211501-37-0Relevant academic research and scientific papers
Optimization of globomycin analogs as novel gram-negative antibiotics
Braun, Marie-Gabrielle,Burdick, Daniel J.,Castanedo, Georgette M.,Chen, Yi-Chen,Cheng, Yun-Xing,Cheong, Jonathan,Daniels, Blake,Deshmukh, Gauri,Fu, Yuhong,Garland, Keira,Gibbons, Paul,Gloor, Susan L.,Hanan, Emily J.,Hua, Rongbao,Kapadia, Sharookh B.,Labadie, Sharada,Liu, Xiongcai,Pantua, Homer,Pastor, Richard,Stivala, Craig,Xu, Min,Xu, Yiming,Zheng, Hao
, (2020)
Discovery of novel classes of Gram-negative antibiotics with activity against multi-drug resistant infections is a critical unmet need. As an essential member of the lipoprotein biosynthetic pathway, lipoprotein signal peptidase II (LspA) is an attractive target for antibacterial drug discovery, with the natural product inhibitor globomycin offering a modestly-active starting point. Informed by structure-based design, the globomycin depsipeptide was optimized to improve activity against E. coli. Backbone modifications, together with adjustment of physicochemical properties, afforded potent compounds with good in vivo pharmacokinetic profiles. Optimized compounds such as 51 (E. coli MIC 3.1 μM) and 61 (E. coli MIC 0.78 μM) demonstrate broad spectrum activity against gram-negative pathogens and may provide opportunities for future antibiotic discovery.
CYCLIC PEPTIDE ANTIBIOTICS
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Paragraph 00416, (2019/04/11)
Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of lipoprotein signal peptidase II (LspA), a key protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.
Development of a supply route for the synthesis of an iNOS inhibitor: Complications of the key SN2 reaction
Rassias, Geracimos,Hermitage, Stephen A.,Sanganee, Mahesh J.,Kincey, Peter M.,Smith, Neil M.,Andrews, Ian P.,Borrett, Gary T.,Slater, Graham R.
body text, p. 774 - 780 (2010/04/22)
The original medicinal chemistry synthesis of an iNOS inhibitor presented several challenges that had to be overcome in order to constitute a supply route suitable for operation on a multikilo scale. The key step in the synthesis is an SN2 reac
