A new series of homosulfocoumarins (3H-1,2-benzoxathiepine 2,2-dioxides) possessing various substitution patterns and moieties in the 7, 8 or 9 position of the heterocylic ring were prepared by original procedures and investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I, II, IX and XII. The 8-substituted homosulfocoumarins were the most effective hCA IX/XII inhibitors followed by the 7-substituted derivatives, whereas the substitution pattern in position 9 led to less effective binders for the transmembrane, tumour-associated isoforms IX/XII. The cytosolic isoforms hCA I and II were not inhibited by these compounds, similar to the sulfocoumarins/coumarins investigated earlier. As hCA IX and XII are validated anti-tumour targets, with one sulphonamide (SLC-0111) in Phase Ib/II clinical trials, finding derivatives with better selectivity for inhibiting the tumour-associated isoforms over the cytosolic ones, as the homosulfocoumarins reported here, is of crucial importance.

中文翻译：

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3H-1,2-苯并x庚因2,2-二氧化物的芳基衍生物作为碳酸酐酶抑制剂。

通过原始程序制备了一系列新的高取代度香豆素香豆素（3H-1,2-苯并噻吩平2,2-二氧化物），在杂环的7、8或9位具有不同的取代模式和部分，并研究了其对四种生理抑制剂的抑制作用。相关的碳酸酐酶（CA，EC 4.2.1.1）亚型，人（h）hCA I，II，IX和XII。8-取代的高磺基香豆素是最有效的hCA IX / XII抑制剂，其次是7-取代的衍生物，而位置9的取代方式导致跨膜，肿瘤相关同工型IX / XII的结合剂效率较低。这些化合物不会抑制胞质亚型hCA I和II，类似于先前研究的磺基香豆素/香豆素。由于hCA IX和XII是经过验证的抗肿瘤靶标，