Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SK-832 32 Bratislava, Slovakia.
Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SK-832 32 Bratislava, Slovakia.
Molecules. 2017 Sep 13;22(9):1533. doi: 10.3390/molecules22091533.
Sulfonamides incorporating 1,3,5-triazine moieties can selectively and potently inhibit carbonic anhydrase transmembrane isoforms IX, XII, and XIV over cytosolic isoforms I and II. In the present work, a highly effective synthetic procedure was proposed for this group of potent cancerostatic drugs and compared with previously used methods. The synthesis of triazinyl-substituted benzene-sulfonamide conjugates with amino acids can be easily carried out using sodium carbonate-based water solution as a synthetic medium instead of -Diisopropylethylamine/Dimethylformamide. The benefits of this synthetic procedure include: (i) high selectivity of the creation of disubstituted conjugates; (ii) several times higher yield (≥95%) than that achieved previously; (iii) elimination of organic solvents by the use of an environmental friendly water medium (green chemistry); (iv) simple and fast isolation of the product. The synthesis and resulting products were evaluated using TLC, IR, NMR, and MS methods. The present work demonstrates a significant advantage in providing shortened routes to target structures.
含 1,3,5-三嗪部分的磺胺类药物可以选择性和有效地抑制碳酸酐酶跨膜同工酶 IX、XII 和 XIV，而对胞质同工酶 I 和 II 则没有作用。在本工作中，提出了一种针对这组强效抗癌药物的高效合成方法，并与以前使用的方法进行了比较。使用基于碳酸钠的水溶液作为合成介质而不是二异丙基乙胺/二甲基甲酰胺，可以很容易地进行三嗪取代的苯磺酰胺与氨基酸的偶联合成。这种合成方法的优点包括：（i） 二取代偶联物的高选择性；（ii） 收率比以前提高了几倍（≥95%）；（iii） 通过使用环保的水介质（绿色化学）消除有机溶剂；（iv） 产物的简单快速分离。采用 TLC、IR、NMR 和 MS 方法对合成和所得产物进行了评价。本工作表明，在提供目标结构的短路线方面具有显著优势。
