{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T09:48:39Z","timestamp":1792316919089,"version":"4.4.0"},"reference-count":37,"publisher":"American Chemical Society (ACS)","issue":"20","license":[{"start":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T00:00:00Z","timestamp":1442880000000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R03 MH087448-01A1"],"award-info":[{"award-number":["R03 MH087448-01A1"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Venezuelan equine encephalitis virus (VEEV) is an emerging pathogenic alphavirus that can cause significant disease in humans. Given the absence of therapeutic options available and the significance of VEEV as a weaponized agent, an optimization effort was initiated around a quinazolinone screening hit 1 with promising cellular antiviral activity (EC50 = 0.8 \u03bcM), limited cytotoxic liability (CC50 &amp;gt; 50 \u03bcM), and modest in vitro efficacy in reducing viral progeny (63-fold at 5 \u03bcM). Scaffold optimization revealed a novel rearrangement affording amidines, specifically compound 45, which was found to potently inhibit several VEEV strains in the low nanomolar range without cytotoxicity (EC50 = 0.02\u20130.04 \u03bcM, CC50 &amp;gt; 50 \u03bcM) while limiting in vitro viral replication (EC90 = 0.17 \u03bcM). Brain exposure was observed in mice with 45. Significant protection was observed in VEEV-infected mice at 5 mg kg\u20131 day\u20131 and viral replication appeared to be inhibited through interference of viral nonstructural proteins.<\/jats:p>","DOI":"10.1021\/jm501203v","type":"journal-article","created":{"date-parts":[[2014,9,22]],"date-time":"2014-09-22T10:09:24Z","timestamp":1411380564000},"page":"8608-8621","source":"Crossref","is-referenced-by-count":56,"title":["Development of (\n                    <i>E<\/i>\n                    )-2-((1,4-Dimethylpiperazin-2-ylidene)amino)-5-nitro-\n                    <i>N<\/i>\n                    -phenylbenzamide, ML336: Novel 2-Amidinophenylbenzamides\nas Potent Inhibitors of Venezuelan Equine Encephalitis Virus"],"prefix":"10.1021","volume":"57","author":[{"given":"Chad E.","family":"Schroeder","sequence":"first","affiliation":[{"name":"University of Kansas Specialized Chemistry Center , , ,","place":["Lawrence, Kansas, United States, 66049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuanli","family":"Yao","sequence":"additional","affiliation":[{"name":"University of Kansas Specialized Chemistry Center , , ,","place":["Lawrence, Kansas, United States, 66049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Sotsky","sequence":"additional","affiliation":[{"name":"University of Louisville , , , ,","place":["Louisville, Kentucky, United States, 40202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Smith","sequence":"additional","affiliation":[{"name":"University of Kansas Specialized Chemistry Center , , ,","place":["Lawrence, Kansas, United States, 66049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeshna","family":"Roy","sequence":"additional","affiliation":[{"name":"University of Kansas Specialized Chemistry Center , , ,","place":["Lawrence, Kansas, United States, 66049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Kyu","family":"Chu","sequence":"additional","affiliation":[{"name":"University of Louisville , , , ,","place":["Louisville, Kentucky, United States, 40202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixun","family":"Guo","sequence":"additional","affiliation":[{"name":"University of Louisville , , , ,","place":["Louisville, Kentucky, United States, 40202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nichole A.","family":"Tower","sequence":"additional","affiliation":[{"name":"Southern Research Institute , , ,","place":["Birmingham, Alabama, United States, 35205"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Noah","sequence":"additional","affiliation":[{"name":"Southern Research Institute , , ,","place":["Birmingham, Alabama, United States, 35205"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"McKellip","sequence":"additional","affiliation":[{"name":"Southern Research Institute , , ,","place":["Birmingham, Alabama, United States, 35205"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Sosa","sequence":"additional","affiliation":[{"name":"Southern Research Institute , , ,","place":["Birmingham, Alabama, United States, 35205"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Southern Research Institute , , ,","place":["Birmingham, Alabama, United States, 35205"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layton H.","family":"Smith","sequence":"additional","affiliation":[{"name":"Sanford-Burnham Medical Research Institute at Lake Nona , , , ,","place":["Orlando, Florida, United States, 32827"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Lucile","family":"White","sequence":"additional","affiliation":[{"name":"Southern Research Institute , , ,","place":["Birmingham, Alabama, United States, 35205"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Aube\u0301","sequence":"additional","affiliation":[{"name":"University of Kansas Specialized Chemistry Center , , ,","place":["Lawrence, Kansas, United States, 66049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen B.","family":"Jonsson","sequence":"additional","affiliation":[{"name":"University of Louisville , , , ,","place":["Louisville, Kentucky, United States, 40202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghoon","family":"Chung","sequence":"additional","affiliation":[{"name":"University of Louisville , , , ,","place":["Louisville, Kentucky, United States, 40202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Golden","sequence":"additional","affiliation":[{"name":"University of Kansas Specialized Chemistry Center , , ,","place":["Lawrence, Kansas, United States, 66049"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,9,22]]},"reference":[{"key":"2026090205174863900_cit1","first-page":"858","article-title":"Alphaviruses","volume-title":"Fields Virology","author":"Johnston","year":"1996","edition":"3"},{"key":"2026090205174863900_cit2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1128\/CMR.7.1.89","article-title":"Medically\nimportant arboviruses of the United States and Canada","volume":"7","author":"Calisher","year":"1994","journal-title":"Clin. 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