Heterocyclyl tetracyclines. 2. 7-Methoxy-8-pyrrolidinyltetracyclines: discovery of TP-2758, a potent, orally efficacious antimicrobial against Gram-negative pathogens

4区 · 医学

Article

作者: Hunt, Diana K ; Deng, Yonghong ; Sun, Cuixiang ; Sutcliffe, Joyce A ; Xiao, Xiao-Yi ; Grossman, Trudy H ; Chen, Chi-Li ; Fyfe, Corey ; Clark, Roger B

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.

2016-02-19·Organic Process Research & Development

Process Development and Scale-up of Fully Synthetic Tetracycline TP-2758: A Potent Antibacterial Agent with Excellent Oral Bioavailability

作者: He, Minsheng ; Niu, John ; Chen, Chi-Li ; Zhu, Zhijian ; Dunwoody, Nicholas ; Zhang, Wu-Yan ; Katz, Christopher E. ; Ronn, Magnus ; Hogan, Philip C. ; Sun, Cuixiang ; Xiao, Xiao-Yi ; Hunt, Diana ; Deng, Yonghong

Process research and development of the fully synthetic broad spectrum tetracycline TP-2758 (I), with a chiral pyrrolidine side chain at the C-8 position, is described.The process utilizes two key intermediates, enone II and pyrrolylbenzoate III, in a convergent approach that allows for manufacturing of sufficient quantities of API to supply preclin. and early clin. development.The pyrrolidine moiety was introduced into the left-hand piece (LHP) III with high enantioselectivity using Ellman's sulfinamide chem., and the absolute configuration was confirmed by X-ray crystal structure anal.

2009-11-01·IDrugs : the investigational drugs journal

Interscience Conference on Antimicrobial Agents and Chemotherapy--49th annual meeting. Part 2. 12-15 September 2009, San Francisco, CA, USA.

Article

作者: Turner, Ben ; Murch, Lisa

The Interscience Conference on Antimicrobial Agents and Chemotherapy held in San Francisco included topics covering new therapeutic developments for the treatment of infectious diseases. This conference report highlights selected presentations on several antibiotics in development including a broad-spectrum penem beta-lactam antibiotic, a novel siderophore monobactam, as well as other novel antibiotics. Investigational drugs discussed include sulopenem and sulopenem etzadroxil (both Pfizer Inc), BAL-30072 (Basilea Pharmaceutica International Ltd), TP-120 and TP-787 (both Tetraphase Pharmaceuticals Inc), NAI-107 (New Anti Infectives Consortium/NexThera Biosciences) and ABI-200 (AdRem Biotech/US Department of Agriculture).

100 项与 TP-2758 相关的药物交易

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