Moreau, Robert J.; Skepper, Colin K.; Appleton, Brent A.; Blechschmidt, Anke; Balibar, Carl J.; Benton, Bret M.; Drumm, Joseph E.; Feng, Brian Y.; Geng, Mei; Li, Cindy; Lindvall, Mika K.; Lingel, Andreas; Lu, Yipin; Mamo, Mulugeta; Mergo, Wosenu; Polyakov, Valery; Smith, Thomas M.; Takeoka, Kenneth; Uehara, Kyoko; Wang, Lisha; Wei, Jun-Rong; Weiss, Andrew H.; Xie, Lili; Xu, Wenjian; Zhang, Qiong; de Vicente, Javier published the artcile< Fragment-Based Drug Discovery of Inhibitors of Phosphopantetheine Adenylyltransferase from Gram-Negative Bacteria>, Computed Properties of 19346-45-3, the main research area is triazolopyrimidinone preparation phosphopantetheine adenylyltransferase inhibitory activity; azabenzimidazole preparation phosphopantetheine adenylyltransferase inhibitory activity.
The discovery and development of new antibiotics capable of curing infections due to multidrug-resistant and pandrug-resistant Gram-neg. bacteria is a major challenge with fundamental importance to our global healthcare system. Part of our broad program at Novartis to address this urgent, unmet need includes the search for new agents that inhibit novel bacterial targets. Here we report the discovery and hit-to-lead optimization of new inhibitors of phosphopantetheine adenylyltransferase (PPAT) from Gram-neg. bacteria. Utilizing a fragment-based screening approach, we discovered a number of unique scaffolds capable of interacting with the pantetheine site of E. coli PPAT and inhibiting enzymic activity, including triazolopyrimidinone. Structure-based optimization resulted in the identification of two lead compounds as selective, small mol. inhibitors of bacterial PPAT: triazolopyrimidinone I and azabenzimidazole II efficiently inhibited E. coli and P. aeruginosa PPAT and displayed modest cellular potency against the efflux-deficient E. coli ΔtolC mutant strain.
Journal of Medicinal Chemistry published new progress about Antibiotics. 19346-45-3 belongs to class pyridine-derivatives, and the molecular formula is C6H5FN2O2, Computed Properties of 19346-45-3.