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Despite this potential and their prevalence in drug discovery, sulfur\u2010substituted thiazole scaffolds remain largely underexplored due to synthetic challenges in their preparation. To overcome the limitations in accessing these motifs, we report a mild, modular strategy for assembling C5\u2010sulfenyl thiazoles from\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010keto sulfoxides via an intermolecular Pummerer rearrangement. This methodology displays an excellent functional group tolerance, furnishing 50 diverse thiazole scaffolds derived from both thioamides and thioureas. The synthetic and medicinal impact of this methodology is showcased in the preparation and evaluation of thioether, sulfoxide and sulfone analogues of the blockbuster \u03b23\u2010adrenoceptor agonist mirabegron. Comparison of key pharmacokinetic properties revealed improved cell permeability, metabolic stability, lipophilicity and plasma protein binding without unduly affecting biological affinity relative to the parent drug.\n                  <\/jats:p>","DOI":"10.1002\/anie.8444671","type":"journal-article","created":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T16:30:50Z","timestamp":1786897850000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Modular Synthesis of C5\u2010Sulfenyl Thiazoles via an Intermolecular Pummerer Rearrangement: An Underexplored Scaffold for Medicinal Chemistry"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3808-5240","authenticated-orcid":false,"given":"Joe L.","family":"Smy","sequence":"first","affiliation":[{"name":"Department of Chemistry School of Life Sciences University of Sussex  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4660-8314","authenticated-orcid":false,"given":"Theo C.","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Chemistry School of Life Sciences University of Sussex  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8416-4955","authenticated-orcid":false,"given":"Barnaby W.","family":"Greenland","sequence":"additional","affiliation":[{"name":"Department of Chemistry School of Life Sciences University of Sussex  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7371-9855","authenticated-orcid":false,"given":"S. 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