Atatürk University, Science Faculty, Department of Chemistry, Erzurum, Turkey.
Bioorg Med Chem. 2010 Jun 15;18(12):4468-74. doi: 10.1016/j.bmc.2010.04.072. Epub 2010 May 28.
Here we propose a novel one-pot synthesis of new tosyl-pyrrole derivatives. By means of the new developed method, pyrrole derivatives were synthesized at room temperature in a single step, and a useful method is proposed for the synthesis of similar compounds. Moreover, inhibitions of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II by 1-tosyl-pyrrole and 1-tosyl-pyrrol-2-on derivatives were investigated. 1-Tosyl-pyrrole, 1-tosyl-1H-pyrrol-2(5H)-one, 5-hydroxy-1-tosyl-1H-pyrrol-2(5H)-one and 5-oxo-1-tosyl-2,5-dihydro-1H-pyrrol-2-yl acetate showed inhibitory action with K(i) values in the range of 14.6-42.4 microM for hCA I and 0.53-37.5 microM for hCA II, respectively. All pyrrole derivatives were competitive inhibitors with 4-nitrophenylacetate as substrate. Some new synthesized pyrrole derivatives showed very effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide acetazolamide, and might be used as leads for generating enzyme inhibitors targeting other CA isoforms.
在这里，我们提出了一种新颖的一锅法合成新型对甲苯磺酰基吡咯衍生物的方法。通过新开发的方法，吡咯衍生物在室温下一步合成，为合成类似化合物提出了一种有用的方法。此外，还研究了 1-对甲苯磺酰基吡咯和 1-对甲苯磺酰基吡咯-2-酮衍生物对两种人胞质碳酸酐酶（hCA，EC 4.2.1.1）同工酶 I 和 II 的抑制作用。1-对甲苯磺酰基吡咯、1-对甲苯磺酰基-1H-吡咯-2(5H)-酮、5-羟基-1-对甲苯磺酰基-1H-吡咯-2(5H)-酮和 5-氧代-1-对甲苯磺酰基-2,5-二氢-1H-吡咯-2-基乙酸酯对 hCA I 的抑制作用具有 K(i)值范围为 14.6-42.4 μM，对 hCA II 的抑制作用具有 K(i)值范围为 0.53-37.5 μM。所有吡咯衍生物均为 4-硝基苯乙酸酯为底物的竞争性抑制剂。一些新合成的吡咯衍生物对 hCA II 具有非常有效的抑制作用，与临床使用的磺胺类药物乙酰唑胺相当，可能被用作针对其他 CA 同工酶的酶抑制剂的先导化合物。
