Identification of potent type I MetAPs inhibitors by simple bioisosteric replacement. Part 2: SAR studies of 5-heteroalkyl substituted TCAT derivatives

Systematic SAR studies on the thiazole ring 5-substituent of TCAT derivatives revealed that the introduction of a β-alkoxy or an amino group enhanced the inhibitory activity significantly. The present compounds are representative of specific Co(II)-MetAP1 inhibitors. Before the physiologically relevant metal ions for MetAPs are established, these small molecular compounds could be used as tools for detailed biological studies.

Graphical abstractSystematic SAR studies on the thiazole ring 5-substituent of TCAT inhibitors of EcMetAP1 and ScMetAP1 revealed that the introduction of a β-alkoxy or an amino group enhanced the inhibitory activity significantly.Figure optionsDownload full-size imageDownload as PowerPoint slide