New molecule? Old, discarded molecule and somebody wanted to publish?.....
J Antibiot (Tokyo). 2017 Jul 26. doi: 10.1038/ja.2017.86. [Epub ahead of print]
Heterocyclyl tetracyclines. 2. 7-Methoxy-8-pyrrolidinyltetracyclines: discovery of TP-2758, a potent, orally efficacious antimicrobial against Gram-negative pathogens.
Sun C1, Deng Y1, Hunt DK1, Fyfe C2, Chen CL1, Clark RB1, Grossman TH2, Sutcliffe JA2, Xiao XY1.
1
Discovery Chemistry, Tetraphase Pharmaceuticals, Inc., Watertown, MA, USA.
2
Department of Microbiology, Tetraphase Pharmaceuticals. Inc., Watertown, MA, USA.
A convergent total synthesis platform led to the discovery of TP-2758 from a series of novel 7-methoxy-8-heterocyclyl tetracycline analogs. TP-2758 demonstrated high in vitro potency against key Gram-negative pathogens including extended spectrum ß-lactamases- and carbapenemase-producing Enterobacteriaceae and Acinetobacter spp. strains. This compound was efficacious when administered either intravenously or orally in multiple murine infection models and displayed a favorable preclinical pharmacological profile supporting its advancement into clinical development. |
