221670-34-4Relevant academic research and scientific papers
Halogenated and di-substituted benzenesulfonamides as selective inhibitors of carbonic anhydrase isoforms
Zak?auskas, Audrius,?apkauskait?, Edita,Jezep?ikas, Linas,Linkuvien?, Vaida,Paketuryt?, Vaida,Smirnov, Alexey,Leitans, Janis,Kazaks, Andris,Dvinskis, Elviss,Manakova, Elena,Gra?ulis, Saulius,Tars, Kaspars,Matulis, Daumantas
, (2020)
By applying an approach of a “ring with two tails”, a series of novel inhibitors possessing high-affinity and significant selectivity towards selected carbonic anhydrase (CA) isoforms has been designed. The “ring” consists of 2-chloro/bromo-benzenesulfonamide, where the sulfonamide group is as an anchor coordinating the Zn(II) in the active site of CAs, and halogen atom orients the ring affecting the affinity and selectivity. First “tail” is a substituent containing carbonyl, carboxyl, hydroxyl, ether groups or hydrophilic amide linkage. The second “tail” contains aryl- or alkyl-substituents attached through a sulfanyl or sulfonyl group. Both “tails” are connected to the benzene ring and play a crucial role in selectivity. Varying the substituents, we designed compounds selective for CA VII, CA IX, CA XII, or CA XIV. Since due to binding-linked protonation reactions the binding-ready fractions of the compound and protein are much lower than one, the “intrinsic” affinities were calculated that should be used to study correlations between crystal structures and the thermodynamics of binding for rational drug design. The “intrinsic” affinities together with the intrinsic enthalpies and entropies of binding together with co-crystal structures were used demonstrate structural factors determining major contributions for compound affinity and selectivity.
Design of two-tail compounds with rotationally fixed benzenesulfonamide ring as inhibitors of carbonic anhydrases
Zak?auskas, Audrius,?apkauskait?, Edita,Jezep?ikas, Linas,Linkuvien?, Vaida,Ki?onait?, Migl?,Smirnov, Alexey,Manakova, Elena,Gra?ulis, Saulius,Matulis, Daumantas
, p. 61 - 78 (2018/07/06)
Rational design of compounds that would bind specific pockets of the target proteins is a difficult task in drug design. The 12 isoforms of catalytically active human carbonic anhydrases (CAs) have highly similar active sites that make it difficult to des
SELECTIVE INHIBITORS OF CARBONIC ANHYDRASE
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Page/Page column 24-25, (2017/02/24)
Invention is related to novel compounds – benzenesulfonamides of general formulas (I) and (II). The compounds can be used in biomedicine as active ingredients in pharmaceutical formulations, because they inhibit enzymes which participate in disease progre
