10445-91-7Relevant articles and documents
Efficient synthesis of a new series of piperidine ring-modified analogs of (±)-threo-methyl phenyl(piperidin-2-yl)acetate
Ojo, Babatunde
, p. 1731 - 1745 (2012)
A series of novel piperidine ring modified analogs of (±)-threo- methyl phenyl (piperidin-2-yl)acetate was synthesized by direct alkylation and reductive amination procedure, using sodium borohydride over molecular sieves. The chemical structures of these compounds were established based on mass spectra, 1H NMR spectra, and CHN elemental analysis data. Several significant modifications in the literature methodologies were made to make the reaction more efficient, and good yields were generally obtained. Copyright Taylor & Francis Group, LLC.
Structure-guided optimization of 1H-imidazole-2-carboxylic acid derivatives affording potent VIM-Type metallo-β-lactamase inhibitors
Yan, Yu-Hang,Li, Wenfang,Chen, Wei,Li, Chao,Zhu, Kai-Rong,Deng, Ji,Dai, Qing-Qing,Yang, Ling-Ling,Wang, Zhenling,Li, Guo-Bo
, (2021/11/17)
Production of metallo-β-lactamases (MBLs) in bacterial pathogens is an important cause of resistance to the ‘last-resort’ carbapenem antibiotics. Development of effective MBL inhibitors to reverse carbapenem resistance in Gram-negative bacteria is still needed. We herein report X-ray structure-guided optimization of 1H-imidazole-2-carboxylic acid (ICA) derivatives by considering how to engage with the active-site flexible loops and improve penetration into Gram-negative bacteria. Structure-activity relationship studies revealed the importance of appropriate substituents at ICA 1-position to achieve potent inhibition to class B1 MBLs, particularly the Verona Integron-encoded MBLs (VIMs), mainly by involving ingenious interactions with the flexible active site loops as observed by crystallographic analyses. Of the tested ICA inhibitors, 55 displayed potent synergistic antibacterial activity with meropenem against engineered Escherichia coli strains and even intractable clinically isolated Pseudomonas aeruginosa producing VIM-2 MBL. The morphologic and internal structural changes of bacterial cells after treatment further demonstrated that 55 crossed the outer membrane and reversed the activity of meropenem. Moreover, 55 showed good pharmacokinetic and safety profile in vivo, which could be a potential candidate for combating VIM-mediated Gram-negative carbapenem resistance.
1 - Substituted - 111H-imidazol -2 - carboxylic acid compound (by machine translation)
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Paragraph 0228-0230, (2020/07/02)
The invention relates to 1 - substituted - 111H-imidazol -2 - carboxylic acid compounds. Experiments prove that the compound provided by the invention can effectively inhibit the activity of various MBL enzymes including VIM-2, NDM-1, ?currcurrcurrcurry ?, VIM-IMP-1 1 and VIM IM IM, especially compounds 11 and 13, 14, 29, 30, 34, 37, 40, and IC of VIM-2 type MBL enzyme. 50 The value is below 2.13 μm, the inhibition effect is more remarkable than that of the positive control medicine, and the MBL enzyme inhibitor has great potential in preparing the MBL enzyme inhibitor. , The compound is combined with β - lactam antibiotics, metal β - lactamase produced by drug-resistant bacteria can be effectively inhibited, the antibacterial activity of the antibiotic is enhanced, and the compound has a very good application prospect in preparation of antibacterial and combined medicines. (by machine translation)