We report for the first time a small series of compounds endowed in vitro with inhibitory properties for the human (h) expressed Carbonic Anhydrase (CAs, E.C. 4.2.1.1) enzymes of physiological interest (i.e. I, II, VA, IX and XII) and bearing the pyrazolo[1,5-a]pyrimidine (PP) scaffold at the tail section. Among the series reported, 1a-3a, 7a, 8a, 1b and 2b resulted effective ligands and with good selectivities for the hCAs II, IX or XII. In consideration of the nearly matching K_I values of 7a for both the hCA II and IX (i.e. 26.4 and 23.0 nM respectively) we explored its binding mode within the CA IX mimic isoform by means of X-ray crystal experiments on the corresponding adduct.

我们首次报告了在体外对人类 (h) 表达的碳酸酐酶 (CAs, EC 4.2.1.1) 具有生理意义的酶（即 I、II、VA、IX 和 XII）具有抑制特性的一小部分化合物并在尾部带有吡唑并[1,5- a ]嘧啶（PP）支架。在报道的系列中，1a-3a、7a、8a、1b和2b是有效的配体，并且对 hCA II、IX 或 XII 具有良好的选择性。考虑到7a几乎匹配的 K _I值 对于 hCA II 和 IX（即分别为 26.4 和 23.0 nM），我们通过对相应加合物的 X 射线晶体实验探索了其在 CA IX 模拟异构体中的结合模式。