Improved synthesis and evaluation of preclinical pharmacodynamic parameters of a new monocyclic β-lactam DPI-2016

Bioorg Med Chem Lett. 2024 Feb 1;99:129615. doi: 10.1016/j.bmcl.2024.129615. Epub 2024 Jan 8.ABSTRACTMonocyclic β-lactams are stable to a number of β-lactamases and are the focus of researchers for the development of antibacterial drugs, particularly against Enterobacterales. We recently synthesized and reported the bactericidal activity of diverse series of aztreonam appended with amidine moieties as siderophores. One of the derivatives exhibiting the highest MIC value in vitro was selected for further preclinical studies. The compound DPI-2016 was reassessed for its synthetic routes and methods that were improved to find the maximum final yields aimed at large-scale synthesis. In addition, the results of the pharmacological studies were determined with reference to aztreonam. It has been found that the compound DPI-2016 showed comparable or slightly improved ADMET as well as pharmacokinetic parameters to aztreonam. It is estimated that the compound could be a potential lead for further clinical evaluation.PMID:38199331 | DOI:10.1016/j.bmcl.2024.129615

Source: Bioorganic and Medicinal Chemistry Letters - January 10, 2024 Category: Chemistry Authors: Lijuan Zhai Jian Sun Jingwen Ji Lili He Pengjuan Zhou Dong Tang Jinbo Ji Haikang Yang Zafar Iqbal Zhixiang Yang Source Type: research