{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T16:09:47Z","timestamp":1775750987145,"version":"3.50.1"},"reference-count":57,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T00:00:00Z","timestamp":1638489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Emerging viral infections, including those caused by dengue virus (DENV) and Venezuelan Equine Encephalitis virus (VEEV), pose a significant global health challenge. Here, we report the preparation and screening of a series of 4-anilinoquinoline libraries targeting DENV and VEEV. This effort generated a series of lead compounds, each occupying a distinct chemical space, including 3-((6-bromoquinolin-4-yl)amino)phenol (12), 6-bromo-N-(5-fluoro-1H-indazol-6-yl)quinolin-4-amine (50) and 6-((6-bromoquinolin-4-yl)amino)isoindolin-1-one (52), with EC50 values of 0.63\u20130.69 \u00b5M for DENV infection. These compound libraries demonstrated very limited toxicity with CC50 values greater than 10 \u00b5M in almost all cases. Additionally, the lead compounds were screened for activity against VEEV and demonstrated activity in the low single-digit micromolar range, with 50 and 52 demonstrating EC50s of 2.3 \u00b5M and 3.6 \u00b5M, respectively. The promising results presented here highlight the potential to further refine this series in order to develop a clinical compound against DENV, VEEV, and potentially other emerging viral threats.<\/jats:p>","DOI":"10.3390\/molecules26237338","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T03:10:38Z","timestamp":1638760238000},"page":"7338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Optimization of 4-Anilinoquinolines as Dengue Virus Inhibitors"],"prefix":"10.3390","volume":"26","author":[{"given":"Pei-Tzu","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7845-9418","authenticated-orcid":false,"given":"Sirle","family":"Saul","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirit","family":"Einav","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5871-3458","authenticated-orcid":false,"given":"Christopher R. M.","family":"Asquith","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,3]]},"reference":[{"key":"ref_1","first-page":"e000530","article-title":"Zika, chikungunya and dengue: The causes and threats of new and re-emerging arboviral diseases","volume":"3","author":"Teixeira","year":"2017","journal-title":"BMJ Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/s41564-020-0714-0","article-title":"The continued threat of emerging flaviviruses","volume":"5","author":"Pierson","year":"2020","journal-title":"Nat. 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