{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:27:53Z","timestamp":1785403673798,"version":"3.56.0"},"reference-count":23,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Minist\u00e8re de l\u2019Education et de la Recherche","award":["none"],"award-info":[{"award-number":["none"]}]},{"DOI":"10.13039\/100015872","name":"University of Lille","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015872","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/02kzqn938","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The angiotensin II type 1 (AT1) receptor is a key component of the renin\u2013angiotensin system (RAS) and a validated target for cardiovascular and renal disorders. Developing small molecules with defined AT1 versus AT2 binding profiles remains important for both therapeutic and mechanistic studies. Here, a series of novel imidazole-based compounds was synthesized and evaluated for their binding affinities toward angiotensin II type 1 (AT1) and type 2 (AT2) receptors. Binding studies were conducted by measuring the displacement of radiolabeled [3H]-angiotensin II ([3H]-AII) in PLC-PRF-5 human hepatoma cells for AT1 receptors and calf cerebellum membranes for AT2 receptors. Structure\u2013activity relationship (SAR) analysis revealed that sulfonamide substitution significantly enhanced AT1 receptor affinity, whereas sterically hindered derivatives and ester-containing compounds were less active. Molecular docking studies using the AT1 receptor crystal structure (PDB: 8TH4) rationalized the observed activity trends. The most active compound showed high AT1 affinity (Ki = 5 nM), comparable to losartan, and all compounds displayed preferential binding for AT1 over AT2 receptors.<\/jats:p>","DOI":"10.3390\/molecules31111971","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:10:42Z","timestamp":1780668642000},"page":"1971","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Imidazole-Based AT1 Receptor Ligands: Design, Synthesis and Pharmacological Evaluation"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-9397","authenticated-orcid":false,"given":"Florian","family":"Descamps","sequence":"first","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172\u2014LilNCog\u2014Lille Neuroscience & Cognition, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marouane","family":"Rami","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172\u2014LilNCog\u2014Lille Neuroscience & Cognition, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8551-0899","authenticated-orcid":false,"given":"Jean-Fran\u00e7ois","family":"Goossens","sequence":"additional","affiliation":[{"name":"University Lille, CHU Lille, ULR 7365 GRITA\u2014Groupe de Recherche sur les Formes Injectables et Technologies Associ\u00e9es, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9555-3446","authenticated-orcid":false,"given":"Patricia","family":"Melnyk","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172\u2014LilNCog\u2014Lille Neuroscience & Cognition, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Liberelle","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172\u2014LilNCog\u2014Lille Neuroscience & Cognition, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00efd","family":"Yous","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1172\u2014LilNCog\u2014Lille Neuroscience & Cognition, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S0031-6997(24)01458-3","article-title":"International union of pharmacology. XXIII. The angiotensin II receptors","volume":"52","author":"Catt","year":"2000","journal-title":"Pharmacol. 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Cheminformatics"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/11\/1971\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:46:24Z","timestamp":1780980384000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/11\/1971"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":23,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["molecules31111971"],"URL":"https:\/\/doi.org\/10.3390\/molecules31111971","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]}}}