The Carbonic Anhydrase (CA, EC 4.2.1.1) activating properties of histamine have been known for a long time. This compound has been extensively modified but only in few instances the imidazole ring has been replaced with other heterocycles. It was envisaged that the imidazoline ring could be a bioisoster of the imidazole moiety. Indeed, we report that clonidine, a 2-aminoimidazoline derivative, was found able to activate several human CA isoforms (hCA I, IV, VA, VII, IX, XII and XIII), with potency in the micromolar range, while it was inactive on hCA II. A series of 2-aminoimidazoline, structurally related to clonidine, was then synthesised and tested on selected hCA isoforms. The compounds were inactive on hCA II while displayed activating properties on hCA I, VA, VII and XIII, with KA values in the micromolar range. Two compounds (10 and 11) showed some preference for the hCA VA or VII isoforms.

中文翻译：

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一系列与可乐定1结构相关的2-氨基-咪唑啉的合成及其碳酸酐酶活化特性。

组胺的碳酸酐酶（CA，EC 4.2.1.1）活化特性早已为人所知。该化合物已被广泛修饰，但仅在少数情况下，咪唑环已被其他杂环取代。设想咪唑啉环可以是咪唑部分的生物等排体。确实，我们报道了可乐定是一种2-氨基咪唑啉衍生物，被发现能够激活几种人类CA亚型（hCA I，IV，VA，VII，IX，XII和XIII），其效力在微摩尔范围内，而无活性在hCA II上。然后合成了一系列与可乐定有关的2-氨基咪唑啉，并在选定的hCA亚型上进行了测试。这些化合物对hCA II无活性，同时在hCA I，VA，VII和XIII上显示出活化特性，KA值在微摩尔范围内。