Department of Chemistry, Faculty of Arts and Sciences, Sakarya University , Sakarya , Turkey.
J Enzyme Inhib Med Chem. 2014 Feb;29(1):18-22. doi: 10.3109/14756366.2012.746972. Epub 2013 Jan 16.
Abstract A new series of 1,4-dihydropyrimidinone (DHPM) substituted diaryl urea and thiourea derivatives were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase (hCA) I and II were evaluated. 4-Nitrophenyl-1,4-DHPM was prepared with dimedone, nitrobenzaldehyde and urea or thiourea and nitro group was reduced to amine derivative. The compound was reacted with isocyanates and isothiocyanates to get the final products. The results showed that all the synthesized compounds inhibited the carbonic anhydrase isoenzyme activity; 4c (IC50=66.23 µM for hCA I) and 4f (IC50=63.09 µM for hCA II) have the most inhibitory effect. The synthesized compounds are very bulky to be able to bind near the zinc ion and they much more probably bind as the coumarins and activators.
合成了一系列新型的 1,4-二氢嘧啶酮（DHPM）取代的二芳基脲和硫脲衍生物，并评估了它们对纯化的人碳酸酐酶（hCA）I 和 II 活性的抑制作用。4-硝基苯基-1,4-DHPM 是由二酮、硝基苯甲醛和脲或硫脲制备的，硝基还原为胺衍生物。然后将化合物与异氰酸酯和异硫氰酸酯反应得到最终产物。结果表明，所有合成的化合物均抑制碳酸酐酶同工酶的活性；化合物 4c（对 hCA I 的 IC50=66.23µM）和 4f（对 hCA II 的 IC50=63.09µM）的抑制作用最强。这些合成的化合物非常大，能够结合到锌离子附近，它们更可能作为香豆素和激活剂结合。
