Abstract

A series of 17 compounds (12–16 b) with 2,4,5-trisubstitutedthiazole scaffold having 5-aryl group, 4-carboxylic acid/ester moiety, and 2-amino/amido/ureido functional groups were synthesised, characterised, and evaluated for their carbonic anhydrase (CA)-III inhibitory activities using the size exclusion Hummel–Dreyer method (HDM) of chromatography. Compound 12a with a free amino group at the 2-position, carboxylic acid moiety at the 4-position, and a phenyl ring at the 5-position of the scaffold was found to be the most potent CA-III inhibitor (K_i = 0.5 μM). The presence of a carboxylic acid group at the 4-position of the scaffold was found to be crucial for the CA-III inhibitory activity. Furthermore, replacement of the free amino group with an amide and urea group resulted in a significant reduction of activity (compounds 13c and 14c, K_i = 174.1 and 186.2 μM, respectively). Thus, compound 12a (2-amino-5-phenylthiazole-4-carboxylic acid) can be considered as the lead molecule for further modification and development of more potent CA-III inhibitors.

 抽象的

合成、表征和表征了一系列 17 种具有 2,4,5-三取代噻唑支架（具有 5-芳基、4-羧酸/酯部分和 2-氨基/酰氨基/脲基官能团）的化合物 ( 12-16 b )使用尺寸排阻 Hummel-Dreyer 色谱法 (HDM) 评估其碳酸酐酶 (CA)-III 抑制活性。发现支架的 2 位有游离氨基、4 位有羧酸部分、5 位有苯环的化合物12a是最有效的 CA-III 抑制剂 ( K _i = 0.5微米）。发现支架 4 位上羧酸基团的存在对于 CA-III 抑制活性至关重要。此外，用酰胺和脲基团取代游离氨基导致活性显着降低（化合物13c和14c ， K _i分别 = 174.1 和 186.2 μM）。因此，化合物12a （2-氨基-5-苯基噻唑-4-羧酸）可被视为进一步修饰和开发更有效的CA-III抑制剂的先导分子。