4.5 Article

Privileged scaffolds in medicinal chemistry: Studies on pyrazolo[1,5-a]pyrimidines on sulfonamide containing Carbonic Anhydrase inhibitors

期刊

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2021.128309

关键词

Pyrazolopyrimidines; Carbonic Anhydrase inhibitors; Privilege scaffolds; X-ray crystallography

资金

  1. TUBITAK (The Scientific and Technological Research Council of Turkey)
  2. Fon-dazione Cassa di Risparmio di Firenze [ECR2018.1001]

向作者/读者索取更多资源

In this study, a small series of compounds with inhibitory properties for human Carbonic Anhydrase enzymes were reported for the first time. Some of these compounds showed good selectivity for specific CAs, and one compound exhibited nearly matching K-I values for both hCA II and IX. X-ray crystal experiments were used to explore the binding mode of this compound within the CA IX mimic isoform.
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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据