Discovery Chemistry, Tetraphase Pharmaceuticals, Inc., Watertown, MA, USA.
Department of Microbiology, Tetraphase Pharmaceuticals. Inc., Watertown, MA, USA.
J Antibiot (Tokyo). 2018 Feb;71(2):287-297. doi: 10.1038/ja.2017.86. Epub 2017 Jul 26.
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 β-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.
一个收敛的全合成平台导致了 TP-2758 的发现，它是一系列新型 7-甲氧基-8-杂环四环素类似物中的一种。TP-2758 对关键的革兰氏阴性病原体具有很高的体外活性，包括产生超广谱β-内酰胺酶和碳青霉烯酶的肠杆菌科和不动杆菌属菌株。该化合物在多种小鼠感染模型中无论是静脉注射还是口服给药都具有疗效，并显示出有利的临床前药理学特征，支持其进入临床开发。
