Latvian Institute of Organic Synthesis, Riga, Latvia.
Institute of Technology of Organic Chemistry, Faculty of Materials Science and Applied Chemistry, Riga Technical University, Riga, Latvia.
J Enzyme Inhib Med Chem. 2020 Dec;35(1):650-656. doi: 10.1080/14756366.2020.1722658.
A series of 3H-1,2-benzoxathiepine 2,2-dioxides incorporating 7-acylamino moieties were obtained by an original procedure starting from 5-nitrosalicylaldehyde, which was treated with propenylsulfonyl chloride followed by Wittig reaction of the bis-olefin intermediate. The new derivatives, belonging to the homosulfocoumarin chemotype, were assayed as inhibitors of the zinc metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Four pharmacologically relevant human (h) isoforms were investigated, the cytosolic hCA I and II and the transmembrane, tumour-associated hCA IX and XII. No relevant inhibition of hCA I and II was observed, whereas some of the new derivatives were effective, low nanomolar hCA IX/XII inhibitors, making them of interest for investigations in situations in which the activity of these isoforms is overexpressed, such as hypoxic tumours, arthritis or cerebral ischaemia.
一系列含有 7-酰氨基部分的 3H-1,2-苯并噁硫嗪 2,2-二氧化物是通过一种原创的方法从 5-亚硝基水杨醛开始获得的，该醛与丙烯基磺酰氯反应，然后对双烯烃中间体进行威蒂希反应。这些新的衍生物属于同型磺酰脲类，被用作锌金属酶碳酸酐酶（CA，EC 4.2.1.1）的抑制剂进行了检测。研究了四种与药理学相关的人（h）同工酶，即胞质 hCA I 和 II 以及跨膜、肿瘤相关的 hCA IX 和 XII。未观察到对 hCA I 和 II 的相关抑制，但其中一些新衍生物是有效的低纳摩尔 hCA IX/XII 抑制剂，这使它们成为在这些同工酶活性过表达的情况下进行研究的有趣候选物，例如缺氧肿瘤、关节炎或脑缺血。
