Structure–activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase

We report on a target-based approach to identify possible Mycobacteriumtuberculosis DXS inhibitors from the structure of a known transketolase inhibitor. A small focused library of analogs was assembled in order to begin elucidating some meaningful structure–activity relationships of 3-(4-chloro-phenyl)-5-benzyl-4H-pyrazolo[1,5-a]pyrimidin-7-one. Ultimately we found that 2-methyl-3- (4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one, although still weak, was able to inhibit M. tuberculosis DXS with an IC50 of 10.6 μM.

Graphical abstract2-Methyl-3-(4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one is identified to inhibit Mycobacteriumtuberculosis DXS with an IC50 of 10.6 μM.Figure optionsDownload full-size imageDownload as PowerPoint slide