5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity: Solution and crystallographic investigations

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• 作者：Jekaterīna Ivanova^a ; ^b ; Agnese Balode^a ; ^b ; Raivis Žalubovskis^a ; ^{raivis@osi.lv} ; Janis Leitans^c ; Andris Kazaks^c ; Daniela Vullo^d ; Kaspars Tars^c ; ^e ; Claudiu T. Supuran^f ; ^{claudiu.supuran@unifi.it}
• 关键词：Carbonic anhydrase ; Thiophene-2-sulfonamide ; Mercaptan ; Inhibitor
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：25
• 期：3
• 页码：857-863
• 全文大小：1542 K
• 卷排序：25

文摘

A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromo-thiophene-2-sulfonamide with 5-substituted-benzyl mercaptans. The new compounds were investigated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The cytosolic human (h) isoforms hCA I was poorly inhibited by the new sulfonamides (KIs in the range of 683–4250 nM), whereas hCA II, and the transmembrane, tumor associated isoforms hCA IX and XII were effectively inhibited in the subnanomolar–nanomolar range. A high resolution X-ray crystal structure of the adduct of hCA II with one of the new sulfonamides allowed us to rationalize the excellent inhibitory activity of these heterocyclic sulfonamides.