一系列6-尿素/酰胺香豆素（5a-p和7a-c）已被设计和合成，用于开发具有强效和可形成选择性的碳酸酐酶hCA XI和XII抑制剂。对所有香豆素衍生物进行了研究，以评估它们对hCA I、II、IX和XII的CA抑制作用。有趣的是，目标香豆素大大抑制了与肿瘤相关的两种同构体hCA IX（KIs：14.7-82.4 nM）和hCA XII（KIs：5.9-95.1 nM），而胞浆型的非靶向同构体hCA I和II同构体则未被所有测试的香豆素抑制，最高浓度为100 μM。这些发现表明目标香豆素具有卓越的选择性谱，可应用于hCA IX和hCA XII同构体的开发，作为有前途的抗癌候选药物。此外，评估了所有目标分子对HCT-116和MCF-7癌细胞的抗癌活性。3,5-双三氟甲基苯基尿素香豆素5i表现出最佳的抗癌活性。总的来说，尿素香豆素，特别是化合物5i，可以作为开发强效抗癌CAIs的有前途的原型。

A series of 6-ureido/amidocoumarins (5a-p and 7a-c) has been designed and synthesised to develop potent and isoform- selective carbonic anhydrase hCA XI and XII inhibitors. All coumarin derivatives were investigated for their CA inhibitory effect against hCA I, II, IX, and XII. Interestingly, target coumarins potently inhibited both tumour-related isoforms hCA IX (KIs: 14.7-82.4 nM) and hCA XII (KIs: 5.9-95.1 nM), whereas the cytosolic off-target hCA I and II isoforms have not inhibited by all tested coumarins up to 100 μM. These findings granted the target coumarins an excellent selectivity profile towards both hCA IX and hCA XII isoforms, supporting their development as promising anticancer candidates. Moreover, all target molecules were evaluated for their anticancer activities against HCT-116 and MCF-7 cancer cells. The 3,5-bis-trifluoromethylphenyl ureidocoumarin 5i, exerted the best anticancer activity. Overall, ureidocoumarins, particularly compound 5i, could serve as a promising prototype for the development of potent anticancer CAIs.