{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:44:41Z","timestamp":1791531881277,"version":"4.3.4"},"reference-count":155,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Department of Ningxia, China","award":["2018BCG01001"],"award-info":[{"award-number":["2018BCG01001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Antibacterial resistance towards the \u03b2-lactam (BL) drugs is now ubiquitous, and there is a major global health concern associated with the emergence of new \u03b2-lactamases (BLAs) as the primary cause of resistance. In addition to the development of new antibacterial drugs, \u03b2-lactamase inhibition is an alternative modality that can be implemented to tackle this resistance channel. This strategy has successfully revitalized the efficacy of a number of otherwise obsolete BLs since the discovery of the first \u03b2-lactamase inhibitor (BLI), clavulanic acid. Over the years, \u03b2-lactamase inhibition research has grown, leading to the introduction of new synthetic inhibitors, and a few are currently in clinical trials. Of note, the 1, 6-diazabicyclo [3,2,1]octan-7-one (DBO) scaffold gained the attention of researchers around the world, which finally culminated in the approval of two BLIs, avibactam and relebactam, which can successfully inhibit Ambler class A, C, and D \u03b2-lactamases. Boronic acids have shown promise in coping with Ambler class B \u03b2-lactamases in recent research, in addition to classes A, C, and D with the clinical use of vaborbactam. This review focuses on the further developments in the synthetic strategies using DBO as well as boronic acid derivatives. In addition, various other potential serine- and metallo- \u03b2-lactamases inhibitors that have been developed in last few years are discussed briefly as well. Furthermore, binding interactions of the representative inhibitors have been discussed based on the crystal structure data of inhibitor-enzyme complex, published in the literature.<\/jats:p>","DOI":"10.3390\/molecules27123832","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T01:39:54Z","timestamp":1655257194000},"page":"3832","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Recent Developments to Cope the Antibacterial Resistance via \u03b2-Lactamase Inhibition"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0387-0920","authenticated-orcid":false,"given":"Zafar","family":"Iqbal","sequence":"first","affiliation":[{"name":"Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Sun","sequence":"additional","affiliation":[{"name":"Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haikang","family":"Yang","sequence":"additional","affiliation":[{"name":"Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Ji","sequence":"additional","affiliation":[{"name":"Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"He","sequence":"additional","affiliation":[{"name":"Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Zhai","sequence":"additional","affiliation":[{"name":"Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbo","family":"Ji","sequence":"additional","affiliation":[{"name":"Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengjuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4667-6239","authenticated-orcid":false,"given":"Dong","family":"Tang","sequence":"additional","affiliation":[{"name":"Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangxiu","family":"Mu","sequence":"additional","affiliation":[{"name":"Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1038\/s41396-019-0494-9","article-title":"Deciphering links between bacterial interactions and spatial organization in multispecies biofilms","volume":"13","author":"Liu","year":"2019","journal-title":"ISME J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3934\/microbiol.2018.3.482","article-title":"An overview of the antimicrobial resistance mechanisms of bacteria","volume":"4","author":"Reygaert","year":"2018","journal-title":"AIMS Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"134","DOI":"10.3389\/fmicb.2010.00134","article-title":"A brief history of the antibiotic era: Lessons learned and challenges for the future","volume":"1","author":"Aminov","year":"2010","journal-title":"Front. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e0196621","DOI":"10.1128\/mBio.01966-21","article-title":"Why Do Antibiotics Exist?","volume":"12","author":"Spagnolo","year":"2021","journal-title":"mBio"},{"key":"ref_5","first-page":"1","article-title":"Chapter 1\u2014Microorganisms and antibiotic production","volume":"Volume 1","author":"Hashmi","year":"2020","journal-title":"Antibiotics and Antimicrobial Resistance Genes in the Environment"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hashmi, M.Z., Strezov, V., and Varma, A. (2017). Antibiotics producing soil microorganisms. Antibiotics and Antibiotics Resistance Genes in Soils: Monitoring, Toxicity, Risk Assessment and Management, Springer International Publishing.","DOI":"10.1007\/978-3-319-66260-2"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.mib.2019.10.008","article-title":"Antibiotics: Past, present and future","volume":"51","author":"Hutchings","year":"2019","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1128\/MMBR.00016-10","article-title":"Origins and Evolution of Antibiotic Resistance","volume":"74","author":"Davies","year":"2010","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6600","DOI":"10.1002\/anie.201506818","article-title":"Targeting Antibiotic Resistance","volume":"55","author":"Chellat","year":"2016","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1007\/s00018-004-4060-9","article-title":"Resistance to beta-lactam antibiotics","volume":"61","author":"Poole","year":"2004","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.3389\/fmicb.2018.02928","article-title":"Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens","volume":"9","author":"Peterson","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1128\/microbiolspec.VMBF-0016-2015","article-title":"Mechanisms of Antibiotic Resistance","volume":"4","author":"Munita","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref_13","first-page":"74","article-title":"Fight against antimicrobial resistance","volume":"67","year":"2018","journal-title":"Epidemiol. Mikrobiol. Imunol. Cas. Spol. Pro Epidemiol. A Mikrobiol. Ceske Lek. Spol. J.E. Purkyne"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"849","DOI":"10.3201\/eid2305.161556","article-title":"The Discovery of Penicillin\u2014New Insights After More Than 75 Years of Clinical Use","volume":"23","author":"Gaynes","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrc2394","article-title":"Paul Ehrlich\u2019s magic bullet concept: 100 years of progress","volume":"8","author":"Strebhardt","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1002\/anie.200461471","article-title":"The Composition of Ehrlich\u2019s Salvarsan: Resolution of a Century-Old Debate","volume":"44","author":"Lloyd","year":"2005","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s10295-009-0553-8","article-title":"Different roads to discovery; Prontosil (hence sulfa drugs) and penicillin (hence beta-lactams)","volume":"36","author":"Bentley","year":"2009","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"ref_18","unstructured":"National Institute of Diabetes and Digestive and Kidney Diseases (2012). Aminoglycosides. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, National Institute of Diabetes and Digestive and Kidney Diseases."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nature17967","article-title":"A platform for the discovery of new macrolide antibiotics","volume":"533","author":"Seiple","year":"2016","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1039\/D1CC06635H","article-title":"Pursuit of next-generation glycopeptides: A journey with vancomycin","volume":"58","author":"Acharya","year":"2022","journal-title":"Chem. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kaur, P., Chandra, A., Tanwar, T., Sahu, S.K., and Mittal, A. (2022). Emerging quinoline- and quinolone-based antibiotics in the light of epidemics. Chememical Biology and Drug Design, Wiley.","DOI":"10.1111\/cbdd.14025"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/ja.2013.49","article-title":"Prospects for new antibiotics: A molecule-centered perspective","volume":"67","author":"Walsh","year":"2014","journal-title":"J. Antibiot."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7957","DOI":"10.1021\/acs.chemrev.1c00138","article-title":"Metallo-\u03b2-lactamases in the Age of Multidrug Resistance: From Structure and Mechanism to Evolution, Dissemination, and Inhibitor Design","volume":"121","author":"Bahr","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1093\/jac\/dki130","article-title":"Revised Ambler classification of \u03b2-lactamases","volume":"55","author":"Barry","year":"2005","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1098\/rstb.1980.0049","article-title":"The structure of \u03b2-lactamases","volume":"289","author":"Ambler","year":"1980","journal-title":"Philos. Trans. R. Soc. London. B Biol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1128\/AAC.01009-09","article-title":"Updated functional classification of beta-lactamases","volume":"54","author":"Bush","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","first-page":"11","article-title":"Extended Spectrum b-lactamases: Definition, Classification and Epidemiology","volume":"17","author":"Ghafourian","year":"2015","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1093\/cid\/ciw243","article-title":"Ceftazidime\/Avibactam and Ceftolozane\/Tazobactam: Second-generation\u03b2-Lactam\/\u03b2-Lactamase Inhibitor Combinations","volume":"63","author":"Duin","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1093\/jac\/dkw239","article-title":"Spotlight on ceftazidime\/avibactam: A new option for MDR Gram-negative infections","volume":"71","author":"Falcone","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s40265-018-0902-x","article-title":"Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections","volume":"78","author":"Shirley","year":"2018","journal-title":"Drugs"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1016\/j.jmb.2019.04.002","article-title":"\u03b2-Lactamases and \u03b2-Lactamase Inhibitors in the 21st Century","volume":"431","author":"Tooke","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1021\/acs.jmedchem.5b00127","article-title":"Discovery of a Cyclic Boronic Acid \u03b2-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases","volume":"58","author":"Hecker","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"dlab092","DOI":"10.1093\/jacamr\/dlab092","article-title":"Extended-spectrum \u03b2-lactamases: An update on their characteristics, epidemiology and detection","volume":"3","author":"Castanheira","year":"2021","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4236\/aim.2021.111004","article-title":"An Overview of Extended Spectrum Beta Lactamases and Metallo Beta Lactamases","volume":"11","author":"Nagshetty","year":"2021","journal-title":"Adv. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/AAC.01076-18","article-title":"Past and Present Perspectives on \u03b2-Lactamases","volume":"62","author":"Bush","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Eiamphungporn, W., Schaduangrat, N., Malik, A.A., and Nantasenamat, C. (2018). Tackling the Antibiotic Resistance Caused by Class A beta-Lactamases through the Use of beta-Lactamase Inhibitory Protein. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082222"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e00108-21","DOI":"10.1128\/mSphere.00108-21","article-title":"Cryptic \u03b2-Lactamase Evolution Is Driven by Low \u03b2-Lactam Concentrations","volume":"6","author":"Gama","year":"2021","journal-title":"mSphere"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.biotechadv.2008.03.002","article-title":"Clavulanic acid: A review","volume":"26","author":"Saudagar","year":"2008","journal-title":"Biotechnol. Adv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.clinmicnews.2021.06.004","article-title":"Novel \u00df-Lactamase Inhibitors: New Weapons in the Arms Race against Antimicrobial Resistance","volume":"43","author":"Deja","year":"2021","journal-title":"Clin. Microbiol. Newsl."},{"key":"ref_40","unstructured":"Uto, L.R., and Gerriets, V. (2020). Clavulanic acid. StatPearls, StatPearls Publishing LLC."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1469-0691.2007.01847.x","article-title":"Sulbactam-containing \u03b2-lactamase inhibitor combinations","volume":"14","author":"Akova","year":"2008","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_42","first-page":"245","article-title":"Ampicillin\/Sulbactam in Combination: A Review of its Use in the Treatment of Severe Bacterial Infections","volume":"2","author":"Blanco","year":"2010","journal-title":"Clin. Med. Rev. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.mib.2011.07.026","article-title":"Diazabicyclooctanes (DBOs): A potent new class of non-\u03b2-lactam \u03b2-lactamase inhibitors","volume":"14","author":"Coleman","year":"2011","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1021\/acs.jmedchem.9b01279","article-title":"\u03b2-Lactamase Inhibitors To Restore the Efficacy of Antibiotics against Superbugs","volume":"63","author":"Rodriguez","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_45","unstructured":"Maxime, L., Jozsef, A., Alan, R.D., and Claude, F. (2003). Azabicyclic Compounds, Preparation Thereof and Use as Medicines, in Particular as Antibacterial Agents. (US20030199541), U.S. Patent."},{"key":"ref_46","unstructured":"Blizzard, T.A., Chen, H., Gude, C., Hermes, J.D., Imbriglio, J.E., Kim, S., Wu, J.Y., Ha, S., Mortko, C.J., and Mangion, I. (2009). Beta-Lactamase Inhibitors. (WO2009091856), WIPO Patent."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.coph.2019.03.004","article-title":"Recently developed synthetic compounds with anti-infective activity","volume":"48","year":"2019","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1039\/C9OB02605C","article-title":"Synthetic approaches towards avibactam and other diazabicyclooctane \u03b2-lactamase inhibitors","volume":"18","author":"Peilleron","year":"2020","journal-title":"Org. Biomol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/jac\/dkg286","article-title":"A review of the antimicrobial activity of clavulanate","volume":"52","author":"Finlay","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1128\/AAC.38.4.767","article-title":"Comparative activities of clavulanic acid, sulbactam, and tazobactam against clinically important beta-lactamases","volume":"38","author":"Payne","year":"1994","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s12275-020-0285-z","article-title":"Recent advances in the development of \u03b2-lactamase inhibitors","volume":"58","author":"Jalde","year":"2020","journal-title":"J. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1021\/acschembio.5b00944","article-title":"Structural and Kinetic Characterization of Diazabicyclooctanes as Dual Inhibitors of Both Serine-beta-Lactamases and Penicillin-Binding Proteins","volume":"11","author":"King","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e03058-20","DOI":"10.1128\/mBio.03058-20","article-title":"Structural Characterization of Diazabicyclooctane \u03b2-Lactam \u201dEnhancers\u201d in Complex with Penicillin-Binding Proteins PBP2 and PBP3 of Pseudomonas aeruginosa","volume":"12","author":"Rajavel","year":"2021","journal-title":"mBio"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Alfei, S., and Zuccari, G. (2022). Recommendations to Synthetize Old and New \u03b2-Lactamases Inhibitors: A Review to Encourage Further Production. Pharmaceuticals, 15.","DOI":"10.3390\/ph15030384"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1021\/ol4031606","article-title":"Practical and Cost-Effective Manufacturing Route for the Synthesis of a \u03b2-Lactamase Inhibitor","volume":"16","author":"Miller","year":"2014","journal-title":"Org. Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5480","DOI":"10.1021\/ol202195n","article-title":"A Concise Synthesis of a \u03b2-Lactamase Inhibitor","volume":"13","author":"Mangion","year":"2011","journal-title":"Org. Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1021\/acs.joc.9b02948","article-title":"Diastereoselective FeCl3\u00b76H2O\/NaBH4 Reduction of Oxime Ether for the Synthesis of \u03b2-Lactamase Inhibitor Relebactam","volume":"85","author":"Chung","year":"2020","journal-title":"J. Org. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1021\/acs.oprd.7b00381","article-title":"Improved Preparation of a Key Hydroxylamine Intermediate for Relebactam: Rate Enhancement of Benzyl Ether Hydrogenolysis with DABCO","volume":"22","author":"Yin","year":"2018","journal-title":"Org. Process Res. Dev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11792","DOI":"10.1021\/jo502319z","article-title":"N-Boc Deprotection and Isolation Method for Water-Soluble Zwitterionic Compounds","volume":"79","author":"Liu","year":"2014","journal-title":"J. Org. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1021\/acs.oprd.1c00149","article-title":"Development of a Practical Manufacturing Process to Relebactam via Thorough Understanding of the Origin and Control of Oligomeric Impurities","volume":"25","author":"Kim","year":"2021","journal-title":"Org. Process Res. Dev."},{"key":"ref_61","unstructured":"(1996). Augmentin reconsidered. Drug Ther. Bull., 2020, 76\u201379."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10340","DOI":"10.1021\/acs.jmedchem.8b01389","article-title":"Orally Absorbed Derivatives of the \u03b2-Lactamase Inhibitor Avibactam. Design of Novel Prodrugs of Sulfate Containing Drugs","volume":"61","author":"Gordon","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"709974","DOI":"10.3389\/fmicb.2021.709974","article-title":"Durlobactam, a New Diazabicyclooctane \u03b2-Lactamase Inhibitor for the Treatment of Acinetobacter Infections in Combination With Sulbactam","volume":"12","author":"Shapiro","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_64","unstructured":"Comita-Prevoir, J., Durand-Reville, T.F., Gauthier, L., O\u2019Donnell, J., Romero, J., Tommasi, R., Verheijen, J.C., Wu, F., Wu, X., and Zhang, J. (2018). Beta-Lactamase Inhibitor Compounds. (WO2018053215), WIPO Patent."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1021\/acsinfecdis.0c00656","article-title":"Interactions of the Diazabicyclooctane Serine \u03b2-Lactamase Inhibitor ETX1317 with Target Enzymes","volume":"7","author":"Shapiro","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1021\/acsinfecdis.0c00575","article-title":"Ceftazidime-Avibactam Resistance Mutations V240G, D179Y, and D179Y\/T243M in KPC-3 beta-Lactamase Do Not Alter Cefpodoxime-ETX1317 Susceptibility","volume":"7","author":"Shapiro","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12511","DOI":"10.1021\/acs.jmedchem.0c00579","article-title":"Discovery of an Orally Available Diazabicyclooctane Inhibitor (ETX0282) of Class A, C, and D Serine beta-Lactamases","volume":"63","author":"Zhang","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"15802","DOI":"10.1021\/acs.jmedchem.0c01535","article-title":"Discovery of ANT3310, a Novel Broad-Spectrum Serine \u03b2-Lactamase Inhibitor of the Diazabicyclooctane Class, Which Strongly Potentiates Meropenem Activity against Carbapenem-Resistant Enterobacterales and Acinetobacter baumannii","volume":"63","author":"Davies","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9650","DOI":"10.1021\/acs.joc.0c00980","article-title":"Synthesis of 2-Thio-Substituted 1,6-Diazabicyclo[3.2.1]octane Derivatives, Potent \u03b2-Lactamase Inhibitors","volume":"85","author":"Fujiu","year":"2020","journal-title":"J. Org. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1021\/acsinfecdis.0c00560","article-title":"Introduction of a Thio Functional Group to Diazabicyclooctane: An Effective Modification to Potentiate the Activity of beta-Lactams against Gram-Negative Bacteria Producing Class A, C, and D Serine beta-Lactamases","volume":"6","author":"Fujiu","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"9496","DOI":"10.1021\/acs.jmedchem.1c00799","article-title":"Discovery of 2-Sulfinyl-Diazabicyclooctane Derivatives, Potential Oral \u03b2-Lactamase Inhibitors for Infections Caused by Serine \u03b2-Lactamase-Producing Enterobacterales","volume":"64","author":"Fujiu","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.1021\/acs.jmedchem.9b02125","article-title":"Diazabicyclooctane Functionalization for Inhibition of \u03b2-Lactamases from Enterobacteria","volume":"63","author":"Bouchet","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"8081","DOI":"10.1002\/chem.201800923","article-title":"Synthesis of Avibactam Derivatives and Activity on \u03b2-Lactamases and Peptidoglycan Biosynthesis Enzymes of Mycobacteria","volume":"24","author":"Edoo","year":"2018","journal-title":"Chem. Eur. J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1021\/acsinfecdis.9b00031","article-title":"IID572: A New Potentially Best-In-Class \u03b2-Lactamase Inhibitor","volume":"5","author":"Reck","year":"2019","journal-title":"ACS Infect. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1021\/acs.oprd.0c00069","article-title":"Scale-Up Synthesis of IID572: A New \u03b2-Lactamase Inhibitor","volume":"24","author":"Furegati","year":"2020","journal-title":"Org. Process Res. Dev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/B978-0-12-800167-7.00016-X","article-title":"Chapter 16-Advances in Inhibitors of Penicillin-Binding Proteins and \u03b2-Lactamases as Antibacterial Agents","volume":"Volume 49","author":"Desai","year":"2014","journal-title":"Annual Reports in Medicinal Chemistry"},{"key":"ref_77","unstructured":"Gu, Y.G., He, Y., Yin, N., Alexander, D.C., Cross, J.B., Metcalf, C.A., and Busch, R. (2015). Isoxazole Beta-Lactamase Inhibitors. (US2015038482), US Patent."},{"key":"ref_78","unstructured":"Gu, Y.G., He, Y., Yin, N., Alexander, D.C., Cross, J.B., Metcalf, C.A., and Busch, R. (2013). 1,3,4-Oxadiazole And 1,3,4-Thiadiazole \u0392-Lactamase Inhibitors. (WO2013149121), WIPO Patent."},{"key":"ref_79","unstructured":"Lampilas, M., Rowlands, D.A., Kebsi, A., Ledoussal, B., and Pierres, C. (2008). Nitrogenous Heterocyclic Compounds, Preparation Thereof And Use Thereof As Antibacterial Medicaments. (WO2008142285), WIPO Patent."},{"key":"ref_80","unstructured":"Comita-Prevoir, J., Du-Rand-Reville, T.F., Guler, S., Romeo, J., Sylvester, M., Tomasi, R., Velez-Vega, C., Wu, X., and Zhang, J. (2018). Compounds and Methods for Treating Bacterial Infections. (WO2018208769), WIPO Patent."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/s41586-021-03899-0","article-title":"Rational design of a new antibiotic class for drug-resistant infections","volume":"597","author":"Miller","year":"2021","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"711","DOI":"10.3762\/bjoc.17.60","article-title":"\u03b2-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes","volume":"17","author":"Iqbal","year":"2021","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1002\/slct.202004620","article-title":"Amidine Derivatives of Avibactam: Synthesis and In Vitro \u03b2-Lactamase Inhibition Activity","volume":"6","author":"Gao","year":"2021","journal-title":"ChemistrySelect"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s00706-021-02888-3","article-title":"Substituted-amidine derivatives of diazabicyclooctane as prospective \u03b2-lactamase inhibitors","volume":"153","author":"Liu","year":"2022","journal-title":"Mon. Chem. Chem. Mon."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.mencom.2021.07.020","article-title":"Synthesis of substituted-amidine derivatives of avibactam and synergistic antibacterial activity with meropenem","volume":"31","author":"Sun","year":"2021","journal-title":"Mendeleev Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/jhet.4360","article-title":"Sulfonylamidine-substituted derivatives of avibactam: Synthesis and antibacterial activity","volume":"58","author":"Ji","year":"2021","journal-title":"J. Heterocycl. Chem."},{"key":"ref_87","unstructured":"Zhai, L., Sun, J., Ji, J., He, L., Gao, Y., Ji, J., Liu, Y., Mu, Y., Ma, X., and Tang, D. (Russ. J. Bioorganic Chem., 2022). Synthesis and \u03b2-lactamase inhibition activity of imidates of diazabicyclooctane, Russ. J. Bioorganic Chem., in press."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4067","DOI":"10.1021\/acs.jmedchem.8b00091","article-title":"Strategic Approaches to Overcome Resistance against Gram-Negative Pathogens Using \u03b2-Lactamase Inhibitors and \u03b2-Lactam Enhancers: Activity of Three Novel Diazabicyclooctanes WCK 5153, Zidebactam (WCK 5107), and WCK 4234","volume":"61","author":"Nguyen","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1016\/S0040-4039(00)88891-7","article-title":"An efficient conversion of nitriles to amidines","volume":"31","author":"Garigipati","year":"1990","journal-title":"Tetrahedron Lett."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"8761","DOI":"10.1016\/0040-4039(95)01925-8","article-title":"Conversion of \u2018obstinate\u2019 nitriles to amidines by Garigipati\u2019s reaction","volume":"36","author":"Moss","year":"1995","journal-title":"Tetrahedron Lett."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4156","DOI":"10.1021\/cr608202m","article-title":"Boron Containing Compounds as Protease Inhibitors","volume":"112","author":"Smoum","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Messner, K., Vuong, B., and Tranmer, G.K. (2022). The Boron Advantage: The Evolution and Diversification of Boron\u2019s Applications in Medicinal Chemistry. Pharmaceuticals, 15.","DOI":"10.3390\/ph15030264"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1042\/bj1690197","article-title":"Reversible inhibitors of penicillinases","volume":"169","author":"Kiener","year":"1978","journal-title":"Biochem. J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.ijantimicag.2015.08.011","article-title":"A resurgence of \u03b2-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens","volume":"46","author":"Bush","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_95","first-page":"1","article-title":"Computational and biological profile of boronic acids for the detection of bacterial serine- and metallo-\u03b2-lactamases","volume":"7","author":"Matteo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1080\/13543776.2020.1767070","article-title":"A 2018\u20132019 patent review of metallo beta-lactamase inhibitors","volume":"30","author":"Reddy","year":"2020","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1080\/14787210.2016.1204911","article-title":"The antibiotic pipeline for multi-drug resistant gram negative bacteria: What can we expect?","volume":"14","author":"Falagas","year":"2016","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e01443-17","DOI":"10.1128\/AAC.01443-17","article-title":"Vaborbactam: Spectrum of Beta-Lactamase Inhibition and Impact of Resistance Mechanisms on Activity in Enterobacteriaceae","volume":"61","author":"Lomovskaya","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4856","DOI":"10.1128\/AAC.00843-15","article-title":"Activity of Meropenem Combined with RPX7009, a Novel \u03b2-Lactamase Inhibitor, against Gram-Negative Clinical Isolates in New York City","volume":"59","author":"Lapuebla","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e01935-19","DOI":"10.1128\/AAC.01935-19","article-title":"Biochemical Activity of Vaborbactam","volume":"64","author":"Tsivkovski","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1016\/j.bmcl.2019.05.031","article-title":"Profiling interactions of vaborbactam with metallo-\u03b2-lactamases","volume":"29","author":"Langley","year":"2019","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5312","DOI":"10.1021\/bi992505b","article-title":"Structure-Based Design Guides the Improved Efficacy of Deacylation Transition State Analogue Inhibitors of TEM-1 \u03b2-Lactamase","volume":"39","author":"Ness","year":"2000","journal-title":"Biochemistry"},{"key":"ref_103","unstructured":"Burns, C.J., Goswami, R., Jackson, R.W., Lessen, T., Li, W., Pevear, D., Tirunahari, P.K., and Xu, H. (2010). Beta-Lactamase Inhibitors. (WO2010130708), WIPO Patent."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"12406","DOI":"10.1038\/ncomms12406","article-title":"Structural basis of metallo-\u03b2-lactamase, serine-\u03b2-lactamase and penicillin-binding protein inhibition by cyclic boronates","volume":"7","author":"Brem","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2000246","DOI":"10.1002\/adtp.202000246","article-title":"Bicyclic Boronate b-Lactamase Inhibitors: The Present Hope against Deadly Bacterial Pathogens","volume":"21","author":"Lence","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1021\/acs.jmedchem.9b01518","article-title":"Discovery of Taniborbactam (VNRX-5133): A Broad-Spectrum Serine- and Metallo-\u03b2-lactamase Inhibitor for Carbapenem-Resistant Bacterial Infections","volume":"63","author":"Liu","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1039\/C9MD00557A","article-title":"Cyclic boronates as versatile scaffolds for KPC-2 \u03b2-lactamase inhibition","volume":"11","author":"Tooke","year":"2020","journal-title":"RSC Med. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e02260-16","DOI":"10.1128\/AAC.02260-16","article-title":"Cyclic Boronates Inhibit All Classes of \u03b2-Lactamases","volume":"61","author":"Cahill","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e00397-20","DOI":"10.1128\/AAC.00397-20","article-title":"Metallo-\u03b2-Lactamases: Structure, Function, Epidemiology, Treatment Options, and the Development Pipeline","volume":"64","author":"Boyd","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"8544","DOI":"10.1021\/acs.jmedchem.9b00911","article-title":"Bicyclic Boronate VNRX-5133 Inhibits Metallo- and Serine-\u03b2-Lactamases","volume":"62","author":"Krajnc","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e01053-21","DOI":"10.1128\/AAC.01053-21","article-title":"Safety and Pharmacokinetics in Human Volunteers of Taniborbactam (VNRX-5133), a Novel Intravenous \u03b2-Lactamase Inhibitor","volume":"65","author":"Dowell","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_112","unstructured":"Burns, C.J., Daigle, D., Liu, B., Mcgarry, D., Pevear, D.C., and Trout, R.E.L. (2014). Beta-Lactamase Inhibitors. (WO2014089365), WIPO Patent."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e00130-20","DOI":"10.1128\/AAC.00130-20","article-title":"Biochemical Characterization of QPX7728, a New Ultrabroad-Spectrum Beta-Lactamase Inhibitor of Serine and Metallo-Beta-Lactamases","volume":"64","author":"Tsivkovski","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"7491","DOI":"10.1021\/acs.jmedchem.9b01976","article-title":"Discovery of Cyclic Boronic Acid QPX7728, an Ultrabroad-Spectrum Inhibitor of Serine and Metallo-\u03b2-lactamases","volume":"63","author":"Hecker","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"7160","DOI":"10.1021\/acs.jmedchem.9b00735","article-title":"Structure-Based Development of (1-(3\u2032-Mercaptopropanamido)methyl)boronic Acid Derived Broad-Spectrum, Dual-Action Inhibitors of Metallo- and Serine-\u03b2-lactamases","volume":"62","author":"Wang","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"115598","DOI":"10.1016\/j.bmc.2020.115598","article-title":"Structural studies of triazole inhibitors with promising inhibitor effects against antibiotic resistance metallo-\u03b2-lactamases","volume":"28","author":"Muhammad","year":"2020","journal-title":"Bioorganic Med. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"834","DOI":"10.2174\/1568026618666180518101028","article-title":"The Development of New Small-Molecule Inhibitors Targeting Bacterial Metallo-\u03b2-lactamases","volume":"18","author":"Wang","year":"2018","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1021\/acs.biochem.5b00106","article-title":"Exploring the Role of Residue 228 in Substrate and Inhibitor Recognition by VIM Metallo-\u03b2-lactamases","volume":"54","author":"Mojica","year":"2015","journal-title":"Biochemistry"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1021\/acsinfecdis.5b00046","article-title":"Bisthiazolidines: A Substrate-Mimicking Scaffold as an Inhibitor of the NDM-1 Carbapenemase","volume":"1","author":"Kosmopoulou","year":"2015","journal-title":"ACS Infect. Dis."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"E3745","DOI":"10.1073\/pnas.1601368113","article-title":"Cross-class metallo-\u03b2-lactamase inhibition by bisthiazolidines reveals multiple binding modes","volume":"113","author":"Hinchliffe","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1021\/acsinfecdis.1c00194","article-title":"2-Mercaptomethyl Thiazolidines (MMTZs) Inhibit All Metallo-\u03b2-Lactamase Classes by Maintaining a Conserved Binding Mode","volume":"7","author":"Hinchliffe","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1039\/D0SC05172A","article-title":"2-Mercaptomethyl-thiazolidines use conserved aromatic\u2013S interactions to achieve broad-range inhibition of metallo-\u03b2-lactamases","volume":"12","author":"Rossi","year":"2021","journal-title":"Chem. Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e03144-19","DOI":"10.1128\/mBio.03144-19","article-title":"Sulfamoyl Heteroarylcarboxylic Acids as Promising Metallo-\u03b2-Lactamase Inhibitors for Controlling Bacterial Carbapenem Resistance","volume":"11","author":"Wachino","year":"2020","journal-title":"mBio"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1128\/AAC.00074-18","article-title":"Discovery of a Novel Metallo-\u03b2-Lactamase Inhibitor That Potentiates Meropenem Activity against Carbapenem-Resistant Enterobacteriaceae","volume":"62","author":"Everett","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1021\/acsinfecdis.8b00246","article-title":"SAR Studies Leading to the Identification of a Novel Series of Metallo-\u03b2-lactamase Inhibitors for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections That Display Efficacy in an Animal Infection Model","volume":"5","author":"Leiris","year":"2019","journal-title":"ACS Infect. Dis."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1021\/acsinfecdis.0c00207","article-title":"ANT2681: SAR Studies Leading to the Identification of a Metallo-\u03b2-lactamase Inhibitor with Potential for Clinical Use in Combination with Meropenem for the Treatment of Infections Caused by NDM-Producing Enterobacteriaceae","volume":"6","author":"Davies","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref_127","first-page":"6","article-title":"Novel Specific Metallo-\u03b2-Lactamase Inhibitor ANT2681 Restores Meropenem Activity to Clinically Effective Levels against NDM-Positive Enterobacterales","volume":"65","author":"Zalacain","year":"2021","journal-title":"Am. Soc. Microbiol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1039\/D1MD00187F","article-title":"N-Aryl mercaptoacetamides as potential multi-target inhibitors of metallo-\u03b2-lactamases (MBLs) and the virulence factor LasB from Pseudomonas aeruginosa","volume":"12","author":"Yahiaoui","year":"2021","journal-title":"RSC Med. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3913","DOI":"10.1021\/acs.jmedchem.1c01755","article-title":"N-Aryl Mercaptopropionamides as Broad-Spectrum Inhibitors of Metallo-\u03b2-Lactamases","volume":"65","author":"Kaya","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"113965","DOI":"10.1016\/j.ejmech.2021.113965","article-title":"Structure-guided optimization of 1H-imidazole-2-carboxylic acid derivatives affording potent VIM-Type metallo-beta-lactamase inhibitors","volume":"228","author":"Yan","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41557-021-00831-x","article-title":"Imitation of beta-lactam binding enables broad-spectrum metallo-beta-lactamase inhibitors","volume":"14","author":"Brem","year":"2022","journal-title":"Nat. Chem."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1016\/j.bmc.2005.11.046","article-title":"New leads of metallo-\u03b2-lactamase inhibitors from structure-based pharmacophore design","volume":"14","author":"Olsen","year":"2006","journal-title":"Bioorganic Med. Chem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1134\/S1070363222020050","article-title":"Synthesis and Antimicrobial Activity of Novel Hydrazone and 1,2,4-Triazole-3-thione Derivatives","volume":"92","author":"Yankin","year":"2022","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1002\/cmdc.201700186","article-title":"1,2,4-Triazole-3-thione Compounds as Inhibitors of Dizinc Metallo-\u03b2-lactamases","volume":"12","author":"Sevaille","year":"2017","journal-title":"ChemMedChem"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Gavara, L., Verdirosa, F., Legru, A., Mercuri, P.S., Nauton, L., Sevaille, L., Feller, G., Berthomieu, D., Sannio, F., and Marcoccia, F. (2020). 4-(N-Alkyl- and -Acyl-amino)-1,2,4-triazole-3-thione Analogs as Metallo-\u03b2-Lactamase Inhibitors: Impact of 4-Linker on Potency and Spectrum of Inhibition. Biomolecules, 10.","DOI":"10.3390\/biom10081094"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"105024","DOI":"10.1016\/j.bioorg.2021.105024","article-title":"4-Alkyl-1,2,4-triazole-3-thione analogues as metallo-\u03b2-lactamase inhibitors","volume":"113","author":"Gavara","year":"2021","journal-title":"Bioorganic Chem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"112720","DOI":"10.1016\/j.ejmech.2020.112720","article-title":"4-Amino-1,2,4-triazole-3-thione-derived Schiff bases as metallo-\u03b2-lactamase inhibitors","volume":"208","author":"Gavara","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Linciano, P., Gianquinto, E., Montanari, M., Maso, L., Bellio, P., Cebri\u00e1n-Sastre, E., Celenza, G., Bl\u00e1zquez, J., Cendron, L., and Spyrakis, F. (2020). 4-Amino-1,2,4-triazole-3-thione as a Promising Scaffold for the Inhibition of Serine and Metallo-\u03b2-Lactamases. Pharmaceuticals, 13.","DOI":"10.3390\/ph13030052"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"113873","DOI":"10.1016\/j.ejmech.2021.113873","article-title":"1,2,4-Triazole-3-thione compounds with a 4-ethyl alkyl\/aryl sulfide substituent are broad-spectrum metallo-\u03b2-lactamase inhibitors with re-sensitization activity","volume":"226","author":"Legru","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e202100699","DOI":"10.1002\/cmdc.202100699","article-title":"1,2,4-Triazole-3-Thione Analogues with a 2-Ethylbenzoic Acid at Position 4 as VIM-type Metallo-\u03b2-Lactamase Inhibitors","volume":"17","author":"Verdirosa","year":"2022","journal-title":"ChemMedChem"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1021\/bi992569m","article-title":"Crystal Structure of the IMP-1 Metallo \u03b2-Lactamase from Pseudomonas aeruginosa and Its Complex with a Mercaptocarboxylate Inhibitor:\u2009 Binding Determinants of a Potent, Broad-Spectrum Inhibitor","volume":"39","author":"Concha","year":"2000","journal-title":"Biochemistry"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/s41467-017-00601-9","article-title":"A general reaction mechanism for carbapenem hydrolysis by mononuclear and binuclear metallo-\u03b2-lactamases","volume":"8","author":"Lisa","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1016\/j.febslet.2015.08.015","article-title":"Overcoming differences: The catalytic mechanism of metallo-\u03b2-lactamases","volume":"589","author":"Meini","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.tips.2018.03.007","article-title":"The Continuing Challenge of Metallo-\u03b2-Lactamase Inhibition: Mechanism Matters","volume":"39","author":"Ju","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e00398-20","DOI":"10.1128\/AAC.00398-20","article-title":"Structural Basis and Binding Kinetics of Vaborbactam in Class A \u03b2-Lactamase Inhibition","volume":"64","author":"Pemberton","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Lang, P.A., Parkova, A., Leissing, T.M., Calvopi\u00f1a, K., Cain, R., Krajnc, A., Panduwawala, T.D., Philippe, J., Fishwick, C.W.G., and Trapencieris, P. (2020). Bicyclic Boronates as Potent Inhibitors of AmpC, the Class C \u03b2-Lactamase from Escherichia coli. Biomolecules, 10.","DOI":"10.3390\/biom10060899"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1021\/acsinfecdis.1c00104","article-title":"Structural Basis of Metallo-\u03b2-lactamase Inhibition by N-Sulfamoylpyrrole-2-carboxylates","volume":"7","author":"Farley","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.jmb.2007.10.036","article-title":"Structural Insights into the Design of Inhibitors for the L1 Metallo-\u03b2-lactamase from Stenotrophomonas maltophilia","volume":"375","author":"Nauton","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"a025247","DOI":"10.1101\/cshperspect.a025247","article-title":"\u03b2-Lactams and \u03b2-Lactamase Inhibitors: An Overview","volume":"6","author":"Bush","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"549","DOI":"10.3389\/fimmu.2019.00549","article-title":"Infectious Disease Threats in the Twenty-First Century: Strengthening the Global Response","volume":"10","author":"Bloom","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Alfei, S., and Schito, A.M. (2022). \u03b2-Lactam Antibiotics and \u03b2-Lactamase Enzymes Inhibitors, Part 2: Our Limited Resources. Pharmaceuticals, 15.","DOI":"10.3390\/ph15040476"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"V\u00e1zquez-Ucha, J.C., Arca-Su\u00e1rez, J., Bou, G., and Beceiro, A. (2020). New Carbapenemase Inhibitors: Clearing the Way for the \u03b2-Lactams. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239308"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e28","DOI":"10.1016\/S1473-3099(20)30868-9","article-title":"The urgent need for metallo-\u03b2-lactamase inhibitors: An unattended global threat","volume":"22","author":"Mojica","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.ijantimicag.2018.07.027","article-title":"Loss of activity of ceftazidime-avibactam due to MexAB-OprM efflux and overproduction of AmpC cephalosporinase in Pseudomonas aeruginosa isolated from patients suffering from cystic fibrosis","volume":"52","author":"Chalhoub","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1093\/jac\/dkz149","article-title":"ESBLs and resistance to ceftazidime\/avibactam and ceftolozane\/tazobactam combinations in Escherichia coli and Pseudomonas aeruginosa","volume":"74","author":"Nordmann","year":"2019","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/12\/3832\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:31:28Z","timestamp":1760139088000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/12\/3832"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,14]]},"references-count":155,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["molecules27123832"],"URL":"https:\/\/doi.org\/10.3390\/molecules27123832","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,14]]}}}