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However, tabun remains among the most dangerous nerve agents due to the low reactivation efficacy of standard pyridinium aldoxime antidotes. Therefore, finding an optimal reactivator for prophylaxis against tabun toxicity and for post\u2010exposure treatment is a continued challenge. In this study, we analyzed the reactivation potency of 111 novel nucleophilic oximes mostly synthesized using the CuAAC triazole ligation between alkyne and azide building blocks. We identified several oximes with significantly improved in vitro reactivating potential for tabun\u2010inhibited human AChE, and in vivo antidotal efficacies in tabun\u2010exposed mice. Our findings offer a significantly improved platform for further development of antidotes and scavengers directed against tabun and related phosphoramidate exposures, such as the Novichok compounds.<\/jats:p>","DOI":"10.1002\/chem.201805051","type":"journal-article","created":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T15:25:42Z","timestamp":1542727542000},"page":"4100-4114","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Reversal of Tabun Toxicity Enabled by a Triazole\u2010Annulated Oxime Library\u2014Reactivators of Acetylcholinesterase"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9863-886X","authenticated-orcid":false,"given":"Zrinka","family":"Kovarik","sequence":"first","affiliation":[{"name":"Institute for Medical Research and Occupational Health  HR-10000 Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"Kalisiak","sequence":"additional","affiliation":[{"name":"Skaggs Institute for Chemical Biology The Scripps Research Institute  La Jolla CA 92037 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1682-8999","authenticated-orcid":false,"given":"Nikolina Ma\u010dek","family":"Hrvat","sequence":"additional","affiliation":[{"name":"Institute for Medical Research and Occupational Health  HR-10000 Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Katalini\u0107","sequence":"additional","affiliation":[{"name":"Institute for Medical Research and Occupational Health  HR-10000 Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Zorbaz","sequence":"additional","affiliation":[{"name":"Institute for Medical Research and Occupational Health  HR-10000 Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzana","family":"\u017dunec","sequence":"additional","affiliation":[{"name":"Institute for Medical Research and Occupational Health  HR-10000 Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Green","sequence":"additional","affiliation":[{"name":"SRI International  Menlo Park CA 94025-3493 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoran","family":"Radi\u0107","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of California at San Diego  La Jolla CA 92093-0650 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery V.","family":"Fokin","sequence":"additional","affiliation":[{"name":"Skaggs Institute for Chemical Biology The Scripps Research Institute  La Jolla CA 92037 USA"},{"name":"The Bridge@USC University of Southern California  Los Angeles CA 90089 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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