Two series, coumarin-linked to thiazolidinone via a pyrazole linker (6a-m, Series 1) and coumarin-linked 1,2,3-triazoles (5a-j, Series 2) were synthesized and the synthesized compounds were subjected for evaluation against the four physiologically and pharmacologically relevant hCA isoforms, hCA I, II, IX and XII. The results indicated selective inhibition of tumor-associated isoforms hCA IX and XII over the off-target isoforms, hCA I and II. The compounds of series 1 exhibited better hCA IX inhibition compared to hCA XII, with compounds 6i, 6h, 6a and 6k, exhibiting notable K_i values of less than 100 nM. Among all the compounds, compound 6i showed the best inhibition with a K_i value of 61.5 nM. Among the compounds of series 2, compounds 5a, 5b, 5c, 5d, 5f and 5j exhibited notable hCA IX inhibition. Compound 5d showed the best inhibition with a K_i value of 32.7 nM. In the case of hCA XII, compound 5i showed the best inhibition with a K_i value of 84.2 nM. Hence, compound 6i from Series 1 and 5d from Series 2 could be taken as lead compounds for the further development of selective and potent hCA IX inhibitors, whereas the compound 5i from Series 2 can be explored further for the design of selective and potent hCA XII inhibitors.

合成了两个系列，通过吡唑接头与香豆素相连的噻唑烷酮（系列1a-m）和与香豆素相连的1,2,3-三唑（系列5a-j，系列2），对合成的化合物进行了抗四种生理和药理相关的hCA亚型，即hCA I，II，IX和XII。结果表明，与脱靶同工型hCA I和II相比，肿瘤相关同工型hCA IX和XII具有选择性抑制作用。与hCA XII相比，系列1的化合物表现出更好的hCA IX抑制，其中化合物6i，6h，6a和6k的K _i值小于100 nM。在所有化合物中，化合物6i表现出最佳的抑制作用，K _i值为61.5 nM。在系列2的化合物中，化合物5a，5b，5c，5d，5f和5j显示出显着的hCA IX抑制。化合物5d表现出最佳的抑制作用，K _i值为32.7 nM。在hCA XII的情况下，化合物5i表现出最佳抑制作用，K _i值为84.2 nM。因此，可以将系列1的化合物6i和系列2的5d用作进一步开发选择性和有效hCA IX抑制剂的先导化合物，而该化合物可以进一步探索系列2的5i，以设计选择性和有效的hCA XII抑制剂。