Methodology for Monobactam Diversification: Syntheses and Studies of 4-Thiomethyl Substituted β-Lactams with Activity against Gram-Negative Bacteria, Including Carbapenemase Producing Acinetobacter baumannii,Journal of Medicinal Chemistry

当前位置： X-MOL 学术 › J. Med. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Methodology for Monobactam Diversification: Syntheses and Studies of 4-Thiomethyl Substituted β-Lactams with Activity against Gram-Negative Bacteria, Including Carbapenemase Producing Acinetobacter baumannii
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2017-10-20 00:00:00 , DOI: 10.1021/acs.jmedchem.7b01164
Serena Carosso ₁ , Rui Liu ₁ , Patricia A. Miller ₁ , Scott J. Hecker ₂ , Tomasz Glinka ₂ , Marvin J. Miller ₁

Affiliation

Bromine induced lactamization of vinyl acetohydroxamates facilitated syntheses of monocyclic β-lactams suitable for incorporation of a thiomethyl and extended functionality at the C(4) position. Elaboration of the resulting substituted N-hydroxy-2-azetidinones allowed incorporation of functionalized α-amino substituents appropriate for enhancement of antibiotic activity. Evaluation of antibacterial activity against a panel of Gram-positive and Gram-negative bacteria revealed structure–activity relationships (SAR) and identification of potent new monobactam antibiotics. The corresponding bis-catechol conjugate, 42, has excellent activity against Gram-negative bacteria including carbapenemase and carbacephalosporinase producing strains of Acinetobacter baumannii, which have been listed by the WHO as being of critical concern worldwide.

中文翻译：

Monobactam多元化的方法论：具有抗革兰氏阴性细菌（包括碳青霉烯酶产生鲍曼不动杆菌）活性的4-硫甲基取代的β-内酰胺的合成和研究

溴诱导的乙酰氧肟酸乙烯基酯的内酰胺化促进了适合于在C（4）位置掺入硫代甲基和扩展功能的单环β-内酰胺的合成。对所得的取代的N-羟基-2-氮杂环丁酮进行精细加工，可以引入适于增强抗生素活性的官能化α-氨基取代基。对一组革兰氏阳性和革兰氏阴性细菌的抗菌活性的评估揭示了结构-活性关系（SAR）和有效的新型单bactamtam抗生素的鉴定。相应的双邻苯二酚偶联物42对革兰氏阴性细菌（包括碳青霉烯酶和产生碳头孢菌素酶的鲍曼不动杆菌）具有优异的活性。，已被WHO列为全球关注的重点。

更新日期：2017-10-20

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11