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Structure\u2013activity relationships previously described for the 5\u2010nitroimidazole series have shown that functionalization at the 2\u2010 and 4\u2010positions can impart better activity against parasites and anaerobic bacteria than metronidazole. Herein we report the synthesis of new 2,4\u2010disubstituted 5\u2010nitroimidazole compounds that show potent antibacterial activity against <jats:italic>C.\u2005difficile<\/jats:italic>. We used a vicarious nucleophilic substitution of hydrogen (VNS) reaction to introduce a phenylmethylsulfone at the 4\u2010position and a unimolecular radical nucleophilic substitution (S<jats:sub>RN<\/jats:sub>1) reaction to introduce an ethylenic function at the 2\u2010position of the 5\u2010nitroimidazole scaffold.<\/jats:p>","DOI":"10.1002\/cmdc.201800784","type":"journal-article","created":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T22:36:16Z","timestamp":1547505376000},"page":"561-569","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["2,4\u2010Disubstituted 5\u2010Nitroimidazoles Potent against <i>Clostridium difficile<\/i>"],"prefix":"10.1002","volume":"14","author":[{"given":"C\u00e9dric","family":"Spitz","sequence":"first","affiliation":[{"name":"Aix-Marseille Universit\u00e9, Institut de Chimie Radicalaire ICR, UMR CNRS 7273 Laboratoire de Pharmaco-Chimie Radicalaire, Facult\u00e9 de Pharmacie  27 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