{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T23:24:54Z","timestamp":1787181894339,"version":"build-2736575974"},"reference-count":79,"publisher":"Georg Thieme Verlag KG","funder":[{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["P20GM103451"],"award-info":[{"award-number":["P20GM103451"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Synthesis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The global HIV\/AIDS epidemic continues to demand durable antiretroviral therapies. HIV-1 protease (HIV-PR) remains a central target, and although darunavir (DRV) exhibits exceptional resilience, resistance evolution necessitates continued innovation. Building on DRV\u2019s success, structural modifications at key positions have yielded promising derivatives. In this work, we report the design and synthesis of over 20 DRV derivatives incorporating pyrazole and amino acid motifs at the P2\u2032 position. These substituents were introduced to strengthen interactions within the protease active site and expand opportunities for resistance coverage. Sulfur(VI) fluoride exchange (SuFEx) chemistry was employed as a robust late-stage diversification strategy, enabling efficient coupling and rapid library generation. This approach highlights the potential to access structurally diverse HIV-1 protease inhibitors, laying the groundwork for the development of next-generation therapeutics.<\/jats:p>","DOI":"10.1055\/a-2930-3820","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:48:18Z","timestamp":1785797298000},"source":"Crossref","is-referenced-by-count":0,"title":["Late-Stage Diversification of HIV-1 Protease Inhibitor via SuFEx Click Chemistry"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1814-5279","authenticated-orcid":false,"given":"Bipin","family":"Khanal","sequence":"additional","affiliation":[{"name":"New Mexico State University, United States","place":["Las Cruces"],"department":["Department of Chemistry and Biochemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Yamanushkin","sequence":"additional","affiliation":[{"name":"New Mexico State University, United States","place":["Las Cruces"],"department":["Department of Chemistry and Biochemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3534-1329","authenticated-orcid":false,"given":"Brian","family":"Gold","sequence":"additional","affiliation":[{"name":"New Mexico State University, United States","place":["Las Cruces"],"department":["Department of Chemistry and Biochemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2009.10.002","volume":"85","author":"S Broder","year":"2010","journal-title":"Antivir Res"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.jacbts.2021.10.017","volume":"7","author":"L Kovacs","year":"2022","journal-title":"JACC Basic Transl 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