synthetic procedure, CA inhibitors for positron emission tomography (PET) applications might be obtained (in the case of utilizing a carrier, which is the non-radioactive derivative itself, since the affinities of such derivatives for the receptor an in the nanomolar range). Further improving of such synthetic procedures might lead to better yields and the respective compounds should be used as selective ligands (also in carrier-free systems) in assessing the role of membrane bound CA isozymes or for new diagnostic tools based on PET. (C) Elsevier, Paris.