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Many synthetic analogues have been investigated for their activity, yet often based on macrolide structures. A notable exception is Ixabepilone, an azalide whose metabolic stability and pharmacokinetics are significantly improved. Exploiting the amide\u2010triazole bioisosterism, in this work we report the synthesis of the first generation of epothilones lacking the macrolide or azalide structure, with the ester or amide linkage replaced by a triazole unit. Together with the synthesis of this new analogue, computational and biological evaluations have been performed too.<\/jats:p>","DOI":"10.1002\/cplu.202400413","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T06:42:01Z","timestamp":1719384121000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Total Synthesis of an Epothilone Analogue Based on the Amide\u2010Triazole Bioisosterism"],"prefix":"10.1002","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9062-4850","authenticated-orcid":false,"given":"Eleonora","family":"Colombo","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Milan  Via Golgi 19 20133 Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3688-8235","authenticated-orcid":false,"given":"Davide A.","family":"Coppini","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Milan  Via Golgi 19 20133 Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8575-1979","authenticated-orcid":false,"given":"Simone","family":"Borsoi","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Milan  Via Golgi 19 20133 Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1819-4483","authenticated-orcid":false,"given":"Valerio","family":"Fasano","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Milan  Via Golgi 19 20133 Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5465-9447","authenticated-orcid":false,"given":"Raffaella","family":"Bucci","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science University of Milan  Via Venezian 21 20133 Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0579-2874","authenticated-orcid":false,"given":"Francesca","family":"Bonato","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Milan  Via Golgi 19 20133 Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3223-9254","authenticated-orcid":false,"given":"Elisa","family":"Bonandi","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Milan  Via Golgi 19 20133 Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3926-8261","authenticated-orcid":false,"given":"Francesca","family":"Vasile","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Milan  Via Golgi 19 20133 Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7672-0720","authenticated-orcid":false,"given":"Stefano","family":"Pieraccini","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Milan  Via Golgi 19 20133 Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6180-9581","authenticated-orcid":false,"given":"Daniele","family":"Passarella","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Milan  Via Golgi 19 20133 Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(03)00141-8"},{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","unstructured":"K.-H. 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