Abstract

A library of variously decorated N-phenyl secondary sulphonamides featuring the bicyclic tetrahydroquinazole scaffold was synthesised and biologically evaluated for their inhibitory activity against human carbonic anhydrase (hCA) I, II, IV, and IX. Of note, several compounds were identified showing submicromolar potency and excellent selectivity for the tumour-related hCA IX isoform. Structure–activity relationship data attained for various substitutions were rationalised by molecular modelling studies in terms of both inhibitory activity and selectivity.

中文翻译：

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基于四氢喹唑的仲磺酰胺作为碳酸酐酶抑制剂：合成、针对异构体 I、II、IV 和 IX 的生物学评价，以及计算研究

摘要

合成了以双环四氢喹唑支架为特征的各种装饰N-苯基仲磺酰胺库，并对其对人碳酸酐酶 (hCA) I、II、IV 和 IX 的抑制活性进行了生物学评估。值得注意的是，鉴定出的几种化合物对肿瘤相关的 hCA IX 异构体具有亚微摩尔级的效力和出色的选择性。各种取代获得的构效关系数据通过分子建模研究在抑制活性和选择性方面进行了合理化。