The Experts below are selected from a list of 195 Experts worldwide ranked by ideXlab platform
Zhongbo Fei - One of the best experts on this subject based on the ideXlab platform.
-
new synthesis for the Monobactam antibiotic lys228
Journal of Organic Chemistry, 2020Co-Authors: Zhongbo Fei, Xianwen Wang, Wenlong Qiu, Jing Guo, Qun Jiang, Like Chen, Hao Wang, Feng Gao, Chi Ming CheungAbstract:A new synthesis of LYS228, fitting for further process development for commercial manufacture, is described. The key features of this synthesis include development of new protocols for acylation reactions, application of an asymmetric hydrogenation via dynamic kinetic resolution, and a late-stage ring closure to form β-lactam 1.
-
Process Development for the Synthesis of a Monobactam Antibiotic—LYS228
Organic Process Research & Development, 2020Co-Authors: Zhongbo Fei, Wanben Gong, Xianwen Wang, Yufeng HanAbstract:A scalable process for the novel Monobactam antibiotic LYS228 has been developed. This paper covers a novel scalable process for producing β-lactam 10 in the multiple kilogram scale. An alternative...
-
process development for the synthesis of a Monobactam antibiotic lys228
Organic Process Research & Development, 2020Co-Authors: Zhongbo Fei, Wanben Gong, Xianwen Wang, Yufeng Han, Yi Zhao, Wenya Zhu, Wenlong Qiu, Jing Guo, Jianguang Zhou, Marco VillaAbstract:A scalable process for the novel Monobactam antibiotic LYS228 has been developed. This paper covers a novel scalable process for producing β-lactam 10 in the multiple kilogram scale. An alternative...
Seungil Han - One of the best experts on this subject based on the ideXlab platform.
-
Pyridone-conjugated Monobactam antibiotics with gram-negative activity.
Journal of medicinal chemistry, 2013Co-Authors: Matthew Frank Brown, Mark J. Mitton-fry, Joel T. Arcari, Jeffrey M. Casavant, Brian S. Gerstenberger, Seungil Han, Rose Barham, Joel R. Hardink, Thomas M. Harris, Thuy HoangAbstract:Herein we describe the structure-aided design and synthesis of a series of pyridone-conjugated Monobactam analogues with in vitro antibacterial activity against clinically relevant Gram-negative species including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Rat pharmacokinetic studies with compound 17 demonstrate low clearance and low plasma protein binding. In addition, evidence is provided for a number of analogues suggesting that the siderophore receptors PiuA and PirA play a role in drug uptake in P. aeruginosa strain PAO1.
-
Pyridone-Conjugated Monobactam Antibiotics with Gram-Negative Activity
2013Co-Authors: Matthew F. Brown, Mark J. Mitton-fry, Joel T. Arcari, Seungil Han, Rose Barham, Joel R. Hardink, Jeffrey Casavant, Brian S. Gerstenberger, Thomas M. Harris, Thuy HoangAbstract:Herein we describe the structure-aided design and synthesis of a series of pyridone-conjugated Monobactam analogues with in vitro antibacterial activity against clinically relevant Gram-negative species including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Rat pharmacokinetic studies with compound 17 demonstrate low clearance and low plasma protein binding. In addition, evidence is provided for a number of analogues suggesting that the siderophore receptors PiuA and PirA play a role in drug uptake in P. aeruginosa strain PAO1
-
Novel Monobactams utilizing a siderophore uptake mechanism for the treatment of gram-negative infections
Bioorganic & medicinal chemistry letters, 2012Co-Authors: Mark J. Mitton-fry, Joel T. Arcari, Matthew Frank Brown, Jeffrey M. Casavant, Steven M. Finegan, Mark Edward Flanagan, Hongying Gao, David M. George, Brian S. Gerstenberger, Seungil HanAbstract:Novel siderophore-linked Monobactams with in vitro and in vivo anti-microbial activity against MDR Gram-negative pathogens are described.
Xianwen Wang - One of the best experts on this subject based on the ideXlab platform.
-
new synthesis for the Monobactam antibiotic lys228
Journal of Organic Chemistry, 2020Co-Authors: Zhongbo Fei, Xianwen Wang, Wenlong Qiu, Jing Guo, Qun Jiang, Like Chen, Hao Wang, Feng Gao, Chi Ming CheungAbstract:A new synthesis of LYS228, fitting for further process development for commercial manufacture, is described. The key features of this synthesis include development of new protocols for acylation reactions, application of an asymmetric hydrogenation via dynamic kinetic resolution, and a late-stage ring closure to form β-lactam 1.
-
Process Development for the Synthesis of a Monobactam Antibiotic—LYS228
Organic Process Research & Development, 2020Co-Authors: Zhongbo Fei, Wanben Gong, Xianwen Wang, Yufeng HanAbstract:A scalable process for the novel Monobactam antibiotic LYS228 has been developed. This paper covers a novel scalable process for producing β-lactam 10 in the multiple kilogram scale. An alternative...
-
process development for the synthesis of a Monobactam antibiotic lys228
Organic Process Research & Development, 2020Co-Authors: Zhongbo Fei, Wanben Gong, Xianwen Wang, Yufeng Han, Yi Zhao, Wenya Zhu, Wenlong Qiu, Jing Guo, Jianguang Zhou, Marco VillaAbstract:A scalable process for the novel Monobactam antibiotic LYS228 has been developed. This paper covers a novel scalable process for producing β-lactam 10 in the multiple kilogram scale. An alternative...
Wanben Gong - One of the best experts on this subject based on the ideXlab platform.
-
process development for the synthesis of a Monobactam antibiotic lys228
Organic Process Research & Development, 2020Co-Authors: Zhongbo Fei, Wanben Gong, Xianwen Wang, Yufeng Han, Yi Zhao, Wenya Zhu, Wenlong Qiu, Jing Guo, Jianguang Zhou, Marco VillaAbstract:A scalable process for the novel Monobactam antibiotic LYS228 has been developed. This paper covers a novel scalable process for producing β-lactam 10 in the multiple kilogram scale. An alternative...
-
Process Development for the Synthesis of a Monobactam Antibiotic—LYS228
Organic Process Research & Development, 2020Co-Authors: Zhongbo Fei, Wanben Gong, Xianwen Wang, Yufeng HanAbstract:A scalable process for the novel Monobactam antibiotic LYS228 has been developed. This paper covers a novel scalable process for producing β-lactam 10 in the multiple kilogram scale. An alternative...
-
Optimization of novel Monobactams with activity against carbapenem-resistant Enterobacteriaceae - Identification of LYS228.
Bioorganic & medicinal chemistry letters, 2018Co-Authors: Folkert Reck, Alun Bermingham, Johanne Blais, Vladimir Capka, Taryn Cariaga, Anthony Casarez, Richard Colvin, Charles R. Dean, Alex Fekete, Wanben GongAbstract:Metallo-β-lactamases (MBLs), such as New Delhi metallo-β-lactamase (NDM-1) have spread world-wide and present a serious threat. Expression of MBLs confers resistance in Gram-negative bacteria to all classes of β-lactam antibiotics, with the exception of Monobactams, which are intrinsically stable to MBLs. However, existing first generation Monobactam drugs like aztreonam have limited clinical utility against MBL-expressing strains because they are impacted by serine β-lactamases (SBLs), which are often co-expressed in clinical isolates. Here, we optimized novel Monobactams for stability against SBLs, which led to the identification of LYS228 (compound 31). LYS228 is potent in the presence of all classes of β-lactamases and shows potent activity against carbapenem-resistant isolates of Enterobacteriaceae (CRE).
Jason C. Gallagher - One of the best experts on this subject based on the ideXlab platform.
-
Beta-Lactam Hypersensitivity and Cross-Reactivity:
Journal of Pharmacy Practice, 2014Co-Authors: Adrienne T. Terico, Jason C. GallagherAbstract:Penicillin is the most frequently reported cause of drug allergy, and cross-reactivity of penicillins with other beta-lactam antibiotics is an area of debate. This review evaluates the available data on immunoglobulin E-mediated penicillin hypersensitivity and cross-reactivity with cephalosporin, carbapenem, and Monobactam antibiotics. A MEDLINE search was conducted from 1950 to October 2013, and selected references from review articles were also evaluated. There is a wide variety in reported incidences of cross-reactivity between penicillins and cephalosporins or carbapenems, with early retrospective studies suggesting up to 41.7% and 47.4% cross-reactivity, respectively. Conversely, the use of Monobactam antibiotics is frequently employed in the case of a penicillin allergy, as prescribers believe that there is no cross-reactivity between the 2 drug classes. More recent prospective studies suggest that the rates of cross-reactivity with cephalosporins and carbapenems are
-
Allergic Cross-Sensitivity Between Penicillin, Carbapenem, and Monobactam Antibiotics: What Are the Chances?
The Annals of pharmacotherapy, 2009Co-Authors: Jane Frumin, Jason C. GallagherAbstract:Objective:To evaluate the literature on the allergic cross-reactivity between penicillin, carbapenem, and Monobactam antibiotics.Data Sources:A MEDLINE search (1950–June 2008) of the English literature was performed using the search terms β-lactam, penicillin, Monobactam, carbapenem, allergy, and cross-reactivity. References of review articles were also screened for inclusion.Study Selection and Data Extraction:All articles in English from the data source were identified. Studies whose primary goal was to evaluate drug hypersensitivity and the potential for cross-reactivity were evaluated.Data Synthesis:Many patients have reported penicillin allergies that have not been verified by skin testing; many healthcare providers avoid the use of other β-lactam antibiotics, namely carbapenems, in these patients due to fear of the potential for immunoglobulin E-mediated allergic cross-reactivity. A wide range of cross-reactivity between penicillins and carbapenems has been reported in various studies; however, more...